Attilio Maseri, MD, FRCP, FACC - Anmco

European PerspectivesCirculation 2009;119;f1-f6DOI: 10.1161/CIRCULATIONAHA.108.191735Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514Copyright © 2009 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online ISSN:1524-4539The online version of this article, along with updated information and services, is locatedon the World Wide Web at:http://circ.ahajournals.orgSubscriptions: Information about subscribing to Circulation is online athttp://circ.ahajournals.org/subscriptions/Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of WoltersKluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Fax:410-528-8550. E-mail:journalpermissions@lww.comReprints: Information about reprints can be found online athttp://www.lww.com/reprintsDownloaded from circ.ahajournals.org by on January 12, 2009

f4Circulation January 6/13, 2009Circulation: European PerspectivesOutside his work in cardiology, Professor Maseri indulges a passionfor sport. One often finds him on the tennis court (in London,he took the game so seriously that he ruptured an Achilles tendon)or skiing or snowboarding (as shown here) in the Swiss–ItalianAlps near Zermatt, Switzerland. Also a keen sailor, he used to owna 64-ft yacht, but the maintenance and management became tootime-consuming. ow, he satisfies his urge to be on the water bytaking out his 16-ft catamaran or by hanging off a windsurfingboard. Photograph courtesy of Professor Maseri.Institutes of Health research fellowship at Johns HopkinsUniversity, Baltimore, Md, where he worked underKenneth Zierler, MD, and others, learning how to useradioisotopes to probe the physiology and pathophysiologyof the cardiovascular system.“Gamma Cameras Became Available and Enabled Usto Carry Out the First Measurements of RegionalBlood Flow in the World”In 1967, Maseri returned to Pisa, then a major centre inEurope for nuclear medicine, which would play a key role inmuch of his future work. Although at first it seemed as if anabsence of 2 years away had scuppered Maseri’s chances of agood job, he went on to set up the Coronary Research Group.Professor Maseri recalls, “When I came back from theUnited States, others had taken over what I had started inthe department, so my boss, Professor Donato, suggested Iset up a coronary care unit and catheter lab, which I did. Iwent to Goteborg, Sweden, to learn angiographic techniques.I wanted to find out what caused symptoms in people withcoronary disease, to understand what was wrong and tomake them feel better. I realised that measuring total oraverage coronary flow was no good and that what weneeded to do was to measure regional blood flow. Nuclearmedicine was the most important innovative tool at thetime, and Pisa was a strong centre for it in Europe. It wasnot a ‘technique in search of a question’—I had the questions,and I borrowed the technique! Gamma camerasbecame available and enabled us to carry out the firstmeasurements of regional blood flow in the world, usingxenon washout techniques during pacing-induced angina.In 1971, we held an international meeting on coronaryflood flow, which gathered all the world experts in the theoryand practice of coronary flow measurements in order tofocus on crucial issues.”“They Didn’t Believe Me [About Spasm]!”Professor Maseri feels passionate about the need to constantlyquestion the “established paradigm.” He cites as anexample his work in Pisa in the early 1970s, when mostothers viewed coronary artery spasm as an artefact inducedby coronary catheterisation. He and his coworkers, in astudy of patients with angina at rest (variant or Prinzmetalangina), showed that during episodes of rest pain, they alsocould detect areas of massive ischaemia, from the initialdistribution of thallium 201, in the absence of catheterisation.He recalls how in 1974 he showed the first 3 cases ina packed lecture hall at the World Congress of Cardiologyheld in Buenos Aires, Argentina. The audience seemedsceptical, and when he got back to Pisa, he said to his wife,“They didn’t believe me!”But, within a few years, as a result of a series of articlesby the Pisa Group, 1–4 the medical community had changedits opinion. An editorial published in 1979 in the BritishMedical Journal 5 acknowledged the work of ProfessorMaseri and his group and concluded that “the weight ofprobability in favour of spasm occurring without catheterisationis now so great that the hypothesis must be taken asproved ... [the Pisa group’s] conclusion seems irrefutable:in some patients spasm may precipitate infarction.”Professor Maseri says, “We had proved convincinglythat spasm is important, but only in a selected group ofpatients. We then showed that nitrates, and later calciumantagonists, dilated the vessels and prevented spasm in thisgroup, but then they were prescribed for all cases. It’s anabuse of the idea! Like our later work on the role ofinflammation in patients threatened with infarction—thatidea has also been abused, and now you find “inflammation”everywhere in cardiovascular research.“We have not yet shown what causes spasm, why arteriesrespond excessively to constrictor stimuli. In the 1990s,we worked with Professor Sasaiama’s group in Japan, andwe have just begun working with Professor Shimokawa’sgroup in Japan, on the molecular mechanisms of spasm,which is common in that country.”The ew England Journal of Medicine First Rejectedan Article Proving That “Intracoronary Injection ofThis Drug [Streptokinase] Could Reopen the Arteryand Abort the Effects of the Infarction” and ThenAccepted the Article Without ChangesTwelve years after returning to Pisa from the United States,Professor Maseri left for London, where he became SirJohn McMichael Professor of Cardiology at the RoyalPostgraduate School of Medicine, universally know as the“Hammersmith” after its major affiliated hospital. There,funded by the UK Medical Research Council, he usedpositron emission tomography to develop techniques forstudying perfusion and metabolism in the myocardium.Emphasising the power of the well-designed, smallscaleclinical experiment to answer a specific question—and relatively quickly—Professor Maseri recalls, “When Iwas at the Hammersmith in the early days of thrombolysisDownloaded from circ.ahajournals.org by on January 12, 2009

Circulation January 6/13, 2009f5with streptokinase, it was not clear, ifyou injected the drug to dissolve thethrombi, whether the resultinginfarction was smaller than it wouldotherwise have been. So, we selectedpatients whose symptoms of theheart attack had started no more than2 hours before, so the myocardiumwas not yet dead, and we proved thatintracoronary injection of this drugcould reopen the artery and abort theeffects of the infarction. We sent apaper based on 9 cases to the ewEngland Journal of Medicine, anditwas rejected. I wrote back to the editor—theonly time I’ve ever done it—saying that the reviewers had notunderstood the importance of what wehad done and that he must be mad notto publish such an important finding!By return, it was accepted withoutchanges and published in 1984 in theMedical Intelligence section.”In London, Professor Maseri’s international reputationgrew as he continued to uncover many key features of IHD,including the role of distal coronary vessel constriction inchronic stable angina, 6 the mechanisms of ischaemic cardiacpain, 7 and the frequent absence of preexisting stenosesin the infarct-related coronary arteries. 8 He started courseson European and American cardiology at the Hammersmith,with a prestigious international faculty, that attracted asmany as 400 participants from all over the world—a uniqueforum for discussion!In 1991, Professor Maseri packed his bags again and leftthe British capital for Rome, Italy, where he became professorof cardiology at the Catholic University and directorof the Institute of Cardiology at the Agostino GemelliPolyclinic and continued to characterise the minutiae of IHD.With his group, he showed elevation of circulating inflammatorymarkers, in particular C-reactive protein, in unstablepatients evolving toward acute infarction 9 and the activationof leukocytes across the coronary bed in these patients. 10Professor Maseri has just changed jobs again, this timetaking on the presidency of the Italian Heart CareFoundation, based in Florence. Unlike many countries,which have single professional bodies for cardiology, Italyhas 2—one for those in academia and the other for hospitalcardiologists. Professor Maseri explains that in 1999 these2 bodies came together to publish the Italian Heart Journal,and he served as its first editor-in-chief, but they did notmanage to agree on a single foundation for increasing thestrength of Italian cardiology and raising research funds.The Heart Care Foundation began as an initiative by hospitalcardiologists. Professor Maseri says, “I decided I didn’twant to be a professor any more, and the idea of beingretired was scary, so I resigned in Milan [Italy] in Decemberlast year [2007], but then I was asked to stay on for a fewProfessor Attilio Maseri with his team in 1985, taken in the Stamp Lecture Theatre atHammersmith Hospital, London, United Kingdom, which was renowned as a site of heatedbrainstorming discussions. Photograph courtesy of Professor Maseri.months. The hospital cardiologists invited me to be thepresident of their foundation—I thought about it for a fewmonths, found the people involved were very nice humanbeings ... and I didn’t want to overstay my welcome inMilan, so I accepted the job. I had always been tremendouslyimpressed by the work of hospital cardiologists in theirGruppo Italiano per lo Studio della Streptochinasi nell’InfartoMiocardico studies, which have a unique potential—particularlyif the focus of observation could be moved fromthe most prevalent average patient behaviour and responseto that of the outliers on both sides of the mean—thosereally unusual cases which, in their network, could be foundin sufficient numbers. The information provided by thesecases, carefully characterised, regularly followed in databases,with biological material stored in biological banks,can provide useful fingerprints for the development of novelworking hypotheses and therapeutic targets.”Wrestling With Accepted ViewsProfessor Maseri’s IHD research has always challenged theaccepted model on the basis of compelling clinical observations.It brings to mind those grand master anatomistswho strutted the Paduan lecture theatres in the 16th century,though, paradoxically, Professor Maseri refuses to acceptinvitations to give “master lectures.” He prefers to reply toquestions from his audience, to engage in a conversation,rather like the students in Rembrandt’s Anatomy Lesson ofDr Nicolaes Tulp in the Mauritshuis Museum, The Hague,The Netherlands. He is always wrestling with a problem,such as the accepted view that plaque fissures in coronaryarteries lead to infarction. He rails, “My students often tellme this, but I forgive them; they have only read it in textbooks.In fact, fissures are common, but 25% of peoplewith atherosclerosis die of noncardiac causes, and 25% to45% of those who die after an infarction show no evidenceCirculation: European PerspectivesDownloaded from circ.ahajournals.org by on January 12, 2009

f6Circulation January 6/13, 2009Circulation: European Perspectivesof fissure. Yet cardiologists, with a reductionist approach,continue to say that plaque fissure causes infarction. Insome cases, this may be the case, but it appears too simplisticto be true!”“We eed a ‘Renaissance of Clinical Observation”Professor Maseri seems scathing about the obsession of thecontemporary medical community with the results of clinicaltrials, which he points out present “average” outcomes.He comments, “This is undoubtedly good but not goodenough! Research and prevention have been focused on thesame target for the past 25 years. Residual adverse eventson current optimal therapy are still too many, and theirreduction is reaching a plateau. Conversely, very many individualswith high levels of risk factors reach old age in goodhealth—maybe we should not try to explain these commondiscrepancies only with what we have learned so far!”Illustrating his point, Professor Maseri says, “Why wouldI ever want to wear the shoes of an average-sized Italian?Within each major cardiovascular syndrome, each subgroupof patients needs to be treated in the way that is appropriatefor the group’s individual causal mechanisms! Just likeanaemia! We need a ‘Renaissance of clinical observation.’ Ifyou follow the [treatment] guidelines in a group of patientswith coronary heart disease—reduce cholesterol, lowerblood pressure, reduce weight, control diabetes, etc.—youwill help some patients, but not others. Following guidelinesmakes it easy for cardiologists and protects them [from legalchallenge], while the very broad spectrum of patientsincluded in clinical trials is good for the industry. But thisapproach provides no incentive to search for the multiplecausal components of each cardiovascular syndrome in specificsubgroups of patients. You only learn by following upcases that do not fit the paradigm! In clinical research, lookingat “the average” does not help—looking at outliers is theway to try and understand something that is still unknown.”Professor Maseri has distilled the essence of his thinkingand research into his textbook, Ischemic Heart Disease, publishedby Churchill Livingstone in 1995. A reviewer in theew England Journal of Medicine [January 30, 1997] calledit “the most comprehensive book published on the subject.”In an age when few textbooks are written by single authors,he admits that Paul Wood’s Diseases of the Heart andCirculation may have provided the model that inspired him.It took 10 years to write, and now, after 13 years, it mightseem inevitably “out of date,” but he says he will not preparea new edition. He comments, “As the subtitle says, it is ‘Arational basis for clinical practice and clinical research.’ Notmuch is new since I wrote it, except for clinical trials.”During a long and distinguished research career,Professor Maseri has served a term as president [appointed2004] of the Italian Federation of Cardiology, during whichtime he attempted to bring together Italian cardiology. Hehas delivered many named lectures, received appointmentsto many visiting professorships, and collected a huge numberof prizes and awards, among which he particularly valueshis election as a Lifetime Member of the John HopkinsSociety of Scholars in 1980 and his receipt of the EuropeanSociety of Cardiology Gold Medal in 2002. He has served onthe editorial boards of many journals, and in 1999 he servedas founding editor-in-chief of the Italian Heart Journal.And his IHD research continues, as he pursues the biologicaltriggers of coronary instability and myocardialinfarction and mechanisms of repair. At the age of 73, onemight naturally think of retirement, but the thought makesProfessor Maseri uncomfortable. He says, “I’m often askedthis question. But if you don’t have a ‘carrot,’ what do youdo? I must always be working with somebody, or for somebody,and I must always be trying to solve some kind ofpuzzle. I received from cardiology much more than I couldever dream, and I wish to give back something of whatmade my fortune: cardiologists with inquisitive mindsshould take care of the patient, not [just] the disease; it iswhat patients expect, and it is rewarding personally. Theyshould listen to patients with unusual stories: they may betrying to reveal something still unknown!”References1. Maseri A, Parodi O, Severi S, Pesola A. Transient transmural reductionof myocardial blood flow demonstrated by thallium-201 scintigraphy,as a cause of variant angina. Circulation. 1976;54:280–288.2. Maseri A, Pesola A, Marzilli M, Severi S, Parodi O, L’Abbate A,Ballestra AM, Maltinti G, De Nes DM, Biagini A. Coronary vasospasmin angina pectoris. Lancet. 1977;1:713–717.3. Maseri A, Severi S, Nes MD, L’Abbate A, Chierchia S, Marzilli M,Ballestra AM, Parodi O, Biagini A, Distante A. “Variant” angina: oneaspect of a continuous spectrum of vasospastic myocardial ischemia.Pathogenetic mechanisms, estimated incidence and clinical and coronaryarteriographic findings in 138 patients. Am J Cardiol.1978;42:1019–1035.4. Maseri A, L’Abbate A, Baroldi G, Chierchia S, Marzilli M, Ballestra AM,Severi S, Parodi O, Biagini A, Distante A, Pesola A. Coronary vasospasmas a possible cause of myocardial infarction. A conclusion derived fromthe study of “preinfarction” angina. EnglJMed.1978;299:1271–1277.5. Coronary artery spasm. Br Med J. 1979;1:969–970.6. Pupita G, Maseri A, Kaski JC, Galassi AR, Gavrielides S, Davies G, CreaF. Myocardial ischemia caused by distal coronary-artery constriction instable angina pectoris. EnglJMed.1990;323:514–520.7. Crea F, Pupita G, Galassi AR, el Tamimi H, Kaski JC, Davies GJ, MaseriA. Effect of theophylline on exercise-induced myocardial ischaemia.Lancet. 1989;1:683–686.8. Hackett D, Davies G, Chierchia S, Maseri A. Intermittent coronary occlusionin acute myocardial infarction. Value of combined thrombolytic andvasodilator therapy. EnglJMed.1987;317:1055–1059.9. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, PepysMB, Maseri A. The prognostic value of C-reactive protein and serumamyloid a protein in severe unstable angina. Engl J Med.1994;331:417–424.10. Buffon A, Biasucci LM, Liuzzo G, D’Onofrio G, Crea F, Maseri A.Widespread coronary inflammation in unstable angina. Engl J Med.2002;347:5–12.Barry Shurlock is a freelance medical journalist.Editor: Helmut Drexler, MD, FESCManaging Editor: Lindy van den Berghe, BMedSci, BM, BSWe welcome comments. E-mail lindy@circulationjournal.orgThe opinions expressed in Circulation: EuropeanPerspectives in Cardiology are not necessarily thoseof the editors or of the American Heart Association.Downloaded from circ.ahajournals.org by on January 12, 2009