Michael D. Klein

ST segment changes post-infarction: predictive value for multivessel coronary disease and left ventricular aneurysm.

SUMMARY To ascertain whether exercise testing might predict multivessel coronary disease and left ventricular aneurysm after a myocardial infarction, 154 patients with a single documented myocardial infarction who had both exercise testing and coronary angiography were grouped according to whether they had 2 1 mm ST depression, > 1 mm ST elevation, or neither during exercise testing: 83 patients developed ST depression alone (group 1); 22 patients had ST elevation with concomitant ST depression in other leads (group 2); 19 patients had ST elevation alone (group 3); and 30 patients had no ST changes (group 4). Multivessel disease, defined as 70% luminal narrowing in two or more coronary vessels, was present in 76% (63 of 83) of group 1, 91% (20 of 22) of group 2, 21% (four of 19) of group 3, and 13% (four of 30) of group 4. A left ventricular aneurysm was present in 31% (26 of 83) of group 1, 68% (15 of 22) of group 2, 79% (15 of 19) of group 3, and 40% (12 of 30) of group 4. We conclude that ST changes during exercise testing in patients after a myocardial infarction can reliably predict the extent of coronary disease and the presence of a left ventricular aneurysm; ST depression with or without ST elevation predicts multivessel disease; ST elevation alone or a negative exercise test suggests single vessel involvement; and ST elevation with or without ST depression predicts left ventricular aneurysm.

Effects of isometric exercise on the end-diastolic pressure, volumes, and function of the left ventricle in man.

Changes induced in left ventricular (LV) hemodynamics by isometric exercise were analyzed in 43 patients: 30 with coronary heart disease (CAD), four with noncoronary heart disease, nine normal. Volumes were angiographically determined and correlated with left ventricular end-diastolic pressure (LVEDP) both at rest and during the fifth minute of 30% sustained handgrip (HNG). All normals and eight with CAD improved LV function during HNG. LVEDP decreased or remained constant, end-diastolic volume (EDV) decreased, end-systolic volume (ESV) decreased, as ejection fraction (EF) remained constant. None of these eight CAD cases altered their regional LV contraction pattern during HNG.Twenty-five patients, 21 CAD and four nonCAD, showed diminished LV function during HNG. LVEDP increased, EDV decreased, ESV increased, as EF declined. In these 21 CAD patients, at least one major coronary vessel was narrowed 70% or more and, with but two exceptions, was not supported by adequate collaterals. In 18, new asynergic zones developed in previously normally contracting areas or pre-existing asynergic zones extended during HNG.

Ventricular arrhythmias during exercise testing: Mechanism, response to coronary bypass surgery and prognostic significance

To investigate the determinants and prognostic significance of ventricular arrhythmias during exercise testing, 86 patients with such arrhythmias were identified from a consecutive series of 446 patients who underwent treadmill exercise testing and cardiac catheterization. The prevalence of these arrhythmias was 19% in the total group but increased to 30% in the 120 patients with 3-vessel or left main coronary artery disease. Patients with exercise-induced arrhythmias were more likely to have 3-vessel or left main coronary artery disease, a lower resting ejection fraction, greater than or equal to 2 mm of ischemic ST depression and more severe segmental wall motion abnormalities than patients without this finding (p less than 0.05). Repeat exercise testing in 22 patients with exercise-induced arrhythmias after coronary bypass surgery revealed that persistence of these arrhythmias was associated with either severe wall motion abnormalities preoperatively or residual ischemic ST depression during the post-operative exercise testing. At a mean follow-up period of 5.3 years, the presence of exercise-induced ventricular arrhythmias was not associated with increased cardiac mortality in the medically treated patients.

Efficacy and safety of incremental doses of diltiazem for the treatment of stable angina pectoris

The safety and efficacy of incremental doses of diltiazem in treating angina pectoris were assessed in 20 patients with functional class II to III exertional angina. During an initial single-blind dose titration phase, dilitiazem produced a dose-related improvement in anginal frequency and exercise capacity. Weekly anginal attacks were reduced to 7.5 +/- 8.9, 5.6 +/- 7.8 and 4.9 +/- 7.3 on diltiazem, 120, 240 and 360 mg per day, respectively, as compared with 11.9 +/- 8.7 on placebo (all p less than 0.001). Treadmill time was significantly enhanced by high dose (360 mg per day) as compared with moderate dose (240 mg per day) diltiazem: 473 +/- 149 versus 424 +/- 146 seconds (p less than 0.05). Time to ischemic ST segment depression was similarly changed: 344 +/- 132 versus 298 +/- 142 seconds (p less than 0.05) by high dose as compared with moderate dose diltiazem. During a subsequent double-blind phase, high dose diltiazem significantly reduced weekly anginal frequency when compared with placebo: 3.1 +/- 3.0 versus 9.3 +/- 7.1 (p less than 0.001); and increased treadmill exercise time: 508 +/- 158 versus 418 +/- 172 seconds on placebo (p less than 0.05). Subjective and objective benefits of high dose diltiazem were sustained during a follow-up period of 6 months without major drug side effects.

Medical and psychosocial outcomes in survivors of major heart surgery

Abstract To assess long-term recovery following major heart surgery, medical and psychosocial outcomes were studied by mailed questionnaire in a sample of 949 patients (724 coronary bypass, 147 mitral and 78 aortic valve) drawn from the membership of Mended Hearts, a nationwide (U.S.A.) voluntary organization of persons having had heart surgery. Survey data were scaled and scored for reported changes, preoperative to present, in psychosocial and social adjustment, and for current emotional status, social network and employment. Medical outcomes included rehospitalization, repeated heart surgery, continuation of angina and dyspnea and limitations of activity requiring bed rest. Although about half of the respondents had been rehospitalized in theaverage 3 built;1 2 year interval since surgery, over 90% were currently free of frequent serious angina or dyspnea and disability requiring bed rest. Post-operative medical complications were more common among persons forced to retire from work, those having Type A behavior, and women with multiple vessel bypasses. Even after seven biomedical variables were controlled statistically, psychosocial outcomes were clearly worse in these same three groups. The findings have implications for patient selection and for post-operative care.

Efficacy and Safety of Sustained-Release Diltiazem in Stable Angina Pectoris

The safety and efficacy of a sustained-release preparation of diltiazem (diltiazem-SR), with dose levels of 240 and 360 mg/day, were assessed in 18 patients with stable angina of effort. A double-blind, placebo-controlled, randomized, crossover protocol was used. Diltiazem-SR, when given twice daily, reduced the frequency of weekly anginal attacks from 9.3 +/- 10.4 with placebo to 3.7 +/- 4.7 with 240 mg/day and to 3.1 +/- 4.7 with 360 mg/day (both p less than 0.01 compared with placebo). Treadmill time was increased from 410 +/- 180 seconds during the placebo phase to 519 +/- 177 seconds during the 240-mg/day dose and to 506 +/- 182 seconds during the 360-mg/day dose of diltiazem-SR (both p less than 0.01 compared with placebo). The time to the onset of angina and ischemic ST-segment depression were similarly prolonged by both doses of diltiazem-SR. The beneficial effects of diltiazem-SR appeared partly due to a reduction in the heart rate during submaximal exercise. Diltiazem-SR is effective and safe for the treatment of angina of effort when given twice daily.

Correlates of angina pectoris among men awaiting coronary by-pass surgery

&NA; Biomedical, behavioral, and psychological correlates of angina pectoris were identified in 204 men awaiting coronary artery by‐pass graft surgery. Angina was rated by use of a precoded series of interview questions. Four circumstances of anginal symptoms were investigated: exertional, emotional, post‐prandial, and while resting or sleeping. These were uncorrelated with one another, except for exertional and post‐prandial. Two‐thirds of these patients experienced angina less often than daily in the most recent unrestricted month. Severity of coronary artery obstruction was not positively associated with frequency or severity of any type of angina, and were primarily behavioral and psychological. Disturbances of sleep, physical inactivity, history of cigarette smoking, distressed response to life crises, life dissatisfactions, hostility, use of propranolol, duration of cardiac illness, and age were among the predictors in the multiple regression equations. These results from selected by‐pass candidates may apply more directly to such persons than to unselected community residents reporting angina symptoms. The findings suggest the need for greater focus on sources of variability in myocardial oxygen supply and demand in understanding the dynamics of angina episodes.

Treatment of stable angina of effort with verapamil: a double-blind, placebo-controlled randomized crossover study.

The effects of verapamil were assessed in 26 patients with stable exertional angina pectoris in a double-blind, placebo-controlled, randomized crossover protocol using serial treadmill tests. Verapamil, 480 mg/day, reduced anginal frequency from 5.6 ± 7.3 to 2.2 ± 3.9 attacks per week (p < 0.001) and nitroglycerin consumption from 3.4 ± 4.9 to 1.2 ± 2.5 tablets.per week (p < 0.05) compared with placebo. Treadmill time increased from 6.4 ± 2.1 minutes during the placebo phase to 7.5 ± 1.8 minutes during the verapamil phase (p < 0.001). Verapamils beneficial effect appeared to be related, in part, to a 10% reduction of the rate-pressure product at rest (p < 0.05) and a 12% reduction during submaximal exercise (p < 0.001). Verapamil also caused less marked ST-segment depressions at peak exercise (p < 0.05) at a similar rate-pressure product, suggesting a favorable redistribution of coronary blood flow to the ischemic zone. Side effects from verapamil were minimal, consisting mainly of constipation (six patients). Verapamil appears to be a safe and effective drug for treating angina of effort.

The role of exercise testing in evaluation of arrhythmias

Exercise testing has been widely applied for the evaluation of patients with coronary artery disease. The principles underlying its use for this indication make it a useful adjunctive technique, when combined with ambulatory monitoring, to diagnose arrhythmias and monitor antiarrhythmic drug therapy. During exercise, there is a withdrawal of vagal tone and a marked increase in circulating catecholamines and sympathetic inputs to the heart. These changes may directly cause arrhythmias (e.g., catecholamines can enhance automaticity and delayed afterpotentials and can shorten myocardial conduction time and refractory periods). However, they also augment myocardial oxygen demands by increasing myocardial inotropy, heart rate and blood pressure. Such changes may cause ischemia in patients with heart disease, which is a powerful stimulus for arrhythmia, or lead to dysfunction in left ventricular contraction and increased myocardial wall stress, factors that also may precipitate arrhythmia. In approximately 10% of patients with a history of serious arrhythmia, exercise represents the only means for exposing arrhythmia. Importantly, this technique is useful for evaluating the effect of antiarrhythmic drugs. These agents work by reducing membrane automaticity, slowing impulse conduction through the myocardium and prolonging membrane refractoriness. In contrast, catecholamines, which are secreted in response to exercise, have the opposite effect. Thus, exercise may negate the important effects of the antiarrhythmic drugs. Additionally, exercise testing may expose potentially serious toxic drug reactions that may not be obvious at rest. These include conduction abnormalities, negative inotropic effects, congestive heart failure and aggravation of arrhythmia. Although the presence and frequency of arrhythmia with exercise is highly variable in patients with benign arrhythmia, results are more consistent in patients with a history of serious arrhythmia. If arrhythmia is reproducibly provoked with exercise, this technique can be used to judge drug effect. Thus, exercise testing is an important, reliable and helpful technique for exposing arrhythmia, evaluating drug efficacy and identifying potentially serious toxic drug effects.

Hepatotoxicity Due to Treatment With Verapamil

Excerpt Verapamil hydrochloride (Isoptin; Knoll Pharmaceuticals, Whippany, New Jersey), a papaverine derivative currently being tested experimentally in the United States, is a calcium channel bloc...