Untitled - Romanian Journal of Cardiology

Vol. 22, No. 2, 2012EDITORIALTHE WORLD OFCARDIOLOGYORIGINAL PAPERSREVIEWSCASE STUDYIMAGES IN CARDIOLOGYESC GUIDEAGENDAINSTRUCTIONS FORAUTHORSAbout speaking in public 79A. PleşuEric J.Topol - pioneer for the creative destruction of medicine 81M. MartinTelemetry monitoring in spontaneously hypertensive rats. Impact ofthe implant procedure, assessment of electrocardiographic signal quality 84Alina Scridon, C. Gallet, Moussa M. Arisha, Valérie Oréa, B. Chapuis, Ch. Barrès, C. Julien, Ph. ChevalierClinical and paraclinical particularities for hypertensive patients withPheochromocytoma- retrospective study 91V. Chioncel, F. Adam, I. Sinescu, Diana Păun, Crina SinescuPredictive factors for atrial fibrillation appearance in dilatedcardiomyopathy 97C. Matei, Ioana Pop, Mihaela Badea, Adriana Saraolu, I. M. Coman, E. ApetreiConflict of interest policies and disclosure requirements amongEuropean Society of Cardiology national cardiovascular journals 107F. Alfonso, A. Timmis, F. J. Pinto, G. Ambrosio, H. Ector, P. Kulakowski, P. VardasALMANAC 2011: acute coronary syndromes. The national societyjournals present selected research that has driven recent advances inclinical cardiology 117Ch. Knight, A. D. TimmisAlmanac 2011: cardiac arrhythmias and pacing. The national societyjournals present selected research that has driven recent advances inclinical cardiology 128R. LiewTherapeutic approach to cardiorenal syndrome 143Minodora Teodoru, I. Maniţiu, A. Teodoru, Raluca Matei, Cristina ChircuAn unusual cause of „mitral” stenosis 151Irina Costache, A. Cozma, L. Stoica, A. O. PetrişVascular Doppler: Glomic tumor – ultrasonographic evaluation 154Ileana ArsenescuCoronary Angiography: A rare case of acute myocardial infarction 155A. Negoiţă, M. Postu, D. DeleanuEcocardiography: Rare case pulmonary hypertension 157B. A. Popescu, Anca Mateescu, Roxana Enache, P. Platon, Carmen GinghinăEAE recommendations for training, competence, and qualityimprovement in echocardiography 159National and International Cardiological agenda 2012 173Instructions for authors 176

Vol. 22, No. 2, 2012Vol. XXII, Nr. 1, 2007EDITORIALDIN LUMEA CARDIOLOGIEIARTICOLE ORIGINALEREFERATE GENERALEPREZENTARE DE CAZIMAGINI ÎN CARDIOLOGIEGHIDAGENDAINSTRUCÞIUNI PENTRUAUTORIDespre vorbitul în public 79A. PleşuEric J. Topol – pionierul distrugerii creatoare a medicinii 81M. MartinTelemetry monitoring in spontaneously hypertensive rats. Impact ofthe implant procedure, assessment of electrocardiographic signal quality 84Alina Scridon, C. Gallet, Moussa M. Arisha, Valérie Oréa, B. Chapuis, Ch. Barrès, C. Julien, Ph. ChevalierParticularităţi clinice şi paraclinice la pacienţii hipertensivi cufeocromocitom – studiu retrospectiv 91V. Chioncel, F. Adam, I. Sinescu, Diana Păun, Crina SinescuFactori predictivi pentru apariţia fibrilaţiei atriale în cardiomiopatiadilatativă 97C. Matei, Ioana Pop, Mihaela Badea, Adriana Saraolu, I. M. Coman, E. ApetreiConflict of interest policies and disclosure requirements amongEuropean Society of Cardiology national cardiovascular journals 107F. Alfonso, A. Timmis, F. J. Pinto, G. Ambrosio, H. Ector, P. Kulakowski, P. VardasALMANAC 2011: acute coronary syndromes. The national societyjournals present selected research that has driven recent advances inclinical cardiology 117Ch. Knight, A. D. TimmisAlmanac 2011: cardiac arrhythmias and pacing. The national societyjournals present selected research that has driven recent advances inclinical cardiology 128R. LiewAbordarea terapeutică a sindromului cardiorenal 143Minodora Teodoru, I. Maniţiu, A. Teodoru, Raluca Matei, Cristina ChircuAn unusual cause of „mitral” stenosis 151Irina Costache, A. Cozma, L. Stoica, A. O. PetrişDoppler Vascular: Tumora glomică - evaluare ultrasonografică 154Ileana ArsenescuCoronarografie: Infarct miocardic acut de cauză rară 155A. Negoiţă, M. Postu, D. DeleanuEcocardiografie: Hipertensiune pulmonară de cauză rară 157B. A. Popescu, Anca Mateescu, Roxana Enache, P. Platon, Carmen GinghinăRecomandările Asociaţiei Europene de Ecocardiografie pentru pregătirea,competenţa şi îmbunătăţirea calităţii în domeniul ecocardiografiei 159Calendarul manifestărilor ştiinţifice cardiologice 173Manifestări ştiinţifice şi cursurile Societăţii Române de Cardiologie 2012Manifestări ştiinţifice internaţionale 2012Instrucţiuni pentru autori 176

THE ROMANIAN SOCIETY OF CARDIOLOGY BOARDPresident:President elect:Former president:Vice-presidents:Secretary:Treasurer:Members:Ioan M. ComanGabriel Tatu-ChiţoiuDan E. DeleanuDragoş VinereanuRadu CiudinBogdan A. PopescuOvidiu ChioncelEduard ApetreiŞerban BălănescuMircea CintezăMarian CroitoruDan GaiţăDaniel GherasimIoana GhiorghiuCarmen GinghinăAdriana IlieşiuDaniel LighezanFlorin MituCălin PopRadu VătăşescuDragoş VinereanuCover images1 - Ecografic se constată că formaţiunea este situată cranial de bifurcaţia carotidiană, între arterele carotidă internă şi carotidă externă. Estebine delimitată şi structura este hipoecogenă, omogenă. La examenul Doppler spectral vitezele şi indicele de rezistenţă sunt normale peartera carotidă internă (pagina 154).2 - Coronarografie - injectare în artera coronară dreaptă (CD) - ocluzie în segmentul I cu aspect de tromb intraluminal -a.2b - disparițiacompletă a spasmului la nivelul întregului vas la administrarea de nitroglicerină intracoronarian (pagina 156).ISSN: 1583-2996

EDITORIAL STAFFEditor-in chiefEduard ApetreiDeputy EditorCarmen GinghinăAssociate editorsMihaela RuginăRuxandra JurcuţBogdan A. PopescuCostel MateiEditorsRadu CăpâlneanuCezar MacarieFounding editorCostin CarpEDITORIAL BOARDŞerban Bălănescu - BucureştiLuigi Paolo Badano - ItaliaIon V. Bruckner - BucureştiAlexandru Câmpeanu - BucureştiGheorghe Cerin - ItaliaMircea Cinteză - BucureştiRadu Ciudin - BucureştiD. V. Cokkinos - GreciaIoan Mircea Coman - BucureştiG. Andrei Dan - BucureştiDan Deleanu - BucureştiGenevieve Derumeaux - FranţaDoina Dimulescu - BucureştiMaria Dorobanţu - BucureştiŞtefan Iosif Drăgulescu -TimişoaraGuy Fontaine - FranţaAlan Fraser - AngliaCătălina Arsenescu-Georgescu -IaşiMihai Gheorghiade - USALeonida Gherasim - BucureştiAurel Grosu - Chişinău,R. MoldovaAssen R. Goudev - BulgariaAlexandru Ioan - BucureştiDan Dominic Ionescu -CraiovaGabriel Kamensky - SlovaciaAndre Keren - IsraelMichel Komajda, FranţaIoan Maniţiu - SibiuMartin S. Martin - SUAGerald A. Maurer - AustriaŞerban Mihăileanu - FranţaNour Olinic - Cluj-NapocaFausto Pinto - PortugaliaCălin Pop, Baia MareTiberiu Nanea, BucureştiGian Luigi Nicolosi - ItaliaWillem J. Remme - OlandaMichal Tendera - PoloniaIon Ţintoiu - BucureştiPanagiotis Vardas - GreciaDragoş Vinereanu - BucureştiMarius Vintilă - BucureştiDumitru Zdrenghea -Cluj-NapocaIssue editorMihaela RuginăSecretaryMihaela SălăgeanTechnical informationResponsibility for the contents of the published articles falls entirely on the authors. Opinions, ideas, results of studies published in the RomanianJournal of Cardiology are those of the authors and do not reflect the position and politics of the Romanian Society of Cardiology. Nopart of this publication can be reproduced, registered, transmitted under any form or means (electronic, mechanic, photocopied, recorded)without the previous written permission of the editor.All rights reserved to the Romanian Society of CardiologyContact: Societatea Română de CardiologieStr. Avrig nr. 63, Sector 2, BucureştiTel./Fax: +40.21.250 01 00, +40.21.250 50 86, +40.21.250 50 87;E-mail: office@cardioportal.ro

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012EDITORIALDespre vorbitul în public *Andrei PleşuUna dintre cele mai perfide agresiuni împotrivasemenilor noştri este proasta administrare a discursuluipublic. Totul, în viaţa culturală curentă, e maiuşor de suportat decît oratoria incontinentă, verbiajultorenţial, limbuţia încîntată de sine. Cunosc foarte puţinioameni capabili să-şi dozeze cuviincios exerciţiileretorice. Cei mai mulţi se lăfăie impudic în propriilepanglici verbale, dinaintea unui public tot mai nerăbdător,exasperat, gata să fugă sau să se refugieze într-oigienică picoteală.A ţine discursuri prea lungi e simptomul unei bolicomplicate, greu de schiţat în cîteva rînduri. Mai întîi, elimpede că vorbitorul e fericit să se audă vorbind. Fie că,în viaţa zilnică, e nevorbit, fie că are o părere excelentădespre talentele sale, despre cuvintele şi ideile de nepreţuitcare îi trec prin cap sau prin gură, insul cu pricinae, practic, de neoprit. Publicul asistă înmărmurit la unîndelung orgasm solitar, la o specie de nevindecabilăimpudoare. Subiectul discursului devine neesenţial, caşi bunăstarea ascultătorilor. Esenţială este exaltarea desine a celui care vorbeşte, sentimentul lui că are de spuslucruri decisive, că nici un preţ nu e prea mare pentrucine vrea să se adape de la neţărmuritele sale competenţe.Viciul de primă instanţă al ipochimenului locvaceeste impoliteţea. Nu se gîndeşte nici o clipă dacă ceidin sală mai au sau nu răbdare, dacă n-au obosit, dacănu cumva mai au şi alte treburi. Auditoriul e tratat, defapt, ca o simplă masă de manevră; carne de tun anonimă,şeptel bun de jertfit. Mai grav e că vorbitorul egolatrudispreţuieşte, fără să vrea, subiectul propriei peroraţii.Nu contează despre ce sau despre cine vorbeşte.Că tema e Shakespeare, Newton, doctrina corporatistă,sau flora sud-africană nu contează. Ceea ce contează e„expertul“ de la pupitru, vasta lui pricepere, farmecullui inegalabil, măreţia prezenţei sale, fragedele lui trăirişi sentimente. În cele din urmă însă, cel lovit de această*Articol reprodus din ”Dilema Veche”, Nr. 427 / 19-25 aprilie 2012,cu încuviințarea autoruluipatimă îşi dăunează deopotrivă sieşi: devine antipatic,de nesuportat, nefrecventabil.Există unele indicii de natură să avertizeze, încă dela început, asupra unui discurs lung. Vorbitorul începe,de pildă, cu un anunţ graţios: „Voi fi scurt...“ (Variantă:„E foarte greu să mai adaugi ceva după minunatele cuvinteale antevorbitorului, aşa că vă voi împărtăşi, doar,cîteva gînduri...“). De cîte ori aud o asemenea introducereintru în panică. Ştiu că nu mai e nimic de făcut, că,în numele acestei drăgălaşe captatio, retorul va socotică îşi poate permite orice (şi oricît!). De menţionat sîntşi cîteva artificii de parcurs (admit că, la răstimpuri, leampracticat eu însumi). Cînd discursul e deja răscoptşi publicul aşteaptă cu sufletul la gură adierea anticipativăa vreunei fraze de încheiere, oratorul îşi ia seamaşi spune: „un ultim cuvînt“, sau „încă două propoziţiişi voi încheia“, sau „aş mai avea doar o problemă deamintit, dacă mai suportaţi...“ „Nu, nu mai suportăm!“– strigă mut cei din sală, dar îşi continuă, neputincioşi,martirajul. Căci, de regulă, după astfel de fente şmechere,discursul continuă nestingherit.Logoreea poate avea însă şi alte explicaţii. Uneori, edamblaua colaterală a celor care stau prost cu situareaîn timp: pur şi simplu nu realizează cît vorbesc, pierdcontactul cu ceasul, nu se pot acomoda la mecanicastrictă a duratei. Alţii sînt atît de absorbiţi de subiectulde care se ocupă, încît uită de ei şi de lume, îşi abandoneazăascultătorii, nu mai percep situaţia concretă încare se află. Practic, monologhează somnambulic, întransă, atenţi numai la desfăşurarea completă şi definitivăa argumentaţiei proprii. Nu ţin o conferinţă, ciscriu un capitol de carte, dacă nu toată cartea. Au unaer genialoid, uşor smintit. Oricum, pentru ei, ceilalţinu există decît ca pretext: o colecţie de spectre pentru ovorbire spectrală...O cauză frecventă a derapajului oratoric este confuzia,mai mult sau mai puţin conştientă, a genurilor.Mulţi vorbitori nu fac nici o diferenţă între o intervenţiela o masă rotundă, o lansare de carte cu patru-cinciprezentatori, o comunicare la un congres sau colocviuşi o conferinţă propriu-zisă. Tendinţa generală e, la noi

Andrei PleºuDespre vorbitul în publicmai mult decît în alte ţări, unde disciplina expunerilorpublice e mai severă, să faci din toate aceste genuri distincteunul singur: totul e construit după tipicul uneiample conferinţe. E un mod de a dezavantaja pe toţicei care vorbesc după tine şi de a-i ofensa, în fond, prinverbiajul tău prepotent. Despre public nu mai vorbesc.E, oricum, ultima roată la căruţă.Romanian Journal of CardiologyVol. 22, No. 2, 2012Prin urmare – şi ca să n-o lungesc eu însumi pestemăsură – recomand tuturor conferenţiarilor să facă dinconcizia expunerilor lor un inflexibil criteriu de eficienţă.Sănătos este ca ascultătorul să plece din sală nesătul,ca oaspetele de la o masă îmbelşugată. Restul eindigestie...

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012DIN LUMEA CARDIOLOGIEI: ISTORIE, PERSONALITĂȚI, OPINII, CONTROVERSEEric J. Topol – pionierul distrugerii creatoare a mediciniiM. S. MartinSunt puţini cardiologiame ricani care se potcom para cu Eric J. Topol,un om care a cunoscut succesul devreme, a conti nuatsă aibă realizări im pre sionante şi - înainte să împlineascăvârsta de cinci zecide ani – a acumulat toateti tlurile posibile şi şi-a legatEric J. Topolnumele de marile pro gre seale cardiologiei, în cea mai bună, curajoasă şi acti vă fazăa evoluţiei istorice a specialităţii. Cardiolog inter venţional,a publicat Textbook of Interventional Car diologyîn 1990 1 , carte devenită o instituţie prin ea însăşi şi carea ajuns deja la ediţia a şasea, anun ţând că o va lua, maimult ca sigur, pe calea altor cărţi devenite celebre şi depăşindlongevitatea autorilor, aşa cum sunt Harrison’sPrinciples of Internal Medicine 2 (ediţia a optsprezecea),sau Braunwald’s Heart Di seases 3 (ediţia a noua). A maipublicat o altă carte de re fe rinţă Manual of CardiovascularMedicine 4 şi cele două cărţi sunt mo nografiile decăpătâi ale oricărui tânăr medic în domeniu.După facultatea de medicină (University of Rochester),rezidenţa de medicină internă (University of Californiaat San Francisco) şi fellowship-ul de cardiologie(Johns Hopkins Medical School Baltimore Maryland),Eric Topol a făcut o carieră de mare succes la Universitateadin Michigan, unde devenit profesor, şeful programuluide cardiologie şi cercetător principal pentruşase ani. A fost primul care a administrat t-PA recombinantîn infarctul miocardic în 1984 5 , de asemeneaprimul care a utilizat ReoPro (abcximab) 6 , noile medicamenteantiplachetare 7 şi heparinele sintetice 8 . Ca investigatorprincipal, a condus peste cincisprezece maritrial-uri care au împins înainte tratamentul în infarctulmiocardic acut (GUSTO, TIMI, EPIC, EPILOG, EPIS-TENT, CAVEAT, TARGET, PURSUIT şi altele). Numitchairmanul departamentului de cardiologie de la ClevelandClinic, a format un mare număr de cardiologiintervenţionali, a ridicat prestigiul serviciului la cel maiînalt nivel, a înfiinţat Colegiul de Medicină Lerner şiCentrul Specializat în Cercetarea Medicală orientatăClinic, menţinând instituţia pe locul întâi pe ţară pentruunsprezece ani consecutivi (US News and WorldReport).Implicat în cercetarea care a dus la descoperirea drogurilorproduse prin inginerie genetică, Topol a învăţatîncă două meserii, cea de genetician şi cea de specialistîn genomics. În cardiologie a fost primul care a descoperitrăspunsul diferit la droguri al diverşilor pacienţi,mai ales în tratamentele cu clopidogrel (Plavix) 9 şi bivalirudin(Angiomax), la geneza cărora a contribuit. Aavut un rol mare în identificarea genelor care mărescriscul de accident coronarian acut 10 . Pe lângă toate celelaltetitluri şi distincţii, a fost numit Doctorul Decadeişi unul dintre cei zece cercetători de frunte între 1993 şi2003 (Institute of Scientific Information), de asemeneaa fost desemnat primul autor ca valoare al lucrărilordin domeniul cardiologiei în aceeaşi perioadă (ScienceWatch). Un adevărat Rock star în cardiologie.În culmea gloriei, a descoperit că un medicamentantiinflamator de largă utilizare (Vioxx Merck) faciliteazătromboza coronariană şi a făcut publice datelefără întârziere 11 . Compania farmaceutică, afectată de ouriaşă pierdere financiară, s-a adresat celui cu care Topolera în competiţie pentru titlul suprem la ClevelandClinic, chirurgul cardiac Delos M. Cosgrove, o somitateîn chirurgia coronariană şi în chirurgia reconstructivăa valvei mitrale. Acesta şi-a folosit influenţa şi putereape care le avea în board-ul clinicii, care a deschis o anchetăinternă privind conflictele de interese ale doctoruluiTopol, angrenat în multiple cooperări şi asociaţiicu diverse companii, totodată foarte activ în investiţia1Diagnostic Cardiology Group. Chattanooga, TennesseeContact address:Martin S Martin, MD. 13421 Bellacoola Rd Soddy Daisy, Chattanooga,Tennessee 37379. Phone: 423 629 4106 (office/answering service); 423 3164505 (cell); Fax: 423 499 2062.

M. MartinEric J. Topol – pionierul distrugerii creatoare a mediciniide fonduri la bursă, multe legate de acţiunile companiilorale căror secrete îi erau mai cunoscute lui, decâtmarelui public. Şi s-a întâmplat ceva de neconceput: încâteva zile, postul lui Topol a fost desfiinţat şi el s-a trezitla uşa instituţiei la gloria căreia contribuise mai multdecât oricine altceva.Astăzi Dr. Topol este profesor de cardiologie la UniversitateaLa Jolla San Diego California şi director alInstitutului de Translaţie al Ştiinţei tot de acolo. A maicreat în California şi Institutul de Sănătate fără Conexiuni(wireless), ultimele două fiind printre primeleinstituţii dedicate unor domenii de pionierat în telemedicinăşi introducerea computeristicii avansate îndiagnosticul şi tratamentul medical.În luna ianuarie a acestui an, Dr. Topol a lansat o carteprovocatoare Distrugerea creatoare a medicinii: cum vaîmbunătăţi revoluţia digitală asistenţa medicală 12 , carene deschide o fereastră către o medicină din viitorulapropiat, complet diferită de cea pe care o cunoaştem şicare este rezultatul îmbinării a trei elemente fundamentale:întâlnirea ştiinţelor biologice cu revoluţia digitalăşi colectarea de date la un volum fără precedent, utilizarealargă a aparaturii portabile şi neconectate (telefoaneinteligente, i-Pad-uri) în medicină şi trecerea dela medicina bazată pe reguli rezultate din studiul unorpopulaţii (doza medie eficace pentru o anumită vârstă,aceeaşi la toţi bolnavii trataţi, standardizarea strategiilorde tratament) la o medicina individualizată, cu tratamentales şi dozat unic pentru bolnavul în cauză.Termenul de distrugere creatoare a fost folosit de maimulţi sociologi şi filozofi, dar a fost impus în anul 1942de către economistul american de origine austriacăJoseph A Schumpeter (1883-1950) 13 , pentru a susţineteoria lui de adaptare a business-ului prin intervenţiaforţelor distructive generate de capitalismul însuşi, cuun efect pozitiv până la urmă, dar cu distrugerea unuimodel vechi, care să facă loc creerii unuia nou, superior.Dr. Topol şi echipele care lucrează la instituţiile deavan gardă create de el au inventat deja microsensoripen tru numeroşi parametri biologici simpli (temperatură,puls, greutate, tensiune arterială, ritm cardiac, glicemie, conţinut de oxigen al sângelui, volumul respi rator),mai complexi (electrocardiogramă, electroencefalogramă,somnogramă, mişcări fetale, contracţii uterine,parametri circulatori ai fătului), sau foarte com plexi(numărul de celule endoteliale eliberate de plă cile coronarieneinstabile, care anunţă iminenţa unui infarct,schimbarea fluxului respirator care anunţă o criză deastm, conţinutul de fluide al corpului indicator al gra-Romanian Journal of CardiologyVol. 22, No. 2, 2012dului de compensare a insuficienţei cardiace, multipliparametri biochimici identificaţi percutan sau prinanalizori permanenţi implantabili) şi multe altele.Ecranul telefonului mobil al Dr. Topol e mai încărcatdecât monitoarele din reanimarea unui spital modernşi monitorul merge cu pacientul peste tot, dândavertismentele necesare, înainte ca bolnavul să intre înfaza care să-l ducă la serviciul de urgenţă. Toate dateleînregistrate pot fi transmise medicului curant, laboratoarelor,colectoarelor de date şi – în principiu- oricui.Introducerea medicinii care transformă bolnavulîntr-un mediu digital poate revoluţiona întreg sistemulme dical. Exceptând serviciile de chirurgie şi terapie intensivă,Dr. Topol nu vede ce loc ar mai avea în spitaleleviitorului serviciile de diagnostic. Şi tratamentelecomplexe intravenoase şi terapia de dializă renală şire petarea analizelor, ca şi obţinerea unei electrocardiograme,echocardiograme sau encefalograme se pot faceîn spaţiul locuinţei, într-un comfort mult mai mare decâtcel al mediului spitalicesc, cu ajutorul bolnavului, alaparaturii automatizate, al cadrelor medicale itineranteşi al telemedicinii.Mai mult, telefonul mobil va face nu numai analizede rutină, dar şi pe cele mai complicate, ca cel desecvenţializare a genomului, a cărui tehnică nouă ceredoar cincisprezece minute pentru a fi complectată, întimp ce pentru mulţi ani această analiză avea nevoiede mai mult de zece zile în laboratoarele normale alespitalelor obişnuite. Cu această armă în mână, mediculva afla, după ce administrează o doză de medicament,dacă bolnavul în cauză va răspunde sau nu la tratament,care este doza optimă pentru acel bolnav şi caresunt şansele de a dezvolta efecte secundare de la terapiaîn cepută.Telemedicina va avea multiple feţe: contact permanentcu bolnavul, identificarea celor la risc pentru multiple afecţiuni (astm, diabet, Alzheimer, infarct, fibrilaţie atrială, moarte subită etc.) sau a complicaţiiloru nora din ele, ghidarea tratamentului lor preventiv saucu rativ şi în fine o aplicaţie fără precedent: extindereaputerii diagnostice în cazurile dificile la forţa medicalăa lumii întregi. Cum se poate face asta? Datele colectatede la un bolnav cu o afecţiune gravă şi neidentificatăîncă vor fi trimise în norul digital (cloud) şi computerulle va confrunta în doar câteva secunde cu tot ces-a scris vreodată în subiect, de asemenea le va trimitepentru ajutor specialiştilor înregistraţi, oriunde ar fi, eiprimind o notificare că li se cere ajutorul. Mii de doctori,dintre cei mai experimentaţi şi mii de instituţii vorfi consultaţi (e), oriunde s-ar afla ei pământ.

Romanian Journal of CardiologyVol. 22, No. 2, 2012Examenele de rutină şi controalele nu vor mai aveanevoie de deplasarea bolnavilor la cabinetele medicale,medicii şi personalul lor vor avea de făcut mult maimultă comunicare cu bolnavii on line, prin e-mail şiprin telefonia cu imagine.Numai comparaţia simplă între valoarea informativăa multitudinii de date complexe, înregistrate continuu,pe de o parte şi rezultatele unui examen obiectiv bazatpe simţurile umane (palpare, ascultare), pe de altăpar te, arată dimensiunea la care se poate ridica nouame dicină. Până şi simbolul vechi de secole al medicinii,stetoscopul (inventat de Rene Laennec în 1816), vadis părea de la gâtul doctorilor în procesul distrugeriive c hii medicini, necesară pentru creerea celei noi. El vafi înlocuit de aparate de echocardiografie miniaturizate,de dimensiuni comparabile cu telefonul mobil din zilelenoastre.Sunt multe alte aspecte în carte, unele legate de ideinovatoare, altele care comentează cea mai mare rezistenţăcare vine din partea conservatorismului profesiuniimedicale, un cocon care nu se lasă pătruns cu usuşinţăde către nou, cum comentează Eric Topol. Forţamotrică care va împinge înainte noua medicină, forţăpe care contează Dr. Topol, este puterea publicului consumator.Ea este cea care poate schimba lumea, în funcţiede intensitatea cererii. Ca un exemplu, primul telefonmobil a fost inventat în anul 1975, apoi perfecţionatîn cele două decade următoare, cu creşteri de vînzăriconforme cu aşteptările şi previziunile. Apoi a urmatexplozia care a schimbat comunicaţiile în lumea întreagă.Astăzi sunt în lume peste 60 de miliarde de telefoanemobile, mai multe decât grupurile sanitare din caseleindividuale. Preţul convorbirilor, inclusiv ale celorinternaţionale a scăzut dramatic şi lumea comunică ladistanţă cu o uşurinţă de neînchipuit, până nu demult.M. MartinEric J. Topol – pionierul distrugerii creatoare a mediciniiCartea e captivantă şi stimulativă. În profesiuneamedicală va juca – probabil – rolul pe care l-a avut Şoculviitorului 14 de Alvin Toffler, apărută în 1970 şi care apregătit generaţiile anilor aceia pentru mari schimbărieconomice şi sociale. Dar nici Toffler, nici nimeni altcinevanu a putut întrezări, la vremea aceea, la ce distanţăvom putea călători cu ajutorul computerelor personale,al device-urilor portabile şi a spaţiilor vaste deschise înfaţa inteligenţei şi imaginaţiei de cyberspace şi de incredibileledezvoltări ale unei tehnologii de basm, plecatăde la câteva fire de nisip. Care iată că se pregăteştesă intre în domeniul medicinii, cu mari şanse să o facăde nerecunoscut în doar câţiva ani.Bibliografie1. Topol EJ: Textbook of interventional cardiology. WB Saunders 19902. Harrison’s principles of Internal Medicine. McGraw Hill 19503. Braunwald’s heart disease.WB Saunders 20114. Topol EJ: Manual of cardiovascular medicine. Lipincott Williams andWilkes 20045. Topol EJ: Acute myocardial infarction: thrombolysis. Heart 83 (122):1136, 20006. The EPIC Investigators: Use of a monoclonal antibody directedagainst the platelet IIb/IIIa receptor in high risk coronary angioplasty.NEJM 330 (14): 956-961, 19947. The CAPRIE Investigators: A randomized blind trial of clopidogrelversus aspirin in patients at high risk for ischemic events. Lancet348(9038): 1329-39, 19968. Topol EJ: A guide to therapeutic decision-making in patients withnon-St segment elevation acute coronary syndromes. JACC 41:123-29,2003 and Topol EJ et al: Use of direct antithrombin hirulog in pla ceof heparin during coronary angioplasty. Circulation 87:1622-9, 19939. Topol EJ: An important miscue in clopidogrel pharmacogenomics.www.theheart.org, Dec 27, 2011 and Wang TH, Topol EJ: Aspirin andclopidogrel resistance.Eur. Heart J. 27 (6): 855-861, 200610. Topol EJ: The genetics of heart attack.Heart 92: 855-861, 200611. Topol EJ: Failing the public health – rofecoxib, Merck and FDA.NEJM 351 (17): 1707-9, 200412. Topol EJ: The creative destruction of medicine: how digital revolutionwill create better health care. Basic Books 201213. Joseph A Schumpeter: Capitalism, Socialism and Democracy. 3rd edition.Harper Perennial Modern Classics 200814. Toffler A: Future shock. Random House 1970

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012ORIGINAL ARTICLETelemetry monitoring in spontaneously hypertensive rats.Impact of the implant procedure, assessment ofelectrocardiographic signal qualityAlina Scridon 1,2 , C. Gallet 2 , Moussa M. Arisha 3 , Valérie Oréa 2 , B. Chapuis 2 , C.Barrès 2 , C. Julien 2 , Ph. Chevalier 2,3Article received on the 14 th February 2012. Article accepted on the 5 th March 2012.Abstract: Objective – Surgical implantation of radiotelemetry devices is not novel, but its impact on spontaneously hypertensiverats (SHR) has not been previously assessed. This study aimed to evaluate the time necessary for recovery after radiotelemetrydevice implantation and the quality of ECG signal in various conditions. Methods – Radiotelemetry ECG transmitterswere implanted in 8 young and 8 aging SHRs. Morbidity and mortality rates were recorded and the time needed for recoveryafter implant procedure was assessed based on body weight evolution. The quality of ECG signal was assessed during baselineconditions and various experimental protocols. Results – None of the animals died during or shortly after implant procedure.Within one week all rats regained their initial body weights. All ECG elements were easily recognizable in both baselineconditions and during various experimental protocols. No significant local changes were presented at the moment of deviceexplantation. Conclusion – In our experience, surgery procedures for implanting radiotelemetry ECG devices in SHRs appearto be safe techniques, with short interval of recovery, low morbidity rates and no mortality, regardless the age of animals. Subcutaneousimplantation of such devices offers high-quality ECG signal and is very well tolerated, even if long-term keeping inplace is needed.Keywords: radiotelemetry, implant procedure, signal quality, spontaneously hypertensive ratRezumat: Obiectiv – Implantarea chirurgicală a dispozitivelor de radiotelemetrie nu este o tehnică nouă, dar impactul eiasupra şobolanilor spontan hipertensivi (SHR) nu a fost încă evaluat. Scopul acestui studiu a fost de a evalua timpul necesarpentru recuperare după implantarea dispozitivelor de telemetrie şi calitatea semnalului ECG în diverse condiţii. Metoda –Dispozitivele de telemetrie au fost implantate la 8 SHR tineri şi 8 bătrâni. Morbiditatea şi mortalitatea au fost înregistrate şitimpul necesar pentru recuperare a fost evaluat pe baza evoluţiei greutăţii corporale. Calitatea semnalului ECG a fost evaluatăîn condiţii bazale şi în cursul unor protocoale experimentale. Rezultate – Niciun animal nu a murit în timpul sau imediatpost-procedural. În decurs de o săptămână toţi şobolanii au recuperat greutatea corporală iniţială. Toate elementele ECG auputut fi uşor recunoscute în condiţii bazale, dar şi în timpul protocoalelor experimentale. La explantare nu au existat modificărilocale semnificative. Concluzii – Procedurile chirurgicale de implant a dispozitivelor de radiotelemetrie la SHR par a fitehnici sigure, cu interval scurt de recuperare, rate scăzute de morbiditate şi mortalitate, indiferent de vârsta animalelor. Implantareasubcutanată a acestor dispozitive oferă un semnal ECG de înaltă calitate şi este bine tolerată, chiar după un intervalde timp îndelungat.Cuvinte cheie: radiotelemetrie, procedura de implant, calitatea semnalului, şobolan spontan hipertensivINTRODUCTIONThe use of surgically implanted radiotelemetry transmittersthat allow monitoring heart rate and ECG hasextended a lot lately because of their ability to monitorsuch functions over several weeks or even months, incon scious, undisturbed animals, without interferencewith handling or stress. Unlike external ECG monitoring,where animals are restrained by ECG leads thatli mit their mobility, these devices allow free motion ofani mals, and manipulation is limited to feeding andcleaning.Although surgical techniques used to implant radiotelemetrydevices in rats are not novel 1-3 , and a numberof studies have assessed the time needed for recoveryfollowing different implant techniques, no such study isavailable for hypertensive rats, which are prone to presentincreased morbidity and mortality rates fol lowinginvasive techniques and general anesthesia. 41University of Medicine and Pharmacy of Târgu Mureş, 540000, Romania2Unité de Neurocardiologie, Université Lyon 1, F-69008, Lyon, France3Hospices Civils de Lyon, Hôpital Louis Pradel, Service de Rythmologie,F-69500, Lyon, FranceContact address:Dr. Alina Scridon, University of Medicine and Pharmacy of Târgu Mureş,Department of Physiology, 38 Gheorghe Marinescu Street, 540000 TârguMureş, Romania. Telephone: 00 40 7 45 30 69 24. Fax: 00 40 2 65 21 04 07E-mail: alinascridon@yahoo.com

Romanian Journal of CardiologyVol. 22, No. 2, 2012This study aims to evaluate morbidity and mortalityrates associated with implant procedures of radiotelemetryECG monitoring devices, and the time neededfor recovery after radiotelemetry devices surgical implantationin spontaneously hypertensive rats (SHR).Radiotelemetry devices only allow analysis in a singleECG lead, which might limit the recognition ofECG elements and complex diagnostics, such as heartrhythm disturbances, mainly during intense animalsomatomotor activity. 5 Thus, we also thought to assessthe quality of the ECG signal obtained during baselineconditions and during various experimental protocolsand the ability to recognize different electrocardiographicfeatures.METHODSAnimalsMale SHRs were purchased from Elevage Janvier (LeGenest Saint Isle, France).Experiments were conducted on 8 male threemonths-old SHRs (311.5 ± 7.7 g) and 8 aging (11moths-old) SHRs (448.1 ± 26.4 g), after one week ofaccom modation.All animals were housed in a climate-controlledroom (at 21-22°C) with a 12-h light/dark cycle (on 7AM / off 7 PM) in an accredited animal facility. Beforeimplant procedure rats were housed in groups of 2-3rats per cage. Once the implant procedure was performed,the rats were housed individually in polycarbonatecages, in order to prevent cannibalism, on standardbedding. All rats were fed standard rat pellets and tapwater ad libitum.All experiments were performed in compliance withthe French Ministry of Agriculture and Food and DrugAdministration guidelines for animal experimentationand were approved by the local Animal Ethics Committee.Transmitter implantation procedureRadiotelemetry ECG transmitters (TA11 CA-F40;Data Sciences International, St. Paul, MN) were implanted under isoflurane anesthesia (2.0 L/min, 4% in airfor induction and 0.5 L/min, 2.5% in air for maintenance).Prophylactic injections of penicillin G (50,000 IUs.c.) and ketoprofen (2 mg/kg s.c.) were performed oneach animal. Body temperature was maintained at 37°Cthroughout the procedure, using a heating blanket.The skin was incised and the body of the transmitterwas placed in a dorsal subcutaneous pocket and suturedto the underlying tissue under aseptic conditions.Alina Scridon et al.Implant procedure of radiotelemetry devices in ratsThe two ECG leads (bare ends terminating with a smallsilastic drop to avoid tissue damage) were subcutaneouslytunnelized in a lead II configuration. The negativeelectrode was placed under the right clavicle, and thepositive in a latero-basal thoracic position, as illustratedin Figure 1.The quality of the signal and correct morphology ofECG elements were evaluated within the procedure.When the quality of the captured ECG signal was satisfactorythe distal ends of the leads were secured tothe underlying tissue to avoid slipping and the skin layerwas sutured.After the procedure, the rats were allowed to recoverunder a warm light lamp and they were monitored untilthey regained their toe-pinch reflex, approximately10-15 min after the end of the anesthesia, when theywere placed in their cages.All incidents that occurred during the procedure orshortly after were recorded.Post-implant procedure monitoringImmediately after the implant procedure the animalswere housed individually in polycarbonate cages. Theywere weighted daily for at least one week after implantationor until body weight has returned to the initialvalue, measured before the implantation procedure. Asingle standard electronic scale was used for all weightingsthroughout the study. The body weight lost becauseof the surgical procedure and the interval neededfor regaining the lost weight were recorded for all animals.Next, weight loss was compared between the twogroups, as well as the time needed for regaining the lostweight.Figure 1. Device and lead placement. The body of the transmitter is placedin a dorsal subcutaneous pocket and the two ECG leads are tunnelized in alead II configuration.

Alina Scridon et al.Implant procedure of radiotelemetry devices in ratsThe rats were checked once a day for at least oneweek after the implant procedure, and twice a weekthe r e after, for general health, morbidity and mortality.Romanian Journal of CardiologyVol. 22, No. 2, 2012ECG recordingA unique 24-h continuous ECG recording was performedon unrestrained, conscious rats.ECG signal capture was accomplished with receivers(RPC-1; Data Sciences International) placed undereach experimental cage. Telemetry ECGs were convertedto analog signal (Analog ECG Output Adapter R08;Data Sciences International) and routed to a personalcomputer equipped with a signal acquisition card (NIPCIe-6251; National Instruments, Austin, TX). Anacquisition program developed in our laboratory usingLabVIEW 2009 software (National Instruments) allowedthe signal to be continuously recorded with a 2000Hz sampling frequency and stored on hard disk.To ensure that the signal from one transmitter wasnot received and recorded by another receiver, the cageswere placed at least 45 cm apart from each other, asrecommended by the producer.ECG analysisECG data were analyzed using a program recentlydeveloped in our laboratory using LabVIEW 2010software (National Instruments) to automatically detectR waves and measure RR intervals. All ECG tra c-ings were visually assessed and artifactual periods werediscarded prior to analysis. ECG analysis was visuallyperformed by two independent cardiologists. All ECGelements were assessed.Experimental protocolsEmotional stress protocol in conscious ratsA mild emotional stress protocol elicited by meansof a jet of air blown into the cage for 20 min was appliedto each animal. 6,7 Baseline recordings of approximately30 min were performed for each animal before the onsetof the protocol. The quality of the ECG signal wasassessed based on ECG recordings obtained duringstre ss protocol.Subcutaneous injection of carbamylcholine in consciousratsA baseline recording was obtained for each animalbefore a 0.4 mg/kg dose of carbamylcholine was injectedsubcutaneously into all SHRs. A 10-min peri od initiated5 min after carbamylcholine injection was analyzed,and the quality of the ECG signal was asse ssedbased on ECG recordings obtained during this in ter val.Subcutaneous injection of isoprenaline in conscious ratsA baseline recording of at least 30 min was obtainedfor each animal before a 0.5 mg/kg dose of isoprenalinewas injected subcutaneously into 4 of the 8 youngSHRs. Experimental protocol was discontinued after 3of the 4 SHRs having received isoprenaline died shortlyafter drug injection. A 10-min period initiated 5 minafter isoprenaline injection was analyzed and the qualityof the ECG signal was assessed based on ECG recordingsobtained during this interval.Local macroscopic structural assessment atexplantationDevices were kept in place for 4 months in agingSHRs and 8 months respectively in young SHRs. Atthe end of these intervals the devices were explantedand local macroscopic evaluation of the device, the twoleads and surrounding tissues was visually performed.StatisticsAll data are expressed as mean ± SD. Between-groupcomparisons were performed using the Student test forpaired or unpaired determinations, as appropriate. Differenceswithin a group were determined by analysis ofvariance for repeated measures. A p value of less than0.05 was considered statistically significant. Statisticalanalyses were undertaken using GraphPad Prism®software (GraphPad Software; San Diego, CA).RESULTSPost-implant evolutionAt the moment of implant procedures, aging SHRshad higher body weight compared to young SHRs(448.1 ± 26.4 g for aging SHRs vs. 311.5 ± 7.7 g for youngSHRs, p < 0.0001).The day after the procedure mean body weight of youngSHRs decreased by 6.1 ± 1.8 g (from 311.5 ± 7.7 gto 305.4 ± 8.3 g, p = 0.003) (Figure 2). In aging SHRsa mean weight loss of 7.1 ± 6.7 g was observed (from448.1 ± 26.4 g before the procedure to 441.0 ± 23.9 gFigure 2. Body weight evolution in young SHRs. Counting of days startswith day 0 (D0), corresponding with the day of implantation. For D0 bodyweight was determined before the implant procedure.

Romanian Journal of CardiologyVol. 22, No. 2, 2012the day after the procedure, p = 0.03) (Figure 3). Thetwo groups did not present significantly different initialweight losses (6.1 ± 1.8 g for young SHRs vs. 7.1 ± 6.7 gfor aging SHRs, p = 0.59).In young SHRs, the initial weight loss maintaineduntil the sixth day after the procedure (D6) (p < 0.0001compared to pre-procedure weight, repeated-measuresANOVA), but there was no significant differencebetween pre-procedural weight and the weight measuredin the seventh day after the implant procedure (D7)(311.5 ± 7.7 g before the implant procedure vs. 309.5 ±9.3 g in D7, p = 0.78). The tenth day after the procedure(D10) animal’s weights (323.6 ± 10.4 g) exceeded thosemeasured before the implant procedure (p < 0.001)(Figure 2). In four of the 8 young SHRs the maximumweight loss was recorded the day after the procedure(D1), in 3 SHRs the minimum body weight was obtainedin D2, while one rat had a minimum weight in D3.In aging SHRs, the initial weight loss also maintaineduntil the sixth day after the procedure (D6) (p

Alina Scridon et al.Implant procedure of radiotelemetry devices in ratsQuality of the ECG signal during emotional stress inconscious ratsThe emotional stress induced significant increase inheart rate in both groups (from 282 ± 17 bpm to 412 ±28 bpm in young SHRs, p < 0.001, and from 273 ± 26bpm to 363 ± 20 bpm in aging SHRs, p < 0.001).The quality of the ECG signal remained satisfactoryduring emotional stress, all ECG elements being recognizablethroughout the duration of the protocol, despitesinus tachycardia (Figure 6).Quality of the ECG signal after carbamylcholineadministration in conscious ratsThe quality of the ECG signal remained satisfactoryafter carbamylcholine was injected, all ECG elementsbeing recognizable on surface ECG tracings. Soon afterthe drug was injected SHRs presented frequent episodesof atrial tachyarrhythmia (Figure 7).Figure 6. ECG tracing in a SHR during emotional stress protocol. All ECGelements remain easily recognizable, despite sinus tachycardia.Romanian Journal of CardiologyVol. 22, No. 2, 2012Quality of the ECG signal after isoprenalineadministration in conscious ratsIn young SHRs, significant initial increase in heartrate was observed immediately after isoprenaline wasinjected (from 296 ± 24 bpm to 450 ± 5 bpm, p = 0.001).Soon after the drug was injected, all SHRs presentedepisodes of torsades de pointes-like polymorphic ventriculartachycardia (Figure 8A). In three of the four youngSHRs this arrhythmia degenerated into ventricularfibrillation (Figure 8B) and led to the death of theseanimals. In the fourth animal the arrhythmia terminatedspontaneously, with restoration of sinus rhythm.Local changes due to the presence of the deviceAt the moment of explantation all devices were inplace. In one young SHR the negative ECG lead hasslipped approximately 0.5 cm compared to its initialposition. In all other animals the leads remained attheir initial placement. No signs of infection were observedneither in the pocket, at the site of ECG leadsplacement, nor in the subcutaneous tunnels used forECG leads placement. Little and thin adherences werepresent in two aging SHRs and in one young SHR, whileno adherences were noticed in the other animals.DISCUSSIONThe main findings of the present study are that i) hypertensive rats, regarding their age, regained their initialweight within one week after subcutaneous radiotelemetrydevice implantation; ii) the initial weightloss after surgical procedure was similar in young andaging SHRs; iii) subcutaneous radiotelemetry deviceimplantation was associated with small morbidity andno deaths were recorded during or shortly after the-Figure 7. ECG tracing in a SHR after carbamylcholine administration showingfrequent episodes of atrial tachyarrhythmia.Figure 8. ECG tracing in a SHR after isoprenaline administration showing(A) torsades de pointes-like polymorphic ventricular tachycardia which (B)degenerates into ventricular fibrillation.

Romanian Journal of CardiologyVol. 22, No. 2, 2012se procedures; iv) high-quality ECG recordings wereobtained in all animals and all ECG elements were easilyrecognizable on surface ECG in both baseline conditionsand after various experimental protocols; v) radiotelemetrydevices induced small or no local changeseven after long periods of time.Usefulness of radiotelemetry monitoringIt is generally accepted that, with the exception ofstu dies of anesthetic drugs, special interest should begranted to achieving data from conscious, unrestrainedanimals, because such conditions optimally mimicphysiological or pathophysiological conditions and theresults of such measurements have the highest chancesof being correctly extrapolated into humans. An importantissue when performing experimental studies isthe ability to measure various physiological parameterswithout the interference of external stressors such ashandling of animals before or during measurements,which could lead to serious inconsistencies and mightaffect the reproducibility of the method.Although wireless telemetry technology for experimentaluses has existed for more than 60 years 8,9 , thesedevices had become largely used only in the last 20years. Thus, radiotelemetry ECG monitoring is a relativelyinnovative technique, useful for studying pathophysiologicalmechanisms of various cardiovasculardi s e a ses.Compared to non-invasive techniques, radiotelemetrydevice implantation offers the advantages of reducingstress, handling, restraint, anesthesia. 1 Moreover,given that decreased animal stress also diminishes inter-individualvariability 10 , the use of radiotelemetryde vices also allows reducing the number of animalsused in single or multiple studies. 11,12Timecourse of recovery after surgical implantationof radiotelemetry transmittersSpontaneously hypertensive rats are one of the mostfrequently used strains for cardiovascular experimentalstudies, and judging by the number of publications,SHRs are the most studied model of hypertension. 13Since the use of radiotelemetry transmitters becomesmore and more used, there is much interest in knowingthe response of SHRs to implant procedures of such devices.Before planning a long-term study for cardiovascularassessment of SHRs by telemetry monitoring,data regarding the time required for recovery after radiotelemetrytransmitter surgical implantation are needed.Especially since SHRs are known to be prone toincreased morbidity and mortality rates following invasivetechniques and general anesthesia. 4 This is the firstAlina Scridon et al.Implant procedure of radiotelemetry devices in ratsstudy to report the time needed for recovery and thusthe time required prior to recordings onset in SHRs ofdifferent ages, based on body weight evolution. Thisparameter has been previously shown to be one of themost sensitive markers of recovery after surgical procedures.14In consistency with previous studies, 15 aging SHRshad higher baseline body weights compared to youngSHRs. In our study, the weight of rats subjected to surgerydecreased slightly the first day after the procedure,and the weight loss maintained for the next six days,regardless the age of the animals. This could be due tostress induced by anesthesia and subsequent surgery, aspreviously reported. 16,17 Young SHRs had a maximumweight loss within the first 3 days, while for aging SHRsthe maximum weight loss was recorded within the first4 days after the procedure.One week after the implant procedure all animals,regardless their age, regained their initial weights.Thus, we concluded that approximately one week is neededfor SHRs to recover after subcutaneous surgicalimplantation of radiotelemetry devices, regardless theirage. However, young SHRs tended to gain weight morerapidly after the procedure compared to aging SHRs.The tenth day after the implant procedure young SHRsalready started to gain weight, while no such tendencywas observed in aging SHRs and this could be due toflattened weight curve in SHRs with age. 18Morbidity and mortality related to telemetry implantprocedures have been shown to be highly variableaccording to various features of the technique usedfor implantation, 19,20 mainly its invasiveness, but also tothe operator’s experience. In our study, small morbidityand no deaths were recorded during or after these proceduresin either young or aging SHRs. Thus, subcutaneousimplantation of ECG radiotelemetry devices underisoflurane anesthesia appears to be a safe techniquein SHRs, regardless of their age.Telemetry devices were well tolerated, even after longperiods of time. Neither young nor aging SHRs presentedserious local side effects due to the presence ofthe device. Local reactions with formation of adherenceswere rare and discrete. No signs of inflammationor infection were observed at the site of implantation.Thus, these devices seem to be well tolerated, allowinglong-term recordings, with potentially important applicationin long-term pharmacological studies.ECG signal qualityIn our study, ECG signals were sampled at 2000 Hzsampling frequency, giving a high-resolution activity,

Alina Scridon et al.Implant procedure of radiotelemetry devices in ratsand the resolution was of 16-bit. The quality of theacquired signal was very good, except for some brief periodswhen animals presented intense movement. Suchperiods should be discarded prior to analysis, especiallyif heart rate variability, or arrhythmia assessment,are the main purposes of the study. The programs developedin our laboratory for recording and analysis ofECG data allowed easy recognition of all ECG elementsin both baseline and experimental conditions.Determination of heart rate is crucial in most cardiovascularexperimental protocols. Handling of animalsbefore or during experimental protocols is a major sourceof error when assessing this parameter. 1 Radiotelemetrymonitoring allows heart rate, as well as otherparameters, to be recorded in stress-free conditions.Moreover, this technique allows the possibility of longtermmonitoring of such parameters, also allowingmore complex evaluations, like circadian rhythm, whichare not possible with standard external measurementdevices.Heart rate analysis indicated that aging SHRs weremore bradycardic compared to young SHRs. In thisstrain, rise in blood pressure has been shown to beginaround 5-6 weeks of age and systolic pressure may reachvalues between 180 and 200 mmHg in the adult. 21Long-term hypertension appears to force the autonomicnervous system to produce a higher vagal andlower sympathetic tone in order to compensate the increasedblood pressure. This hypothesis is further sustainedby previous studies showing that after the age of4-5 weeks mean arterial pressure presents rapid increase,in association with progressive bradycardia. 22ConclusionsIn our experience, surgery procedures for implantingradiotelemetry ECG devices in SHRs appear tobe safe techniques, with short interval of recovery, lowmorbidity rates and no mortality, regardless the age ofanimals. Subcutaneous implantation of such devicesoffers high-quality ECG signal and is very well tolerated,even if long-term keeping in place is needed.Conflict of interest: none declaredReferences1. Kramer K, Kinter LB. Evaluation and applications of radio telemetryin small laboratory animals. Physiol Genomics, 2003; 13: 197–205.2. Brockway BP, Mills PA, Azar SH. A new method for continuous chronicmeasurement and recording of blood pressure, heart rate and ac-Romanian Journal of CardiologyVol. 22, No. 2, 2012tivity in the rat via radio telemetry. Clin Exp Hypertens A, 1991; 13:885–95.3. Deveney AM, Kjellström Å, Forsberg T, Jackson DM. A pharmacologicalvalidation of radiotelmetry in conscious, freely moving rats. JPharmacol Toxicol Methods, 1998; 40: 87–93.4. Howell SJ, Sear JW, Foëx P. Hypertension, hypertensive heart diseaseand perioperative cardiac risk. Br J Anaest, 2004; 92(4): 570–83.5. Sgoifo A, Stilli D, Medici D, et al. Electrode Positioning for ReliableTelemetry ECG Recordings During Social Stress in UnrestrainedRats. Physiol Behav, 1996; 60(6): 1397–401.6. Burke SL, Head GA. Cardiac and renal baroreflex control duringstress in conscious renovascular hypertensive rabbits: effect of rilmenidine.J Hypertens, 2009; 27(1): 132–41.7. Kanbar R, Oréa V, Barrès C, Julien C. Baroreflex control of renal sympatheticnerve activity during air-jet stress in rats. Am J Physiol RegulIntegr Comp Physiol, 2007; 292(1): R362–7.8. Brockway BP, Hassler CR. Application of radio-telemetry to cardiovascularmeasurements in pharmacology and toxicology. In New Technologiesand Concepts for Reducing Drug Toxicity. Eds: Salem H,Baskin SI. Boca Raton: CRC, 1993, 109–32.9. Kramer K, Kinter L, Brockway BP, et al. The use of radiotelemetry insmall laboratory animals: recent advances. Contemp Top Lab AnimSci, 2001; 40: 8–16.10. Schnell CR, Gerber P. Training and remote monitoring of cardiovascularparameters in non-human primates. Prim Rep, 1997; 49: 61–70.11. van Acker SA, Kramer K, Grimbergen JA, et al. Doxorubicin-inducedcardiotoxicity monitored by ECG in freely moving mice. A new modelto test potential protectors. Cancer Chemother Pharmacol, 1996;38: 95–101.12. Kinter LB. Cardiovascular telemetry and laboratory animals welfare:New reduction and refinement alternatives. In: General Pharmacology/SafetyPharmacology Meeting. Philadelphia, PA: 1996.13. Pinto YM, Paul M, Ganten D. Lessons from rat models of hypertension:from Goldblatt to genetic engineering. Cardiovasc Res, 1998; 39:77–88.14. Greene AN, Clapp SL, Alper RH. Timecourse of recovery after surgicalintraperitoneal implantation of radiotelemetry transmitters inrats. J Pharmacol Toxicol Methods, 2007; 56(2): 218–22.15. Labat C, Cunha RSA, Challande P, Safar ME, Lacolley P. Respectivecontribution of age, mean arterial pressure, and body weight on centralarterial distensibility in SHR. Am J Physiol Heart Circ Physiol,2006; 290(4): H1534–9.16. Kuntz C, Wunsch A, Bay F, et al. Prospective randomized study ofstress and immune response after laparoscopic vs conventional colonicresection. Surg Endosc, 1998; 12(7): 963–7.17. O’Neil PJ, Kaufman LN. Effects of indwelling arterial catheters orphysical restraint on food consumption and growth patterns of rats:Advantages of noninvasive blood pressure measurements techniques.Lab Anim Sci, 1990; 40: 641–3.18. 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Romanian Journal of Cardiology | Vol. 22, No. 2, 2012ORIGINAL ARTICLEParticularităţi clinice şi paraclinice la pacienţii hipertensivi cufeocromocitom – studiu retrospectivV. Chioncel 1 , F. Adam 1 , I. Sinescu 2 , Diana Păun 3 , Crina Sinescu 1Articol primit în data de 08 mai 2012. Articol acceptat la data de 14 mai 2012.Rezumat: Mult timp văzute ca nişte rarităţi, formele de hipertensiune arterială de cauză suprarenală sunt cu siguranţă subdiagnosticateîn multe părţi ale lumii. În cazul pacienţilor hipertensivi cu feocromocitom diagnosticul de certitudine reprezintădeseori o provocare pentru medicul generalist (uneori şi pentru cardiolog), iar evoluţia şi complicaţiile sunt de multe ori dramatice.Lotul studiat de 42 de pacienţi cu feocromocitoame a confirmat în general datele din literatură, atât în privinţa datelordemografice, cât şi a caracteristicilor clinice şi paraclinice. Hipertensiunea arterială a fost elementul central în feocromocitom,existând diferite relaţii între profilul hipertensiv şi nivelele de catecolamine. Indiferent de formă (paroxistică sau permanentă),hipertensiunea arterială a fost direct implicată în apariţia hipertrofiei ventriculare stângi şi a complicaţiilor cardiace și cerebrovasculare.Cuvinte cheie: hipertensiune secundară, feocromocitom, metanefrine, hipertrofie ventriculară.Abstract: Long time seen as some rare forms, hypertension due to adrenal are certainly underdiagnosed in many parts ofthe world. In hypertensive patients with pheochromocytoma accurate diagnosis is often a challenge for general practitioner(and sometimes for cardiologist too) and the evolution and complications are often dramatic. Our group of 42 patients withpheochromocytoma generally confirmed the literature data, in terms of demographic, clinical and laboratory characteristics.Hypertension was the central element in pheochromocytoma, with different relations between hypertensive profile and catecholamineslevels. Regardless of the form (paroxysmal or permanent), hypertension was directly involved in the developmentof left ventricular hypertrophy and cardiac/cerebrovascular complications.Keywords: secondary hypertension, pheochromocytoma, metanephrine, ventricular hypertrophy.INTRODUCEREPacienţii cu hipertensiune arterială secundară de cauzăsuprarenală constituie un grup eterogen, atât prinprezentarea clinică, cât şi prin particularităţile legate deman agement.Feocromocitoamele sunt tumori neuroendocrinede ri vate din ţesutul cromafin (localizate în 90% din cazuri la nivelul medulosuprarenalei), caracterizate prinsecreţie excesivă de catecolamine şi care asociază semneleşi simptomele specifice ale hiperproducţiei catecolaminice.Feocromocitomul este o cauză rară de hipertensiunearterială, prevalenţa lui printre cazurile de hipertensiunefiind de 0,3-1% 1,2 . Cu toate acestea, se asociazăcu prezenţa unor forme severe, deseori maligne, de hipertensiunearterială, cu răspuns incomplet la terapiauzuală.Diagnosticul este deseori dificil, implicând confirmareabiochimică a hiperfuncţiei adrenergice la pacienţiicu index clinic de suspiciune, precum şi evidenţiereatumorii prin investigaţii imagistice. Suspiciuneaclinică de feocromocitom se întemeiază pe triada cefalee-palpitaţii-transpiraţii(Thomas-Roth-Kvale), însoţitădeseori de hipertensiune.Explorarea imagistică (CT sau RMN) are un rolfoarte important, nu doar pentru localizarea tumorii(adrenală sau extraadrenală, unică sau bilaterală), ci şipentru că oferă date utile în cazul suspiciunii de malignitate.Cu toate acestea, nu există criterii clinice, biochimicesau imagistice care să poată face cu acurateţediagnosticul diferenţial dintre feocromocitoamele benigneşi cele maligne, rolul decisiv avându-l examenulhistopatologic.Evoluţia pacientilor cu feocromocitom este dictatăde apariţia complicaţiilor cardiace şi cerebrovasculare,1Spitalul Clinic de Urgenţă „Bagdasar Arseni”, UMF „Carol Davila”Bucureşti2Centrul de Chirurgie Urologică şi Transplant Renal Fundeni, UMF „CarolDavila” Bucureşti3Institutul de Endocrinologie „C. I. Parhon”, UMF „Carol Davila” BucureştiContact address:Dr. Valentin Chioncel, Spitalul Clinic de Urgenţă „Bagdasar Arseni”, UMF„Carol Davila” Bucureşti

V. Chioncel et al.Pheochromocytoma and hypertensiondar şi de prezenţa malignitaţii, mortalitatea în cazulacestora din urmă fiind de peste 80% la 5 ani 3 .Pentru managementul feocromocitomului, rezecţiachirurgicală a tumorii reprezintă pasul decisiv, terapiamedicamentoasă fiind utilă în controlul hipertensiuniişi (cu rezultate neconcludente) la formele maligne.Persistenţa hipertensiunii arteriale severe postoperatorpoate fi explicată prin rezecţia incompletă a tumorii,coexistenţa unei hipertensiunii esenţiale, ligatura accidentalăa arterei renale sau prezenţa formelor extraadrenalesau maligne.OBIECTIVELE STUDIULUIEvaluarea caracteristicilor demografice, clinice şi paracliniceale pacienţilor cu hipertensiune arterială secundarăşi feocromocitom.METODOLOGIELotul studiat a cuprins 42 de pacienţi diagnosticaţi cuhipertensiune arterială secundară şi feocromocitom,ce au fost internaţi consecutiv la Centrul de ChirurgieUrologică şi Transplant Renal Fundeni, în perioada2004-2009, în vederea intervenţiei chirurgicale. Pacienţiiau fost diagnosticaţi la Clinica de Cardiologie aSpitalului „Bagdasar Arseni”, la Institutul „C. C. Iliescu”şi Institutul de Endocrinologie „C. I. Parhon”.Studiul a fost retrospectiv, observaţional, incluzândpacienţi diagnosticaţi cu feocromocitom pe baza determinărilorbiologice ale excesului de metanefrine(sanguine sau urinare) şi investigaţiilor imagistice (CT,RMN, scintigrafie MIBG).Protocolul de evaluare iniţială a inclus examenul clinic,electrocardiograma, Holter TA, ecografie cardiacăşi determinări seriate ale metanefrinelor plasmatice sauurinare. Măsurătorile ecocardiografice au inclus fracţiade ejecţie a ventriculului stâng (FEVS) şi parametriireprezentativi pentru hipertrofie ventriculară: indexulde masă ventriculară (IMVS) şi îngroşarea relativă apereţilor ventriculari (RWT). S-au folosit metodele decalcul cunoscute: IMVS (M-mod)= ((1.05 x [(DTD +PP + SIV)3 - DTD3] - 13.6))/m 2 , valori normale 91±20g/m 2 , iar RWT (M-mod)= [(PP + SIV) /2]/ DTD, valorinormale 0.33 - 0.44 (4).Determinarea plasmatică şi urinară a catecolaminelorşi a metaboliţilor s-a efectuat în laboratorul SpitaluluiFundeni, laboratorul Institutului „C. I. Parhon” sau2 laboratoare private, certificate ISO.S-a folosit metoda ELISA de tip competitiv pentrudeterminarea metanefrinelor plasmatice, respectiv cromatografiede lichide sub înaltă presiune pentru doza-Romanian Journal of CardiologyVol. 22, No. 2, 2012rea metanefrinelor urinare sau metoda cromatograficăspectrofotometricăpentru acidul vanilmandelic urinar.Sugestive pentru diagnosticul de feocromocitom aufost valorile situate de cel puţin 4 ori peste limita superioarăa normalului.Postoperator pacienţii au fost evaluaţi la 2 săptămâni,6 luni şi 1 an, prin examen clinic si electrocardiografie.La 2 săptămâni şi 1 an după operaţie au fost repetatedeterminările metanefrinelor, iar ecografia cardiacă afost repetată la 6 luni.Bolnavii au fost urmăriţi pe o perioadă de timp cuprinsăîntre 26 luni şi 6 ani, cu o valoare medie de 4,1ani. S-au pierdut din evidenţă doi pacienţi care nu aumai revenit la controalele recomandate.RezultateÎn perioada menţionată pentru înrolarea pacienţilor,populaţia studiată a reprezentat o proporţie de ~1 la150 de intervenţii din patologia chirurgicală a Centrulde Chirurgie Urologică şi Transplant Renal Fundeni.Din punct de vedere demografic, vârsta medie înlo tul de studiu a fost de 43,4 ani, iar raportul femei/băr baţi a fost de 1,62:1 (26 femei şi 16 bărbaţi), predominenţasexului feminin păstrându-se şi la analiza lotuluipe grupe de vârstă, exceptând decadele extremede vârstă.Analiza lotului pe grupe de vârstă a evidenţiat o distribuţiemai densă a pacienţilor între 31 şi 50 ani (Figura1). Vârsta la care s-a pus diagnosticul a fost cuprinsăîntre 14 şi 65 ani, cu o vârstă medie 43,1 ani; diagnosticuls-a pus mai devreme în cazul sexului feminin decâtîn cazul sexului masculin, fără ca diferenţa să fie semnificativăstatistic.Tabelul 1. Sensibilitatea şi specificitatea testelor biochimiceTest Sensibilitate SpecificitateMetanefrine plasmatice 99% 89%Metanefrine urinare fracţionate 97% 69%Catecolamine plasmatice 84% 81%Catecolamine urinare 86% 88%Acid vanilmandelic urinar 64% 95%Figura 1. Repartiţia pe grupe de vârstă a feocromocitoamelor.

Romanian Journal of CardiologyVol. 22, No. 2, 2012V. Chioncel et al.Pheochromocytoma and hypertensionTabelul 2. Semne şi simptome întâlnite la pacienţii cu feocromocitomSemne/simptomeFrecvenţa apariţieiHipertensiune arterială 100%Cefalee 100%Transpiraţii 97,6%Palpitaţii 95,2%Tremor 61,9%Anxietate 59,5%Dureri abdominale, greaţă 47,6%Scădere ponderală 42,8%Din punct de vedere al prezentării clinice, pacienţiidin lotul studiat au avut o diversitate de semne şi simptome(Tabelul 2).Formele clinice de manifestare ale HTA întâlniteîn lotul studiat au fost: forma permanentă (cu valorimari sistolice, dar şi diastolice) (47,6%), şi variantelecu salturi paroxistice simptomatice, cu răspuns dificilla tratament, suprapuse pe un fond de HTA susţinută(40,5%) sau paroxisme ale TA la pacienţi normotensiviîn afara acceselor (11,9%); nu am luat în calcul formacu normotensiune/hipotensiune ortostatică (mai rarîn tâl nită), având în vedere scopul studiului, cantonat însfe ra hipertensiunii.Doi pacienţi au prezentat neoplazie endocrină multiplă– sindromul MEN 2A, care include, pe lângă feocromocitom,carcinom medular tiroidian şi hiperparatiroidism.Aceştia au prezentat, pe lângă semnelespecifice feocromocitomului, şi manifestări secundarehipotiroidiei şi hipercalcemiei.Diagnosticul de feocromocitom s-a pus combinândsuspiciunea clinică cu probele biologice specifice şi explorărileimagistice concludente (formaţiuni adrenale/extraadrenale).Testele biologice utilizate cel mai frecvent au fostmetanefrinele plasmatice fracţionate, metanefrine urinare/24ore, catecolamine plasmatice şi acidul vanilmandelicsanguin; mai rar s-a lucrat Cromogranin A (2cazuri), iar într-un caz s-a efectuat testul de provocarela Clonidină.Au fost determinate metanefrinele plasmatice la 37de pacienţi, metanefrinele urinare fracţionate/24 de orela 16 bolnavi, acidul vanilmandelic urinar la 8 pacienţi,iar catecolaminele plasmatice la 4 cazuri.Valorile obţinute au fost următoarele (Tabelul 3):Pentru confirmarea imagistică a feocromocitomului,31 dintre cei 42 de pacienţi au făcut tomografie computerizată,iar 14 au fost examinaţi prin rezonantă magneticănucleară. Chiar dacă ambele investigaţii imagisticeau sensibilitate crescută (5) pentru detectarea tumorilorsecretante de catecolamine, folosirea uneia sau celeilalteexplorări a fost influenţată, în general, de disponibilitateaşi de experienţa locală a centrului. Iniţialexplorarea imagistică s-a focalizat pe abdomen şi pelvis,iar în cazul nedetectării unei mase tumorale la acestnivel (atunci când indexul de suspiciune a fost înalt),investigaţia a urmărit structurile toracice şi cervicale.În două cazuri localizarea extraadrenală a feocromocitomului(paragangliomului) s-a făcut prin scintigrafiecu I 123 -MIBG (efectuată în afara ţării), ce a identificattumori cromafine în mediastin şi la nivelul gâtului. Nus-au putut efectua (datorită lipsei disponibilităţii) alteinvestigaţii imagistice de tip PET sau Octreoscan.În 5 cazuri am găsit feocromocitoame bilaterale, înanaliză luându-se tumora cu cele mai mari dimensiunidintre cele două.Dintre cei 21 de pacienţi, 5 au prezentat forme extraadrenalede feocromocitom (paragangliom), cu localizarela nivelul vezicii urinare (2 pacienţi), gâtului (2pacienţi) sau mediastin (un pacient).Vechimea hipertensiunii arteriale în momentul diagnosticuluia fost în medie de 2,77 ani, cu variaţii mariîn funcţie de grupul de vârstă: 1,2 ani la grupul celorsub 40 de ani, 3,22 ani la cei între 40-60 de ani şi respectivde 6,5 ani la pacienţii peste 60 de ani.La cei cu hipertensiune arterială permanentă, amobservat nivele crescute predominant ale normetanefrineiplasmatice/urinare, în schimb, la pacienţii cu paroxismeale tensiunii arteriale am găsit – în proporţiisimilare – concentraţii crescute atât ale metanefrinei/epinefrinei (plasmatice/urinare), cât şi ale normetanefrinei/norepinefrinei.În 6 cazuri am dozat metanefrinele plasmatice fracţionateîn afara şi în timpul crizei de feocromocitom şiam observat nivele crescute în medie cu 68% faţă devalorile bazale (Figura 2).La pacienţii urmariţi a fost studiată relaţia dintre severitateahipertensiunii (exprimată prin valorile tensi-Tabelul 3. Valori medii ale metanefrinelor plasmatice şi urinareTestMetanefrina plasmaticăNormetanefrina plasmaticăMetanefrina urinarăNormetanefrina urinarăValorile medii±SD(min-max)1348 ± 347 Pg/ml(419-3804 pg/ml)2455 ± 648 Pg/ml(895-5243 pg/ml)2132 ± 462 Μg/24ore (1286-3893μg/24 ore)3452 ± 853 Μg/24ore (2235-4956μg/24 ore)Valori normale5-90 Pg/ml10-180 Pg/ml

V. Chioncel et al.Pheochromocytoma and hypertensionunii arteriale medii şi ale tensiunii arteriale sistolice) şihiperfuncţia adrenergică, însă nu am gasit nicio corelaţieîntre nivelul catecolaminelor/metanefrinelor plasmaticeşi valorile TA (Figura 3).De altfel, datorită expunerii prelungite a receptoriloradrenergici la catecolamine, apare o desensibilizare aacestor receptori şi – ca urmare – răspunsul tisular lacatecolamine e inconstant, iar reacţia hipertensivă nuva fi proportională cu concentraţia hormonală 6 .Toţi pacienţii au făcut electrocardiograme, iar 39dintre ei au efectuat cel puţin o ecografie cardiacă.Prezenţa hipertrofiei ventriculare stângi a fost detectatăelectrocardiografic într-un procent de 38,1%,16 dintre cei 42 de bolnavi prezentând criterii electricede hipertrofie după scorul Romhilt Estes (cel puţin 4puncte).La ecocardiografie, 14 dintre cei 39 pacienţi examinaţi(35,89%) prezentau criterii de hipertrofie ventricularăstângă (Index masă VS >111 g/m 2 şi RWT >0.44).Pentru întreg lotul de studiu, valoarea medie a IMVS afost de 116 g/m 2 , iar RWT a fost de 0,4. În grupul pacienţilorcu hipertrofie ventriculară, IMVS a fost 183 g/m 2 , iar RWT a fost 0,51.Am observat o asociere între nivelele crescute denormetanefrine plasmatice şi prezenţa hipertrofiei ventriculare,atât electrică, cât şi cea definită prin criteriileRomanian Journal of CardiologyVol. 22, No. 2, 2012ecografice (Figura 4 şi 5). Nu acelaşi lucru se poate spuneşi despre metanefrine, nivelul acestora fiind similarla pacienţii cu hipertrofie şi la cei fără hipertrofie ventriculară.Dintre cei 14 pacienţi cu hipertrofie ventriculară, 2pacienţi aveau disfuncţie sistolică de ventricul stâng,reversibilă la evaluarea ecocardiografică efectuată după7 zile. În acest caz, descărcarea excesivă de catecolaminepe un cord neadaptat prin hipertrofie poate constituiexplicaţia cea mai probabilă pentru reversibilitatearapidă a funcţiei sistolice a ventriculului stâng .Nu a fost găsit niciun caz de hipertrofie apicală deventricul stâng, toţi cei 5 pacienţi prezentând hipertrofieconcentrică ventriculară.DISCUŢIIDeşi feocromocitomul reprezintă o patologie rară, primulpas cu adevărat important este să luăm în considerareaceastă tumoră atunci când ne gândim la o posibilăcauză de hipertensiune arterială secundară.Confirmarea diagnosticului necesită dovada biochimicăa unei producţii exagerate de catecolamine.Determinarea nivelului catecolaminelor urinare a fostmult timp testul cel mai utilizat, însă, datorită acurateţiiscăzute a acestei metode, în prezent, măsurarea în urinăFigura 2. Valori medii ale normetanefrinei plasmatice în criza de feocromocitomFigura 4. Metanefrine şi normetanefrine plasmatice în relaţie cu HVS electricFigura 3. Lipsa de relaţie între nivelul metanefrinelor serice şi valorile TAFigura 5. Metanefrine şi normetanefrine plasmatice în relaţie cu HVS ecografic

Romanian Journal of CardiologyVol. 22, No. 2, 2012CONCLUZIIÎn ceea ce priveşte ţara noastră, probabil că feocromocitomuleste în continuare subdiagnosticat, patologiasuprarenală fiind mai dificil de dovedit atunci când seexplorează un nou caz de hipertensiune arterială. Cauzelear putea fi atât testele specifice de diagnostic biochimic(metanefrinele plasmatice sau urinare), care nusunt încă larg accesibile, dar şi explorările imagistice:lipsa investigaţiilor de tip metabolic pentru localizareatumorilor extraadrenale, multiple sau metastazelor(MIBG, PET) şi poate, în unele centre, disponibilitateamai restrânsă chiar a investigaţiilor imagistice standardpentru feocromocitom: tomografia computerizată saurezonanţa magnetică nucleară. Deasemenea, probabilcă evaluarea riscului de transmitere ereditară sau demalignitate este incompletă, atâta vreme cât nu suntlarg disponibile testele genetice pentru depistarea eventualelormutaţii la nivelul celor 5 gene discutate.Observăm multe asemănări în privinţa profiluluiclinic şi a datelor paraclinice ale pacienţilor cu feocromocitoamedin lotul studiat faţă de cazurile descrise înliteratură; diferenţele provin poate din disponibilitateamai largă a metodelor de diagnostic biochimic şi imagistic,permiţând astfel o identificare mai precisă a pacienţilorşi o adresare mai rapidă către chirurgie.Limita principală a studiului este reprezentată denu mărul relativ mic de pacienţi, nepermiţând astfel oprelucrare statistică completă. De altfel, multe dintrestu dii le de referinţă privind această patologie au inclusloturi cu dimensiuni cuprinse între 19 şi 439 pacienţi1,27-30 .Studiul a fost retrospectiv şi datele colectate au reprodusinformaţiile înregistrate în documentele medisauîn sânge a metaboliţilor catecolaminici reprezintămetodele recomandate pentru diagnosticul feocromocitomului7 . Conform cu datele din literatură, secreţiaexcesivă de norepinefrină determină de obicei hipertensiunearterială permanentă 8,9 , pe când în formele cusalturi hipertensive paroxistice decelăm concentraţiicrescute atât de norepinefrină, cât şi de epinefrină 10 .Opinia experţilor sugerează că investigaţiile imagisticepentru localizarea feocromocitomului trebuieiniţiate doar după ce există dovezi clinice ale prezenţeitumorii suprarenale.După localizarea tumorii (adrenale/extraadrenale),este necesară deseori continuarea investigaţiilor pentruprecizarea caracterului malign sau ereditar al feocromo citomului. Dacă pentru stabilirea malignitaţii,exa menul histopatologic este decisiv, evidenţierea carac terului ereditar necesită teste genetice specifice.Feo cro mocitoamele ereditare pot fi cauzate de mutaţiila nivelul a 5 gene dovedite până acum ca fiind implicatein apariţia tumorilor cromafine: RET, VHL, NF1,SDHB, SDHD, iar predispoziţia ereditară pentru feocromocitomeste de 20-30%. Cu toate acestea, experţiinu recomandă o testare genetică de tip screening lapacienţii cu tumori cromafine (măsura fiind vazută cafiind non-cost-eficientă).Explorarea funcţiei cardiace (ECG, ecografie, HolterTA) este obligatorie la toţi pacienţii cu feocromocitom,prezenţa hipertensiunii arteriale greu controlabile determinânddeseori hipertrofie ventriculară stângă (vizibilăelectrocardiografic sau ecografic).Din punct de vedere demografic, eşantionul studiat aavut un procent mai mic de bărbaţi, în contrast cu dateledin literatură, care descriu distribuţie egală între celedoua sexe 1,2 . Datele statistice raportate în literatură auarătat şi că feocromocitoamele pot apărea practic la oricevârstă, dar că sunt mai frecvente (ca şi carcinoamelecorticosuprarenale) în decadele 4 şi 5 de vârstă 11-14 .Relaţia între profilul hipertensiunii şi nivelele decatecolamine este deasemenea similară cu observaţiileraportate în diverse lucrări 15,16 , ca şi decelarea unorconcentraţii catecolaminice crescute în timpul crizei defeocromocitom 10 .Prevalenţa hipertrofiei ventriculare stângi în lotulstudiat este similară datelor din celelalte studii, hipertrofiaelectrică fiind descrisă în 27-36% din cazuri, pecând criteriile ecografice au fost prezente în 25-41%dintre pacienţii cu feocromocitom 17-19 .Pacienţii cu normetanefrine plasmatice crescuteprezintă mai frecvent hipertensiune arterială permanentă,această asociere fiind unul din motivele care ex-V. Chioncel et al.Pheochromocytoma and hypertensionplică prezenţa mai frecventă a hipertrofiei ventricularela aceşti pacienţi.De asemenea, literatura descrie suficiente cazuri depacienţi cu feocromocitom la care au fost observatemodificări ecografice în timpul descărcărilor catecolaminice,reversibile ulterior 20-23 ; sunt menţionate deasemeneaşi cazuri de cardiomiopatie TakoTsubo la pacienţicu feocromocitom 24,25 sau – mai recent – un caz decardiomiopatie TakoTsubo inversată 26 .Prezenţa malignităţii modifică sever prognosticulpacienţilor: dacă la feocromocitoamele benigne profilulde risc este legat de parametri clinico-biologici (cahipertrofia ventriculară, nivelul tensiunii arteriale saual catecolaminelor), la formele maligne prognosticulvital este legat de numărul, localizarea şi dimensiunilemetastazelor.

V. Chioncel et al.Pheochromocytoma and hypertensioncale ale pacienţilor, fără a exista posibilitatea verificăriiacurateţii acestora.Tensiunea arterială sistolică (parametru vital şi carea permis diagnosticarea acestor pacienţi) este o dată cumare variabilitate biologică, dar este şi legată de tehnicade măsurare; nu a existat însă un protocol standardizatde măsurare a sa în criza de feocromocitom.O altă limitare a studiului ţine de explorarea incompletăa unor bolnavi, motivul principal fiind legat delipsa de complianţă a unor pacienţi în respectarea controalelorrecomandate.În ciuda limitelor prezentate, lotul celor 42 de pacienţiconsecutivi urmăriţi în studiul nostru constituie,probabil, un eşantion util în evaluarea patologiei tumorilorcromafine din ţara noastră.Conflicte de interese: niciunul.Bibliografie1. Anderson, G.H., Jr., Blakeman, N., and Streeten, D.H. (1994) TheEffect of Age on Prevalence of Secondary Forms of Hypertension in429 Consecutively Referred Patients. 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New York:McGraw-Hill; 947–963; 1983.Romanian Journal of CardiologyVol. 22, No. 2, 201212. Loh KC et al. Phaeochromocytoma: a ten year survey. Q J Med1997;90:51;13. Stenstrom G, Svardsudd K. Pheochromocytoma in Sweden 1958-1981. An analysis of the National Cancer Registry Data. Acta MedScand. 1986;220(3):225-32.14. Walther MM, Keiser HR, Linehan WM Pheochromocytoma: evaluation,diagnosis, and treatment. 1999 World J Urol 17:35–3915. Smythe GA, Edwards G, Graham P, Lazarus L 1992 Biochemicaldiagnosis of pheochromocytoma by simultaneous measurement ofurinary excretion of epinephrine and norepinephrine. Clin Chem38:486–49216. Bravo, E.L. and Tagle, R. (2003) Pheochromocytoma: State-of-the-Artand Future Prospects Endocr Rev 24: 539–553.Genest J, Kuchel O,Cantin M, eds. Hypertension: physiopathology and treatment - Pheochromocytoma.,2nd Ed. New York: McGraw-Hill; 947–963; 1983.17. Stein PP, Black HR.A simplified diagnostic approach to pheocromocytoma.A review of the literature and report of one institution’s experience.Medicine (Baltimore) 1991;70:46-66.18. Shub C, Cueto-Garcia L, Sheps S, Ilstrup DM, Tajik A. Echocardiographicfindings in pheochromocytoma. Am J Cardiol 1986;57:971-5;19. Jae-Hyeong Park,Kyu Seop Kim, Ji-Young Sul, Sung Kyun Shin, HwanLee, MD, Si Wan Choi, Jin-Ok Jeong, In-Prevalence and Patterns ofLeft Ventricular Dysfunction in Patients with Pheochromocytoma JCardiovasc Ultrasound 2011; 19(2): 76-8220. Yamanaka O, Yasumasa F, Nakamura T, Ohno A, Endo Y, YoshimiK, Miura K, Yamaguchi H. “Myocardial stunning”-like phenomenonduring a crisis of pheochromocytoma. Jpn Circ J 1994;58:737-42.21. Shaw TR, Rafferty P, Tait GW. Transient shock and myocardial impairmentcaused by phaeochromocytoma crisis. Br Heart J 1987;57:194-8.22. Schuiki ER, Jenni R, Amann FW, Ziegler WH. 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Inverted-Tako -tsubo pattern cardiomyopathy secondary to pheochromocytoma: aclinical case and literature review. Clin Cardiol 2010;33:200-527. Schiavi F, Boedeker CC, Bausch B, Peçzkowska M, Gomez CF, StrassburgT, Pawlu C, Buchta M, Salzmann M, Hoffmann MM, Berlis A,Brink I, Cybulla M, Muresan M, Walter MA, European-AmericanParaganglioma Study Group Predictors and prevalence of paragangliomasyndrome associated with mutations of the SDHC gene. JAMA.2005;294(16):2057.28. Stenstrom G, Svardsudd K 1986 Pheochromocytoma in Sweden1958–1981. An analysis of the National Cancer Registry data. ActaMed Scand 220:225–23229. Bhansali, Anil; Behera, Arunanshu; Singh, Shravan Kumar; Menon,Anil Shankar; Khandelwal, Niranjan; Das Radotra, Bishan Pheochromocytoma:A Study of 95 Patients Endocrinologist: January/February2009 - Volume 19 - Issue 1 - pp 19-2330. Melicow MM. 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Romanian Journal of Cardiology | Vol. 22, No. 2, 2012ORIGINAL ARTICLEPredictive factors for atrial fibrillation appearance in dilatedcardiomyopathyC. Matei 1,2 , Ioana Pop 3 , Mihaela Badea 4 , Adriana Saraolu 1 , I. M. Coman 1,2 , E. Apetrei 1,2Article received on May 21 st 2012. Article accepted on May 31 st 2012.Abstract: Supraventricular arrhythmias are common in patients with dilated cardiomyopathy. Among them, atrial fibrillation(AF) plays an important role, especially in terms of negative hemodynamic consequences and embolic risk. Aim – To identifypredictive factors of AF presence in patients with dilated cardiomyopathy and to quantify their predictive power. Secondary,these factors have been pursued with the overall risk of death and how the presence of AF influences the long term evolutionof these patients. Materials and methods – The retrospective study included 348 patients diagnosed with dilated cardiomyopathy,in sinus rhythm, divided according to etiology in subgroup A – non-ischemic etiology – and subgroup B – ischemicetiology –. Patients were followed clinically, ECG, echocardiography for a mean of 60.1 months (4-126 months). Statisticalanalysis was performed using EpiInfo 6.0, EpiInfo 3.5.1 (CDC Atlanta, USA) and MedCalc 12.2.1.0 (Medcalc Software BVBA,Belgium). Results – During follow-up, AF was identified in subgroup A and subgroup B as paroxystic AF in 7% and 5% respectively,and permanent AF in 12% and 10% respectively of patients. Univariate and multivariate analysis (Cox) showed a goodprediction of paroxysmal AF for 2 parameters in univariate analysis: left ventricular end diastolic diameter (HR = 2.7, p 63mm and presence of mitral regurgitation, whilepermanent AF was associated with heart failure NYHA class, LA diameter and presence of mitral regurgitation. With a highenough prevalence, AF is a condition that can contribute to lower quality of life and heart failure worsening. Overall mortality,on the other hand, was not significantly influenced by the presence of AF.Keywords: atrial fibrillation, dilated cardiomyopathy, heart failureRezumat: Tulburările de ritm supraventriculare sunt frecvent întâlnite la pacienţii cu cardiomiopatie dilatativă. Între acestea,fibrilaţia atrială (AF) joacă un rol important, mai ales prin prisma consecinţelor hemodinamice negative şi a riscului embolic.Scopul lucrării – Identificarea factorilor de predicţie privind apariţia AF la pacienţii cu cardiomiopatie dilatativă şi cuantificareaputerii de predicţie a acestora. Secundar au fost urmărite corelarea acestor factori cu riscul global de mortalitate şi modulîn care prezenţa AF influenţează evoluţia pe termen lung a acestor pacienţi. Material şi metodă – Studiul retrospectiv a inclus348 de pacienţi diagnosticaţi cu cardiomiopatie dilatativă, în ritm sinusal, împărţiţi în funcţie de etiologie în lotul A – etiologienon-ischemică – şi lotul B – etiologie ischemică –. Pacienţii au fost urmăriţi clinic, ECG, ecocardiografic pe o perioadă mediede 60,1 luni (4–126 luni). Analiza statistică s-a făcut cu EpiInfo 6.0 şi EpiInfo 3.5.1 (CDC Atlanta, SUA) şi MedCalc 12.2.1.0(Medcalc Software BVBA, Belgia). Rezultate – Pe perioada urmăririi, AF a fost identificată în lotul A şi în lotul B sub formă deAF paroxistică la 7%, respectiv 5%, iar ca AF permanentă la 12%, respectiv 10%, din pacienţi. Analiza univariată şi multivariată(Cox) a arătat o predicţie bună pentru apariţia AF paroxistice a 2 parametri în analiza univariată: diametrul telediastolic alventriculului stâng (HR= 2,7, p

C. Matei et al.Atrial fibrillation predictors in DCMRomanian Journal of CardiologyVol. 22, No. 2, 20121,74, p 63mm,diametrul telesistolic VS> 47mm, diametrul AS> 41 mm au avut sensibilitate crescută (peste 70%, semnificativă statistic doarpentru diametrul AS în relaţie cu instalareaA F permanente). Concluzii – Studiul a identificat ca factori de predicţie în apariţiaAF paroxistice un diametru telediastolic VS >63mm şi prezenţa regurgitării mitrale, în timp ce apariţia AF permanente s-acorelat cu clasa de insuficienţă cardiacă, diametrul AS şi prezenţa regurgitării mitrale. AF reprezintă una din condiţiile ce potcontribui la scăderea calităţii vieţii prin agravarea fenomenelor de insuficienţă cardiacă. Mortalitatea globală, pe de altă parte,nu a fost semnificativ influenţată de prezenţa AF.Cuvinte-cheie: fibrilaţie atrială, cardiomiopatie dilatativă, insuficienţă cardiacăIntroductionIdiopathic dilated cardiomyopathy (DCM) is a myocardialdisease characterized by the dilatation of theleft ventricle or biventricular dilatation, combined withthe decrease of myocardial contractility in the absenceof abnormal filling conditions (valve diseases, systemicarterial hypertension) or coronary heart disease to causedecrease of the global systolic function. In the pastfew years more evidences have been presented supportingthe implication of an autoimmune process (bothhumoral and cellular) in the pathogenesis of dilatedcardiomyopathy 1 . Most of the patients are diagnosedbetween the ages of 20 and 50 years, but the disease canalso manifest in children and elders.The most common first clinical manifestation of idiopathicdilated cardiomyopathy is heart failure (HF),which develops in 75-85% of the patients. Just certaincategories of patients present arrhythmias with a highprevalence. They mark a negative prognostic, thus evokingthe special importance of determining some predictionfactors for the onset of such arrhythmias. Theliterature gives special attention to ventricular arrhythmias,which can lead to one of the two death mechanismsin DCM, sudden death. Less studied, supraventriculararrhythmias contribute to hemodynamic deterioration,frequently modifying the functional statusand the patient quality of life.Among supraventricular arrhythmias, atrial fibrillation(AF) is the most common in dilated cardiomyopathyassociated with heart failure. Loss of the atrialcontraction contribution to ventricular filling, rapidventricular rate and the increased risk of embolism arejust some of the negative effects of atrial fibrillation onsetin patients with DCM.The prevalence of atrial fibrillation in DCM increasesproportionally with heart failure class as definedby the New York Heart Association (NYHA). The riskof AF increases as the global ejection fraction (EF) decreases.Thus, the presence of congestive heart failureis one of the most important independent predictivefactors for AF, with a 6-fold increase of the relative risk.On the other hand, atrial fibrillation can significantlyaggravate congestive heart failure symptoms in patientswho were in a compensated stage of the disease whenAF occurred, being one of the most important causesfor decompensated heart failure.It is also known that patients having AF with highventricular rate can develop ventricular dilatation anddecrease of the systolic function (the so-called tachyarrhythmiccardiomyopathy), so it is sometimes difficultto establish whether the atrial fibrillation occurred inthe evolution of the DCM, or it is one of its causes.Even patients with recurrent AF episodes can developin time such tachy-cardiomyopathies, which can disappearonce the arrhythmia has been eliminated. R-to-Rinterval irregularity can also participate in the developmentof ventricular dysfunction 2 .Finding some prediction factors for the onset of AFin patients diagnosed with DCM can be useful to improvethe prognosis, generally reserved, of these patients.ObjectivesThe main objective of the study was to identify somepredictors for the onset of AF in patients with DCMand quantify their predictive power. As secondary objectiveswe correlate these factors with the overall riskmortality and the relationship between presence of AFand the long term evolution of these patients.Materials and methodsThe patients included in our study were selected fromthe electronic database of the “Prof. Dr. C.C. Iliescu”Emergency Institute for Cardiovascular Diseases,

Romanian Journal of CardiologyVol. 22, No. 2, 2012Bucharest between January 2003 and December 2007using search criteria “dilated cardiomyopathy” as dischargediagnosis. From the 562 patients found, onlypatients in sinus rhythm and without pacemaker implantationat the time of the diagnosis, or at the firstevaluation, were selected for our study. Three hundredforty-eight patients (85.6% men, 14.4% women) withages between 18 and 83 (mean age 54.9±12.8) wereidentified in the database and formed the study group.Considering the etiology of DCM the patients weredivided in subgroup A - 186 patients with non-ischemicDCM and subgroup B - 162 patients with ischemicDCM. The ischemic etiology was accepted based on themyocardial infarction history or on objective evidenceof coronary artery disease (CAD) at angiography in patientswith LV systolic dysfunction 3,4 . It is important tomention that in subgroup A the most frequent etiologywas idiopathic cardiomyopathy (58%), followed by alcoholiccardiomyopathy (26%), whilst the remaining16% were determined by other etiologies.Data regarding clinical parameters (NYHA class, 6minutes walking test), the presence of cardiovascularrisk factors (arterial hypertension, diabetes, smoking,dyslipidemia), ECG parameters (QRS duration, presenceof conduction abnormalities), 24h ambulatoryECG readings (the number, frequency and systematizationdegree of supraventricular events), echocardiographydata (LV ejection fraction, LV and LA dimensions,presence of mitral and/or aortic regurgitation, thepresence and degree of the LV diastolic dysfunction), aswell as the treatment used (drugs classes) were recordedfor the study group patients at inclusion.C. Matei et al.Atrial fibrillation predictors in DCMThe patients were followed for a mean period of 60.1months (4-126 months). Their final status and followupduration were decided by two factors: 1) hospital/ambulatory visit for clinical check-up or admission or2) interrogation of the Romanian National Health InsuranceHouse Integrated Information System (SIUI)available online at http://siui.casan.ro:82/Asigurati/(for those who were not registered in the Institute electronicdatabase for more than 12 months). For the lastcategory of patients, it was decided that in case of deaththe date would be approximated at 3 months after theirlast presence in the Institute (thus obtaining informationin 139 of the total 158 deaths). In case the patientwas not dead, the follow-up period would be consideredup to December 2011 (date of the last reported databefore the SIUI interrogation). Data collection and thestatistic analysis were made taking into account theconfidentiality rules.When available, the same data recorded at inclusionwere captured at follow-up. The atrial fibrillation history(clinically documented and confirmed by a 12 leadsECG) was also noted. The patients were divided accordingto the European Society of Cardiology recommendationsfor the management of atrial fibrillation intwo categories (paroxistical / permanent). “Persistent”atrial fibrillation could not be identified in the studiedpatients due to the lack of information about the lengthof the paroxistical episodes not converted to sinusrhythm during admission.Statistical analysis was done using EpiInfo 6.0 andEpiInfo 3.5.1 (CDC, Atlanta, 2008) and MedCalc12.2.1.0 (Medcalc Software BVBA, Belgium). Continu-Table 1. Clinical characteristics of the patientsCharacteristicStudy group(n=348)Subgroup A(n=186)Subgroup B(n=162)Sex (M:F) 6:1 4,2:1 10,6:1

C. Matei et al.Atrial fibrillation predictors in DCMRomanian Journal of CardiologyVol. 22, No. 2, 2012Table 2. Laboratory parameters and therapeutic classes used for treatmentCharacteristicStudy group(n=348)Subgroup A(n=186)Subgroup B(n=162)Anemia (Hgb

Romanian Journal of CardiologyVol. 22, No. 2, 2012C. Matei et al.Atrial fibrillation predictors in DCMTable 4. Echocardiographic characteristics (mean +/-SD)CharacteristicStudy group(n= 348)Subgroup A(n= 186)Subgroup B(n= 162)LVEF (%) 30,6 ± 7,8 29,5 ± 8,1 31,8 ± 7,3 < 0,01LVEDD (mm) 67,6 ± 7,8 68,1 ± 8,2 67,1 ± 7,4 nsLVESD (mm) 55,6 ± 8,4 56,7 ± 9,0 54,4 ± 7,6 nsLA diameter (mm) 46,8 ± 7,4 47,2 ± 8,0 46,4 ± 6,6 nsPulmonary systolic pressure (mmHg) 46,1 ± 14,6 44,5 ± 14,7 48,7 ± 14,1 nsLVEF - Left ventricular ejection fraction, LVEDD - Left ventricular end-diastolic diameter, LVESD - Left ventricular end-systolic diameter, LA - left atrium (antero-posterior diameter).pble 5). As a general observation, we note that the NPVwere very good for all the parameters taken into consideration,whereas the PPV were low. The best value(PPV= 33%) - statistically significant (p35%, the presence of a more than moderatemitral regurgitation or pulmonary artery systolic pressure(PAsP) > 60mmHg had a high specificity (over70%, statistically significant only for the presence of anytype of fibrillation), whereas QRS duration 63 mm, LVESD > 47 mm or LA diameter> 41 mm had high sensitivity (statistically significantonly for the LA diameter, in relation to the presence ofpermanent AF).The univariate and multivariate analysis (Table 6)revealed a good prediction for paroxystic AF onset,realized by 2 parameters in the univariate analysis:LVEDD (HR= 2.7, 95% CI 1.02–7.11, p< 0.05) and thepresence of mitral regurgitation (HR= 2.7, 95% CI=1.02–7.11, p< 0.05); the predictive power was better incase of presence of grade 3 mitral regurgitation (HR=3.78, 95% CI= 1.27–11.28, p

C. Matei et al.Atrial fibrillation predictors in DCMRomanian Journal of CardiologyVol. 22, No. 2, 2012Table 5. Predictive values, sensitivity and specificity of the studied parameters for presence of atrial fibrillationVariableStudy group (n=348) Subgroup A (n=186) Subgroup B (n=162)AUC St Sp PPV NPV p AUC St Sp PPV NPV p AUC St Sp PPV NPV pPermanent and paroxystic atrial fibrillation (n=59)NYHA functional class > 3 0,61 27% 89% 33% 85% 35% 0,51 27% 80% 21% 84% ns 0,59 31% 85% 32% 84% 0,13 0,59 21% 74% 12% 84% 0,14LVEDD >63 mm 0,51 75% 33% 17% 82% ns 0,53 77% 32% 20% 85% ns 0,54 78% 28% 16% 88% nsLVESD >47 mm 0,53 86% 13% 18% 86% ns 0,51 94% 14% 20% 91% ns 0,60 74% 13% 13% 74% 0,11LA diameter >41 mm 0,55 89% 24% 19% 91% ns 0,57 91% 27% 22% 93% 0,13 0,50 87% 21% 16% 90% nsMitral regurgitation grade > 2 0,54 43% 69% 22% 85% ns 0,54 39% 73% 25% 84% ns 0,54 47% 65% 19% 87% nsPAsP >60 mmHg§ 0,56 18% 88% 23% 84% ns 0,54 13% 90% 23% 82% ns 0,63 30% 86% 27% 88% nsPermanent atrial fibrillation (n=38)NYHA functional class > 3 0,58 29% 89% 24% 91% 0,10 0,59 31% 89% 27% 91% ns 0,58 25% 89% 20% 91% nsQRS duration ≤110ms 0,56 79% 32% 12% 92% 0,15 0,57 77% 35% 14% 92% ns 0,56 81% 30% 11% 93% nsLV ejection fraction >35% 0,54 26% 79% 13% 79% ns 0,65 36% 84% 23% 91% 0,02 0,62 13% 74% 5% 89% 0,08LVEDD > 63 mm 0,52 76% 34% 12% 92% ns 0,51 78% 32% 13% 92% ns 0,54 74% 36% 11% 93% nsLVESD > 47mm 0,53 83% 13% 10% 86% ns 0,53 91% 13% 12% 91% ns 0,56 74% 13% 8% 82% nsLA diameter > 41 mm 0,59 95% 26% 14% 98% 0,05 0,62 95% 29% 15% 98% 0,01 0,52 93% 22% 12% 97% nsMitral regurgitation grade > 2 0,53 39% 70% 14% 90% ns 0,54 35% 73% 15% 89% ns 0,54 43% 66% 12% 91% nsPAsP >60 mmHg§ 0,62 20% 88% 17% 90% 0,09 0,58 15% 90% 17% 89% ns 0,69 28% 79% 13% 91% 0,05Paroxystic atrial fibrillation (n=29)NYHA functional class > 3 0,57 17% 87% 11% 92% 0,14 0,58 23% 86% 14% 92% ns 0,54 8% 88% 5% 92% nsQRS duration ≤ 110ms 0,51 76% 34% 10% 94% ns 0,53 64% 37% 9% 91% ns 0,60 92% 31% 10% 98% 0,12LV ejection fraction >35% 0,51 31% 80% 12% 93% ns 0,55 35% 84% 18% 93% ns 0,56 25% 75% 7% 92% nsLVEDD > 63mm 0,52 79% 33% 10% 94% ns 0,54 75% 31% 10% 92% ns 0,52 83% 35% 9% 96% nsLVESD > 47mm 0,54 86% 13% 8% 91% ns 0,51 94% 13% 10% 96% ns 0,59 75% 12% 6% 86% nsLA diameter > 41 mm 0,55 79% 22% 8% 92% ns 0,55 81% 25% 10% 93% ns 0,56 75% 20% 7% 91% nsMitral regurgitation grade > 2 0,53 43% 68% 11% 93% ns 0,57 43% 72% 13% 93% ns 0,51 44% 64% 9% 93% nsPAsP > 60mmHg§ 0,56 13% 87% 8% 92% ns 0,57 8% 89% 7% 91% ns 0,53 25% 84% 11% 93% ns§ PAsP was determined in a small number of casesAUC - area under curve, St - sensitivity, Sp - specificity, PPV - positive predictive value, NPV - negative predictive value, LV -left ventricle, LVEDD - left ventricular end-diastolic diameter, LVESD - left ventricular end-systolic diameter,LA - left atrium, PAsP - pulmonary arterysystolic pressure

Romanian Journal of CardiologyVol. 22, No. 2, 2012C. Matei et al.Atrial fibrillation predictors in DCMTable 6. Univariate and multivariate Cox proportional-hazards regression analysis for AF predictionDependant variableUnivariate analysisMultivariate analysisHR 95% CI p HR 95% CI pParoxystic atrial fibrillationSexNYHA classEjection fraction >35%LVEDD >63 mmLVESD >47 mmLA diameter >41 mmMitral regurgitationGrade2Grade 3Grade 4PAsP >60 mmHg§SVPB presence on Holter monitoringPermanent atrial fibrillationSexNYHA classEjection fraction >35%LVEDD >63 mmLVESD >47 mmLA diameter >41 mmMitral regurgitationGrade 2Grade 3Grade 4PAsP >60 mmHg§Parox/perm atrial fibrillationSexNYHA classEjection fraction>35%LVEDD >63 mmLVESD >47 mmLA diameter >41 mmMitral regurgitationGrade 2Grade 3Grade 4PAsP >60 mmHg§SVPB presence on Holter monitoring1,301,501,752,701,271,402,711,903,783,131,503,230,53 - 3,220,85 - 2,650,79 - 3,861,02 - 7,110,44 - 3,660,56 - 3,491,17 - 6,280,61 - 5,891,27 - 11,280,78 - 12,490,33 - 6,770,39 - 26,610,56180,15540,16560,04510,65980,46280,02040,26460,01730,10660,59300,27731,911,412,571,320,561,482,371,993,351,530,612,040,58 - 6,190,67 - 2,980,72 - 9,070,27 - 6,320,07 - 4,330,29 - 7,410,72 - 7,790,60 - 6,621,09 - 10,270,28 - 8,180,06 - 5,500,20 - 20,500,28360,35910,14450,72770,58850,63150,15620,25980,03530,61600,66130,54600,641,741,371,801,087,962,141,052,471,621,030,25 - 1,651,07 - 2,810,66 - 2,820,85 - 3,810,45 - 2,581,91 - 33,071,04 - 4,420,41 - 2,671,04 - 5,880,45 - 5,741,00 - 1,060,36210,02410,38790,12320,85900,00450,03930,91070,04080,45430,01200,591,331,590,970,965,201,501,092,201,101,700,19 - 1,850,72 - 2,460,43 - 5,820,26 - 3,580,14 - 6,220,67 - 40,130,54 - 4,160,42 - 2,850,91 - 5,300,28 - 4,200,47 - 6,030,37490,36130,48420,96460,96860,11540,43330,85350,08030,88650,41280,861,890,991,021,011,032,491,383,192,111,020,490,42 - 1,761,27 - 2,810,96 - 1,020,99 - 1,050,98 - 1,041,00 - 1,071,39 - 4,470,63 - 3,011,56 - 6,550,76 - 5,801,00 - 1,040,16 - 1,480,69830,00150,74660,12550,40280,04270,00230,41290,00160,14950,02860,21230,911,541,931,130,933,301,641,492,851,221,430,290,37 - 2,190,93 - 2,560,75 - 4,950,41 - 3,100,21 - 4,050,76 - 14,220,72 - 3,760,66 - 3,341,37 - 5,920,38 - 3,880,47 - 4,290,08 - 1,090,83570,09300,17090,80380,93180,11090,23980,32880,00520,72770,52120,0687§PAsP was determined in a small number of casesHR - hazard ratio, CI - confidence interval, NYHA - New York Heart Association, LVEDD - left ventricular end-diastolic diameter, LVESD - left ventricular end-systolic diameter, LA - left atrium (anteroposteriordiameter), PAsP - pulmonary artery systolic pressure, SVPB - supraventricular premature beatstice that small number of determinations in the studygroup (only the abnormal values were recorded) caninfluence the statistical analysis for this parameter.The presence of supraventricular premature beatson Holter monitoring, their number (total, maximum/hour, mean/hour), as well as therapeutic drug classesused were also studied in the uni- and multivariateanalysis but none of them showed statistically significantvalues, so they were not mentioned.The analysis of NYHA class changes between inclusionand end of the follow-up showed no significant differencesboth in patients with, or without, paroxysticatrial fibrillation; in contrast, the evolution of patientswith permanent atrial fibrillation shows a slight increasein the functional class, compared to those withoutpermanent AF which maintains almost the same value(Table 7).The survival of patients with or without paroxysticAF episodes was similar (Figure 2A). Looking atpatients with permanent AF, as it is shown in Figure2B, the survival curves diverges after a period of 45months, but without reaching statistically significance(p= 0.13). The analysis of survival curves in patientswith permanent AF (Figure 2C, D) shows that patientswith ischemic DCM (subgroup B), although initiallyseem to have a better prognosis despite the presence

C. Matei et al.Atrial fibrillation predictors in DCMRomanian Journal of CardiologyVol. 22, No. 2, 2012Figure 2. Kaplan - Meyer survival curves in DCM patients, with or without AFDiscussionsInteraction and inter-relationship between AF andheart failure, as well as information on their prevalenofAF, have a lower long term survival probability thanthose in non-ischemic DCM group (subgroup A). Wemust also consider the potential biases in the appreciationof mortality of DCM patients, as death can be theconsequence of both the pump dysfunction, as well asof presence of malignant ventricular arrhythmias. Oneof the limitations of this study is the absence informationregarding the mechanisms of death.Twenty-one patients received permanent pacemakersduring the follow-up period, in three, already havingAF at the time of cardiac stimulation, only biventricularre-synchronization was performed.Table 7. The mean of the NYHA functional class for patients with, or without permanent, or paroxystic atrial fibrillationParoxystic atrial fibrillationAbsentPresentPermanent atrial fibrillationAbsentPresentInclusion 95%CI Follow-up 95%CI p2,843,002,803,032,77 - 2,912,77 - 3,232,73 - 2,872,78 - 3,272,792,792,743,112,71 - 2,872,54 - 3,052,65 - 2,822,89 - 3,320,0830,5230,0410,370

Romanian Journal of CardiologyVol. 22, No. 2, 2012of atrial interstitial fibrosis, promoting the structuralatrial remodeling. Neurohormonal modulation andadrenergic receptors blockage with angiotensin conversionenzyme inhibitors 15 and beta-blockers, respectively,could explain the effectiveness of these drugs inAF prevention in patients with heart failure and DCM.However, in our study, the presence of these drug classesin the therapeutic scheme did not represent a significantrisk factor or protection factor against AF. Itis noticeable as a possible explanation for this fact thehigh prevalence (over 90%) of patients treated withboth ACE-I and beta-blockers even from the inclusionin the study.DCM patients with a low ejection fraction and increasedLV end-diastolic pressure have an increasedrisk of LA dilatation, an important predictive factorfor the onset and development of AF 17 . It is yet unclearwhether the prognostic significance of the left atriumdilation (quantified by diameter, area or volume - itwas recently showed that LA dimension increase is bestquantified by volume) is the result of the diastolic dysfunctionof the left ventricle, of the mitral regurgitation,or even that of the AF itself. All of these pathologicalconditions contribute to the dilation of the LA, havinga negative influence on the prognostic of patientssuffering from DCM and low ejection fraction. It is alsopossible that the LA dilation in patients with DCM canbe caused by the myopathic atrial affliction, caused bythe extension of the primary pathological process tothe atrial myocardium. Pathological anatomy studiescould bring further information on this subject.Atrial fibrillation also represents one of the independentfactors influencing mortality in patients withheart failure. As Macarie and colab. 14 have shown, AFis a negative prognostic factor, being responsible fora 14% increase in the death risk (univariate analysis),together with the ejection fraction. Its improvementby even one unit determines a significant 3% decreaseof the risk. In our study, the survival curves show thesame tendency for a less favorable evolution for patientswith DCM who in the course of their evolutionenter permanent atrial fibrillation, without reachingstatistical significance parameters; we also note that thesame phenomenon is independent of the non-ischemicetiology of dilated cardiomyopathy.The limitations of the study are mostly connected tothe retrospective nature of the selected patient’s groupanalyses. Thus, regarding the echocardiography data,we did not have more sensitive parameters for thequantification of the LA dimensions and function, becewere outlined starting from the Framingham study,estimating that it is important to consider the temporalsequence between AF and heart failure when observingrelative risk for mortality associated with AFor heart failure patients, the second condition havinga detrimental impact on survival 7,8 . With a reportedprevalence between 13% and 27% in different studies,atrial fibrillation is one of important co-morbidities thepatient with heart failure may face during disease evolution8-11 .Trying to determine potential predictor factors forthe risk of patients with DCM and heart failure to develop atrial fibrillation during disease progression, eitherparoxysmal or permanent, can be difficult, as wellas with malignant ventricular arrhythmias associatedwith this disease. Many factors, some permanent, othersjust with temporary appearance during disease progression(precipitating factors) may lead to an episodeof AF. The presence of a systolic ventricular dysfunction(often accompanied by diastolic dysfunction) canin its turn influence the evolution of such an episode(AF) towards becoming permanent, thorough the hemodynamicmodifications it induces. It is a well-knownfact that the success rate of conversion to sinus rhythmand relapse prevention is when compared to the situationthe above mentioned factors are absent.Recent investigations of structural and physiologicalchanges of atrial myocardium (both structural andelectrical remodeling!) revealed that the presence ofneurohormonal activation, fibrosis and apoptosis inthe evolution of idiopathic DCM are important triggersfor atrial fibrillation. In our study we found a relativelylow prevalence of permanent atrial fibrillation (12% inthe patients with idiopathic DCM and 9% in patientswith ischemic etiology), somewhat at the lower comparedwith existing literature on patients with heart failurewithout take account of the etiology. Thus, when theDCM patient becomes symptomatic with heart failuresymptoms, the risk of developing atrial fibrillation increases6 times 12 . In our study we found a relativelylow prevalence of permanent atrial fibrillation (12% inthe idiopathic DCM group and 9% in patients with ischemicetiology), somewhat at the lower limit of thedata existing in literature on patients with heart failurewithout take account of the etiology 11,13,14 .At the same time, the well known implication of therenin-angiotensin-aldosterone system in the pathogenesisof heart failure contributes to the onset and mai n-taining of the atrial fibrillation. The increase in the productionof angiotensin II contributes to the stimulationC. Matei et al.Atrial fibrillation predictors in DCM

C. Matei et al.Atrial fibrillation predictors in DCMcause the routine examinations performed on patients’admission do not have a systematic record of such parameters,which generally require a large amount of timeto measure. Another important limit was the absenceof details concerning the causes of death, this leadingto the impossibility to separate deaths caused by cardiovascularevents from those caused by other factors.ConclusionsOur study identified factors that can predict atrial fibrillationappearance in patients with dilated cardiomyopathy,regardless of its etiology (ischemic or nonischemic).The left ventricular end-diastolic diameter>63 mm and the presence of mitral regurgitationproved to be significantly correlated to the onset ofparoxystic atrial fibrillation, whereas permanent atrialfibrillation proved to be correlated to the heart failureNYHA class, the LA diameter and the presence of mitralregurgitation.With a fairly high prevalence (7%, respectively 5%for the paroxystic atrial fibrillation and 12%, respectively9% for the permanent atrial fibrillation in the 2subgroups) atrial fibrillation represents one of the conditionsthat can contribute to the deterioration of thequality of life, by aggravating the heart failure symptoms.On the other hand, global mortality was not significantlyinfluenced by the presence of atrial fibrillation,other factors, such as the presence of malignantventricular arrhythmias, being to be also quantified.List of abbreviationsACE-I angiotensin II converting enzyme inhibitorsAF atrial fibrillationARB angiotensin II receptors blockersAUC area under curveCAD coronary artery diseaseCI confidence intervalDCM dilated cardiomyopathyEF ejection fractionHgb hemoglobinHF heart failureHR hazard ratioLA left atriumLV left ventricleLVEDD left ventricular end-diastolic diameterLVEF left ventricular ejection fractionLVESD left ventricular end-systolic diameterNPV negative predictive valueNYHA New York Heart AssociationPAsP pulmonary artery systolic pressurePPV positive predictive valueROCSDSIUISpStSVPBRomanian Journal of CardiologyVol. 22, No. 2, 2012receiver operator characteristicstandard deviationUnique Computerized Integrated SystemspecificitySensitivitysupraventricular premature beatsConflict of interest: none declaredBibliography1. Elliott P, Andersson B, Arbustini E et al. Classification of the cardiomyopathies:a position statement from the European Society of CardiologyWorking Group on Myocardial and Pericardial Diseases. EurHeart J 2008;29:270-6.2. Steinhoff JP, Sheahan RG. Tachycardia-Induced Cardiomyopathy:Atrial Fibrillation and Congestive Heart Failure. Am J Med Sci2005;329:18-21.3. Gheorghiade M, Bonow RO. Chronic Heart Failure in the UnitedStates: A Manifestation of Coronary Artery Disease. Circulation1998;97:282-9.4. Felker GM, Shaw LK, O’Connor CM. A standardized definition of ischemiccardiomyopathy for use in clinical research. J Am Coll Cardiol2002;39:210-8.5. Guidelines for the management of atrial fibrillation. Developed withthe special contribution of the European Heart Rhythm Association(EHRA). Endorsed by the European Association for Cardio-ThoracicSurgery (EACTS). Eur Heart J 2010;31:2369-429.6. K/DOQI Clinical Practice Guidelines on Chronic Kidney Disease.Evaluation, classification, and stratification. Kidney Disease OutcomesQuality Initiative. Am J Kidney Dis 2002;39:S1-S266.7. Wang TJ, Larson MG, Levy D et al. Temporal Relations of Atrial Fibrillationand Congestive Heart Failure and Their Joint Influence onMortality. Circulation 2003;107:2920-5.8. Middlekauff HR, Stevenson WG, Stevenson LW. Prognostic significanceof atrial fibrillation in advanced heart failure. A study of 390patients. Circulation 1991;84:40-8.9. Carson PE, Johnson GR, Dunkman WB, Fletcher RD, Farrell L, CohnJN. The influence of atrial fibrillation on prognosis in mild to moderateheart failure. The V-HeFT Studies. The V-HeFT VA CooperativeStudies Group. Circulation 1993;86:VI102-VI110.10. Senni M, Tribouilloy CM, Rodeheffer R et al. Congestive Heart Failurein the Community : A Study of All Incident Cases in OlmstedCounty, Minnesota, in 1991. Circulation 1998;98:2282-9.11. Swedberg K, Olsson LG, Charlesworth A et al. Prognostic relevanceof atrial fibrillation in patients with chronic heart failure on longtermtreatment with beta-blockers: results from COMET. Eur Heart J2005;26:1303-8.12. Kanoupakis EM, Kallergis EM, Mavrakis HE et al. Electrophysiologicaland electroanatomical mapping of the right atrium in patientswith dilated cardiomyopathy: relation to the collagen turnover and toincreased propensity for AF. Europace 2009;11 (suppl 2):Abstract 287.13. Apetrei E. Fibrilatia atriala si insuficienta cardiaca. Rom Journal ofCardiol 2012;1:1-3.14. Macarie Tepes Piser I, Macarie C. Atrial fibrilation and survival inpatients with heart failure and low ejection fraction. Rom Journal ofCardiol 2012;1:4-13.15. Healey JS, Baranchuk A, Crystal E et al. Prevention of Atrial FibrillationWith Angiotensin-Converting Enzyme Inhibitors andAngiotensin Receptor Blockers: A Meta-Analysis. J Am Coll Cardiol2005;45:1832-9.16. Abi Nasr I, Bouzamondo A, Hulot JS, Dubourg O, Le Heuzey JY, LechatP. Prevention of atrial fibrillation onset by beta-blocker treatmentin heart failure: a meta-analysis. Eur Heart J 2007;28:457-62.17. Abhayaratna WP, Seward JB, Appleton CP et al. Left Atrial Size: PhysiologicDeterminants and Clinical Applications. J Am Coll Cardiol2006;47:2357-63.

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012REVIEWSConflict of interest policies and disclosure requirements amongEuropean Society of Cardiology national cardiovascular journalsFernando Alfonso MD PhD FESC 1 , Adam Timmis MD PhD FESC 2 , Fausto J. Pinto MD PhD FESC 3 , GiuseppeAmbrosio MD PhD FESC 4 , Hugo Ector MD PhD FESC 5 , Piotr Kulakowski MD PhD FESC 6 , and Panos VardasMD PhD FESC 7 , on behalf of the Editors’ Network European Society of Cardiology Task Force.Article received on the 9 th January 2012. Article accepted on the 21 st February 2012.Loizos Antoniades MD 1 , Mansoor Ahmad MD 2 , Eduard Apetrei MD 3 , Kaduo Arai MD 4 , Jean-Yves Artigou MD 5 ,Michael Aschermann MD 6 , Michael Böhm MD 7 , Leonardo Bolognese MD 8 , Raffaele Bugiardini MD 9 , ArielCohen MD 10 , Istvan Edes MD 11 , Joseph Elias MD 12 , Javier Galeano MD 13 , Eduardo Guarda MD 14 , Habib HaoualaMD 15 , Magda Heras MD 16 , Christer Höglund MD 17 , Kurt Huber MD 18 , Ivan Hulin MD 19 , Mario Ivanusa MD 20 ,Rungroj Krittayaphong MD 21 , Chi-Tai Kuo MD 22 , Chu-Pak Lau MD 23 , Victor A. Lyusov MD 24 , Germanas MarinskisMD 25 , Manlio F Márquez MD 26 , Izet Masic MD 27 , Luiz Felipe Pinho Moreira MD 28 , Alexander Mrochek MD 29 ,Rafael G. Oganov MD 30,31 , Dimitar Raev MD 32 , Mamanti Rogava MD 33 , Olaf Rødevand MD 34 , Vedat SansoyMD 35 , Hiroaki Shimokawa MD 36 , Valentin A. Shumakov MD 37 , Carlos Daniel Tajer MD 38 , Ernst E. van der WallMD 39 , Christodoulos Stefanadis MD 40 , Jørgen Videbæk MD 41 , Thomas F. Lüscher MD 42 .Affiliations:1Editor-in-Chief, Cyprus Heart Journal; 2 Editor-in-Chief, Pakistan Heart Journal; 3 Editor-in-Chief, Romanian Journal of Cardiology; 4 Editor-in-Chief,Avances Cardiológicos; 5 Editor-in-Chief, Archives des maladies du cœur et des vaisseaux Pratique; 6 Editor-in-Chief, Cor et Vasa; 7 Editor-in-Chief, ClinicalResearch in Cardiology; 8 Editor-in-Chief, Giornale Italiano Di Cardiologia; 9 Editor-in-Chief, Journal of Cardiovascular Medicine; 10 Editor-in-Chief,Archives of Cardiovascular Diseases; 11 Editor-in-Chief, Cardiologia Hungarica; 12 Editor-in-Chief, Heart News; 13 Editor-in-Chief, Journal of the ParaguayanSociety of Cardiology; 14 Editor-in-Chief, Revista Chilena de Cardiologia; 15Editor-in-Chief, Cardiologie Tunisienne; 16Editor-in-Chief, Revista Española deCardiología; 17 Editor-in-Chief, Svensk Cardiologi; 18 Editor-in-Chief, Journal für Kardiologie; 19 Editor-in-Chief, Cardiology Letters/Kardiológia; 20Editorin-Chief,Kardio List; 21 Editor-in-Chief, Thai Heart Journal; 22 Editor-in-Chief, Acta Cardiologica Sinica; 23 Editor-in-Chief, Journal of the Hong KongCollege of Cardiology; 24 Editor-in-Chief, Russian Cardiology Journal; 25 Editor-in-Chief, Seminars in Cardiovascular Medicine; 26 Editor-in-Chief, Archivosde Cardiología de México; 27 Editor-in-Chief, Medical Archives; 28 Editor-in-Chief, Arquivos Brasileiros de Cardiologia; 29 Editor-in-Chief, Cardiology in Belarus;30 Editor-in-Chief, Cardiovascular Therapy and Prevention; 31 Editor-in-Chief, Rational Pharmacotherapy in Cardiology; 32Editor-in-Chief, BulgarianCardiology; 33 Editor-in-Chief, Cardiology and Internal Medicine XXI; 34 Editor-in-Chief, Hjerteforum; 35 Editor-in-Chief, Archives of the Turkish Society ofCardiology; 36 Editor-in-Chief, Circulation Journal; 37 Editor-in-Chief, Ukrainian Journal of Cardiology; 38 Editor-in-Chief, Revista Argentina de Cardiologia;39Editor-in-Chief, Netherlands Heart Journal; 40 Editors-in-Chief, Hellenic Journal of Cardiology; 41 Editor-in-Chief, Cardiologisk Forum; 42 Editor-in-Chief,Kardiovaskuläre Medizin.This is a joint simultaneous publication initiative involving all interested National and Affiliated CardiovascularJournals of the European Society of CardiologyAbstract: Disclosure of potential conflicts of interest (COI) is used by biomedical journals to guarantee credibility and transparencyof the scientific process. COI disclosure, however, is not systematically nor consistently dealt with by journals. Recentjoint editorial efforts paved the way towards the implementation of uniform vehicles for COI disclosure. This paper providesa comprehensive editorial perspective on classical COI-related issues. New insights into current COI policies and practicesamong European Society of Cardiology national cardiovascular journals, as derived from a cross-sectional survey using astandardised questionnaire, are discussed.Key Words: Conflict of interest. Disclosure. Editorial ethics. Journals.1Chairman Editors´Network2Editor-in-Chief, Heart3Editor-in-Chief, Revista Portuguesa de Cardiologia4Nucleus Member Editors´Network5Editor-in-Chief, Acta Cardiologica6Editor-in-Chief, Kardiologia Polska7Editor-in-Chief, Hellenic Journal of Cardiology.Contact address:Fernando Alfonso MD, PhD, FESC. Interventional Cardiology. CardiovascularInstitute. Clínico San Carlos University Hospital. Plaza de Cristo Rey.Ciudad Universitaria. Madrid. Spain.Tel: +34 91 549 4082, Fax: +34 91 330 3289E-mail: falf@hotmail.com

Fernando Alfonso et al.Conflict of interest policies and disclosures in JournalsIntroductionThe scientific process relies on trust and credibility 1-5 .The scientific community demands high ethical standardsin biomedical research and the publication of scientificcontent 1-5 . During the past decade, disclosure ofconflicts of interest (COI) (also called competing loyalties,competing interests or dual commitments) hasbeen considered as key to guaranteeing the credibilityof the scientific process 6-10 . Biases in design, analysisand interpretation of studies may arise when authors orspon sors have vested interests 6-10 . Therefore, COI shouldbe made clear to the readers to facilitate their ownjud gement and interpretation of their relevance andpo tential implications. Authors are responsible for fullydisclosing potential COI 6-10 . Failure to do so has shakenthe confidence of the public, health professionals andscientists in the peer-reviewed medical literature 6-10 .According to the International Committee of MedicalJournal Editors (ICMJE) COI exist when an author(or the author´s institution), reviewer or editor havefinancial or personal relationships that inappropriatelyinfluence (bias) his or her actions 1,11,12 . The potential forCOI exists regardless of whether the individual believesthat the relationships affect his or her scientific judgement.Aside from financial relationships, COI mayem e rge from personal relationships, academic competitionand intellectual passion. To prevent ambiguity,authors should be explicitly asked to state whether COIexist or do not exist. Editors should publish this informationif they believe it is important in judging the manuscript1,11,12 .Traditionally, biomedical journals have followedstan dard practices to ensure COI disclosure. Furtherefforts to improve transparency and protect the integrityof research, including specific recommendationsand guidelines to disclose COI, have been recently proposedby many organisations 1-10 . However, ensuringadequate reporting of all sources of financial support isbecoming increasingly challenging for editors as a resultof the growing complexity of funding mechanisms.Furthermore, journals have different policies aboutCOI disclosure which can cause confusion as the sameauthor may report different information in differentjournals which, in turn, might jeopardise the confidenceof the readers 11,12 . To overcome these problems, theICMJE proposed the use of a common vehicle to reportCOI and, in October 2009, launched an electronic ‘uniform’format for COI disclosure 11,12 .The editors´ network of the European Society ofCar diology (ESC) is committed to promoting the disse-Romanian Journal of CardiologyVol. 22, No. 2, 2012mination and implementation of high-quality editorialstandards among ESC National Societies CardiovascularJournals (NSCJ) 13-16 . This report examines the issueof COI from a global and didactic perspective and providesnew insights into current policies and practicesamong ESC NSCJ.Conflict of Interest questionnaire and surveyTo determine the status of COI and disclosure requirementsamong ESC NSCJ a web-based, comprehensive,structured and standardised questionnaire was specificallydevised. The questionnaire was exhaustive anddealt with all relevant editorial topics related to COI.Pre vious publications on COI (from year 2005 to 2010)were retrieved from PubMed (Medline search terms:‘conflict of interest’, ‘competing interest’ and ‘disclosure’)and carefully reviewed to identify issues relevant toCOI. Items included in the questionnaire were eventuallydetermined after an internal discussion amongthe nucleus members of the Editors´ Network. For thesake of simplicity some related items and confusingor redundant topics were subsequently removed fromthe final questionnaire. Eventually, a total of 48 differentitems were included in the survey. Questions weregrouped into three main areas of interest: (1) authors;(2) reviewers; (3) editors. Furthermore, additionalfeed back about the interest generated by the ICMJE‘un i form’ COI disclosure initiative was also explicitlyre quested. Spaces for free text comments were madeava ilable for each main area of interest.In June 2010 the web-based survey was sent from theESC European Heart House to all editors-in chief of theESC NSCJ and, in a second wave (July 2010), to the ESCAffiliated Cardiac Societies. A specific claim was madefor the editor-in-chief in person to complete the survey.The invitation suggested that a meeting betweenthe editor-in-chief, associated editors and correspondingjournal staff should be organised, to discuss theresults of the requested information, before returningthe questionnaire. A URL link to the web-based surveywas provided in the invitation letter to allow editorsto enter the survey. When no answer was obtained thecorresponding National Cardiac Society was contacteddirectly. Conventional mailing was also used as required.Up to five separate requests were sent over the yearand thereafter missing journals were classified as nonresponders.The final electronic records were carefully analyzedby ESC personnel at the European Heart House andby the nucleus members of the ESC Editors´ Network.Attention was paid to detecting missing data, major in-

Romanian Journal of CardiologyVol. 22, No. 2, 2012consistencies or errors. Additional clarifications werere quested from the corresponding editors as needed.Data are presented as global results and anonymous forindividual journals.Conflict of Interest survey resultsA total of 46 journals answered the survey. Of these, 35belong to the ESC NSCJ and 11 to journals of AffiliatedCardiac Societies. This represents a response of 83%(35/42) of known NSCJ and 58% (11/19) for AffiliatedCardiac Societies. ESC NSCJ are highly heterogeneousin objectives, format and in scientific content 13 . Accordingly,some editors declined to answer the survey becausethey felt that COI policies did not apply to theirjournals (lack of original articles, small bulletins, contentswith just social news, etc) (data not shown).Table 1 summarizes the main data regarding auth o-rs´ COI. Nearly half of the journals had a specific policyon author COI. In most cases, emphasis was onlyon financial COI and on COI directly related to thesub mitted work. Few journals provided definitions orexa mples of COI. In nearly all cases where COI wererequested this policy affected all kinds of submittedarticles. Written attestation by the authors was widelyrequested. However, procedures to verify the accuracyFernando Alfonso et al.Conflict of interest policies and disclosures in Journalsof authors’ COI disclosure were rarely implemented,although, under special circumstances, most editorseventually contact authors to clarify COI related issues.Policies to deal with authors who fail to disclose COIwere seldom in place. In most journals the editors decidedwhen authors´ COI should be published but, insome journals, this information was systematically published(Table 1).Table 2 discloses data related to reviewers´ COI.Only one-quarter of the journals had policies for reviewers´COI. In more than half of the journals reviewerswere asked to decline the invitation to review if potentialCOI existed. However, recusal of reviewers due topotential COI was rare.Table 3 displays the status of editors´ COI amongthe corresponding journals. In most cases, policies inthis regard were not implemented. Furthermore, veryfew journals had policies for delegating decisions toother editors or to invited guest editors. Only one-thirdof the editors were familiar with the new ‘Uniform DisclosureForm’ ICMJE initiative when they received thesurvey invitation. However, 90% of the editors consideredthe ICMJE COI proposal of potential value to theirparticular journals and most of them declared that theyTable 1. Journals policies on authors´ conflicts of interest1) The journal has a specific policy on authors´ COI: 20/45 (44%)If yes:a. Described in the instruction for authors: 19/20 (95%)b. Described in dedicated forms required for manuscript submission: 12/19 (63%)2) The journal provides definition of different types of COI: 6/45 (13%)3) The journal provides examples of different COI: 5/45 (11%)4) COI are detailed by items and specified according to journal´s definition: 9/45 (20%)If Yes:a. Financial COI are specifically considered: 8/9 (89%)b. Non-financial COI are specifically considered: 2/9 (22%)5) Editors recommend an “inclusive” policy where all potential COI (even those minor and vaguely related) should be disclosed: 13 /44 (30%)6) Editors favour a “restrictive” policy where only potential COI that are relevant and directly related to the submitted work, should be disclosed: 19/42(45%)7) Resources from third parties received via the authors´ institution are considered: 8/42 (19%)8) Financial relationships involving family members are specified: 4/44 (9%)9) COI are just disclosed as free text directly by the authors: 29/40 (73%)10) Authors must submit a written attestation of potential COI: 18/44 (41%)If yes:a. Signature is required only from the corresponding/responsible author:10/18 (55%)b. Every author should sign the form: 6/18 (33%)11) Authors´ COI disclosures apply to “all” submitted articles: 23/44 (52%)12) Specific procedures are followed to verify that authors’ COI disclosures are accurate: 6/44 (14%)13) Under specific circumstances efforts are made to contact authors owing to concerns about disclosed or undisclosed COI (eg, complaint by reviewers/readers): 27/41 (66%)14) Specific policies to deal with authors who fail to disclose COI of published papers: 11/45 (24%)15) Specific policies to “restrict” author publication of articles with a stated COI: 10/44 (23%)16) The journal “publishes” all the authors’ COI disclosures in all submissions: 13/40 (33%)17) The editors decide, on an individual basis, when authors´ COI should be “published”: 23/43 (53%)18) If authors’ COI are not published, the information is made available upon request: 21/46 (46%)Data from the 46 journals answering the questionnaire (number of journals answering each question is presented). Not all journals responded to all questions. COI, conflicts ofinterest.

Fernando Alfonso et al.Conflict of interest policies and disclosures in JournalsRomanian Journal of CardiologyVol. 22, No. 2, 2012Table 2. Journals policies on peer-reviewers´ conflicts of interest1) The journal has a specific policy on reviewers´ COI: 11/43 (25%)2) Reviewers are required to explicitly state whether they have potential COI: 10/43 (23%)3) Reviewers must submit a written attestation of potential COI: 7/43 (16%)4) Frequency of request to disclose potential COI: only first invitation: 7/46 (15%); always: 10/46 (22%); yearly: 5/46 (11%)5) Specific procedures are followed to verify that peer-reviewers´ COI disclosures are accurate: 5/44 (11%)6) It is suggested to reviewers that they “decline” the invitation if potential COI exists: 21/39 (54%)7) There is a policy for “recusal” of reviewers with a declared COI: 6/42 (14%)8) Peer-reviewers´ COI are always published: 1/44 (2%)9) Editors decide, on an individual basis, when reviewers´ COI should be published: 20/44 (45%)10) If reviewers’ COI are not published, the information is made available upon request: 15/46 (33%)COI, conflicts of Interest.Table 3. Journals policies on editors´ conflicts of interest1) The journal has a specific policy on editors´ COI: 8/45 (18%)2) Editors must submit a written attestation on potential COI: 6/83) Frequency to disclose potential COI: only when appointed: 5/6; yearly: 1/64) Specific procedures are followed to verify that editors’ COI disclosures are accurate: 3/85) There is a policy for “recusal” of editors with a declared COI: 3/86) There is a policy for “delegating” handling decision to other (invited) editors: 4/77) Editors’ COI are always published: 2/78) If Editors’ COI are not published, the information is made available upon request: 5/6COI, conflicts of Interest.were willing to implement it within a relatively shortperiod of time (Table 4).DISCUSSIONIndustry-sponsored studies: friend or foe?Research is becoming progressively complex andquality standards increasingly demanding 17-24 . As a result,conducting clinical studies is becoming more expe n sive and the role of sponsors to ensure the viabilityof research projects is becoming critical. However, fundingfrom different sources may directly affect investigators and COI may inappropriately influence theiractions or judgment 17-24 . Subtle biases in design andinterpretation may arise when a sponsor stands to gainfrom the report 17 .Pharmaceutical and technological companies areresponsible for most important advancements in medicalknowledge 17-24 . Patients, doctors and society asa whole benefit from this unique effort and should begrateful for the research commitment by the industry.More than 75% of all clinical trials are funded by drugcompanies 25,26 . Likewise, the bulk of research has mo-Table 4. Feedback on the ICJME “uniform disclosure form” initiative1) Editor was familiar with the ICMJE initiative “before” receiving the survey: 15/42 (36%)2) The initiative was considered of value to the “particular” journal: 38/42 (90%)3) Editors willing to implement the initiative within 3 years: 31/46 (67%)4) Main perceived advantages of the initiative (top 5):a. Provides a common “uniform” platform for all journals: 42b. All relevant information about COI is nicely presented and explained: 18c. Allows easy update of the requested information: 12d. Facilitates sequential submissions (if the paper is rejected by a journal): 11e. Allows archiving of the requested information: 105) Main perceived disadvantages of the initiative (top 5):a. Increases the complexity of the submission process: 29b. Publishing in the journal all potential COI of every author is not feasible: 17c. Verification of the disclosed/undisclosed COI remains impossible: 17d. Increases editorial bureaucracy: 15e. Too detailed and exhaustive: 14f. The meaning of some potential COI (travel grants to meetings, etc) might be perceived differently by American and European authors/journals/readers:14COI, conflicts of interest; ICMJE, International Committee Medical Journals Editors.

Romanian Journal of CardiologyVol. 22, No. 2, 2012ved from academic centers to direct contracts betweensponsors and private organizations 27,28 . For-profit,contract research organizations, currently consumemore than 60% of research funding from industry 25-28 .This could be a result of their ability to complete trialsmore rapidly than academic institutions 8,25 . This phenomenonexplains the gradual loss of the academicestablishment’s influence on the ‘research agenda’ 25-29 .Although the most cited articles continue to be generatedby authors with academic affiliations, the numberof trials financed exclusively by industry has increasedexponentially 30 .This paradigm shift has major consequences 25-29 .First, many scientifically relevant issues are decreasinglylikely to be investigated (orphan studies). Second,many studies 8,31,32 suggest that, in comparison withnon-sponsored research, sponsored trials are publishedless frequently, raising the concern of publication bias 29 .Although the industry has been blamed for preferentialpublication of studies with positive outcomes, thisproblem also affects government-funded research 8,31-35 .To reduce the effect of publication bias, trials must beregistered in publicly accessible repositories 29 . Industry-supportedresearch has also been associated withmultiple reporting of studies with positive outcomes 8,36 .This practice might affect results of subsequent re views,meta-analyses and even clinical practice guide lines. Alternatively,industry sponsorship has been associatedwith publication delays or restrictions 8 .Finally, industry-sponsored trials have a three- tofour-fold greater probability of obtaining favorable resultsthan their non-sponsored counterparts 8,31-33,37,38 .Interestingly, all these differences do not appear to berelated to inferior methodology in industry-financedtrials. Bekelman et al 8 performed a systematic reviewof 1140 original studies demonstrating a statisticallysig nificant association between industry sponsorshipand pro-industry conclusions. The study showed thatfinancial relationships between industry, scientific investigatorsand academic institutions were widespreadand that COI arising from these ties might significantlyinfluence biomedical research. It was considered possible,however, that given limited resources, industrybecame selective enough to fund only potentially ‘winingtreatments’ 8 . More recently, in a provocative studythat included 324 cardiovascular trials published in thethree medical journals with the highest impact factors,Ridker and Torres 39 analyzed the probability of positiveresults according to the source of finance. Industry-financedtrials more frequently obtained results favora-Fernando Alfonso et al.Conflict of interest policies and disclosures in Journalsble to drug or device than those financed by not-forprofitorganizations. This was particularly evident intrials using surrogate end points 39 .Previous editorial surveys on conflicts of interestsIn 1997, Krimsky and Rothenberg found that only16% of journals across all scientific disciplines hadCOI policies 40 . In addition, existing editorial policieswere often not readily available to submitting authors 41 .However, a substantial increase in the prevalence ofCOI disclosure occurred over time. Initially, most journalsonly required authors to disclose potential COI.Subsequently, journals encouraged authors to signCOI disclosure statements. If signed statements are notobtained from all authors, it remains possible that onlythe first author has reviewed the COI policy of the journal,leading to systematic under-reporting 6 . Interestingly,some journals that theoretically adhere to ICMJErecommendations do not have clear COI policies whencritically analyzed 6 . However, the journals with highestimpact factors are more likely to have published COIpolicies 6,41 .To better characterize COI policies, in 2006, Cooperet al 7 performed a cross-sectional web-based survey ofa convenience sample of 135 editors of peer-reviewedbiomedical journals. The survey included questionsabout the existence of specific policies for authors,peer reviewers and editors, specific restrictions basedon COI and the public availability of these disclosures.Ninety-three per cent of journals reported having anauthor COI policy but only 82% of these required awritten attestation. While 77% reported collecting COIinformation on all author submissions, only 57% publishedall author disclosures. Eleven per cent of journalsreported restricting author submissions based on COI.A minority of journals reported having a policy onreviewers´ COI (46%) or editors´ COI (40%); amongthese, 25% and 31% of journals stated that they requirerecusal of peer-reviewers and editors if they report aCOI. Only 3% of respondents published COI disclosuresof peer reviewers and 12% published editors’ COIdisclosures, while 11% and 24%, respectively, reportedthat this information was available upon request.In this survey, estimates were directly provided by thecorresponding editors but no information was takendirectly from the actual publications 7 .Other studies were more critical and analyzed theinformation available directly from the journals yieldinga different perspective. Interestingly, some of thesestudies focused on COI disclosures in cardiology. Weinfurtet al 42 searched in PubMed for English-language

Fernando Alfonso et al.Conflict of interest policies and disclosures in Journalsrelied on self-reporting by journal editors. However,given the anonymous nature of our survey, we do notbelieve there is any reason to question the accuracy oftheir reports.ICMJE Uniform Disclosure InitiativeIn October 2009 the ICMJE proposed an electronic‘uniform’ format for COI disclosure 11 . Four main areaswere addressed: authors´ associations with entities thatsupported the submitted manuscript (indefinite timeframe), associations with commercial entities with potentialinterest in the general area of the manuscript(time frame 36 months), financial association of theirspouse and children and, finally, non-financial associationspotentially relevant to the submitted manuscript.Each author should disclose resources receiveddirectly, or via the corresponding institution, whichwere used to complete the investigation. Additionally,all sources of revenues relevant to the submitted workpaid by any third party before the submission and anyrelevant long-term relationship, even if ended, shouldbe disclosed. Financial revenues should be disclosedregardless of the amount. A guide for authors and acompleted sample was provided in PDF format. Thereporting form was made available at www.icmje.org/coi_disclosure.pdf to be downloaded, completed andsent to the journal 11 . The form can be saved and usedagain—adding updated information—for a new manuscript.Each author should submit a separate form andis responsible for the accuracy and completeness of thesubmitted information 11 .The ICMJE allowed a period of beta-testing untilApril 2010 when submission of suggestions was encouraged12 . As a result of the feedback comments, theform was modified. Concerns raised were mainly technicaland ethical regarding inquiries about non-financialassociations. Accordingly, clarity was enhancedfor non-native English speakers (including a glossaryof terms). Additionally, owing to the difficulties detectedin defining non-financial COI, this section was alsomodified to be less intrusive (currently presented as anopen query) while keeping its locus. Finally, queriesabout COI in family members were removed from theupdated form 12 .The idea behind this initiative was to facilitate andstandardize uniform disclosure of COI and to make theprocess easier for authors and less confusing to readers.This uniform ‘universal’ vehicle allows authors to savethe electronic forms that can be updated as needed andeliminates the need for reformatting disclosure informationfor each new submission. Finally, this will eliarticlespublished in 2006 that provided evidence orguidance about the use of coronary artery stents. Asa premise, it was considered reasonable to expect thatauthors´ COI were disclosed in similar ways in articleson the same topic published around the same time. Atotal of 746 articles with 2985 authors published in 135journals, were analyzed. Articles were examined to determinewhether authors’ financial interests were consistentlyreported. Eighty-three per cent of the articlesdid not contain disclosure statements for any author,72% did not identify any funding source and only 6%of authors had an article with a disclosure statement.Additionally, author disclosure statements varied significantlyfrom article to article. Notably, articles publishedin journals that endorsed the ICMJE guidelineswere more likely to have disclosure statements for allauthors. Similarly, articles in which all authors had disclosurestatements were more likely to appear in journalswith higher impact factors (median impact factor11.6 vs 3.1).These investigators concluded that evenrarely disclosed financial interests were not disclosedconsistently, suggesting that there are problems withtransparency in the cardiac literature with potentialimplications for patient care. Data suggested that theobserved inconsistencies were a result of both journals´policies and authors´ behavior 42 . Many would ar guethat an inconsistent system of disclosure is more har m-ful than no disclosure at all.More recently, Blum et al 6 analyzed COI policiesof the top 10% of medical journals according to theirim pact factor. Instructions to authors and manuscriptsub mission documents were electronically searchedfor phrases relating to COI using a standardized form.A total of 262 journals were analyzed. Of these, 85%requested COI disclosure in the instruction to authorsand an additional 4% in other submission documents.Links to specific policies on COI were found within theinstruction for authors in only 25% of journals. Although77% of journals provided definitions on COI, signeddisclosure statements were required by only 54%of journals. Travel grant disclosure was requested by12% of journals. Interestingly, journal category influencedCOI disclosure requirements. This request washigher for internal medicine journals than for specialtyjournals, for journals in the top quartile according toimpact factor and for journals endorsing the ICMJEguidelines 6 .Our data on ESC NSCJ COI policies and disclosurerequirements suggest that this topic remains controversialand is not uniformly addressed by journals. WeRomanian Journal of CardiologyVol. 22, No. 2, 2012

Romanian Journal of CardiologyVol. 22, No. 2, 2012minate apparent inconsistencies in the report of COI asa result of different journal policies 11,12 .Additional editorial perspectives regarding Conflictsof interestsConcerns about COI are not new. In his play Le MaladeImaginaire Molière satirized the relationship betweenthe doctor and the druggist as they exploited thehypochondriac Argan for their own economic benefit21 . Biomedical journals are particularly vulnerable toCOI-related problems. As Richard Smith, the formereditor-in-chief of the British Medical Journal, stated‘‘the quality of the journal will bless the quality of thedrug’’ 43 . Therefore, it is easy to understand the extrascrutiny of industry-sponsored research by reviewersand editors 33 . Some editors require that authors of industry-associatedresearch have their data analysis confirmedby a different source and others even ask for theraw data to be analyzed by an independent academicstatistician 20,33 . Some editors do not commission editorialor review articles from authors with potential COIas these may blur objectivity 19,44,45 . These pieces relyespecially on interpretation and objectivity. However,assessing the importance of COI in opinion articles maybe challenging. The dilemma is obvious: those authorswith the greatest expertise are usually those with clearerpotential COI 44 . Last, but not least, editors shouldalso avoid the existence of marketing masquerading aseducation in their journals. Of note, industry supportaccounts for most of the funding of accredited continuingmedical education (CME) programs 19 . Somesuggest that CME has become an insidious vehicle forthe aggressive promotion of drugs and medical devices(even with off-label indications). Others consider CMEa marketing machine and a lucrative process—withconcealed payments to doctors—that undermines theindependence of medical societies 19,46 .Sometimes medical literature is produced in obscureways. Professional writers, hired by the industry,may act as ‘ghostwriters’ to produce papers for whichcredibility will be subsequently increased by invitingacademic physicians to act as a ‘guest author’ 33 . Unfortunately,these guest authors rarely make significantcontributions to the design, analysis and data interpretation33 . Conversely, many deserving industry scientistsmay be removed from the byline directly by the sponsors.Affiliation with a drug company should not be viewedas evidence of wrongdoing because, as previouslyemphasized, most important medical discoveries aregenerated by the pharmaceutical industry.Journals typically use two main weapons to deal withCOI: disclosure and exclusion 44 . However, as discussed,Fernando Alfonso et al.Conflict of interest policies and disclosures in Journalspolicies for COI vary widely among editors. Disclosureshould not be considered as a panacea to deal with COIbut, from an editorial perspective, casting daylight onthe relationship between doctors and pharmaceuticalcompanies represents the best way to untie this Gordianknot 44 . Editors should decide whether to publish theinformation disclosed by authors about potential COI.Editors have the ‘discretion’ to decide if the potentialCOI is important enough to be revealed 6 . However, itis unclear how editors decide whether to publish disclosures.Moreover, the extent to which such ‘‘secretdisclosure’’ may affect the integrity of the journal orthe published work remains unknown 7 . Some journalssystematically disclose all reported potential COI 6 .However, this strategy consumes major editorial resourcesand has been blamed for introducing prejudice inthe judgment of manuscripts by readers and for taintingthe full content of the article. The value of an exhaustivesystematic disclosure of all potential COI remains highlycontroversial. This practice does not guarantee thatthe readers will be able to determine whether COI aremeaningful or not. Indeed, this practice may be misleadingbecause bias may be perceived when not presentand overlooked when relevant. Although COI do notimply any improper behavior, a McCarthyesque reactionto the term would wrongly support the presumptionof guilty until proven innocent 23,33,47 . The pendulum isswinging towards increased oversight, but responsibleeditors should ensure that their readers enjoy the sweetspot in the middle, at least for the time being.Editors are very busy and cannot conduct a forensiccheck on every submitted trial. Our survey is consistentwith prior reports 7 suggesting that almost no journalhas a formal policy of ‘verification’ of COI disclosures 7 .Editors are not policemen but, at the same time, it becomesclear that some action is expected when misconductis detected. Many times editors behave as a ‘toothlesswatchdog’ regarding COI. Alternatively, othereditors suggest that allegation of under-reported COIshould be rigorously investigated 9 . However, editors donot have the resources required to conduct a full investigationto clarify elusive and multifaceted COI-relatedissues. In most cases their final role is just to raisethe issue with the corresponding dean. Notably, formal‘corrections’ about COI are rarely published.All authors of this review support the importanceof disclosing potential COI when a scientific paper issubmitted for consideration to any ESC NSCJ. Moreover,when in doubt it is better to err on the side ofover-disclosure and let the editors make the decision.

Fernando Alfonso et al.Conflict of interest policies and disclosures in JournalsThe ICMJE Uniform Disclosure Initiative represents amilestone in this regard and paves the way for furthertransparency in biomedical publishing 11,12 . Therefore,we encourage ESC NSCJ to progressively adapt theirpolicies in order to be able to adhere to this editorialproposal. However, in this journey, some potential caveatsshould be carefully heeded. First, exhaustive disclosureof multiple, minor and vaguely related potentialCOI might ‘dilute’ the relevance of real major COIthat most readers would be interested to know. Second,some relevant institutional COI are not openly disclosedto all corresponding researchers and, accordingly,these may be impossible to declare. Third, many majorjournals frequently allow senior international opinionleaders with clear (definitive and well-known) COI tosystematically declare the absence of COI in their papers.Young scientists may perceive this as confusingand disturbing while others will regard this inconsistencyas evidence that the whole process is completelyhypocritical. Finally, major socio-cultural differencesamong countries should be also taken into account.Most European doctors (including most editors in thebyline of this article) frequently receive occasional travelgrants from diverse pharmaceutical companies toattend medical society meetings and, up to now, thesehave not been systematically disclosed as potentialCOI. The situation, however, is quite different on theother side of the Atlantic where such practices havebeen considered inadequate or even misconduct fora number of years. In North America, direct support(including travel) of CME programs by industry isprohibited while this practice is considered acceptablein most European countries 19 . NSCJ editors should bealerted to the need to deal with these vexing problemsin their respective journals in line with local policiesand practices 48 . Progressive steps should be taken toensure a systematic approach to these COI-related editorialissues. However, commonsense and reason shouldprevail in order to achieve a balance between thepragmatic and utopian.Final remarksConsumers of medical scholarship expect a reliablesystem of disclosure, in which journals and authorsmake disclosures appropriately and consistently. Thereis a stigma surrounding the reporting of COI that shouldbe progressively overcome. The ESC has recentlydefined a general policy for COI 49 . This review providesanother framework to better understand COI froman editorial perspective. This survey on ESC NSCJ COIpolicies and disclosure requirements confirms thatRomanian Journal of CardiologyVol. 22, No. 2, 2012this topic is poorly—and not uniformly—dealt withby journals. Further actions are required to increaseawareness of the importance of COI disclosure and topromote policies aimed at enhancing transparency inbiomedical research.Disclosures: None of the editors authors of this paperhad any potential conflict of interest that needs tobe disclosed in relation to this manuscript.Acknowledgements: We are grateful for the supportand assistance of Iris Chapuis, Lone Kristoffersen, IsabelleCollin and Muriel Mioulet from the ESC NationalCardiac Societies Relations Department at the HeartHouse.References1. International Committee of Medical Journals Editors. Uniform Requirementsfor Manuscript Submitted to Biomedical Journals: Writingand Editing for Biomedical Publication. (Updated October2008). Available: http://www.icmje.org/.2. Council of Science Editors. 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Romanian Journal of CardiologyVol. 22, No. 2, 2012Fernando Alfonso et al.Conflict of interest policies and disclosures in JournalsJokhadar M, Haouala H, Sansoy V, Shumakov V, Timmis A. EuropeanNational Society cardiovascular journals. Background, rationale andmission statement of the “Editors’ Club”. Rev Esp Cardiol. 2008 Jun;61(6):644-50.14. Alfonso F, Ambrosio G, Pinto FJ, Ector H, Vardas P, Kulakowski P,Timmis A; Editors’ Network ESC Task Force. European Society ofCardiology national cardiovascular journals: the ‘Editors’ Network’.Eur Heart J. 2010 Jan;31(1):26-8.15. Mills P, Timmis A, Huber K, Ector H, Lancellotti P, Masic I, Ivanusa M,Antoniades L, Aschermann M, Laucevicius A, Mustonen P, ArtigouJY, Vardas P, Stefanadis C, Chiarello M, Bolognese L, Ambrosio G, vander Wall EE, Kułakowski P, Pinto FJ, Apetrei E, Oganov RG, KamenskyG, Lüscher TF, Lerch R, Haouala H, Sansoy V, Shumakov V, Tajer CD,Lau CP, Márquez M, Krittayaphong R, Arai K, Alfonso F. The role ofEuropean national journals in education. Heart. 2009 Dec;95(24):e3.16. Alfonso F. The Editors’ Network of the European Society of Cardiology.Eur Heart J. 2011 Apr; 32(8):919-21.17. Schwartz RS, Curfman GD, Morrissey S, Drazen JM. Full disclosureand the funding of biomedical research. N Engl J Med 2008;358(17):1850-1.18. Simone J. More interest in conflicts of interest. Lancet Oncol. 2009;10:836-7.19. Conti RC. Conflict of interest. Clin Cardiol 2009; 32:666-66720. Fontanarosa PB, Flanagin A, DeAngelis CD. Reporting conflicts ofinterest, financial aspects of research and role of sponsors in fundedstudies. JAMA 2005; 294(1):110-11.21. Alpert JS. Doctors and the drug industry: how can we handle potentialconflicts of interest? Am J Med. 2005 Feb; 118(2):99-100.22. Alpert JS. Doctors and the drug-industry: Further thoughts for dealingwith potential conflicts of interest? Am J Med 2008 Apr; 121(4):253-5.23. Lanier WL. Bidirectional conflicts of interest involving industry andmedical journals: who will champion integrity? Mayo Clin Proc. 2009Sep;84(9):771-5.24. Bove A. Relations with industry: thoughts on claims of a broken system.J Am Coll Cardiol 2009; 54(2):177-79.25. Bodenheimer T. The uneasy alliance: Clinical investigators and thepharmaceutical industry. N Engl J Med 2000; 342(20):1539-44.26. Goldacre B. Is the conflict of interest unacceptable when drug companiesconduct trials on their own drugs? Yes. BMJ. 2009 Nov 27;339:b4949.27. Davidoff F, de Angelis CD, Drazen JM, Hoey J, Hjgaard L, Horton R,Kotzin S, Nicholls MG, Nylenna M, Overbeke JP, Sox HC, van derWeyden MB, Wilkes MS; International Committee of Medical JournalEditorset al. Sponsorship, authorship and accountability. Lancet.2001; 358:854-6.28. Johns MM, Barners M, Florencio PS. Restoring balance to industryacademiarelationships in an era of institutional financial conflicts ofinterest: promoting research while maintaining trust. JAMA. 2003;289(6):741-6.29. Alfonso F, Segovia J, Heras M, Bermejo J. Publication of clinical trialsin scientific journals: Editorial issues. Rev Esp Cardiol. 2006 Nov;59(11):1206-14.30. Patsopoulos NA, Analatos AA, Ioannidis JP. Origin and funding ofthe most frequently cited papers in medicine: database analysis. BMJ.2006; 332(7549):1061-4.31. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industrysponsorship and research outcome and quality: systematic review.BMJ. 2003; 326(7400):1167-70.32. Finucane TE, Boult CE. Association of funding and findings of pharmaceuticalresearch at a meeting of a medical professional society.Am J Med. 2004; 117(11):842-5.33. Hirsch LJ. Conflicts of interest, authorship, and disclosures in industry-relatedscientific publications: The tort bar and editorial oversightof medical journals. Mayo Clin Proc 2009; 84(9):811-821.34. Krzyanowska MK, Pintilie M, Tannock IF. Factors associated withfailure to publish large randomized trials presented at an oncologymeeting. JAMA. 2003; 290(4):495-501.35. Chan AW, Krleza-Jerić K, Schmid I, Altman DC. Outcome reportingbias in randomized trials funded by the Canadian Institutes of HealthResearch. CMAJ. 2004;171(7):735-740.36. Alfonso F, Bermejo J, Segovia J. Duplicate or redundant publication:can we afford it?. Rev Esp Cardiol. 2005 May;58(5):601-4.37. Hirsch L. Randomized clinical trials: what gets published, and when?CMAJ. 2004; 170(4):481-483.38. Kjaergard LL, Als-Nielsen B. Association between competing interestsand authors’ conclusions: epidemiological study of randomisedclinical trials published in the BMJ. BMJ. 2002; 325(7358):24939. Ridker PM, Torres J. Reported outcomes in major cardiovascularclinical trials funded by for profit and not-for-profit organizations:2000-2005. JAMA. 2006; 295(19):2270-4.40. Krimsky S, Rothenberg LS. Conflict of interest policies in science andmedical journals: editors practices and authors disclosures. Sci EngEthics 2001;7(2):205-218.41. Ancker JS, Flanagin A. A comparison of conflict of interest policiesat peer-reviewed journals in different scientific disciplines. Sci EngEthics 2007;13(2):147-57.42. Weinfurt KP, Seils DM, Tzeng JP, Lin L, Schulman KA, Califf RM.Consistency of financial interest disclosures in the biomedical literature:The case of coronary stents. PLoS ONE 2008;3(5):e2128.43. Smith R. Medical journals are an extension of the marketing arm ofpharmaceutical companies. PLoS Med 2005;2(5):e138.44. The Editors. Publishing commentary by authors with potential conflictsof interest: When, Why and How. Annals Intern Med 2004; 141(1):73-74.45. Vorobiof G. Do conflict of interest really matter or does no one readthe fine print anyway? J Am Coll Cardiol 2008; 51(19):1911.46. Tanne JH. US Senate committee investigates conflicts of interest inindustry funded medical education. BMJ. 2009 Aug 4; 339:b3139.47. Rothman KJ. Conflict of interest. The new McCarthyism in science.JAMA 1993;269(21):2782-2784.48. Avanzas P, Bayes-Genis A, Pérez de Isla L, Sanchis J, Heras M. Ethicalconsiderations in the publication of scientific articles. Rev Esp Cardiol.2011 May; 64(5):427-9.49. ESC Statement on COI policy. PENDING PUBLICATION. SimultaneousIssue of EHJ in 2012

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012National Society Cardiovascular Journals of Europe:Almanac 2011Timmis A, Alfonso F, Ambrosio G, Ector H, Kulakowski P, Pinto FJ, Vardas P, on behalf of the Editors’ NetworkThe Editors’ Network is a task force of the EuropeanSociety of Cardiology (ESC), representing the 44National Society Cardiovascular Journals that are publishedacross 37 countries 1 . Among the operationalgoals enshrined in its mission statement is a commitmentto improve the diffusion of scientific knowledgethrough distribution of common academic materialand joint education initiatives 2 . Heart already has astrong education section and its content, approved bythe European Board for Accreditation in Cardiology(EBAC), is available for free access via the Heart andESC websites. However, a recent joint publication ofthe Editors’ Network called for educational initiativesto be extended throughout the national cardiology journalsof Europe 3 , and it is in response to that call thata series of Almanac 2011 papers are appearing moreor less simultaneously in many of the Network Journals.Almanac - a late Middle English word derived viamedieval Latin from Greek almenikhiaka - is definedas an annual calendar containing important dates andstatistical information. It provides an approximate descriptionof the new series of papers presenting selectedrecent research that has driven clinical advances in sixmajor topic areas. The content is educative and clinicallyrelevant and its presentation across the nationalsociety cardiovascular journals of Europe represents amilestone in collaborative publishing. Plans for Almanac2012 are yet more ambitious and pave the way fora new era of joint educational initiatives driven by theEditors’ Network of the ESC.References1. Alfonso F, Ambrosio G, Pinto FJ, Ector H, Vardas P, Kulakowski P,Timmis A; Editors’ Network ESC Task Force. European Society ofCar diology national cardiovascular journals: the ‘editors’ network’.Eur Heart J. 2010;31:26-8.2. Grupo de trabajo de la Sociedad Europea de Cardiología, AlfonsoF, Ambrosio G, Pinto FJ, Van der Wall EE, Kondili A, Nibouche D,Adamyan K, Huber K, Ector H, Masic I, Tarnovska R, Ivanusa M,Stanĕk V, Videbaek J, Hamed M, Laucevicius A, Mustonen P, ArtigouJY, Cohen A, Rogava M, Böhm M, Fleck E, Heusch G, Klawki R, VardasP, Stefanadis C, Tenczer J, Chiariello M, Elias J, Benjelloun H, RødevandO, Kułakowski P, Apetrei E, Lusov VA, Oganov RG, ObradovicV, Kamensky G, Kenda MF, Höglund C, Lüscher TF, Lerch R, JokhadarM, Haouala H, Sansoy V, Shumakov V, Timmis A. European Na tionalSociety cardiovascular journals. Background, rationale and mis sionstatement of the “editors’ club”. Rev Esp Cardiol 2008; 61:644-50.3. Mills P, Timmis A, Huber K, Ector H, Lancellotti P, Masic I, IvanusaM, Antoniades L, Aschermann M, Laucevicius A, Mustonen P, ArtigouJY, Vardas P, Stefanadis C, Chiarello M, Bolognese L, AmbrosioG, van der Wall EE, Kułakowski P, Pinto FJ, Apetrei E, Oganov RG,Ka mensky G, Lüscher TF, Lerch R, Haouala H, Sansoy V, ShumakovV, Tajer CD, Lau CP, Márquez M, Krittayaphong R, Arai K, AlfonsoF. The role of European national journals in education. Heart. 2009;95:e3.Contact address:Professor Adam D Timmis, Barts and the London School of Medicine andDentistry London, Chest Hospital, London E2 9JX, UK; adamtimmis@mac.com

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012REVIEWSAlmanac 2011: acute coronary syndromes. The national societyjournals present selected research that has driven recent advancesin clinical cardiology*C. Knight 1 , A. D. Timmis 2Article received on the 9 th January 2012. Article accepted on the 12 st January 2012.Summary: This overview highlights some recent advances in the epidemiology, diagnosis, risk stratification and treatment ofacute coronary syndromes. The sheer volume of new studies reflects the robust state of global cardiovascular research but thefocus here is on findings that are of most interest to the practising cardiologist.Incidence and mortality rates for myocardial infarction are in decline, probably owing to a combination of lifestyle changes,particularly smoking cessation, and improved pharmacological and interventional treatment. Troponins remain central fordiagnosis and new high-sensitivity assays are further lowering detection thresholds and improving outcomes. The incrementaldiagnostic value of other circulating biomarkers remains unclear and for risk stratification simple clinical algorithms such asthe GRACE score have proved more useful.Primary PCI with minimal treatment delay is the most effective reperfusion strategy in ST elevation myocardial infarction(STEMI). Radial access is associated with less bleeding than with the femoral approach, but outcomes appear similar. Manualthrombectomy limits distal embolization and infarct size while drug-eluting stents reduce the need for further revascularisationprocedures. Non-culprit disease is best dealt with electively as a staged procedure after primary PCI has been completed.The development of antithrombotic and antiplatelet regimens for primary PCI continues to evolve, with new indications forfondaparinux and bivalirudin as well as small-molecule glycoprotein (GP) IIb/IIIa inhibitors. If timely primary PCI is unavailable,fibrinolytic treatment remains an option but a strategy of early angiographic assessment is recommended for all patients.Non-ST segment elevation myocardial infarction (NSTEMI) is now the dominant phenotype and outcomes after the acutephase are significantly worse than for STEMI. Many patients with NSTEMI remain undertreated and there is a large body ofrecent work seeking to define the most effective antithrombotic and antiplatelet regimens for this group of patients. The benefitsof early invasive treatment for most patients are not in dispute but optimal timing remains unresolved.Cardiac rehabilitation is recommended for all patients with acute myocardial infarction but take-up rates are disappointing.Home-based programmes are effective and may be more acceptable for many patients. Evidence for the benefits of lifestylemodification and pharmacotherapy for secondary prevention continues to accumulate but the argument for omega-3 fattyacid supplements is now hard to sustain following recent negative trials. Implantable cardioverter-defibrillators for patientswith severe myocardial infarction protect against sudden death but for primary prevention should be based on left ventricularejection fraction measurements late (around 40 days) after presentation, earlier deployment showing no mortality benefit.Incidence and mode of presentationTemporal trends for the global coronary epidemic varyby region but in most developed countries mortalityis in decline. 1 Lifestyle adjustments have contributedto this decline—most recently, the implementation ofcomprehensive smoke-free legislation in many countriesthat has already caused significant reductions inacute coronary events. 2 Smoking, a potent thrombogenicstimulus, is a major determinant of STEMI 3 anda recent analysis from Kaiser Permanente in Califor-nia—where smoke-free legislation is strictly enforced—showeda 62% decline in STEMI between 1999and 2008 while NSTEMI increased by 30%. 4 Overall,there was a 24% reduction in hospitalisations for acutecoronary syndromes despite lowering of diagnosticthresholds by sensitive troponin biomarkers. 5 This wasaccompanied by improvement in the age- and sex- adjusted30-day mortality from 10.5% in 1999 to 7.8% in2008. Increasing rates of interventional managementno doubt contributed to the improved outcomes but1London Chest Hospital, NIHR Cardiovascular Biomedical Research Unit,London, E2 9JX, UK.2Barts and the London School of Medicine and Dentistry London ChestHospital, London, UK* As previously published in Heart, 2011;97(22):1820-7.Contact address:Dr. Charles Knight, London Chest Hospital, NIHR Cardiovascular BiomedicalResearch Unit, London, E2 9JX, UK.E-mail: charles.knight@bartsandthelondon.nhs.uk

C. Knight et al.Almanac 2011: acute coronary syndromesparallel increases in plaque-stabilising treatment withhigh-dose statins must also have played a role6 becausevulnerable thin-cap fibroatheromas, often remote fromthe infarct-related artery and unrelated to stenosis severity,are the sites at which recurrent plaque eventsusually occur. 7,8DiagnosisDiagnostic definitions of acute coronary syndromes areinternationally agreed based on troponin release andsymptomatic, electrocardiographic, or functional criteria.9TroponinsDemonstration of a changing troponin concentrationin the first 24 h with at least one value above thedecision limit is central to the diagnosis of acute myocardialinfarction. Now available are high-sensitivitytroponin assays permitting significant reductions inthe threshold for detection. An early study evaluatedfour high-sensitivity assays in 718 patients with suspectedacute coronary syndrome, 17% of whom hadacute myocardial infarction. Diagnostic performancewas excellent, the area under the receiver operatorcurves ranging from 0.95 to 0.96 compared with 0.90for the standard assay. 10 The implications for cardiacoutcomes and clinical management were assessed in amore recent study in which high-sensitivity troponinI was measured in 1038 patients with suspected acutecoronary syndrome. 11 Values below the previous limitof detection (0.20 ng/ml)—conventionally considered‘normal’—showed graded association with death ornon-fatal myocardial infarction, with rates of 7% and39% for troponin concentrations of

Romanian Journal of CardiologyVol. 22, No. 2, 2012with suspected myocardial infarction presenting withleft bundle branch block (LBBB). However, a retrospectiveanalysis of 892 patients in a Mayo Clinic STEMIregistry, found that of the 36 who presented with newLBBB, only 12 (33%) had a final diagnosis of acutemyocardial infarction. 17 These data show that LBBB isof limited diagnostic utility in suspected myocardialinfarction and provide a case for new diagnostic strategiesin this high-risk group. Also at high risk are patientswith acute myocardial infarction caused by proximalleft anterior descending coronary artery (LAD)occlusion. A report that this may be associated with adistinct ECG pattern has now been confirmed in a seriesof 35 patients who underwent primary PCI of theLAD, all of whom showed ST-segment depression atthe J-point with up-sloping ST segments and tall, symmetricalT-waves in the pre cordial leads of the 12-leadECG. 18,19 The authors recommend that this ECG patternin patients presenting with suspected myocardialinfarction should prompt triage for immediate reperfusiontherapy.ImagingEchocardiography provides the most readily availableimaging modality for acute phase diagnosis of myocardialinfarction by identifying new left ventricularregional wall motion abnormality. A new diagnosticapplication for identifying those patients with NSTEMIwho have complete coronary occlusions was recentlydescribed. 20 In such patients, circumferential strainmeasured within 1 h of admission was independentlydiagnostic, values ≥10% showing 90% sensitivity and88% sensitivity for angiographic coronary occlusion.The authors suggest that strain measurements in theacute phase of NSTEMI might be used for triaging patientsfor immediate reperfusion therapy.Risk stratificationThe risk of death and other ischaemic events in patientswith acute coronary syndromes varies considerablyacross diagnostic phenotypes. Objective criteria toquantify risk are now increasingly used to guide treatmentand determine prognosis.Clinical factorsClinical factors are used intuitively by clinicians.They recognise that risk increases with age and showsimportant gender differences—young women withSTEMI, for example, having a 15–20% higher mortalityrisk than men. 21 ECG criteria 22 and routine biochemistryare also used for risk stratification, outcomesworsening with admission hyperglycaemia and also itC. Knight et al.Almanac 2011: acute coronary syndromesseems with admission hypoglycaemia. 23,24 Despite clinicians’reliance on clinical assessments of risk it is nowclear that they often get it wrong and a recent study hasshown little association with objective measures of riskusing validated risk scores. 25Diagnostic biomarkersIncreasing troponin release in NSTEMI is associatedwith a proportionate increase in the risk of lethalarrhythmias, cardiogenic shock, new heart failure anddeath. 26 C-reactive protein, the most widely studiedprognostic biomarker, is also moderately predictive ofadverse outcomes in acute coronary syndromes, a recentmeta-analysis reporting a pooled RR of 2.18 (1.77to 2.68) for the top (>10 mg/l) compared with the bottom(≤3 mg/l) category of values, 27 Generally speaking,however, individual biomarkers have yet to find a usefulclinical role—a recent 5-year follow-up of patientswith NSTEMI included in FRISC II reporting thatnone of N-terminal pro-brain natriuretic peptide (NTproBNP),C-reactive protein, cardiac troponin I andestimated glomerular filtration rate provided incrementalprognostic value to established risk indicators,except NT-proBNP for 6-week outcomes. 28 Combiningmultiple biomarkers may improve predictive power foradverse outcomes but confirmation of incremental valueover established risk scores is still awaited. 29Risk scoresValidated risk scores based on a range of readilyavailable factors provide the most effective means ofrisk stratifying patients with acute coronary syndromes.The GRACE score is widely used and in a comparativevalidation study involving 100 686 cases of acutecoronary syndromes its discriminative performance inpredicting mortality compared favourably with a rangeof other risk models including PURSUIT, GUSTO-1,GRACE, SRI and EMMACE. 30 The GRACE scoreappe ars to have lost none of its clinical value with theavai lability of high-sensitivity cardiac troponin assays.In an international cohort of 370 patients with acutecoronary syndromes, the area under the curve of theGRACE score was 0.87 and 0.88 for in-hospital and1-year mortality, and addition of high-sensitivity cardiactroponin produced no improvement in the mortalityprediction. 31Primary percutaneous coronary interventionThe MINAP public report for England and Wales recordsthat 70% of all patients with STEMI received reperfusiontherapy in 2010/2011, of whom 81% receivedprimary PCI. 32 The drive towards primary PCI, based

C. Knight et al.Almanac 2011: acute coronary syndromeson evidence of a sustained mortality benefit comparedwith fibrinolysis, 33 has been underpinned by the establishmentof regional networks that have defined localstandards of care and provided infrastructure for staffingheart attack centres. 34,35Timely treatment is essential to maximise prognosticbenefit, 36,37 and important as it is to achieve doorto-balloontimes within 90 min, other intrinsic delayswithin the healthcare process also need consideration.Thus, a Danish registry analysis of 6209 patients withSTEMI found that ‘system delay’ (time from first contactwith the healthcare system to the initiation of reperfusiontherapy)—as well as door-to-balloon time—was a key modifiable risk factor, with an HR for mortalityduring the next 3.4 years of 1.22 (95% CI 1.15to 1.29; p

Romanian Journal of CardiologyVol. 22, No. 2, 2012to be inversely related to inflammatory burden 60 andmay be enhanced by intracoronary administration, arecent meta-analysis reporting improved clinical outcomesby this route. 61 However, abciximab is expensiveand there are now studies confirming non-inferiorityof ‘small-molecule’ GPIIb/IIIa receptor blockers. Thus,investigators using the Swedish Coronary Angiographyand Angioplasty Registry compared 2355 primary PCIpatients who received eptifibatide with 9124 who receivedabciximab and found similar rates of death ormyocardial infarction during 1-year follow-up (15.0%vs 15.7%). 62 In a smaller study, 427 patients randomisedeither to eptifibatide or abciximab showed comparablerates of complete ST-segment resolution 60 minafter primary PCI (62.6% vs 56.3%) with no significantdifferences between cardiovascular outcomes. 63 In theOn-TIME 2 trial, another small molecule compound,tirofiban, in combination with aspirin and clopidogrel,provided more effective platelet inhibition than aspirinand clopidogrel alone in patients undergoing primaryPCI. The degree of platelet inhibition showed significantrelationship with major adverse cardiac events,including stent thrombosis. 64 These findings have yetto penetrate international guidelines but many centresare now switching from abciximab to small-moleculecompounds to reduce pharmacological costs.Other antithrombotic drugsFondaparinuxIntravenous heparin during primary PCI further enhancesthrombus resolution during primary PCI butongoing treatment with low molecular weight heparinhas now given way to fondaparinux, a syntheticfac tor Xa inhibitor. A recent individual patient-levelcom bined analysis of 26 512 patients from the OASIS5 and 6 trials who were randomised to fondaparinux2.5 mg daily or a heparin-based strategy has resolvedun certainty about the clinical value of fondaparinux inpa tients undergoing primary PCI by showing a betternet clinical composite of death, myocardial infarction,stroke, or major bleeding (10.8% vs 9.4%; HR=0.87;p=0.008) in the subset of 19 085 patients treated invasively.65 A similar benefit was found in patients treatedconservatively. Fondaparinux is now widely used inpreference to heparin in acute coronary syndromes.BivalirudinBivalirudin is a direct thrombin inhibitor that showedsuperiority to a combined regimen of heparin plusa GPIIb/IIIa inhibitor in HORIZONS-AMI, largelyowing to a lower rate of major bleeding (4.9% vs 8.3%). 66All-cause mortality at 30 days was also lower in the biworseningmyocardial reperfusion with time fromadmission to primary PCI was effectively abolishedby thrombus aspiration, suggesting particular benefitsin the event of procedural delay. 53 More complexthrombectomy devices are not recommended for usein STEMI. Thus assessments of infarct size reduction intwo trials—JETSTENT comparing Angiojet rheolyticthrombectomy with primary direct stenting and PRE-PARE comparing simultaneous proximal embolic protectionand manual thrombus aspiration with manualthrombus aspiration—showed no significant benefitof these device strategies. 54,55 Consistent with this is ameta-analysis of thrombectomy trials showing that themortality benefit for patients randomised to thrombusextraction is confined to patients treated with manualthrombectomy. 56Antiplatelet strategiesCurrent recommendations are for loading doses ofaspirin and clopidogrel immediately before primaryPCI followed by maintenance treatment. Adjunctivetreatment with GPIIb/IIIa receptor blockers providesmore intensive platelet inhibition in the acute phase.The main purpose of treatment is to enhance thrombusresolution and to prevent recurrent thrombotic events,particularly stent thrombosis in the 9–12 monthsit takes for drug-eluting struts to endothelialise(1–3 months for bare metal struts). Newer, drugs thatblock the ADP P2Y12 receptor more potently than clopidogrel are now available 57 and have been evaluatedin combination with aspirin in patients undergoingprimary PCI. In the TRITON-TIMI 38 trial of dualantiplatelet treatment, prasugrel reduced the primaryoutcome of cardiovascular death, non-fatal myocardialinfarction and non-fatal stroke compared with clopidogrel(6.5% vs 9.5%), but this was associated with asignificantly greater risk of major bleeding, includingfatal bleeding, raising important safety concerns. 58 Ticagrelorhas also been evaluated against clopidogrelin a substudy of the PLATO trial and like prasugrel itproved more effective in reducing the primary outcomeof cardiovascular death, myocardial infarction or stroke,although the absolute difference was small (9.0%vs 10.7%). 59 Strikingly, however, there appeared to beenhanced bleeding, and ticagrelor now has a guidelinerecommendation for use in primary PCI, although itsfinal place in the therapeutic arsenal must await costeffectivenessand long-term safety studies.Abciximab, given intravenously, has been the mostwidely used GPIIb/IIIa receptor blocker in patientswith STEMI undergoing primary PCI. Benefits appearC. Knight et al.Almanac 2011: acute coronary syndromes

C. Knight et al.Almanac 2011: acute coronary syndromesvalirudin group, with persistent benefit after 3 years(5.9% vs 7.7%), assuring a guideline recommendationfor bivalirudin in primary PCI. 46 It should be noted,however, that femoral artery access was used in 94.1%of the HORIZONS-AMI population and whether thereduction in bleeding with bivalirudin applies equallyto centres where radial access is the preferred approachis not known.Fibrinolytic treatmentEvidence that fibrinolysis is less effective than primaryPCI in the emergency management of STEMI, has nowbeen reinforced by evidence of reduced cost-effectiveness,67 yet a significant minority of patients in Englandand Wales continue to be treated with it. 32 This may bejustified if fibrinolysis can be delivered within 30 minafter presentation when primary PCI is not immediatelyavailable, because treatment delays by either modalityare associated with substantial increases in mortality.36 This has provided justification for programmes ofpre-hospital thrombolysis, particularly in rural regionswhere transport times are prolonged, but enthusiasmfor this approach may now be diminished by evidencefrom the MINAP registry showing higher rates ofreinfarction compared with in-hospital thrombolytictreatment for patients with STEMI. 68 The difference inreinfarction rates was only significant for tenecteplase(9.6% vs 6.4%), not reteplase, and was particularlymarked when transport times exceeded 30 min. It wasattributed to differences in the use of adjunctive antithrombotictreatment in the two treatment environments.Interestingly, bleeding complications were morecommon in the hospital environment where adjunctiveantithrombotic treatment was more aggressive, consistentwith recent data from RIKS-HIA showing that majorbleeding complications among patients receivingfibrinolytic treatment continued to increase from 2001to 2006 as antithrombotic treatments became moreeffective. 69 The availability of potent ADP P2Y12 receptorblockers has raised further concerns about bleedingcomplications, and it was gratifying, therefore, that thePLATO trial substudy confirmed that event rates couldbe reduced with ticagrelor compared with clopidogrelwithout an increase in bleeding risk. 70,71The role of invasive treatment after fibrinolytic treatmentin STEMI has been clarified in two recent meta-analysesof small and medium-size trials comparingstrategies of routine early angiography for all patientswith deferred or ischaemia-guided angiography. 72,73Both meta-analyses reported that routine early angio-Romanian Journal of CardiologyVol. 22, No. 2, 2012gra phy was associated with reductions in the rates ofre current myocardial infarction and death and thisstra tegy is now recommended in international guidelines.Non-ST-segment elevation myocardialinfarctionNSTEMI has become the dominant mode of presentationfor patients with acute myocardial infarction andin the recent analysis from Kaiser Permanente accountedfor 66.9% of cases. 4 There has been a perceptionthat NSTEMI is relatively benign despite evidence thatprognosis after 2 months becomes substantially worsethan with STEMI. 21,74 This may explain the tendency ofdoctors to under-treat NSTEMI based on a mismatchbetween perceived and actual risk that distorts managementdecisions, perpetuating the ‘treatment–risk paradox’.25 Thus, despite a worse prognosis, patients withNSTEMI are less likely than patients with STEMI toreceive optimal secondary prevention treatment. 75 Moreover,in a study of 13 489 NSTEMI admissions re cordedin the MINAP registry, invasive management wasassociated with better outcomes but was applied inequitably, with lower rates in high-risk groups, includingolder patients, women and those with cardiac comorbidities.76Emergency managementDual antiplatelet treatment with aspirin and clopidogrelis central to the management of NSTEMI. 77The role of newer more potent ADP P2Y12 receptorblockers remains undetermined, although ticagrelorlo oks promising, based on its ability to reduce ischaemicevents compared with clopidogrel in NSTEMIas well as STEMI, without increasing the risk of bleeding.78 Si multaneous treatment with fondaparinux isnow recommended in preference to enoxaparin, basedon the findings in OASIS 5 which compared thesea gents in 20 078 patients with acute coronary syndromes.79 Patients randomised to fondaparinux showeda 50% reduction in major bleeding compared witheno xap arin, with no difference in the incidence of ischaemicevents. The reduction in bleeding risk wascompa rable whether clopidogrel or GPIIb/IIIa receptorblockers were co-prescribed 80 and cost-effectivenesshas now been confirmed. 81 Indications for bivalirudinin NSTEMI have been harder to define and although ithas a licence for use in combination with aspirin andclo pidogrel, this is based principally on its safety profile(lower bleeding risk), its efficacy for reducing ischaemicevents being no greater than either heparin plus

Romanian Journal of CardiologyVol. 22, No. 2, 2012GPIIb/IIIa receptor blocker or bivalirudin plus GPIIb/IIIa receptor blockers. 82The majority of patients with NSTEMI benefit frominterventional management, 83 but recent data suggestthis could be delayed for at least 24 h unless continuingclinical instability unresponsive to GPIIb/IIIa receptorblockers calls for earlier action. Thus, in a randomisedcomparison of immediate versus deferred PCI in251 patients, the incidence at 30 days of the primaryend point, a composite of death, non-fatal myocardialinfarction or unplanned revascularisation, was significantlyhigher in the group receiving immediate PCI(60% vs 39%). 84 The difference persisted at 6 months’follow-up. Delaying intervention beyond 96 h is unlikelyto be helpful, yet registry data show that this iscommon, particularly in high-risk patients who havemost to gain from revascularisation. 85 The evidence fortimely revascularisation is largely based on PCI databut a small proportion of patients require coronary arterybypass grafting (CABG). An analysis of US registrydata showed that the timing of CABG has no palpableeffect on outcomes, the composite of death, myocardialinfarction, congestive heart failure, or cardiogenicshock being similar (12.6% vs 12.4%) whether CABGis done within 48 h of admission or later. 86 In general,therefore, early surgery is recommended to limit hospitalstay and reduce resource use.Secondary preventionCardiac rehabilitationThe benefit of cardiac rehabilitation among 30 161Medicare beneficiaries, 20.5% of whom had recentmyo cardial infarction, was confirmed by a strong dose–responserelationship between the number of rehabilitationsessions attended and long-term rates ofdeath and myocardial infarction. 87 Yet a contemporaryreport of cardiac rehabilitation in the UK found thatonly 26% of eligible patients with myocardial infarctionare recruited, with adherence rates of 65-85%. 88 Reasonsfor the poor uptake are complex but include thefact that many patients do not want to participate incentre-based group programmes. A systematic reviewhas now reported that home-based programmes areequally effective in improving clinical and health-relatedquality-of-life outcomes and are more acceptable tomany patients. 89 Healthcare costs are similar, supportingthe further provision of home-based cardiac rehabilitationsuch as that described by investigators inBirmingham. 90 The recent demonstration of improvedC. Knight et al.Almanac 2011: acute coronary syndromesmyocardial blood flow plus reductions in circulatingangiogenic cytokines in patients undergoing cardiacrehabilitation provides some reassurance that clinicalimprovement is physiologically based. 91Lifestyle modificationAn important component of cardiac rehabilitation islifestyle adjustment to help protect against further coronaryevents. Top of the list is smoking cessation. Arecent study of 1581 patients followed up for 13 yearsshowed that the adjusted HR for all-cause mortalitywas lower by 43% in lifelong non-smokers and by 43%in patients who quit after myocardial infarction. 92 Anew finding was that among persistent smokers, eachreduction of five cigarettes smoked per day reduced therisk of death by 18%, providing some comfort for thosepatients for whom complete abstinence proves impossible.Even among patients who mange to quit, thereremains the hazard of second-hand smoke exposure, asreflected by data from Scotland showing that adjustedall-cause and cardiovascular mortality among neversmokingsurvivors of myocardial infarction increasesaccording to smoke exposure measured by serum cotinineconcentration. 93 The message is clear that protectionagainst recurrent events in survivors of myocardialinfarction requires smoking cessation by the patientand also by those with whom the patient makes contact,particularly family members.Together with smoking cessation, advice about exerciseand diet delivered in formal programmes can havea salutary effect on modifiable risk profiles, includingserum cholesterol, blood pressure and body mass index.94 Dietary recommendations usually include w-3fatty acid supplements 95 but this has now been questionedby the findings of two studies. In the first, 4837patients with previous myocardial infarction were randomisedto margarines containing marine n-3 fattyacids and plant-derived a-linolenic acid in a 2×2 factorialdesign. 96 The rate of adverse cardiovascular eventsdid not differ significantly among the study groups. Inthe second study, highly purified w-3 fatty acids wererandomly allocated to 3851 patients with acute myocardialinfarction followed up for 12 months. 97 Therewere no significant differences in rates of sudden cardiacdeath (1.5% vs 1.5%), total mortality (4.6% vs 3.7%),or major adverse cerebrovascular and cardiovascularevents (10.4% vs 8.8%) between treatment and placebogroups. The results of these two trials make recommendationsfor secondary prevention with w-3 fattyacid supplements after myocardial infarction difficultto sustain.

C. Knight et al.Almanac 2011: acute coronary syndromesPharmacotherapyThe importance of optimal secondary preventionafter myocardial infarction was emphasised in a modellingstudy, in which greater absolute gains in survivalwere achieved by optimising secondary preventiontreatments compared with in-hospital reperfusiontreatments (104 vs ≤30 lives/10 000). 98 Recommendedare aspirin, b blockers, statins, renin–angiotensinsystem blockers and thienopyridines—a study of 5353patients showing that treatment with all five drugs reduced1-year mortality by 74% compared with treatmentwith one or none of them, with consistent effectsin STEMI and NSTEMI. 75 Evidence that statins andclopidogrel provide the greatest independent pharmacologicalbenefit (ORs for death 0.85 (0.73 to 0.99) and0.84 (0.72 to 0.99)) was provided by the GRACE investigatorsin a nested case–control study of 5148 patientswith acute coronary syndromes, 99 and two separate studieshave now reported the adverse consequences of failingto adhere to treatment with these drugs during thefirst year after discharge. 100,101 The message is clear thatprescribing secondary prevention treatment accordingto guideline recommendations and promoting adherenceto treatment can together produce further mortalityreductions in patients with myocardial infarction.Implantable cardioverter-defibrillators(ICDs)Left ventricular ejection fraction (LVEF) after acutemyocardial infarction remains predictive of suddendeath in the primary PCI era 102 and is the key determinantof which patients should be offered an ICDfor primary prevention. 103 However, LVEF in the acutephase is an unreliable guide to LVEF at 3 months whensignificant recovery of contractile function has oftenoccurred. But there is another reason for delaying decisionsabout ICDs beyond the guideline-recommended40 days. Thus a recent randomised trial of ICD therapyin 898 patients with LVEF ≤40%, recruited within31 days of acute myocardial infarction, showed no overallmortality reduction for the patients who receivedan ICD because a high rate of non-sudden death negatedprotection against sudden arrhythmic death providedby the ICD. 104 A secondary analysis of DINAMIThas now confirmed a high risk of non-sudden deathin patients who receive ICDs early after myocardialinfarction, while the VALIANT investigators have reportedthat recurrent infarction or cardiac rupture arecommon causes of death during this period. 105,106 Takentogether, these findings explain why ICDs fail toRomanian Journal of CardiologyVol. 22, No. 2, 2012protect against death if implanted early after myocardialinfarction. Decisions should, therefore, be deferred,and patients selected for ICD therapy according tomeasurement of LVEF at 40 days.ConclusionThe management of acute coronary syndromes continuesto evolve and improve. The challenge for cardiovascularresearchers is to maintain this momentum andto ensure that the improvements in outcome seen inthe developed world have a global impact.Conflict of interests: None.Provenance and peer review: Commissioned; internallypeer reviewed.References1. Mirzaei M, Truswell AS, Taylor R, et al. Coronary heart disease epidemics:not all the same. Heart 2009;95:740–6.2. Mackay DF, Irfan MO, Haw S, et al. Meta-analysis of the effect of comprehensivesmoke-free legislation on acute coronary events. Heart2010;96:1525–30.3. Björck L, Rosengren A, Wallentin L, et al. Smoking in relation to STsegmentelevation acute myocardial infarction: findings from the Registerof Information and Knowledge about Swedish Heart IntensiveCare Admissions. Heart 2009;95:1006–11.4. 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Romanian Journal of Cardiology | Vol. 22, No. 2, 2012REVIEWSAlmanac 2011: cardiac arrhythmias and pacing. The nationalsociety journals present selected research that has driven recentadvances in clinical cardiology*R. LiewArticle received on the 4 th January 2012. Article accepted on the 12 st January 2012.Atrial fibrillationClinical trialsIn the past 2 years, a number of landmark clinicaltrials have been published which further our understandingand clinical management of patients with atrialfibrillation (AF). Two of the major goals in the treatmentof this condition include reducing progression orrecurrence of the arrhythmia and decreasing the risk ofcardiovascular events, thereby improving quality of lifeand decreasing morbidity. Following on from a largebody of evidence from preclinical studies, small clinicaltrials and meta-analyses suggesting that blockadeof the renin–angiotensin system has beneficial effectson the pathophysiology of AF, 1 two large multicentre,placebo-controlled, randomised trials were conductedto determine the effects of angiotensin II receptorblockers (ARBs) on AF.The first of these trials, published in 2009, tested thehypothesis that the ARB valsartan could reduce the recurrenceof AF in patients with underlying cardiovasculardisease, diabetes or left atrial enlargement and ahistory of documented AF, in addition to establishedtreatments. 2 A total of 1442 patients were enrolled intothe study—722 assigned to the valsartan group (targetdose 320 mg) and 720 to the placebo group. Theinvestigators found that treatment with valsartan hadno significant effect on AF recurrence (AF recurrence51.4% in the valsartan group and 52.1% in the placebogroup, p=0.73) over a relatively short follow-up periodof 1 year.The second large ARB randomised controlled trial(RCT) published this year evaluated whether irbesartanwould reduce the risk of cardiovascular events inpatients with AF. 3 Patients with a history of risk factorsfor stroke and a systolic blood pressure of at least110 mm Hg were randomly assigned to receive eitherirbesartan (target dose of 300 mg once daily) or placebo.Patients for this study were already enrolled inone of two other AF trials looking at clopidogrel plusaspirin versus aspirin alone or versus oral anticoagulants.The investigators found that irbesartan did notreduce cardiovascular events or hospitalisation ratesfor AF (total of 9016 enrolled with a mean follow-upof 4.1 years) and that, not surprisingly, more patientsin the irbesartan group had symptomatic hypotensionand renal dysfunction than those in the placebo group.Although the main findings from both of these largeRCTs were negative, it should be noted that they weresecondary prevention studies—that is, patients alreadyhad established AF, and also had more advanced stagesof disease (over 80% of patients in both studies had ahistory of persistent or permanent AF), implying thatthe substrate for AF was already well established inboth study groups. It might be argued that blockade ofthe renin–angiotensin system may be a more effectivestrategy if performed earlier during the natural historyof the disease or even before AF develops (ie, primaryprevention), since ACE inhibitors and ARBs maypre vent, but not necessarily reverse, the electrical andstructural remodelling that leads to the developmentand progression of the arrhythmia. In support of this,a smaller randomised single-centre study of 62 patientswith lone AF, with no history of hypertension orheart disease, presenting to the emergency departmentreported that patients given ramipril (5 mg/day) hadsignificantly fewer AF relapses during a 3-year followupperiod than patients given placebo. 41Department of Cardiology, National Heart Centre Singapore, Duke-NUSGraduate Medical School, Singapore, Singapore* As previously published in Heart, 2011;97(21):1734-43.Contact address:Dr. Reginald Liew, Department of Cardiology, National Heart CentreSingapore, 17 Third Hospital Avenue, Singapore 168752, Singapore.E-mail: reginald.liew.k.c@nhcs.com.sg

Romanian Journal of CardiologyVol. 22, No. 2, 2012A significant new addition to the pharmacologicaloptions available for treating AF has been the emergenceof dronedarone, a multichannel blocker with similarstructural and electrophysiological properties to amiodaronewith the main exception being removal of iodineand the addition of a methane-sulphonyl group. 5These structural changes result in decreased lipophilicity,shortened half-life (to approximately 24 h), reducedtissue accumulation and theoretically fewer sideeffects than associated with amiodarone.The ATHENA (A placebo-controlled, double-blind,parallel-arm Trial to assess the efficacy of dronedarone400 mg twice daily for the prevention of Hospitalisationor death from any cause in patiENts with Atrialfibrillation/flutter) trial was a ground-breaking studypublished in early 2009 evaluating the effect of dronedaroneon cardiovascular events in patients with AF. 6In this trial, 4628 patients with AF (paroxysmal or persistent)or atrial flutter who had an additional risk factorfor death (age ≥70 years, diabetes, history of stroke/transient ischaemic attack (TIA), systemic embolism,left atrial diameter ≥50 mm and ejection fraction≤40%) were randomly assigned to receive dronedarone(400 mg twice daily) or placebo. Over a mean follow-upof 21±5 months, the investigators found that patients inthe dronedarone group had significantly lower primaryoutcome of first hospitalisation due to cardiovascularevents or death than the placebo group (734 (32%) vs917 (39%), respectively, p

R. LiewAlmanac 2011: cardiac arrhythmias and pacingwithin 90 min in the vernakalant group compared withthe amiodarone group (60/116 (51.7%) compared with6/116 (5.2%), p

Romanian Journal of CardiologyVol. 22, No. 2, 2012for treatment of stroke and systemic embolism, anothermajor advantage is that there is no need for internationalnormalisation ratio (INR) monitoring. However,disadvantages include the lack of a specific antidote(its half-life is 12–17 h) and a slightly increased risk ofnon-haemorrhagic side effects, including dyspepsia.How this promising new oral anticoagulant drug willbe incorporated into current local practices around theworld will require future evaluation and consideration.For example, there may be little to be gained fromswitching patients already receiving warfarin and withexcellent INR control to dabigatran, while patients withpoor INR control or those who have newly started oralanticoagulation may derive greater benefit. Local standardsof care for anticoagulation control and follow-upmay also be an important consideration, as concludedin a subanalysis of the RE-LY study, in which the investigatorsfound that sites with poor INR control and greaterbleeding from warfarin may receive greater benefitfrom dabigatran 150 mg twice daily. 26 Other substudiesfollowing on from the original RE-LY trial have shownthat the benefits of dabigatran are similar between patientswho have never received a vitamin K antagonist(VKA-naive patients) and VKA-experienced patients, 27and that dabigatran can be used as a safe alternative towarfarin in patients requiring cardioversion. 28In the ACTIVE A study, the ACTIVE (AF ClopidogrelTrial with Irbesartan for prevention of VascularEvents) investigators evaluated whether the addition ofclopidogrel to aspirin would reduce the risk of vascularevents compared with aspirin alone in patients forwhom a VKA was considered unsuitable. 29 The ACTI-VE W trial had previously demonstrated that the combinationof aspirin and clopidogrel was inferior to oralanticoagulation for the prevention of vascular events inpatients with AF at high risk of stroke. 30 In the ACTIVEA study, involving 7554 patients and a median followupof 3.6 years, the investigators found that the combinationof both antiplatelet agents reduced the risk ofmajor vascular events, especially stroke, compared withaspirin alone but at the price of increased risk of majorhaemorrhage. The clinical implications of the ACTIVEA and ACTIVE W trials are that oral anticoagulation isbetter than the combination of aspirin and clopidogrelin stroke prevention in patients with AF, but for patientsfor whom oral anticoagulation is unsuitable, thecombination of antiplatelet agents is better than aspirinalone, although the risk of major haemorrhage is alsogreater. This reinforces the need for appropriate counsellingand risk stratification of patients when decidingR. LiewAlmanac 2011: cardiac arrhythmias and pacingupon the most suitable strategy to lower the risk of vascularevents in patients with AF.Another important randomised controlled clinicaltrial including patients for whom a VKA was not suitableinvolved the use of new oral direct and competitiveinhibitor of factor Xa, apixaban. 31 The AVERROES(Apixaban vs acetylsalicylic acid to prevent stroke inpatients with AF who have are unsuitable for vitaminK antagonist treatment or for whom this treatmenthas failed) study involved the random assignment of5599 patients with AF (involving 522 centres in 36countries) to apixaban (5 mg twice daily) or aspirin(81–324 mg/day). 32 In that study, patients with AF wereaged ≥50 years and had to have at least one risk factorfor stroke in addition to being unable to take a VKA,either because it had already been shown to be unsuitableor was deemed to be unsuitable. The investigatorsfound that apixaban reduced the risk of stroke orsystemic embolism without significantly increasing therisk of bleeding or intracranial haemorrhage and alsoreduced the risk of a first hospitalisation for a cardiovascularcause.Recent studies in the field of new mechanical approachesto stroke prevention in AF include the PROTECTAF (Watchman Left Atrial Appendage System for EmbolicProtection in Patients with AF) study. 33 In thisnon-inferiority study, the efficacy and safety of a newpercutaneous left atrial appendage (LAA) closure devicewas compared with warfarin treatment in 707 patientswith non-valvular AF. Study participants had tohave at least one risk factor for stroke (in addition toAF) and were assigned in a 2:1 ratio to receive the LAAclosuredevice and subsequent discontinuation of warfarinor warfarin alone (with a target INR of between2.0 and 3.0). The LAA-closure device was successfullyimplanted in 88% of subjects assigned to the interventiongroup. After a mean follow-up of 18±10 months,the primary efficacy event rate of stroke (ischaemic orhaemorrhagic) was 3.0 per 100 patient-years (95% CI1.9 to 4.5) in the intervention group and 4.9 per 100patient-years (95% CI 2.8 to 7.1) in the control group.Primary safety events were more common in the interventiongroup than in the control group, and weremainly related to periprocedural complications (pericardialeffusion in 4.8%, major bleeding in 3.5% andperiprocedural ischaemic stroke in 1.1%). This importantstudy demonstrates that the Watchman (Atritech,Plymouth, Minnesota, USA) LAA-closure device mayprovide an alternative strategy to oral anticoagulationfor the prevention of stroke in patients at high risk with

R. LiewAlmanac 2011: cardiac arrhythmias and pacingnon-valvular AF and at high thromboembolic risk,although the trade-off is an increased risk of periproceduralcomplications related to device implantation.As with all new interventional procedures, safety ofthe Watchman LAA-closure device is likely to improvewith increased operator experience and familiaritywith the new technology. 34 Longer-term follow-updata with an earlier percutaneous LAA-closure device,PLAATO (percutaneous left atrial appendage transcatheterocclusion) system, 35 suggest that such devicescan lower the annualised risk of stroke/TIA comparedwith the expected stroke/TIA risk assessed using theCHADS2 score (3.8% a year and 6.6% a year, respectively),although event rates still remain significant. 36Epidemiology and genetics of AFEpidemiological studies have shed further light onthe mechanisms underlying AF and identified newrisk factors. Using data from the Framingham HeartStudy, investigators identified a prolonged PR interval(>200 ms) as a predictor of incident AF, pacemaker implantationand all-cause mortality in 7575 individuals(mean age 47 years; 54% women). 37 This study contradictsthe previously held belief that first-degree heartblock is benign 38 and raises further questions about themechanism by which a prolonged PR interval might increasethe risk of developing AF. In another study using4764 participants from the Framingham Heart Study,a new risk score was developed aimed at predicting anindividual’s absolute risk for developing AF. 39 Age, sex,body mass index, systolic blood pressure, treatment forhypertension, PR interval, clinically significant cardiacmurmur and heart failure were all found to be associatedwith AF (p

Romanian Journal of CardiologyVol. 22, No. 2, 2012Catheter ablation of AFIn a large prospective, multicentre trial involving 19centres, the use of catheter ablation was compared withantiarrhythmic drug treatment. 55 A total of 167 patientswith paroxysmal AF for whom at least one antiarrhythmicdrug had failed and who had experiencedat least three AF episodes in the preceding 6 monthswere randomised (2:1) to undergo catheter ablation ormedical treatment. After a 9 month follow-up period,the investigators found that catheter ablation resultedin a longer time to treatment failure and significantlyimproved quality-of-life scores. Major 30-day treatment-relatedadverse events occurred in five of 103 patients(4.9%) treated with catheter ablation and five of57 patients (8.8%) treated with antiarrhythmic drugs.An improvement in the quality of life was also demonstratedin a prospective follow-up study of 502 symptomaticsubjects who underwent AF ablation. 56 The improvementin quality of life was sustained at 2 years inpatients with and without recurrence of AF, althoughthe change was greatest in patients who remained freefrom AF and without antiarrhythmic drug treatment.Several well-respected, high-volume centres haverecently published their long-term outcomes followingcatheter ablation for AF. The Bordeaux group reportedtheir 5 year follow-up data on 100 patients (86%male; age 55.7±9.6 years; 63% paroxysmal AF; 36%with structural heart disease). 57 Arrhythmia-free survivalrates after a single catheter ablation procedurewere 40%, 37% and 29% at 1, 2 and 5 years, respectively(most recurrences occurred over the first 6 months). Atotal of 175 procedures were performed with a medianof two for each patient (51 patients underwent a secondprocedure and 17 a third). There were no periproceduraldeaths, although major complications (cardiac tamponaderequiring drainage) occurred in three patients(3%), and minor complications (arteriovenous (AV)fis tula, femoral pseudoaneurysm and asymptomaticpul monary vein stenosis) occurred in another threepa tients. The important point to note from this studyis that even in experienced hands with a selected AFpo pulation (patients who are referred for AF ablationtend to be younger and have fewer comorbidities), thereis a steady decline in arrhythmia-free survival withre currences seen up to 5 years after ablation, althoughthe majority occur within the first 6–12 months.An experienced German centre also recently reportedtheir long-term follow-up data of catheter ablationin 161 patients (75% male; age 59.8±9.7 years) withsymptomatic paroxysmal AF and normal left ventricu-R. LiewAlmanac 2011: cardiac arrhythmias and pacinglar function. 58 They found that 75 patients (46.6%) werein sinus rhythm after the initial procedure during a medianfollow-up period of 4.8 years (0.33 to 5.5 years).A second procedure was performed in 66 and a thirdprocedure in 12 patients. One patient had an aspirationpneumonia that was successfully treated and two developeda sterile pericardial effusion that did not requiredrainage (no other procedural complications were noted).There was a low rate of progression to chronic AFduring the follow-up period, which was seen in onlyfour patients (2.5%).A group from London, UK, similarly reported theirlong-term results following catheter ablation for AF in285 patients (75% male; mean age 57 (SD 11) years;53% paroxysmal AF; 20% with structural heart disease)undergoing a total of 530 procedures. 59 During amean follow-up of 2.7 years (0.2 to 7.4 years), freedomfrom AF/atrial tachyarrhythmia was 86% for patientswith paroxysmal AF and 68% for those with persistentAF. Complications included three strokes/TIAs.Late recurrence was three per 100 years of follow-upafter >3 years. The investigators also found that targetingcomplex fractionated atrial electrograms (CFAEs)during the ablation procedure improved outcome inpatients with persistent AF. However, this was not seenin a randomised study performed by another group inwhich 119 patients with persistent AF were randomisedto additional CFAE ablation following pulmonaryvein isolation or no additional ablation. 60In summary, the reports on long-term success ratesfollowing catheter ablation for AF demonstrate that theprocedure is effective in a selected group of symptomaticpatients with AF, although a significant proportionrequire more than one ablation procedure, there arerisks of periprocedural complications and AF recurrenceremains a possible problem, even after follow-up periodsas long as 5 years. It should be noted that reportedoutcomes from the different centres cannot be directlycompared, since there are differences in patient population(eg, percentage of patients with paroxysmal andpermanent AF, patients with structural heart disease),techniques used (segmental pulmonary vein isolationvs wide area circumferential ablation), length of followupand methods used to detect AF recurrence.A number of studies have been performed to searchfor new non-invasive parameters which may help topredict AF recurrence following catheter ablation. Thesefactors include renal impairment, 61 novel echo parameterssuch as the atrial electromechanical interval, 62atrial fibrosis assessed with echo 63 or MRI 64 and B-typenatriuretic levels. 65

R. LiewAlmanac 2011: cardiac arrhythmias and pacingVentricular arrhythmias and sudden cardiacdeathVentricular arrhythmias after myocardial infarctionTo further understand the significance of the occurrenceand timing of ventricular arrhythmias in the contextof primary percutaneous coronary intervention(PCI), a secondary analysis of the APEX AMI (Assessmentof PEXelizumab in Acute Myocardial Infarction)trial was undertaken. 66 Of the 5745 patients with STelevationmyocardial infarction presenting for primaryPCI (across 296 hospitals in 17 countries), ventriculartachycardia/ventricular fibrillation (VT/VF) occurredin 329 (5.7%). Clinical outcomes and 90-day mortalitywere found to be worse in those with VT/VF than inthose without. Furthermore, outcomes were worse ifthe VT/VF occurred late (after the end of cardiac catheterisation)rather than early (before the end of cardiaccatheterisation). The occurrence of ventriculararrhythmias remained associated with a significantlyincreased mortality after adjustment for potential confounders,although whether they were causally relatedto a poorer prognosis or simply a reflection of more severeheart disease is not yet clear.In the Occluded Artery Trial-ElectrophysiologicalMechanisms (OAT-EP) study, PCI to open a persis tentlyoccluded infarct-related artery after an acute myocardialinfarction (AMI) phase was compared withop timal medical treatment alone to determine whichstra tegy reduced markers of vulnerability to ventriculararrhythmias. 67 There were no significant differencesin heart rate variability, time-domain signal-averagedECG, or T-wave variability parameters (all surrogatemarkers of ventricular instability) between eithergroup at 30 days and 1 year after the AMI, which isconsistent with the lack of clinical benefit from PCI instable patients after AMI with persistently occluded infarct-relatedarteries in the main OAT study.The Cardiac Arrhythmias and Risk Stratification AfterMyocardial Infarction (CARISMA) trial was designedto investigate the incidence and prognostic significanceof arrhythmias detected by an implantable cardiacmonitor among patients after AMI with impaired leftventricular (LV) function. 68 A total of 297 patients (outof 5969 initially screened) who had had a recent AMIand had reduced LV ejection fraction (LVEF; ≤40%) receivedan implantable loop recorder within 11±5 daysof the AMI and were followed up every 3 months for anaverage of 1.9±0.5 years. The investigators detected aclinically significant number of bradyarrhythmias andtachyarrhythmias in these patients (28% new-onset AF,Romanian Journal of CardiologyVol. 22, No. 2, 201213% non-sustained VT, 10% high-degree AV block, 7%significant sinus bradycardia, 3% sinus arrest, 3% sustainedVT and 3% VF). In particular, intermittent highdegreeAV block was associated with a very high risk ofcardiac death. The arrhythmogenic substrate for ventriculararrhythmias following reperfusion therapy forAMI was investigated in a study of 36 AMI survivorsreferred for catheter ablation of VT (13±9 years afterthe AMI). 69 Of these, 14 patients had early reperfusionduring AMI, while 22 were non-reperfused. The investigatorsfound, using detailed electroanatomical mapping,that scar size and pattern were different betweenVT patients with and without reperfusion during AMI,with early reperfusion and less confluent electroanatomicalscar being associated with faster VTs.Risk stratification for sudden cardiac death andimplantable cardioverter defibrillatorsA continuing area of active research in ventriculararrhythmias and sudden cardiac death (SCD) is inimproved methods of risk stratification and selectionof appropriate implantable cardioverter defibrillator(ICD) recipients. 70 A number of non-invasive cardiovasculartests have recently been evaluated among patientswith an increased risk of SCD (eg, AMI survivorsand patients with coronary artery disease and cardiomyopathies)with promising results. These include T-wave alternans, 71,72 single-photon emission CT myocardialperfusion imaging, 73 sympathetic nerve imagingwith 123-iodine metaiodobenzylguanidine 74 and lategadoliniumenhancement on cardiac MRI. 75 In addition,plasma biomarkers, such as serum collagen levels,which reflect extracellular matrix alterations that mayplay a part in the generation of the arrhythmogenicsubstrate, 76 may have a future role in risk stratification.Genetic markers may also be relevant, as suggested bythe observation from a combined population of 19 295black and white adults from the Atherosclerosis RiskIn Communities Study and the Cardiovascular HealthStudy that sequence variations in the nitric oxide synthase1 adaptor protein (NOS1AP) were associated withbaseline QT interval and the risk of SCD in white (butnot black) US adults. 77,78Another important area requiring further clarificationis the optimal timing of ICD insertion among AMIsurvivors who are deemed to be at greatest risk of SCD.The landmark DINAMIT study (Defibrillation IN AcuteMyocardial Infarction Trial), which did not showany mortality benefit from prophylactic ICD insertionin patients after AMI if the device was inserted within40 days of the index event, 79 has been used to guide

Romanian Journal of CardiologyVol. 22, No. 2, 2012current recommendations on ICD insertion amongAMI survivors. A recent secondary analysis of this trialconfirmed the original findings that the reduction insudden death in ICD patients was offset by an increasein non-arrhythmic deaths, which was greatest in thosewho received ICD shocks. 80A postmortem study looking at 105 autopsy recordsof patients from the VALIANT (VALsartan In Acutemyocardial infarctioN Trial) study who had died suddenlyshowed that recurrent myocardial infarction orcardiac rupture accounted for a high proportion ofsudden death in the early period after an AMI, therebypartly explaining the lack of benefit of early ICD insertionon overall mortality. 81 Arrhythmic death was morelikely to occur later on (after 3 months), which is consistentwith the findings of improved survival amongICD recipients from other major ICD trials in whichthe devices were inserted at a later stage. It should benoted, however, that 20% of sudden deaths in the firstmonth after AMI were presumed arrhythmic as therewas no specific postmortem evidence of any additionalabnormality that might have caused the sudden death.A significant proportion of patients who have an AMItherefore appear to continue to die suddenly in theearly postinfarction period from cardiac arrhythmias.These patients are not included in current internationalguidelines for ICD insertion and remain a groupfor which more research is required. Another group ofpatients who are not covered by current primary preventionICD guidelines are those with relatively preservedLVEF after an AMI. Although these patients areat lower risk of SCD than those with poor LVEF, theyrepresent a larger proportion of AMI survivors.Data from a multicentre Japanese study suggestthat in the era of primary PCI there is a low incidenceof SCD among AMI survivors (overall mortality was13.1% and SCD 1.2% over an average follow-up periodof 4.2 years among 4122 patients). 82 The risk was highestfor those with poor LVEF (40%).The Intermediate Risk Stratification Improves Survival(IRIS) trial published in 2009 further tested thehypothesis that early implantation of an ICD soon afteran AMI could improve survival compared with optimalmedical treatment.83 This was a randomised, prospective,multicentre trial which enrolled 898 patients,5–31 days after their AMI, who met the following clinicalcriteria: LVEF ≤40% and a heart rate ≥90 bpm on thefirst available ECG or non-sustained VT (≥150 bpm)R. LiewAlmanac 2011: cardiac arrhythmias and pacingduring Holter monitoring. The main difference betweenthis study and DINAMIT was a contemporary patientpopulation (70% had undergone PCI and the majoritywere receiving optimal long-term medication) andadditional non-invasive criteria to identify a populationat potentially higher risk. However, the investigatorsdid not find that ICD therapy reduced overall mortalityafter a mean follow-up of 37 months. Consistent withthe findings from DINAMIT, the reduced incidence ofSCD among ICD recipients in the IRIS study was offsetby an increased incidence of non-SCD.Catheter ablation of ventricular arrhythmiasThe VTACH (Ventricular Tachycardia Ablation inCoronary Heart disease) study, involving 16 centres infour European countries, assessed the potential benefitof catheter ablation of VT before ICD implantationin patients with a history of VT, myocardial infarctionand LVEF ≤50%. 84 Patients (n=110) were randomlyallocated to receive catheter ablation and an ICD oran ICD alone and followed-up for a mean period of22.5 months (SD 9.0). The investigators found thatprophylactic VT ablation before ICD implantationprolonged the time to VT recurrence from 5.9 months(IQR 0.8–26.7) in the ICD only group to 18.6 months(lower quartile 2.4 months; upper quartile could not bedetermined) in the ablation and ICD group. Complicationsrelated to the ablation procedure occurred intwo patients. This study is in accordance with an earlierprospective randomised study of 128 patients, whichdemonstrated that prophylactic catheter ablation ofthe ventricular arrhythmogenic substrate reduced theincidence of ICD therapy in patients with a historyof myocardial infarction and previous ventricular arrhythmias.85 It should be noted that VT ablation wasperformed in experienced centres in both these trialsand that there was no significant effect of catheter ablationon overall mortality. Whether VT ablation shouldroutinely be performed before ICD insertion for secondaryprevention of SCD in stable patients with previousmyocardial infarction remains to be determined.There has been an increase in the number of publicationson epicardial ablation for VT over the past fewyears in view of the realisation that not all VTs can besuccessfully eliminated by an endocardial-only approach.86,87 In a retrospective study of 156 epicardialabla tions for VT (out of a total of 913 VT ablations)in three tertiary centres evaluating the safety and midtermcomplications of epicardial VT ablation, the riskof major acute (epicardial bleeding, coronary stenosis)

R. LiewAlmanac 2011: cardiac arrhythmias and pacingred with the ICD group (17.2% compared with 25.3%,respectively, p=0.001). Although these results appearimpressive at first glance, closer examination of thedata reveals that the main superiority of CRT-D wasin reducing the rate of hospitalisation for heart failureand that there was no significant difference in mortalitybetween the two groups (which was 3% annually).Furthermore, the study failed to show that NYHA classI patients fulfilling the enrolment criteria benefitedfrom CRT-D.In RAFT (Resynchronisation-Defibrillation forAm bu latory Heart Failure Trial), CRT-D was comparedwith ICD alone in patients with NYHA class II orIII heart failure, LVEF≤30%, intrinsic QRS duration≥120 ms or a paced QRS duration of ≥200 ms. 94 The investigatorsfound that over a mean period of 40 months,the primary outcome (all-cause mortality or heart failurehospitalisation) occurred in fewer patients in theCRT-D group (33.2% compared with 40.3% in the ICDgroup, p1000/day) from the right or left ventricular outflowtract, a significant negative correlation between PVCprevalence and δLVEF and positive correlation withδLV diastolic diameter was observed over a 5.6 (SD1.7)-year period. 89 In addition to PVC burden, otherfactors such as longer PVC duration, presence of nonsustainedVT, multiform PVCs and right ventricularPVCs may be associated with a decline in LV function.90,91 Although it is well known that catheter ablationof frequent PVCs can improve and restore LV functionin some patients, the potential benefits of ablation in patientswith normal LV function have been less well studied.A prospective study of 49 patients with frequentPVCs and normal baseline LVEF demonstrated thatcatheter ablation can improve the subtle LV dysfunction-detectedpre-ablation using speckle tracking imaginganalysis. 92 However, unanswered questions remain,including benefits of catheter ablation on hard endpoints (especially mortality) and when ablation shouldbe performed (degree of PVC burden, LV function, aftera trial of antiarrhythmic medication?).Cardiac resynchronisation therapy andpacingTwo pivotal cardiac resynchronisation therapy (CRT)clinical trials have been published in the past 2 yearsthat potentially expand the indications for CRT in patientswith heart failure to those in NYHA class I andII symptoms. MADIT-CRT (Multicenter AutomaticDe fi brillator Implantation Trial-CRT) compared theuse of ICD alone with CRT-D (CRT with a defibrillatorcom ponent) in patients with asymptomatic or mildlysym ptomatic heart failure symptoms (NYHA class I orII), LVEF≤30% and QRS duration of ≥130 ms. 93 Duringan average follow-up of 2.4 years, fewer patients in theCRT-D group experienced the primary composite endpoint (all-cause mortality and heart failure) compa-Romanian Journal of CardiologyVol. 22, No. 2, 2012

Romanian Journal of CardiologyVol. 22, No. 2, 2012riod, the investigators found that the mean LVEF wassignificantly lower in the RV-pacing group than in thebiventricular-pacing group (54.8±9.1% vs 62.2±7.0%,p50 mm HgR. LiewAlmanac 2011: cardiac arrhythmias and pacingand who were refractory to other drugs, after follow-upperiods of up to 10 years. 107 Another group of patientsin whom the role of pacing has remained controversialare those with carotid sinus hypersensitivity (CSH)with syncope. In a double-blind, placebo-controlled,crossover study, 34 patients (aged >55 years) with CSHand more than three unexplained falls in the preceding6 months were randomised to receive a dual-chamberpacemaker with rate-drop response programming whichwas switched on or off. 108 The investigators foundthat the pacing intervention had no effect on the numberof falls and concluded that the role of pacing forthis group of patients remains controversial. A similarconclusion was reached in a multicentre study of 141pa tients (mean age 78 years) with cardioinhibitoryCSH. 109Inherited arrhythmogenic diseasesMajor advances have been made in our understandingof the basic mechanisms, genetics and clinical featuresof the inherited arrhythmogenic diseases (IADs) overthe past 2 years. Since these cannot all be covered inthis short overview, only some of the major studies withimportant implications for general cardiologists will bementioned. The rapid expansion in our knowledge ofthe genetic basis of the IADs and rise in commerciallyavailable clinical genetic services has brought with it anadditional dimension to how we manage these conditions.The reader is referred to a number of useful recentlypublished reviews that examine these issues inmore detail. 110–112SCD without morphological evidence of heart diseaseaccounted for 23% of cases in a recent pathologicalstudy of UK athletes. 113 Potential causes of unexplainedcardiac arrest were systematically evaluated in aprospective study involving 63 patients in nine centresacross Canada. 114 The tests, which included cardiacMRI, signal-averaged ECG, exercise testing, drug challengeand selective electrophysiology (EP) testing, resultedin a specific diagnosis (IAD, early repolarisation,coronary spasm and myocarditis) in 35 patients (56%).The remaining 28 patients were considered to have idiopathicVF. Subsequent genetic testing performed in 19patients found evidence of causative mutations in nine(47%) of these. Family screening of 64 family membersof the nine patients with causative mutations led to thediscovery of mutations in 15 individuals (23%), whowere subsequently treated. This study provides evidencethat targeted genetic testing may play a part inhelping to diagnose genetically mediated arrhythmia

R. LiewAlmanac 2011: cardiac arrhythmias and pacingsyndromes, which may result in successful family screening.An important study that investigated the presenceof genetic factors or modifiers that could partly explainthe phenomenon of incomplete penetrance seen incongenital long QT syndrome (LQTS) identified thenitric oxide synthase 1 adaptor protein (NOS1AP) asone such candidate. 115 This protein was chosen on thebasis of previous studies that showed an associationbetween genetic variants of NOS1AP and small quantitativeincreases in the QT interval and an increasedrisk of death in a general population. 77,116 In the studyinvolving a South African LQTS population (500 subjects,205 mutation carriers), NOS1AP variants werefound to be significantly associated with the occurrenceof symptoms, clinical severity (including cardiac arrestand SCD) and a greater likelihood of having a QTinterval in the top 40% of values among all mutationcarriers. In another study involving 901 patients enrolledin a prospective LQTS registry, three NOS1AP markersingle nucleotide polymorphisms (SNPs rs4657139,rs16847548 and rs10494366) were genotyped to assessthe effect of variant alleles on QTc and on the incidenceof cardiac events. 117 The investigators found that variantalleles tagged by SNPs rs4657139 and rs16847548 wereassociated with an average QTc prolongation of 7 and8 ms, respectively, whereas rs4657139 and rs10494366were associated with an increased incidence of cardiacevents. Furthermore, the rs10494366 minor allelewas an independent prognostic marker among patientswith QTc

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Romanian Journal of Cardiology | Vol. 22, No. 2, 2012REVIEWSTherapeutic approach to cardiorenal syndromeMinodora Teodoru 1 , I. Maniţiu 2 , A. Teodoru 2 , Raluca Matei 3 , Cristina Chircu 3Article received on the 12 th December 2012. Article accepted on the 3 rd February 2012.Abstract: Cardiorenal syndrome is often described in heart failure patients and it represents the deterioration of renal functionin the context of heart failure. When it occurs, the prognosis of these patients is affected by the combination of thesepathologies. The treatment for cardiorenal syndrome should be applied individually in order to achieve the improvement ofthe patient’s clinical status, the preservation of the heart and kidney function and a better outcome. Along with traditionaltherapies (diuretics, inotropes), which often develop resistance, the beneficial effect of new therapeutic options (ultrafiltration,vasopressin and adenosine antagonists) is being evaluated in different trials.Keywords: cardiac insufficiency, renal insufficiency, cardiorenal syndromeRezumat: Sindromul cardiorenal se întâlneşte deseori în cursul evoluţiei insuficienţei cardiace şi reprezintă deteriorarea funcţieirenale în contextul insuficienţei cardiace. Atunci când el apare, prognosticul pacienţilor este grevat de combinaţia acestorpatologii. Tratamentul sindromului cardiorenal trebuie aplicat individualizat pentru a realiza performanţele sperate, avândmereu în vedere ameliorarea statusului pacientului, prezervarea funcţiei cordului şi a rinichiului şi îmbunătăţirea prognosticului.Alături de tratamente clasice (diuretice, medicaţia inotropă), care deseori se însoţesc de rezistenţă, este în curs de evaluareeficienţa unor opţiuni terapeutice noi (ultrafiltrarea, antagonşti ai vasopresinei şi ai adenozinei).Cuvinte cheie: insuficienţă cardiacă, insuficienţă renală, sindromul cardiorenalDefinition and importanceCardiorenal syndrome (CRS) is an individual pathologyrather than a simple association between heartand renal failure. CRS develops a different, complexphysiopathology, requiring a special treatment, whichhas not been studied sufficiently. CRS represents “theheart and kidneys’ physiopathological modifications,when the acute or chronic dysfunction of one organdetermines the failure of the other” as it was definedby Ronco at the World Nephrology Congress in 2008 1 .CRS was classified in 5 types according to the organwhich generated the lesion and to its debut (acute orchronic). This classification is presented in Table 1 1 .Table 1. The classification of cardiorenal syndromesCRS type Primary affliction Secondary affliction1. Acute Cardiorenal S. Acute heart failure Acute renal lesion2. Chronic Cardiorenal S Chronic heart failure Chronic renal failure3. Acute Renocardiac S. Acute renal lesion Acute heart failure4. Chronic Renocardiac S. Chronic renal failure Chronic heart failure5. Secondary S. Systemic disease Heart and renalfailureThese types of CRS are in fact five different syndromesfrom an epidemiologic, clinical and therapeuticpoint of view. Often different components, from the differenttypes of CRS, interact with one another.In this article we will refer mostly to the first twotypes (cardiorenal syndromes).Renal dysfunction associated with heart failure leadsto a severe prognostic. According to some studies, thisassociation increases the mortality rate in these patientswith up to 20% 2-4 .The physiopathological mechanisms which intermediatethe disequilibrium present in CRS is presented inFigure 1, according to the Guyton model 5 .The profile of patients at risk of developing CRS ispresented in Table 2.In daily practice, the diagnosis of CRS is based onthe existence of an association between heart failureand the onset, or exacerbation, of a renal dysfunction.Current diagnostic elements include the increase of serumcreatinine levels by more than 30% compared toinitial levels, reducing the diuresis with adequate dosesof diuretics, the aggravation of heart failure signs andsymptoms, or the absence of regression of hemodyna-1“Victor Papilian” Faculty of Medicine2Sibiu County Emergency Clinical Hospital, “Victor Papilian” Faculty ofMedicine3Sibiu County Emergency Clinical HospitalContact address:Minodora Teodoru, Cardiology Clinic, Sibiu County Emergency ClinicalHospital, 2-4 Corneliu Coposu Bvd., SibiuE-mail: dbedreaga@yahoo.com

Minodora Teodoru et al.Therapeutic approach to CRSRomanian Journal of CardiologyVol. 22, No. 2, 2012Table 2. Risk factor for CRSClinical risk factorsCardiac pathologyRenal pathologyAdvanced ageComorbidities (diabetes, arterial hypertension,anemia)Drug administration: non steroidal anti inflammatorymedication, diuretics, conversion enzyme inhibitors/sartans,aldosterone receptors antagonistsPersonal history of heart failureAcute myocardial infarctionIncreased troponin levelsChronic renal failureOptimizing the treatment for heart and renal failureThe best means to control CRS is to prevent it fromoccurring. This implies adapting heart failure therapyto hemodynamic and clinical conditions, to the presenceof associated diseases and to the use of therapeuticagents capable of preserving or improving the renalfunction. The patient requires permanent hemodynamicdisturbances and biological constants modifications.Because a consensus regarding the definition ofacute renal lesions could not be reached in practice,differing from one study to another, the Acute DialysisQuality Initiative defined the RIFLE criteria based onthe increase of serum creatinine values and decreasingurinary debit values 6 .Defining chronic renal failure requires the estimationof the glomerular filtration rate (the MDRD andCockroft - Gault formulas) 7 . But there are limitations inboth cases when these criteria apply to patients sufferingfrom heart failure 8 .More recently, biomarkers have been promoted asdiagnostic instruments for the various types of CRS,risk stratification tools, as well as “targets” for its treatment9 .Diuretics resistanceResistance to diuretic drugs is not entirely defined andpresents a great diversity of terms characterizing it. Apractical definition is the persistence of pulmonarycongestion despite the repeated use of 80 mg of furosemide,or of more than 240 mg of furosemide per dayTable 3. Causes and mechanisms of developing resistance todiureticsCauses of resistance toMechanismdiuretic drugs in patientssuffering from heart failure1. Noncompliant patient Lack of drug administration, increasedNa input, inadequate diuretic dose2. Low intestinal absorption Abdominal venous congestion3. Low tubular secretion Low cardiac output, chronic renal failure4. Simultaneous drugs: nonsteroidal anti inflammatorymedication5. Diuretic tolerance andincrease of Na reabsorption6. Neurohormonal activation(sympathetic nervoussystem, renin - angiotensin- aldosterone system)Inhibiting sodium cleansing and vasodilatatoryprostaglandin synthesisDistal tubules hypertrophyProlonged treatment with diuretic drugs,heart failure(including continuous perfusion), or in spite of the useof combined diuretics (loop and thiazide diuretics, oraldosterone antagonists).The development of resistance to diuretics can beconsidered a bad prognostic indicator in patients sufferingfrom chronic heart failure 10 .There are numerous mechanisms involved in thisprocess. Two types of diuretics resistance were described:short and long term resistance. The first appearsafter the administration of a single first dose due to neurohormonalactivation. Long term resistance developsafter long term treatment with loop diuretics, inducingmodifications in the renal structure, such as epithelialcell hypertrophy in the distal tubules, increasing Na reabsorptionand decreasing diuresis 11 .A summary of the mechanisms involved in the developmentof resistance to diuretics is illustrated in Table 3.CRS managementConsidering the complex and heterogeneous physiopathologyof CRS, patient management is a real challenge.Up to the present time, there is no treatmentensuring guaranteed success because each patient hashis/her own personal history, risk profile and a combinationof comorbidities. The medication used for thetreatment of CRS is illustrated in Table 4.Figure 1. Mechanisms involved in CRS.

Romanian Journal of CardiologyVol. 22, No. 2, 2012Table 4. The medication used for the treatment of CRSDrug classDiureticsACE inhibitors/ARBBeta blockersAldosterone antagonist diureticVasodilators: Nitroglycerine, NesiritideInotrope positive: Dopamine, Dobutamine,Milrinone, LevosimendanVasopressin antagonists: Tolvaptanvasopresină: TolvaptanAdenosine antagonists: RolofyllineUltrafiltrationSynthetic natriuretic peptide CD - NPSoluble guanylate cyclase activatorsIndicationAcute and chronic CRSChronic CRSChronic CRSChronic CRSAcute CRS and hypertensionAcute CRS and hypotensionAcute CRSAcute and chronic CRSAcute and chronic CRSAcute CRSAcute CRSCRS - cardiorenal syndrome, ACE inhibitors - angiotensin converting enzyme inhibitors, ARB -angiotensin receptor blockersmic monitoring, especially in case of arterial hypotensionand a limitation of the sodium input to less than2g, as well as a fluid intake limitation to less than 1000ml/24h, in case the patient presents hyponatremia. It isnecessary to monitor weight, ionogram, serum valuesfor urea and creatinine, GFR, diuresis. A serial echocardiographymonitoring is also useful. The use of bioimpedancevector analysis has significant prognosticresults, positively correlating itself with the BNP valuesin heart failure 12 . This could prove useful in the managementof these patients, to maintain hemodynamicstability and an optimal volemic control 13 .Neurohormonal medicationThere are therapies used in heart failure which haveproved their importance in the increase of survival,which target mostly the neurohormonal modifications.Such therapeutic schemes include beta blockers, ACEinhibitors and aldosterone antagonists.a) Although the use of ACE inhibitors is frequentlyavoided, or interrupted, in order to prevent thealteration of the renal function, the increase ofcreatinine levels after initiating a treatment withACE inhibitors can actually identify a subgroup ofpatients which will have a maximum benefit fromtheir use. This requires careful monitoring of therenal function and blood pressure. In addition toall of these, interrupting the use of ACE inhibitorsfor this group of patients leads to the increase ofthe mortality risk. The effects of ACE inhibitorsin the treatment of heart failure with associatedrenal failure are difficult to evaluate, because theextended studies which assessed their effects didnot include patients with altered renal function.Minodora Teodoru et al.Therapeutic approach to CRSMost of these studies had an exclusion thresholdof 2 mg/dL for the serum creatinine 14 . Even whenrenal failure was present, ACE inhibitors demonstratedthe reduction of proteinuria and long termbenefits regarding survival 15 .b) Beta blockers represent a heterogeneous class ofdrugs which have beneficial effects on the evolutionof heart failure when renal dysfunction isassociated. This is due to the higher levels of plasmaticnorepinephrine, compared to individualswith a normal renal function 16 . This prompts theenquiry as to what beta blocker is the most appropriateto be used in CRS; metoprolol and carvedilolare eliminated through the liver, leaving openthe opportunity to be administered in unmodifieddoses, whereas bisoprolol is eliminated throughboth the liver and the kidneys, necessitating anadjustment of the dose to the renal function.Diuretic treatmentDiuretics have represented for a long time the initialand essential component in the management of patientssuffering from heart failure. They also represent animportant element in the elimination of volemic overloadin CRS, but they must be used judiciously, undercareful monitoring of the renal function and of the volemicstatus.Diuretics increase neurohormonal activity, the activityof plasmatic renin and aldosterone and the plasmaticlevels of norepinephrine and arginine-vasopressin.They also increment peripheral vascular resistance andindirectly deteriorate left ventricle function. By cumulatingthese effects, diuretics increase the mortalityrisk 17,18 .The first therapeutic measure is to administer intravenouslya loop diuretic for a better effect on a renallevel. It is often necessary to double the dose when anappropriate diuretic effect is not obtained. It can beadministered in a continuous venous perfusion, withdoses adjusted to the severity of the renal dysfunction,for 2-4 hours 19 . Some authors have observed the increaseof urinary output, the decrease of the frequencyof ototoxicity and a shorter period of admittance 20 .This practice was not confirmed by the randomizedprospective trial The Diuretic Optimization StrategiesEvaluation (DOSE), which included 308 patients withacute decompensated heart failure. DOSE did not revealsignificant differences in the evolution of patientsafter receiving diuretic treatment in bolus, comparedto those who received the treatment through continuo-

Minodora Teodoru et al.Therapeutic approach to CRSus endovenous perfusion. As a result of administeringhigh doses of diuretics, as opposed to the administrationof low doses, a transitory deterioration of the renalfunction could be observed. This had no adverse effectsregarding the patient’s prognostic 21 . Another optiontaken into study when hypoalbuminemia is associatedconsiders the combined use of furosemide with lowsodium albumin. A furosemide - albumin complex isformed, increasing the disponibility of the diuretic bymaintaing it in the vascular stream 22 .Romanian Journal of CardiologyVol. 22, No. 2, 2012UltrafiltrationUltrafiltration is a treatment option which is increasinglyused in the treatment of CRS. It successfully eliminatesthe liquid excesses in cases with severe heart failure,associated with refractory hydrosaline retentionand resistance to optimal diuretic treatment. Ultrafiltrationis a mechanical process which consists of removingisotonic liquid and low molecular weight moleculesfrom the circulatory system, based on a pressuregradient and using a semi permeable membrane. In aclassic manner a central venous catheter is required, especiallyfor patients with edema, but modern methodsallow the use of the cubital vein and the use of a lowflow catheter 23 . Its effects include the decrease of the rightatrial pressure and the downgrade of the pressureblocked in the pulmonary capillaries, without a significantimpact on the cardiac output and stroke volume 24 .Ultrafiltration eliminates a larger quantity of water andsodium compared to diuretics, without neurohormonalactivation, allowing the elimination of approximately3-4 liters of liquid per session. Because of the benefitsobserved in the treatment of CRS patients a largenumber of studies were dedicated to the evaluation ofthe efficiency of ultrafiltration in their treatment. RA-PID CHF studied liquid elimination and the evolutionof some patients admitted for CRS, finding better resultsin cases where ultrafiltration was used, rather thana classic treatment 25 .Another study conducted on patients with acuteheart failure was the UNLOAD trial. Patients whoun der went ultrafiltration lost more weight than thosewho were given diuretics, but without any statisticallysignificant differences concerning the reductionof dyspnea or the improvement of the renal function.How ever, the lot of patients treated with ultrafiltrationhad a lower re-admittance rate after 90 days from theini tial admission 26 .The indications of ultrafiltration in the treatment ofheart failure are limited in day to day practice to patientswith edema syndromes refractory to optimal dosesof diuretics, or in cases with aggravating renal failure.Due to the high costs it implies and the need for a betterpatient surveillance, new studies are needed to evaluateultrafiltration from the perspective of cost-efficiency,moment of administration (clinical context, the gravityof the organ dysfunction) and protocol (type of treatment,rhythm and period of administration). The CardiorenalRescue Study in Acute Decompensated HeartFailure (CARRESS) study is currently in progress andtries to answer some of these questions. The patientsincluded in this controlled and randomized trial havebeen hospitalized for acute, destabilized heart failureand developed cardiorenal syndrome. Serum creatinineand weight were monitored for any modifications at96 h after admission. Considering the already existingproof, ultrafiltration should be considered and used asfirst line therapy in CRS.Vasodilatation treatmentVasodilatation treatment determines the rapid reductionof the ventricular filling pressure, central venouspressure and myocardial oxygen consumption, improvingcardiac function.a) Nitroglycerin is frequently used in heart failure toreduce pulmonary congestion. The reduction ofvenous pressure could be benefic in CRS by reducingthe renal venous pressure. However, thebenefits to overall survival and renal function improvementderiving from the use of nitroglycerinin CRS are not yet known.b) Nesiritide is a recombined BNP (brain natriureticpeptide) which induces vasodilatation withthe reduction of cardiac afterload and preload, increasingthe cardiac output 27 . Several clinical studieshave confirmed anterior favorable results onhemodynamic parameters and have also shownsymptomatic improvement. When nesiritide wascompared to an inotrope intravenous medicationor to vasodilatation therapy, a symptom improvementand increase of diuresis were observed.Wang’s study was the first to explore the effects ofnesiritide on the renal function, in patients with provencardio-renal dysfunction. The expectations werenot matched by the results. This study concluded thatnesiritide had no effect on the glomerular filtrationrate, renal plasma flow and urine volume or sodium excretion29 . Although the initial hypothesis was not confirmed,the study does not exclude all possibilities forthis agent to play a role in the treatment of heart failuresymptoms.

Romanian Journal of CardiologyVol. 22, No. 2, 2012Recently, the Acute Study of Clinical Effectivenessof Nesiritide in Decompensated Heart Failure Trial(ASCEND-HF) trial included over 7000 patientswith acute, decompensated heart failure. The patientsincluded in this study received standard heart failuretherapy associated with nesiritide in a continuous perfusion,or placebo. It concluded that nesiritide can besafely administered without adverse effects regardingthe renal function or mortality and that it lead to a minorimprovement concerning the dyspnea 30 . There areother studies which have tested the effects of nesiritideadministered in a single dose per week, evaluating thistype of treatment for high risk patients, Fusion II. However,these studies did not prove any significant improvementsin the quality of life, or survival 31 . The RenalOptimization Strategies Evaluation in Acute Heart Failure(ROSE) trial is currently in progress. It includespatients with acute heart failure, treated with 3 differenttypes of drugs: diuretic treatment, optimal whenassociated with nesiritide, low doses of dopamine andplacebo. At the same time, the efficiency and the studyprofile of this therapy was studied on patients with acuteheart failure.Positive inotropic agentsSuch agents like dopamine, dobutamine, phosphodiesteraseinhibitors and levosimendan are used in thetreatment of CRS in order to facilitate diuresis, preservingor improving the renal function due to their capacityto increase the cardiac index and renal perfusion32,33 . Low doses of dopamine (lower than 5 µg/kg/min) were often used in order to improve renal function,but it appears that this effect is owed mostly tothe increase of the cardiac output, rather than a localeffect 34 . Clinical studies have been conducted on theeffects of dopamine and they have not revealed any clinicalbenefit 35 . Also, in a study performed on patientswith acute renal failure it was noticed that dopaminecan actually worsen the renal perfusion 36 .The OPTIME study investigated the use of milrinonefor patients suffering from chronic heart failure. Itshowed that patients in advanced stages of the diseasedo not have an improved prognostic if they follow thistreatment 37 .Inotrope medication can be introduced in the treatmentof patients suffering from CRS only in cases inwhich renal failure develops secondary to low cardiacoutput. The medication will be administered on shortterm and under careful monitoring due to the risk ofdeveloping arrhythmia. It does not represent a routineMinodora Teodoru et al.Therapeutic approach to CRStreatment for patients suffering from chronic or acuteheart failure because it increases the mortality risk andhas multiple adverse effects on the heart.The ROSE study, previously mentioned, proposesthe optimization of heart failure therapy, wishing to administerlow doses of dopamine in acute heart failure.The treatment of anemiaThe cardiorenal-anemia syndrome was extensively describedin the literature. It develops as a result of thecombination between heart failure and renal failure,through plurifactorial mechanisms 38 . In its turn, anemiacan exacerbate heart failure and CRS. Thus, a newconcept appeared considering a new syndrome, with adifferent pathology than the one associated with classicCRS and with a diverse impact on patients’ morbidityand mortality.The treatment of anemia with erythropoietin demonstrateda favorable impact on the cardiac function,increasing left ventricular ejection fraction and physicalperformance 39 . However, the correction of the anemiamust be only partial, because an aggressive correctionis accompanied by a high rate of adverse effects.Alpha darbepoetin also demonstrated a favorableeffect in the treatment of patients suffering from heartfailure 41 . The RED-HF trial studies the effects of longterm administration of alpha darbepoetin to patientswith left ventricular dysfunction 42 .Future directions in the study and treatmentof cardiorenal dysfunctionIn order to develop new approaches to this syndromethere are several ongoing research projects, testing newtherapies. Other options include the early introductionof dialysis and ultrafiltration; in severe cases, leftventricular devices and intra aortic counter pulsationballoons can be used for short term management ofthese patients.a) Vasopressin antagonists: anti diuretic hormone,also known as arginin vasopressin (AVP), is secretedwhen the circulatory volume decreases, orwhen hyperosmolarity occurs. It exerts its effectthrough three kinds of receptors, of which the V2receptors are located in the kidney, more preciselyin the distal and collector tubes. AVP acts at thislevel causing vasoconstriction and water reabsorption.AVP serum levels can be low in heartfailure with hypotension and low sanguine circulatoryvolume. A class of drugs called vaptans wasde veloped in order to antagonize the effects ofAVP, increasing water excretion by enhancing the

Minodora Teodoru et al.Therapeutic approach to CRSclearance of water and increasing serum sodiumlevels, useful especially in hyponatremic states 43 .The ACTIV study focused on the effects of administeringtolvaptan in acute heart failure. It was observedthat patients treated with tolvaptan presented a morerapid weight loss and an increased urinary debit comparedto those who have received the standard treatment,without modifications to serum creatinine valuesat discharge 44 .A more ample study, EVEREST, confirmed the dataalready known from ACTIV, but did not demonstrateany prognostic benefits from long term administrationof tolvaptan in acute heart failure 45 .b) Adenosine receptors antagonists: the energy consumedduring sodium excretion in the kidney isgenerated by adenosine, resulted from the transformationof ATP in ADP in the renal tubules,determining the constriction of the afferent arterythrough the binding of the A1 receptor, reducingthe renal flux and determining sodium reabsorption.Adenosine receptors antagonists represent aclass of drugs that determine the increase of renalperfusion, diuresis and sodium excretion. Thesedrugs are prescribed in heart failure with hypervolemiaand hyponatremia 46 . Previous studies indicateda possible role played by these agents inavoiding the decline of the renal function due tothe use of loop diuretics 47 .Rolofylline stands out from this class of drugs as theone able to increase diuresis and natriuresis in associationwith lower doses of diuretics 48 . Rolofylline wasstudied in the PROTECT multicenter trial, including300 patients with acute heart failure and altered renalfunction at the time of admission. It was administeredin different doses in continuous perfusion, togetherwith the standard therapy. The final data did not showany benefits regarding the renal function or the prognostic.New studies are necessary in order to test thesehypotheses 49 . The REACH-UP study did not demonstratea clear benefit of rolofylline in the treatment of patientswith acute heart failure and renal dysfunction 50 .The potential role can exist, in particular cases, suchas the prevention of contrast nephropathy or in case ofhypotension and in patients at risk of developing resistanceto diuretics 51 .c) The synthetic natriuretic peptideSynthetic natriuretic peptides are molecules synthesizedfrom natural natriuretic peptides, created withthe purpose of optimizing the pharmacological actionsand minimizing the side effects 52 . Of these, the synthe-Romanian Journal of CardiologyVol. 22, No. 2, 2012tic peptide CD-NP was created starting from the typeC and type D natriuretic peptide and was used in thetreatment of acute heart failure, without inducing arterialhypotension 53 .In the first clinical trial favorable effects were provenregarding natriuresis and the preservation of therenal function. Unlike native natriuretic peptides, CD-NP suppresses aldosterone synthesis 54 . The success ofsynthetic peptides paves the way to their study and usein the treatment of heart failure and CRS.d) Soluble guanylate cyclase activators (cinaciguat,atisciguat) can be used in the treatment of heartfailure to reduce systemic vasoconstriction by increasingthe vasodilatation effect of nitric oxide,thus preventing the development of resistance tonitrates, which usually appears in heart failure 55 .An experimental study showed the reduction ofthe preload and afterload, with the increase of thecardiac output in a heart failure model 56 . The observedrenal effect was the preservation of glomerularfiltration, possible because of the effects onrenal resistance.e) The intrarenal administration of medication canbe an alternative to the classic administration ofdrugs in CRS, in order to increase the local concentrationand inducing local renal effects, withless systemic exposure and side effects. By administeringfenoldopam (a dopaminergic agonist)or nesiritide locally, in the renal arteries the renalmetabolization occurring when the drug is administeredintravenously is by-passed, inducing lesssystemic side-effects 48,57 refI . Phosphodiesteraze Vinhibitors are also in study as a possible therapy,administered in association with BNP in order tooffer a new vision of CRS physiopathology and toestablish a new therapeutic combination, with influencein the treatment and prevention of heartfailure 58 .Sympathetic renal denervation can have a potentialrole in the prevention and management of cardiorenalsyndrome, without having any clinical or experimentaltrials to confirm the therapeutic effects of this procedure.ConclusionsAccording to the presented facts we can safely affirmthat the onset of cardiorenal syndrome is a bad, butfrequent development in the evolution of chronic heartfailure. Understanding the mechanisms involved in thedevelopment of CRS is rudimentary at best, lackingefficient therapies. The treatment of heart failure is

Romanian Journal of CardiologyVol. 22, No. 2, 2012nowadays mostly the same as it was a few decades ago,especially from the point of view of cardiorenal interactions.Our hope is that new and efficient therapieswill be developed in order to prevent this challengingsyndrome.Funding: Research conducted through the POSDRU/88/1.5/S/60370 - The integration of Romanian researchin the context of European research projects - doctoralfellowships, co-financed from the European SocialFund, via the Sectoral Operational Programme HumanResources Development 2007-2013.Bibliography1. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R., Cardiorenalsyndrome, J Am Coll Cardiol. 2008;52(19):1527-39.2. Giamouzis G, Kalogeropoulos A, Georgiopoulou V, et al. Hospitalizationepidemic in patients with heart failure: risk factors, risk prediction,knowledge gaps, and future directions. J Card Fail. 2011;17(1):54–753. Bhatia RS, Tu JV, Lee DS, et al. 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Romanian Journal of Cardiology | Vol. 22, No. 2, 2012CASE STUDYAn unusual cause of „mitral” stenosisIrina Costache 1 , A. Cozma 1 , L. Stoica 2 , A. O. Petriş 1Article received on the 25 th February 2012. Article accepted on the 4 th May 2012.Abstract: Left atrial myxoma is one of the most common tumors of the heart, with a variety of nonspecific clinical signs andsymptoms that often masquerade as many other cardiovascular or systemic diseases. We report a case of left atrial myxomain a 73 year-old woman who initially presented with dyspneea on minimal exertion. Following the diagnosis, based on 2-Dtransthoracic and transesophageal echocardiography, the patient was refered to surgery for resection of the tumor - a left atrialmyxoma - which was successfully removed under general anaesthesia and cardiopulmonary bypass.Keywords: left atrial myxoma, dyspnea, echocardiography, resectionCase StudyA 73 year-old woman was admitted to the hospitalbecause of dyspnea on minimal exertion. The patienthad several cardiovascular risk factors, such as 20-year history of hypertension, high levels of cholesterol,obesity and diabetes mellitus type I treated with insulin.Recently, the patient complained about dyspneaon minimal exertion and palpitations and for a whilewas considered to have respiratory failure and treatedaccording to this diagnosis. Clinical examination revealed2 nd degree obesity, sinus rythm with 3-4 prematurebeats per minute and a diastolic murmur at the leftlower sternal border. The blood pressure was normaland the electrocardiogram indicated sinus rythm withventricular ectopic beats and no significant ST segmentor T wave changes. Chest X-ray showed enlargement ofthe left ventricle silhouette. Two-dimensional transthoracicechocardiography (TTE) identified an echodensemass within the left atrium (40/52 mm), protrudingaccross the mitral valve during diastole (Figure 1) andattached to the interatrial septum with a thin stalk. Theleft atrium diameters were 52/59 mm and left ventricleend-diastolic diameter was normal. The mitral annuluspresented a small calcification and a mild mitral regurgitation.Doppler echocardiography revealed a peakpressure gradient through the mitral valve of 29 mmHgand a mean gradient of 19 mmHg, corresponding to asevere “relative”, „functional” mitral stenosis.Left ventricle ejection fraction was normal. Rightventricle and right atrium were enlarged (RA = 50/58mm). Systolic pulmonary pressure was remarkably high(83 mmHg) as calculated using the peak pressure gradientof tricuspid regurgitation and the estimated rightatrial pressure based on the diameter and respirato ry va -ri a tion of the inferior vena cava. Transesophageal echocardiography(TEE), the most sensitive method for thediagnosis of intracardiac masses, confirmed the pre -sence of an echodense, non homogenous mass attachedto the interatrial septum (Figure 2, Panel A and B).The patient was refered to Cardiovascular SurgeryDepartment in order to continue the investigations andfor treatment. The patient was operated under generalanesthesia. TEE was used before and after extracorporealcirculation (ECC) to localize the tumor, to verifythe mitral valve function and to control the presenceof air in the heart cavities and the ventricular function.The tumor occupied the entire volume of the leftatrium and almost blocked the mitral valve and, despitethis, there was no mitral regurgitation. The ECC wasestablished by means of an ascending aorta cannulaand by two caval cannulas. The heart was arrested with1000 ml cold blood hyperpotassemic antegrade cardioplegiainjected in the aortic root. The arresting cardiactime was 32 minutes. The left atrium was open by theinteratrial groove. The tumor was exposed and resectedpiece by piece because of it`s big size and friability(Figure 3).The tumor had a pedicle inserted on the interatrialseptum. The pedicle was resected and the small atrialseptal defect was directly sutured. The mitral valve was11 st Medical Cardiology Clinic, University of Medicine and Pharmacy “Gr.T. Popa” Iaşi, “St. Spiridon” Hospital Iaşi, Romania2Department of Cardio-Vascular Surgery, Institute for Cardio-VascularDiseases IaşiContact address:Dr. Antoniu Octavian Petriş, 1 st Medical Cardiology Clinic, University ofMedicine and Pharmacy “Gr. T. Popa” Iaşi, “St. Spiridon” Hospital Iaşi,Romania.E-mail: antoniupetris@yahoo.com

Irina Costache et al.An unusual cause of „mitral” stenosisRomanian Journal of CardiologyVol. 22, No. 2, 2012AFigure 1. Transthoracic echocardiography (parasternal long-axis view)showed a huge left atrial mass (5,3 cm×4 cm) attached to the atrial septumpro truding into the left ventricle during diastole.ses. Left ventricular inflow tract obstruction because ofthe myxoma can mimic a mitral stenosis and can be acause of pulmonary hypertension and congestive heartfailure 2 . Common systemic symptoms are: fever, malaise,weight loss, fatigue, aneamia, elevated erythrocytesedimentation rate (ESR). Both symptoms and signsresolve immediately after surgery and seems to be dueby the releasing of inflammatory mediators from tumourcells 1,2 . Myxomas are of two types: one with round,nonmobile surface and other polypoid type with irregularsurface, mobile with an increased risk of embolisation2,11 . Surgical removal is the treatement of choicefor myxomas. The site of the attachement should be resectedwith clear margin, even if that is followed by theartificial creation of an atrial septal defect that needsto be closed by a pericardial patch 4,7-11 . The reccurendilated,with supple leaflets; moreover, with surprise, amajor regurgitation was detected after saline injection.Mitral annuloplasty was done using a 28 Edwards Cosgroveannular band with trivial residual regurgitation.Aorta was unclamped and the heart restarts promptlyits activity in sinus rhythm. The ECC was stopped underinotropic support. The anatomo-pathological examconfirmed that the tumor was a myxoma. At the followup, 6 weeks after the operation, the patient was doingwell and an echocardiographic Doppler examinationshowed a drop of the systolic pulmonary artery pressureat 43 mmHg.DiscussionMyxomas are the most common primary benign tumorsof the heart with an incidence of 0.5 per millionpopulations 1,6 . Between 75-80% of primary tumors arebenign and about 50% of benign tumours are myxomas.They occur twice as much in females than in malesand the mean year of detection is 55 years 3 . Commonly,myxomas derive from the left atrium but 25%may arise in the right atrium or even in the ventricles 7 .Most cases are sporadic, but up to 10% are familial andtheir transmittance appears to be autosomal dominant 4 .Usually, symptoms are non-specific and early diagnosisis rather difficult. Clinically myxomas are characterizedby Goodwin’s triad: embolisation, obstruction of bloodflow and constitutional symptoms such as fever andweight loss 1-5 . A sizeable number of patients (17 to 59%)with myxoma present clinically with an embolic event,usually in the cerebral territory 9 . Obstruction of bloodflow can cause heart failure or syncope in 41-79% of ca-BFigure 2. Two-dimensional transesophageal echocardiographic image, midesophagealview at: A. 126 degree demonstrates the large atrial mass (M)protruding into the left ventricle during diastole and B. 126 degree, showinga large (5 cm×3.5 cm), ovoid and heterogeneous mass (M) in the left atriumsurronded by the color Dopller flow.

Romanian Journal of CardiologyVol. 22, No. 2, 2012Irina Costache et al.An unusual cause of „mitral” stenosisce of myxomas has been reported to be less than 2%,thus, follow up is important especially for the detectionof recurrent myxomas and is easily done by clinicalexamination combined with 2D echocardiography 4 . Asseen in this case, atrial myxomas may develop into giantmasses without producing major symptoms whichmay develop late in the course of tumour life and beeither vague or nonspecific. In elderly patients presentingwith dyspnea but no pulmonary disease, cardiacproblems must be considered as the cause of pulmonarysymptoms and complaints. Echocardiography,thus in these patients as well, proves to be very usefulfor detecting cardiac causes for dyspnoea 12 .Figure 3. The large atrial mass after surgical excision. Histopathology examconfirm the diagnosis of myxoma.Conflict of interests: none declaredReferences1. Mac Gowan SW, Sidhy P, AhemeT şi col. Atrial myxoma: national incidencediagnosis and surgical management. Isr J Med Sci 1993; 162:223-26.2. Pradhan B, Acharya SP. A Case of atrial myxoma: anaesthetic management.Kathmandu University Medical Journal 2006; 15: 349-353.3. Fang BR, Chiang CW, Hung JS şi col. Cardiac myxoma – clinical experiencein 24 patients. Int J Cardiol 1990; 29: 335-341.4. Gaspar M, Laufer G, Antretter H şi col. Mixomul cardiac – spectrulclinic variat care întîrzie diagnosticul. TMJ 2002; 2: 63-65.5. Reynen K. Cardiac myxomas. N Engl J Med 1995; 14: 1610-7.6. Castells E, Ferran V, Octavio F şi col. Cardiac myxomas: surgical treatement,long term results and recurrence. J Cardiovasc Surg 1993; 34:49-53.7. Centofanti P, Di Rosa E, Deorsola L şi col. Primary cardiac tumors:early and late results of surgical treatement in 91 patients. Ann ThoracSurg 1999; 68: 1236-41.8. Panagiotu M, Nikolaos D, Panagopoulos D, Panagiota Ravazoula,Loukas Kaklamanis and Efstratios N Koletsis. Large asymtomatic LeftAtrial Myxoma with ossification: case report. Journal of CardiothoracicSurgery 2008; 3:19.9. Meng Q, Lai H, Lima J, Tong W, Qian Y, Lai S şi col. Echocardiographicand pathologic characteristics of primary cardiac tumors: a studyof 149 cases. Int J Cardiol 2002; 84: 69-75.10. Bhan A, Mehrotra R, Choudhary S şi col. Surgical experience withintracardiac myxomas: long-term follow up. Ann Thorac Surg 1998;66: 810-3.11. Ha JW, Kang WC, Chung N şi col. Echocardiographic and morphologicalcharacteristics of left atrial myxoma and their relation to systemicembolisation. Am J Cardiol 1999; 83: 1579-82.12. Mustafa B, Erol A. Giant left atrial myxoma causing mitral valve obstructionand pulmonary hypertension. Can J Surg 2008; 51: 97-98.

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012IMAGES IN CARDIOLOGY - VASCULAR DOPPLERGlomic tumor – ultrasonographic evaluationIleana ArsenescuArticle received on the 21 st May 2012. Article accepted on the 28 th May 2012.28 year old patient, clinically presenting a right lateralcervicaltumoral formation.Figure 1. 2D and color ecography shows a mass (TU) situated cranial to thecarotid bifurcation, between the internal and external carotid arteries. It iswell - defined with a hypoechogenic, homogeneous structure.Figure 3. At spectral Doppler exam, speed and the resistance indices arenormal on the internal carotid artery.Figure 2. Decreasing Doppler speed scale, we note that the described mass ishighly vascularized, with slow flow speeds.Figure 4. At the level of the external carotid artery, systolic velocities arehigher, indicating an increased flow. The resistance index is low due to theincrease in the diastolic velocity, showing that the artery is irrigating a lowresistance area, that is the glomic tumor.1„Prof. Dr. C. C. Iliescu” Emergency Institute for Cardiovascular Diseases,BucharestContact address:„Prof. Dr. C. C. Iliescu” Emergency Institute for Cardiovascular Diseases,Bucharest

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012IMAGES IN CARDIOLOGY - CORONARY ANGIOGRAPHYCoronary spasm - A rare case of acute myocardial infarctionA. Negoiţă, M. Postu, D. DeleanuArticle received on the 23 rd May 2012. Article accepted on the 28 th May 2012.Male, 59 years old, known with arterial hypertension,dyslipidemia, smoker presented at the emergencyroom 3 hours after the beginning of a retrosternalpain, typical for angina. The patient is brought aftera resuscitated cardiopulmonary arrest, being intubatedin the emergency room, mechanically ventilated, with aBP of 80/60 mmHg. Initial ECG shows a sinus rhythmwith AV of 90 bpm, a maximum 1mm ST segment elevationin DIII, aVR, right leads with negative T wavesat this level, ST segment depression in aVL (Figure 1).Based on the clinical and paraclinical data, the diagnosisof acute coronary syndrome with ST segment elevationis set 3 hours from the resuscitated cardiopulmonaryarrest. Emergency coronary surgery is decided.When injecting the left arterial coronary, importantdiffuse spasm isnoted at the level of the left main coronaryartery, the anterior dedcending artery and thecircumflex artery with distal occlusion on the circumflexartery (Figure 2A). Nitroglycerine is administratedintracoronary and the remission of spasm at the level ofthe the whole left coronary artery is noted (Figure 2B).When injecting the right coronary artery, we notedthe oclusion of the proximal segment with intraluminalthrombotic aspect (Figure 3). Taking into considerationthe spasm existent at the level of the left coronaryartery, nitroglycerin is repeateadly administred intracoronaryleading to a complete remission of the spasmfor the whole blood vessel (Figure 3B).Bibliography1. Rashid H, Marshall RJ, Diver DJ, Breall JA. Spontaneous and diffusecoronary artery spasm unresponsive to conventional intracoronarypharmacological therapy: a case report. Catheter Cardiovasc Interv2000; 49:188–91.2. Yasue H, Nakagawa H, Itoh T, Harada E, Mizuno Y. Coronary arteryspasm – clinical features, diagnosis, pathogenesis, and treatment. JCardiol 2008; 51:2–17.Figure 1. ECG: Sinus rhythm, 90 bpm, ST segment elevation in DIII, aVR, right leads of maximum 1mm with negative T waves at this level, ST segmentdepression in aVL.1„Prof. Dr. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases,258, Fundeni Street, BucharestContact address:„Prof. Dr. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases,258, Fundeni Street, Bucharest

A. Negoiþã et al.Coronary spasm - A rare case of acute myocardial infarctionRomanian Journal of CardiologyVol. 22, No. 2, 2012Figure 2. Coronary angiography – injection in the left coronary artery- one can notice the left main (TC), the anterior descending artery (ADA) and the circumflexartery (CX) with important diffuse spasm producing occlusion of the 2 nd segment of the anterior descendent aorta and distal oclusion at the levelof the CX (Figure 2A). After intracoronary nitroglycerine administration we noted the absence of the spasm at the level of the whole left coronary artery(Fi gure 2B).Figure 3. Coronary angiography – injection in the right coronary artery (CD) – proximal oclusion, with intraluminal thrombotic aspect (Figure 3A). Figure3B – complete complete remission of the spasm after intracororonary nitroglycerine administration.

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012IMAGES IN CARDIOLOGY - ECHOCARDIOGRAPHYHipertensiune pulmonară de cauză rarăB. A. Popescu 1,2 , Anca Mateescu 2 , Roxana Enache 1,2 , P. Platon 2 , Carmen Ginghină 1,2Articol primit în data de 7 iunie 2012. Articol acceptat în data de 12 iunie 2012.Pacienta P.M., în vârstă de 18 ani, se prezintă pentrudispnee şi fatigabilitate la eforturi moderate, instalateprogresiv în ultimii doi ani, de când a constatat şiapariţia cianozei. O ecocardiografie efectuată în 2010nu decelează modificări notabile, iar în aprilie 2012 sedecelează pentru prima oară hipertensiune arterialăpulmonară severă, fără etiologie detectabilă ecocardiografic.Ecocardiografia transtoracică a evidenţiat suprasolicitarede presiune ventriculară dreaptă (VD), hipertrofieVD şi hipertensiune pulmonară severă (Figura1). În plus, examinarea din secţiunea modificată de axscurt la baza marilor vase a ridicat suspiciunea unei ferestreaorto-pulmonare cu şunt bidirecţional şi s-a indicatecocardiografie transesofagiană.Ecografia transesofagiană a evidenţiat o comunicaredirectă, largă, între aorta ascendentă şi trunchiul artereipulmonare (Figura 2), cu diametru maxim de 23 mm.Examenul Doppler color, ca şi examenul cu substanţăde contrast (Figura 3) au confirmat comunicarea, cuşunt bidirecţional la acest nivel. Datele ecografice auconfirmat diagnosticul de fereastră aorto-pulmonarălargă cu şunt bidirecţional, cu hipertensiune arterialăpulmonară severă prin fiziologie de tip Eisenmenger.Diagnosticul a fost confirmat prin cateterism cardiacşi angiografie.Datorită poziţionării particulare a acestei rare anomaliicongenitale, diagnosticul nu este facil, necesitândun indice de suspiciune înalt şi adesea utilizarea combinatăa mai multor modalităţi (examinare transtoracică,transesofagiană, inclusiv cu substanţă de contrast).Conflict de interese: niciunulFigura 1. Înregistrare Doppler continuu a fluxului de regurgitare tricuspi dia nă din secţiune apicală 4 camere, evidenţiind hipertensiune arterială pul monarăseveră (gradient maxim VD-AD de 88 mmHg, presiunea arte rială sistolică pulmonară estimată la 98 mmHg).1Universitatea de Medicină şi Farmacie “Carol Davila” Bucureşti2Institutul de Urgenţă pentru Boli Cardiovasculare „Prof. Dr. C.C. Iliescu”BucureştiContact address:Dr. Bogdan A. Popescu, Universitatea de Medicină şi Farmacie “CarolDavila” Bucureşti – Laboratorul Euroecolab Institutul de Urgenţă pentruBoli Cardiovasculare „Prof. Dr. C.C. Iliescu” BucureştiSos. Fundeni 258, sector 2, 022328 – Bucurestiemail: bogdan.a.popescu@gmail.com

B. A. Popescu et al.Rare case pulmonary hypertensionRomanian Journal of CardiologyVol. 22, No. 2, 2012Figura 2. Examinare transesofagiană 2D din secţiune de ax scurt la nivelulaortei ascendente, imagine sistolică: se observă aorta ascendentă în comunicaredirectă, largă, cu trunchiul arterei pulmonare. AO=aorta ascendentă;AP=trunchiul arterei pulmonare.Figura 3. Examinare transesofagiană cu substanţă de contrast din secţiunede ax scurt la nivelul aortei ascendente. La injectarea substanţei de contrast(ser fiziologic barbotat) se opacifiază trunchiul arterei pulmonare şi seevidenţiază şunt bidirecţional între aceasta şi aorta ascendentă.AO=aorta ascendentă; AP=trunchiul arterei pulmonare.

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012Recomandările Asociaţiei Europene de Ecocardiografie pentrupregătirea, competenţa şi îmbunătăţirea calităţii în domeniulecocardiografieiAutori: Bogdan A. Popescu (Preşedinte) 1 *, Maria J. Andrade (Co-Preşedinte) 2 , Luigi P. Badano 3 , Kevin F. Fox 4 , Frank A.Flachskampf 5 , Patrizio Lancellotti 6 , Albert Varga 7 , Rosa Sicari 8 , Arturo Evangelista 9 , Petros Nihoyannopoulos 10 , şi Jose L.Zamorano 11 , comitet din partea Asociaţiei Europene de EcocardiografieReferenţi: Genevieve Derumeaux a , Jaroslaw D. Kasprzak b , Jos R.T.C. Roelandt c1Universitatea de Medicină şi Farmacie “Carol Davila”, Institutul de Boli Cardiovasculare, Bucureşti, România; 2 Departamentul de Cardiologie, SpitaloulSanta Cruz, Carnaxide, Portugalia; 3 Departamentul de Ştiinţe Cardiopulmonare, Universitatea Spitalului “S. Maria della Misericordia”, Udine, Italia; 4 ColegiulImperial, Londra, Marea Britanie; 5 Universitatea Erlangen, Erlangen, Germania; 6 Departamentul de Cardiologie, Universitatea Spitalului Sart Tilman,Liege, Belgium; 7 Departamentul de Medicină şi Cardiologie, Universitatea de Ştiinţe, Szeged, Ungaria; 8 Institutul de Fiziologie Clinică, Pisa, Italia; 9 SpitalulVall d’Hebron, Barcelona, Spania; 10 Spitalul Hammersmith, NHLI, Colegiul Imperial Londra, UK; 11 Spitalul Clinic San Carlos, Madrid, Spania.aInserm U886, Universitatea Claude Bernard Lyon, Franţa; b Departamentul de Cardiologie, Universitatea Medicală Lodz, Polonia; c Departamentul deCardiologie, Thoraxcentre, Erasmus MC, Rotterdam, Olanda.*Autor corespondent: Universitatea de Medicină şi Farmacie “Carol Davila”, Institutul de Boli Cardiovasculare “Prof. Dr. C. C. Iliescu”, Şos. Fundeni 258,sector 2, 022328, Bucureşti, România. Tel/Fax: +4021 3175227; e-mail: bogdan.a.popescu@gmail.comVarianta originală a fost publicată în Eur J Echocardiogr 2009;10(8):893-905.Traducerea în limba română a fost făcută de Mihaela-Silvia Amzulescu, Florina Voinea şi Maria-Magdalena Gurzun, sub coordonarea Bogdan A. Popescu şiDragoş Cozma.RezumatScopul principal al Asociaţiei Europene de Ecocardiografie (AEE) este „de a promova excelenţa în diagnosticulclinic, cercetare, dezvoltarea tehnicii şi educaţieiîn imagistica cardiovasculară europeană”. Deoarececompetenţa şi controlul calităţii sunt recunoscute decătre pacienţi, medici şi contribuabili, AEE a stabilitrecomandări pentru pregătire, competenţă şi îmbunătăţireacalităţii în domeniul ecocardiografiei.Scopul acestui document este de a furniza date desprecerinţele pentru pregătirea şi competenţa în ecocardiografie,de a sublinia principiile evaluării calităţii şide a recomanda un set de măsuri pentru îmbunătăţireacalităţii, cu scopul final de a ridica standardele practicăriiecocardiografiei în Europa.AbstractThe main mission statement of the European Associationof Echocardiography (EAE) is ‘to promote excellencein clinical diagnosis, research, technical development,and education in cardiovascular ultrasoundin Europe’. As competence and quality control issuesare increasingly recognized by patients, physicians,and payers, the EAE has established recommendationsfor training, competence, and quality improvement inecho cardiography.The purpose of this document is to provide the requirementsfor training and competence in echocardiography,to outline the principles of quality measurement,and to recommend a set of measures for improvement,with the ultimate goal of raising the standardsof echocardiographic practice in Europe.IntroducereEcocardiografia a schimbat practica medicinii cardiovasculare,îmbunătăţind prevenţia, diagnosticul şi managementuldiverselor boli cardiovasculare. Ecocardiografiaeste modalitatea imagistică cel mai frecvent utilizatăîn cardiologia clinică, deoarece permite o evaluareextensivă şi imediată a anatomiei şi funcţiei cardiace şivasculare. Disponibilitatea, portabilitatea, natura neinvazivăşi raportul cost-eficienţă, precum şi multitudineade informaţii furnizate conferă ecocardiografieistatutul de tehnică imagistică de primă alegere pentrudiagnosticul şi urmărirea majorităţii bolilor cardiace. 1,2În ultimele decenii ecocardiografia a înregistrat odez voltare tehnologică rapidă, în prezent putându-seobţine o cantitate impresionantă de date prin diferitetehnici (mod M, bi- şi tri-dimensional, Doppler), abordări(transtoracic- ETT, transesofagian- ETE, intravascular,epicardic) şi aplicaţii (de ex. ecocardiografia de

EAE RecommendationsDurata pregătiriiRecomandările privind cerinţele minime de pregătire(de ex. durată, număr de cazuri) au fost publicateanterior. 3-7Acest comitet al Asociaţiei Europene de Ecocardiografierecomandă două nivele de expertiză privind pregătireaîn domeniul ecocardiografiei: nivel de bază şiavansat. Nivelul de bază poate fi atins de orice cardiologgeneralist care utilizează ecocardiografia pentru a luadecizii clinice în legătură cu îngrijirea bolnavului. Nivelulavansat se adresează cardiologilor care aleg ecostres,cu contrast). Cu toate acestea, ecocardiografia rămâneo tehnică operator-dependentă. Pentru a efectuao examinare ecocardiografică comprehensivă şi utilăclinic este necesară o bună cunoaștere a anatomiei şifiziopatologiei cardiovasculare, precum şi o bună pregătiretehnică. Cunoştinţele şi tehnica necesară se potobţine doar prin educaţie şi antrenament supravegheatîntr-un mediu corespunzător. Publicaţii anterioare, atâtdin Europa, 3-5 cât şi din SUA, 6,7 s-au axat pe cerinţelepregătirii pentru competenţa clinică în ecocardiografie.ScopScopul acestui document este de a oferi criterii pentrupregătire, competenţă şi creşterea calităţii în ecocardiografiaclinică modernă.Formatul documentuluiAcest document elaborat de AEE este în acord cuprincipiile subliniate în Core Curiculum al SocietăţiiEuropene de Cardiologie şi intenţia sa este de a-l completa,oferind mai multe detalii cu privire la circumstanţespecifice legate de ecocardiografie. Core Curiculumal Societăţii Europene de Cardiologie 8 defineştenivelele de competenţă pentru diferitele tehnici diagnosticeşi stabileşte nivelul care trebuie atins pentru oanumită arie de interes.Nivelul I - experienţă în selectarea metodei diagnosticepotrivite şi în interpretarea rezultatelor; acest nivelnu include efectuarea metodei (de ex. metode imagisticeavansate, cum ar fi rezonanţă magnetică cardiacă,RM)Nivelul II - experienţă practică, dar nu ca operatorindependent (cel ce se pregăteşte a asistat la sau a efectuatexaminări supravegheate)Nivelul III - efectuează examinarea independent,fără ajutor (pentru cardiolog, examinarea include şiETE).Pregătirea practicăAspecte generale ale pregătirii în ecocardiografieIndiferent de metoda ecocardiografică folosită, existăun nivel de cunoştinţe minim necesar oricărei persoaneimplicate în efectuarea sau interpretarea ecocardiografiilor.Cunoştinţele de bază necesare pentrucompetenţa în ecocardiografie sunt sumarizate în Tabelul1 şi prezentate pe larg în Core Syllabus al SocietăţiiEuropene de Ecocardiografie. 9Cunoaşterea principiilor şi fizicii ultrasunetelor esteîn mod deosebit importantă.În esenţă cei ce se pregătesc ar trebui să cunoascăpro prietăţile ultrasunetelor, elementele ecografului,Romanian Journal of CardiologyVol. 22, No. 2, 2012for marea imaginii ecografice şi postprocesarea. 8,9 Dease menea ar trebui să cunoască setările ecografului şiar trebui să fie familiari cu artefactele tipice şi efectelebio l ogice ale ultrasunetelor. Nu în ultimul rând, cei cese pregătesc ar trebui să înţeleagă principiile ecocardiografiei Doppler, fiind capabili să aleagă dintre diferitelemo dalităţi (Doppler pulsat, continuu, color, Doppler tisular)pe cele care se pot aplica pentru a obţine măsurătoride utilitate clinică specifică.Tabelul 1. Cunoştinţe de bază pentru competenţa în ecocardiografieFizica ultrasunetelor şi efectele biologicePrincipiile formării imaginii ecocardiografice şi măsurării fluxului sanguin/velocităţii tisulareSetările ecografului şi reglarea unei imagini de calitateAnatomia cardiovasculară normală, incluzînd variante posibile ale normaluluiModificări patologice ale anatomiei cardiovasculare în diferite boliFiziologia cardiovasculară normală şi dinamica fluxului normal de sângeModificări patologice ale fluxului sanguin în diferite boliIndicaţii, contraindicaţii şi criterii de eficienţăTehnici diagnostice alternative pentru o anumită situaţieComplicaţii posibile (de ex. pentru ETE, eco de stres, contrast )Pregătirea pentru competenţa de ecocardiografie artrebui să includă abilitatea de a comunica şi raporta rezultateecocardiografice medicilor şi pacienţilor şi de acoopera cu cardiologi intervenţionişti, electrofiziologi,anestezişti, medici de medicină de urgenţă şi terapie intensivăşi chirurgi cardiovasculari. 8,10În ultimii ani, au apărut mai multe modalităţi ecocardiografice,fiecare dintre acestea cu aplicaţii specifice,care necesită cunoaştere, pricepere şi antrenament.Astfel este cazul ecocardiografiei de stres, ETE şi ecocardiografieiintra-operatorii, ecocardiografiei în bolicardiace congenitale, ecocardiografiei cu contrast, ecocardiografiei3D, ecografiei intracardiace şi intravasculare.Recent alte modalităţi imagistice neinvazive, cum arfi imagistica prin rezonanţă magnetică şi computer tomografiamulti-slice au cunoscut o dezvoltare rapidă.Ecocardiografiştii ar trebui să înţeleagă avantajele şi limitelefiecărei astfel de tehnici şi să le integreze pen trua îngriji mai bine pacientul.

Romanian Journal of CardiologyVol. 22, No. 2, 2012Nivelul avansatNivelul avansat de pregătire în ecocardiografie esterezervat celor care deja au atins nivelul de bază, dar caredoresc să se implice în ecocardiografii transtoracice maicomplexe şi să atingă un nivel superior de competenţă(nivel III) în: examinări ETT speciale (ecocardiografie3D, ecocardiografie de contrast sau ecocardiografie întimpul procedurilor intervenţionale), ecocardiografiitransesofagiene şi ecocardiografii de stres.Exemple de examinări ETT care necesită expertizăspecială şi care nu sunt de competenţa unui cardiologgeneralist cu pregătire ecocardiografică de bază sunt:evaluarea extensivă a hemodinamicii la un pacient cupatologie valvulară complexă (incluzînd cuantificarecompletă), evaluarea pacienţilor candidaţi pentru terapiade resincronizare cardiacă şi efectuarea unor ETTmai complexe (de exemplu deformare miocardică, detectareaafectării subclinice în cardiomiopatii, eligibilitateapentru înlocuirea valvulară percutană).Nivelul avansat presupune independenţă în efectuareaşi interpretarea ETE - minim 75 examinări efectuateindependent şi ecocardiografie de stres- minim 100de examinări efectuate independent (Tabelul 2).Nivelul avansat de competenţă implică o perioadăsuplimentară de antrenament în ecocardiografie deminim 6 luni şi efectuarea unui număr de 750 de ecocardiografia ca sub-specialitate principală şi care ar trebuisă efectueze examinări ecocardiografice completeşi să furnizeze informaţii pertinente, permiţând altorcli nicieni să gestioneze abordarea pacientului.Pentru fiecare nivel sunt publicate cerinţele minimepri vind durata pregătirii şi numărul de examinări efectuate.Deoarece nu sunt suficiente dovezi bazate pe evidenţepentru durata pregătirii şi numărul examinărilor,cifrele menţionate în Tabelul 2 reprezintă un consensal membrilor comitetului de elaborare, bazat pe experienţapractică.Deşi recomandările referitoare la durata pregătiriisunt utilizate pentru a facilita organizarea unui programde antrenament ţintit, accentul nu se pune pe oanu mită durată temporală, ci pe obţinerea expertizeine cesare. Deşi numărul de ecocardiografii la care participă cei ce se pregătesc este important, cazuistica este lafel de importantă şi ar trebui să acopere întreaga gamăa patologiei cardiovasculare (Tabelul 3).Din acest motiv este recomandat ca medicii în pregătiresă păstreze un „jurnal” care să fie marker al implicăriilor directe în examinările ecocardiografice, incluzânddiagnosticele pacienţilor pe care i-au examinat.Tabelul 2. Cerinţele de pregatire pentru nivelul de competenţă de bază şiavansatTehnicaecocardiograficăNumăr minim de examinăriefectuate pentru a dobândicompetenţaNivelul decompetenţăNumăr minim deexaminări efectuate/an pentru a păstracompetenţaETT 350 (bază) III neprecizat (rezonabil)750 (avansat) III 100*ETE 75 (avansat) III 50Ecocardiografie de100 (avansat) III 100stresNivelul III, abilitatea de a efectua examinarea independent (nesupravegheat).*Detalii la referinţa 32.Nivelul III de competenţă pentru ETT la adulţi conformrecomandărilor din Core Curriculum al SocietăţiiEuropene de Cardiologie pentru cardiologi generalişti. 8Nivelul de bazăUn medic în pregătire cu un nivel de expertiză debază ar trebui să efectueze independent o examinareecocardiografică transtoracică (nivel III pentru ETT)conform recomandărilor Asociaţiei Europene de Ecocardiografieprivind standardizarea examinării, stocareadigitală şi raportarea rezultatului. 10Cel ce se pregăteşte ar trebui să acumuleze suficientecunoştinţe şi abilităţi tehnice pentru a putea răspundeîntrebărilor clinice şi a fi util în situaţii de urgenţă.Un stagiu de ecocardiografie de 6 luni este perioadaminimă de antrenament recomandată pentru a atingeEAE Recommendationsnivelul de bază în ETT. Timpul de practică ar trebuicontabilizat şi folosit exclusiv în acest scop. Dacă aceastăperioadă nu permite cursantului să acumuleze numărulde examinări sau o cazuistică diversă, perioadade pregătire ar trebui extinsă.În timpul pregătirii pentru nivelul de bază medicular trebui să efectueze minim 350 de examinări ETT. 8Acest portofoliu ar trebui completat în decursul celor6 luni de antrenament continuu şi ar trebui să includăo cazuistică corespunzătoare, după cum a fost descrisăîn Tabelul 3.Este de aşteptat ca după încheierea cu succes a acestuinivel de pregătire, cursantul să susţină şi să promovezeexaminarea de acreditare în ETT a SocietăţiiEuropene de Ecocardiografie. Medicii în pregătire vorasista la ETE şi ecocardiografii de stres, fiind capabilisă înţeleagă indicaţiile, contraindicaţiile, avantajele şidezavantajele acestor tehnici (nivelul I de competenţă).Nu este obligatoriu să efectueze ei înşişi aceste tehnici.Aşadar, nivelul de bază al pregătirii corespunde niveluluiIII de competenţă în ecocardiografia transtoracică laadult şi nivelului I de competenţă în ETE şi ecocardiografiede stres.

EAE Recommendationscardiografii transtoracice, în plus faţă de cele efectuatepentru nivelul de bază (Tabelul 2).Acest nivel de antrenament poate fi atins în laboratoarede ecocardiografie care îndeplinesc criteriile AsociaţieiEuropene de Ecocardiografie pentru acreditareavansată. 11Nivelele de competenţă pentru practicieni/ecocardiografiştisunt sumarizate în Tabelul 4.Romanian Journal of CardiologyVol. 22, No. 2, 2012Programul de pregătireMedicul ar trebui să urmeze un program de pregătirestructurat astfel încât să corespundă obiectivelor salede studiu. Acest program ar trebui să includă instruirepractică, teoretică şi, ideal, activitate de cercetare.Programul de antrenament trebuie să fie complet şi artrebui să includă atât acumularea de cunoştinţe şi aptitudini,cât şi dezvoltarea unui comportament şi a uneiTabelul 3. Cazuistica pentru nivelul de bază pentru ecocardiografia transtoracicăPatologia cardiacă/ clinicăCunoştinţe şi aptitudini spre a fi însuşitePatologia cardiacă valvularăStenoza aorticăAchiziţie de imagini diagnosticeInsuficienţa aorticăRecunoaşterea criteriilor diagnosticeStenoza mitralăEvaluarea/cuantificarea severităţiiInsuficienţa mitralăDiferenţierea între leziuni cronice şi acute (insuficienţe valvulare)Stenoza tricuspidianăEvaluarea consecinţelor asupra dimensiunilor, geometriei şi funcţiei cavităţilor cardiaceInsuficienţa tricuspidianăCriteriile şi oportunitate intervenţie, aprecierea indicaţiei de reparare chirurgicală şi eligibilitatea pentru intervenţia percutanăStenoza pulmonarăEvaluarea ecocardiografică (2D şi Doppler) a funcţiei normale şi malfuncţiei valvelor mecanice şi biologiceInsuficienţa pulmonarăAprecierea necesităţii unor investigaţii diagnostice complementareProteze valvulareStabilirea necesităţii unei urmăriri periodiceBoala coronariană ischemicăInfarct miocardicCardiopatie ischemicăCardiomiopatiiCardiomiopatie dilatativăMiocardităCardiomiopatie hipertroficăCardiomiopatii restrictive şi infiltrativeInsuficienţa cardiacăHipertensiuneEndocardita infecţioasăEcocardiografia de urgenţăBoli cardiace congenitale simpleTumori şi mase cardiaceSurse de embolismEmbolie pulmonarăHipertensiune pulmonarăPatologia aorteiPatologia pericarduluiExaminări normaleRecunoaşterea semnelor şi consecinţelor ischemiei şi infarctului miocardicLocalizarea tulburărilor de cinetică într-un format standardizatEvaluarea extinderii infarctului şi a miocardului la riscEvaluarea funcţiei sistolice segmentare şi regionale a VS şi funcţiei diastolice VSDiagnosticul complicaţiilor mecanice ale infarctului miocardic şi consecinţele hemodinamice ale acestoraRecunoaşterea implicaţiilor prognostice ale parametrilor structurali şi funcţionaliEfectuarea unei examinări complete (mod M, 2D, Doppler) care să permită stabilirea diagnosticului, cuantificarea cu acurateţe a severităţiibolii şi care să ajute la alegerea modalităţii terapeutice adecvateStabilirea diagnosticului diferenţial între cordul atletului şi cardiomiopatia hipertroficăIdentificarea pacienţilor candidaţi pentru terapia de resincronizare cardiacăEvidenţierea trăsăturilor ecocardiografice ale cardiomiopatiilor, bolii coronariene ischemice, patologiei valvulare, miocarditei, pericarditeiconstrictive, hipertensiunii pulmonare şi altor patologii asociate cu insuficienţă cardiacăIdentificarea cauzelor insuficienţei cardiace acuteRecunoaşterea implicaţiilor prognostice ale parametrilor funcţionaliRecunoaşterea complicaţiilor tipice ale insuficienţei cardiace (contrast spontan, trombi, lichid pericardic, etc)Calcularea masei VS, grosimii relative a pereţilor, evaluarea geometriei VSEvaluarea funcţiei sistolice şi diastolice a VSEstimarea presiunilor de umplere VSNu mai mult de o treime din totalul examinărilorTabelul 4. Sumarul nivelelor de competenţă pentru practicieni/ecocardiografiştiEcocardiografie nivel de bază (corespundecerinţelor Core Curriculum al SocietăţiiEuropene de Cardiologie pentru antrenamentulcardiologilor generalişti)Ecocardiografie nivel avansat (pentru cardiologiicu subspecialitate in ecocardiografie)ETT, ecocardiografie transtoracică; ETE, ecocardiografie transesofagianăNivelul III de competenţă în ETT la adultNivelul I de competenţă ETENivelul I de competenţă în ecocardiografia de stresNivelul III de competenţă în ETT la adultNivelul III de competenţă în ETT complexăNivelul III de competenţă în ETENivelul III de competenţă în ecocardiografie de stresatitudini adecvate. 8 Pentru a fi coerent, se recomandăca programul să fie realizat într-un singur centru acreditat,care poate îndeplini cerinţele pregătirii.Pe parcursul perioadei de pregătire, medicul ar trebuisă participe în mod constant şi activ la întrunirilepe teme ştiinţifice, la prezentarea cazurilor interesantediscutând indicaţiile, rezultatele şi complicaţiile legatede procedură, comparaţii cu alte metode (incluzând ca-

Romanian Journal of CardiologyVol. 22, No. 2, 2012teterismul şi chirurgia cardiacă). Cei ce se pregătesc artrebui să participe cel puţin o dată pe an la o reuniuneecocardiografică acreditată, naţională şi/sau internaţională.Este recomandată implicarea celui care se pregăteşteîn proiectele de cercetare ale laboratorului.De asemenea este importantă atitudinea de autoevaluare,programele educaţionale on-line jucând unrol important în experienţa de studiu, atât în timpul,cât şi după terminarea perioadei de pregătire. Medicular trebui să aibă suficiente cunoştinţe de cardiologie corespunzătoarepentru fiecare nivel de pregătire ecocardiograficăşi ar trebui să efectueze numărul recomandatde ecocardiografii.Centrele de pregătireAEE a publicat standarde pentru acreditarea laboratoarelorde ecocardiografie în ETT, ETE şi ecocardiografiede stres. 11 Aceste recomandări se referă la douănivele de acreditare: standard şi avansat, depinzînd defacilităţi, personal, echipament şi alte criterii de organizareinterioară considerate esenţiale pentru cercetare.Laboratoarele de ecocardiografie în care se desfăşoarăpregătirea ar trebui să îndeplinească recomandărileAsociaţiei Europene de Ecocardiografie, preferabilpentru nivel avansat. 11 În special, dedicarea personaluluididactic este esenţială pentru a asigura calitateapregătirii. Cel care este implicat în pregătirea medicilorar trebui să supervizeze, să critice şi să corecteze ecocardiografiileefectuate sau interpretate şi să promovezeparticiparea activă la activităţile de cercetare. Mai mult,centrul de pregătire ar trebui să organizeze în mod regulatactivităţi educaţionale săptămânale.Un laborator de pregătire în ecocardiografie poateexista independent sau poate fi integrat într-un centrude imagistică cardiacă sau într-un departament de cardiologie.Existenţa în aceeaşi instituţie a unei unităţi deterapie coronariană, a altor modalităţi imagistice neinvazive(de ex. scintigrafie, rezonanţă magnetică, CTmulti-slice), precum şi a diferitelor subspecialităţi (deex. cardiologie intervenţională, electrofiziologie, chirurgiecardiacă) permite medicului să ia contact cu tehnicidiferite de explorare şi să confrunte rezultatul ecocardiograficcu cel provenit din tehnici complementare.În mod ideal, ar trebui să existe un program educaţionalcare să asigure o rotaţie în stagii de ecocardiografie,scintigrafie, rezonanţă magnetică şi CT, dacă acesteasunt disponibile. 12 Laboratorul de ecocardiogra fiear trebui să colaboreze îndeaproape cu serviciile noninva zive şi invazive, deoarece aceste abordări sunt complementare şi nu competitive.EAE RecommendationsEcocardiografia transtoracică în cazul pacienţiloradulţiPentru a putea utiliza ecocardiografia transtoracicăla adulţi, au fost publicate criterii de competenţă 13 cucla se diferite de indicaţie pentru scenarii clinice specifice.Deoarece dependenţa de operator poate fi importantă,medicul trebui să înţeleagă, să achiziţioneze şi sădocumenteze toate imaginile standard conform recomandărilor.10 Cu toate acestea, limitarea examinării laimaginile standard poate uneori să ducă la trecerea cuvederea a unor date patologice importante şi/sau la raportareafără acurateţe a unor date. Aşadar, este esenţialca ecocardiografistul să poată adapta examinarea pebaza interpretării în context clinic. Personalul destinata pregăti cursanţii are un rol cheie în învăţarea moduluide utilizare corectă a transductorulului şi în înţelegereaa ceea ce reprezintă achiziţia optimă şi calitatea tehniciiîn cazul individual al fiecărui pacient.Pregătirea specifică şi competenţelerecomandate pentru procedurile specialeEcocardiografia transesofagianăETE furnizează o fereastră imagistică excelentă a inimiişi a vaselor mari. Indicaţiile detaliate, contraindicaţiile,riscurile şi potenţialele complicaţii ale ETE au fostpublicate 14,15 şi nu reprezintă scopul acestei prezentări.Pentru a atinge nivelul avansat III de compentenţă înETE este recomandată efectuarea fără supraveghere aunui număr minim de 75 de ETE.Pentru a fi eligibil acreditării în ETE de către AEE,este necesară completarea în termen de 1 an a 75 cazuride ETE pentru candidaţii care deţin o acreditare ETTşi a 125 de cazuri pentru cei ce nu deţin o acreditareETT. Acreditarea naţională sau acreditarea AEE estenecesară pentru medicii care efectuează independent şiraportează ETE.Cunoştinţele şi aptitudinile necesare pentru a devenicompetent în efectuarea şi raportarea ETE sunt menţionateîn Tabelul 5.În mod ideal, antrenamentul în ETE ar trebui săincludă ETE intra-operatorii şi ETE în timpul procedurilorintervenţionale. ETE intervenţională (de ex.închidere percutană a unui defect de sept interatrial,val vuloplastie mitrală cu balon şi înlocuire valvularăper cutană) necesită cunoaşterea fiecărei proceduri şi apo tenţialelor sale problemelor.Ecografia transesofagiană intra-operatorieEcografia transesofagiană intra-operatorie se referăla aplicaţiile ecocardiografiei la pacienţii care sunt su-

EAE Recommendationspuşi intervenţiilor chirurgicale în timpul acestora, pecând ecocardiografia peri-operatorie se referă la ecocardiografia efectuată în perioada imediat post-operatorie.Aceste examinări sunt efectuate mai ales prinETE, deşi tehnicile epicardice continuă să aibă un rolîn cazuri specifice.Ecocardiografia intra-operatorie se bazează pe majoritateamodalităţilor ecocardiografice utilizate în contextulne-chirurgical, astfel încât se pot aplica cerinţelemenţionate pentru competenţă în ETE. În plus, ETEintra-operatorie necesită înţelegerea particularităţilorsălii de operaţie, luând în considerare hemodinamicavariabilă a pacienţilor cu sau fără circulaţie extracorporeală,discutarea datelor cu chirurgii şi înţelegerea proceduriichirurgicale, incluzând potenţialele complicaţii,care adesea necesită cunoştinţe speciale de tehnică sauvo cabular. Indicaţiile pentru ETE intra(peri)-operatorieau fost publicate anterior. 16 Rezultatul chirurgicalpoate fi evaluat ecocardiografic şi pot fi efectuate pro ceduri adiţionale dacă se consideră necesar pe baza ecocardiografiei.În multe ţări europene ETE intra-operatorie esteefec tuată de anestezişti cu pregătire specială în ETE.Ecocardiografia de stresAEE a publicat recent un consens al experţilor referitorla ecocardiografia de stres. 17 Documentul prezintăîn detaliu diferitele tipuri de agenţi stresori şi protocoale,indicaţiile şi contraindicaţiile pentru fiecare tip deRomanian Journal of CardiologyVol. 22, No. 2, 2012stres, criteriile diagnostice şi prognostice ale ecocardiografieide stres, complicaţiile şi efectele adverse posibile.17 Nu este rezonabil să se utilizeze ecocardiografia destres fără o pregătire completă în ETT şi fără deţinereaacreditării naţionale sau AEE. Aptitudinile de bazăce rute pentru ecocardiografia de repaus nu diferă substanţialde cele necesare pentru ecocardiografia de stres.Cu toate acestea, s-a dovedit că interpretarea ecocardiografiilor de stres de către un ecocardiografist fărăantrenament în ecocardiografia de stres subestimeazăconsiderabil potenţialul diagnostic al acestei tehnici. 18Pentru încadrarea corectă în curba de învăţare şi atingereanivelului de platou al acurateţii diagnostice estenecesară efectuarea a 100 de ecocardiografii de stres. 18Recomandarea AEE este de a efectua 100 de examinărisub supravegherea unui expert în ecocardiografie,în cadrul unui laborator cu activitate intensă, cu posibilitateaverificării angiografice. 17Pentru a dobândi acurateţe de diagnostic intra-observator şi pentru a reduce variabilitatea inter-observator,interpretarea trebuie făcută împreună cu uneco cardiografist cu experienţă. 19 Utilizarea imaginilordi gitale în locul imaginilor video poate îmbunătăţi acurateţea, 20 cu toate că reproductibilitatea este de obiceimică la pacienţii cu imagini de repaus de o calitate la limită.La pacienţii cu fereastră ecocardiografică dificilă,native second harmonic imaging 21 şi utilizarea agenţi-Tabelul 5. Cunoştinţe şi aptitudini necesare pentru dobândirea competenţei în ecocardiografia transesofagianăCunoştinţeCunoştinţe generale de bază legate de ecocardiografie (Tabelul 1)Avantaje/ dezavantaje ale ETE pentru o anumită indicaţieInformaţia adiţională în comparaţie cu alte tehnici imagistice, în particular ETT şi alte tehnici tomograficeIndicaţiile, contraindicaţiile, riscurile, şi complicaţiile procedurii de ETEPrevenirea / controlul infecţiilor şi aritmiilor legate de utilizarea ETERiscurile şi tehnicile de anestezie locală şi sedare; farmacologia medicamentelor implicateAnatomia tractului gastrointestinal superior cu atenţie specială asupra potenţialelor probleme şi pericole în timpul intubaţiei esofagieneCunoştinţe despre anatomia cardiovasculară normală şi patologică la ETE şi a incidentelor tipiceAbilitatea de a comunica rezultatele examinării pacientului şi altor mediciAbilităţiAbilitatea de a efectua o examinare ETT completăAbilitatea de a obţine un istoric ţintit al bolilor gastrointestinaleFolosirea sondei ETE şi piesei bucale, inclusiv manipularea vârfului sondei şi schimbarea orientării planului imaginiiAbilitatea de a folosi ecograful, inclusiv setările care afectează calitateaTehnici de intubare esofagiană (şi la pacienţii ventilaţi şi la cei neventilati) inclusiv tehnici de sedare, monitorizare adecvată, disponibilitatea echipamentului suportivCompetenţă în resuscitarea cardiopulmonarăManipularea sondei pentru a genera incidentele necesare pentru a răspunde întrebărilor clinice specificeCunoştinţe în obţinerea seturilor tipice de imagini şi alte date (secţiuni transversale, date Doppler, şi altele) care urmează a fi obţinute în timpul ETE pentru indicaţii specifice (ex. căutarea sursei cardiace aembolismului, disfuncţii ale valvelor prostetice, etc.), inclusiv injectarea intravenoasă a substanţei de contrast pentru detectarea şuntuluiAbilitatea de a recunoaşte anomaliile structurale şi funcţionale cardiace aşa cum sunt vizualizate prin ETE şi de a recunoaşte artefacteleAbilitatea de a efectua analize calitative şi cantitative ale datelor ecocardiograficeAbilitatea de a face un raport scris logic şi comprehensiv al concluziilor ecocardiografiei, inclusiv al posibilelor implicaţii cliniceCunoştiinţe în dezinfecţia sondei şi în detectarea defectelor tehnice, în special la izolaţia electrică

Romanian Journal of CardiologyVol. 22, No. 2, 2012lor de contrast pot îmbunătăţi acurateţea şi reduce variabilitatea.22,23 Medicii trebuie să înveţe şi să înţeleagăaspectele legate de siguranţa ecocardiografiei de stres şiimportanţa unui personal bine antrenat.Tabelul 6. Cerinţele legate de personal în cazul ecocardiografiei de stresCerinţele pregătirii pentru efectuarea şi interpretarea ecocardiografiei de stresÎnţelegerea principiilor de bază, indicaţii, aplicaţii şi limitele tehnice ale ecocardiografieiNivel III de pregătire în ecocardiografiePregătire specială în ecocardiografia de stres, cu efectuarea şi interpretarea a minim 100 deecocardiografii de stres sub supravegherea unui ecocardiografist cu nivelul III de competenţă înecocardiografia de stres.Păstrarea competenţei în ecocardiografie de stresEfectuarea şi interpretarea a cel puţin 100 ecocardiografii de stres/anParticiparea la educaţie medicală continuă în ecocardiografieSunt necesare cel puţin două persoane pentru a înregistra şi monitoriza ecocardiografiile de stres,dintre care una ar trebui să aibă calificare pentru resuscitare cardio-pulmonară avansată.O asistentă ar trebui să fie prezentă în permanenţă pentru a ajuta medicul care efectueazăecocardiografia. Dacă ecocardiografia este efectuată de un sonografer/tehnician, trebuie sa fieprezent un medic cu experienţă în ecocardiografie şi resuscitare, în cazul în care apare o complicaţieameninţătoare de viaţă.Pentru a atinge o abordare diagnostică generală caresă se adreseze nevoilor individuale ale pacienţilor, esteimportantă cunoaşterea tuturor tipurilor de agenţi destres (farmacologic şi exerciţiu fizic). Cu toate acestea,deoarece dificultatea evaluării, interpretării şi siguranţavariază în funcţie de caracteristicile fiecărui pacient, detipul de stres şi protocolul utilizat, este recomandat săse înceapă cu cele mai uşoare şi sigure şi apoi să se treacăla cele mai solicitante şi cu risc mai înalt. 17Cursanţii trebuie să înţeleagă că pentru o anumităacu rateţe a diagnosticului, fiecare observator are o curbăproprie de sensibilitate/specificitate, care depinde demo delul de interpretare a imaginilor ca fiind anormaleşi de aceea este importantă utilizarea unui consens dein ter pretare a ecocardiografiilor cu contrast. 17,24Cerinţele pregătirii pentru competenţa în ecocardiografiesunt menţionate în Tabelul 2 şi cerinţele personaluluidin laboratorul de ecocardiografie sunt prezentateîn Tabelul 6. 17,25,26EAE RecommendationsEcocardiografia adulţilor cu boală cardiacăcongenitalăEcocardiografia a devenit metoda de diagnostic şieva luare seriată de primă alegere la nou-născuţi, copiişi adulţi cu boală cardiacă congenitală.Pentru a efectua ETT la pacienţii cu suspiciune saucu boală cardiacă congenitală cunoscută, ecocardiografiştiitrebuie să cunoască protocolul de analiză standard,esenţial când datele sunt achiziţionate secvenţiat.27 Învăţarea ferestrelor ecocardiografice adecvate, amă surătorile corecte şi luarea în calcul a posibilităţiiexistenţei unei patologii multiple fac parte din pregătire.La adulţii cu imagine transtoracică de calitate nesatisfăcătoaresau în situaţiile în care este necesară odefinire mai bună a anatomiei sau fluxului, pot fi utileETE sau ecocardiografia de contrast cu soluţie salină.Medicul ar trebui să cunoască indicaţiile ETE şi ecocardiografieicu contrast. În plus, trebuie cunoscutelimitările ecocardiografiei şi rolul complementar al altortehnici imagistice (de ex. evaluarea dimensiunii şifuncţiei VD prin rezonanţă magnetică). Cardiologii cuantrenament ecocardiografic de bază (nivel III în ETTgenerală) ar trebui să recunoască variantele anato mi ceale normalului şi defectele cardiace congenitale obiş -nuite (de ex. defecte izolate de sept interatrial şi interventricular, persistenţa de canal arterial, patologieva l vulară congenitală izolată, membrană subaortică,coarctaţie de aortă, transpoziţie corectată de mari vase,tetralogie Fallot, anomalie Ebstein, persistenţa de venăcavă superioară), să aprecieze necesitatea şi frecvenţaecocardiografiilor de urmărire şi să evalueze necesitateaintervenţiei percutane sau chirurgicale.Ecocardiografia de contrastMultă vreme soluţia salină agitată a fost utilizată caagent de contrast (de ex. pentru a determina prezenţa,mărimea şi semnificaţia funcţională a şunturilor interatrialela pacienţi cu suspiciune de foramen ovale patent).Introducerea agenţilor de contrast intravenos cupasaj transpulmonar a îmbunătăţit evaluarea structuriişi funcţiei VS.Recent, AEE a publicat recomandările pentru utilizareaclinică a ecocardiografiei de contrast. 23 Documentuldescrie în detaliu caracteristicile agenţilor decontrast disponibili la ora actuală, modalităţile de imagisticăcu contrast, indicaţiile, eficienţa clinică şi siguranţaagenţilor de contrast utilizaţi în ecocardiografie.Înainte de efectuarea ecocardiografiilor cu agenţi decontrast, medicii şi ecocardiografiştii trebuie să atingănivelul de antrenament de bază şi ar fi de preferat sădeţină acreditarea în ETT. Cei care utilizează agenţi decontrast în ecocardiografia de stres trebuie să deţinăacreditare sau cel puţin să fi efectuat pregătire pentruecocardiografia de stres. Pe lângă pregătirea în ecocardiografiade repaus şi de stres, utilizarea agenţilor decontrast necesită un nivel de experienţă dobândită subsupraveghere corespunzătoare. Medicii care efectueazăecocardiografie de contrast ar trebui să cunoască modulde administrare al agenţilor de contrast, indicaţiileşi contraindicaţiile acestora, precum şi managementulefectelor adverse. 23 Experienţa folosirii agenţilor decontrast pentru opacifierea VS este o condiţie necesarăpentru trecerea la evaluarea perfuziei miocardice.

EAE RecommendationsCompetenţaCerinţele privind competenţa în cadrul diferitelortehnici ecocardiografice, alături de cele privind o pregătireminimă au fost discutate în capitolul anterior.Prezentul capitol descrie principiile generale pentruobţinerea şi menţinerea competenţei şi statusul actualal AEE privind acreditarea şi reacreditarea pentru diferitetehnici ecocardiografice.Dovada competenţei: acreditareaDeşi, în mod teoretic, finalizarea unui program corespunzătorde pregătire ar trebui să asigure competenţa,toate sistemele necesită verificări suplimentare. Maimult decât atât, competenţa individuală nu poate fi separatăde cea a echipei şi de condiţiile de lucru. Aceastălegătură este ilustrată atât de faptul că laboratoarele caresolicită acreditarea AEE trebuie să demonstreze că tehnicienii/ultrasonografiştiilor sunt acreditaţi, precum şică sistemul american de acreditare a laboratoarelor deecocardiografie solicită prezentarea de mostre a activităţiifiecărui individ ca parte a procesului de obţinere aacreditării 28 . De aceea, obţinerea competenţei necesităevaluarea cunoştinţelor şi abilităţilor practice ale fiecăruiindivid şi ale laboratorului de ecocardiografie încadrul căruia acesta lucrează.Dovada competenţei individualeCompetenţa necesită obţinerea acelor date conformcărora candidatul are cunoştinţele teoretice, abilităţilepractice şi atitudinea potrivite, 6,8 acestea putând fi apreciateprintr-o combinaţie de trei metode:(a) dovada /declaraţia celor responsabili de pregătiresau ale supervizorilor;(b) verificări ale cunoştinţelor teoretice prin exa minări;(c) dovada abilităţilor practice.(a) Scrisorile de recomandare şi simpla verificare apregătirii în subspecialitate ar putea să nu re pre zintesub stitute adecvate pentru evaluarea inde pendentă agra dului de abilitate şi pregătire a unui ecocardiografist.Modul ideal de evaluare a competenţei unui individeste prin observare directă în timpul efectuării uneiexa minări, folosind evaluarea abilităţilor proceduraleobservate direct. 29De aceea, importanţa celor responsabili de pregătireşi a supervizorilor nu poate fi subestimată. Supervizorular trebui să fie acreditat naţional/AEE şi în modobişnuit ar trebui să fie conducătorul laboratorului încare se desfăşoară pregătirea.La finalul pregătirii, supervizorului i se va solicita sădemonstreze că respectivul candidat:Romanian Journal of CardiologyVol. 22, No. 2, 2012(i) a urmat un program de pregătire,(ii) a obţinut competenţa adecvată.(b) examinările, ca metodă de evaluare, sunt supusecriticilor şi sunt, într-adevăr, predispuse multor erori.Ele testează, în principal, cunoştinţele efective. Totuşi,ele sunt acceptate, validate şi folosite pe scară largă înpro cesele de evaluare.În ecocardiografie, întrebările ar trebui să testeze cunoştinţeleteoretice şi, de asemenea, interpretarea imaginilorprezentate candidaţilor. Imaginile pot fi prezentate în cadrul unei prezentări de caz (cel mai util încazul ecografiei transtoracice) sau ca imagini independente(metodă folosită pentru ecografia transesofagiană).De aceea, ca parte a procesului de evaluare a competenţeifolosit pentru obţinerea acreditării AEE, candidaţiise vor supune unei examinări cu întrebări tiprăs puns multiplu:(i) 100 de întrebări ce testează cunoştinţele teoretice,(ii) 50 de întrebări ce testează abilitatea de a interpretaimagini din studii ecocardiografice.Deşi o astfel de examinare are un punctaj de promovarestabilit anterior, este adecvat ca acesta să poată fiajustat de către comitetul de examinare după fiecare sesiunepe baza unei combinaţii de metode care includrepere anterioare versus un comitet de experţi şi repereanterioare versus unor cohorte de candidaţi (care tindsă aibă un nivel de competenţă similar), derivate dinanalize statistice ale răspunsurilor la întrebări.Examinarea ar trebui să fie constant revizuită şi reevaluată.30,31(c) Natura foarte practică a ecocardiografiei presupunenecesitatea unui element practic pentru evaluare.Deşi acesta ar putea fi integral asigurat de declaraţia supervizorului(sistemul american NBE/CCI/ARDMS),acestea sunt argumente solide pentru includerea sa înprocesul de evaluare (procesul de acreditare AEE).Un jurnal permite evaluatorilor să revizuiască nivelulde activitate al unui individ aflat în procesul de pregătire şi să obţină o evaluare prin analiza (calitativă) are latărilor. O abordare adiţională sau alternativă esteaceea prin care i se solicită candidatului să prezintemos tre ale activităţii sale în format electronic pe un suporttip disc sau prin internet. Aceasta trebuie sa fie încon formitate cu reglementările locale privind protecţiada telor. Examinările pot fi supuse aprecierii calitative.În ambele cazuri, este important ca aprecierea să fieobiec tivă şi reproductibilă şi presupune ca procesele decon trol ale calităţii şi pregătirii să fie ac ti ve.

Romanian Journal of CardiologyVol. 22, No. 2, 2012Elementul practic pentru acreditarea AEE constă înprezentarea unui jurnal de cazuri (250 pentru ecografiatranstoracică (ETT), 125 pentru ecografia transesofagiană(ETE), cu excepţia cazului în care candidatul areacreditare pentru ETT, în această situaţie 75 de cazurifiind suficiente şi 250 pentru bolile congenitale cardiace)efectuate de către candidat într-o perioadă de 12luni după absolvirea examenului scris. Asocierea de cazuritrebuie să acopere gama de patologie observată înmod normal în practică.Iniţial, 15 cazuri extrase aleator din jurnalul de activitatesunt evaluate de către doi examinatori. Începândcu 2009 s-a introdus însă un jurnal electronic pentruETT şi este planificat pentru ETE din 2010. Acesta implicăincluderea a 6 studii care să acopere o gamă depatologii cheie şi o gamă completă de imagini şi modalităţiecocardiografice. Candidaţii încarca examinărileîn sistemul conectat la internet la Heart House (ima ginistatice şi clipuri, anonimizate corespunzător) alături derezultatele lor pentru aceste studii. Acest jurnal electroniceste ulterior notat de către evaluatorii independenţiai AEE. 32În combinaţie, declaraţia supervizorului, examinareascrisă şi jurnalul de ecocardiografii dovedesc nivelulde competenţă şi decizia acreditării AEE.Menţinerea competenţei individualeReacreditareaCompetenţa permanentă nu poate fi asumată înprac tica ecocardiografie. Natura sa practică şi dezvoltareaconstantă de noi tehnici necesită pregătire şi studiucon tinuu pentru a menţine competenţa. Acesta este unaspect important al controlului calităţii în ecocardiografie.Doar cifrele sunt un sistem insuficient de orientare,însă nu există alt sistem practic pentru a solicita ecocardiografiştilorsă reia evaluările practice şi pe cele bazatepe cunoştinţe teoretice la intervale regulate. Majoritateasistemelor de reacreditare combină cerinţele pentrupractica continuă cu obţinerea de credite de educaţiecontinuă prin participarea la întâlniri relevante sau alteactivităţi de studiu continuu. 28,32 Altă cerinţă pentru caun criteriu să fie inclus într-un program de control alcalităţii este introducerea sa în anumite sisteme. Sistemelede sănătate în care medicii raportează frecventexaminările efectuate de ecocardiografişti ar putea facedistincţia între numărul de examinări raportate şi celeefectuate pentru continuarea menţinerii competenţei.Deşi acreditarea AEE este valabilă timp de 5 ani, reacreditareanecesită dovada practicii continue (declaraţiea conducătorului laboratorului sau a unui asistent)EAE Recommendationsşi, de asemenea, dovada activităţii de educaţie medicalăcontinuă (ex. certificat de participare).Cerinţele de bază pentru reacreditarea AEE în ecocardiografietranstoracică (ETT) sunt:• 250 de examinări pe an şi 40 ore de educaţie medicalăcontinuă (centre cu volum intens)• 100 de examinări pe an şi 50 ore de educaţie medicalăcontinuă (centre cu volum redus) 32Acreditarea laboratoruluiS-au stabilit criterii pentru determinarea calităţiiunui laborator de ecocardiografie. Există programeample de acreditare a laboratoarelor în Europa 11,32 şiStatele Unite. 28 Principalele aspecte evaluate sunt:• facilităţi (mediu şi echipament);• fluxul de activitate;• educaţie şi pregătire;• asigurarea calităţii.Există criterii separate pentru ETT, ETE şi ecocardiografiade stres, iar sistemul AEE are două nivele, standardşi avansat, ultimul aplicabil acelor laboratoare careoferă pregătire şi cercetare recunoscute internaţional.Pe scurt, AEE solicită candidaţilor să urmeze un pro -gram supravegheat de pregătire într-un laborator adecvatde ecocardiografie şi să demonstreze cunoştin ţeleteoretice printr-un examen scris dar şi abilităţile practiceprin depunerea unui jurnal de raportare a examinărilorecocardiografice.Îmbunătăţirea calităţiiÎn ciuda faptului că asigurarea unui nivel înalt deca litate a devenit un aspect important pentru pacienţi,medici şi forurile finanţatoare, s-a acordat o atenţie relativlimitată măsurilor de îmbunătăţire şi control a calităţiiîn ecocardiografie.Principiile de evaluare a calităţiiÎn prezent, evaluarea calităţii serviciilor ecocardiograficeîn Europa se face aproape exclusiv prin acreditarevoluntară. Atât Societatea Americană de Ecocardiografieprin Comisia Intersocietală pentru AcreditareaLaboratoarelor de Ecocardiografie, 28 cât şi AEE auintrodus acreditări atât individuale 30-32 cât şi pentrulaboratoare de ecocardiografie 11,32 . Totuşi, este limpedecă măsurarea şi monitorizarea calităţii sunt necesaredincolo de acreditare deoarece aceasta reflectă în modtipic condiţiile pe parcursul unui interval limitat detimp şi ar fi de dorit să se implementeze monitorizareacontinuă pentru îmbunătăţirea şi controlul calităţii. 33Dobândirea calităţii în ecocardiografiePrimul pas este acela de a crea măsuri specifice deeva luare a calităţii. 34 Modelul AEE constă în patru do-

EAE Recommendationsmenii distincte care ar putea să influenţeze rezultatulclinic: selecţia pacienţilor, efectuarea examinării, interpretareaşi raportarea (Figura 1). Infrastructura laboratorului(logistică, echipament, personal) şi organizarea(proceduri şi protocoale) influenţează şi susţin acestepatru domenii.• Primul pas către un serviciu ecocardiografic deînaltă calitate este asigurarea selecţiei adecvate apacienţilor pentru o modalitate ecocardiograficăanume pe baza dovezilor şi a consensului, care săfie convenabilă şi eficientă din punct de vedere alcostului. Aceasta va afecta gestionarea ulterioarăa pacientului şi va determina beneficiu clinic.• Al doilea pas este reprezentat de efectuarea exa -mi nării folosind echipament adecvat, 11 teh ni ci e niecografişti şi medici 11,31 acreditaţi pen tru a ob ţineinformaţii complete şi exacte lega te de în tre -bările derivate din clinică. 10 Toate exa mi nă riletre buie să fie înregistrate, ideal în format di gital.10• Toate imaginile şi măsurătorile sunt obţinute cuprecizie, calitativ şi cantitativ.• În cele din urmă, trebuie să existe o raportare adatelor într-o manieră clară, concisă şi orientatăclinic pentru a servi gestionării ulterioare a pacientuluişi pentru a îmbunătăţi rezultatele actuluimedical.Măsurile de evaluare a calităţii sunt propuse pentrufiecare pas al schemei descrise în Figura 1.Selecţia pacienţilorExpansiunea continuă a aplicaţiilor clinice ale ecocardiografieialături de îmbunătăţirile tehnice continueau determinat o creştere explozivă a numărului de examinăriecocardiografice efectuate. Pentru a identificapacienţii care vor beneficia cel mai mult de pe urmaecocardiografiei au fost publicate 13 ghiduri cu recomandăriprivind indicaţiile pentru care ecocardiografiaar putea fi considerată adecvată. Din moment ce ma-Romanian Journal of CardiologyVol. 22, No. 2, 2012joritatea examinărilor sunt efectuate numai ca urmarea indicaţiilor medicului generalist, fără o consultareprealabilă cu cardiologul care analizează şi raporteazăexaminarea, trebuie depuse eforturi educaţionale,menite să crească nivelul de competenţă al mediculuigeneralist în ceea ce priveşte ghidurile existente. Pentrua veni în ajutorul medicilor generalişti care trimitpacienţi către serviciile de ecocardiografie şi colecteazădate pentru indicaţiile de monitorizare a examinării, arfi utilă generarea unor formulare specifice de solicitare.De asemenea, ar trebui asigurat un răspuns ulterior decătre medicii care au făcut respectivele solicitări.Deşi necesită efort şi o colectare adecvată a datelor,optimizarea şi monitorizarea selecţiei pacienţilor suntimportante datorită impactului lor asupra testării ulterioare,menţinerii abilităţilor practice, procedurilor şicosturilor.Efectuarea examinării şi siguranţa pacientuluiAchiziţia de imagini de înaltă calitate şi caracterulcomplet al examinării depind de protocoale specificecare optimizează probabilitatea ca o examinare ecocardiograficăsă fie completă şi precisă. 10 Aderenţa la astfelde recomandări şi precizia monitorizării, completitudineaşi calitatea globală a examinărilor ecocardiograficear putea fi instrumente utile pentru evaluarea calităţiiserviciilor ecocardiografice (Tabelul 7). Factori precumincidenţa complicaţiilor pe parcursul examinărilorecografice transesofagiene sau de stres sau procentulde intubări incomplete în tentativele de examinaretransesofagiană sunt indicatori care trebuie utilizaţipentru a evalua siguranţa pacientului. Antrenamentulşi acreditarea ultrasonografiştilor şi/sau a cardiologilorcare efectuează examinările ecografice sunt, de asemenea,indicatori importanţi ai calităţii. Totuşi, simplaacreditare individuală a ecocardiografiştilor nu poategaranta examinări de înaltă calitate. De asemenea, estenecesar să existe sisteme de ecocardiografie, gestionareşi organizare adecvate, şi aceasta constituie temeliaFigura 1. Schema de evaluare a calităţii în ecocardiografie şi influenţa asupra gestionării pacientului. Modelul propus constă în 4 domenii principale care arputea influenţa evoluţia clinică. Infrastructura şi organizarea laboratorului susţin întregul proces ecocardiografic.

Romanian Journal of CardiologyVol. 22, No. 2, 2012fundamentului procedural atât pentru acreditarea individuluicât şi a laboratorului. 32Interpretarea examinăriiAEE a dezvoltat proceduri pentru a evalua competenţapentru ETT şi ETE standard la adulţi precum şipentru ecocardiografia în boala cardiacă ischemică. 32Totuşi, interpretarea de înaltă calitate a examinăriinu este garantată de existenţa ecocardiografiştilor acreditaţi.Laboratoarele eco de înaltă calitate ar trebui săofere dovada atât a acurateţii cât şi a reproductibilităţiiinterpretării examinărilor ecocardiografice (Tabelul 7).Există abordări diferite pentru a evalua acurateţea înecocardiografie: re-raportarea întâmplătoare a examinărilor;compararea rezultatelor eco cu cele obţinuteprin alte modalităţi imagistice; analiza bazelor de datecomputerizate; 35 revizuirea unui set etalon de cazuri decătre fiecare dintre cei care interpretează în cadrul laboratorului.36Reproductibilitatea ar trebui să fie evaluată prin măsurareavariabilităţii intra şi inter-examinator a celormai importanţi parametri (ex.fracţia de ejecţie sau volumeleventriculului stâng, gradienţii transaortici, ariilevalvulare).Laboratoarele pot alege să dezvolte un set etalon decazuri conţinând cele mai frecvente diagnostice pentrua calibra interpretările şi a reduce variabilitatea interexaminator.Pe scurt, este important să se desfăşoare verificări periodicede rutină a preciziei şi reproductibilităţii pentrua confirma că sunt îndeplinite standardele convenabilepentru ambele aspecte.RaportareaUn rezultat ecocardiografic de înaltă calitate ar trebuisă fie precis, complet şi să răspundă fără ambiguitateîntrebărilor clinice care au dus la solicitarea examinării.De asemenea, ar trebui să fie uşor de înţeles decătre medicul care a făcut solicitarea. Setul minim deparametri care ar trebui să fie conţinuţi într-un rezultatecocardiografic a fost publicat de către AEE. 10 Înplus, AEE a publicat măsurile şi parametrii de descrieremorfologică a structurilor cardiovasculare care ar trebuifolosite pentru a dezvolta baze de date structuratede raportare. Odată ce astfel de baze de date sunt implementate,monitorizarea calităţii raportării poate fiefectuată cu uşurinţă prin măsurarea procentului dere zultate ce conţin parametri esenţiali pentru o condiţieclinică dată.Nu în ultimul rând, rezultatele ar trebui trimise latimp medicilor solicitanţi. Rezultatele examinărilorde rutină ar trebui, de obicei, să fie emise în ziua cândacestea au fost efectuate. Pentru examinările urgenteEAE Recommendationssau ale pacienţilor spitalizaţi, ar trebui emis imediat celpuţin un rezultat preliminar şi ar trebui generate standardelegate de limitele de timp pentru situaţii cliniceparticulare (ex. constatarea de elemente cu risc înalt artrebui prompt comunicată medicului solicitant).Implementarea recomandărilor pentruîmbunătăţirea calităţiiEsenţa îmbunătăţirii calităţii unui laborator de ecocardiografieeste aceea ca toţi profesioniştii implicaţi înrealizarea unei examinări ecocardiografice (cardiologi,ecocardiografişti, asistente, personal administrativ,mana geri şi alţi profesionişti din domeniul calităţii) sălucreze ca o echipă. Scopul unei astfel de echipe esteacela de a identifica şi analiza probleme folosind măsuriobiective de performanţă a calităţii (Tabelul 7), dea genera soluţii posibile şi de a implementa modificări.Este inutil ca doar conducătorul laboratorului de ecocardiografiesă fie implicat în procesul de îmbunătăţirea calităţii.Una dintre dificultăţile principale în iniţierea unuiprogram de îmbunătăţire a calităţii este preocupareapentru rezolvarea erorilor umane detectate pe parcursulevaluării calităţii. Ar trebui subliniat că scopul oricăruiprogram de îmbunătăţire a calităţii nu este acelade a găsi erori, ci, mai curând, de a identifica dimensiunileîngrijirii care necesită îmbunătăţire. Accentultre buie întotdeauna pus pe pacient şi pe ecocardiografie,şi nu pe identificarea erorilor profesionale. Totuşi,pen tru a creşte aderenţa la program, este obligatoriusă se genereze mecanisme care să permită corectareaero ril or, fără expunerea la răspundere a profesioniştilorpar ti cipanţi.Alt obstacol important care trebuie depăşit la iniţiereaunui program de îmbunătăţire a calităţii este reprezentatde disponibilitatea măsurilor adecvate. Elaborareadiferitelor măsuri necesare pentru a monitorizaprocesul impune expertiză, timp şi resurse financiare şinu poate fi făcută fără o bază de date adecvată care săîncorporeze parametri de măsurare a calităţii (ex. ordonareaadecvată a informaţiilor, clasa de prioritate clinică,tipul de aparat folosit, raportarea standardizată).Punerea la punct a unui astfel de sistem de informareeste costisitor. Analiza externă, în special dacă este implicatun laborator cheie sau o comisie de experţi, arputea creşte costurile chiar şi mai mult.De aceea, este obligatoriu ca fiecare program de îmbunătăţirea calităţii să împărtăşească importanţa unuiastfel de proces cu directorii spitalelor locale care trebuiesă fie de acord să investească în proceduri care auca ţintă îmbunătăţirea îngrijirii pacientului.

EAE RecommendationsRomanian Journal of CardiologyVol. 22, No. 2, 2012Tabelul 7. Puncte de acţiune şi măsuri ale asigurării calităţii în cadrul schemei “dimensiuni ale îngrijirii” pentru ecocardiografieEtapă Scopurile asigurării calităţii Puncte de acţiune Măsuri ale asigurării calităţiiInfrastructura laboratoruluiAsigurarea standardelor de bazăpentru competenţa echipamentelorşi a personalului• Aplicarea pentru acreditarea standard a laboratorului• Certificarea AEE/naţională pentru ecocardiografişti şi medici• Stabilirea ca obiectiv a acreditării avansate pentru ecografia de stres şiETE 11• Monitorizarea numărului de examinări efectuate/raportate de către fiecareecocardiografist/medicSelecţia pacienţilor Adecvare • Introducerea de criterii de adecvare pentru ETT, ETE şi ecocardiografia destres• Proiectarea de formulare specifice de solicitare a examinării menitesă ajute medicii care trimit pacienţii către ecocardiografie să selectezeindicaţiile potrivite.• Monitorizarea examinărilor ecocardiografice pe baza cazuisticiiEfectuarea examinăriiInterpretareaexaminăriiExaminări diagnostice de calitateSiguranţa pacientuluiAcurateţeReproductibilitate• Adoptarea recomandărilor AEE pentru standardizarea efectuării, înmagazinareadigitală şi raportarea examinărilor ecocardiografice 10• Adoptarea recomandărilor AEE pentru ecocardiografia de stres 17• Adoptarea recomandărilor AEE pentru ETE 14• Asigurarea duratei de timp adecvate pentru fiecare modalitate eco 11• Dezvoltarea de protocoale specifice pentru utilizarea contrastului- Monitorizarea listei de aşteptare a pacienţilor internaţi şi din ambulator- Proiectarea unui program specific de examinare în conformitate cuprioritatea clinică- Monitorizarea complicaţiilor majore ale ecocardiografiei de stres (deces,IMA, aritmii majore) şi ale ETE.• Adoptarea standardelor existente pentru măsurarea şi interpretareaexaminărilor eco 10,37• Compararea rezultatelor cu cele ale altor tehnici imagistice sau cu descopeririintraoperatorii• Adoptarea arhivării digitale a datelor şi imaginilor 10- dezvoltarea de proceduri pentru determinarea variabilităţii intra şi interexaminator a medicilor raportanţiRaportarea Caracterul complet • Dezvoltarea de programe computerizate în vederea raportării structuratepentru toate modalităţile eco 10• Adoptarea de seturi minime de date pentru raportarea comprehensivă aexaminărilor eco 10Îmbunătăţireaîngrijirii pacientului(rezultate)• Procentul de examinări eco efectuate de către ecocardiografiştiacreditaţi• Procentul de examinări eco efectuate/raportate de către mediciacreditaţi• Credite EMC pentru ecocardiografişti şi clinicieni• Procentul de examinări care îndeplinesc criteriile de adecvare• Procentul de examinări ale pacienţilor internaţi şi din ambulatorraportate ca normale• Numărul de examinări revizuite lunar – ca fiind sau nu complete– de către conducătorul tehnic şi/sau clinic al laboratorului• Procentul de studii complete în conformitate cu recomandărileAEE 10• Procentul de examinări neinterpretabile• Numărul de examinări efectuate/interpretate zilnic de cătrefiecare ecocardiografist/medic• Procentul de examinări efectuate utilizând contrast- Procentul de pacienţi examinaţi într-un interval de timppredefinit pentru fiecare prioritate clinică- Procentul de pacienţi având consimţământ informat semnatanterior ETE sau ecocardiografiei de stres- Procentul de intubări nereuşite la pacienţii la care s-aîncercat efectuarea ETE• Procentul de pacienţi cu indicaţie clinică explicită pentru eco• Procentul de pacienţi cu eco de stres anormal şi artere coronarenormale la coronarografie• Erori şi limite ale concordanţei volumelor VS vs. RM cardiacsau medicină nucleară• Erori şi limite ale concordanţei gradienţilor transaortici cumăsurătorile efectuate prin cateterism cardiac• Numărul de studii revizuite lunar ca interpretare de cătreconducătorul clinic al laboratorului• Reproductibilitatea intra şi inter examinator a FEVS• Reproductibilitatea intra şi inter examinator a ariei funcţionaleaortice/protetice• Procentul de raportări care îndeplinesc cerinţele setului minimde date necesar pentru raportare 10• Procentul de raportări în cazul cărora s-a stabilit clar indicaţiaclinică pentru efectuarea examinării• Procentul de raportări la care s-a efectuat o comparaţie cuexaminările anterioare (dacă sunt disponibile)Limitări legate de timp- definirea de proceduri care să ofere raportarea în timp util a rezultatelorexaminărilor către medicii solicitanţiGradul de satisfacţie • Proiectarea de mijloace de evaluare a satisfacţiei clientului • Procentul de pacienţi/medici solicitanţi care au raportat un scorde satisfacţie peste o valoare predeterminatăImpactul asupra managementuluiclinic- Proiectarea de metode pentru evaluarea rezultatelor pacientului şiimpactul asupra luării de decizii- Procentul de pacienţi trimişi către scintigramă miocardicădupă un test eco de stres franc pozitiv sau negativ efectuatpentru boala coronariană ischemică

Romanian Journal of CardiologyVol. 22, No. 2, 2012O posibilă abordare este descrisă în detaliu în celece urmează:• După obţinerea de resurse adecvate pentru a derulaun program de îmbunătăţire a calităţii, sevor împărţi toţi cei care lucrează în laboratorulde ecocardiografie în grupuri de lucru pentruanaliza componentelor specifice ale schemei descriseîn Figura 1.• Se va începe prin analizarea parametrilor simpli(ex. numărul de cazuri, calificarea cardiologuluişi a ecocardiografistului) şi analiza diferitelor recomandări publicate în acest document.• În continuare, grupurile de lucru ar trebui organizatepentru a evalua diferitele componentedes crise în schemă. Pe parcursul acestei etape,me todele şi măsurile de calitate ar trebui testatepentru a monitoriza zone diferite din cadrul fiecăreidimensiuni iar problemele specifice ar trebuiidentificate.• În continuarea acestui proces, se vor propuneşi testa soluţii pentru diverse probleme şi se vorim plementa acelea care s-au dovedit eficientede-a lungul timpului.Deoarece tehnologia folosită în ecocardiografie evoluează,iar scopul aplicaţiilor se modifică şi creşte, recomandărileincluse în acest document vor necesita revizuireşi actualizare în continuare.Bibliografie1. Cheitlin MD, Armstrong WF, Aurigemma GP, Beller GA, BiermanFZ, Davis JL et al. ACC/AHA/ASE 2003 guideline update for the clinicalapplication of echocardiography: summary article: a report of theAmerican College of Cardiology/American Heart Association TaskForce on Practice Guidelines (ACC/AHA/ASE Committee to Updatethe 1997 Guidelines for the Clinical Application of Echocardiography).J Am Soc Echocardiogr 2003; 16:1091–110.2. Flachskampf FA, Voigt JU, Daniel WG. Cardiac ultrasound. In: CammJA, Lüscher TF, Serruys PW, editors. The ESC Textbook of CardiovascularMedicine. Second edition. Oxford University Press, 2009.3. British Society of Echocardiography Guidelines. Training in echocardiography.Br Heart J 1994;71(suppl):2-5.4. Roudaut R, Touche T, Cohen A, Cormier B, Dehant P, Diebold B etal. Guidelines of the French Society of Cardiology on the training ofechocardiographers and the performing of echocardiography. ArchMal Coeur Vaiss 1994; 87:791-8.5. Decoodt P, Gillebert TC. European certification of clinical competencein adult echocardiography issued in Belgium. The Steering Committ ee of the Belgian Working Group on Echocardiography and CardiacDoppler. Acta Cardiol 1995; 50:265-71.6. Quiñones MA, Douglas PS, Foster E, Gorcsan J 3rd, Lewis JF, PearlmanAS et al. ACC/AHA clinical competence statement on echocardiography:a report of the American College of Cardiology/AmericanHeart Association/American College of Physicians-American Societyof Internal Medicine Task Force on Clinical Competence. J Am CollCardiol 2003; 41:687-708.7. Ryan T, Armstrong WF, Khandheria BK. ACCF COCATS 3 Trainingstatement: Task Force 4: Training in echocardiography. J Am Coll Cardiol2008; 51;361-7.8. The European Society of Cardiology Core Curriculum for the generalcardiologist. http://www.escardio.org/education/coresyllabus/Pages/core-curriculum.aspxEAE Recommendations9. The European Association of Echocardiography Core Syllabus. http://www.escardio.org/communities/EAE/education/Pages/core-syllabus.aspx10. Evangelista A, Flachskampf F, Lancellotti P, Badano L, Aguilar R,Monaghan M et al. European Association of Echocardiography recommendationsfor standardization of performance, digital storageand reporting of echocardiographic studies. Eur J Echocardiogr 2008;9:438–48.11. Nihoyannopoulos P, Fox K, Fraser A, Pinto F. EAE laboratory standardsand accreditation. Eur J Echocardiogr 2007; 8:80–7.12. Fraser AG, Buser PT, Bax JJ, Dassen WR, Nihoyannopoulos P,Schwitter J et al. The future of cardiovascular imaging and non-invasivediagnosis. A joint statement from the European Association ofEchocardiography, the Working Groups on Cardiovascular MagneticResonance, Computers in Cardiology, and Nuclear Cardiology, of theEuropean Society of Cardiology, the European Association of NuclearMedicine, and the Association for European Paediatric Cardiology.Eur J Echocardiogr 2006; 7:268-73.13. Douglas PS, Khandheria B, Stainback RF, Weissman NJ, Brindis RG,Patel MR et al. ACCF/ASE/ACEP/ASNC/SCAI/SCCT/SCMR 2007appropriateness criteria for transthoracic and transesophageal echocardiography: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness CriteriaWorking Group, American Society of Echocardiography, AmericanCollege of Emergency Physicians, American Society of Nu clear Cardiology, Society for Cardiovascular Angiography and In ter -ve n tions, Society of Cardiovascular Computed Tomography, andthe So ciety for Cardiovascular Magnetic Resonance endorsed by theAme ri can College of Chest Physicians and the Society of Critical CareMe dicine. J Am Coll Cardiol 2007; 50:187-204.14. Flachskampf FA, Decoodt P, Fraser AG, Daniel WG, Roelandt JR;Subgroup on Transesophageal Echo cardiography and Valvular HeartDisease; Working Group on Echocardiography of the European Societyof Cardiology. Guidelines from the Working Group. Recommendationsfor performing transesophageal echocardiography. Eur JEchocardiogr 2001;2:8-21.15. Shanewise JS, Cheung AT, Aronson S, Stewart WJ, Weiss RL, MarkJB et al. ASE/SCA guidelines for performing a comprehensive intraoperativemultiplane transesophageal echocardiography examination:recommendations of the American Society of EchocardiographyCouncil for Intraoperative Echocardiography and the Society of CardiovascularAnesthesiologists Task Force for Certification in PerioperativeTransesophageal Echocardiography. J Am Soc Echocardiogr1999;12:884-900.16. Practice guidelines for perioperative transesophageal echocardiography:a report by the American Society of Anesthesiologists and theSociety of Cardiovascular Anesthesiologists Task Force on TransesophagealEchocardiography. Anesthesiology 1996; 84:986–1006.17. Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P,Poldermans D et al. Stress echocardiography expert consensus statement:European Association of Echocardiography (EAE)(a registeredbranch of the ESC). Eur J Echocardiogr 2008; 9:415-37.18. Picano E, Lattanzi F, Orlandini A, Marini C, L’Abbate A. Stress echocardiographyand the human factor: the importance of being expert. JAm Coll Cardiol 1991;24:928–33.19. Varga A, Picano E, Dodi C, Barbieri A, Pratali L, Gaddi O. Madnessand method in stress echo reading. Eur Heart J 1999;20:1271–5.20. Ali SM, Egeblad H, Saunamnaki K, Carstensen S, Steenscard-HansenF, Hausno S. Reproducibility of digital exercise echocardiography. EurHeart J 1995; 16:1510–9.21. Franke A, Hoffmann R, Kuhl HP, Lepper W, Breithardt OA, SchormannM et al. Non-contrast second harmonic imaging improvesinter observer agreement and accuracy of dobutamine stress echocardio graphy in patients with impaired image quality. Heart 2000;83:133–40.22. Zamorano J, Sánchez V, Moreno R, Almería C, Rodrigo J, Serra V etal. Contrast agents provide a faster learning curve in dipyridamolestress echocardiography. Int J Cardiovasc Imaging 2002; 18:415–9.23. Senior R, Becher H, Monaghan M, Agati L, Zamorano J, VanoverscheldeJL et al. Contrast echocardiography: evidence-based recommen-

EAE RecommendationsRomanian Journal of CardiologyVol. 22, No. 2, 2012dations by European Association of Echocardiography. Eur J Echo -cardiogr 2009; 10:194-212.24. Imran MB, Palinkas A, Pasanisi EM, De Nes M, Picano E. Optimal readingcriteria in stress echocardiography. Am J Cardiol 2002;90:444–5.25. Becher H, Chambers J, Fox K, Jones R, Leech GJ, Masani N et al. BSEprocedure guidelines for the clinical application of stress echocardiography,recommendations for performance and interpretation ofstress echocardiography: A report of the British Society of EchocardiographyPolicy Committee. Heart 2004; 90;23-30.26. Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG. AmericanSociety of Echocardiography Recommendations for Performance,Interpretation, and Application of Stress Echocardiography. J AmSoc Echocardiogr 2007; 20:1021-1041.27. Deanfield J, Thaulow E, Warnes C, Webb G, Kolbel F, Hoffman A etal. Management of grown up congenital heart disease. The Task Forceon the Management of Grown Up Congenital Heart Disease of theEuropean Society of Cardiology. Eur Heart J 2003; 24:1035-84.28. http://www.intersocietal.org/icael/apply/standards.htm (accessed 05/09/2009)29. Lopez-Sendon J, Mills P, Weber H, Michels R, Di Mario C, FilippatosGS et al. Recommendations on sub-speciality accreditation in cardiology:The Coordination Task Force on Sub-speciality Accreditation ofthe European Board for the Speciality of Cardiology. Eur Heart J 2007;28:2163-71.30. Fox KF, Flachskampf F, Zamorano JL, Badano L, Fraser AG, Pinto FJ.Report on the first written exam held as part of the European Associationof Echocardiography Accreditation Process in Adult TransthoracicEchocardiography. Eur J Echocardiogr 2004; 5:320-5.31. Fox KF, Popescu BA, Janiszewski S, Nihoyannopoulos P, Fraser AG,Pinto FJ. Report on the European Association of EchocardiographyAccreditations in Echocardiography: December 2003 to September2006. Eur J Echocardiogr 2007; 8:74-9.32. http://www.escardio.org/communities/EAE/accreditation/Pages/welcome.aspx33. Recommendations for continuous quality improvement in echocardiography.American Society of Echocardiography. J Am Soc Echocardiogr1995; 8:S1-S28.34. Douglas P, Iskandrian AE, Krumholz HM, Gillam L, Hendel R, JollisJ et al. Achieving quality in cardiovascular imaging: proceedings fromthe American College of Cardiology-Duke University Medical CenterThink-Tank on quality in cardiovascular imaging. J Am Coll Cardiol2006; 48:2141-51.35. Berger AK, Gottdiener JS, Yohe MA, Guerrero JL. Epidemiologicalapproach to quality assessment in echocardiographic diagnosis. J AmColl Cardiol 1999; 34:1831-6.36. Fox KF, Porter A, Unsworth B, Collier T, Leech G, Mayet J. Report ona national echocardiography quality control exercise. Eur J Echocardiogr2009; 10:614-18.37. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, PellikkaPA et al. Recommendations for chamber quantification. Eur J Echocar -diogr 2006; 7:79-108.

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012AGENDAMANIFESTĂRILOR CARDIOLOGICE INTERNE ŞI INTERNAŢIONALE - 2012Luna DENUMIRE CURS DATA LOCAŢIAIunieIunie6 th Congress of Asian Society of Cardiovascular Imaging 7-9 iunie 2012Cazuri clinice complexe în cardiopatia ischemicăDirectori de curs: Prof. Dr. Doina Dimulescu, Conf. Dr. Ş. BălănescuImagistica bolilor valvulareDirectori de curs: Conf. Dr. Adriana Ilieşiu, Dr. B. A. PopescuEHRA certification exam in Certification in Cardiac Pacing andImplantable Cardioverter Defibrillators (ICDs)EHRA Certification exam in Invasive Cardiac ElectrophysiologyCertificationBangkok,Thailand8 iunie 2012 Bucureşti8 iunie 2012 Bucureşti13 iunie 2012 Nice, France14 iunie 2012 Nice, FranceEHRA certification exam for allied professionals 14 iunie 2012 Nice, FranceIulieExpert Meeting CARDIODIABCoordonatori: Prof. Dr. D. Vinereanu, Prof. Dr. D. Gaiţă23 rd annual meeting of the American Society of Echocardiography (ASE)August ESC Congress 2012SeptembrieOctombrieActualităţi în aritmologie (ARCA 3)Directori de curs: Dr. R. Vătăşescu, Prof. Dr. D. Dobreanu,Prof. Dr. G. A. Dan36 th Meeting of the European Working Group on Cardiac CellularElectrophysiologyZiua Mondială a InimiiMagnetic Resonance in CardiologyCONGRESUL NAŢIONAL DE CARDIOLOGIEXIII National Congress of Cardiology of the Bulgarian Society ofCardiologyREDRISC (REDucerea RISCului Rezidual)Directori de curs: Prof. Dr. Cătălina Arsenescu Georgescu,Prof. Dr. G. A. Dan, Prof. Dr. D.VinereanuParticularităţi ale bolilor cardiovasculare la vârstnic (CARDIOSEN)Directori de curs: Conf. Dr. F. Mitu, Dr. D. GherasimAcute Cardiac Care 2012Cazuri clinice dificile în cardiologia de urgenţăDirector de curs: Conf. Dr.C. Pop, Dr. G. Tatu-Chiţoiu, Dr. A. PetrişLipid School – Ghidul dislipidemii 2011 (LIPS)Directori de curs: Prof. Dr. D. Gaiţă, Prof. Dr. D.Vinereanu28-30 iunie201230 iunie -3 iulie201225-29 august20127 septembrie201215-16septembrie201229 octombrie20124-6 octombrie20124-6 octombrie20124-7 octombrie201213 octombrie201219 octombrie201220-22octombrie 201226 octombrie201226 octombrie2012SinaiaNationalHarbor,Maryland, USAMunich,GermanyConstanţaNantes, FranceBucureştiRiva DelGarda, ItalySinaia,RomâniaSofia, BulgariaBucureştiClujIstanbul,TurkeyBaia MareTimişoara

AgendaRomanian Journal of CardiologyVol. 22, No. 2, 2012NoiembrieDecembrieAmerican Heart Associatioan Annual Scientific SessionsCazuri clinice complexe în cardiopatia ischemicăDirectori de curs: Prof. Dr. Doina Dimulescu, Conf.Dr.S. BalanescuSoluţii terapeutice în infarctul miocardic acut de la teorie la practică -cazuri clinice în directDirectori de curs: D. Deleanu, A. Iancu, M. CroitoruCazuri clinice în Insuficienţa CardiacăDirectori de curs: Prof. Dr. Cezar Macarie, Prof. Dr. D. Vinereanu,Prof.Dr. O. ChioncelICI Meeting 2012EURECHO 20123-7 noiembrie201216 noiembrie201217 noiembrie201224 noiembrie20112-4 decembrie20125-8 decembrie2012Los Angeles,USAContanţaClujTimişoaraTel Aviv, IsraelAthens, Greece

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012SOCIETATEA ROMÂNĂ DE CARDIOLOGIEREVISTA ROMÂNĂ DE CARDIOLOGIEANUNŢÎncepând cu anul 2012, numărul 1, Revista Română de Cardiologiedorește să publice articole în limba engleză. Această decizie a fost luatăpentru a crește vizibilitatea Revistei în cercetarea ştiinţifică internaţională șipentru a facilita includerea în baze internaţionale.Articolele pot fi trimise în limba engleză sau în limba română.În cazul trimiterii articolelor în limba română, editura asigură traducerea(contra cost/pagină) ce va fi suportată de către autor.Romanian Journal of CardiologyContinuă acordarea de premii pentru lucrări originale(prim autori sub 40 ani)

Romanian Journal of Cardiology | Vol. 22, No. 2, 2012INSTRUCŢIUNI PENTRU AUTORIInformaţii generaleRevista Română de Cardiologie publică articole originale din domeniul fiziologiei și patologiei cardiovasculare sub forma studiilor clinice,de laborator, experimentale, epidemiologice etc. Autorii vor respecta principiile eticii și adevărului știinţific în realizarea studiului, obţinereadatelor și prezentarea rezultatelor.Pentru publicare, articolele vor fi trimise într-un exemplar, împreună cu toate fișierele pentru text (în format MS Word) și imaginile peCD. Formatul manuscrisului este de tip A4 (21 × 29,7 cm), scris la două rânduri, cu caractere Times New Roman 12, cu diacritice pentrulimba română.Fiecare manuscris trebuie să fi e însoţit de o scrisoare de intenţie a autorilor, semnată în original, care să afirme că articolul nu a maifost trimis simultan niciunei alte publicaţii și nu a mai fost publicat în altă revistă într-o formă substanţial similară. Responsabilitatea asupraconţinutului articolului aparţine în întregime autorilor.Textele trimise pentru a fi publicate vor fi referate fără cunoașterea autorilor, de către 2 referenţi. Refuzul publicării unui articol va fimotivat și comunicat în scris autorilor. Manuscrisele nepublicate nu se returnează autorilor.Articolele trimise vor fi semnate de toţi autorii. Autorii vor semna o declaraţie privind existenţa conflictelor de interese. Primul autor areobligaţia de a colecta declaraţiile privind conflictele de interese de la toți co-autorii.Pregătirea manuscrisuluiTitlu: Pe pagina de titlu se va scrie titlul articolului, numele complet al autorilor, gradul academic, afilierea acestora, adresa de corespondenţă,precum și un titlu scurt (între 3-6 cuvinte) pentru paginile următoare ale articolului, și cuvintele cheie (max. 6) ale articolului.Numărul autorilor se va limita la 10. Totodată vor fi precizate sursele de finanţare ale lucrării (acolo unde este cazul).Rezumatul: Rezumatul, în limba română și engleză, va cuprinde cel mult 200 de cuvinte. Va fi alcătuit din obiectivele studiului, metodologiafolosită, principalele rezultate și concluziile studiului. Nu se vor folosi în rezumat tabele sau prescurtări.Textul manuscrisului: Textul manuscrisului nu va depăși 12 pagini pentru studiile originale sau referatele generale și 5 pagini pentrupre zentările de caz, fiind necesară numerotarea acestora. Prescurtările vor fi definite la prima lor folosire. Pentru denumirile medicamente lorsau ale altor substanţe folosite în studiile prezentate vor fi utilizate denumirile comune internaţionale. Aparatele utilizate în studii vor fi prezentate cu denumirea comercială, cu indicarea producătorului. Eventualele mulţumiri pentru colaborare vor fi inserate la sfârșitul textului.Bibliografia: Bibliografia se va dactilografia pe coli separate și se va nota cu cifre arabe în ordinea crescătoare a apariţiei în text, unde vorfi notate superscript. Referinţele bibliografice vor cuprinde numele autorilor (până la 5 autori vor fi precizaţi toţi autorii, dacă sunt mai mulţide 5 autori se vor preciza doar primii trei autori urmaţi de locuţiunea și col.), titlul complet al articolului, revista, anul apariţiei, volumul,paginile. Prescurtarea numelui revistei se va face după cea folosită în Index Medicus.Recomandăm introducerea referinţelor bibliografice actuale. De asemenea, se recomandă citarea referinţelor bibliografice româneşti,iar în cazul în care autorii au mai publicat în Revista Română de Cardiologie, citarea acestor publicaţii.Ex: Ridker PM, Rifai N, Pfeffer M et al. Elevation of TNF-a and increased risk of recurrent coronary events aft er myocardial infarction. Circulation,2000; 101: 2149-53 [pentru articole din reviste] Madahi J. Myocardial perfusion imaging for the detection and evaluation of coronary artery disease.InCardiac Imaging: A Companion to Braunwald’s Heart Disease, Second edition. Eds: DJ Skorton, HR Schelbert, GL Wolf et al. WB Saunders,London, 1996, 193-203 [capitole în cărţi]Figurile: Calitatea figurilor trebuie să fie excelentă pentru a permite reproducerea corectă. Ele nu vor fi inserate în interiorul textuluimanuscrisului ci vor fi prezentate pe coli separate, și vor fi trimise în format alb-negru, iar în format electronic vor fi trimise separat cafișiere imagine (JPG, TIFF etc.). Fiecare figură va fi însoţită de o legendă, în care vor fi explicate, în mod concis, principalele date referitoarela respectiva figură. Pentru identificare, figurile vor fi numerotate cu cifre arabe în ordinea apariţiei lor în text. În text va fi precizat întreparanteze rotunde numărul figurii la care se face referire (Ex: Figura 3). Dacă este cazul, în paranteză va fi precizată sursa bibliografică afigurii, și, în acest caz, utilizarea figurii trebuie făcută cu avizul autorilor articolului princeps. Prezentarea sursei bibliografice va fi urmatăde cifra corespunzătoare din bibliografie.Tabelele: Tabelele vor fi numerotate cu cifre arabe în ordinea apariţiei în text și vor fi însoţite de titlul concis al tabelului și eventualeleexplicaţii. Vor fi precizate prescurtările utilizate în tabel. Dacă este cazul, în paranteză va fi precizată sursa bibliografică a tabelului.Manuscrisele și suportul lor electronic (CD) vor fi trimise prin poștă sau e-mail la următoarea adresă:Societatea Română de Cardiologie; În atenţia d-lui redactor-șef al Revistei Române de Cardiologie Prof. Dr. Eduard ApetreiInstitutul de Boli Cardiovasculare „Prof. Dr. C. C. Iliescu“, Șos. Fundeni nr. 258; 022328 București, România; Tel./Fax: +40-21-318.35.92E-mail: eapetrei@gmail.com sau mihaela_salagean@yahoo.com.www.mediamed.roPublishing House: Media Med PublicisAdvertising: office@mediamed.roDistribution: The Romanian Journal of Cardiology is distributedto the members of the Romanian Society of CardiologySubscription: office@mediamed.ro