Regis A. DeSilva

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.

Cardioversion and defibrillation

The use of electrical energy for the immediate treatment of atrial and ventricular arrhythmias is practical and easily applied. The method, though simple, is the most effective method for terminating cardiac arrhythmias and is associated with only a low risk if properly employed. In symptomatic patients, the utilization of cardioversion reduces patient discomfort and complications which may occur while awaiting pharmacologic reversion of arrhythmia. At present, transthoracic defibrillation is the only practical method for terminating VF. Despite the safety of electrical reversion, proper precautions are necessary to prevent complications. In particular, the discharge of excessive energies, especially in the presence of digitalis toxicity, promises grave and life-threatening consequences. The use of antiarrhythmic medications is not supplanted by cardioversion and defibrillation. Rather, ongoing drug therapy is frequently necessary to prevent recurrence of arrhythmia.

Roles of psychologic stress and autonomic nervous system changes in provocation of ventricular premature complexes.

Neural and psychologic factors have been implicated as risk factors for ventricular arrhythmias and sudden death in man. However, the relation between these factors and arrhythmia has hitherto not been systematically explored. We examined the effect of psychologic stress testing in 19 patients with advanced grades of ventricular arrhythmias. Psychologic stress consisted of mental arithmetic, reading from colored cards and recounting emotionally charged experiences. Such testing induced a significant increase in ventricular premature beat frequency in 11 of 19 patients (P less than 0.05). One patient experienced paroxysms of ventricular tachycardia. In 14 of these 19 patients elicitation of vagal or sympathetic autonomic reflexes failed to induce significant arrhythmia in all but one patient. It is concluded that (1) objective psychologic tests may precipitate ventricular arrhythmia in susceptible patients, and (2) evocation of peripheral autonomic reflexes is an insufficient trigger for enhanced ventricular ectopic activity.

The effects of psychological stress and vagal stimulation with morphine on vulnerability to ventricular fibrillation (VF) in the conscious dog

Ventricular vulnerability to fibrillation was assessed in 12 conscious dogs in aversive and nonaversive environments using the repetitive extrasystole (RE) threshold method. In the average environment, RE threshold was 45 per cent lower than in the nonaversive setting and heart rate and blood pressure were significantly elevated. This decrease in RE threshold occurred within 10 minutes of exposing the animals to stress. In contrast, the recovery in RE threshold in the nonaversive setting occurred over a 40 minute period. When morphine sulfate (MS) 0.25 mg./Kg was administered to dogs in the aversive environment, the RE threshold was significantly increased. Cholinergic blockade of vagal efferent activity with atropine (0.2 mg./Kg) annulled partially the effect of MS on RE threshold MS was without effect in the nonaversive environment. It is concluded that MS exerts a significant protective effect on increased ventricular vulnerability associated with psychological stress. This effect is mediated by the vagotonic and sedative actions of morphine.

CENTRAL NERVOUS SYSTEM RISK FACTORS FOR SUDDEN CARDIAC DEATH

Experimental studies to verify the long-postulated connection between acute emotional perturbations and sudden death have been initiated only relatively recently. William Harvey, from whom we date the modern era in cardiology, had already commented on this association when he wrote: “Every passion of the mind which troubles men’s spirits, either with grief, joy, hope or anxiety and gets access to the heart, there makes it to change from its natural constitution, by distemperament, pulsation and the rest. . . .” Sudden death is most often due to ventricular fibrillation occurring in the setting of coronary heart disease. Epidemiologic studies suggest that psychosocial risk factors exist for the development of both coronary heart disease and sudden cardiac death. While it is likely that both conditions share the same standard and some behavioral and environmental risk factors, the sudden onset of ventricular fibrillation in a heart that has been long-diseased requires the operation of additional factors. Gairdner, who is cited by McWilliam, observed a century ago that “it is plainly out of the question to suppose that a chronic and by its very nature, gradually advancing lesion like fatty degeneration or disease of the coronary vessels, is the direct and immediate cause of a death which occurs in a moment.”2 McWilliam, who also first suggested that sudden death was due to ventricular fibrillation, boldly advanced the view that sympathetic discharge may be an important factor in inciting this fatal arrhythmia.3.4 Since early this century, several experimental and clinical studies have attempted to demonstrate that the activity of the central nervous system contributes to the onset of ventricular arrhythmias and sudden death.

Episodic drug treatment in the management of paroxysmal arrhythmias

The use of maintenance medication in the treatment of episodic cardiac arrhythmia is often complicated by problems of patient compliance with therapy and adverse side effects. Furthermore, repeated hospitalizations and cardioversions are both costly and inconvenient. A method of intermittent drug therapy is described in which antiarrhythmic medication is taken only at the onset of an episode of arrhythmia. This approach was effective in terminating both supraventricular and ventricular arrhythmias in 24 of 32 patients and obviated the need for hospitalization and further treatment. In cases in which maintenance therapy was required because of the frequent occurrence of arrhythmia, periodic drug therapy was still of value in the treatment of breakthrough episodes. The use of intermittent drug therapy is a safe and effective approach to the management of episodic cardiac arrhythmia and, in addition, results in significant financial saving.

Ventricular premature beats, stress, and sudden death.

Abstract Sudden death is the major cause of mortality in the western hemisphere. Coronary artery disease is the usual underlying pathologic condition associated with sudden death; however, it is apparent that additional inputs to the heart are necessary before sudden death occurs in man. Current evidence supports the role of higher nervous activity as a major contributor to destabilization of normal cardiac rhythm and, in turn, to sudden death.

Usefulness of left ventricular size and function in predicting survival in chronic dialysis patients with diabetes mellitus

To identify patients at high risk for sudden death, a group of stable patients on maintenance dialysis with diabetes mellitus were studied for up to 135 months to determine if there were clinical, laboratory or echocardiographic predictors of high risk. Eighty-two patients on maintenance dialysis who underwent clinical, laboratory evaluation and echocardiography were enrolled and followed for a mean of 25 months for cardiac and noncardiac complications. Thirty-seven patients with normal wall motion and left ventricular (LV) internal diameter had a mean survival of 35.8 months; 28 patients survived greater than 12 months. Seven patients with normal LV wall motion and dilated LV cavities had a mean survival of 45.7 months; 7 patients survived greater than 12 months. Fifteen patients with abnormal LV wall motion and normal internal LV dimensions had a mean survival of 17 months; 7 patients survived greater than 12 months. Twenty-three patients with both abnormal LV wall motion and dilated LV cavities had a mean survival of 7.8 months; 5 patients survived greater than 12 months. Although echocardiographic abnormalities predicted cardiac mortality at 6 and 12 months, the combination of an abnormal standard electrocardiogram at baseline, clinical history of angina pectoris, and prior documented myocardial infarction or congestive heart failure did not. When the study group was divided by mode or duration of dialysis, presence or absence of diabetes, or use of cardioactive drugs, echocardiographic LV wall motion abnormalities remained the most important determinant of survival.

George Ralph Mines, Ventricular Fibrillation and the Discovery of the Vulnerable Period

The discovery of the vulnerable period of the ventricle unmasked one of the major electrical properties of the heart. Since its description by George Ralph Mines in 1914, it has become a crucial concept in understanding the electrophysiologic basis for ventricular fibrillation. Mines also proposed the theoretical basis for the occurrence of reentrant arrhythmias. Although these concepts are widely known, Mines himself remains an obscure figure since his own sudden death at a young age. Mines was a talented researcher who had a short but prolific career in electrophysiology. The historical importance of his work lies in the influence he had on our understanding and treatment of cardiac arrhythmias as well as in the experimental methods he developed, which inspired a new era of quantitative thinking in electrophysiology.

Preliminary Screening of the Relationship of Serum Lipids to Survival of Chronic Dialysis Patients

To assess the predictive value of serum lipid measurements in dialysis patients once the initial decrease on early dialysis had occurred, we obtained random serum cholesterol and triglyceride levels in stable, chronic dialysis patients who were then followed up to 9 years. Derived LDL (DLDL) was estimated by the Friedewald formula, calculated for all HDL levels between 30 and 45 mg/dL, and evaluated statistically against a panel of vascular disease markers, including clinical assessment for coronary, peripheral, and cerebrovascular disease; ECG, both standard and ambulatory; two-dimensional echocardiogram; and medications. Survival was calculated from entry (not dialysis onset) for 58 hemodialysis and 33 peritoneal dialysis patients. The 91 patients (49 males, 74 diabetics) were divided by cholesterol level (> or = 175 mg/dL = 53, < 175 = 38), triglyceride (> or = 175 mg/dL = 55, < 175 = 36), and DLDL (> or = 75 = 58, < 75 = 24). High total cholesterol was present in a larger proportion of females than low cholesterol, but groups were not different with respect to all vascular determinants, including survival (mean = 33.4 months vs. 43.2, p = NS). High vs. low triglyceride groups were not different with respect to vascular indicators, except for both incidence of abnormal standard ECG (69% vs. 42%, p < 0.05) and survivals (mean = 42.0 vs. 30.7, p < 0.05; 1 year = 80% vs. 56%, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)