Left Ventricular Function in Mitral Stenosis*

Left Ventricular Function in Mitral Stenosis*Lau:rence D. Horwitz, M.D.;"' Charles B. Mullins, M.D.;?Robert M. Payne, M.D.;$ and George C. Curry, AI.D.1 IThe effects of isometric exercise on left ventricular performance were studiedduring cardiac catheterization in six patients with mitral stenosis and six patientswithout significant cardiac disease. Quantitative analyses of left ventricular cineangiogramswere completed to correlate changes with the findings during exercise.During exercise, left ventricular function curves were abnormal in five ofthe six patients with mitral stenosis. In addition, ejection fractions were sipificantlylower in the group with mitral stenosis as compared with the normalsubjects. The lower ejection fractions in the patients with mitral stenosis weredue to localized abnormalities in the posterobasal and anterior left ventricularwalk. It is concluded that left ventricular function is abnormal in mitral stenosisdue to localized wall motion abnormalities, which are probably due to fibrosisnear or in the papillary muscles.he poor exercise tolerance of patients with mitralTstenosis is a well known phenomenon. An inabilityto appropriately increase cardiac output in responseto exercise or other stress is the cause of theimpairment.' It has been generally assumed thatobstruction to left ventricular filling at the mitralvalve is the major factor limiting cardiac output.'However, several reportsz4 have suggested that leftventricular function is abnormal in mitral stenosisand that myocardial impairment may be an importantfactor in the limitation in cardiac reserve. Evidencethat poor cardiac performance may persistafter surgical correction of mitral stenosis5 supportsthis view.Since most forms of exercise are associated withsubstantial tachycardia, and the resultant decrease'From the Pauline and Adolph Weinberger Laboratory forCardiopulmonary Research, Department of Internal Medicine,University of Texas southwestern Medical School atDallas, Dallas, Texas."Assistant Professor of Internal Medicine.+Associate Professor of Internal Medicine and TeachingScholar of the American Heart Association.$Formerly NHLI Research Fellow supported by traininggrant HL 05812.I IAssistant Professor of Radiology.This study was supported in part by grant HL 06296 fromthe National Heart and Lung Institute and by a rant fromthe American Heart Association, Dallas county ctapter.Manuscript received February 1; revision accepted May 9.Reprint reqrrests: Dr. Howitz, University of Texas SotrthwesternMedical School, Dallas 75235in diastolic filling time exaggerates the effects ofmitral valve obstr~ction,~ it is difficult to evaluatethe importance of a myocardial factor in the abnormalresponse to strenuous activity of patientswith mitral stenosis. However, isometric exercise7-"induces relatively modest increases in heart rate andoffers a means by which the left ventricular responseto exercise can be evaluated without excessive complicationfrom a rate-related increase in inhibition toventricular filling.In this study, the hemodynamic response to isometricexercise was compared between a group ofpatients without significant heart disease and agroup of patients with moderate to severe puremitral stenosis. Since previous studies have concludedthat left ventricular wall motion abnormalitiesoccur in mitral stenosi~,~~ a quantitative analysisof left ventricular cineangiograms was performedto ascertain whether focal or generalized abnormalitiesof contraction correlate with an impaired hemodynamicresponse to isometric stress.Studies were performed in six patients without significantheart disease and six patients with pure mitral stenosis. Thepatients without organic heart disease undenvent cardiaccatheterization because of unexplained chest pain or murmurs.Left ventricular pressure wa.5 obtained with a No. 8 FNIH catheter introduced into the right brachial artery; sys-CHEST, VOL. 64, NO. 5, NOVEMBER, 1973Downloaded From: http://publications.chestnet.org/ on 03/03/2015

FIGURE 1. Schematic illustration of method for quantitativeanalysis of left ventricular cineangiograms. Length (L) andhemiaxes (H,-,) were measured at end-diastole (solid outerline) and end-systole (broken inner line). H,H, denoteanterior hemiaxes, with H,-H, denoting posterior.temic arterial pressure was monitored with a 6-in length of 5F polyvinyl tubing introduced percutaneously into the leftbrachial artery. Cardiac output was measured by the indicator-dilutionmethod using indocyanine green dye injected intothe pulmonary artery and sampled from the left brachialartery.Isometric exercise was performed at the beginning of thecardiac catheterization. Each patient's maximal voluntaryhandgrip contraction (MVC) was determined with a handgripdynamometer (CH Stoelting Co.) held in the left hand.Control measurements of left ventricular and brachial artervpressures, heart rate, and cardiac output were obtained withthe patient at rest. A handgrip at 25 percent of MVC wasthen held for 3 4 min and the measurements were repeated.After a 5-min recovery period, the measurements were repeatedat 50 percent of MVC held for 1 min. Care was takento assure that the patients breathed normally and did notperform Valsalva's maneuver during the isometric exercise.Ventricular function curves were constructed by plottingstroke work index as a function of left ventricular enddiastolicpressure at rest and at each level of handgripexercise. Stroke work index was calculated from:where:LVSWI = SV X ( LVS-LVEDP) X 1.36100 x BSATable 1Resting ~em&narnics inAgePAP S/DPatient, No. (Yrs) Sex (mm Hg)LVSWI = left ventricular stroke work index (g-m/M2);SV = stroke volume ( ml/beat );LVS = left ventricular mean ejection pressure (mm Hg);LVEDP = left ventricular end-diastolic pressure (mm Hg);BSA = body surface area ( M2).Approximately 15 min after the isometric exercise, leftventricular cineangiograms were performed in the 30° rightanterior oblique position using a framing sequence of 60frames per second. A power injection of 40-50 ml of megluminediatrizoate and sodium diatrizoate (Renografin 76 percent) was made over a 2-3 # sec period.The outline of the left ventricle at end-systole and enddiastolewas traced from individual 35-mm cine frames. Itwas assumed that within each individual cardiac cycle theframe with the largest left ventricular volume was enddiastoleand the frame with the lowest volume was endsystole.Premature beats and postextrasystolic beats wereexcluded. The magnification factor was obtained by filming across-hatched grid placed 10 crn above the table top.End-systolic and end-diastolic left ventricular volumeswere determined by the area-length method of Dodge et all2as modified by Kasser and Kennedy." Ejection fractionswere calculated by dividing the difference between the enddiastolicand end-systolic volumes by the end-diastolic volume.Ventricular wall motion was analyzed by constructingthree perpendiculars to the long axes at quarter lengthintervals (Fig 1). The perpendiculars are bisected by thelong axis into anterior wall hemiaxes ( and posteriorwall hemiaxes (H4.6). The percentage changes of eachhemiaxis and the long axis from end-diastole to end-systolewere calculated.4In the six patients with mitral stenosis, valve areas werecalculated as described by Gorlin and Corlin,l4 substitutingthe pulmonary wedge pressure for left atrial pressure. Nomitral insufficiency was present in any subject. Selectivecoronary angiography was performed in all of the normalpatients and four of the patients with mitral stenosis.The six control subjects ranged in age from 24 to58 years. The resting hemodynamics and selectivecoronary arteriograms were normal. Five patientshad heart catheterization because of unexplainedchest pain. Catheterization was performed on onepatient because of a murmur. A slight prolapse ofthe posterior mitral valve ledet was noted in onepatient, and a calcification of the mitral annuluswas noted in another patient. The remainder had nodetectable cardiac abnormalities.The six subjects with mitral stenosis ranged in ageSix Patients with Mitral Stenosis-X PW LVEDP MVA M VI(mm Hg) (mm Hg) (em2) (cmVM9)Abbreviations: PAP = pulmonary artery pressure (S/D = systolic/diastolic) ; ;iZ PW = mean pulmonary wedge pressure; LVEDP =left ventricular end-diastolic pressure; MVA =mitral valve area; MVI =mitral valve index.CHEST, VOL. 64, NO. 5, NOVEMBER, 1973Downloaded From: http://publications.chestnet.org/ on 03/03/2015

-LEFT VENTRICULAR FUNCTION IN MITRAL STENOSIS 61 1Table 2--Hemdynamic Response to lrometric Exercise in Six Normal SubjectsRest25% of MVCLVEDP HR SV LVMEP SWI(mm Hg) (B/Min) (ml/B) (mm Hg) (R-m/MP)of MVC--- ~-- - -- -- - - - - -Abbreviations: MVC=maximal voluntary contraction; LVEDP=left ventricular end-diastolic pressure; HR=heart rate; SV=stroke volume; LVMEP=left ventricular mean ejection pressure; SWI =stroke work index. Values shown are mean f standarddeviation. p values are from a t test of significance comparing each exercise value with its resting control. ns=p 1 0.05.from 21 to 48 years. No symptoms, physical findings, ventricular end-diastolic pressure increased in eachor electrocardiographic changes suggestive of coro- subject during the handgrip. Statistically significantnary artery disease were present. Selective coronary increases in heart rate, cardiac output, and left vencineangiographywas normal in two ( patients, 2,4 ),tricular mean ejection pressure occurred.and in two others the coronary arteries appeared The ventricular function curves for the controlnormal on aortogram (patients, 3,6). In one patient subjects are shown in Figure 2. All were considered(no. 5), selective coronary arteriograms showed an normal because of a progressive increment in strokeisolated 50 percent stenosis of the middle portion of work as left ventricular end-diastolic pressure intheright coronary artery, but no wall motion ab- creased. This was interpreted as an appropriate renonnalitiesor other findings attributable to this le- sponse to an increase in preload, whereby augsionwere present. Three of the patients with mitral mentation in venous retm increased left ventricularstenosis were in atrial fibrillation and taking a digi- end-diastolic pressure and volume and, through thetalis preparation ( patients 4,581 ; the remainder Frank-Starling mechanism, resulted in an increasedwere in normal sinus rhythm and were not taking force of contraction,15~16cardiac medications. The resting hemodynamics in The responses in the patients with mitral stenosisthe patients with mitral stenosis are shown in Table are shown in ~ ~ 3 and b ~i~~~~ l ~ 3. ~i~~~~ 3, the1. All had significant gradients between the pulmo- patients with atrial fibrillation are distinguished bynary artery wedge and the left pressure the dashed lines. As in the group, left venduringdiastole. No mitral regurgitation or lesions oftricular end-diastolic pressure rose in subjectother cardiac valves were present.during handgrip exercise. Left ventricular meanejection pressure rose significantly. Heart rate andIsometric Exercisecardiac output tended to increase, but these wereThe hemodynamic response to handgrip exercise not statistically sigmficant. In contrast to the controlin the control group is summarized in Table 2. Left subjects, the changes in stroke work were variableand not significant.rAs shown in Figure 3, stroke work fell as leftventricular end-diastolic pressure rose in three of thepatients with mitral stenosis, a clearly abnormal response.In two others stroke work was only slightlySWIelevated over the resting value at 50 percent ofMVC, an equivocal response. Only one subjectwith mitral stenosis had a rise in stroke work comparablein amplitude to the control ventricular func-40tion curves.30Except for lower resting stroke work, there was nodifference between the isometric exercise responsein the three patients with atrial fibrillation and thosein normal sinus rhythm in the mitral stenosis group.Of the three patients with atrial fibrillation, one(patient 6) had a normal ventricular function curve,while the curves in the other two patients weremarkedly abnormal.20 0 5 10 15 20LV END-DIASTOLIC PRESSURE ,(mmHg1FIGURE 2. Left ventricular function curves in six control subjects.SWI indicates stroke work index. Note all curves showincrease in stroke work as left ventricular pressure increasesduring handgrip.CHEST, VOL. 64, NO. 5, NOVEMBER, 1973Downloaded From: http://publications.chestnet.org/ on 03/03/2015

Table %Hernodynamic Response to Isometric Exercise in Six Patients with Mitral Stenosis *LVEDP HR SV LVMEP SWI(mm Hg) (B/Min) (ml/B) (mm Hg) (g-m/MP)Rest 6+2 88 f 18 48 + 9 116 f 11 42 k 925% of MVC50% of MVC 11 +3 102 + 26 48 + 13 131 + 11 42 + 8p < 0.05 ns ns p < 0.01 ns*Abbreviations and symbols same as in Table 2.Angiocardwgraphic AnalysesLeft ventricular volume measurements are summarizedin Table 4. The end-diastolic volumes weresimilar in the two groups, but the end-systolic volumeswere significantly greater in the group withmitral stenosis. Ejection fractions ranged from 64 to83 percent in the control subjects and from 37 to 62percent in the patients with mitral stenosis. Thereduced ejection fraction in the group with mitralstenosis was highly significant ( p < 0.001 ) .The results of the ventricular wall motion analysesare shown in Table 5. Shortening of the hemiaxes inthe posterobasal (Hq and Hg) and in the mid anddistal anterior (Hz and Hs) walls was significantlydecreased in the group with mitral stenosis. Shorteningin the anterobasal (HI) and posteroapical (Hs)regions was not significantly different in the twogroups. Representative angiograms from a normalsubject and a subject with mitral stenosis are shownin Figures 4,s.The nature of the changes in left ventricular enddiastolicpressure and dimensions in normal subjectsperforming dynamic exercise has been clarified inSWI(gmm/mt )recent studies.17,18 When the exercise stress is severe,a Frank-Starling response with an increase inleft ventricular end-diastolic pressure and dimensionsoccurs.17.18 Lack of an increase in end-diastolicpressure during dynamic exercise is associatedwith very mild effort only.18 A similar increase inleft ventricular end-diastolic pressure occurs in subjectswith normal left ventricular function duringstrenuous isometric exercise as performed in thisst~dy.~,'l Occasional cases in which normal subjectshave been reported not to display an increase in leftventricular end-diastolic pressure probably reflect alow level of exercise stress.It is well established that a Frank-Starling response,as indicated by an increase in left ventricularend-diastolic pressure, will, in a normal subject, resultin improved ventricular performance, as indicatedby an increase in strokeThus,as left ventricular end-diastolic pressure increasesduring isometric exercise, a normal left ventricularreserve is expressed as an increase in stroke work,whereas a fill or lack of change in stroke work isevidence of impaired left ventricular function.In patients with mitral stenosis, left ventricularfilling is seriously limited at high heart rates.6 Thus,the high heart rates during dynamic exercise prohibitadequate diastolic in0ow to the left ventricleand limit cardiac output and stroke work on thisbasis. However, only small increases in heart rateoccur with isometric exercise, and it is apparent thatthe failure to increase stroke work in the patientswith mitral stenosis was due to abnorinal left ventricularfunction, rather than serious inhibition ofTable 4--Left Ventricular Volumes(N = Six in Each Group) *201 I 1 I 10 5 10 15 20LV END-DIASTOLIC PRESSURE(mmHg)FIGURE 3. Left ventricular function cnrves in six subjects withmitral stenosis. Solid lines denote three patients in normalsinus rhythm. Dashed lines designate three patients in atrialfibrillation. SWI indicates stroke work indexEDV ESV EF(ml) (ml) (%INormal subjects 164 + 36 50 + 18 70 f 6Mitral stenosis 178 f 36 95 32 47 + 8ns p < 0.02 p < 0.001*Values are mean + standard deviation. p values were obtainedby a t test for unpaired variates. ns=p 2 0.05.EDV = end-diastolic volume; ESV =end-systolic volume;EF =ejection fraction.CHEST, VOL. 64, NO. 5, NOVEMBER, 1973Downloaded From: http://publications.chestnet.org/ on 03/03/2015

LEFT VENTRICULAR FUNCTION IN MITRAL STENOSISTable LAngimardiographic Analyru of Axia ShorteningL HI Hz It I4 H, HsNormal Subjects, No.7 8 20 33 42 23 35 648 40 55 46 100 24 26 1009 18 67 42 47 n 38 5 110 21 67 35 49 42 52 0411 38 05 49 53 38 61 10012 28 67 31 50 35 54 63Mean 26 58 39 57 32 44 74SD 12 16 7 21 8 13 29Subjects with mitral stenosis, No.1 14 45 29 43 20 18 412 13 40 22 18 20 32 303 24 68 31 42 18 19 414 5 8 12 21 10 15 175 12 39 21 25 18 21 336 4 57 27 16 18 27 23Mean 12 43 25 28 17 20 31SD 7 20 7 12 4 7 10P

HORWITZ ET ALFIGURE 5. Photographs of RAO left ventricular cineangiogramat end-diastole (a) and end-systole (b) in subject with mitralstenosis. There is decreased motion in distal portion ofanterior wall ( H,, H,) and in posterobasal region ( H,. H, ).study is a similar limitation in motion due to adherenceof the scarred, shortened anterior papillarymuscle to the contiguous ventricular wall.ACKNOWLEDChlENTS: We wish to acknowledge the valuabletechnical assistance of Miss Joyce Dillard, Mr. JamesHarper, and Mr. James Hirsch.1 Hugenholtz PC, Ryan TJ, Stein SW, et al: The spectrumof pure mitral stenosis; hemodynamic studies in relationto clinical disability. Am J Cardiol 10:773, 19622 Heller SJ, Carleton RA: Abnormal left ventricular con-traction in patients with mitral stenosis. Circulation 42:1099, 19703 Feigenbaum H, Campbell RW, Wunsch CM, et al: Evaluationof the left ventricle in patients with mitral stenosis.Circillation 34 :462, 19664 Cilny CC, Elliott LP, Ramsey HW: Quantitative leftventricular angiocardiographic findings in mitral stenosis:Detailed analysis of the anterolateral wall of the leftventricle. Am J Cardiol29:621, 19725 Bergy GG, Bruce RA: Discrepancies between subjectiveand objective responses to mitral commissurotomy. NEngl J Med 253:887, 19556 Arani DT, Carleton RA: The deleterious role of tachycardiain mitral stenosis. Circulation 36:511, 19677 Mullins CB, Leshin SJ, Mierzwiak DS, et al: Isometricexercise (handgrip) as a stress test for evaluation of leftventricular function. Circulation 42: 111-122, 19708 Helfant RH, devilla MA, Meister SG: Effect of sustainedisometric handgrip exercise on left ventricular performance.Circulation 44:982, 19719 Kivowitz C, Parmley UrW, Donoso R, et al: Effects ofisometric exercise on cardiac performance: The grip test.Circulation 44:994. 197110 Bruce RA, Lind AR, Franklin D, et al: The effects ofdigoxin on fatiguing static and dynamic exercise in man.Clin Sci 34:29, 196811 Payne RM, Horwitz LD, Mullins CB: Comparison ofisometric exercise and angiotensin infusion as stress testfor evaluation of left ventricular function. Am J Cardiol31:428, 197312 Dodge HT, Sandler H, Ballew DW, et al: The use ofbiplane angiocardiography for the measurement of leftventricular volume in man. Am Heart J 60:762,196013 Kasser IS, Kennedy JW: Measurement of left ventricularvolumes in man by single-plane cineangiocardiography.Invest Radio1 4:83,196914 Gorlin R, Gorlin SG: Hydraulic formula for calculation ofthe area of the stenotic mitral valve, other cardiac valves,and central circulatory shunts. Am Heart J 41: 1, 195115 Sarnoff SJ. Berglund E: Ventricular function. I. Starling'slaw of the heart studied by means of simultaneous rightand left ventricular function curves in the dog. Circulation9:706, 195416 Ross J, Braunwald E: The study of left ventricular functionin man by increasing resistance to ventricular ejectionwith angiotensin. Circulation 29:739, 196417 Erickson HH, Bishop VS, Kardon MB, et al: Left ventricularinternal diameter and cardiac function duringexercise. J Appl Physiol30:473, 197118 Horwitz LD, Atkins JM, Leshin SJ: The role of the Frank-Starling mechanism in exercise. Cir Res 31:868, 197219 Brock RC: The surgical and pathological anatomy of themitral valve. Br Heart J 14:489, 195220 Grant RP: Architectonics of the heart. Am Heart J 46:405, 1953CHEST, VOL. 64, NO. 5, NOVEMBER, 1973Downloaded From: http://publications.chestnet.org/ on 03/03/2015