The management of acute coronary insufficiency

THE MANAGEMENT OF ACUTE CORONARY INSUFFICIENCY JOHN BAKER GALEN S. WAGNER JOSEPH O. GREENFIELD, JR.

TABLE

OF CONTENTS

CORONARY INSUFFICIENCY:

PREtIOSPITAL PIIASE

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CORONARY INSUFFICIENCY:

HOSPITAL PHASE . . . . . . .

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Antifibrillatory Prophylaxis . . . . . . . . . . . .

6

Diagnosis: U n s t a b l e A n g i n a or Infarction . . . . . . .

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M a n a g e m e n t of U n s t a b l e A n g i n a . . . . . . . . . .

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H e a r t F a i l u r e in Acute Myocardial Infarction Prophylactic T e m p o r a r y P a c i n g

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CORONARY INSUFFICIENCY: POSTHOSPITAL PHASE

Permanent Pacemakers

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E a r l y Discharge . . . . . . . . . . . . . . . .

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CORONARY INSUFFICIENCY: TIlE FUTURE . . . . . . . .

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SUMMARY .

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received his Doctorate of Medicine from Harvard Medical School in 1971 before serving an internship and residency in medicine and Fellowship in Cardiology at the Duke University Medical Center. After two years in the U.S. Air Force at Keesler Air Force Base he will return to Duke University as an Assistant Professor of Medicine and Director of the Coronary Care Unit at the Durham Veterans Administration Hospital. Itis research interests include the management of the clinical manifestations of coronary artery disease.

is Associate Professor of Medicine and Director of the Cardiac Care Unit, Duke University Medical Center. Doctor Wagner received his M.D. degree and his training in internal medicine and cardiology from Duke University. His research goals include the development of quantitative criteria for localization of infarction by vectorcardiography, the establishment of the prognostic significance of common complications of acute myocardial infarction, and the development of the computerized data bank to facilitate improved management of chronic illnesses.

is Professor of Medicine, Duke University Medical Center. A staff member at the Durham Veterans Administration Hospital, Dr. Greenfield received his M.D. degree from Emory University and completed his training in internal medicine at Duke University. tte also served as Clinical Associate at the National tIeart Institute from 1959-1962. tiis principal research interests are myocardial blood flow, myocardial mechanics, and clinical electrocardiography.

CORONARY INSUFFICIENCY* is a term that describes a pathologic state in which the available coronary blood flow is inadequate to meet the metabolic demands of the myocardium. Its clinical expression is variable, but is most commonly manifested as chest pain occurring in a spectrum of clinical syndromes ranging f r o m infrequent episodes of stable angina pectoris to acute myocardial infarction. The purpose of this review is to present recently acquired data about the natural history and pathophysiology of coronary insufficiency and, where possible, to attempt to reach conclusions about the management of these various clinical manifestations. Only information deemed to be useful to the clin.ician in approaching the patient with coronary insufficiency Will be presented. Therapeutic approaches that are controversial or unproved will be avoided except to indicate avenues of future investigative effort. The over-all format will be to examine, in the sequence in which they are likely to arise, some common problems presented by the patient with coronary insufficiency during the period between the onset of symptoms and the resolution of the acute episode. This period arbitrarily will be divided into prehospital, hospital and posthospital phases of acute coronary insufficiency.

CORONARY INSUFFICIENCY: PREHOSPITAL PHASE The most devastating manifestation of coronary insufficiency is sudden death. It is estimated that 40-60% of patients with acute coronary insufficiency die outside the hospital, the majority within the first hour after the onset of symptoms.2 If the annual mortality from existing coronary artery disease is to be reduced significantly, these patients must be identified and treated either before or within minutes after the onset of the acute event. It is unfortunate that the acute symptoms may be nonspecific, causing both the patient and the physician not to suspect coronary insufficiency. Alonzo et al? have demonstrated that 64% of patients who died suddenly outside a hospital had been experiencing prodromal symptoms *Dr. Paul Wood ~ used this same phrase to denote a specific clinical syndrome that we prefer to call "unstable angina."

(defined as a significant deviation from normal or usual health) for a mean period of 30 days. However, only 36% of the patients with prodromal symptoms consulted a physician. In 79% of this group, dyspnea and/or chest pain were described in the symptom complex. Chest pain probably is a very sensitive* (but unfortunately a very common and nonspecific) indicator of coron a ry insufficiency. In the F r a m i n g h a m study of 269 myocardial infarctions documented by electrocardiography, 60 (23%) were detected only during the routine biennial examinations. 4 A careful retrospective history, however, revealed some type of chest pain in 20 of the patients and only 10 reported no interim illness of any sort. Thus, 85% of electrocardiographically documented myocardial infarctions occurred in patients who experienced chest pain and only 3.7% in patients who were completely asymptomatic. Jeo p ar d y of sudden death is produced by ischemia and does not require the onset of acute infarction. Patients with coronary a r t e r y disease m ay develop ventricular fibrillation, from which they are resuscitated successfully and d e mo n s tr ate no subsequent evidence of myocardial infarction.5.6 This observation is supported by the demonstration t h a t experimentally reversible occlusion of a coronary art e ry iri the dog m ay be m a i nt a i ne d for up to 20 minutes without the production of necrosis. ~ W i t h i n seconds, however, the ischemic muscle ceases to contract and the ventricle is prone to electrical instability and fibrillation. Indeed, reperfusion of an ischemic segment at a critical time ( 1 5 - 2 0 minutes following occlusion) prior to the onset of necrosis may result in ventricular fibrillation. It is apparent from both clinical and experimental data t h a t coronary insufficiency of br i e f duration, inadequate to produce myocardial necrosis, can initiate ventricular fibril*The terms sensitivity and specificity will be used frequently in this review and are defined as follows: An indicator is considered 100% sensitive when it is present in every patient with the disease in question. An indicator is considered 100% specificwhen it always is absent in patients without the disease. The absence of an extremely sensitive indicator is good evidence for exclusion of the disease. The presence of an extremely specific indicator is good evidence for the presence of the disease. The absence of an insensitive indicator or the presenceofa nonspecificindicator is not diagnostically helpful. 5 .

lation and sudden death and that this terminal event often is heralded by prodromal symptoms. For this reason, the patient with symptoms suggesting acute coronary insufficiency must be placed under "coronary care" during the period of establishment of a definitive diagnosis. "Coronary care" should include: (1) electrocardiographic monitoring by trained personnel, (2) a stable intravenous line, (3) lidocaine prophylaxis unless specifically contraindicated and (4) the availability of a defibrillator and emergency medications. Webb and co-workerss have documented many important aspects of the prehospital phase during 10 years of clinical research in Belfast. It is unusual for patients encountered during the first half hour to have both heart rate and arterial pressure within "normal" limits. Indeed, 55% of patients with acute posterior involvement had both hypotension and bradycardia. Most were managed successfully with atropine. Warren and Lewis 9 have confirmed this observation and have demonstrated that it does not always remit in the absence of atropine therapy. Furthermore, patients who have rhythm stabilization within the first hour have a remarkably low (5%) incidence of subsequent cardiogenic shock when compared with other patients managed in the same coronary care unit (13%). ~~ This suggests that additional myocardium is infarcted as a result of poor coronary perfusion and high myocardial demands during the period of unstable rhythm and hemodynamics prior to the onset of "coronary care." Thus, future modifications during the hospital phase may indeed salvage ischemic myocardium, but only if the prehospital phase can be remarkably reduced. CORONARY INSUFFICIENCY: HOSPITAL PHASE ANTIFIBRILLATORY PROPHYLAXIS

When the patient with suspected coronary insufficiency has been identified and.placed under observation, therapy should be directed at the prevention of sudden death from ventricular fibrillation. Initial efforts in the specialized coronary care areas were directed at the identification and electrical conversion of potentially lethal rhythm distur-

bances. The inadequacy of this approach became apparent for two reasons. First, occasionally episodes of ventricular fibrillation are refractory to electrical reversion. Second, the hypotension and trauma surrounding cardiac arrest and successful defibrillation could have an adverse effect on infarct size and increase subsequent morbidity and mortality. Lown et al. 11 suggested that intravenous lidocaine could prevent ventricular fibrillation if used prophylactically. These investigators identified specific "warning arrhythmias"* that commonly precede ventricular fibrillation, and the presence of these became widely accepted as an indication to initiate intravenous lidocaine therapy. Several studies have questioned the significance of these warning arrhythmias. Most recently, Lie et al. ~ withheld antiarrhythmic therapy from 262 patients with acute myocardial infarction. Twenty developed ventricular fibrillation. Eight of these had no "warning arrhythmias" and 11 episodes were initiated by late diastolic premature ventricular contractions. Moreover, 50% of the total group of patients displayed "warning arrhythmias" but never developed ventricular tachycardia or fibrillation. These data documented the need for a uniform, effective prophylaxis independent of"warning arrhythmias." Lie et al. ~3 have also demonstrated the effectiveness of lidocaine as the prophylactic agent (Table 1). Two hundred twelve consecutive patients under age 70 who were admitted to the hospital w i t h i n 6 h o u r s of the onset of symptoms of an acute myocardial infarction were randomized in a double-blind fashion to a control group or a treatment group that received intravenous lidocaine for 48 hours. After randomization, patients were removed from the study only if they developed ventricular tachycardia Or ventricular fibrillation. The "warning arrhythmias" were n o t used as a criterion for removal from either study group. Nine patients in the control group developed ventricular fibrillation and none in the treatment group, a highly significant difference. Eight of the 9 patients with ventricular fibrillation were defibrillated successfully. Four of these 9 patients *These were defined as greater than 5 premature ventricular contractions (PVC) per minute, multifocal PVCs, two or more consecutive PVCs or a PVC falling on the T wave of the preceding Q R S - T complex.

TABLE 1.--212 CONSECUTIVE PATIENTS WITH ACUTE MYOCARDIAL INFARCTION-6 HOURS FOLLOWING ONSET OF SYMPTOMSRANDOMLY ALLOCATED TO LIDOCAINE* AND CONTROL GROUPSt LIDOCAINE

CO/~rROL

Number of patients 107 105 No ventricular arrhythmias 27 14 "Warning arrhythmia" 34 61 Ventricular fibrillation 0 11 "Lidocaine reaction" 16 *100 mg bolus, then 3 rag/rain x 48 hours. tAdapted from Lie et al., N. Engl. J. Med. 291:1324, 1974. had no antecedent "warning arrhythmias" and would not have received lidocaine by commonly accepted criteria for the initiation of therapy. Several points about this study deserve emphasis. First, the study population was restricted to patients who were admitted within 6 hours of the onset of symptoms. Since the frequency of ventricular fibrillation is greatest in the early hours following the onset of symptoms, the study involved a select, high-risk subgroup of patients in whom the benefit of antifibrillatory prophylaxis was easily demonstrated. Early admission and initiation of therapy are the critical first steps in establishing effective intravenous lidocaine prophylaxis. A second point, of equal importance, is that 32% of the treatment group developed "warning arrhythmias" despite the high dose of lidocaine used (100 mg bolus followed by a constant infusion at the rate of 3 mg/min), yet there were no episodes of ventricular fibrillation in this group. This would imply that the therapeutic end point should not be the total suppression of the so-called warning arrhythmias but rather the maintenance of lidocaine blood levels that are adequate to raise the fibrillatory threshold and to prevent ventricular fibrillation during the critical early hours following the onset of coronary insufficiency. With the dose of lidocaine used in this study, 15% of the treated patients developed drowsiness, paresthesias, dizziness or speech disturbances. These symptoms required reduction of the infu-

sion rate in 7 patients. Thus, further increases in the infusion rate directed at suppression of the "warning arrhythmias" quite likely would have resulted only in more frequent or more serious side-effects with no therapeutic gain. It is possible that an infusion rate of 2 mg/min may be equally effective and may produce fewer side-effects. Proof of this awaits a similarly well-designed study comparing 2 mg/min with 3 mg/min. We have developed the following protocol for lidocaine prophylaxis: (1) Initiate 1 mg/kg bolus and 2 mg/min drip when the patient with symptoms suggesting acute coronary insufficiency is first encountered. (2) Use drip control device on the intravenous line. (3) Do not depend on the drip to achieve sufficient blood levels until 1 hour. Give additional 1 mg/kg bolus injections at 20 and 40 minutes. (4) Do not increase the lidocaine in response to "warning arrhythmias." (5) Discontinue drip abruptly at 36-48 hours in the absence of recurrent symptoms of coronary insufficiency. This provides time for continuous ECG monitoring to facilitate decisions regarding the necessity for long-term antiarrhythmia prophylaxis. DIAGNOSIS: UNSTABLE ANGINA OR INFARCTION

After patients with suspected coronary insufficiency have been admitted to the hospital, they can be divided into two groups: (1) those who have and (2) those who have not experienced myocardial necrosis as a result of ischemia. The detection of myocardial necrosis (the diagnosis of acute myocardial infarction) is based on the presence of combinations of chest pain, electrocardiographic changes, changes in serum enzymes and abnormalities detected by radionuclide scanning techniques. In experimental animals, the duration of coronary occlusion is related to the appearance of cellular necrosis distal to the occlusion.~ Clinically, the duration of chest pain has been used as one clue to the presence of myocardial necrosis. Yet, chest pain, regardless of its duration, is too nonspecific to be diagnostic by its presence alone, and other clinical indices, i.e., the electrocardiogram, serum enzymes or myocardial imaging, must be used to detect necrosis. The only electrocardiographic change that is specific for

myocardial necrosis is the appearance of new Q waves. Isolated ST segment shifts and T wave changes are nonspecific and, by themselves, should not be used to influence the diagnosis. However, new Q waves do not appear in 3 4 - 44% of acute infarctions as documented by serum enzymes, or they cannot be assessed because of the presence of previous infarction, left ventricular hypertrophy or left bundlebranch block. '4, 15 New Q waves are a specific but relatively insensitive indicator of necrosis; their appearance is diagnostic but their absence is not helpful. The reverse is true for the enzymes serum glutamic oxaloacetic transaminase (SGOT), lactic dehydrogenase (LDH) and creatine phosphokinase (CPK). They are sensitive indicators of myocardial necrosis, and it is unusual for any of the three to remain normal during the 4 8 - 7 2 hours after the onset of symptoms in the presence of necrosisJ ~ They are nonspecific, however, and can be elevated in a variety of other conditions. The physician can overcome this disadvantage to some extent by collecting serial serum samples over several days and b y o b s e r v i n g a characteristic pattern of elevation and resolution as noted in Figure 1. The CPK rises and peaks early, followed by SGOT and finally the LDIt. It is .important to realize that the curves that one is Fig 1.-Typical pattern of evolution of serum enzymes following myocardial necrosis: serum glutamic'oxaloacetic transaminase (SGOT), lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and the myocardial specific isoenzyme of creatine phosphokinase (CPK-MB). (See text for further details.)

Serum

Enzyme Level

~

0

I

_N.~r.~L______~___ _ H

2

3

4 boy

10

S zz

I0

able to construct will depend on the proximity of the times of sampling and the onset of symptoms. The most recent advance in diagnostic enzymology has been the identification of tissue specific isoenzymes. Isoenzymes are enzymes that catalyze the same chemical reaction b u t differ in certain physical properties, which facilitates their separation and identification. Five LDH isoenzymes have been identified and are numbered 1 through 5. The normal serum pattern is an L D H 1 level that is less than the LDI-I2 level. With myocardial necrosis, this pattern is reversed, and the level of LDH~ exceeds that of LDH 2. Since this pattern may persist after the CPK level has fallen to normal, i t s presence m a y be helpful in patients who present several days after the onset of symptoms with a normal level of CPK. The LDH1 > LDH 2 pattern is not specific for myocardium and can appear with hemolysis of red blood cells, either in vivo or in vitro, and with renal cellular necrosis. The most important recent advance in the detection of myocardial necrosis has been the identification of CPKMB, an isoenzyme of CPK that is specific for myocardium. Clinical studies now have been published that indicate that it is both highly sensitive and highly specific, x4-'8 Absence* of CPK-MB from the serum during the 24 hours following the onset of symptoms virtually excludes a diagnosis of myocardial infarction. Its presence in the serum is transient, however, and its absence is meaningful only if frequent sampling (every 8 hours) has been initiated during the 24 hours following the onset of symptoms. The presence of CPK-MB in the serum is virtually diagnostic of myocardial necrosis in patients who have not had a previous resuscitative effort that involved closed chest massage or intracardiae needle puncture. '9 There are certain limitations to the diagnostic capability of CPK-MB. The isoenzyme has been reported to be absent from the serum of several patients with a clinical history and serial electrocardiographic changes that are diagnostic of myocardial necrosis. These patients had low levels of *We use the terms "present" and "absent" in this discussion because the electrophoretic assays do not detect CPK-MB in normal serum. Other methods do detect CPK-MB in normal serum, but at extremely low levels. 11

total CPK, and the intervals between serum samples were greater than 12 hours. CPK-MB has been found in the serum of patients with myocardial t r a u m a of various types, ~9 myositis, 2~ Duchenne's muscular dystrophy 2~ and Reye's syndrome. 2" The latter groups of patients had no evidence of myocardial damage at autopsy, suggesting that the CPK-MB had originated from the diseased skeletal muscle. However, these diseases usually are obvious clinically and are not likely to be confused with coronary insufficiency. Roark e t al. ~c have observed the myocardial infarction diagnostic process in a community hospital. CPK isoenzymes were determined but the results were not revealed to the physicians. Remarkably, there was no occasion when CPK-MB was detected but the physician did not diagnose infarction. However, in 30% of the instances of diagnosis of infarction, CPK-MB was never detected. Indeed, no patient in whom either total CPK, LDt-I or SGOT remained within normal limits had CPK-MB and only 50% of those without QRS changes on ECG and elevated levels of all three enzymes had CPK-MB. Thus, the physician errs toward overdiagnosis, and many patients are incorrectly labeled as having acute myocardial infarction. Newer techniques may further enhance the sensitivity and specificity of diagnosis of infarction and might even permit quantitation of the amount of ischemic or infarcted myocardium. Imaging of both normal and necrosing myocardium using a variety of radioactive agents currently is an area of active research and may provide additional diagnostic capability. Myocardial scintigraphy using technetium-99m stannous pyrophosphate, which appears to bind with calcium complexes that form in the mitochondria of necrotic cells, has been evaluated clinically. Willerson e t a l Y 3 determined that scans performed 12 hours to 6 days (optimal time 1 - 3 days) after the onset of symptoms in patients with both "transmural" and "subendocardial" myocardial infarction are 100% sensitive indicators of necrosis. However, using similar diagnostic techniques, this same group reported a 34% incidence of positive scans in patients with unstable angina but no evidence of acute infarction (failure to evolve Q waves and normal total serum enzymes; CPKMB was not measured). 2~ Using the presence of CPK-MB to 12

define necrosis in 168 patients, Klein e t al. 25 found the technetium-99m stannous pyrophosphate scan to be 80% sensitive and 100% specific. Obviously, further comparative studies must be performed before the precise value and limitations of technetium-99m pyrophosphate scanning can be determined. Studies comparing the early transient appearance of CPK-MB to the somewhat later optimal time for scanning may resolve some apparent discrepancies and may demonstrate that these two techniques are temporally complementary. Other reported causes of false positive scans include direct-current countershock producing skeletal muscle necrosis, 26 left ventricular aneurysms from previous infarction, 27 primary cardiomyopathies, 2s penetrating myocardial t r a u m a and carcinoma metastatic to the myocardium. 29 In summary, chest pain, although probably a very sensitive indicator of coronary insufficiency, is too nonspecific to be useful in the identification of myocardial necrosis. It places a patient under suspicion, but definitive diagnosis depends on changes in the electrocardiogram and various serum enzymes. ST segment changes, T wave changes and isolated elevation of a single enzyme concentration are nonspecific and must be interpreted cautiously. Only the appearance of new Q waves, the evolution of a characteristic pattern of serial enzyme determinations and the presence of CPK'-MB a.re specific for necrosis and are diagnostic by their presence. CPK-MB is extremely sensitive and is useful in excluding myocardial necrosis if absent in appropriately timed serum samples. Myocardial scintigraphy may prove to be a valuable additional diagnostic tool. None of these indicators, however, can exclude coronary insufficiency as a cause of chest pain. They are useful only in confirming or excluding the presence of myocardial necrosis. MANAGEMENT OF UNSTABLE ANGINA

One subgroup of patients admitted to the hospital because of suspected acute coronary insufficiency has ST segment and T wave changes b u t neither QRS nor enzymatic changes diagnostic of an acute myocardial infarction. Several rigidly structured and randomized clinical trials of 13

~hedical versus surgical therapy in these patients are in progress; preliminary results published to date provide useful information regarding the clinical approach to patients with this syndrome?~ Coronary angiography can be performed safely d u r i n g t h e period when symptoms are unstable. Eight per cent to 10% of these patients do not have angiographically demonstrable "significant" coronary arterial occlusions. All patterns of coronary occlusions have been observed in patients in each category of ST segment and T wave change. Maseri e t a l ? 3 have determined the pathoanatomic process in variant (Prinzmetal's) angina. Repeat angiography during periods of ST segment elevation demonstrated complete occlusion of vessels that previously had been normal or less than totally occluded. Decreased perfusion was documented by absence of thallium-. 201 uptake? 4 Reversal of this acute occlusion after sublingual nitroglycerin suggested that variant angina in these patients was produced by coronary artery spasm. In a minority of patients, the unstable angina is refractory to medical therapy, and surgery is indicated if the anatomy is compatible. When the ongoing randomized studies3.~1 of patients with potentially operable anatomy have been completed, perhaps the role of surgery in the prevention of infarction and the prolongation of survival will be revealed. HEART FAILURE IN ACUTE MYOCARDIAL INFARCTION

PATHOPHYSIOLOGY.- A s noted previously, severe myocardial ischemia promptly causes loss of mechanical function as well as electrical instability. If a significant portion of the ventricular myocardium fails to contract, t h e stroke volume and cardiac output will decrease. Internal compensatory mechanisms and therapeutic measures initiated by the patient interact to determine whether the problem will resolve or myocardial infarction will occur. Either massive infarction alone or lesser infarction accompanied by excessive intrinsic or extrinsic "compensation" can produce clinical signs and symptoms of heart failure. Heart failure as a complication of acute myocardial infarction can be defined in several ways. Failure to provide an adequate cardiac output results in the clinical syndrome

14

of cardiogenic shock. This is a form of heart failure that is defined by manifestations of inadequate organ perfusion, such as pallor, confusion and oliguria. The more classic definition of heart failure relates to abnormal pressures rather than to inadequate flow. An elevated left ventricular filling pressure produces a ventricular gallop, pulmonary rales and chest x-ray findings of pulmonary venous hypertension and pulmonary edema. This form of heart failure commonly is referred to as "congestive heart failure" because of the fluid that accumulates in the lungs as pulmonary venous pressure rises. Thus, the heart can fail to perform its function adequately in terms of either "forward" blood flow or "backward" diastolic filling. There are four major determinants of the cardiac output: (1) heart rate, (2) ventricular afterload, the impedance t o ventricular ejection during systole, (3) ventricular contractility and (4) ventricular preload, the pressure that fills the ventricle during diastole. Increases in ventricular preload produce augmentation of stroke volume by the Starling mechanism. It may seem to be somewhat of a paradox that an excess of one of the prime determinants of the cardiac output, ventricular filling pressure, is responsible for producing the clinical manifestations of "congestive heart failure." A clear understanding of this apparent paradox is important to understanding the management of patients with myocardial infarction that is complicated by pulmonary edema and/or cardiogenic shock. Clinical experience now has clearly demonstrated.that a moderate increase in ventricular filling pressure may be considered compensatory, indeed critical to the maintenance of an adequate cardiac output by the heart that has a significant part acutely infarcted. Our understanding of the relationship of ventricular filling pressure to "heart failure" and to the cardiac output during acute myocardial infarction has been facilitated by the introduction of the flow-directed, balloon-tipped catheter by Swan and Ganz e t a l ? ~ This catheter has permitted safe and accurate indirect measurement of left ventricular filling pressure in acutely ill patients. In the absence of increased pulmonary vascular resistance and mitral valve obstruction, the pulmonary artery diastolic pressure may be considered an indirect measure~5

ment of left ventricular filling pressure. In the presence of chronic pulmonary disease, or pulmonary embolism, this pressure may be higher than the true left ventricular filling pressure. In this setting, a more accurate approximation of left ventricular filling pressure is a balloon-occluded, mean "wedge" pressure. This is obtained by inflating the balloon on a flow-directed catheter that has been positioned in the pulmonary artery. This wedge pressure reflects mean left atrial pressure, which, in the absence of mitral valve obstruction, determines left ventricular filling. The pulmonary artery diastolic pressure and the balloonoccluded mean wedge pressure are elevated in the majority of patients with acute myocardial infarction, and a correlation exists between an increase in these pressures and the severity of the clinical illness. In patients who survive, the natural history seems to be a slow, progressive decline toward normal. Patients with extensive infarction and persistent pulmonary congestion, however, may have persistent elevation of these pressures. Rotman e t a l ? 6 correlated the pulmonary artery diastolic pressure with the classic clinical manifestations of elevated left ventricular pressures: (1) the ventricular gallop, (2) pulmonary rales and (3) the roentgenographic findings of pulmonary congestion. The chest films were portable, 6foot, posteroanterior views taken with the patient sitting. Of the patients with a pulmonary artery diastolic pressure of 15 mm Hg or above, 60% had a ventricular gallop, 72% had rales and 88% had an abnormal chest x-ray. Of those with a pressure of 14 mm Hg or below, 8% had a ventricular gallop, 20% had rales and 20% had an abnormal chest x-ray. If "abnormal chest x-ray" is limited to patients with cephalization of the pulmonary veins,* vascular blurring and perihilar haze, 70% of those with elevated pressures but none with normal pressures had an "abnormal" film. Results of applying these criteria are summarized in Table 2. Rales are neither sensitive nor specific and therefore are not diagnostically helpful. A ventricular gallop, although quite specific, is absent in 40% of patients with abnormal pressure. Therefore, it is helpful when present, but its ab*Cephalization of the pulmonary veins: Diameter of superior veins greater than diameter of inferior veins. 16

TABLE 2.-SENSITIVITY AND SPECIFICITY OF CLINICAL INDICATORS OF ELEVATED VENTRICULARFILLING PRESSURE* PULMONARY

RALES

VENTRICULAR

GALLOP

Wedge pressure + + (mm Hg) _>15 72% 28% 60% 40% <15 20% 80% 8% 92% *Adapted from Rotmanet al., Am. J. Cardiol. 33:357, 1974.

ABNORMAL CILEST X-RAY

+

-

70% 30% 0% 100%

sence does not exclude an elevated pressure. The abnormal chest x-ray (as defined here) is comparable in value to the ventricular gallop in its diagnostic accuracy. Because of the insensitivity of these objective data, the category clinically u n c o m p l i c a t e d (defined as no ventricular gallop or pulmonary rales) myocardial infarction includes a significant number of patients with distinctly abnormal hemodynamics. In this study, 47% of patients with no rales and no ventricular gallop had elevated pulmonary artery diastolic pressures. Ratshin et al. 37 have determined the prognostic significance of various hemodynamic measurements. They have identified two subgroups of patients with a hospital mortality rate of 100% using therapeutic measures available prior to 1972: those with clinical evidence of shock and (a) LV filling pressure _> 28 mm Hg or (b) LV filling pressure _> 15 mm Hg and cardiac index _< 2.21/miniM2. This observation facilitates the objective evaluation of the therapeutic techniques developed subsequently. The effects of intravenous furosemide on the hemodynamics of patients with acute myocardial infarction and elevated pulmonary artery diastolic pressure have also been evaluated by Rotman et al. 3s In 14 patients with an elevated pulmonary artery diastolic pressure (>- 15 mm Hg) but w i t h o u t clinical evidence of pulmonary edema, 40 mg of furosemide intravenously resulted in an average diuresis of 1 liter within 3 hours. This was accompanied by an acute decrease in pulmonary artery diastolic pressure in 13 patients and a decrease in the cardiac output of 12 of these. One patient became acutely hypotensive and died following 17

a brisk diuresis. Isolated episodes of sudden hypotension following diuresis have been noted by others, a~ Control patients demonstrated a gradual decline in their pulmonary pressure toward normal in the absence of therapy. Therefore, the relatively benign natural history of patients w i t h elevated filling pressure in the absence of signs or symptoms of pulmonary edema or cardiogenic shock would not indicate the necessity for abrupt intervention with a potent intravenous diuretic agent. When diuresis is necessary in patients with symptoms of congestion, an initial dosage of less than 40 mg of intravenous furosemide is indicated. Russell et al. 4~ studied the effects of acutely increasing left ventricular filling pressure in patients with myocardial infarction by infusing low molecular weight dextran. This maneuver consistently resulted in an increase in pulmonary artery diastolic pressure. Cardiac output also increased as the pulmonary artery diastolic pressure approached 2 0 - 2 4 mm Hg. An increase in pressure above this level resulted in no further increase in the cardiac output (or an actual decrease in a few patients) as clinical signs of pulmonary congestion began to appear. More recently, Crexells et al. 41 evaluated 23 patients with acute myocardial infarction; balloon-occluded mean wedge pressure and cardiac output were monitored. Left ventricular filling pressure was manipulated downward by diuresis or upward with volume expansion. In patients with mean wedge pressure below 14 mm Hg, volume expansion consistently increased the mean wedge pressure and cardiac output. Increases in wedge pressure above 18 mm Hg had minimal effect on the cardiac output, although it did decrease in a few patients. An "optimal" mean wedge pressure of 1 4 - 18 mm Hg was confirmed by documentation of decreasing levels of cardiac output as filling pressure was reduced by diuresis. Luz et al. 42 have documented the onset of pulmonary edema at various levels of pulmonary wedge pressures in a group of 23 patients with acute myocardial infarction. They demonstrated that this level depended principally on the plasma oncotic pressure. They developed a clinical "oncometer" to facilitate measurement of this factor and have used the oncotic-hydrostatic pressure gradient to determine the risk of pulmonary edema. 18

Both the left ventricular filling pressure above which pulmonary edema develops and that above which further increase in stroke volume is unlikely vary among patients. tIowever, it is fortunate that relatively few will develop congestion at levels of < 1 8 - 2 0 mm Hg and few will increase stroke volume above these levels. The relationship between cardiac output and the left ventricular filling pressure (approximated by mean pulmonary capillary wedge pressure) is summarized in Figure 2. As filling pressure is increased from low levels (A), the cardiac output increases to a maximum (B). An elevated or "abnormal" filling pressure is required to obtain a "normal" cardiac output when a significant amount of the left ventricular muscle has been infarcted. Above this level of filling pressure, the cardiac output usually remains constant (C) although occasionally it has been noted to decrease (C'). As the filling pregsure increases to very high levels, pulmonary congestion increases and eventually severe pulmonary edema will occur. Several points should be stressed regarding the application of the values in Figure 2 to the clinical situation. The pressures within the hatched area should be considered guidelines and for any given patient may vary to some extent. Additionally, the pulmonary artery diastolic pressure often is a few millimeters higher than the balloon-occluded mean wedge pressure. It should be noted that no absolute Fig 2.--The relationship between preload and cardiac output: the range between 14 and 18 mm Hg is "optimal" for the majority of patients with moderate to large infarcts. Increase toward point C rarely will increase output and could cause slight decrease. Pulmonary congestion often appears. Movement toward point A is associated with decrease in stroke volume. "Maximal cardiac output" is the limit that could be achieved by manipulation of preload. (See text for further details.)

V"///,,) E""r~ MaximGICordioc

V

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Output

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co.o*s~io.

V///A ,

v

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5 10 15 20 25 B01100n-0ccludedMeanWedgePressure,ramHg

19

numbers are present on the cardiac output scale; the curve simply indicates that a maximal cardiac output can be achieved by manipulation of the filling pressure. The exact value of the maximal cardiac output that can be attained will vary from patient to patient. In patients with cardiogenic shock, it may be less than adequate to supply the circulation. In those with minimal infarction, it may be greater than normal and, therefore, is unnecessary and m a y cause excessive oxygen demands for the ischemic myocardium. Therapeutic application of these concepts will be discussed by examining patients with categories determined by the severity of the clinical illness. A modification of the Killip-Kimball classification 43 will be used as follows*: Class I patients are asymptomatic and have neither a ventricular gallop nor an elevation in pulmonary venous pressure as determined by chest x-ray. Class H patients are asymptomatic but have either a ventricular gallop or an abnormal chest x-ray, or both. Class HI patients have symptomatic pulmonary edema without cardiogenic shock. Class I V patients fulfill the accepted criteria for cardiogenic shock, consisting of hypotension with clinical evidence of inadequate renal, cerebral or cutaneous blood flow. Class I and class II patients are asymptomatic; class III and class IV patients are symptomatic. Class III patients are manifesting "heart failure" primarily as an elevation in ventricular filling pressure (producing pulmonary edema) but with preservation of an adequate blood flow. Class IV patients are manifesting "heart failure" as inadequate forward blood flow regardless of the filling pressure. ALTERATIONS OF PRELOAD.--CIass IV patients have an extremely high mortality rate and require nearly constant evaluation by a physician if they are to have any chance of survival. Although initial emergency measures m a y be directed at increasing the blood pressure to an acceptable level with sympathomimetic amines to maintain coronary and cerebral perfusion, subsequent efforts must be directed

*Pulmonary rales are not used in this classification because of their lack of sensitivity and specificity in predicting elevations of filling pressure. 20

toward improving the cardiac output and total body perfusion. Every effort should be made to optimize and maintain left ventricular filling pressure: an increase in a low filling pressure from point A to point B (Fig. 2) may produce a dramatic increase in cardiac output in these patients. Ind e e d , a low filling pressure is one of the few reversible causes of cardiogenic shock in acute myocardial infarction. If, when first encountered, the patient in cardiogenic shock has no clinical evidence of an excessive filling pressure, volume therapy m a y be initiated while preparations are being made for insertion of a flow-directed catheter into the pulmonary artery. When there are no facilities available for monitoring the filling pressure, volume expansion should be continued either until the patient is stable or until definite evidefice of pulmonary congestion appears. Occasionally patients will maximize cardiac output at a very high filling pressure (20-25 m m Hg), and it becomes necessary to accept some degree of pulmonary congestion to support blood flow at a level that is adequate to sustain life. Maintenance of an adequate and optimal filling pressure is necessary before initiating other interventions for the m a n a g e m e n t of shock. Class III patients will have high filling pressures when studied. Preload must be reduced to make the patient comfortable, but this m a y induce a low-output state. It is important, therefore, to determine the cardiac output at the outset. If this is reduced despite the elevated filling pressure, it frequently will drop to inadequate levels during further diuretic therapy. In this situation, elevation of cardiac output, using a vasodilator that reduces afterload, becomes the t r e a t m e n t of choice (see Alterations of afterload). Reliance on diuretic therapy should be restricted to those class III patients with normal or elevated cardiac output. Diuresis will move the great majority from point C to point B in Figure 2 with little change in cardiac output but with definite improvement in pulmonary congestion. Occasionally, a patient will increase cardiac output as the filling pressure moves in this direction (C' to B). The therapeutic goal is improved patient comfort, greater ease of oxygenation of the arterial blood and sometimes an increase in forward blood flow. One can also speculate that the decrease in excess filling pressure will lower the de21

mand for myocardial oxygen by decreasing left ventricular volume and systolic wall stress and will improve myocardial oxygen supply by improving diastolic blood flow as diastolic wall stress diminishes. In theory, these effects of diuresis could decrease myocardial infarct size. Patients in class III who had no significant response to a diuretic have been demonstrated to respond to nitroglycerin with a decrease in filling pressure as blood pools in the capacitance bed, a sort of internal diuresis. 44 Since this vasodilator has more effect on preload than on afterload, 4~ it should be used with caution when cardiac output is decreased. Overdiuresis of class III patients can be determined if the filling pressure falls below point B toward point A, resulting in a decrease in cardiac output and tissue perfusion. Optimal m a n a g e m e n t of these patients, therefore, requires m e a s u r e m e n t of ventricular filling pressure and, if possible, cardiac output. Diuresis should stop if the cardiac output falls dramatically or when the balloon-occluded wedge pressure approaches 15 m m Hg. Class II patients have clinical findings suggesting an elevated left ventricular filling pressure but no symptoms. Their pulmonary artery diastolic or mean wedge pressures almost always are elevated. Although class I patients have neither a ventricular gallop sound nor congestion on chest x-ray, a large percentage have elevated filling pressures. Because of the hazard of precipitous decreases in cardiac output, diuretics should not be used to treat these asymptomatic patients in either class I or class II. Class I patients with a normal filling pressure have an excellent prognosis. Although it is possible to move them along the curve from point A to point B with a volume challenge and to increase their cardiac output to higher resting levels, there is no evidence to indicate that this is necessary. The brisk diuresis that usually follows such-a maneuver in these patients is the most convincing evidence that the low filling pressure is an adequate filling pressure and that the therapeutic intervention was unnecessary. In theory, such an intervention could increase infarct size. Nitroglycerin is used routinely for relief from angina pectoris, but it causes marked reduction in preload by ve22

nous dilatation. This may precipitate movement toward point A (Fig. 2) in the patient with significant infarction. This change may be more abrupt than that produced by diuretics and thus compensatory mechanisms may not occur. Come and Pitt 46 have observed sudden severe hypotension in 1 of 14 patients who received 0.3 mg nitroglycerin sublingually and in 3 of 40 patients receiving intravenous nitroglycerin infusion. Only 1 of these 4 patients had "low" filling pressure (4 mm Hg) prior to receiving nitroglycerin. These. observations emphasize the potentially serious consequences that may occur with less than "optimal" preload in acute myocardial infarction. They create concern about the relationship between the self-administration of nitroglycerin and the high mortality rate during the prehospital phase. DIRECTLY

POSITIVE

INOTROPIC

AGENWS.--Digitalis.--The

controversy concerning the use of digitalis preparations in the setting of acute myocardial infarction remains unresolved.~7 The administration of digitalis to patients in the early stages of myocardial infarction results in no reproducible hemodynamic improvement.43,45.4s-51 Its use adds confusion to the evaluation and management of ventricular arrhythmias, and it has been proved to increase infarct size in animals and perhaps in man. 52,53 For these reasons, it probably should be administered only as an alternative to vasodilator therapy when the cardiac output is decreased despite an elevated filling pressure. However, patients on chronic digitalis therapy who sustain an acute myocardial infarction may be continued on the drug, since firm data indicating that it is harmful in this setting are lacking.

Shock associated with propranolol.-In recent years, pro~ pranolol has proved effective in the medical management of angina pectoris and often is used in doses of 360-400 mg per day. In one prospective study of propranolol and angina pectoris with a 6-8-year follow-up, 12 of 63 patients had an acute myocardial infarction; 6 died in cardiogenic shock. 54 This suggests that patients on high doses of propranolol for chronic therapy of angina pectoris may have a higher incidence of cardiogenic shock if acute myocardial infarction comPlicates their clinical course. In this setting, glucagon may emerge as the treatment of choice, since it appears to 23

augment myocardial contractility via a mechanism other than activation of the beta-adrenergic receptor. Glucagon has been reported to have produced striking improvement in a single case of propranolol intoxication. 55 ALTERATIONS OF A F T E R L O A D . - Experimentally, the degree of myocardial fiber shortening is inversely proportional to the tension generated, or afterload. If initial fiber length and the level of contractility are held constant, the degree of fiber shortening increases as the afterload is decreased. I n c r e a s e d fiber shortening in a linear dimension is translated into an increased ejection fraction in the three-dimensional ventricle and a larger stroke volume if end-diastolic volume is held constant. Until recently, therapy for heart failure had not been directed at the acute or chronic manipulation of ventricular afterload. Vasodilator therapy, which can decrease ventricular afterload, fills this gap and Offers a new and potent method of increasing cardiac output. To avoid confusion, one must be careful not to equate the term vasodilator with reduction in ventricular afterload. Vasodilators have different and mixed effects on the venous capacitance bed and the arteriolar resistance bed. Increasing venous capacitance results in an internal phlebotomy and decreases ventricular preload. Nitroglycerin appears to have its major effect on this venous bed 4~and, therefore, has been considered under alterations of preload as an alternative way of moving down the curve in Figure 2 from C to B to A. Regardless of the agent used, however, one must remain cognizant of the relationship of cardiac output to ventricular filling pressure in acute myocardial infarction. Unanticipated, precipitous reduction of ventricular preload by any vasodilator can cause a severe reduction in cardiac output. Phentolamine has its major effect on the arteriolar resistance bed or ventricular afterload. In acute myocardial infarction, it has been demonstrated to increase cardiac index and stroke index whereas heart rate and mean arterial pressure remain constant. 5G Intravenous nitroprusside appears to have mixed venous and arterial effects (preload and afterload effects)? 5 Both are reduced and, depending on which effect predominates and the initial filling 24

pressure, one might expect the cardiac output to increase or decrease. The afterload effect can be isolated, however, by countering the preload effects with volume expansion to maintain filling pressure constant. Thus, when contemplating afterload therapy in a patient, one must remember that preload remains the cornerstone of the cardiac output; and if filling pressure is allowed to fall below the suggested optimal levels, the anticipated increase in cardiac output may not occur. This is not failure of afterload therapy but rather a failure to provide or maintain an adequate diastolic load to permit the systolically unloaded ventricle to actually increase its stroke volume. Clinically, nitroprusside and phentolamine have been used in severely ill patients with high filling pressures, pulmonary edema and various degrees of depressed cardiac output but with an adequate systolic arterial pressure? 7, 5~ They can produce a controlled reduction in filling pressure and improvement in pulmonary congestion at a time when cardiac output increases, an event rarely seen when diuretics are used. More important, this over-all hemodynamic improvement may occur with a decrease in myocardial oxygen requirement. Thus, reduction of afterload could reverse the vicious circle of decreasing cardiac output, increasing myocardial oxygen demand, decreasing oxygen supply and increasing infarct size that occurs in cardiogenic shock. Chatterjee e t al. ~9 have reported their experience with afterload reduction by nitroprusside and phentolamine in patients with cardiogenic shock. Seventeen patients satisfied the hemodynamic criteria for 100% mortality proposed by Ratshin e t al. 37 (filling pressure __ 15 mm Hg and C.I. _< 2.2 1/min/M2). Hospital mortality rate was reduced to 53%. Vasodilators have predictable but potentially lethal hemodynamic effects if not monitored properly. Intravenous infusions must be accurately controlled with a pump, and pulmonary and systemic arterial pressures must be monitored frequently as the dose is adjusted. Phentolamine would be preferable to nitroprusside because its lesser effect on venodilation would necessitate less compensatory volume expansion. However, its prohibitive expense has dictated that most clinical experience with afterload reduction has involved nitroprusside. Afterload 25

reduction is accomplished principally by dilation of arterioles (resistance vessels). Thus, vasodilators such as nitroprusside could "steal" blood flow from already maximally dilated isehemic zones, inducing further coronary insufficiency.6~Phentolamine would be expected to have a similar effect. Nitroglycerin's predominant effect on larger arteries (conductance vessels) would eliminate the coronary "steal"* but would have lesser capability to reduce afterload. Nitroprusside thus is the most effective available afterload reducing agent. It should be 'the vasodilator of choice only when afterload reduction is indicated to r e v e r s e t h e syndrome of decreased cardiac output despite elevated (> 15 mm Hg) filling pressures. Preliminary personal experience suggests that i t is successful only when peripheral resistance exceeds 15-20 Wood units.t Hemodynamic improvement may occur despite arterial hypotension when resistance is excessive. An abrupt drop in filling pressure may occur initially; infusion should be begun at a level of 5 - 1 0 mg/min. Tachyphylaxis may occur. Hemodynamic improvement rarely will continue beyond that achieved by infusion of 200 mg/min. Volume expansion frequently is required as the infusion is increased and diuresis is necessary as it is tapered. The end point of infusion should be improvement in total body perfusion. Earlier attempts to achieve a "normal" cardiac index and AV 02 difference have provided the current hypothesis that lesser levels of hemodynamic improvement may be "optimal." Proof must await the availability of a technique to accurately assess the quantities of ischemic and infarcted myocardium. Withdrawal of nitroprusside may be accompanied by a return of markedly reduced cardiac output. Recent studies have documented the usefulness of nitroglycerin ointment,6~ phenoxybenzamine~2 and hydralazinec~ in achieving chronic afterload reduction. Intra-aortic balloon pumping is a mechanical form of afterload therapy. By rapidly deflating with the onset of sys*Coronary "steal": Increase of blood flow to nonischemic areas but decrease of blood flow to ischemic areas. tWood units: Mean systemic arterial pressure minus mean right atrial pressure divided by the cardiac output.

26

tole, it abruptly decreases ventricular afterload, resulting in an increased ejection fraction. During diastole, the balloon is inflated, elevating aortic pressure and producing improved peripheral and coronary perfusion. The technique will produce significant hemodynamic improvement in 80% of patients in cardiogenic shock and has been combined with coronary artery bypass surgery in selected patients. Hospital mortality in a rigidly defined group of patients with severely compromised hemodynamics treated with the balloon assist device alone is about 80%G4; over-all hospital mortality when combined with surgery is 70%2 ~ No comparisons of the intra-aortic balloon pump with vasodilators currently are available. As with the vasodilators, use of the intra-aortic balloon pump requires continuous hemodynamic monitoring to maintain preload at optimal levels and to assess the changes in cardiac output. Additionally, expensive equipment and minor surgery (arteriotomy) for insertion are necessary, making it a less readily available form of therapy than pharmacologic vasodilation. This procedure may be complicated by thrombosis, aortic dissection, hemorrhage at the site of arteriotomy or renal insufficiency. At present, both forms of afterload therapy, pharmacologic and mechanical, appear to be capable of some reduction in hospital mortality from severe heart failure in acute myocardial infarction. PROPIIYLACTIC TEMPORARY PACING The acute and long-term prognosis of complete heart block in acute myocardial infarction depends on the site of infarction and the level of the conduction disturbance. Atrioventricular (AV) nodal block may appear gradually with pesteroinferior infarcts of any size. Prognosis varies' with the size of infarction26 Infranodal or trifascicular block occurs suddenly and often persistently with large anterior infarcts and the prognosis is affected by both the infarct size and the conduction disturbance, sT,6s AV nodal block with a posteroinferior myocardial infarction manifests itself initially as a prolonged PR interval. Subsequently, increasing ratios of second degree heart block (Type I) frequently occur and there is occasional progression to complete heart block. When the latter occurs, 27

the QRS configuration usually is normal and the ventricular rate is hemodynamically adequate, indicating an escape focus in the common bundle of His. The AV block gradually resolves after several hours to several days. Permanent high-degree block is extremely rare. Because of the adequacy of the escape rate, the majority of patients with posteroinferior myocardial infarction do not develop symptoms of pulmonary congestion or evidence of inadequate tissue perfusion as a result of this transient complete heart block. Thus, prophylactic temporary pacemaker insertion is not suggested. Exceptions do occur and occasionally a patient with a very slow rate or no escape focus is seen. In an emergency, atropine or isoproterenol can be used to accelerate the escape r a t e o r decrease the degree of block. Use of these drugs can cause urinary retention (atropine), can produce sustained sinus tachycardia (both) or can augment contractility unnecessarily, causing extension of the infarction (isoproterenol). For these reasons, temporary pacemaker insertion is recommended in those few patients who require a faster ventricular rate to provide more precise control of heart rate w i t h o u t jeopardizing the ischemic myocardium. Complete heart block in anterior myocardial infarction tends to occur abruptly, but it almost always is preceded by either right or left bundle-branch block. 67, 68 Asystolic periods are common because the only available escape foci are located in the bundle branches distal to the site of block. Despite pacing and maintenance of an adequate ventricular rate, many (33%) of the patients die in cardiogenic shock. 6s However, other patients survive as a result of yentricular pacing and, for this reason, many authorities 67' ~s recommend prophylactic, temporary pacemaker insertion in patients at high risk of developing complete heart block. Prophylactic insertion is preferred because the block occurs abruptly, usually with severe hemodynamic compromise before an adequate ventricular rate can be re-established. The point at which the risk of complete heart block is sufficient to justify the time, expense, discomfort and risk of prophylactic pacemaker insertion is, again, a matter of judgment. The studies noted above recommend insertion with the appearance of "bifascicular block" defined as (1) right bundle-branch block with left anterior hemiblock, (2) 28

right bundle-branch block with left posterior hcmiblock or (3) left bundle-branch block.

CORONARY INSUFFICIENCY: POSTHOSPITAL PHASE PERMANENT PACEMAKERS

Although infranodal complete heart block with acute myocardial infarction is associated with a high in-hospital mortality from cardiogenic shock, some patients who do not develop shock survive as a result of temporary transvenous pacing. Such patients are at high risk of sudden death following discharge from the hospital.6 ''69 Several reports suggest that the prognosis is improved by permanent pacing. Atkins et al. 67 reported a group of patients with fascicular conduction disturbances complicating acute myocardial infarction. Sixteen patients had transient complete heart block preceded by bifascicular block and survived hospitalization. One patient was lost to follow-up. Of the remaining 15 (13 with right bundle-branch block and left anterior hemiblock and 2 with left bundle-branch block), 9 received permanent pacemakers and 6 did not. Five of 6 patients without pacemakers died suddenly within months of discharge whereas all patients with permanent pacemakers still were alive. Waugh e t al. ~s reported a similar experience in 17 patients with infranodal complete heart block complicating acute myocardial infarction. Sixteen of the patients had fascicular block (14 bifascicular) preceding complete heart block. Of the 17 patients, 7 received permanent pacemakers and 10 did not. In the first year of follow-up, 5 patients without pacemakers died suddenly and 2 experienced syncope. Patients with pacemakers had no syncope or sudden death and 6 were alive after 1 year. Although these studies are retrospective, the data available suggest that permanent pacing may prolong survival and is indicated in patients with bifascicular block complicating acute myocardial infarction who progress to complete heart block. In addition, patients with extensive ischemic damage to the His-Purkinje conduction system, who do not develop high-degree block during the acute period, 29

have a moderately increased risk of sudden death and should be considered for permanent pacemaker insertion. EARLY DISCHARGE

Levine and Lown ;~ broke with tradition and suggested that patients with acute myocardial infarction could be mobilized early in their hospital course without deleterious results. Subsequently, numerous studies have been published comparing groups of patients ambulated and discharged at different intervals. Hutter et al.n evaluated two different programs in patients without complications. Patients with the following complications were excluded from the study: ventricular tachycardia or asystole, second' or third degree heart block, persistent warning arrhythmias or congestive heart failure after day 5, hypotension requiring vasopressor agents, thromboembolic complications, persistent pain or a previous myocardial infarction within the preceding 6 months. The remaining "uncomplicated" patients were randomized to an "early group" that was discharged on day 14 or a "late group" that was discharged on day 21. After 6 months of follow-up, no difference in morbidity or mortality was detected between the two groups. Hayes et al. TM conducted a similar study in patients without complications. The early group was allowed to walk after day 2 and discharged on day 9; the late group did so on days 9 and 16, respectively. After 6 weeks of follow-up, no difference was apparent between the two groups. In both of these studies, the mortality during the follow-up period in each group ranged from 4% to 7%. McNeer et a l Y examined the clinical courses of 522 consecutive patients with acute myocardial infarction. Fifty-one per cent of these patients experienced no "serious complication" during the first 4 days in the hospital (death, ventricular tachycardia or fibrillation, symptomatic heart failure, extension of infarction, 2~ or 3 ~ AV block, atrial flutter or fibrillation, persistent sinus taehyeardia or hypotension). None of these "serious complications" occurred during the remainder of their hospital stay, and the patients were discharged an average of 17 days after admission. Mortality 6 months following discharge was 8%. It is apparent that approximately 50% of patients with 30

acute myocardial infarction have a benign course during the early, days of their illness and have an excellent prognosis. Discharge for these patients between days 7 and 10 seems justified based on current controlled studiesY 4 Earlier discharge for selected subgroups may become feasible after further clinical trials. Trained paramedical personnel can work in the home to facilitate the rehabilitation process, to make physical assessment and to enhance the transition to a functioning state. Transtelephonic ECG transmission permits routine surveillance for changes of rhythm or ischemia during the recovery phase following acute myocardial infarction.

CORONARY INSUFFICIENCY: THE FUTURE There is a great deal of experimental and clinical interest today in the concept of reducing or minimizing infarct size using numerous interventions. In theory, this could reduce both short-term and long-term morbidity and mortality. Although studies that measure effects on morbidity and mortality can be designed, it is not yet possible to deal more directly with infarct size because a proved method of quantitating exact infarct size is lacking. Quantitation of CPK isoenzymes in the serum and measurement of ST segment changes on the precordium have been proposed as measures of infarct size, but the reliability of these sera and precordial phenomena in quantitatively reflecting events in the myocardium has not been proved. 75' 7G Reduction of infarct size, however, offers little to the many individuals who die suddenly and unexpectedly from coronary insufficiency. Any program that seeks to effect a significant reduction in over-all mortality from existing coronary artery disease must attack this prehospital phase. Many communities are beginning this by establishing teams of specially trained paramedical personnel in mobile emergency units who can reach patients within minutes of the onset of symptoms and by establishing community-wide training programs in cardiopulmonary resuscitation. Ideally, one would like to prevent coronary insufficiency. Coronary artery bypass grafting is a form of secondary prevention. Although initially it was offered only for relief from angina pectoris, it now is being performed in less 31

symptomatic patients with extensive disease in the belief that it prolongs survival. Caution in this area and constant re-evaluation are indicated, since controlled studies have not been done comparing medical and surgical therapy. It is hoped that the debate in this area will be settled as new data are acquired in the next few years. Primary prevention of atherosclerosis in the coronary vessels must be the ultimate goal. Although numerous risk factors have been identified, guilt is by association only. A cause-and-effect relationship and the exact pathophysiology of atherosclerosis remain to be identified.

SUMMARY 1. Coronary insufficiency is a pathophysiologic state that can initiate lethal cardiac arrhythmias in the absence of myocardial necrosis. Patients with suspected coronary insufficiency should be monitored until they are stabilized and a diagnosis is confirmed. 2. Early and adequate intravenous antiarrhythmic prophylaxis with lidocaine:to raise the fibrillation threshold in the setting of coronary insufficiency can prevent primary ventricular fibrillation. Classic "warning arrhythmias" are not predictive of ventricular fibrillation. Their persistence during adequate antifibrillatory prophylaxis does not indicate therapeutic failure. 3. The isoenzyme ofcreatine phosphokinase, CPK-MB, is an extremely sensitive and specific indicator of myocardial necrosis if measured serially during the 24 hours following the onset of symptoms suggesting coronary insufficiency. It may prove most useful in eliminating the false positive diagnosis of myocardial infarction in difficult clinical cases. 4. The management of heart failure in myocardial infarction requires an understanding of the relationship between ventricular preload and the cardiac output. The treatment of clinical manifestations of an elevated ventricular preload in asymptomatic patients is not justified and may be detrimental. In symptomatic patients, however, judicious manipulation of ventricular preload should be the first therapeutic consideration, and an optimal filling pressure should be achieved and maintained when other determinants of the cardiac output are manipulated. 32

5. Indications for the prophylactic insertion of a temporary transvenous pacing electrode for heart block associated with myocardial infarction must be individualized. Most authorities agree that prophylactic pacing may be justified in patients with evidence of new infranodal block involving two of the three fascicles. Patients with bifascicular block who progress to complete heart block transiently may benefit from permanent transvenous pacemaker insertion before discharge. 6. Hospitalized patients with persistent pain of suspected cardiac origin but without evidence of myocardial infarction can be studied safely with coronary angiography. A small percentage will be normal or have diffuse disease that is inoperable. Of those with operable disease, shortterm mortality appears to be similar for medical and surgical therapy. 7. Patients with an uncomplicated myocardial infarction may be safely discharged from the hospital by day 7 - 10. 8. Expeiimental evidence indicates that modification of infarct size is possible. Application of these concepts to human subjects presently is limited by the absence of a proved method of measuring infarct size in vivo in humans. ACKNOWLEDGMENTS

.

The authors wish to thank Dr. Cheryl Mahony for her helpful review and Virginia Utley for preparing the manuscript. QUIZ

1. What are the criteria for initiation of intravenous lidocaine in patients with acute coronary insufficiency? 2. How does one differentiate between acute coronary insufficiency with and without myocardial infarction? 3. What is the definition of coronary care? 4. What are the possible etiologies of sudden death in the presence of acute coronary insufficiency? 5. At what phase during the acute event does one have maximal opportunity for limitation of infarct size? 6. Of what value are "warning arrhythmias"? 33

7. Can one minimize the likelihood o f lidocaine reactions while also minimizing the likelihood of ventricular fibrillation? 8. Do physicians who do not have access to CPK isoenzyme determination tend to "overdiagnosis" or "underdiagnosis" of myocardial infarction? 9. What is the optimal frequency of serum sampling to ensure detection of CPK-MB? 10. What pathophysiologic phenomenon commonly occurs 9in variant (Prinzmetal's) angina? 11. Can heart failure exist in the absence of "congestion" in acute myocardial infarction? 12. What effect do changes in preload or afterload have on cardiac output? 13. How do signs of failure such as gallop r h y t h m or rales correlate with findings obtained during Swan-Ganz catheterization? 14. Can patients in a "100% mortality subgroup" be salvaged by use of afterload reduction therapy? 15. Can a significant number of patients in cardiogenic shock be salvaged by use of intravenous fluids alone? 16. Do all patients develop pulmonary edema at this same level of filling pressure? 17. Is there a role for glucagon in cardiogenic shock? 18. What are the 9 of afterload reduction in the absence of left-sided filling pressure monitoring? 19. What are the different actions of phentolamine, nitroglycerin and nitroprusside? 20. What are the indications for intraortic balloon pumping in acute myocardial infarction? 21. What are the differences in acute and long:range prognosis of heart block accompanying 9 and anterior infarction? REFERENCES 1. Wood, P.: Acute and subacute coronary insufficiency,Br. Med. J. 1:1779, 1961. 2. McNeilly,R. H., and Pemberton, J.: Duration of last attack in 998 fatal cases of coronary artery disease and its relation to possible cardiac resuscitation, Br. Med. J. 3:139, 1968. 3. Alonzo,A. A., Simon, A. B., and Feinleib, M.: Prodromata of myocardial infarctionand sudden death, Circulation52:1056, 1975. 34

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