Drugs 41 (Supp!. 2): 1-8, 1991 0012-6667/91/0200-0001/$04.00/0 © Adis International Limited All rights reserved. DRSUP2141a
Sudden Cardiac Death After Myocardial Infarction Ross D. Fletcher Cardiology Section Georgetown University, and Veterans Affairs Medical Center, Washington, DC, USA
SlImmary
Recent advances in the understanding of the mechanisms of sudden cardiac death have been paralleled by technical advances in diagnosis and treatment, involving ambulatory Holter monitoring and the use of implantable defibrillators. Risk factors predisposing toward sudden cardiac death in the postmyocardial infarction setting and in patients with congestive heart failure include the presence of ventricular ectopy [> 10 premature ventricular contractions (PVC) per hour], frequent episodes of ventricular pairs and nonsustained ventricular tachycardia on 24-hour Holter monitoring, and a depressed left ventricular ejection fraction. Additional risk factors for sudden cardiac death in coronary artery disease include arterial stenosis in coronary vessels supplying intact myocardium remote from the infarction site, the presence of late potentials on the signal averaged ECG, and attenuation of the normal variation in heart rate. The ability to induce sustained ventricular tachycardia (SVT) on electrophysiological testing is highly predictive of sudden cardiac death after myocardial infarction. Conversely, the ease of suppression of the induced tachycardia with antiarrhythmic agents is correlated with the risk of subsequent lethal ventricular arrhythmia. The detrimental effect of frequent ventricular ectopy (> 10 PVC/h) on survival in coronary artery disease is particularly pronounced in patients with moderately well preserved left ventricular function [ejection fraction (EF) > 30%], thereby suggesting that these patients may be better served by antiarrhythmic therapy than those with severely depressed left ventricular function. In light of the findings from the Cardiac Arrhythmia Suppression Trial (CAST), that indicated an increased mortality rate associated with the use of the Class Ic antiarrhythmics encainide and tlecainide in postmyocardiaI infarction patients, it is feasible that the use of Class III antiarrhythmics (which prolong cardiac repolarisation rather than conduction) may be more appropriate in this setting. A number of clinical studies are currently addressing the question of whether amiodarone reduces the incidence of sudden cardiac death in coronary artery disease and congestive heart failure.
Sudden cardiac death is one of the few medical syndromes defined by the speed of dying rather than by specific underlying pathology. The syndrome attempts to differentiate lethal arrhythmias from circulatory or pump failure, distinguishing patients who might survive after reversal of electrical instability from those with a critical irreversible loss
of myocardium. The potential 'reversible' nature of this form of 'death' has stimulated extensive efforts to detect and rapidly treat the events, first in coronary care units and then in community resuscitation programmes. The installation of implantable defibrillators, complete with 24-hour monitoring, is the latest development in correcting lethal
Drugs 41 (Supp/. 2) 1991
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rapid ventricular arrhythmias. Prevention of the final event is more difficult and may require antiarrhythmic therapy. Other preventive therapies correct specific underlying pathology. Although the underlying pathology of sudden cardiac death is heterogeneous, the syndrome has helped to focus the epidemiology of cardiac disease and the search for appropriate therapies. The incidence of 400 000 sudden cardiac deaths per year in the United States is enough to generate concern and mobilise investigations and health care resources (Gordon & Kannel 1971).
1. Mechanisms for Sudden Cardiac Death Progress in documenting the mechanisms of sudden cardiac death has paralleled technical advances in diagnosis and therapy. These advances include continuous monitoring in cardiac care units and the ambulatory Holter ECG recordings. The arrhythmia recorded by Holter monitoring (pandis & Morganroth 1983; Pratt et al. 1983) and cardiac care units is usually ventricular fibrillation, frequently preceded by sustained ventricular tachycardia (SVT) > 180 beats/min and often polymorphic in type. Monomorphic tachycardia < 180 beats/min may deteriorate to ventricular fibrillation, especially when it causes poor perfusion. More recently, a group of patients with severe congestive heart failure (CHF) [Luu et al. 1989] awaiting cardiac transplant had unexpected cardiac arrests associated with a high incidence of bradyarrhythmia < 55 beats/min [sinus bradycardia 43% and atrioventricular (A V) block 10%]. Electromechanical dissociation occurred in 10%. Ventricular tachycardia (VT) leading to ventricular fibrillation occurred in 38%. Precipitating causes could not be found in 40%, while pulmonary and coronary emboli, hyperkalaemia and hypoglycaemia caused the other arrests. Ventricular fibrillation is still likely to be the arrhythmia in most patients with sudden death after myocardial infarction who have not yet deteriorated to the point where they require cardiac transplant. Many of these patients have a high prevalence of frequent premature ventricular contractions (PVC) or ventricular repetitive beats, but
may also require the participation of additional neurohormonal mechanisms since the sympathetic and parasympathetic systems seem to set the stage for fatal arrhythmia. Postmortem studies demonstrating a fresh thrombus in coronary arteries suggest a new structural cause for electrical instability, but chronic fibrosis is an equally frequent underlying finding (Davies & Thomas 1984).
2. Definitions of Sudden Cardiac Death Sudden cardiac death is easily recognised in individual patients, but when large clinical trials attempt to formulate precise definitions the results are varied and may alter the conclusions that can be drawn. The World Health Organization defines sudden cardiac death as death occurring within 24 hours of the onset of cardiac symptoms. After an extensive review, Gillum et al. (1984) published criteria for events which define sudden death due to coronary disease as: (a) death witnessed as occurring within I hour after the onset of severe cardiac symptoms or within I hour after the patient was seen without symptoms; (b) no myocardial infarction within the 4 weeks before death; and (c) no known nonatherosclerotic or noncardiac process that was probably lethal. 'Rapid death' in this classification is reserved for patients with severe cardiac symptoms for I to 24 hours before death. Hinkle et al. (1969) classified 142 deaths into I (arrhythmic deaths; 58%), II (circulatory deaths; 40%) and III (unclassifiable; < 1%). Acute ischaemia occurred in 37% of arrhythmic deaths and 10% of circulatory deaths. This Hinkle classification has been modified by other investigators. Kannel et al. (1979), the CONSENSUS investigators and many others use the more restrictive definition of death within I hour after the onset of symptoms. In studies of possible methods for preventing arrhythmia, such as long term amiodarone therapy (Herre et al. 1989), the definition of sudden cardiac death includes deaths which occurred instantaneously, unwitnessed, during sleep or as a direct result of documented arrhythmia. Others exclude as sudden those instantaneous deaths that occurred in the presence of deteriorating clinical symptoms. Dar-
Sudden Cardiac Death After Myocardial Infarction
gie et al. (1987) calculated 2 sudden cardiac death rates in a group of patients with CHF: 71 % if unexpected, with deterioration < 24 hours prior to death, and 55% when patients with clinical deterioration in the previous month were excluded. In each instance arrhythmia was the final mechanism of death, but this was associated with increasing circulatory failure in 16%. Antiarrhythmic therapy, pharmacological and non pharmacological, may help both the group with worsening circulatory failure and those patients who are apparently stable. Arrhythmia control provides the time to achieve a state of compensated heart failure. Follow-up of individual patients in our defibrillator clinic leads to the realisation that many may have progressive worsening of circulatory failure prior to these arrhythmic episodes. By some definitions, this is irreversible 'circulatory' sudden death and therefore not amenable to antiarrhythmic therapy. Given a second or third chance of surviving, the patient with a defibrillator is often literally shocked into the realisation that his overindulgence in salt or fluid went too far, and after a brief hospitalisation to achieve circulatory compensation he returns home, surviving many more months without similar episodes. Other patients may be noncompliant with their iJ-blocker or other antiarrhythmic agent, or may indulge in sudden heavy exercise and must be 'saved' by their implantable defibrillator after ventricular fibrillation. Renewed adherence to medication and cardiac rehabilitation provides long event-free periods. The newer defibrillators can document and save the intervals before and after such episodes of VT or ventricular fibrillation (fig. I). They will soon provide stored electrograms so that long term arrhythmia monitoring will further clarify the mechanisms of sudden cardiac death and provide an insight with regard to patients not in need of implantable defibrillators.
3. Factors Predisposing to Arrhythmia and Sudden Cardiac Death For some time, many researchers have characterised groups of patients at high risk for sudden cardiac death. This is particularly intensive for
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postmyocardial infarction patients, but has also been examined for patients with CHF from any cause. In most studies, mortality rises with an increased frequency of ventricular arrhythmia. Patients with > 10 PVC/h often have a risk 2 to 3 times greater than those with < 10 PVC/h. Patients with repetitive beats or VT (3 or more consecutive PVC) have a higher mortality rate than those with increased PVC frequency (> 10 PVC/ h) [Ruberman et al. 1981]. Data from Bigger et al. (1984) show an increased risk with 3 to 9 PVC/h. Repetitive firing of > 6 beats (Glicksman et al. 1988) predicts sudden cardiac death more consistently than 2 to 3 beats in a row. While ventricular arrhythmia is a strong predictor of cardiac mortality, haemodynamic compromise such as ejection fraction (EF) < 40% has been an equally strong indicator (Schulze et al. 1977). In a vasodilator trial for acute myocardial infarction (Fletcher et al. 1982), pulmonary wedge pressure was measured in all patients at the time of their myocardial infarction. The 3-month mortality after myocardial infarction was predicted by a wedge > 20mm Hg and independently by ventricular repetitive beats. Not surprisingly, patients with both ventricular repetitive beats (~ 3) on 14day 24-hour Holter monitoring and a high wedge pressure showed a 6-fold increase in mortality (29.6%) over patients with neither high wedge pressure nor ventricular repetitive beats (5.2%), while patients with either phenomenon alone showed a 3-fold increase. Ventricular arrhythmia was an independent predictor of mortality. The Central Holter Lab for subsequent vasodilator trial in CHF (Cohn et al. 1986) showed that ventricular arrhythmia was an independent predictor of mortality. This was true irrespective of whether the patients had coronary disease or other aetiologies (Fletcher et al. 1986). Those with coronary disease had a higher annual mortality rate (37% with VT, 17% without VT; p < 0.01), but in noncoronary disease VT predicted a similar increase in mortality (23% with VT, 11 % without VT). An important finding is the fact that ventricular arrhythmia in patients with coronary artery disease predicted mortality not only in the immediate
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Ventricular tachycardia Last -19. -18. -,17. -16. -15. -14. -13. -12. -11. -10. -9. -8. -7. -6. -5. -4. -3. -2. -1. -0. -0.
episode detection sequence: R-R interval = 570 msec R-R interval = 580 msec R-R interval = 580 msec R-R interval = 420 msec R-R interval = 460 msec R-R interval = 870 msec R-R interval = 560 msec R-R interval = 420 msec R-R interval = 340 msec R-R interval = 330 msec R-R interval = 330 msec R-R interval = 340 msec R-R interval = 340 msec R-R interval = 350 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec Ventricular tachycardia detected
Ventricular fibrillation Last -19. -18. -17. -16. -15. -14. -13. -12. -11. -10. -9. -8. -7. -6. -5. -4. -3. -2. -1. -0. -0.
episode detection sequence: R-R interval = 150 msec R-R interval = 170 msec R-R interval = 130 msec R-R interval = 180 msec R-R interval = 120 msec R-R interval = 130 msec R-R interval = 210 msec R-R interval = 130 msec R-R interval = 290 msec R-R interval = 140 msec R-R interval = 150 msec R-R interval = 140 msec R-R interval = 140 msec R-R interval = 130 msec R-R interval = 130 msec R-R interval = 240 msec R-R interval = 130 msec R-R interval = 120 msec R-R interval = 140 msec R-R interval = 140 msec Ventricular fibrillation detected
Fig. 1. The precise R-R intervals before and after therapy with an implantable pacemaker cardioverter defibrillator document ventricular tachycardia and ventricular fibrillation . Successful cardioversion after ventricular tachycardia employed 3 premature paced beats at 81 % of the R-R interval ; successful cardioversion ventricular fibrillation required 34J. Use of a brady pacemaker at 60 beats/ min (1000 msec) is also noted after the patient was defibrillated by the implantable device.
postmyocardial infarction period, but also > 9 months after myocardial infarction. The annual mortality rate in these patients was constant over 3 years. A low EF (below a median of 28%) was an independent risk factor. Those with EF < 28% had annual mortality rates of 32% with VT and 21 % without VT, while those with EF > 28% had rates of 16% with VT and 9% without VT. Since more deaths occur with both ventricular arrhythmia and low EF, the temptation is to direct therapy only at the group with both low EF « 30%) and high levels of arrhythmia. There are 2 reasons why this should not be the sole approach. Firstly, a large number of the patients dying suddenly do not meet these criteria. Secondly, therapies relieving heart failure, such as vasodilators, may work better when the heart failure is severe (CONSENSUS Trial Study Group 1987), but patients with moderate levels of ventricular impairment and complex ventricular arrhythmia also have increased mortality, especially sudden cardiac death. In the Vasodilator Heart Failure Trial (V HeFT) [Fletcher et al. 1988], ventricular repetitive beats increased the relative
risk of dying more for patients with EF > 30%, and especially those with EF > 40%, than for those with EF < 30%. An analysis of the effect of PVC frequency > lO/h and EF < 30% and 30 to 50% was made for a subgroup of these patients with coronary artery disease only (fig. 2). Note that high PVC frequency was associated with a more striking increase in mortality rates over a 3-year period in the high EF group (30 to 50%) than in the low EF group « 23%). Thus, patients with moderate impairment of ventricular function and arrhythmia may be better served by antiarrhythmic therapy. Other factors predicting death and sudden cardiac death include coronary stenosis in those vessels supplying significant remaining myocardium, especially remote from the infarction (Schuster & Bulkley 1981). The presence of late potentials on the signal-averaged electrocardiogram (SAEGG) 10 to 12 days after infarct predicts the inducibility of sustained ventricular arrhythmia and is a marker for sudden cardiac death and other arrhythmias. Kuchar et al. (1987), in a prospective postmyocardial infarction study, showed that the risk of arrhythmia associated with the combination of an EF
Sudden Cardiac Death After Myocardial Infarction
< 40% and an abnormal SAECG was 34%. The risk with a depressed EF alone was 4%. Gomes et al. (1984) in another study of similar patients after myocardial infarction showed an arrhythmia event rate with positive SAECG of 29% versus 3.5% in those with a normal SAECG. This was comparable to high grade ventricular arrhythmias. While not significant, the rate of clinical arrhythmia events after high grade venticular arrhythmias on the 24-hour Holter ECG was 23% versus 9% without. High grade ventricular arrhythmias in this study included PVC> lO/h as well as the occurrence of couplets and/or triplets. The event rate when both an abnormal SAECG and depressed EF were present was 36% versus 9% when both the SAECG and EF were normal. The event rate when the EF, SAECG and Holter recording were all abnormal was 50% versus 0% when all the tests were normal. Previous studies by Simson (1981) and Braithardt et al. (1981) also demonstrated the ability of the SAECG to predict arrhythmia events. Abnormal SAECG values vary slightly but are usually < 20 to 25J.L V for the mean amplitude of the root
100
80
~
60
03 >
.~
:>
UJ
40
D EF < 50 > 30, PVC < 10/h • EF < 50 > 30, PVC> 10/h EF < 30, PVC < 10/h • EF < 30, PVC> 10/h
o
20
o
2
3
Time (years)
Fig. 2. Effect of ejection fraction (EF) and premature ventricular contraction (PVC) frequency on survival. in patients with congestive heart failure (CHF) due to coronary artery disease. In the high EF group (30 to 50%). PVC frequencies > 10jh were associated with a more marked decrease in survival than in patients with a low EF « 30%).
5
mean square in the last 40 msec, QRS duration> 0.120 or 0.118 sec and duration of low amplitude signal> 39 msec. The predictability of late potentials in multiple studies suggests that delayed conduction in a structural scar is a precursor for sudden cardiac death. The disappearance of normal heart rate variability is another noninvasive predictor of arrhythmia events after myocardial infarction. Variable heart rates reflect normal parasympathetic and sympathetic tone. In cardiac disease, this normal modulation becomes much less. The quantification requires only algorithms on Holter tapes. When added to late potentials in a recent study (Farrell et al. 1990), it has a 33% positive predictive accuracy with a 97% negative predictive accuracy and a sensitivity of 56% with specificity of 97%. In addition, programmed electrical stimulation identifies a high risk group. Richards et al. (1983), Denniss et al. (1986) and others have shown that patients with inducible SVT are at a high risk for arrhythmic events after myocardial infarction. It is important to note that in the study of Denniss et al. (1986) and others, inducible ventricular fibrillation (VF) did not predict subsequent clinical events. SVT was induced by somewhat different protocols in each study. Several variables shorten the ventricular effective refractory period and, therefore, the duration of the test intervals. These include the basic drive rate, the number of test intervals in a row, and the strength of the test stimulus. When only I drive rate (600 msec) or only 2 extra stimuli were used, a higher output (20mA) produced the decreased coupling intervals seen in other studies with multiple drive rates (600 to 400 msec) and up to 3 extra stimuli. Two right ventricular stimulation sites were usually used. The ability to induce sustained monomorphic VT rather than VF or polymorphic VT is less likely to be influenced by differences in protocols. SVT is rarely inducible unless underlying structural abnormality exists. While some studies have not confirmed this finding, the data suggest that electrophysiological testing is highly predictive of sudden cardiac death and SVT. Thus a high percentage of patients who will have arrhythmic events may have them on the
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basis of the substrate that produces late potentials, spontaneous high grade ventricular arrhythmia and inducible SVT. Treatment based on electrophysiological testing has been successful in several studies. If SVT is rendered noninducible with antiarrhythmic drugs, the percentage with lethal arrhythmic events falls from 50% (19 of 38 patients) to 9% (4 of 47 patients) [these percentages represent the combined results of 3 studies by Buxton et al. (1984), Klein & Machell (1989) and Wilber et al. (1990)]. While these results, obtained in small numbers of patients, are encouraging, electrophysiological testing will not be standard practice until these data are also demonstrated in large scale trials. Several such trials have been started. Given the pathophysiological heterogeneity of this syndrome it is not surprising to see that therapies as varied as sulfinpyrazone (Anturane Reinfarction Trial Research Group 1980), iJ-blockers (Chadda et al. 1986), amiodarone (Herre et al. 1989), electrophysiologically guided drug therapy (Wilber et al. 1990), coronary artery bypass surgery (Holmes et al. 1989) and implantable defibrillators (Winkle et al. 1989) all reduce the incidence of sudden cardiac death. While antiarrhythmic therapy to date has limited scientific support, it may yet playa role. The results of the Cardiac Arrhythmia Suppression Trial (CAST) [Rogers & CAST Investigators 1989] showed that the very potent PVCsuppressing agents flecainide and encainide caused increased mortality. The low mortality rate of the placebo group in that study made it difficult for any intervention to show benefit. The study did suggest that patients who respond well to antiarrhythmic drugs may have increased survival rates. Antiarrhythmic drugs with less potential for arrhythmia aggravation , started early in the postmyocardial infarction period, may still benefit these patients at high risk. The efficacy of these drugs may be improved if they are directed less at decreasing 'triggers', such as PVC, and more at preventing the re-entrant circuits from sustaining rapid arrhythmias. The adverse effect of class Ie drugs which prolong conduction may point to the possible beneficial effect of class III drugs, which prolong repolarisation. Amiodarone is being used in
Drugs 41 (Suppl. 2) 1991
several postmyocardial infarction and CHF trials. Dr Steven Singh and myself began a Veterans Affairs cooperative trial involving 25 hospitals in September 1989 [The Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF STAT)]. This cooperative trial is directed at patients with CHF and includes a large sample with previous myocardial infarction. In this trial, patients with CHF, EF < 40% and PVC frequency > 10lh will be randomised to amiodarone or placebo. Until this and other new trials are completed, we remain much better at establishing prognosis than at prescribing appropriate therapy.
4. Diagnostic Evaluation and Patient Management Most physicians agree on the management procedures for the patient who has had an episode of sudden cardiac death after myocardial infarction, but managing a patient to prevent sudden death is less well defined. After an episode of sudden cardiac death, electrophysiological testing is indicated, since therapy based on this procedure has been successful. However, if drug failures occur, or if the targets of electrophysiological testing are not present, the patient becomes a candidate for an implantable defibrillator. Close monitoring of these patients will enhance our concepts and capacity to prevent sudden cardiac death without electrical therapy. For the individual patient who has not had an episode of sudden cardiac death, the prognosis should be established by assessing known risk factors, including PVC frequency and ventricular repetitive beats on the 24-hour ECG, 10 to 14 days after myocardial infarction. A low level exercise stress test will assess perfusion of the remaining normal myocardium and the presence of arrhythmia with exercise. A SAECG should be obtained to assess the presence of late potentials. Heart rate variability from the Holter tape should be obtained. Myocardial function as assessed by MUGA or, less reliably, by echocardiogram will further quantify the prognosis. In some centres, patients have undergone further risk stratification and
Sudden Cardiac Death After Myocardial Infarction
therapy based on electrophysiological testing. Common management also includes the control of neurohormonal mechanisms with t3-blockers, treatment of CHF with vasodilators and the use of platelet inhibitors such as aspirin (acetylsalicylic acid) [80 to 325 mg/day]. Many physicians attempt to reduce abnormal blood lipids through diet or drug therapy. Critically narrowed vessels leading to the remaining normal myocardium are revascularised with angioplasty or surgery.
5. Conclusion At present, treatment for the high risk patient does not include any antiarrhythmic therapy other than t3-blockers; physicians feel more secure in omitting antiarrhythmic therapy since the results of CAST. A more effective antiarrhythmic agent of a different class may still prove to be beneficial. Until such data are available, the high risk patient should be carefully monitored for abnormal electrolytes, undue hypoxaemia and precursors of sudden electrical death such as episodes of sustained tachycardia, symptoms of extended palpitations, dizziness or syncope. We await the results of several ongoing trials designed to guide diagnostic and therapeutic interventions more effectively, especially those involving the use of antiarrhythmic drugs.
References Anturane Reinfarction Trial Research Group. Sulfinpyrazone in the prevention of sudden death after myocardial infarction. New England Journal of Medicine 302: 250, 1980 Bigger JT, Fleiss JF, Kliger R, Miller JR, Rohnitzky 1M. The multicenter postinfarction research group: the relationship among ventricular arrhythmias, left ventricular dysfunction and mortality in the two years after myocardial infarction. Circulation 69: 250, 1984 Breithardt G , Becker R, Seipel L, Abendroth RR, Ostermeyer J. Non-invasive detection oflate potentials in man: a new marker for ventricular tachycardia. European Heart Journal 2: I-II, 1981 Buxton AE, Marchlinski FE, Waxman HL, Flores BT, Cassidy OM, et al. Prognostic factors in non-sustained ventricular tachycardia. American Journal of Cardiology 53: 1275-1279, 1984 Chadd a K, Goldstein S, Byington R, Curb JD. Effect of propranolol after acute myocardial infarction in patients with congestive heart failure. Circulation 73: 511-517, 1986 Cohn IN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, et al. Effect of vasodilator therapy on mortality in chronic con-
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gestive heart failure. New England Journal of Medicine 314: 1547,1986 CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). New England Journal of Medicine 316: 1429-1435, 1987 Dargie HJ, Cleland JGF, Leckie BJ, Inglis CG, East BW, et al. Relation of arrhythmias and electrolyte abnormalities to survival in patients with severe chronic heart failure. Circulation 75 (Suppl. IV): IV-98, 1987 Davies MJ, Thomas A. Thrombosis and acute coronary artery lesions in sudden cardiac ischaemic death. New England Journal of Medicine 310: 1138, 1984 Denniss AR, Richard DA, Cody DV, Russell FA, Young AA, et al. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 74: 731745, 1986 Ferrell T, Bashir Y, Cripps T, Malik M, Bennett ED, et al. Accurate risk stratification for arrhythmic events based only on Holter variables in post infarction patients. Circulation 82 (Suppl. III): 139, 1990 Fletcher R, Archibald 0, Cohn J , and VA Study Group. Day I and day 14 24-hour electrocardiogram as predictors of post myocardial infarction mortality. Circulation 66: II-II, 1982 Fletcher RD, Archibald 0, Orndorff J, Cohn J. Cooperative Study Group. Dysrhythmias on short term Holter as an independent predictor of mortality in congestive heart failure. Journal of the American College of Cardiology 7 (Suppl. A): 143A, 1986 Fletcher RD, Johnson G, Cohn J, VHeFT VA Coop Study. Increased risk of ventricular arrhythmia with mild ventricular dysfunction in CHF. Circulation 78 (Suppl. II): 346, 1988 Gillum RF, Fortmann SP, Prineas RJ, Kottke TE. International diagnostic criteria for acute myocardial infarction and acute stroke. American Heart Journal 108: 150, 1984 Glicksman FL, Huikuri HV, Dwyer EM, Anthony RM, Castellanos A, et al. Differential prognostic significance of 2-5 or ~ 6 repetitive ventricular ectopic beats. Circulation 78: 279, 1988 Gomes JA, Winters SL, Stewart 0, Horowitz X, Milner M, et al. A new noninvasive index to predict sustained ventricular tachycardia and sudden death in the first year after myocardial infarction: based on signal-averaged electrocardiogram, radionuclide ejection fraction and Holter monitoring: criteria for acute myocardia infarction and acute stroke. American Heart Journal 108: 150, 1984 Gordon I, Kannel WB. Premature mortality from coronary heart disease: Framingham study. Journal of the American Medical Association 215: 1617-1625, 1971 Herre JM, Sauve MJ, Malone P, Griffin Jc, Helmy I, et al. Longterm results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. Journal of the American College of Cardiology 13: 442-449, 1989 Hinkle LE, Whitney LM, Lehman EW, Dunn J, Benjamin S, et al. Occupation, education and coronary heart disease. Science 161: 283, 1969 Holmes Jr DR, Davis X, Gersh BJ, Mock MB, Pettinger MB, et al. Risk factor profiles of patients with sudden cardiac death and death from other cardiac causes: a report from the Coronary Artery Surgery Study. Journal of the American College of Cardiology 13: 524-530, 1989 Kannel WB, Sorlie P, McNamara PM. Prognosis after initial myocardial infarction. American Journal of Cardiology 44: 53, 1979 Klein RC, Machell C. Use of electrophysiologic testing in patients with non-sustained ventricular tachycardia: prognostic and
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therapeutic implications. Journal of the American College of Cardiology 14: 155-161, 1989 Kuchar DL, Thorburn CW, Sam mel NL. Prediction of serious arrhythmic events after myocardial infarction: signal-averaged electrocardiogram Holter monitoring and radionuc1ide ventriculography. Journal of the American College of Cardiology 9: 531-538, 1987 Luu M, Stevenson WG, Stevenson LW, Baron K, Walden J. Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 80: 1675-1680, 1989 Pandis I, Morganroth J. Sudden death in hospitalised patients: cardiac rhythm disturbances detected by ambulatory electrocardiographic monitoring. Journal of the American College of Cardiology 2: 798, 1983 Pratt CM, Francis MJ, Luck JC Wyndham CR, Miller PR, et al. Analysis of ambulatory tapes in 15 patients during spontaneous ventricular fibrillation with special reference to preceding arrhythmic events. Journal of the American College of Cardiology 2: 795, 1983 Richards DA, Cody DV, Denniss AR, Russell PA, Young AA, et al. Ventricular electrical instability: a predictor of death after myocardial infarction. American College of Cardiology 51: 75, 1983 Rogers WJ, CAST investigators. The Cardiac Arrhythmia Suppression Trial (CAST). New England Journal of Medicine 321: 406-412,1989 Ruberman W, Weinblatt E, Goldberg JD, Frank CW, Chaudhary
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BS, et al. Ventricular premature complexes and sudden death after myocardial infarction. Circulation 64: 297, 1981 Schulze RA, Strauss HW, Pitt B. Sudden death in the year following myocardial infarction: relation to ventricular premature contractions in the late hospital phase and left ventricular ejection fraction. American Journal of Medicine 62: 192-199, 1977 Schuster EH, Bulkley BH. Early post-infarction angina-ischemia at a distance and ischemia in the infarct zone. New England Journal of Medicine 305: 1101, 1981 Simson MB. Use of signals in the terminal QRS complex to identify patients with ventricular tachycardia after myocardial infarction. Circulation 64: 235-242, 1981 Wilber DJ, Olshansky B, Moran JF, Scanlon PJ. Electrophysiological testing and non-sustained ventricular tachycardia: use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation 82: 350-358, 1990 Winkle RA, Mead RH, Ruder MA, Guadiani VA, Smith NA. Long-term outcome with the automatic implantable cardiovcrter defibrillator. Journal of the American College of Cardiology 13: 1353-1361, 1989
Correspondence and reprints: Assoc. Prof. Ross D. Fie/chI'/', Cardiology Section, Veterans Affairs Medical Center, 50 Irving Street NW, Washington, DC 20422, USA.
Sudden Cardiac Death After Myocardial Infarction Ross D. Fletcher Cardiology Section Georgetown University, and Veterans Affairs Medical Center, Washington, DC, USA
SlImmary
Recent advances in the understanding of the mechanisms of sudden cardiac death have been paralleled by technical advances in diagnosis and treatment, involving ambulatory Holter monitoring and the use of implantable defibrillators. Risk factors predisposing toward sudden cardiac death in the postmyocardial infarction setting and in patients with congestive heart failure include the presence of ventricular ectopy [> 10 premature ventricular contractions (PVC) per hour], frequent episodes of ventricular pairs and nonsustained ventricular tachycardia on 24-hour Holter monitoring, and a depressed left ventricular ejection fraction. Additional risk factors for sudden cardiac death in coronary artery disease include arterial stenosis in coronary vessels supplying intact myocardium remote from the infarction site, the presence of late potentials on the signal averaged ECG, and attenuation of the normal variation in heart rate. The ability to induce sustained ventricular tachycardia (SVT) on electrophysiological testing is highly predictive of sudden cardiac death after myocardial infarction. Conversely, the ease of suppression of the induced tachycardia with antiarrhythmic agents is correlated with the risk of subsequent lethal ventricular arrhythmia. The detrimental effect of frequent ventricular ectopy (> 10 PVC/h) on survival in coronary artery disease is particularly pronounced in patients with moderately well preserved left ventricular function [ejection fraction (EF) > 30%], thereby suggesting that these patients may be better served by antiarrhythmic therapy than those with severely depressed left ventricular function. In light of the findings from the Cardiac Arrhythmia Suppression Trial (CAST), that indicated an increased mortality rate associated with the use of the Class Ic antiarrhythmics encainide and tlecainide in postmyocardiaI infarction patients, it is feasible that the use of Class III antiarrhythmics (which prolong cardiac repolarisation rather than conduction) may be more appropriate in this setting. A number of clinical studies are currently addressing the question of whether amiodarone reduces the incidence of sudden cardiac death in coronary artery disease and congestive heart failure.
Sudden cardiac death is one of the few medical syndromes defined by the speed of dying rather than by specific underlying pathology. The syndrome attempts to differentiate lethal arrhythmias from circulatory or pump failure, distinguishing patients who might survive after reversal of electrical instability from those with a critical irreversible loss
of myocardium. The potential 'reversible' nature of this form of 'death' has stimulated extensive efforts to detect and rapidly treat the events, first in coronary care units and then in community resuscitation programmes. The installation of implantable defibrillators, complete with 24-hour monitoring, is the latest development in correcting lethal
Drugs 41 (Supp/. 2) 1991
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rapid ventricular arrhythmias. Prevention of the final event is more difficult and may require antiarrhythmic therapy. Other preventive therapies correct specific underlying pathology. Although the underlying pathology of sudden cardiac death is heterogeneous, the syndrome has helped to focus the epidemiology of cardiac disease and the search for appropriate therapies. The incidence of 400 000 sudden cardiac deaths per year in the United States is enough to generate concern and mobilise investigations and health care resources (Gordon & Kannel 1971).
1. Mechanisms for Sudden Cardiac Death Progress in documenting the mechanisms of sudden cardiac death has paralleled technical advances in diagnosis and therapy. These advances include continuous monitoring in cardiac care units and the ambulatory Holter ECG recordings. The arrhythmia recorded by Holter monitoring (pandis & Morganroth 1983; Pratt et al. 1983) and cardiac care units is usually ventricular fibrillation, frequently preceded by sustained ventricular tachycardia (SVT) > 180 beats/min and often polymorphic in type. Monomorphic tachycardia < 180 beats/min may deteriorate to ventricular fibrillation, especially when it causes poor perfusion. More recently, a group of patients with severe congestive heart failure (CHF) [Luu et al. 1989] awaiting cardiac transplant had unexpected cardiac arrests associated with a high incidence of bradyarrhythmia < 55 beats/min [sinus bradycardia 43% and atrioventricular (A V) block 10%]. Electromechanical dissociation occurred in 10%. Ventricular tachycardia (VT) leading to ventricular fibrillation occurred in 38%. Precipitating causes could not be found in 40%, while pulmonary and coronary emboli, hyperkalaemia and hypoglycaemia caused the other arrests. Ventricular fibrillation is still likely to be the arrhythmia in most patients with sudden death after myocardial infarction who have not yet deteriorated to the point where they require cardiac transplant. Many of these patients have a high prevalence of frequent premature ventricular contractions (PVC) or ventricular repetitive beats, but
may also require the participation of additional neurohormonal mechanisms since the sympathetic and parasympathetic systems seem to set the stage for fatal arrhythmia. Postmortem studies demonstrating a fresh thrombus in coronary arteries suggest a new structural cause for electrical instability, but chronic fibrosis is an equally frequent underlying finding (Davies & Thomas 1984).
2. Definitions of Sudden Cardiac Death Sudden cardiac death is easily recognised in individual patients, but when large clinical trials attempt to formulate precise definitions the results are varied and may alter the conclusions that can be drawn. The World Health Organization defines sudden cardiac death as death occurring within 24 hours of the onset of cardiac symptoms. After an extensive review, Gillum et al. (1984) published criteria for events which define sudden death due to coronary disease as: (a) death witnessed as occurring within I hour after the onset of severe cardiac symptoms or within I hour after the patient was seen without symptoms; (b) no myocardial infarction within the 4 weeks before death; and (c) no known nonatherosclerotic or noncardiac process that was probably lethal. 'Rapid death' in this classification is reserved for patients with severe cardiac symptoms for I to 24 hours before death. Hinkle et al. (1969) classified 142 deaths into I (arrhythmic deaths; 58%), II (circulatory deaths; 40%) and III (unclassifiable; < 1%). Acute ischaemia occurred in 37% of arrhythmic deaths and 10% of circulatory deaths. This Hinkle classification has been modified by other investigators. Kannel et al. (1979), the CONSENSUS investigators and many others use the more restrictive definition of death within I hour after the onset of symptoms. In studies of possible methods for preventing arrhythmia, such as long term amiodarone therapy (Herre et al. 1989), the definition of sudden cardiac death includes deaths which occurred instantaneously, unwitnessed, during sleep or as a direct result of documented arrhythmia. Others exclude as sudden those instantaneous deaths that occurred in the presence of deteriorating clinical symptoms. Dar-
Sudden Cardiac Death After Myocardial Infarction
gie et al. (1987) calculated 2 sudden cardiac death rates in a group of patients with CHF: 71 % if unexpected, with deterioration < 24 hours prior to death, and 55% when patients with clinical deterioration in the previous month were excluded. In each instance arrhythmia was the final mechanism of death, but this was associated with increasing circulatory failure in 16%. Antiarrhythmic therapy, pharmacological and non pharmacological, may help both the group with worsening circulatory failure and those patients who are apparently stable. Arrhythmia control provides the time to achieve a state of compensated heart failure. Follow-up of individual patients in our defibrillator clinic leads to the realisation that many may have progressive worsening of circulatory failure prior to these arrhythmic episodes. By some definitions, this is irreversible 'circulatory' sudden death and therefore not amenable to antiarrhythmic therapy. Given a second or third chance of surviving, the patient with a defibrillator is often literally shocked into the realisation that his overindulgence in salt or fluid went too far, and after a brief hospitalisation to achieve circulatory compensation he returns home, surviving many more months without similar episodes. Other patients may be noncompliant with their iJ-blocker or other antiarrhythmic agent, or may indulge in sudden heavy exercise and must be 'saved' by their implantable defibrillator after ventricular fibrillation. Renewed adherence to medication and cardiac rehabilitation provides long event-free periods. The newer defibrillators can document and save the intervals before and after such episodes of VT or ventricular fibrillation (fig. I). They will soon provide stored electrograms so that long term arrhythmia monitoring will further clarify the mechanisms of sudden cardiac death and provide an insight with regard to patients not in need of implantable defibrillators.
3. Factors Predisposing to Arrhythmia and Sudden Cardiac Death For some time, many researchers have characterised groups of patients at high risk for sudden cardiac death. This is particularly intensive for
3
postmyocardial infarction patients, but has also been examined for patients with CHF from any cause. In most studies, mortality rises with an increased frequency of ventricular arrhythmia. Patients with > 10 PVC/h often have a risk 2 to 3 times greater than those with < 10 PVC/h. Patients with repetitive beats or VT (3 or more consecutive PVC) have a higher mortality rate than those with increased PVC frequency (> 10 PVC/ h) [Ruberman et al. 1981]. Data from Bigger et al. (1984) show an increased risk with 3 to 9 PVC/h. Repetitive firing of > 6 beats (Glicksman et al. 1988) predicts sudden cardiac death more consistently than 2 to 3 beats in a row. While ventricular arrhythmia is a strong predictor of cardiac mortality, haemodynamic compromise such as ejection fraction (EF) < 40% has been an equally strong indicator (Schulze et al. 1977). In a vasodilator trial for acute myocardial infarction (Fletcher et al. 1982), pulmonary wedge pressure was measured in all patients at the time of their myocardial infarction. The 3-month mortality after myocardial infarction was predicted by a wedge > 20mm Hg and independently by ventricular repetitive beats. Not surprisingly, patients with both ventricular repetitive beats (~ 3) on 14day 24-hour Holter monitoring and a high wedge pressure showed a 6-fold increase in mortality (29.6%) over patients with neither high wedge pressure nor ventricular repetitive beats (5.2%), while patients with either phenomenon alone showed a 3-fold increase. Ventricular arrhythmia was an independent predictor of mortality. The Central Holter Lab for subsequent vasodilator trial in CHF (Cohn et al. 1986) showed that ventricular arrhythmia was an independent predictor of mortality. This was true irrespective of whether the patients had coronary disease or other aetiologies (Fletcher et al. 1986). Those with coronary disease had a higher annual mortality rate (37% with VT, 17% without VT; p < 0.01), but in noncoronary disease VT predicted a similar increase in mortality (23% with VT, 11 % without VT). An important finding is the fact that ventricular arrhythmia in patients with coronary artery disease predicted mortality not only in the immediate
Drugs 41 (Supp/. 2) 1991
4
Ventricular tachycardia Last -19. -18. -,17. -16. -15. -14. -13. -12. -11. -10. -9. -8. -7. -6. -5. -4. -3. -2. -1. -0. -0.
episode detection sequence: R-R interval = 570 msec R-R interval = 580 msec R-R interval = 580 msec R-R interval = 420 msec R-R interval = 460 msec R-R interval = 870 msec R-R interval = 560 msec R-R interval = 420 msec R-R interval = 340 msec R-R interval = 330 msec R-R interval = 330 msec R-R interval = 340 msec R-R interval = 340 msec R-R interval = 350 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec R-R interval = 370 msec Ventricular tachycardia detected
Ventricular fibrillation Last -19. -18. -17. -16. -15. -14. -13. -12. -11. -10. -9. -8. -7. -6. -5. -4. -3. -2. -1. -0. -0.
episode detection sequence: R-R interval = 150 msec R-R interval = 170 msec R-R interval = 130 msec R-R interval = 180 msec R-R interval = 120 msec R-R interval = 130 msec R-R interval = 210 msec R-R interval = 130 msec R-R interval = 290 msec R-R interval = 140 msec R-R interval = 150 msec R-R interval = 140 msec R-R interval = 140 msec R-R interval = 130 msec R-R interval = 130 msec R-R interval = 240 msec R-R interval = 130 msec R-R interval = 120 msec R-R interval = 140 msec R-R interval = 140 msec Ventricular fibrillation detected
Fig. 1. The precise R-R intervals before and after therapy with an implantable pacemaker cardioverter defibrillator document ventricular tachycardia and ventricular fibrillation . Successful cardioversion after ventricular tachycardia employed 3 premature paced beats at 81 % of the R-R interval ; successful cardioversion ventricular fibrillation required 34J. Use of a brady pacemaker at 60 beats/ min (1000 msec) is also noted after the patient was defibrillated by the implantable device.
postmyocardial infarction period, but also > 9 months after myocardial infarction. The annual mortality rate in these patients was constant over 3 years. A low EF (below a median of 28%) was an independent risk factor. Those with EF < 28% had annual mortality rates of 32% with VT and 21 % without VT, while those with EF > 28% had rates of 16% with VT and 9% without VT. Since more deaths occur with both ventricular arrhythmia and low EF, the temptation is to direct therapy only at the group with both low EF « 30%) and high levels of arrhythmia. There are 2 reasons why this should not be the sole approach. Firstly, a large number of the patients dying suddenly do not meet these criteria. Secondly, therapies relieving heart failure, such as vasodilators, may work better when the heart failure is severe (CONSENSUS Trial Study Group 1987), but patients with moderate levels of ventricular impairment and complex ventricular arrhythmia also have increased mortality, especially sudden cardiac death. In the Vasodilator Heart Failure Trial (V HeFT) [Fletcher et al. 1988], ventricular repetitive beats increased the relative
risk of dying more for patients with EF > 30%, and especially those with EF > 40%, than for those with EF < 30%. An analysis of the effect of PVC frequency > lO/h and EF < 30% and 30 to 50% was made for a subgroup of these patients with coronary artery disease only (fig. 2). Note that high PVC frequency was associated with a more striking increase in mortality rates over a 3-year period in the high EF group (30 to 50%) than in the low EF group « 23%). Thus, patients with moderate impairment of ventricular function and arrhythmia may be better served by antiarrhythmic therapy. Other factors predicting death and sudden cardiac death include coronary stenosis in those vessels supplying significant remaining myocardium, especially remote from the infarction (Schuster & Bulkley 1981). The presence of late potentials on the signal-averaged electrocardiogram (SAEGG) 10 to 12 days after infarct predicts the inducibility of sustained ventricular arrhythmia and is a marker for sudden cardiac death and other arrhythmias. Kuchar et al. (1987), in a prospective postmyocardial infarction study, showed that the risk of arrhythmia associated with the combination of an EF
Sudden Cardiac Death After Myocardial Infarction
< 40% and an abnormal SAECG was 34%. The risk with a depressed EF alone was 4%. Gomes et al. (1984) in another study of similar patients after myocardial infarction showed an arrhythmia event rate with positive SAECG of 29% versus 3.5% in those with a normal SAECG. This was comparable to high grade ventricular arrhythmias. While not significant, the rate of clinical arrhythmia events after high grade venticular arrhythmias on the 24-hour Holter ECG was 23% versus 9% without. High grade ventricular arrhythmias in this study included PVC> lO/h as well as the occurrence of couplets and/or triplets. The event rate when both an abnormal SAECG and depressed EF were present was 36% versus 9% when both the SAECG and EF were normal. The event rate when the EF, SAECG and Holter recording were all abnormal was 50% versus 0% when all the tests were normal. Previous studies by Simson (1981) and Braithardt et al. (1981) also demonstrated the ability of the SAECG to predict arrhythmia events. Abnormal SAECG values vary slightly but are usually < 20 to 25J.L V for the mean amplitude of the root
100
80
~
60
03 >
.~
:>
UJ
40
D EF < 50 > 30, PVC < 10/h • EF < 50 > 30, PVC> 10/h EF < 30, PVC < 10/h • EF < 30, PVC> 10/h
o
20
o
2
3
Time (years)
Fig. 2. Effect of ejection fraction (EF) and premature ventricular contraction (PVC) frequency on survival. in patients with congestive heart failure (CHF) due to coronary artery disease. In the high EF group (30 to 50%). PVC frequencies > 10jh were associated with a more marked decrease in survival than in patients with a low EF « 30%).
5
mean square in the last 40 msec, QRS duration> 0.120 or 0.118 sec and duration of low amplitude signal> 39 msec. The predictability of late potentials in multiple studies suggests that delayed conduction in a structural scar is a precursor for sudden cardiac death. The disappearance of normal heart rate variability is another noninvasive predictor of arrhythmia events after myocardial infarction. Variable heart rates reflect normal parasympathetic and sympathetic tone. In cardiac disease, this normal modulation becomes much less. The quantification requires only algorithms on Holter tapes. When added to late potentials in a recent study (Farrell et al. 1990), it has a 33% positive predictive accuracy with a 97% negative predictive accuracy and a sensitivity of 56% with specificity of 97%. In addition, programmed electrical stimulation identifies a high risk group. Richards et al. (1983), Denniss et al. (1986) and others have shown that patients with inducible SVT are at a high risk for arrhythmic events after myocardial infarction. It is important to note that in the study of Denniss et al. (1986) and others, inducible ventricular fibrillation (VF) did not predict subsequent clinical events. SVT was induced by somewhat different protocols in each study. Several variables shorten the ventricular effective refractory period and, therefore, the duration of the test intervals. These include the basic drive rate, the number of test intervals in a row, and the strength of the test stimulus. When only I drive rate (600 msec) or only 2 extra stimuli were used, a higher output (20mA) produced the decreased coupling intervals seen in other studies with multiple drive rates (600 to 400 msec) and up to 3 extra stimuli. Two right ventricular stimulation sites were usually used. The ability to induce sustained monomorphic VT rather than VF or polymorphic VT is less likely to be influenced by differences in protocols. SVT is rarely inducible unless underlying structural abnormality exists. While some studies have not confirmed this finding, the data suggest that electrophysiological testing is highly predictive of sudden cardiac death and SVT. Thus a high percentage of patients who will have arrhythmic events may have them on the
6
basis of the substrate that produces late potentials, spontaneous high grade ventricular arrhythmia and inducible SVT. Treatment based on electrophysiological testing has been successful in several studies. If SVT is rendered noninducible with antiarrhythmic drugs, the percentage with lethal arrhythmic events falls from 50% (19 of 38 patients) to 9% (4 of 47 patients) [these percentages represent the combined results of 3 studies by Buxton et al. (1984), Klein & Machell (1989) and Wilber et al. (1990)]. While these results, obtained in small numbers of patients, are encouraging, electrophysiological testing will not be standard practice until these data are also demonstrated in large scale trials. Several such trials have been started. Given the pathophysiological heterogeneity of this syndrome it is not surprising to see that therapies as varied as sulfinpyrazone (Anturane Reinfarction Trial Research Group 1980), iJ-blockers (Chadda et al. 1986), amiodarone (Herre et al. 1989), electrophysiologically guided drug therapy (Wilber et al. 1990), coronary artery bypass surgery (Holmes et al. 1989) and implantable defibrillators (Winkle et al. 1989) all reduce the incidence of sudden cardiac death. While antiarrhythmic therapy to date has limited scientific support, it may yet playa role. The results of the Cardiac Arrhythmia Suppression Trial (CAST) [Rogers & CAST Investigators 1989] showed that the very potent PVCsuppressing agents flecainide and encainide caused increased mortality. The low mortality rate of the placebo group in that study made it difficult for any intervention to show benefit. The study did suggest that patients who respond well to antiarrhythmic drugs may have increased survival rates. Antiarrhythmic drugs with less potential for arrhythmia aggravation , started early in the postmyocardial infarction period, may still benefit these patients at high risk. The efficacy of these drugs may be improved if they are directed less at decreasing 'triggers', such as PVC, and more at preventing the re-entrant circuits from sustaining rapid arrhythmias. The adverse effect of class Ie drugs which prolong conduction may point to the possible beneficial effect of class III drugs, which prolong repolarisation. Amiodarone is being used in
Drugs 41 (Suppl. 2) 1991
several postmyocardial infarction and CHF trials. Dr Steven Singh and myself began a Veterans Affairs cooperative trial involving 25 hospitals in September 1989 [The Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF STAT)]. This cooperative trial is directed at patients with CHF and includes a large sample with previous myocardial infarction. In this trial, patients with CHF, EF < 40% and PVC frequency > 10lh will be randomised to amiodarone or placebo. Until this and other new trials are completed, we remain much better at establishing prognosis than at prescribing appropriate therapy.
4. Diagnostic Evaluation and Patient Management Most physicians agree on the management procedures for the patient who has had an episode of sudden cardiac death after myocardial infarction, but managing a patient to prevent sudden death is less well defined. After an episode of sudden cardiac death, electrophysiological testing is indicated, since therapy based on this procedure has been successful. However, if drug failures occur, or if the targets of electrophysiological testing are not present, the patient becomes a candidate for an implantable defibrillator. Close monitoring of these patients will enhance our concepts and capacity to prevent sudden cardiac death without electrical therapy. For the individual patient who has not had an episode of sudden cardiac death, the prognosis should be established by assessing known risk factors, including PVC frequency and ventricular repetitive beats on the 24-hour ECG, 10 to 14 days after myocardial infarction. A low level exercise stress test will assess perfusion of the remaining normal myocardium and the presence of arrhythmia with exercise. A SAECG should be obtained to assess the presence of late potentials. Heart rate variability from the Holter tape should be obtained. Myocardial function as assessed by MUGA or, less reliably, by echocardiogram will further quantify the prognosis. In some centres, patients have undergone further risk stratification and
Sudden Cardiac Death After Myocardial Infarction
therapy based on electrophysiological testing. Common management also includes the control of neurohormonal mechanisms with t3-blockers, treatment of CHF with vasodilators and the use of platelet inhibitors such as aspirin (acetylsalicylic acid) [80 to 325 mg/day]. Many physicians attempt to reduce abnormal blood lipids through diet or drug therapy. Critically narrowed vessels leading to the remaining normal myocardium are revascularised with angioplasty or surgery.
5. Conclusion At present, treatment for the high risk patient does not include any antiarrhythmic therapy other than t3-blockers; physicians feel more secure in omitting antiarrhythmic therapy since the results of CAST. A more effective antiarrhythmic agent of a different class may still prove to be beneficial. Until such data are available, the high risk patient should be carefully monitored for abnormal electrolytes, undue hypoxaemia and precursors of sudden electrical death such as episodes of sustained tachycardia, symptoms of extended palpitations, dizziness or syncope. We await the results of several ongoing trials designed to guide diagnostic and therapeutic interventions more effectively, especially those involving the use of antiarrhythmic drugs.
References Anturane Reinfarction Trial Research Group. Sulfinpyrazone in the prevention of sudden death after myocardial infarction. New England Journal of Medicine 302: 250, 1980 Bigger JT, Fleiss JF, Kliger R, Miller JR, Rohnitzky 1M. The multicenter postinfarction research group: the relationship among ventricular arrhythmias, left ventricular dysfunction and mortality in the two years after myocardial infarction. Circulation 69: 250, 1984 Breithardt G , Becker R, Seipel L, Abendroth RR, Ostermeyer J. Non-invasive detection oflate potentials in man: a new marker for ventricular tachycardia. European Heart Journal 2: I-II, 1981 Buxton AE, Marchlinski FE, Waxman HL, Flores BT, Cassidy OM, et al. Prognostic factors in non-sustained ventricular tachycardia. American Journal of Cardiology 53: 1275-1279, 1984 Chadd a K, Goldstein S, Byington R, Curb JD. Effect of propranolol after acute myocardial infarction in patients with congestive heart failure. Circulation 73: 511-517, 1986 Cohn IN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, et al. Effect of vasodilator therapy on mortality in chronic con-
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gestive heart failure. New England Journal of Medicine 314: 1547,1986 CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). New England Journal of Medicine 316: 1429-1435, 1987 Dargie HJ, Cleland JGF, Leckie BJ, Inglis CG, East BW, et al. Relation of arrhythmias and electrolyte abnormalities to survival in patients with severe chronic heart failure. Circulation 75 (Suppl. IV): IV-98, 1987 Davies MJ, Thomas A. Thrombosis and acute coronary artery lesions in sudden cardiac ischaemic death. New England Journal of Medicine 310: 1138, 1984 Denniss AR, Richard DA, Cody DV, Russell FA, Young AA, et al. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation 74: 731745, 1986 Ferrell T, Bashir Y, Cripps T, Malik M, Bennett ED, et al. Accurate risk stratification for arrhythmic events based only on Holter variables in post infarction patients. Circulation 82 (Suppl. III): 139, 1990 Fletcher R, Archibald 0, Cohn J , and VA Study Group. Day I and day 14 24-hour electrocardiogram as predictors of post myocardial infarction mortality. Circulation 66: II-II, 1982 Fletcher RD, Archibald 0, Orndorff J, Cohn J. Cooperative Study Group. Dysrhythmias on short term Holter as an independent predictor of mortality in congestive heart failure. Journal of the American College of Cardiology 7 (Suppl. A): 143A, 1986 Fletcher RD, Johnson G, Cohn J, VHeFT VA Coop Study. Increased risk of ventricular arrhythmia with mild ventricular dysfunction in CHF. Circulation 78 (Suppl. II): 346, 1988 Gillum RF, Fortmann SP, Prineas RJ, Kottke TE. International diagnostic criteria for acute myocardial infarction and acute stroke. American Heart Journal 108: 150, 1984 Glicksman FL, Huikuri HV, Dwyer EM, Anthony RM, Castellanos A, et al. Differential prognostic significance of 2-5 or ~ 6 repetitive ventricular ectopic beats. Circulation 78: 279, 1988 Gomes JA, Winters SL, Stewart 0, Horowitz X, Milner M, et al. A new noninvasive index to predict sustained ventricular tachycardia and sudden death in the first year after myocardial infarction: based on signal-averaged electrocardiogram, radionuclide ejection fraction and Holter monitoring: criteria for acute myocardia infarction and acute stroke. American Heart Journal 108: 150, 1984 Gordon I, Kannel WB. Premature mortality from coronary heart disease: Framingham study. Journal of the American Medical Association 215: 1617-1625, 1971 Herre JM, Sauve MJ, Malone P, Griffin Jc, Helmy I, et al. Longterm results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. Journal of the American College of Cardiology 13: 442-449, 1989 Hinkle LE, Whitney LM, Lehman EW, Dunn J, Benjamin S, et al. Occupation, education and coronary heart disease. Science 161: 283, 1969 Holmes Jr DR, Davis X, Gersh BJ, Mock MB, Pettinger MB, et al. Risk factor profiles of patients with sudden cardiac death and death from other cardiac causes: a report from the Coronary Artery Surgery Study. Journal of the American College of Cardiology 13: 524-530, 1989 Kannel WB, Sorlie P, McNamara PM. Prognosis after initial myocardial infarction. American Journal of Cardiology 44: 53, 1979 Klein RC, Machell C. Use of electrophysiologic testing in patients with non-sustained ventricular tachycardia: prognostic and
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therapeutic implications. Journal of the American College of Cardiology 14: 155-161, 1989 Kuchar DL, Thorburn CW, Sam mel NL. Prediction of serious arrhythmic events after myocardial infarction: signal-averaged electrocardiogram Holter monitoring and radionuc1ide ventriculography. Journal of the American College of Cardiology 9: 531-538, 1987 Luu M, Stevenson WG, Stevenson LW, Baron K, Walden J. Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 80: 1675-1680, 1989 Pandis I, Morganroth J. Sudden death in hospitalised patients: cardiac rhythm disturbances detected by ambulatory electrocardiographic monitoring. Journal of the American College of Cardiology 2: 798, 1983 Pratt CM, Francis MJ, Luck JC Wyndham CR, Miller PR, et al. Analysis of ambulatory tapes in 15 patients during spontaneous ventricular fibrillation with special reference to preceding arrhythmic events. Journal of the American College of Cardiology 2: 795, 1983 Richards DA, Cody DV, Denniss AR, Russell PA, Young AA, et al. Ventricular electrical instability: a predictor of death after myocardial infarction. American College of Cardiology 51: 75, 1983 Rogers WJ, CAST investigators. The Cardiac Arrhythmia Suppression Trial (CAST). New England Journal of Medicine 321: 406-412,1989 Ruberman W, Weinblatt E, Goldberg JD, Frank CW, Chaudhary
Drugs 41 (Suppl. 2) 1991
BS, et al. Ventricular premature complexes and sudden death after myocardial infarction. Circulation 64: 297, 1981 Schulze RA, Strauss HW, Pitt B. Sudden death in the year following myocardial infarction: relation to ventricular premature contractions in the late hospital phase and left ventricular ejection fraction. American Journal of Medicine 62: 192-199, 1977 Schuster EH, Bulkley BH. Early post-infarction angina-ischemia at a distance and ischemia in the infarct zone. New England Journal of Medicine 305: 1101, 1981 Simson MB. Use of signals in the terminal QRS complex to identify patients with ventricular tachycardia after myocardial infarction. Circulation 64: 235-242, 1981 Wilber DJ, Olshansky B, Moran JF, Scanlon PJ. Electrophysiological testing and non-sustained ventricular tachycardia: use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation 82: 350-358, 1990 Winkle RA, Mead RH, Ruder MA, Guadiani VA, Smith NA. Long-term outcome with the automatic implantable cardiovcrter defibrillator. Journal of the American College of Cardiology 13: 1353-1361, 1989
Correspondence and reprints: Assoc. Prof. Ross D. Fie/chI'/', Cardiology Section, Veterans Affairs Medical Center, 50 Irving Street NW, Washington, DC 20422, USA.
