Effects of enhanced afterload and contractile state on the left ventricular late systolic wall stress-dimension relation

October 1, 1984

state facilitated induction of arrhythmias with very rapid rates and pleomorphic characteristics. We believe that rhythms of this type, the induction of which results in part from the open-chest state, may have been inappropriately classified as VT in other studies. Thus, we are essentially in agreement with Patterson. The real area of disagreement is over what should and what should not be considered analogous to human VT. We believe that this is a very important area of controversy, because there is a possibility that conclusions drawn from models that do not truly mimic the human condition could lead to misconceptions and suboptimal therapies. Debra S. Echt, MD Stanford, California

Jay W. Mason, MD Salt Lake City, Utah 1. Echt DS, Griffin JC, Ford AJ, Knuttl JW, Feldman RC, Mason JW. Nature of inducible ventricular tachyarrhythmtas in a canine chronic myocardial infarction model. Am J Cardiol 1983;52:1127-1132. 2. Mlchelson EL, Spear JF, Meace EN. Electrophyslologlc and anatomic correlates of sustained ventrlcular tachyarrhythmlas in a model of chronic myocardial infarction. Am J Cardiol 1980;45:583-590. 3. Knraguezlan HS, Fenogllo J,J Jr, Weiss MB, wn AL Protranted tachycardla induced by premature stimulation of the canine heart after coronary artery occlusion and reperfusion. Circ Ras 1979;44:834-846. 4. Petter~m E, GIl~ion JK, LucchaM BR. Prevention of chronic centce ventricular tachyan'hythmlas with bretyllam tosylate. Circulation 1981;64:1045-1050. 5. Gang ES, Bigger JR, Uvelll FD. A model of chronic ischemic arrhythmlas: the relation between elecbicaUy inducible ventricular tachycardla, ventricular fibrillation threshold and myocardial Infarct size. Am J Cardiol 1982;50:469-477. 8. Wetsteln L, Mlchelaon EL, Slmson MB, Spear J, Moore EN, Harker AH. The Initiation of ventricular tachyarrhythmlas with programmed pacing. Reevaluation of sensitivity and specificity in an experimental model. Surgery 1982;92:208-211. 7. Brogada P, Green M, Abdollah H, Wellens HJJ. Significence of ventrlcular arrhythmlas Initiated by programmed ventricular stimulation: the importance of the type of vantrlcular arrhythmla Induced and the number of premature stimuli required. Circulation 1984;69: 87-92. 8. Swardlow cg, Winkle RA, Griffin JC, Ross DL, Mason JW. Decreasedincidence of antlarrh~la drug efficacy at electrophysiologlc study associated with the use of the third extrastlmulus. Am Heart J 1982;104:10041010.

LEFT VENTRICULAR DYSFUNCTION DISCRIMINATED NONINVASIVELY BEAT-TO-BEAT

Dinaburg and Zuckerman's report 1 is a superb contribution to noninvasive methodology and applications. It establishes further usefulness for systolic time intervals and renews interest in ballistocardiography (BCG). The particular contribution of beatto-beat measurement in which percentages of "normal" and "abnormal" heart beats are identified has special promise if substantiated. We introduced beat-to-beat evaluation of Valsalva maneuver and demonstrated its statistical superiority to time division of the results, 2 but we did not have the powerful computer backup of this study. The authors have not given any "raw" data, but appear to discriminate between normal men and those with myocardial infarcts or systemic hypertension by the fact that in the latter, the ratio of preejection period to ejection time (PEP/

THE AMERICAN JOURNAL OF CARDIOLOGY

LVET) did not vary significantly with the respiratory cycle, especially for the normalized respiratory value for both the P E P / L V E T and the BCG I-wave data. Because of previous work by our group on the effects of respiration on systolic time intervals,3, 4 the authors' results are difficult to understand. Both in a group of patients with coronary artery disease3, 4 and in a mixed group of normal patients and patients with coronary disease, 3 we found significant differences in P E P / L V E T (as well as other systolic time intervals) between the respiratory phases. Can the authors address this discrepancy? Irrespective of whether the differences in their findings and ours can be reconciled, the methods introduced--both for computer handling and for statistical data analysis (e.g., the nonlinear quadratic discriminant function)--are distinct contributions that should enhance truly noninvasive studies. One possible reason for the discrepancy is that they may have used in-hospital patients with active disease and dysfunction. We used ambulatory outpatients because we believed that diagnostic testing would be much less useful in patients already hospitalized with known conditions. In other studies, we compared the effects of head-up tilt s between normal subjects and hospitalized patients with cardiac disease.5, 6 The latter showed an extremely blunted response. Because acute tilting may be even more of a "stress test" than ordinary breathing, perhaps the (presumably) hospitalized patients in their series showed a blunted or absent respiratory response owing to the "buffering" effect of cardiac dysfunction. David H. Spodlck, MD, DSc Worcester, Massachusetts 1. Dlnaburg AG, Zuckarman BR. Left vantricular dys-

functiondiscriminatednonlnvaslvelybeatby beet. Am

J Cardlol 1984;53:238-242. 2. F l e ~ AP, Kumar S, Spodlck DH. Effectsof the Valsalva maneuver on the cardiac systolic intervals: beatto-beat versus time analysis. Am Heart J 1970;80: 522-531. 3. Nandl PS, PlgotlVM, SpodlckDH. Sequential cardiac responses during the respiratory cycJe: patterns of change in systolic intervals. Chest 1973;63:380-385. 4. Plgon VM, Spodlck DH. Effects of normal breathingand expiratory apnea on duration of the phases of cardiac systole.Am HeartJ 1971;82:786-793. 5. Spodlck I)1t, Meyer M, St Plen'e JR. The effect of updgllt tilt Onthe phases of ~ cardiac cycle in normal subjects. Cardlovasc Res 1971;5:210-214. 8. Sa~,chez-ZambranoS, SpodlckDH. Comparativeresponses to orthostatlc stress In normal and abnormal subjects: evaluation by impedance cardiography. Chest 1974;65:394-396.

REPLY: The praise from Spodick, a pioneer in this field, is welcome. We reported a significant t test difference in PEP/LVET ratios in 2 or 4 distinct phases of respiration, in a group of patients with coronary disease (Ref. 4 above) or mixed normal subjects and patients with cardiac disease (Ref. 3 above), but without explicitly contrasting normal with abnormal persons. We studied the beat-bybeat association of the entire respiratory cycle and associated STI and BCG measures, contrasting normal subjects with coronary and hypertensive patients. In our Table I, analysis of covariance, which combines features of regression and analysis of variance, revealed a significant relation between respiratory phase and P E P / L V E T in normal subjects, but not in the other 2 groups. We

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can only point to the large degree of variability of the data for the latter 2 groups, as shown by their low F ratios. In contrast, all 3 groups showed highly significant relations between respiration and I-wave amplitude of the BCG, reflecting aortic flow acceleration. However, respiratory variation in our measures of cardiac function was not a sufficiently powerful discriminator alone between normal and coronary heart beats. When all 36 measurements per beat were tested with the use of the various statistical methods, the 9 leading variables were identiffed that by their simultaneous interactions, characterize the differences between the normal and "coronary" beats. Thus the nonlinear quadratic discriminant function was able to identify the leading variables, their relative importance and the assignment of a score to each heart beat, which then placed it in the "normal" or "coronary" group. We hope that the power and utility of this method in extracting maximal information from complex multivariate data will lead to its further application in other areas, as has • already begun. Aaron G. Dlnaburg, MD Barry R. Zuckerman, BA Berkeley, California

EFFECTS OF ENHANCED AFTERLOAD AND CONTRACTILE STATE ON THE LEFT VENTRICULAR LATE SYSTOLIC WALL STRESS-DIMENSION RELATION

We congratulate Colan et al for their recent study, 1 which confirms that during left ventricular (LV) ejection, the late systolic wall stress-dimension relation is linear and affected by changes in inotropic state. In addition, their data also clearly indicate that the slope of this relation is afterload-dependent during physiologically loaded contractions. Accordingly, the clinical value of this index could be as limited as that of the other ejection phase indexes. To interpret the differences in afterload dependence observed between his and our previous study, 2 Colan correctly points out the differences in formula used for wall stress computation and the differences in aortic impedance changes produced in 1 way by aortic clamping in dogs and in the other by methoxamine administration in humans. We would like to draw his attention to 2 other experimental differences between our studies. First, we computed wall thickness, assuming a constant ventricular mass; in their study direct wall thickness values were used. Considering the importance of local wail thickness changes in stress computation, our approach might have been an oversimplification. Second, we used in dogs a right-sided heart bypass preparation, thus keeping the right ventricle empty and opening the parietal pericardium. In contrast, the parietal pericardium in humans is intact, and changes in pericardial pressure or mechanical interferences between the ventricles are likely to occur when the LV volume increases, as is the case during methoxamine administration. Other differences in LV contractile behavior

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IPII~RS

have been observed between isolated heart preparations and clinical studies. In the isolated heart, an inotropic stimulation increases the slope of the end-systolic pressure-dimension relation, with negligible change in volume intercept, 3 whereas in humarls a significant change in intercept is found. 4 Because of these differences, the influence of the parietal pericardium and of the right ventricle on LV stress-volume relation during ejection might be worth investigating.

H. Pouleur, MD M. F. Rousseau, MD C. van Eyll, MSEE Brussels, Belgium

1. Colan SD, Borow KM, Gamble WJ, Sanders SP. Effects of enhanced aflerload (methoxamlna) and contractile state (dobutamine) on the left ventrlcular late-systolic wall stress-dimension relation. Am J Cardlol 1983; 52:1304-1309. 2. Pouleur H, Roe~eau MF, van Eyll C, Van Mechekm H, Bras~mr I.A, Chadlar ~ Assessmentof left venfrlcular contractility from late systolic stress-volume relations. Circulation 1982;65:1204-1212. 3. Suga H, Sagawa K, Shouku JUt. Load independence of the instantaneouspressure-volumeratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 1973;32:314-322. 4. Borow KM, Neumann A, Wynne J. Sensitivity of endsystolic pressure-dimension and pressure-volame relations to the inotropic state in humans. Circulation 1982;65:988-997.

R E P L Y : W e appreciate the additional comments by Pouleur, Rousseau and van Eyll concerning our study. W e are in agreement with their observations and do not feelthat we have anything further to add. Steven D. Colan, MD Boston, Massachusetts THE CASE FOR EXERCISE

I read with interest "The Case for Exercise" by Dr. George Sheehan in the January 1984 issue of the Journal. I believe that he is somewhat evading the issue of discussing data regarding exercise in medical practice today. Though not as scientifically well studied as we would like, there are certainly definite published data to support that exercise is beneficial in both primary and secondary management of coronary artery disease. "Evidence in American and European studies and in epidemiologic surveys is convincing. It is time for us to be more scientific about the role of exercise in the practice of medicine today rather than candidly saying that it "improves the quality and quantity of life," causes "renewed self-esteem" and lowers "negative emotions." Exercise capacity in medical practice is determined by a physician-supervised exercise test and administered by means of prescriptive exercise programs. Exercise is a science and widely used both in basic and clinical research particularly in the specialty of cardiovascular medicine. We therefore need to treat exercise with the scientific respect it deserves. Gerald F. Fletcher, MD Atlanta, Georgia

REPLY: I agree with Fletcher that exercise should be treated with scientific respect. What I propose is that we take the fully re-

searched and proved physiologic effects of exercise and use them in practice. That is the "quantity" I write of--increased physical work capacity and improved maximal oxygen uptake. I too dislike the word "quality." It is much too soft, but psychological studies do show favorable changes in specific qualities needed for the good life--vigor, coping, creativity and self-esteem. I believe we should not be mired down in this unending debate over the effect of exercise on pathology. Fletcher feels the evidence is there, and many equally knowledgable observers think not. As a result, practitioners are immobilized and still awaiting direction. What I claimed for exercise can be proved--things that are "as scientifically well-studied as we would like." Both Fletcher and I are in the same camp. We both want patients to exercise, but our tactics are different. My years in the field have convinced me that the best case for exercise is the one for fitness. This whole exercise phenomenon arose, not from health care specialists, but the people themselves; for those reasons I recommend the quantity and quality of life they receive from the hours spent in motion. George Sheehan, MD Red Bank, New Jersey

U S E F U L N E S S OF EXERCISE

Every age has itsgreat myths--emotionally appealing ideas,sustained in the public mind without supporting evidence. T w o of ours currently are (1) that coronary heart disease is caused by "stress" (typically defined as the daily occupation of the person afflicted), and (2) that exercise is both preventive and therapeutic. Exercise prevention (or deceleration) of coronary atherosclerosis is based, so far at least, on equal parts wishful thinking and anecdotal "evidence" that would embarrass a 1950s Anacin commercial. Worse, our current enthusiasm for postinfarction rehabilitation has convinced much of the public that exercise is uniformly beneficial in this setting--a concept equally devoid of experimental justification, an~! carrying the potential for real harm to some patients. Sheehan ("The Case for Exercise") deserves our thanks for a clear-headed restatement of the benefits of exercise, refreshingly free of myth entanglement. He lucidly describes the real value of conditioning to persons, sick or well, who possess both the coronary anatomy and the self-discipline to safely pursue physical fitness. A copy of his article should be required reading for patients who have been deluded by the current hysteria into thinking that they are depriving themselves of life, liberty and the pursuit of happiness by not exercising systematically. We should keep in mind that exercise, like virtue, is pretty much its own reward--and a sizeable one at that. We do not have to kid ourselves or our patients that it will make us live longer, in order to justify it. Even if it did, we might remember Shaw's aphorism: "Do not try to live forever--you will not succeed." John V. Russo, MD Washington, DC

T R E N D S IN C O R O N A R Y H E A R T DISE A S E Roberts, 1 in a recent editorial, pointed out the

numerous benefits that may result from regular exercise in the form of running. He also provided a portrait of Sheehan, whose philosophy and practical advice on exercise have been of interest and assistance for many years. Although in full agreement with Roberts' viewpoint, I wish to correct him on 1 matter. He stated, "The death rate from coronary heart disease is decreasing in the U.S., and the U.S. is the only country in the Western world where this is so." In fact, similar trends have been observed in New Zealand and Australia, 2-4 which are generally classified as Western countries. It is important to note this, for only by long-term monitoring on an international basis as proposed by the World Health Organization s will a full understanding of these trends emerge. D. Norman Sharpe, MD Auckland, New Zealand 1. Roberts WR. An agent with lipid-lowering, antihypartenslve, positive laotroplc, negative chronotroplc, vasodilating, diuretic, anorexlgenic, weight.reducing, cathartic, hypoglycamlc, tranquilizing, hypnotic and antldepressive qualities. Am J Cardlol 1984;53:261262. 2. Beaglehole R, Hay DR, Foster FH, Sharpe DN. Trends In coronary heart disease mortality and associated risk factors in New Zealand. NZ Med J 1981;93:371-375. 3. Beaglahole R, Bonita R, Jacksofl R, Stewart A, Sharpe DN, Fraser GE. Trends in coronary heart disease event rates in New Zealand. Am J Epidemlol. In press. 4. Plna Z, Uemara K. Trends of mortality from ischeemlc heart disease and other cardlavascular diseases in 27 countries, 1968-77. World Health Stat Q 1982;35: 11-45. 6. World Hea]~ Organization. Proposal for multinational monitoring o! ~rendsand detarmlnants in cardiovascular disease and protocol (MONICA Project). Geneva 1983. WHO Document WHO/MNC/82.1 Rev 1.

M Y O C A R D I A L UPTAKE OF TECHNETIUM-99m P Y R O P H O S P H A T E IN SYSTEMIC AMYLO I D O S I S

In response to Leinonen's report (Am J Cardial 1984;53:380-381), certain points must be emphasized about technetium-99m pyrephosphate scanning in amyloid cardiomyapathy. First, the positivity of the scan will be related to the mass of amyloid in the myocardial tissues and its calcium content. The echocardiographic findings of granularity of myocardium reflects the presence of amyloid but does not reflect its magnitude. It would have been better if they had supplied echocardiographic evidence quantitating the extent of replacement. Second, it is unconvincing that the demonstration of amyloid material in a distant organ (i.e., rectum or kidney) will reflect the degree of involvement of the heart. To confirm heavy amyloid deposition, myocardial biopsy should have been performed. Third, they failed to comment on why AA protein does not bind to technetium-99m pyrophosphate. As biopsy material was available, it would have been interesting to look at the calcium content of the AA protein. Theoretically, it would be much lower than ASc and AL amyloid proteins, which bind avidly to technetium-99m pyrephosphate. Because of this, it is not reason-