- Email: [email protected]
Coronary artery disease and the concept of cardiac failure
Coronary
Artery Disease and the Concept of Cardiac
Failure
LOUIS A. SOLOFF, M.D. Philadelphia,
Pennsylvania
E
LSEWHERE’~~ I wrote that the unqualified term heart fazlure has no operational meaning because it fails to spell out which function or functions the heart fails to perform in a normal fashion. Many r,tudents use the term as a synonym for congestive heart failure. This is unfortunate because it perpetuates the concept and leads to the assumption that there is only one way in which the heart can fail. That this is untrue is recognized operationally by all physicians who treat patient,3 with heart disease, particularly patients with coronary artery disease and myocardial infarc:tion. As a matter of fact, almost all life-threatening dysfunctions of the heart are associated with abnormalities in blood pressures regardleas of the presence or absence of congestion. This statement is especially true today, now that powerful diuretics frequently can dissipate congestion but rarely can normalize pressures. Indeed, decongestive therapy can worsen a pressure type of failure. On the other hand, common definitions of heart failure, such as “no longer able to pump blood normally” and “unable to pump an adequate supply of blood in relation to the venous return and to the metabolic needs of the body,” are generalities that usually cannot be documented on clinical grounds; if taken literally, they include many clinical states that are not acceptable as heart failure by those very physicians who so define it. Congestive heart failure is a clinical syndrome characterized by dyspnea, generalized venous hypertension and congestion and edema attributable to the presence of heart disease, which is usually obvious and advanced. This clinical stat? represents the body’s reaction-reflex,
hormonal and environmental-to the heart’s failure to expel its contents in a normal fashion. The inability of the heart to expel blood in the normal fashion can be due not solely to intrinsic myocardial disease but also to other disturbances engrafted upon or producing myocardial faults. Some of these disturbances are valvular dysfunctions, arrhythmias, drug toxicity, hypoxia, acid-base imbalance, physical activity and the ingestion of salt. These extramyocardial factors are particularly apt to precipitate congestive heart failure in subjects with coronary artery disease because of the limited capacity of the left ventricle in this disorder to increase its ejection rate, stroke volume and cardiac output.3 Nonetheless, incapacitating cardiac disability and death frequently occur in patients with coronary artery disease without clinical evidence of congestive heart failure; yet no one doubts that the heart has failed in its most important function-to sustain life. Regardless of the type of cardiac failure present in subjects with coronary artery disease, the primary and fundamental cause resides in the myocardium, almost always in the left ventricle. MYOCARDIAL INFARCTION, VENTRICULAR ANEURYSM and CARDIAC FUNCTION Orias4 was the first to show that coronary artery occlusion deleted or impaired contraction in the block of myocardium deprived of its blood supply by the occluded vessel. Tennant and Wiggerss were the first to show that the ischemic region expanded in systole. Therefore, after coronary artery occlusion, a portion of the myocardium fails to contract normally. Wigger# also pointed out that myocardial disturbances
From the Division of Cardiology, Temple University Health Sciences Center, Philadelphia, Pa. This study was supported by U. S. Public Health Service Grant HE-05712-02 and by The Council For Tobacco Research-U.S.A. Address for reprints: Louis A. Soloff, M.D., Division of Cardiology, Temple University Health Sciences Center, 3401 N. Broad St., Philadelphia, Pa. 19140. VOLUME
22,
JULY
1968
43
Soloff produced by coronary occlusion frequently lead These to failure of normal electrical conduction. failures may be manifested by a variety of arrhythmias and conduction disturbances that further impair the ability of the heart to contract The degree and subsequent types normally. of failures will depend upon the size of the block of tissue deprived of its blood supply, its location, the capacity of the uninvolved portion of the myocardium to compensate for the lesion, the extracardiac effects of abnormal vascular pressures, reflex and hormonal reactions to the injury and the integrity of organs other than the heart. Tennant and Wiggerss clearly demonstrated the physiologic significance of interruption of coronary flow. Within a minute, aortic and pulse pressures are reduced and the form of the aortic pressure is altered; both phenomena indicate an immediate reduction in systolic discharge of the left ventricle. The heart has, therefore, failed to maintain normal contraction, More output and peripheral arterial pressure. sophisticated methods indicate that failure to maintain a normal ventricular ejection rate may be the earliest finding in myocardial infarction.7 This decreased ejection rate and decreased acceleration of ejected blood can be graphically illustrated by infusing a pellet of contrast substance into the left ventricle of a dog before and after ligation of a coronary artery.* A decreased, weakened and abnormally contracting segment of the left ventricle is, therefore, probably constantly present in myocardial infarction. This region may be too small to be recognized clinically and may be overlooked at necropsy because the left ventricle is motionless. Even aneurysmal lesions large enough to be recognized clinically and fluoroscopically may be overlooked at necropsy because the left ventricle is not examined under the influence of the pressure pulses which had been present during life. These abnormal and asynchronous contractions of the left ventricle, other factors being equal, will Indeed, a large tend to decrease cardiac output. infarcted segment of the left ventricle may act as a regurgitant chamber by distending when the normal left ventricular muscle is contracting. Such observations are not new. They were demonstrated (within the limitations of the method) decades ago, when kymography was popular, by the electrokymograph soon after this instrument was developed in our institution, and they were observed fluoroscopically over a generation ago.9 The angiocardiographic tech-
nic has permitted a more precise delineation of the contours of the left ventricular cavity and demonstration of these abnormal contractions. these abRecently, Gorlin et al. 10 documented normal contractions by tracing the angiocardiographic contours of the left ventricle throughIt is very likely, however, out the cardiac cycle. that their verbal distinctions are much sharper than those which actually occur in nature. Clinical Implications of Ventricular Aneurysm: Although abnormal contractions of the infarcted muscle are of great importance in contributing to cardiac dysfunction, it is our experience as well as that of others” that clinical disability, hemodynamic abnormalities and congestive heart failure are not necessarily related to the extent of the recognized asynchronous contracEven a huge asynchronous contracting tions. ventricular aneurysm is compatible with wellOn the other hand, debeing for decades. terioration can occur rapidly in persons in whom the heart fails to show asynchronous contraction Indeed, the survival angiocardiographically. rate of patients with ventricular aneurysm is not significantly different from the long-term survival of all patients with myocardial infarction. lo These observations, based upon clinical and necropsy data, appear to be inconsistent with the implications of a recent biomathematical analysis of the hemodynamic findings in subjects with ventricular aneurysm. l2 Although such work is laudable as a first approach, one should be aware of the methodologic errors and the questionable assumptions upon which conclusions are based. * OTHER
FACTORS DETERMINING HEART
FUNCTION IN MYOCARDIAL
INFARCTION
The clinical and pathologic anatomic observations suggest that there must be factors in addition to aneurysmal formation which de* I refer to the identity of left ventricular volume determined by the dye-dilution method and by angiothe subtraction of stroke volume detercardiography; mined by the dye-dilution method from the end-diastolic volume of the left ventricle determined by angiocardiography; the assumption that the apex of the heart is at the mid-left ventricular level; the use of undefined systolic radius and its error of measurement; the frame by frame measurement of left ventricular volume from films in one plane of a ventricle which is admittedly contracting abnormally and asymmetrically; the measurement of the volume of an aneurysm from films in one plane; and the assumption that the heart is a thin wall sphere. Finally, the characteristics of the non-aneurysmal muscle are unknown. THE AMERICANJOURNAL OF CARDIOLOGY
Coronary
Artery
Disease
termine how well and for how long the heart will function. Ehewhere I suggested* that some of these factors may be : I. Patchy Fibrosis: Patchy fibrosis may distort the architecture of the individual myocardial fibers and thereby distort the vectors produced by them.2v’3 The normal peristaltic contraction of the left ventricle may be partly disrupted by abnormal but grossly invisible asynchronous contracting myocardial fibers. The forces produced by the individual myocardial fibers may modify and even cancel each other; or myocardial fibers may be completely transfixed by an unyielding scar so that they cannot contribute to contraction. 2. The Location of the Infarct: For many years I have been impressed with the marked impairment of myocardial contraction when constrictive pericardi tis involves the left lower pole of the heart and with how often constriction is of little importance when it is limited to the free wall of the left ventricle. It may be that infarction is particularly disastrous if it involves a significant portion of the septum. Parenthetically, it is worth noting that in most patients who die with myocardial infarction the septum is involved. 3. Mitral Regurgitation: The commonest cause of an apical systolic murmur in the adult is coronary artery disease. Mitral regurgitation in ischemic heart disease may be (a) an insignificant lesion of little hemodynamic importance; (b) a significant contributing factor to cardiac disability, pulmonary hypertension and congestive heart failure; and (c) the predominant cause of failure of forward output of the left ventricle and elevated pressure behind it. It is important to distinguish between these three types. The last will require surgical correction of the mitral valve.14 The first requires no specific valvular treatment, and the second may or may not require such treatment, depending on the relative contribution of mitral regurgitation and intrinsic myocardial involvement to cardiac dysfunction. In our experience, a moderately loud and prolonged apical systolic murmur in a patient with coronary artery disease almost always is associated with subnormal cardiac output and response to effort. l5 An apical systolic murmur together with a localized, visible and forceful apical thrust in patients with ischemic heart disease indicates significant mitral regurgitation or an apical aneurysm. Apical aneurysms are characterized VOLUME
22,
JULY 1968
and Cardiac
Failure
45
by soft, relatively localized murmurs and a normal to slightly enlarged left ventricle. In mitral regurgitation the left ventricle is large, and the murmur has a mid-systolic accentuation and is widely distributed both toward the left axilla and toward the base of the heart. On the other hand, a large left ventricle in the absence of a localized, visible and forceful apical impulse indicates predominance of myocardial disease. In place of the apical thrust, there is a diffuse systolic heave of the precordium which may extend as far as the anterior axillary line and up to the third or even second intercostal space, findings indicative of aneurysmal enlargement of the left ventricle. In such instances, a soft apical murmur is secondary to cardiac enlargement. If such a heaving motion is accompanied by a localized and forceful apical thrust, one cannot exclude on clinical grounds significant hemodynamic mitral regurgitation and its contribution to cardiac disability. Roentgen-ray studies may be decisive for this differentiation. With significant mitral regurgitation, the pulsations of the left ventricular border are vigorous and wider than those of the ascending aorta. When mitral regurgitation is insignificant or absent, pulsations of the left ventricular wall are feeble and shallow. Because differentiation is potentially so important from the therapeutic standpoint, the ejection fraction of the left ventricle should be determined by angiocardiography. Indeed, the ejection fraction, the stroke volume and the end-diastolic pressure of the left ventricle are in my experience the most important objective data in evaluating the prognosis of ischemic heart disease. Strangely, the one exception in our experience has been the occasional presence of a large eccentric aneurysm of the left ventricle. I have already stated that patients with such lesions may lead comfortable lives for years. In such patients angiocardiography will demonstrate markedly exaggerated pulsations of the uninvolved portions of the myocardium, a finding which suggests that the ejection fraction of the nonaneurysmal myocardial portion is actually larger than normal. We have made similar observations, of hypercontractility of uninvolved myocardium in subjects with localized constrictive pericarditis. 4. The Capacity of the Uninvolved Portion of the Myocardium to Compensate for the Loss of Functioning Tennant and Wiggers.6 demonstrated Muscle: that hyperfunction of the uninvolved myocardium can quickly restore the myocardial
Soloff by myocardial infarction. power depressed Tachycardia, fever and increased secretion of catecholamines released from muscle and by reflex and hormonal reaction are some of the immediate methods of improving myocardial function. More important in the long run is the very old observation that hearts increase in weight soon after they are exposed to abnormally large loads. The complex biochemical mechanisms responsible for myocardial growth are now under intense investigation. l6 Equally important is an elucidation of the signals that initiate vascular and muscular growth. There is evidence that after myocardial infarction mitosis appears in the smooth muscle of vessel walls and thereby produces smooth muscle hyperplasia with increase in the volume of vessel walls.i7 Hypoxia itself appears to be a stimulus to the synthesis and growth of myocardial protein. l* Indeed, it would appear that there are only two ways in which spontaneous recovery from congestive heart failure (a frequent clinical phenomenon) can occur: one is self-limitation of the precipitating cause of congestive heart failure, and the other is growth of the myocardium including its vascular supply, mitochondria enzymatic activity and myoglobin content. 5. Extramyocardial Factors: The limited capacity of the ischemic left ventricle to increase its ejection rate, stroke volume and cardiac output makes it particularly vulnerable to extramyocardial factors such as ingestion of salt, physical activity, hypoxia, arrhythmia, acidbase balance and drug toxicity. Equally important, the ischemic heart, through reflex and hormonal action and through environmental changes, can impair functions of organs that are vital to optimal function of the heart and thereby can establish a number of vicious circles. These are some of the reasons why there is so little correlation between the size of infarcted myocardium observed at necropsy and the clinical data. Thus, a transient change in rhythm, rate, or electrical conduction may produce lethal metabolic acidosis unless the acidosis is quickly corrected. Diminished peripheral flow coupled with increased peripheral resistance may also produce metabolic acidosis. Diminished aortic pressure may further compromise coronary arterial flow and pulmonary flow. Elevated left ventricular end-diastolic pressure may raise pulmonary artery pressure high enough to produce lethal pulmonary edema or produce marked structural and functional pul-
monary changes with resultant hypoxia severe enough to intensify myocardial derangement. All these factors indicate that it is not solely the size of the infarct that determines the outcome of rnyocardial infarction. Although power failure and conduction failure have been useful in directing efforts to treat myocardial infarction, frequently each is present in variable degrees and each may be both cause and effect of the other. It is because of all these factors and in this sense that most ischernic hearts are too good to die. CLINICAL Sxxis OF FAILURE ISCHEMICHEART
OF
The cardinal and first manifestations of the failure of the ischemic heart to function normally are pain, dyspnea and syncope. The last is commonly due to failure of the normal electrical conduction; the second to failure to maintain a normal left ventricular end-diastolic pressure ; the first is probably due to many factors, some of which are as yet undetermined. Certainly angina pectoris is not caused solely by left ventricular end-diastolic hypertension19 or by inadequate blood flow to muscle and to anaerobic metabolism, because either condition may be present without cardiac pain. Cardiac Pain: Pain indistinguishable from angina pectoris can be produced by infusing norepinephrine into subjects with coronary, hypertensive and rheumatic valvular disease. Similar pain is frequently present during acute spontaneous elevations of arterial pressure in ischemic heart disease and in pheochromocytoma. A rise in blood pressure is a frequent accompaniment of cardiac pain that ushers in a myocardial infarction. It would appear, therefore, that a sudden release of norepinephrine and other unidentified substances that acutely stress the heart can produce angina pectoris in a conscious person with a responsive nervous system. Intracardiac Pressure Failure: The first clinical signs of failure of the ischemic heart to function in a normal manner are the appearance of an additional heart sound, usually the fourth, rarely the third and frequently both the third and fourth heart sounds accompanied by accentuation of the pulmonic component of the second heart sound. These findings are due to failure of the left ventricle to maintain a normal end-diastolic pressure, as indicated by elevation of the pulmonary artery and right ventricular pressures.20 The importance of this pressure THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Coronary
Artery
Disease
failure is emphasized in one series in which no deaths occurred m subjects with normal pulmonary artery pressures. l8 This type of Eailure is not necessarily correlated with strok.e volume but is also affected by anxiety, pain, metabolic rate, hypoxia, temperature and heart rate; the last is an important determin.nnt of cardiac output. It is obvious that the smaller the stroke volume, the faster the heart rate must be to maintain cardiac output. It is also noteworthy that, when acute, such failures are usually not accompanied by pulsus alternans. Perhaps pulsus alternans is absent because the noninfarcted muscle is the main contributor to the ejection of blood from the left ventricle. This pressure failure does not imply the presen’ce of congestive heart failure because pulmonary blood volume is not or only insignificantly increased.21 In addition to modifications produced by arrhythmias, rupture and extramyocardial factors, this pressure failure may develop in several different directions: 1. The pressure failure may disappear spontaneously with or without a normal cardiac output at rest. The outlook. in such instances is good and particularly so if the cardiac output is normal. 2. The pressure failure potentiated by catecholamine-stimulated vasoconstrictors may reach such a degree that venous hypertension, pulmonary edema and even hepatomegaly may appear. This clinical syndrome resembles the clinical syndrome of congestive heart failure, but even in this syndrome the circulating b:lood volume can be less than normal. The decrease is caused not only by a redistribution of blood with stagnation but also by internal and external losses of plasma. It is particularly likely to be present when there is a marked fall in forward cardiac output so that the peripheral tissues are not adequately irrigated.22 True congestive heart failure may, of course, occur after salt and water are given to the patient. Pressure will be modified by the interactions of the amount of blood returning to the lungs, hypcxia and metabolic acidosis. The diminutioIi in forward cardiac output not only affects blood returning to the lungs but redistributes blood Ii-om the kidneys, liver and skin to the brain and heart. This redistribution of blood is similar to that which takes place during exercise in hea1th.y subjects, and, indeed, exercise will accentuate redistribution of blood in a subject with ischemic heart disease. The clinical manifestations of excessive and harmful redistribution of blood are oliguria and cold, clammy VOLUME
22,
JULY
1968
and
Cardiac
Failure
47
skin. The systemic blood pressure is frequently low because decreased forward cardiac output predominates over catecholamine-stimulated vasoconstriction, but the reverse may be true and the pressure may be as high as at the onset of acute myocardial infarction. On the other hand, low blood pressure (in acute myocardial infarction) may result from predominant peripheral vascular dilatation due to (a) reflexes from myocardium,23 (b) bradycardia (sinus or atrioventricular block, and (c) sedatives (morphine, Demerol@). In these syndromes the skin may be warm and dry even though urinary flow is decreasing. It should be remembered that heart rate and stroke volume, which may vary independently, are determinants of blood pressure and cardiac output. With bradycardia, the mean systemic blood pressure may be so low as to compromise renal function. I urge that the term shock, like the term heart failure unqualified, be abolished from medical literature because it has no precise operational or communicative meaning. Indeed it is because it lacks precise meaning that lethal therapy is still common practice. It should be remembered that a drop in blood pressure is a common event when a patient is recovering from acute myocardial infarction and that a systolic pressure below 90 mm. Hg is consistent with health and longevity. 3. The pressure failure may persist. This pressure failure with or without other types of failure is the commonest type of failure producing clinical disability in chronic coronary artery disease. P mitrale, a sustained systolic thrust of the lower third of the sternum, hilar clouding, increased vascularity of the upper lobes and decreased vascularity of the lower lobes of the lungs are signs of back pressure from a high left ventricular end-diastolic pressure and indicate a grave prognosis. Such patients will frequently die of a future acute myocardial infarction, pulmonary infarction, an arrhythmia, or some other complication without ever developing congestive heart failure or after having recovered from the acute congestive heart failure described in the previous paragraph. They are, however, the most prone to develop congestive heart failure. Modern medical therapy can frequently dissipate congestive failure should it be present and slightly lower pulmonary and left ventricular pressures through the mechanism of Laplace’s law and by a reduction in the pressure gradient between the coronary artery and coronary sinus, but if high pressure persists
48
Soloff
the prognosis may be changed little or not at all unless myocardial growth occurs.
SUMMARY A plea is made to abandon the abstract, nonoperational term heart failure and to describe the ways in which the heart functions abnormally. Such an operational approach clearly shows that any type of failure-clinical, biophysical, biochemical, molecular-may be present in the absence of congestive heart failure, a type that requires the participation of Furthermore, the extramyocardial factors. operational approach clearly indicates that one cannot distinguish the cause from effect without knowledge of the temporal relations of the two. Lastly, an event may be the effect of one phenomenon and the cause of another which, in turn, can modify the first. It is because of these vicious circles that death is usually not caused by exhaustion of the heart but by extracardiac factors that are incompatible with life. The fundamental cause of failme of the ischemic heart to function normally lies in loss of contractile power of the block of muscles supplied by the occluded artery. The degree and subsequent types of failures will depend upon the size of the block of tissue deprived of its blood supply, its location, reactive fibrosis, the capacity of the uninvolved portion of the myocardium to compensate for the lesion, the extracardiac effects of abnormal vascular pressures, reflex and hormonal relations to the injury and the integrity of organs other than the heart. Each of these factors is discussed. REFERENCES I. SOLOFF, L. A. On the lack of meaning of heart failure. Am. Heart J., 66: 2, 1963. 2. SOLOFF, L. A. On Heart Failure: Observations and Concepts in Cardiovascular Drug Therapy, p. 380. New York and London, 1965. Grune & Stratton. A clinical and hemodynamic 3. MALMBORG, R. 0. analysis of factors limiting the cardiac performance in patients with coronary artery disease. Acta med. scandinao., Suppl. 426: 1, 1965. 4. ORIAS, 0. Dynamic changes in ventricles following ligation of ramus descendens anterior. Am. J. Physiol., 100: 629, 1932. 5. TENNANT, R. and WIGGERS, C. J. Effect of coronary occlusion on myocardial contraction. Am. J. Physiol., 112: 351, 1935.
6. WIGGERS, C. J. Physiology in Health and Disease, ed. 3, p. 710. Philadelphia, 1939. Lea & Febiger. 7. NOBLE, M. I. M., TRENCHARD, D. and Guz, A. Left ventricular ejection in conscious dogs. 1. Measurement and significance of the maximum acceleration of blood from the left ventricle. Circulation Ra., 19: 139, 1966. 8. SALAZAR, A. and SOLOFF, L. A. Unpublished observations. 9. GARLAND, L. H. and THOMAS, S. F. Roentgen diagnosis of myocardial infarction. J.A.M.A., 137: 762, 1948. IO. GORLIN, R., KLEIN, M. D. and SULLIVAN, J. M. Prospective correlative study of ventricular aneurysm; mechanistic concept and clinical recognition. Am. J. Med., 42: 512, 1967. 11. ABRAMS, D. L., EDILIST, A., LURIA, M. H. and MILLER, A. J. Ventricular aneurysm. A reappraisal based on a study of sixty-five consecutive autopsied cases. &a&km, 28: 164, 1963. 12. KLEIN, M. D., HERMAN, M. V. and GORLIN, R. A hemodynamic study of left ventricular aneurysm. Circulation, 35: 614, 1967. 13. HERMAN, M. V., HEINLE, R. A., KLEIN, M. D. and GORLIN, R. Localized disorders in myocardial contraction: Asynergy and its role in congestive heart failure. Nem England J. Med., 277: 222, 1967. 14. RAFFERTY, E. B.,OAKLEY, C. M. and GOODWIN, J. F. Acute subvalvular mitral incompetence. Lamt, 2: 360, 1966. 15. FRANKL, W. S., WINTERS, W. L. and SOLOFF, L. A. Cardiac output at rest and during exercise in patients with healed myocardial infarction. Am. J. M. SC., 249: 676, 1965. 16. MEERSON, F. Z. On mechanism of compensatory hyperfunction and insufficiency of heart. Car et uasa,3: 161, 1961. 17. SCHAPER, W. and VANDESTEENE,R. The rate of growth of interarterial anastamoses in chronic coronary artery occlusion. Life SC., 6: 1673, 1967. 18. HOLLENBERG, M., STENZEL, K. H. and RUBINS, A. L. Hypoxia: a stimulus to myocardial cell growth. (kbstr.). Circulation, 11 : i43, 1967. 19. MULLER, 0. and RORIK. K. Hemodvnamic consequencks of coronary heart disease ‘with observations during angina1 pain and the effect of nitroglycerin. Bril. Heart J., 20: 302, 1958. 20. POUMAILLOUX, M. Le Pouls Alternant. Paris, 1930. Masson et Cie. 21. SCHREIMER,B. F., MURPHY, G. W. and Yu, P. N. Pulmonary blood volume in congestive heart failure. Circulation, 34: 249, 1966. 22. AGRESS, C. M., ROSENBURG,M., SCHNEIDERMAN, A. and BROTMAN, E. J. Blood volume studies in shock resulting from myocardial infarction. I. Studies with Evans blue dye. J. Clin. Inuest., 29: 1267, 1950. 23. SLEIGHT, I’. A cardiovascular depressor reflex from the epicardium of the left ven!xicle in the dog. J. Pfzysiol., 173: 321, 1964.
Part II of Symposium will appear in August issue.
THE AMERICANJOURNALOF CARDIOLOGY
Artery Disease and the Concept of Cardiac
Failure
LOUIS A. SOLOFF, M.D. Philadelphia,
Pennsylvania
E
LSEWHERE’~~ I wrote that the unqualified term heart fazlure has no operational meaning because it fails to spell out which function or functions the heart fails to perform in a normal fashion. Many r,tudents use the term as a synonym for congestive heart failure. This is unfortunate because it perpetuates the concept and leads to the assumption that there is only one way in which the heart can fail. That this is untrue is recognized operationally by all physicians who treat patient,3 with heart disease, particularly patients with coronary artery disease and myocardial infarc:tion. As a matter of fact, almost all life-threatening dysfunctions of the heart are associated with abnormalities in blood pressures regardleas of the presence or absence of congestion. This statement is especially true today, now that powerful diuretics frequently can dissipate congestion but rarely can normalize pressures. Indeed, decongestive therapy can worsen a pressure type of failure. On the other hand, common definitions of heart failure, such as “no longer able to pump blood normally” and “unable to pump an adequate supply of blood in relation to the venous return and to the metabolic needs of the body,” are generalities that usually cannot be documented on clinical grounds; if taken literally, they include many clinical states that are not acceptable as heart failure by those very physicians who so define it. Congestive heart failure is a clinical syndrome characterized by dyspnea, generalized venous hypertension and congestion and edema attributable to the presence of heart disease, which is usually obvious and advanced. This clinical stat? represents the body’s reaction-reflex,
hormonal and environmental-to the heart’s failure to expel its contents in a normal fashion. The inability of the heart to expel blood in the normal fashion can be due not solely to intrinsic myocardial disease but also to other disturbances engrafted upon or producing myocardial faults. Some of these disturbances are valvular dysfunctions, arrhythmias, drug toxicity, hypoxia, acid-base imbalance, physical activity and the ingestion of salt. These extramyocardial factors are particularly apt to precipitate congestive heart failure in subjects with coronary artery disease because of the limited capacity of the left ventricle in this disorder to increase its ejection rate, stroke volume and cardiac output.3 Nonetheless, incapacitating cardiac disability and death frequently occur in patients with coronary artery disease without clinical evidence of congestive heart failure; yet no one doubts that the heart has failed in its most important function-to sustain life. Regardless of the type of cardiac failure present in subjects with coronary artery disease, the primary and fundamental cause resides in the myocardium, almost always in the left ventricle. MYOCARDIAL INFARCTION, VENTRICULAR ANEURYSM and CARDIAC FUNCTION Orias4 was the first to show that coronary artery occlusion deleted or impaired contraction in the block of myocardium deprived of its blood supply by the occluded vessel. Tennant and Wiggerss were the first to show that the ischemic region expanded in systole. Therefore, after coronary artery occlusion, a portion of the myocardium fails to contract normally. Wigger# also pointed out that myocardial disturbances
From the Division of Cardiology, Temple University Health Sciences Center, Philadelphia, Pa. This study was supported by U. S. Public Health Service Grant HE-05712-02 and by The Council For Tobacco Research-U.S.A. Address for reprints: Louis A. Soloff, M.D., Division of Cardiology, Temple University Health Sciences Center, 3401 N. Broad St., Philadelphia, Pa. 19140. VOLUME
22,
JULY
1968
43
Soloff produced by coronary occlusion frequently lead These to failure of normal electrical conduction. failures may be manifested by a variety of arrhythmias and conduction disturbances that further impair the ability of the heart to contract The degree and subsequent types normally. of failures will depend upon the size of the block of tissue deprived of its blood supply, its location, the capacity of the uninvolved portion of the myocardium to compensate for the lesion, the extracardiac effects of abnormal vascular pressures, reflex and hormonal reactions to the injury and the integrity of organs other than the heart. Tennant and Wiggerss clearly demonstrated the physiologic significance of interruption of coronary flow. Within a minute, aortic and pulse pressures are reduced and the form of the aortic pressure is altered; both phenomena indicate an immediate reduction in systolic discharge of the left ventricle. The heart has, therefore, failed to maintain normal contraction, More output and peripheral arterial pressure. sophisticated methods indicate that failure to maintain a normal ventricular ejection rate may be the earliest finding in myocardial infarction.7 This decreased ejection rate and decreased acceleration of ejected blood can be graphically illustrated by infusing a pellet of contrast substance into the left ventricle of a dog before and after ligation of a coronary artery.* A decreased, weakened and abnormally contracting segment of the left ventricle is, therefore, probably constantly present in myocardial infarction. This region may be too small to be recognized clinically and may be overlooked at necropsy because the left ventricle is motionless. Even aneurysmal lesions large enough to be recognized clinically and fluoroscopically may be overlooked at necropsy because the left ventricle is not examined under the influence of the pressure pulses which had been present during life. These abnormal and asynchronous contractions of the left ventricle, other factors being equal, will Indeed, a large tend to decrease cardiac output. infarcted segment of the left ventricle may act as a regurgitant chamber by distending when the normal left ventricular muscle is contracting. Such observations are not new. They were demonstrated (within the limitations of the method) decades ago, when kymography was popular, by the electrokymograph soon after this instrument was developed in our institution, and they were observed fluoroscopically over a generation ago.9 The angiocardiographic tech-
nic has permitted a more precise delineation of the contours of the left ventricular cavity and demonstration of these abnormal contractions. these abRecently, Gorlin et al. 10 documented normal contractions by tracing the angiocardiographic contours of the left ventricle throughIt is very likely, however, out the cardiac cycle. that their verbal distinctions are much sharper than those which actually occur in nature. Clinical Implications of Ventricular Aneurysm: Although abnormal contractions of the infarcted muscle are of great importance in contributing to cardiac dysfunction, it is our experience as well as that of others” that clinical disability, hemodynamic abnormalities and congestive heart failure are not necessarily related to the extent of the recognized asynchronous contracEven a huge asynchronous contracting tions. ventricular aneurysm is compatible with wellOn the other hand, debeing for decades. terioration can occur rapidly in persons in whom the heart fails to show asynchronous contraction Indeed, the survival angiocardiographically. rate of patients with ventricular aneurysm is not significantly different from the long-term survival of all patients with myocardial infarction. lo These observations, based upon clinical and necropsy data, appear to be inconsistent with the implications of a recent biomathematical analysis of the hemodynamic findings in subjects with ventricular aneurysm. l2 Although such work is laudable as a first approach, one should be aware of the methodologic errors and the questionable assumptions upon which conclusions are based. * OTHER
FACTORS DETERMINING HEART
FUNCTION IN MYOCARDIAL
INFARCTION
The clinical and pathologic anatomic observations suggest that there must be factors in addition to aneurysmal formation which de* I refer to the identity of left ventricular volume determined by the dye-dilution method and by angiothe subtraction of stroke volume detercardiography; mined by the dye-dilution method from the end-diastolic volume of the left ventricle determined by angiocardiography; the assumption that the apex of the heart is at the mid-left ventricular level; the use of undefined systolic radius and its error of measurement; the frame by frame measurement of left ventricular volume from films in one plane of a ventricle which is admittedly contracting abnormally and asymmetrically; the measurement of the volume of an aneurysm from films in one plane; and the assumption that the heart is a thin wall sphere. Finally, the characteristics of the non-aneurysmal muscle are unknown. THE AMERICANJOURNAL OF CARDIOLOGY
Coronary
Artery
Disease
termine how well and for how long the heart will function. Ehewhere I suggested* that some of these factors may be : I. Patchy Fibrosis: Patchy fibrosis may distort the architecture of the individual myocardial fibers and thereby distort the vectors produced by them.2v’3 The normal peristaltic contraction of the left ventricle may be partly disrupted by abnormal but grossly invisible asynchronous contracting myocardial fibers. The forces produced by the individual myocardial fibers may modify and even cancel each other; or myocardial fibers may be completely transfixed by an unyielding scar so that they cannot contribute to contraction. 2. The Location of the Infarct: For many years I have been impressed with the marked impairment of myocardial contraction when constrictive pericardi tis involves the left lower pole of the heart and with how often constriction is of little importance when it is limited to the free wall of the left ventricle. It may be that infarction is particularly disastrous if it involves a significant portion of the septum. Parenthetically, it is worth noting that in most patients who die with myocardial infarction the septum is involved. 3. Mitral Regurgitation: The commonest cause of an apical systolic murmur in the adult is coronary artery disease. Mitral regurgitation in ischemic heart disease may be (a) an insignificant lesion of little hemodynamic importance; (b) a significant contributing factor to cardiac disability, pulmonary hypertension and congestive heart failure; and (c) the predominant cause of failure of forward output of the left ventricle and elevated pressure behind it. It is important to distinguish between these three types. The last will require surgical correction of the mitral valve.14 The first requires no specific valvular treatment, and the second may or may not require such treatment, depending on the relative contribution of mitral regurgitation and intrinsic myocardial involvement to cardiac dysfunction. In our experience, a moderately loud and prolonged apical systolic murmur in a patient with coronary artery disease almost always is associated with subnormal cardiac output and response to effort. l5 An apical systolic murmur together with a localized, visible and forceful apical thrust in patients with ischemic heart disease indicates significant mitral regurgitation or an apical aneurysm. Apical aneurysms are characterized VOLUME
22,
JULY 1968
and Cardiac
Failure
45
by soft, relatively localized murmurs and a normal to slightly enlarged left ventricle. In mitral regurgitation the left ventricle is large, and the murmur has a mid-systolic accentuation and is widely distributed both toward the left axilla and toward the base of the heart. On the other hand, a large left ventricle in the absence of a localized, visible and forceful apical impulse indicates predominance of myocardial disease. In place of the apical thrust, there is a diffuse systolic heave of the precordium which may extend as far as the anterior axillary line and up to the third or even second intercostal space, findings indicative of aneurysmal enlargement of the left ventricle. In such instances, a soft apical murmur is secondary to cardiac enlargement. If such a heaving motion is accompanied by a localized and forceful apical thrust, one cannot exclude on clinical grounds significant hemodynamic mitral regurgitation and its contribution to cardiac disability. Roentgen-ray studies may be decisive for this differentiation. With significant mitral regurgitation, the pulsations of the left ventricular border are vigorous and wider than those of the ascending aorta. When mitral regurgitation is insignificant or absent, pulsations of the left ventricular wall are feeble and shallow. Because differentiation is potentially so important from the therapeutic standpoint, the ejection fraction of the left ventricle should be determined by angiocardiography. Indeed, the ejection fraction, the stroke volume and the end-diastolic pressure of the left ventricle are in my experience the most important objective data in evaluating the prognosis of ischemic heart disease. Strangely, the one exception in our experience has been the occasional presence of a large eccentric aneurysm of the left ventricle. I have already stated that patients with such lesions may lead comfortable lives for years. In such patients angiocardiography will demonstrate markedly exaggerated pulsations of the uninvolved portions of the myocardium, a finding which suggests that the ejection fraction of the nonaneurysmal myocardial portion is actually larger than normal. We have made similar observations, of hypercontractility of uninvolved myocardium in subjects with localized constrictive pericarditis. 4. The Capacity of the Uninvolved Portion of the Myocardium to Compensate for the Loss of Functioning Tennant and Wiggers.6 demonstrated Muscle: that hyperfunction of the uninvolved myocardium can quickly restore the myocardial
Soloff by myocardial infarction. power depressed Tachycardia, fever and increased secretion of catecholamines released from muscle and by reflex and hormonal reaction are some of the immediate methods of improving myocardial function. More important in the long run is the very old observation that hearts increase in weight soon after they are exposed to abnormally large loads. The complex biochemical mechanisms responsible for myocardial growth are now under intense investigation. l6 Equally important is an elucidation of the signals that initiate vascular and muscular growth. There is evidence that after myocardial infarction mitosis appears in the smooth muscle of vessel walls and thereby produces smooth muscle hyperplasia with increase in the volume of vessel walls.i7 Hypoxia itself appears to be a stimulus to the synthesis and growth of myocardial protein. l* Indeed, it would appear that there are only two ways in which spontaneous recovery from congestive heart failure (a frequent clinical phenomenon) can occur: one is self-limitation of the precipitating cause of congestive heart failure, and the other is growth of the myocardium including its vascular supply, mitochondria enzymatic activity and myoglobin content. 5. Extramyocardial Factors: The limited capacity of the ischemic left ventricle to increase its ejection rate, stroke volume and cardiac output makes it particularly vulnerable to extramyocardial factors such as ingestion of salt, physical activity, hypoxia, arrhythmia, acidbase balance and drug toxicity. Equally important, the ischemic heart, through reflex and hormonal action and through environmental changes, can impair functions of organs that are vital to optimal function of the heart and thereby can establish a number of vicious circles. These are some of the reasons why there is so little correlation between the size of infarcted myocardium observed at necropsy and the clinical data. Thus, a transient change in rhythm, rate, or electrical conduction may produce lethal metabolic acidosis unless the acidosis is quickly corrected. Diminished peripheral flow coupled with increased peripheral resistance may also produce metabolic acidosis. Diminished aortic pressure may further compromise coronary arterial flow and pulmonary flow. Elevated left ventricular end-diastolic pressure may raise pulmonary artery pressure high enough to produce lethal pulmonary edema or produce marked structural and functional pul-
monary changes with resultant hypoxia severe enough to intensify myocardial derangement. All these factors indicate that it is not solely the size of the infarct that determines the outcome of rnyocardial infarction. Although power failure and conduction failure have been useful in directing efforts to treat myocardial infarction, frequently each is present in variable degrees and each may be both cause and effect of the other. It is because of all these factors and in this sense that most ischernic hearts are too good to die. CLINICAL Sxxis OF FAILURE ISCHEMICHEART
OF
The cardinal and first manifestations of the failure of the ischemic heart to function normally are pain, dyspnea and syncope. The last is commonly due to failure of the normal electrical conduction; the second to failure to maintain a normal left ventricular end-diastolic pressure ; the first is probably due to many factors, some of which are as yet undetermined. Certainly angina pectoris is not caused solely by left ventricular end-diastolic hypertension19 or by inadequate blood flow to muscle and to anaerobic metabolism, because either condition may be present without cardiac pain. Cardiac Pain: Pain indistinguishable from angina pectoris can be produced by infusing norepinephrine into subjects with coronary, hypertensive and rheumatic valvular disease. Similar pain is frequently present during acute spontaneous elevations of arterial pressure in ischemic heart disease and in pheochromocytoma. A rise in blood pressure is a frequent accompaniment of cardiac pain that ushers in a myocardial infarction. It would appear, therefore, that a sudden release of norepinephrine and other unidentified substances that acutely stress the heart can produce angina pectoris in a conscious person with a responsive nervous system. Intracardiac Pressure Failure: The first clinical signs of failure of the ischemic heart to function in a normal manner are the appearance of an additional heart sound, usually the fourth, rarely the third and frequently both the third and fourth heart sounds accompanied by accentuation of the pulmonic component of the second heart sound. These findings are due to failure of the left ventricle to maintain a normal end-diastolic pressure, as indicated by elevation of the pulmonary artery and right ventricular pressures.20 The importance of this pressure THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Coronary
Artery
Disease
failure is emphasized in one series in which no deaths occurred m subjects with normal pulmonary artery pressures. l8 This type of Eailure is not necessarily correlated with strok.e volume but is also affected by anxiety, pain, metabolic rate, hypoxia, temperature and heart rate; the last is an important determin.nnt of cardiac output. It is obvious that the smaller the stroke volume, the faster the heart rate must be to maintain cardiac output. It is also noteworthy that, when acute, such failures are usually not accompanied by pulsus alternans. Perhaps pulsus alternans is absent because the noninfarcted muscle is the main contributor to the ejection of blood from the left ventricle. This pressure failure does not imply the presen’ce of congestive heart failure because pulmonary blood volume is not or only insignificantly increased.21 In addition to modifications produced by arrhythmias, rupture and extramyocardial factors, this pressure failure may develop in several different directions: 1. The pressure failure may disappear spontaneously with or without a normal cardiac output at rest. The outlook. in such instances is good and particularly so if the cardiac output is normal. 2. The pressure failure potentiated by catecholamine-stimulated vasoconstrictors may reach such a degree that venous hypertension, pulmonary edema and even hepatomegaly may appear. This clinical syndrome resembles the clinical syndrome of congestive heart failure, but even in this syndrome the circulating b:lood volume can be less than normal. The decrease is caused not only by a redistribution of blood with stagnation but also by internal and external losses of plasma. It is particularly likely to be present when there is a marked fall in forward cardiac output so that the peripheral tissues are not adequately irrigated.22 True congestive heart failure may, of course, occur after salt and water are given to the patient. Pressure will be modified by the interactions of the amount of blood returning to the lungs, hypcxia and metabolic acidosis. The diminutioIi in forward cardiac output not only affects blood returning to the lungs but redistributes blood Ii-om the kidneys, liver and skin to the brain and heart. This redistribution of blood is similar to that which takes place during exercise in hea1th.y subjects, and, indeed, exercise will accentuate redistribution of blood in a subject with ischemic heart disease. The clinical manifestations of excessive and harmful redistribution of blood are oliguria and cold, clammy VOLUME
22,
JULY
1968
and
Cardiac
Failure
47
skin. The systemic blood pressure is frequently low because decreased forward cardiac output predominates over catecholamine-stimulated vasoconstriction, but the reverse may be true and the pressure may be as high as at the onset of acute myocardial infarction. On the other hand, low blood pressure (in acute myocardial infarction) may result from predominant peripheral vascular dilatation due to (a) reflexes from myocardium,23 (b) bradycardia (sinus or atrioventricular block, and (c) sedatives (morphine, Demerol@). In these syndromes the skin may be warm and dry even though urinary flow is decreasing. It should be remembered that heart rate and stroke volume, which may vary independently, are determinants of blood pressure and cardiac output. With bradycardia, the mean systemic blood pressure may be so low as to compromise renal function. I urge that the term shock, like the term heart failure unqualified, be abolished from medical literature because it has no precise operational or communicative meaning. Indeed it is because it lacks precise meaning that lethal therapy is still common practice. It should be remembered that a drop in blood pressure is a common event when a patient is recovering from acute myocardial infarction and that a systolic pressure below 90 mm. Hg is consistent with health and longevity. 3. The pressure failure may persist. This pressure failure with or without other types of failure is the commonest type of failure producing clinical disability in chronic coronary artery disease. P mitrale, a sustained systolic thrust of the lower third of the sternum, hilar clouding, increased vascularity of the upper lobes and decreased vascularity of the lower lobes of the lungs are signs of back pressure from a high left ventricular end-diastolic pressure and indicate a grave prognosis. Such patients will frequently die of a future acute myocardial infarction, pulmonary infarction, an arrhythmia, or some other complication without ever developing congestive heart failure or after having recovered from the acute congestive heart failure described in the previous paragraph. They are, however, the most prone to develop congestive heart failure. Modern medical therapy can frequently dissipate congestive failure should it be present and slightly lower pulmonary and left ventricular pressures through the mechanism of Laplace’s law and by a reduction in the pressure gradient between the coronary artery and coronary sinus, but if high pressure persists
48
Soloff
the prognosis may be changed little or not at all unless myocardial growth occurs.
SUMMARY A plea is made to abandon the abstract, nonoperational term heart failure and to describe the ways in which the heart functions abnormally. Such an operational approach clearly shows that any type of failure-clinical, biophysical, biochemical, molecular-may be present in the absence of congestive heart failure, a type that requires the participation of Furthermore, the extramyocardial factors. operational approach clearly indicates that one cannot distinguish the cause from effect without knowledge of the temporal relations of the two. Lastly, an event may be the effect of one phenomenon and the cause of another which, in turn, can modify the first. It is because of these vicious circles that death is usually not caused by exhaustion of the heart but by extracardiac factors that are incompatible with life. The fundamental cause of failme of the ischemic heart to function normally lies in loss of contractile power of the block of muscles supplied by the occluded artery. The degree and subsequent types of failures will depend upon the size of the block of tissue deprived of its blood supply, its location, reactive fibrosis, the capacity of the uninvolved portion of the myocardium to compensate for the lesion, the extracardiac effects of abnormal vascular pressures, reflex and hormonal relations to the injury and the integrity of organs other than the heart. Each of these factors is discussed. REFERENCES I. SOLOFF, L. A. On the lack of meaning of heart failure. Am. Heart J., 66: 2, 1963. 2. SOLOFF, L. A. On Heart Failure: Observations and Concepts in Cardiovascular Drug Therapy, p. 380. New York and London, 1965. Grune & Stratton. A clinical and hemodynamic 3. MALMBORG, R. 0. analysis of factors limiting the cardiac performance in patients with coronary artery disease. Acta med. scandinao., Suppl. 426: 1, 1965. 4. ORIAS, 0. Dynamic changes in ventricles following ligation of ramus descendens anterior. Am. J. Physiol., 100: 629, 1932. 5. TENNANT, R. and WIGGERS, C. J. Effect of coronary occlusion on myocardial contraction. Am. J. Physiol., 112: 351, 1935.
6. WIGGERS, C. J. Physiology in Health and Disease, ed. 3, p. 710. Philadelphia, 1939. Lea & Febiger. 7. NOBLE, M. I. M., TRENCHARD, D. and Guz, A. Left ventricular ejection in conscious dogs. 1. Measurement and significance of the maximum acceleration of blood from the left ventricle. Circulation Ra., 19: 139, 1966. 8. SALAZAR, A. and SOLOFF, L. A. Unpublished observations. 9. GARLAND, L. H. and THOMAS, S. F. Roentgen diagnosis of myocardial infarction. J.A.M.A., 137: 762, 1948. IO. GORLIN, R., KLEIN, M. D. and SULLIVAN, J. M. Prospective correlative study of ventricular aneurysm; mechanistic concept and clinical recognition. Am. J. Med., 42: 512, 1967. 11. ABRAMS, D. L., EDILIST, A., LURIA, M. H. and MILLER, A. J. Ventricular aneurysm. A reappraisal based on a study of sixty-five consecutive autopsied cases. &a&km, 28: 164, 1963. 12. KLEIN, M. D., HERMAN, M. V. and GORLIN, R. A hemodynamic study of left ventricular aneurysm. Circulation, 35: 614, 1967. 13. HERMAN, M. V., HEINLE, R. A., KLEIN, M. D. and GORLIN, R. Localized disorders in myocardial contraction: Asynergy and its role in congestive heart failure. Nem England J. Med., 277: 222, 1967. 14. RAFFERTY, E. B.,OAKLEY, C. M. and GOODWIN, J. F. Acute subvalvular mitral incompetence. Lamt, 2: 360, 1966. 15. FRANKL, W. S., WINTERS, W. L. and SOLOFF, L. A. Cardiac output at rest and during exercise in patients with healed myocardial infarction. Am. J. M. SC., 249: 676, 1965. 16. MEERSON, F. Z. On mechanism of compensatory hyperfunction and insufficiency of heart. Car et uasa,3: 161, 1961. 17. SCHAPER, W. and VANDESTEENE,R. The rate of growth of interarterial anastamoses in chronic coronary artery occlusion. Life SC., 6: 1673, 1967. 18. HOLLENBERG, M., STENZEL, K. H. and RUBINS, A. L. Hypoxia: a stimulus to myocardial cell growth. (kbstr.). Circulation, 11 : i43, 1967. 19. MULLER, 0. and RORIK. K. Hemodvnamic consequencks of coronary heart disease ‘with observations during angina1 pain and the effect of nitroglycerin. Bril. Heart J., 20: 302, 1958. 20. POUMAILLOUX, M. Le Pouls Alternant. Paris, 1930. Masson et Cie. 21. SCHREIMER,B. F., MURPHY, G. W. and Yu, P. N. Pulmonary blood volume in congestive heart failure. Circulation, 34: 249, 1966. 22. AGRESS, C. M., ROSENBURG,M., SCHNEIDERMAN, A. and BROTMAN, E. J. Blood volume studies in shock resulting from myocardial infarction. I. Studies with Evans blue dye. J. Clin. Inuest., 29: 1267, 1950. 23. SLEIGHT, I’. A cardiovascular depressor reflex from the epicardium of the left ven!xicle in the dog. J. Pfzysiol., 173: 321, 1964.
Part II of Symposium will appear in August issue.
THE AMERICANJOURNALOF CARDIOLOGY