Medical management of myocardial infarction.

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Annu. Rev. Med. 1976.27:89-108. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 11/22/14. For personal use only.

Copyright 1976. All rights reserved

MEDICAL MANAGEMENT OF

+7184

MYOCARDIAL INFARCTION Milton S. Klein, MD. and Burton E. Sobel, MD. Cardiovascular Division, Washington University School of Medicine, 660 South Euclid, St. Louis, Missouri 63110

INTRODUCTION

Several new therapeutic approaches have been designed to protect jeopardized ischemic myocardium (1). Despite their promise, their effect on overall mortality may be limited by high pre-hospital mortality and low long-term survival even in patients resuscitated from ventricular fibrillation (2); and the importance of the extent of vascular disease as a determinant of long-term prognosis (3). The Dynamic Nature of Myocardial Infarction After experimental coronary occlusion, infarction appears to evolve slowly. After 45 minutes, many cells within the ultimate infarct remain viable (4). Reperfusion within several hours protects some regions otherwise destined to undergo necrosis (5) and several other interventions favorably modify the ultimate extent of infarction when instituted early (6). Analogous results have been demonstrated in patients (7). Accordingly, several interventions have been designed to favorably influence the evolution of infarction by improving the balance between myocardial energy re quirements and supply. These include reduction of ventricular afterload, and aug mentation of myocardial oxygen supply or substrate availability (8-10). Other approaches, such as those designed to reduce lysosomal hydrolase activity in is chemic tissue (11), have not yet been explored as thoroughly. Detection of Infarction The diagnosis of infarction has been based traditionally On history, serum enzyme elevations, and evolution ofJocalized electrocardiographic changes. Recently, serum creatine phosphokinase (CPK) isoenzyme determinations have proven useful since the MB CPK isoenzyme in man is found almost exclusively in myocardium ( 1 2-14). Other biochemical indexes of infarction are being evaluated, such as elevated serum myoglobin, detected by radioimmunoassay ( 1 5), and anti-myocardial antibodies (16). However, myoglobin from the heart and from skeletal muscle cannot yet be differentiated, and antibodies lack specificity as criteria of infarction. 89


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KLEIN & SOBEL

Infarction has been detected by scintigraphy with 99mTc (Sn) pyrophosphate ( 1 7) and 99mTc-tetracycline (18). The combination of scintigraphy and analysis of MB CPK improves detection and reduces the incidence of false positive diagnosis of infarction (19), particularly among patients admitted late after the onset of infarc tion or in those undergoing coronary artery bypass surgery. Positron emission transaxial tomography is a potentially useful new diagnostic tool (20). Cross-sectional computer reconstructed images of the heart can be ob tained after intravenous injection of short-lived, positron-emitting, cyclotron-pro duced physiological substrates of myocardium (e.g. IIC-palmitate). In contrast to conventional scintigraphic techniques, superimposition of myocardium on a two dimensional image is avoided. Evaluation 0/ Left Ventricular Function Because central venous pressure and left ventricular filling pressure may be discordant (21), assessment of cardiac output and pulmonary artery occlusive pressure (PAo) with a Swan-Ganz balloon-tipped thermodilution catheter is often essential. Although normal PAo is < 12 mm Hg, higher pressures (14-24 mm Hg) are frequently required to sustain cardiac output in patients with infarction (22), or to differentiate hypovolemic from cardiogenic shock (23). Changes in PAo reflect altered hemodynamics more rapidly than radiographic indexes of left ven tricular failure. The rare complications of bedside cardiac catheterization, including hemoptysis, dysrhythmia, and pulmonary thromboembolism, can be generally avoided with appropriate precautions. HEMODYNAMICS

Left ventricular ejection fraction and stroke vol ume have been evaluated echocardiographically. However, localized dyskinesis im pairs reliability and suitable echocardiograms are obtainable in less than 60% of patients (24). Ejection fraction, mitral regurgitation, and intracardiac shunts can be estimated serially with radionuclide techniques utilizing ECG gating and intravenous injection of 99mTc labelled albumin, pertechnetate, and red blood cells (25, 26). Reproducible estimates of ejection fraction have also been obtained with intravenous injections of 113mIn detected at the bedside with a precordial probe (27).

NON-INVASIVE TECHNIQUES

Estimation 0/ the Extent 0/ Ischemic Injury Infarct size has been estimated from ST-segment elevations on multiple lead precor dial electrocardiographic recordings (ST mapping) (28). After experimental coro nary occlusion, epicardial ST-segment elevation is related to the distribution of myocardial injury, correlates with changes in surface leads, and reflects altered myocardial perfusion or oxygen requirements (6). Changes in precordial ST maps in patients reflect spontaneous extension of infarction (29), or protection of myocar dium induced pharmacologically (10, 30). Although ST mapping is rapid, noninva sive, and inexpensive, it is not applicable to all patients; it may be influenced by drugs, electrolyte shifts, or pericarditis; and it reflects ischemia rather than infarc tion per se.

MYOCARDIAL INFARCTION

91

Quantification of infarct size with current scintigraphic techniques is impaired by:


(a) superimposition; (b) resolution; (c) border recognition; and (d) dependence of

tracer accumulation on heterogeneous blood flow in ischemic zones. Thus, despite the diagnostic sensitivity of scintigraphy, its use in quantifying infarct size is limited. Infarct size has been estimated enzymatically from serial CPK changes in hourly serum samples (31) since myocardial CPK depletion after experimental coronary occlusion correlates with infarct size (32), corresponds to early ST-segment eleva tion (6), and correlates with serial serum CPK changes analyzed according to a simple mathematical model. In patients, enzymatic and morphologic estimates of infarct size correlate closely (33). The ultimate extent of evolving infarction has been predicted with the use of curve fitting techniques applied to early serial CPK changes (34), and effects of interventions on myocardial viability have been evalu ated by comparing projected CPK values to those observed after implementation of the intervention (7,35). Unfortunately, the long interval required to obtain best-fit curves from early CPK changes prior to the intervention may mask its efficacy, since the evolution of infarction may already be virtually complete. THERAPEUTIC APPROACHES

Management of hospitalized patients with myocardial infarction was initially di rected toward maintenance of blood pressure and urine output. Subsequently, it incorporated prophylaxis and vigorous treatment of malignant ventricular dys rhythmia with consequent marked reduction of mortality. Most recently, therapy has been directed also toward protection, and, if possible, salvage of jeopardized is chemic myocardium, based on two concepts: that infarct size is an important determinant of prognosis, and that the ultimate extent of infarction can be modified favorably by early interventions. It is now clear that infarct size is one important determinant of prognosis. Thus, (a) patients who succumb from infarction complicated by cardiogenic shock exhibit extensive myocardial necrosis (36); (b) the high six month mortality rate associated with large infarcts contrasts with a low «5%) six month mortality rate seen with small infarcts (37, 38); (c) patients surviving without cardiac decompensation ex hibit much less apparent myocardial damage than those surviving with impaired ventricular function (38); and (d) a poor prognosis is presaged by impaired ventricu lar function, which in turn is correlated with infarct size (39-41). It is also clear that infarct size can be limited in experimental animals, and preliminary analogous results have been obtained in patients (7, 10). Although it is not yet clear whether protection of myocardium will alter long-term patient sur vival. therapeutic nihilism is not justified. The situation may be similar to that in patients with essential hypertension; high mortality was recognized and antihyper tensive drugs were available long before improved survival with treatment was demonstrable. In patients with myocardial infarction the balance between myocardial oxygen supply and demand is favored by several general measures, including (a ) regulation of fluid and electrolyte balance; (b) control of cardiac rate, rhythm, and atrial


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KLEIN & SOBEL

transport function; (c) reduction of arrhythmogenic stimuli such as excess cate cholamine or free fatty acid levels; (d) avoidance of hypoxemia, anemia, alkalosis, or acidosis; and (e) management of concomitant disorders such as hypertension, diabetes mellitus, or thyrotoxicosis. In addition to these general measures, several specific therapeutic approaches have been developed to protect jeopardized myocardium, maintain ventricular per formance, and support hemodynamics (Table I) (41a). Agents with Positive Inotropic Effects DIGITALIS GLYCOSIDES After experimental myocardial infarction complicated by left ventricular failure, digitalis glycosides diminish ischemic injury, presumably since myocardial oxygen consumption (MV02) is reduced by diminished left ven tricular volume and wall tension. However, digitalis increases MV02 and augments ischemic injury after experimental infarction without failure because of its effect on contractility. After experimental coronary occlusion, acetylstrophanthidin fails to improve ventricular performance initially, but improves it after one week (42). The absence of early effects may be due to insensitivity of ischemic tissue to digitalis, the already maximal stimulation of contractility by circulating catecholamines, or dissipation of ventricular contraction in transiently dyskinetic areas (43). Toxic electrophysiological effects of digitalis are common early after the onset of myocardial infarction, especially when hypokalemia is present. Peripheral vasocon striction exerting an increased cardiac burden may be induced by rapid administra tion of digitalis glycosides intravenously (44). In addition, digitalis does not appear to alter the outcome of cardiogenic shock (23). Thus, administration of digitalis to patients with myocardial infarction entails definite risk with little likelihood of substantial benefit unless the drug is being used to treat specific dysrhythmias. /3-ADRENERGIC AGONISTS Although /3-adrenergic agonists such as iso proterenol hydrochloride improve ventricular performance, they increase MV02 and lactate production (45) and augment the extent of experimentally induced infarction (6, 46). Norepinephrine may increase MV02 even more markedly because of its vasocon strictor as well as positive inotropic effects. As with isoproterenol hydrochloride, malignant dysrhythmias may be precipitated, leading to further deterioration of cardiac function and viability. Congeners such as dopamine and Dobutamine with cardioselective (/3-l) and predominantly positive inoptropic effects may be useful in patients with decreased cardiac output and increased PAo. Fortunately, Dopamine exerts alpha adrenergic vasoconstrictor effects only at rather high doses and the vasoconstriction is blocka ble with a-antagonists. However, its prominent non-adrenergic renal arterial vasodilatation and its cardiotonic action generally improve hemodynamics and renal function (47, 48). Dobutamine, an investigational drug, is similar and increases cardiac output without substantial changes in mean arterial pressure or heart rate in experimental animals (49). Perhaps because of its relatively modest chronotropic


Table

I Potentially useful therapeutic interventionsa

Hemodynamic categoryb

1. Normal

2. Hyperdynamic state

3. LV failure: Mild

Mean PAc

Suggested interventions

PAOc

::::I S mm Hg ::::IS

::::12 mm

�lS after volume

::::1 8

::::12

Hg

None Il-adrenergic blockade

Heart rate is usually increased

Diuretics

Dyspnea, hypoxemia, or mild pulmonary vascular congestion

repletion when hypovolemia Severe

is present initially

�IS

Remarks

>18

Diuretics + vasodila tors

With severe pulmonary vascular congestion and pulmonary edema, positive pressure ventilation may be useful

4. Cardiogenic hypotension or shock

�IS

Vasodilator therapy.

�18 after

Circulatory assist may

positive inotropic effects such

when hypovolemia is

be useful

as Dopamine may be

present initially

S. Hypovolemic hypotension

::::15

::::12

6. Acute cor p ulmonale

>IS

::::12

or shock

Cardioselective agents with

volume repletion

particularly useful

Repletion of vascular

Hemodynamic reclassification

volume

may be necessary after PAO is

Correction of

Usually due to isola ted or

hypoxemia and

concomitant pulmonary

conventional

embolism

adequate (PA systolic:::: SO)

(normal i n the

face

of increased P A pressure)

management of under lying cause

aModified from (41a). bpatients in all categories require adequate analgesia, usually best accomplished with i.v. morphine. cPulmonary artery and pulmonary artery occlusive pressures.

�

g:> �

s:

t"'

Z �

� � '-CI .....

94

KLEIN

&

SOBEL


effects, Dobutamine improves left ventricular performance in patients without aug menting enzymatic�lly estimated infarct size (50). GLUCAGON After experimental infarction without cardiogenic shock, glucagon increases the contractility of non-ischemic myocardium, improves left ventricular performance, and decreases ventricular irritability (51). In patients,glucagon (70 /Lglkg) may improve ventricular performance,increase A-V conduction,and accelerate A-V nodal automaticity (52), but it does not appear to improve survival in patients with cardiogenic shock. Side effects, especially nau sea and vomiting, occur frequently. Thus, except for specific indications such as pharmacological antagonism of excessive ,a-adrenergic blockade, glucagon is not generally useful for treatment of acute myocardial infarction. Unfortunately, agents with positive inotropic effects have not altered the outcome of severe left ventricular failure or cardiogenic shock, and may precipitate malignant dysrhythmias and augment infarct size. However, preliminary findings indicate that recently available cardioselective ,a-adrenergic agents may reduce preload and im prove ventricular function and coronary perfusion at a relatively low oxygen cost.

Therapy Designed to Decrease Myocardial Oxygen Requirements ,a-Adrenergic blocking agents have been employed to preserve ischemic myocardium by decreasing MVOz. Among patients with un complicated infarction, propranolol decreases cardiac index, stroke volume, and mean arterial pressure while increasing PAo only slightly. Myocardial lactate ex traction increases and chest pain is often relieved (53). Benefit is most apparent in patients with sinus tachycardia,high circulating catecholamine levels, and elevated cardiac output without elevated PAo. ,a-Blockade has been administered only with considerable trepidation to patients with bradycardia or impaired left ventricular function (54). However, when ,a-blockade effectively suppresses tachyarrhythmia, improved ventricular function often results. When the prevailing heart rate is high, ventricular dysrhythmia responds poorly to lidocaine and other conventional antiar rhythmic agents. Thus,initial administration of ,a-blocking agents may be advanta geous. ,a-Blockade in patients decreases ST-segment elevation in surface electrocardio grams (30). In addition,it decreases mortality during the first 24 hours after infarc tion and for as long as two years, judging from results of large, randomized prospective studies (J. M. Barber, Belfast, personal communication). Tachycardia per se increases infarct size in conscious dogs (46). In concert,these findings suggest that ,a-blockade may preserve myocardium. Coupled with recent observations in dicating that J3-blockade is relatively safe even when left ventricular function is impaired, particularly when accompanied by hemodynamic monitoring, these findingsjustify its use in patients with rapid heart rate, persistent pain, or progressive infarction (Table 1). I3-ADRENERGIC BLOCKADE

MVOz depends on left ventricular wall stress which in turn is proportional to peakREDUCTION OF VENTRICULAR AFTERLOAD PHARMACOLOGICALLY



95

developed ventricular pressure and volume. Accordingly, patients with myocardial infarction complicated by hypertension, congestive heart failure, or mitral regurgita tion have been treated with vasodilator agents to decrease impedence to ventricular ejection and reduce MV02 (Table 1). The need for hemodynamic monitoring with serial determinations of cardiac output and PAo in patients treated with vasodila tors cannot be overemphasized since improvement of myocardial energetics based on this approach requires: 1. Reduction of impedance to ventricular ejection 2. Maintenance of effective coronary perfusion pressure 3. Reduction of ventricular volume sufficient to lower wall stress without lowering output 4. Avoidance of reflex tachycardia With judicious use, administration of vasodilator agents improves hemodynam ics, mollifies refractory left ventricular failure, and appears to protect ischemic myocardium. Reduction of ven tricular afterload with intravenous infusions of trimethaphan. 100--1000 fLg/min in patients with acute myocardial infarction associated with acute or chronic hyperten sion protects myocardium (7) and reduces one month mortality. Trimethaphan is less likely to produce reflex tachycardia than direct acting vasodilators because of its mechanism of action-ganglionic blockade. Intravenous infusion of 10-100 fLglmin of nitroprusside increases cardiac output, decreases PAo (55, 56), decreases MV02, relieves chest pain, and diminishes the frequency of premature ventricular complexes (PVCs) (56). Improved cardiac out put occurs even in patients with cardiogenic shock. in whom arterial diastolic and coronary perfusion pressure is maintained by external counterpulsation (57). Similar results have been obtained with phentolamine hydrochloride. an a-adren ergic blocking agent (55. 58). Unfortunately, its expense is prohibitive. Despite traditional reluctance to administer nitroglycerin in the face of acute myocardial infarction. it has been employed recently. based on some provocative experimental findings, including augmentation of endocardial and collateral coro nary flow (59). increased cardiac output and decreased MVOz (60). and increased threshold and decreased incidence of spontaneous ventricular fibrillation (61). Salu tary effects on dysrhythmia, myocardial CPK depletion, ST-segment elevation, and infarction detected morphologically were potentiated by maintenance of diastolic pressure with methoxamine hydrochloride (62). In patients with low PAo, venodilatation induced by nitroglycerin may compro mise cardiac output (63). However, output improves, MV02 decreases, and ST elevation regresses because of decreased afterload when failure is present (64). It is apparent that beneficial effects depend primarily on peripheral vasodilatation since intracoronary administration is ineffective (65).

TRIMETHAPHAN. NITROPRUSSIDE. AND NITROGLYCERIN

FUROSEMIDE AND ETHACRYNIC ACID Many of the immediate cardiovascular effects of these diuretics are mediated by altered preload resulting from systemic and

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KLEIN & SOBEL


pulmonary venodilatation rather than diuresis (66). For example, in patients with left ventricular failure furosemide decreased LY filling pressure and increased ve nous capacitance within 15 minutes, well before any diuretic effect was evident. Unfortunately, diuresis may complicate recovery when these agents are used injudi ciously and without adequate hemodynamic monitoring (Table I). Intra aortic balloon counterpulsation augments diastolic aortic pressure, and decreases ventricular afterload by augmenting runoff into the dilated peripheral vasculature during systole. Counterpulsation in experimental animals improves hemodynamics (67, 68) and decreases ST-segment elevation (69). Left ventricular wall stress and contractile element work decrease by approximately 25% (70). Although the development of morphological criteria of necrosis is delayed, the ultimate extent of infarction, estimated from myocardial CPK depletion (71), is not diminished. In patients, the incidence of ventricular tachycardia and fibrillation decreases (72), but overall coronary flow is not substantially increased (73). Necrosis is less marked in patients who succumb with cardiogenic shock after balloon counterpulsa tion than in those with other forms of medical treatment (74). Hemodynamics improve (75), but increased long-term survival has not been observed consistently (76). Accordingly, counterpulsation may be most useful in stabilizing patients hemodynamically prior to infarctectomy and emergency coronary bypass surgery. or prior to surgery for catastrophic complications of infarction (77). External circulatory assist devices apply pressure to the lower limbs during diastole and promote increased runoff during systole. In contrast to intraaortic counterpulsation, preload may decrease because of constraints on venous return (78). It is not yet clear whether prognosis is improved consistently (79). External counterpulsation decreases the number of PYCs early after the onset of myocardial infarction. but the effect is transitory and not associated with decreased enzymati cally estimated infarct size (80). REDUCTION OF AFTERLOAD WITH CIRCULATORY ASSIST DEVICES

Augmentation of Myocardial Oxygen Supply Oxygen is administered almost routinely to patients with myocardial infarction. Although cardiac output is improved in patients with hypoxemia (81), oxygen may produce disadvantageous peripheral vasoconstriction when PAo is normal (82). Thus, even though most patients with myocardial infarction exhibit hypoxemia, arterial desaturation on room air should be documented before continued adminis tration of oxygen is utilized. In experimental animals with infarction. hyperbaric oxygen increased mean ar terial pressure, stroke work, and left ventricular end diastolic pressure, and de creased myocardial lactate production (83). Forty percent compared to 20% oxygen at'atmospheric pressure decreased ST-segment elevation after coronary occlusion persisting for 24 hours (84). Hyperbaric oxygen may decrease early mortality in. patients slightly (85), but data are inconclusive.



97

Augmentation of myocardial oxygen supply can be best achieved a priori by myocardial reperfusion. Reperfusion initiated three hours after experimental coro nary occlusion preserved myocardium (86), but reperfusion after five hours pro duced disparate results. Fifty-six percent of conscious dogs exhibited the anticipated salvage of myocardium,but 44% exhibited frank extension of infarction (35). Exten sion was associated with myocardial hemorrhage, apparently due to insults to vessels in the ischemic zone. Comparable deleterious effects have been observed in patients as well as in experimental animals (87, 88). The high mortality rate accompanying bypass surgery for acute myocardial in farction may be due to a related phenomenon (89). Only on rare occasions is surgical intervention feasible so rapidly after the onset of infarction that net preservation of myocardium can be anticipated. One example is the occurrence of infarction during cardiac catheterization (90). Administration of mannitol is another means by which coronary flow has been enhanced experimentally, presumably by means of decreased cell swelling and consequent reduction of the "no reflow" phenomenon. Under defined conditions, protection of ischemic myocardium is demonstrable (91, 92), although this thera peutic approach has not yet been widely evaluated clinically. Metabolic Interventions Energy production in hypoxic myocardium depends on glycolysis. Thus, after ex perimental infarction, hypoglycemia increases ST-segment elevation, myocardial CPK depletion, and necrosis (93). Conversely, intraveneous administration of glu cose-insulin-potassium (GIK) decreases all three (94). In patients, GIK decreased the incidence of arrhythmia but did not change the overall mortality (95). Although administration of GIK immediately after the onset of infarction decreased peak serum CPK values in retrospective studies (9),adminis tration of GIK beginning several hours after the initial serum CPK elevation did not preserve myocardium, judging from serial serum CPK changes (96). Hyaluronidase, presumably capable of facilitating diffusion of substrate in is chemic myocardium, reduced epicardial ST-segment elevation, myocardial CPK depletion, and microscopic criteria of infarction in animals (97). In patients doses of 500 J1.glkg every 6 hours for 48 hours led to reduced ST-segment elevation (10) and diminished evolution of Q waves (E. Braunwald, personal communication). Since activation of lysosomal hydrolases may contribute to myocardial injury (II), corticosteroids have been used to protect the ischemic heart (98). Hydrocorti sone administered to dogs 30 minutes after coronary occlusion decreased myocar dial CPK depletion and necrosis (99). Decreased early mortality has been reported in patients treated with methylpred nisolone compared to non-randomized controls studied retrospectively (100), and high doses administered seven hours after the initial serum CPK elevation allegedly protected myocardium (I01). However, in other studies administration of methyl prednisolone in doses of 30 mg/kg intravenously every six hours for 48 hours was clearly deleterious. Increases in enzymatically estimated infarct size, malignant


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KLEIN & SOBEL

ventricular dysrhythmia, ventricular rupture, early mortality, and persistent eleva tion of MB CPK were observed (102). Impaired healing with diminution of scar formation may be responsible for an increased incidence of myocardial rupture (103). Despite intensive study, sufficient data are not yet available to justify routine clinical use of these or other specific metabolic interventions. This may in part reflect difficulties inherent in methods available for evaluation of their efficacy in patients. For example, studies designed to compare observed to predicted infarct size based on serial CPK changes entail a prolonged interval prior to implementation of the intervention that may contribute to apparent lack of efficacy. Nevertheless, on the basis of experimental findings, it seems likely that specific metabolic interventions will ultimately prove useful in preserving ischemic myocardium in selected patients with acute myocardial infarction.

MANAGEMENT OF DYSRHYTHMIA Dysrhythmias associated with infarction require treatment when they precipitate hemodynamic impairment; compromise myocardial viability by increasing MV02; or predispose or progress to malignant dysrhythmias, including ventricular fibrilla tion or asystole. Recent evidence suggests that both the diminished threshold to ventricular fibrillation (104) and the incidence of malignant ventricular dysrhythmia (105) are related to infarct size. A- V Block Block proximal to the His bundle is often transitory (resolving within several days), associated with inferior myocardial infarction, and readily managed with temporary pacemaker therapy. Infra-His bundle trifascicular block is usually persistent, seen with anterior infarction, and associated with high mortality, probably because the underlying infarction is so extensive. The incidence of sudden death in survivors is substantial and justifies permanent pacemaker therapy (106). In patients with acute myocardial infarction, watchful waiting is indicated when newly developing block is first or second degree, proximal, associated with narrow QRS complexes, demon strably bifascicular (without P-R or H-V prolongation) (107), or right or left bundle branch block alone (108). However, trifascicular, or progressive block, known to be associated with a high overall mortality (109-112), should be treated with tempo rary pacing to improve hemodynamics or reduce ventricular irritability, since pace maker therapy may be lifesaving in a small subset of patients. Bradycardia Hypotension associated with sinus bradycardia, or bradycardia due to A-V block, within minutes after the onset of myocardial infarction often responds to atropine; this is the acknowledged treatment of choice (113). However, bradycardia occurring later may have different implications,particularly when hypotension is not present. In open-chest dogs with coronary occlusion, vagal tone and bradycardia increase


99

the threshold to ventricular fibrillation (114). Furthermore, acceleration of heart rate increases infarct size in experimental animals (46). Thus, bradycardia after the initial phase of infarction may not require treatment, and treatment in the absence of hypotension may be deleterious.


Ventricular Dysrhythmia PVCs occur in most patients with acute myocardial infarction. Contrary to earlier expectations, ventricular tachycardia appears to accompany late, as often or more frequently than early PVCs (115) (G.C. Oliver and R. E. Kleiger, personal commu nication). Similarly, ventricular tachycardia can be induced most readily experimen tally by paced beats with long coupling intervals (116). Suppression of PVCs and reduction of pre-hospital ventricular fibrillation results from intramuscular administration of lidocaine sufficient to produce blood levels of 2 IAg/ml for one hour (117). In the CCU, lidocaine (118), quinidine (119), or procainamide hydrochloride (120) reduce the incidence of ventricular fibrillation substantially. However, because PVCs and other premonitory dysrhythmias as well as ventricular fibrillation itself can be treated (with lidocaine and other antiarrhyth mics) so successfully in the CCU, prophylaxis with lidocaine does not lower mortal ity demonstrably. Because lidocaine depresses cardiac performance only minimally (121), exhibits few side effects, and is readily titratable, it has become the established treatment of choice for PVCs and ventricular tachyarrhythmias in the CCU. PVCs resistant to suppression with lidocaine occur with high prevailing heart rates (122), and may respond after heart rate has been reduced. Investigational antiarrhythmic' agents such as QX 572, a lidocaine derivative, may ultimately prove particularly useful in suppressing lidocaine-resistant PVCs (123). Other agents (investigational in the United States) such as Verapamil, capable of blocking calcium transport across the cell membrane and inhibiting slow current automaticity are likely to be effective antiarrhythmic agents in patients with infarction (124). Bretylium tosylate (investigational in the United States) sometimes suppresses refractory PVCs. The early catecholamine release induced by the drug may be a useful attribute in patients with left ventricular failure or A-V block (125). When life-threatening ventricular dysrhythmias persist, overdrive suppression with ventricular pacing (126) or excision of a region of the ventricle responsible for re-entry (127) has occasionally been useful. However, these approaches are rarely indicated in patients with acute myocardial infarction. Recently, /3-adrenergic blocking agents have been used to treat ventricular as well as supraventricular tachyarrhythmias associated with acute myocardial infarction, particularly when left ventricular failure is not prominent. For example, Acebutolol, a /3-blocker with less of the negative inotropic effects seen with propranolol, suppressed PVCs and decreased the incidence of ventricular fibrillation (128). When tachyarrhythmias persist and result in impaired ventricular performance, electrical cardioversion is usually required. If digitalis intoxication is suspected, cardioversion of many supraventricular tachycardias (but not atrial fibrillation) may be accomplished by rapid atrial pacing (129).

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KLEIN & SOBEL

MANAGEMENT OF OTHER LIFE-THREATENING


COMPLICATIONS

Three catastrophic complications of myocardial infarction require surgical interven tion: rupture of the ventricular free wall, the interventricular septum, or a papillary muscle. Intraaortic balloon counterpulsation may provide hemodynamic stabiliza tion prior to immediate surgery or permit its delay until some healing has occurred (130). Cardiac rupture occurs with extensive infarction which is not confined to the inferior left ventricular wall. Its incidence is approximately 5% (131) and its progno sis is dismal (132). Abrupt bradycardia or electromechanical dissociation may her ald its occurrence (133). Rupture of the interventricular septum occurs in approximately 1% of patients with anteroseptal infarction with a high mortality in the first hour (134). Sur gery may be successful when hemodynamic support is sufficient to allow fibrous healing for three weeks prior to operation (135). A similar approach is often required to deal with papill ary muscle rupture. ANTICOAGULATION AND FIBRINOLYTIC THERAPY

Improved survival has not been observed consistently after fibrinolytic therapy (136--139), but sporadic reports of favorable effects of anticoagulants on mortality continue to appear (140), despite the absence of conclusive findings after more than two decades of evaluation. Although salutary effects on the underlying coronary disease, progression or recurrence of infarction, and long-term survival have not been demonstrable consistently, it is clear that anticoagulation decreases the inci dence of cerebral emboli after myocardial infarction from approximately 4 to 1 % (141). Furthermore, mini-dose heparin reduces the incidence of deep vein thrombo sis substantially (142, 143). Recently, the possible role of platelets (144) and altered blood viscosity (145) in mediating or potentiating coronary artery disease has been considered. However, the value of anti platelet drugs such as aspirin or dipyridamole to patients with acute infarction remains conjectural. -

SUMMARY AND GUIDELINES FOR PATIENT MANAGEMENT

As with many medical emergencies, initial evaluation of the patient must be rapid and treatment must often be initiated prior to definitive diagnosis. Infarction is usually confirmed electrocardiographically and by serial changes in plasma en zymes. Detection of elevated MB CPK may be definitive, particularly in patients with other enzymes released from non-cardiac sources (146, 147). Scintigraphy is useful when hospital admission is delayed and elevated enzyme activity may have regressed. In the Coronary Care Unit, prophylactic administration of antiarrhythmic drugs is not necessary, since conscientious manual monitoring or computer monitoring

MYOCARDIAL INFARCTION (capable of detecting more than

99%

of PVCs

(148),

101

coupled with aggressive

treatment of premonitory dysrhythmias and prompt defibrillation, can reduce mor tality as effectively. Derangements underlying dysrhythmias such as hypoxemia; alkalosis or acidosis; altered plasma potassium, calcium, or magnesium; digitalis


toxicity; or hypovolemia should be identified and corrected. Sinus tachycardia not due to hypovolemia, pericarditis, or congestive heart failure may respond to reduc tion of anxiety, mild sedation, effective analgesia with morphine, or }3-adrenergic blockade. Sinus bradycardia associated with hypotension in the early phase of myocardial infarction should be treated with atropine. Newly developed trifascicu lar block or hemodynamically compromising bradycardia due to persistent A-V block often can be best managed with a temporary transvenous pacemaker. PVCs should be treated aggressively to reduce the likelihood of ventricular fibrillation. Ventricular fibrillation or sustained ventricular tachycardia with hemodynamic sequelae requires immediate electrical countershock. Asystole requires immediate pacing, usually best achieved with a transthoracic pacemaker. Hemodynamic monitoring is useful in any patient with complications such as hypotension, tachycardia, or pulmonary edema. Serial determinations of

PAo

and

cardiac output with the use of a Swan-Ganz thermodilution catheter are useful in adjustment of drug and fluid therapy. A guide for management for subsets of patients categorized hemodynamically is summarized in Table I. The therapeutic approaches outlined are designed to improve hemodynamics without compromising myocardial viability. Although additional interventions such as administration of GIK, hyaluronidase, and mannitol may become established adjuncts, their efficacy in preserving myocardium in the clinical setting has not yet been demonstrated. Anticoagulation with mini-dose heparin is useful early after the onset of infarc tion, particularly in patients with left ventricular failure. Discharge from the hospi tal after one to two weeks is not associated with increased morbidity or mortality unless specific complications persist after the first six days, including newly devel oped bundle branch block, ventricular dysrhythmia, recurrent chest pain, left ven tricular failure, hypotension, or ST-segment elevation

(149-151).

When infarction

is extensive or complicated, prolonged electrocardiographic monitoring and hospi talization for several weeks are generally required.

ACKNOWLEDGMENT Original work from the authors' laboratory was supported in part by the National Heart and Lung Institute, Washington University SCOR in Ischemic Heart Disease HL

17646.

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KLEIN & SOBEL


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Medical and surgical management of myocardial infarction.

Management of myocardial infarction.

Management of acute myocardial infarction.

Management of myocardial infarction in young women.

Management of myocardial infarction in the community.

Letter: Management of acute myocardial infarction.

Letter: Management of arrhythmia in myocardial infarction.

Pre-hospital management of acute myocardial infarction.

Psychological management of the myocardial infarction patient.

Management of acute myocardial infarction. Pathophysiological considerations.

The Emergency Medical Care of Patients With Acute Myocardial Infarction.

Diseases of the cardiovascular system. Management of acute myocardial infarction.

Management of cardiogenic shock complicating acute myocardial infarction.

[Advance in diagnosis and management of myocardial infarction (author's transl)].

Vasodilators in the management of acute myocardial infarction.

Sequential management of post-myocardial infarction ventricular septal defects.

Ambulant management of patients with recent myocardial infarction.

Management of intractable ventricular tachyarrhythmias after myocardial infarction.

Management of acute myocardial infarction in the very elderly.

Complicated myocardial infarction with chronic pulmonary disease. Problems in management.

Type-II myocardial infarction--patient characteristics, management and outcomes.

Acute myocardial infarction: initial manifestations, management, and prognosis.

Medical management of acute myocardial infarction in Ireland: information from the Second International Study of Infarct Survival (ISIS-2).

Hyperlipidemia medication management in patients admitted for a myocardial infarction.