Risk stratification after myocardial infarction using signal-averaged electrocardiographic criteria adjusted for sex, age, and myocardial infarction location.

BACKGROUND: The objectives were to investigate the factors influencing signal-averaged ECGs (SAECGs) recorded in patients after myocardial infarction (MI) and to develop criteria for predicting arrhythmic events (AEs) that account for these factors. METHODS AND RESULTS: SAECGs were recorded 5 to 15 days after MI in 2461 patients without bundle-branch block. The duration (QRSd), terminal potential (VRMS), and terminal duration (LAS) of the filtered QRS were measured. During follow-up (17 +/- 8 months), AEs (arrhythmic death; ventricular tachycardia, VT; ventricular fibrillation, VF) occurred in 80 patients (3.3%). Receiver operating characteristic curves showed that QRSd discriminated patients with all types of AEs, but VRMS and LAS discriminated only VT patients; QRSd minus LAS also discriminated AE patients. Sex, age, and MI location significantly affected the SAECG; survivors without VT or VF were divided into subgroups (2 sex x 4 age x 2 MI), and QRSd values exceeding the 70th percentile in each subgroup predicted AEs with a sensitivity of 65.4%. An unadjusted QRSd criterion showed the same overall sensitivity and specificity but with less uniform values for each subgroup. A Cox model was constructed by use of multiple prognostic indicators, and in rank order, QRSd, previous MI, and Killip class were predictive of AEs. CONCLUSIONS: SAECG adjustments for sex, age, and MI location did not improve sensitivity and specificity but produced a more uniform predictive performance. The proposed criteria are based only on QRSd, because late potentials (VRMS and LAS) did not discriminate patients with sudden death. Duration of high-level activity during QRS (QRSd-LAS) can predict AEs, suggesting that the arrhythmogenic substate involves a large mass of myocardium.

Unstable angina--report from a Canadian expert roundtable.

Unstable angina is generally considered to encompass a spectrum of symptomatic manifestations of ischemic heart disease, intermediate between stable angina and acute myocardial infarction. Approximately 75,000 Canadians are hospitalized yearly with unstable angina. The pathophysiology of unstable angina is still imperfectly understood, but is related to the same pathophysiological factors underlying myocardial infarction and sudden cardiac death. In March 1995 a group of Canadian cardiologists met to review the current understanding of unstable angina and to define a Canadian approach to this common problem. Important issues and questions regarding the diagnosis and management of unstable angina were defined. The objective was to outline approaches to the management of unstable angina that would be appropriate in Canada. Topics discussed included definition, incidence, clinical presentations, pathophysiology, initial diagnostic and risk stratification approaches, acute medical management, role of invasive interventions and long term management.

PROTECT (Prospective Reinfarction Outcomes in the Thrombolytic Era Cardizem CD Trial): a randomized, double-blind clinical trial of diltiazem versus atenolol in secondary prophylaxis post non-Q wave myocardial infarction.

OBJECTIVE: To describe the rationale and design of the Prospective Reinfarction Outcomes in the Thrombolytic Era Cardizem CD Trial (PROTECT). DESIGN: A multicentre, randomized, double-blind, parallel-group comparison of once daily beta-therapy versus heart rate lowering calcium channel blocker therapy, in the reduction of one-year nonfatal reinfarction and cardiovascular death (combined primary end-point) initiated 24 to 96 h post non-Q wave myocardial infarction. SETTING: One hundred and twenty hospitals across Canada. PATIENTS: Over 7500 women and men aged 21 years or older with enzyme-confirmed non-Q wave infarction and without significant left ventricular systolic dysfunction will be recruited over two years. INTERVENTIONS: Once daily beta-blocker therapy (oral atenolol, 50 to 200 mg) versus once daily calcium channel blocker therapy (oral diltiazem 120 to 360 mg) with follow-up for up to three years. CONCLUSIONS: The PROTECT will be the largest all-Canadian cardiovascular trial to date and will compare two commonly prescribed agents for secondary prophylaxis following non-Q wave infarction. The scientific question addressed by the PROTECT is of major public health importance and the results of the study will directly affect current clinical practice.

Myocardial infarction patients in the 1990s--their risk factors, stratification and survival in Canada: the Canadian Assessment of Myocardial Infarction (CAMI) Study.

OBJECTIVES: This study sought to evaluate the in-hospital and postdischarge mortality of patients with an acute myocardial infarction in the 1990s. BACKGROUND: The widespread implementation of therapeutic interventions that modify the natural history of coronary artery disease has led to changes in the profile and survival of patients with an acute myocardial infarction. Although data exist for selected subsets of patients with an acute myocardial infarction, at this time there is little recent prospective information on all patients presenting with an acute myocardial infarction, particularly for survival after hospital discharge. METHODS: All patients < or = 75 years old presenting with an acute myocardial infarction between July 1, 1990 and June 30, 1992 at nine Canadian hospitals were prospectively evaluated and followed up for 1 year. From November 1991, patients of all ages were included. In two centers, recruitment continued until December 31, 1992. A total of 3,178 patients were recruited. RESULTS: The in-hospital mortality rate of patients < or = 75 years old was 8.4%, and that at 1 year after hospital discharge was 5.3%. For patients of all ages recruited after November 1, 1991, the in-hospital mortality rate was 9.9% and 7.1% for 1 year after hospital discharge. For patients < or = 75 years old, age carried an independent in-hospital but no post discharge risk. Female patients had a twofold greater risk of dying in hospital. After hospital discharge, only 1.7% of patients < or = 75 years old and 1.9% of patients of all ages died of a presumed arrhythmic death. Premature ventricular contractions had no independent prognostic value. The relatively low in-hospital (5.3%) and postdischarge (6.1%) reinfarction rate may have contributed to improved survival. A greater reinfarction rate in patients >75 years old (17.4% vs. 9.6%, p < 0.001) may have contributed to their poorer outcome. CONCLUSIONS: One-year mortality after acute myocardial infarction continues to decrease, and changes in the prognostic value of traditional methods of risk stratification have occurred.

Antianginal efficacy and safety of controlled-delivery diltiazem QD versus an equivalent dose of immediate-release diltiazem TID.

Controlled-delivery once-daily diltiazem (qd), 180 mg and 360 mg, was assessed in two multicenter, randomized, double-blind, placebo-controlled trials using a 3 x 3 Latin square design. Both studies compared the controlled-delivery dosage form to the same total daily dose of immediate-release diltiazem administered three times daily (tid) and to placebo. The primary measure of efficacy was the time to termination of the exercise tolerance test (ETT) at 2, 8, and 24 hours after the morning dose. There were no significant differences in time to ETT termination between the qd and tid formulations at any time, except at 24 hours with 180 mg qd versus 60 mg tid. The comparison to placebo showed that diltiazem 180 mg qd, 360 mg qd, and 120 mg tid significantly lengthened the time to ETT termination (p < 0.05) at all time points, while diltiazem 60 mg tid did not differ from placebo at any time point. The qd formulation also increased the time to 1-mm ST-segment depression and reduced the number of angina attacks and the amount of nitroglycerin used when compared to placebo. No new or unusual adverse events were noted. Diltiazem controlled-release capsules administered once daily are safe and effective for the treatment of patients with chronic stable angina.

Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise.

BACKGROUND: Silent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear. METHODS AND RESULTS: Sixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p = 0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 +/- 148 from 296 +/- 154 seconds (p = 0.005). Although less frequent with diltiazem administration (45 versus 54 patients, p less than 0.03), exercise-induced ST depression was more often asymptomatic (98% versus 72% of patients, p less than 0.0001). CONCLUSIONS: Diltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease.

Role of diltiazem in the treatment of silent myocardial ischemia.

Silent myocardial ischemia is a frequent finding when Holter monitoring is done in patients with advanced coronary disease. Silent ischemia is associated with a worse prognosis in patients with stable or unstable angina, survivors of myocardial infarction, and populations at risk for coronary disease. Whether medical therapy for silent ischemia improves prognosis is not known. In a randomized, placebo-controlled, multicenter trial of 60 patients with documented coronary disease, positive exercise tests, and ischemic episodes on Holter monitoring, long-acting diltiazem reduced ischemic episodes by 50% compared to placebo, from a mean of 5.6 to 2.8 (p less than 0.0001). Efficacy was maintained over 24 h and diltiazem also significantly improved exercise test parameters. Three smaller studies also demonstrated that diltiazem effectively reduces ambulatory ischemia; however, results with nifedipine are conflicting, with several studies showing no benefit. In contrast, beta-blockers reliably reduce ischemic episodes. The role of medical therapy for silent ischemia will be clarified only when its effect upon morbidity and mortality are determined.

Usefulness of sustained-release diltiazem for stable angina pectoris.

Sustained-release diltiazem, 120 and 180 mg twice daily, was assessed in a multicenter, double-blind, randomized, placebo-controlled trial in 65 stable angina patients with exercise-induced ST depression. Exercise testing was performed 12 +/- 1 hours after the last dose at the end of each of the 3 treatment weeks. Both dose levels of drug reduced spontaneous angina (p less than 0.001) and increased exercise duration (p less than 0.01) and time to 1-mm ST depression (p less than 0.001). No differences were noted between the 2 dose levels. Rate-pressure product at maximal exercise was similar for the 3 groups. Only 1 patient terminated the study because of adverse drug effects; severe adverse effects occurred in 1 placebo and 1 low-dose period. Sustained-release diltiazem is safe and efficacious monotherapy for patients with stable angina.

The effect of swimming exercise of rat myocardial ornithine decarboxylase activity.

Within 30 minutes of swimming exercise there was an increase in myocardial ornithine decarboxylase activity. The activity continued to increase throughout the two hour period of exercise, after which it decreased again. Two hours after exercise, the enzyme activity had returned to the resting level, and four hours after exercise myocardial ornithine decarboxylase activity was slightly less than the resting level. Repeated daily exercise was associated with a diminished response on the second and third days. Subsequently however, myocardial ornithine decarboxylase activity was again stimulated by two hours of swimming exercise.