Bernard Lown

Approaches to sudden death from coronary heart disease.

Sudden cardiac death (SCD) continues unabated. Coronary care units, while effective in lowering hospital mortality, cannot significantly reduce SCD which occurs primarily outside the hospital and accounts for the majority of deaths from coronary heart disease (CHD). In view of the frequent precipitous nature of SCD, only a program which identifies and protects the victim prior to the event can hope to be successful in preventing the majority of SCD. Since it is likely that SCD is due to an arrhythmia, drug prophylaxis might prove effective. In view of the toxicity of currently available agents, it is mandatory to preselect a population at highest risk before embarking on a drug trial. Ventricular premature beats (VPB) may identify subjects susceptible to SCD. Epidemiologic and physiologic information on VPB is reviewed, and proposals are made for studies designed to establish the usefulness of VPB as a risk factor for SCD.

Neural Activity and Ventricular Fibrillation

Ventricular fibrillation is the likely mechanism for sudden death and the leading cause of fatality among patients with coronary heart disease. In this country alone, ventricular fibrillation claim...

Aggravation and provocation of ventricular arrhythmias by antiarrhythmic drugs.

Antiarrhythmic drugs may aggravate or even induce ventricular arrhythmias. This type of adverse reaction is becoming more prevalent as the use of antiarrhythmic agents becomes more widespread. In a retrospective analysis of antiarrhythmic drug action, a worsening of arrhythmia was observed in 80 of 722 (11.1%) antiarrhythmic drug tests in 53 of 155 patients being treated for ventricular tachyarrhythmias. Aggravation of arrhythmias was defined by occurrence of a fourfold -increase in the frequency of ventricular premature complexes, a 10-fold increase in repetitive forms, or the first emergence of sustained ventricular tachycardia coincident with time course of action of the particular drug under study. Such aggravation was noted with each of nine drugs tested: quinidine, procainamide, disopyramide, propranolol, metoprolol, aprindine, mexiletine, tocainide and pindolol. The frequency of this complication for a specific drug ranged from 5.9-15.8%. Blood drug concentrations were consistently in the therapeutic range. A study of the variability of ventricular arrhythmia during 48-hour Holter monitoring and exercise stress testing in no instance showed arrhythmia enhancement commensurate with that defining aggravation. Our data suggest that this potentially serious complication is not readily predictable and requires a systematic approach to antiarrhythmic drug testing before a patient is prescribed a long-range maintenance program.

Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs

The protective effect of antiarrhythmic agents for patients with malignant ventricular arrhythmia (defined as noninfarction ventricular fibrillation or sustained hemodynamically compromising ventricular tachycardia) remains uncertain. We have analyzed survival among 123 such patients (98 males, 25 females, average age 53.6 years) dependent on the abolition of antiarrhythmic drugs of salvos of ventricular tachycardia and R-on-T ventricular premature beats (Lown grades 4B and 5). Over an average follow-up of 29.6 months there were 35 deaths (11.2 percent annual mortality rate) of whom 23 patients succumbed suddenly (8.2 percent annual mortality rate). Among 98 patients in whom antiarrhythmic drugs abolished grades 4B and 5 ventricular premature beats, only 6 sudden deaths occurred for a 2.3 percent annual mortality rate. Of the 25 patients in whom advanced ventricular premature beats were not controlled, 17 died suddenly. Seventy-nine patients had left ventricular studies suitable for analysis. Among 44 patients with left ventricular dysfunction, control of ventricular premature beats was a critical element predicting survival. The annual sudden death rate for the 12 noncontrolled patients with left ventricular dysfunction was 41 percent contrasting with only 3.1 percent for the 32 patients with similar abnormalities in ventricular function in whom advanced ventricular premature beats were abolished. It is concluded that antiarrhythmic drugs can protect against the recurrence of life-threatening arrhythmias in patients who have manifest ventricular fibrillation or ventricular tachycardia and that abolition of certain advanced grades of ventricular premature beats provides an effective therapeutic objective.

Sudden cardiac death: The major challenge confronting contemporary cardiology

In the industrially developed countries, sudden cardiac death is the leading cause of death. It was recognized at the dawn of recorded history and even depicted in Egyptian relief sculpture from the tomb of a noble of the Sixth dynasty approximately 4,500 years ago. Sudden cardiac death has left no age untouched. Sparing neither saint nor sinner, it has burdened man with a sense of uncertainty and fragility. The enormity of this problem demands attention. In the United States, sudden cardiac death claims about 1,200 lives daily, or approximately one victim every minute. It is the leading cause of death among men aged 20 to 64 years, accounting for 32 percent of the fatalities in this group. Nearly 25 percent of persons dying suddenly have had no prior recognized symptoms of heart disease.The excess of widows observed in retirement communities is accounted for by the three- to fourfold greater incidence of sudden cardiac death among men. Sudden death in old age might be a blessing rather than a scourge, but instead it frequently explodes a mans life at its prime, at a median age of only 59 years. The medical profession has sensed the issue but has largely ignored sudden death as a problem amenable to solution. This indifference has not been the result of a lack of interest or concern but a reflection of the belief that sudden cardiac death was the inevitable culmination of coronary atherosclerosis. Because sudden death was unpredictable and afflicted the apparently healthy subject outside the hospital, the physician considered it an act of fate before which he was largely helpless. The advent of the coronary care unit has promoted a reassessment of this complex problem. It has become clear that sudden death is not the inexorable culmination of advanced coronary atherosclerosis but instead is the result of ventricular fibrillation and therefore is readily reversible. 7,8 If ventricular fibrillation were only the consequence of severe coronary atherosclerosis, once reversed it would promptly recur. However, patients treated for ventricular fibrillation seldom have recurring episodes, and they usually recover and survive for long periods. 9,10 The new concept that ventricular fibrillation is an electrical accident suggests that its cause is not anatomic and thereby contributes to the growing interest in redefining the basis for sudden death and developing methods for its containment. Until recently our inability to deal with sudden cardiac death has not been due to a gap in the application of knowledge but to a gap in knowledge itself. The purpose of this review is to indicate how much we know and to sketch the path of possible further progress.

Cardioversion of atrial fibrillation. A report on the treatment of 65 episodes in 50 patients.

ATRIAL fibrillation is one of the most prevalent of the chronic rhythm disorders of the heart. It is a derangement with serious implications. Even when the patient is asymptomatic the arrhythmia is...

Basis for recurring ventricular fibrillation in the absence of coronary heart disease and its management.

A 39-year-old man twice experienced ventricular fibrillation and exhibited numerous ventricular premature beats. Coronary arteries were normal, and no impaired cardiac function was found upon catheterization. Evidence was adduced that the ventricular premature beats were related to higher nervous activity. The patient had serious psychiatric problems; the ventricular premature beats were provoked by psychophysiologic stress, increased during REM sleep, were reduced by meditation, and were controlled by beta-adrenergic blockade, phenytoin and digitalization. We conclude that psychologic and neurophysiologic factors may predispose to life-threatening cardiac arrhythmia in the absence of organic heart disease. Effective management of the recurrent ventricular arrhythmia involved; acute drug testing for assessing antiarrhythmic efficacy; use of programmed trendscription to provide on-line information on drug action; a treatment program involving more than one agent; and use of measures to reduce sympathetic nervous activity.

Comparison of alternating current with direct current electroshock across the closed chest

I T IS BECOMING increasingly recognized that ventricular fibrillation is an important cause of sudden death. The treatment of this arrhythmia is by electrical countershock delivered to the heart either directly or indirectly through the intact chest wall. From the onset of ventricular fibrillation only a few minutes are available for restoring an integrated cardiac mechanism. Until recently the successful use of countershock has been largely limited to the operating room where this brief time could be prolonged by the prompt institution of direct cardiac massage. The demonstration by Kouwenhoven and co-workers1 that in the arrested heart pressure on the lower sternum maintains blood flow to vital organs has greatly extended the time available for effective use of electrical defibrillation. Recently it has been shown2-4 that electrical countershock across the closed chest will abolish cardiac arrhythmias other than ventricular fibrillation. It is therefore pertinent to determine whether alternating current, widely accepted for inducing countershock, is indeed the best available method. The present study compared the action on the heart of alternating current and three types of direct current both during ventricular fibrillation and during normal sinus rhythm.

The effect of vagus nerve stimulation upon vulnerability of the canine ventricle: role of sympathetic-parasympathetic interactions.

The effect of vagus nerve stimulation (VNS) upon ventricular vulnerability was studied in 30 mongrel dogs subjected to varying levels of adrenergic stimulation. Vulnerability was assessed both by determining the minimum current required to produce ventricular fibrillation (VF threshold) and by plotting VF threshold throughout the vulnerable period (VF zone). Chloralose-anesthetized animals were studied by means of sequential pulses applied to the apex of the right ventricular endocardium. Testing was carried out in closed-chest dogs, in open-chest dogs with and without left stellate ganglion stimulation (LSGS), and in open- and closed-chest dogs pretreated with propranolol. In the absence of adrenergic stimulation, VNS was without significant effect on either the VF threshold or the VF zone under closed- or open-chest conditions. During LSGS, however, VNS was associated with a 93 ± 22% (mean ± se) increase in VF threshold (P < 0.01) and constriction of the VF zone. Vagus nerve stimulation combined with LSGS raised VF threshold to the control value, but not beyond. After beta-adrenergic blockade with propranolol, VNS was without effect on VF threshold in either open- or closed-chest animals. It is concluded that augmented sympathetic tone is a precondition for a VNS-induced elevation in VF threshold. The vagal effect is indirect and is expressed by opposing the effects of heightened adrenergic tone on ventricular vulnerability.

Neural and psychologic mechanisms and the problem of sudden cardiac death

Brain stimulation can provoke a variety of arrhythmias and lower the ventricular vulnerable threshold. In the animal with acute myocardial ischemia such stimuli suffice to provoke ventricular fibrillation. Vagal neural traffic or adrenal catecholamines are not the conduits for this brain-heart linkage. Accompanying increases in heart rate or blood pressure are not prerequisites for the changes in cardiac excitability. Increased sympathetic activity, whether induced by neural or neurohumoral action, predisposes the heart to ventricular fibrillation. Protection can be achieved with surgical and pharmacologic denervation or reflex reduction in sympathetic tone. With acute myocardial ischemia, augmented sympathetic activity accounts for the early surge of ectopic activity frequently precipitating ventricular fibrillation. Asymmetries in sympathetic neural discharge may also contribute to the genesis of serious arrhythmias. The vagus nerve, through its muscarinic action, exerts an indirect effect on cardiac vulnerability, the consequence of annulment of concomitant adrenergic influence, rather than of any direct cholinergic action on the ventricles. There exist anatomic, physiologic as well as molecular bases for such interactions. Available experimental evidence indicates that environmental stresses of diverse types can injure the heart, lower the threshold of cardiac vulnerability to ventricular fibrillation and, in the animal with coronary occlusion, provoke potentially malignant ventricular arrhythmias. Available evidence indicates that in man, as in the experimental animal, administration of catecholamines can induce ventricular arrhythmia, whereas vagal activity exerts an opposite effect. Furthermore, in certain subjects diverse stresses and various psychologic states provoke ventricular ectopic activity.