Francis M. Weld

Prevalence, characteristics and significance of ventricular tachycardia (three or more complexes) detected with ambulatory electrocardiographic recording in the late hospital phase of acute myocardial infarction

A 24 hour electrocardiographic recording was performed before hospital discharge in 430 patients who survived the cardiac care unit phase of acute myocardial infarction. Fifty patients (11.6 percent) had ventricular tachycardia, that is, three or more consecutive ventricular complexes. In 25 (50 percent) of these 50 patients, there was only one episode of ventricular tachycardia and, in 15 patients (30 percent), the longest run of ventricular tachycardia was only three consecutive ventricular premature depolarizations. The average rate of tachycardia was 119/min. Tachycardia rarely started with R on T ventricular premature complexes (4 of 1,370 episodes in 50 patients). There was no difference between the groups with and without ventricular tachycardia with respect to age and sex, but the patients with tachycardia had a significantly greater prevalence of previous myocardial infarction, left ventricular failure in the cardiac care unit, atrial fibrillation, ventricular tachycardia or ventricular fibrillation in the cardiac care unit and significantly more frequent use of digitalis and diuretic and antiarrhythmic drugs at the time of hospital discharge. The group with tachycardia had a 38.0 percent 1 year mortality rate compared with the rate of 11.6 percent in the group without tachycardia. Ventricular tachycardia had a strong association with 1 year mortality (odds ratio = 4.7). Although ventricular tachycardia had a significantly association with many other postinfarction risk factors, it was still significantly associated with the 1 year mortality (p less than 0.05) when other important risk variables were controlled statistically using a multiple logistic regression model. The 36 month cumulative mortality rate was 54.0 percent in the group with ventricular tachycardia compared with 19.4 percent in the group without tachycardia.

Risk stratification after acute myocardial infarction

One hundred patients admitted to the hospital with acute myocardial infarction who lived 10 days and agreed to enroll were studied. Data from the history, hospital course and a 24 hour Holter electrocardiographic recording were related to cardiac mortality in the 6 months after enrollment. Fifteen cardiac deaths occurred during this period; 12 of these were sudden. The univariates with the strongest association with mortality were (in descending order): blood urea nitrogen level, serum creatinine level, serum uric acid level, enlarged heart 2 weeks after infarction, ventricular tachycardia 2 weeks after infarction, peak creatine kinase level and left ventricular failure in the coronary care unit. The odds of dying if one of these factors was present rather than absent ranged from 3.6 to 11.5. Groups with two or these univariates had up to 20 times the odds of dying in 6 months. A period of greately enhanced risk for cardiac death persists for about 6 months after acute myocardial infarction. Relatively simple clinical variables can identify the groups at highest and lowest risk. This information is useful for designing management strategies.

Analysis of prognostic significance of ventricular arrhythmias after myocardial infarction. Shortcomings of Lown grading system.

The Lown grading system for ventricular arrhythmias has been used in observational and experimental studies of ischaemic heart disease. This grading system uses three levels of ventricular premature depolarisation frequency and four complex features to assign patients to one of seven grades. We tested several of the major assumptions of the Lown grading system in a group of 400 patients who had recently experienced acute myocardial infarction. The Lown grading system assumes that the frequency of ventricular extrasystoles exerts a negligible risk force in patients who have complex ventricular extrasystoles. We found, however, that the frequency of ventricular extrasystoles contributed significant additional risk for cardiac death even in the three highest Lown grades, 4A, 4B, and 5. The Lown grading system assumes that, of the four complex features used, R on T ventricular extrasystoles have the greatest risk for subsequent cardiac death. We found that paired ventricular extrasystoles and ventricular tachycardia had more prognostic significance than R on T ventricular extrasystoles. It is important for prognostic stratification that subgroups which are merged into a given Lown grade should be relatively homogeneous with respect to outcome. We found a lack of homogeneity in the three highest Lown grades. Grade 5 contained 16 subgroups with a mortality risk which ranged from 0 to 75 per cent; statistically significant differences in subsequent mortality were found among these subgroups. Most of the shortcomings of the Lown grading system in our acute myocardial infarction population resulted from failure to give sufficient weight to ventricular extrasystoles frequency and to repetitive ventricular extrasystoles.

Usefulness of low-level exercise testing early after acute myocardial infarction in patients taking beta-blocking agents

The value of low-level exercise testing early after acute myocardial infarction (AMI) in 207 patients taking beta-blocking drugs was evaluated in a multicenter study of prognosis after AMI. After stratifying patients according to the absence of significant rales upon admission or pulmonary congestion on the admitting chest x-ray, the results of the exercise test (ability to complete the 9-minute protocol) permitted a large cohort (108 patients, 52% of exercising patients) with no deaths from cardiac causes in the year after AMI to be identified. The results suggest that even in patients taking beta-blocking agents, low-level exercise testing together with clinical stratification has value in identifying a large group of patients with a good prognosis after AMI.

Which postinfarction ventricular arrhythmias should be treated

There is still no consensus on which arrhythmias should be treated in the 6- to 12-month high-risk period after acute myocardial infarction. To examine this question, we analyzed 24-hour ECG recordings in 430 patients who survived for at least 2 weeks after myocardial infarction and studied these patients for at least 1 year. During the year after infarction, 63 cardiac deaths occurred. High ventricular premature depolarization (VPD) frequency increased the risk of dying; 26% of the patients had greater than or equal to 10 VPDs/hr and were 2.6 times as likely to die within a year as those with lower frequencies. Repetitive VPDs (pairs or ventricular tachycardia) also were strongly associated with mortality. Thirty-one percent had repetitive VPDs, and these patients were 3.2 times as likely to die as those who lacked this characteristic. Frequent or repetitive VPDs were strongly associated with many other important postinfarction risk factors (e.g., left ventricular dysfunction or digitalis treatment). Nevertheless, frequent or repetitive VPDs contributed significantly to death in the first year after infarction independent of other risk factors; about 90% of these arrhythmias can be controlled satisfactorily with antiarrhythmic drugs. As yet, no definitive trial has been conducted to show whether controlling frequent or repetitive VPDs will significantly reduce the mortality in the first year after infarction. The principal design features for such a trial are discussed.

Shortcomings of the Lown grading system for observational or experimental studies in ischemic heart disease

The Lown grading system uses three levels of frequency and four complex features to grade ventricular arrhythmias. The seven Lown grades are mutually exclusive (a patient can be in only one grade) and hierarchical (higher grades indicate increased likelihood of death). We evaluated the ability of the Lown arrhythmia grading system to predict death in 400 patients who were convalescing from acute myocardial infarction. Lown grading produced a poor distribution among grades of the population, lacked a monotonic increase in risk with increasing arrhythmia grade, lacked a substantial risk gradient between grades, and showed a lack of isometry in the higher grades. Also, the Lown grading system thwarts the use of standard multivariate techniques for relating the frequency and characteristics of ventricular premature depolarizations (VPDs) to cardiac death. We also examined the utility of the Lown arrhythmia equation for evaluating the results of antiarrhythmic drug therapy. The Lown grading system failed to reveal clearly the change in VPD frequency and characteristics as a function of drug dose. We propose an alternative grading system that is not mutually exclusive or hierarchical. This grading system lacks many of the flaws of the Lown grading system and is suitable for standard multivariate analyses but, like the Lown grading system, still fails to show the relationships among ventricular arrhythmias, time, drug dose, and activity.

DRUGS AND SUDDEN CARDIAC DEATH

In this section of the volume we will discuss the role of drugs in sudden coronary death. After a brief consideration of drug-induced sudden death, the discussion will focus on the use of drugs for the secondary prevention of coronary death. Drug trials for secondary prevention are complex. Good design requires an adequate control group, random assignment to treatment and, if possible, a double-blind study. Every drug has a dose-response relationship, and individualized dose adjustment should improve the chance of efficacy in a trial. However, individualization of dosage presents substantial logistic difficulties in drug trials. A major intervention trial should have a rationale and test a well-defined hypothesis. The latter consideration implies careful selection of the study group on the basis of likelihood of beneficial or adverse effects. The statistical and pharmacologic principles of drug intervention trials will be discussed thoroughly in the following papers. Drugs that show promise for secondary prevention trials or those that have been used already have been selected for discussion.

The Prognostic Significance of Ventricular Arrhythmias After Acute Myocardial Infarction: Is It Independent of Left Ventricular Function?

Ventricular arrhythmias in the convalescent phase of acute myocardial infarction are associated with an increased risk for cardiac death after hospital discharge, but whether ventricular arrhythmias exert this increased mortality risk independent of left ventricular function is not known. In order to answer this question we performed 24-h ambulatory (Holter) ECG recordings in patients two weeks after acute myocardial infarction, and analyzed the outcome with regard to both Holter arrhythmias and measures of left ventricular function. We found that both ventricular arrhythmias and left ventricular function are important determinants of survival following acute myocardial infarction, and that each exerts an independent risk force in the year after hospital discharge.

Cardiac Cellular Pharmacology: Automaticity in Cardiac Muscle—Its Alteration by Physical and Chemical Influences

The heart rhythmically and spontaneously activates itself many times in a minute. The process responsible for this behavior has been termed the “normal automatic mechanism” and is a property of only a few cell types in the heart. Cells in the sinoatrial node, atrioventricular rings, and ventricular specialized conducting tissues possess the capacity for automaticity of this type whereas ordinary atrial and ventricular muscle cells do not. This mechanism not only is the basis for normal cardiac rhythmicity but also can generate arrhythmias in the heart. Although the normal automatic mechanism is complex and probably varies somewhat in different types of automatic cells and in different species, much is now known about the cell membrane behavior which underlies automaticity and about alterations in this behavior caused by a variety of physical and chemical influences. In this chapter, it is our intention to discuss the factors which generate and modify the automaticity brought about in heart muscle by spontaneous diastolic depolarization.