An evaluation of EASI electrocardiography was made in 50 non-consecutive patients lodged ir? a CCU. EASI 5-lead ECG was recorded simultaneously with standard 12-lead ECG and I re-essembled into a 12-lead format via a Dower conversion box. Excellent agreement between EASI cardiograms and 12-lead ECG was observed for PR, QRS, Qr intervals, for cardiac arrhythmias (3 atrial fibrillation I ventricular tachycardia) and for ventricular conduction disorders. Concordance between EASI and 12-lead standard ECG for presence or absence of MI was 89%. EASI had a sensitivity and specificity for Q-wave MI detection of 94% and 93% respectively.These results suggest that the EASI 5-lead ECG shows a high correlation with standard 12-lead ECG and could be adapted for diagnostic use in a CCU.

Atrial fibrillation has been found to be a significant risk factor for stroke independent of the contribution this common arrhythmia makes via its previously established stroke risk factors. Results of four recent trials in patients with nonrheumatic atrial fibrillation show that warfarin anticoagulant therapy can substantially reduce the risk of stroke without major bleeding complications.

The effectiveness of a sustained-release preparation of verapamil (verapamil-SR) was compared with the regular formulation of verapamil and with placebo in 12 patients with chronic stable angina pectoris. All patients completed an 8-week, double-blind, double-crossover, randomized protocol with 2-week treatment periods of verapamil-SR, 240 mg twice daily; regular-formulation verapamil, 120 mg 4 times daily; and 2 placebo therapies. The frequency of weekly anginal episodes was reduced from 7.6 ± 10.0 with placebo to 3.1 ± 4.2 after the regular formulation of verapamil (p = 0.09) and from 6.4 ± 7.6 with placebo to 2.8 ± 4.8 after verapamil-SR (p = 0.06). Treadmill time increased from 384 ± 144 seconds during the first placebo phase to 468 ± 138 seconds after the regular formulation of verapamil (p < 0.01) and from 354 ±102 seconds during the second placebo phase to 462 ± 138 seconds after verapamil-SR (p < 0.01). Time to the onset of angina was similarly prolonged by both formulations of verapamil. There were no significant adverse effects after 1 year in any patient taking verapamil-SR, 240 mg twice daily. Thus, a twice-aday verapamil-SR dose regimen is safe and is as effective for treatment of angina of effort as the regular formulation given 4 times a day.

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.

Calcium entry blocker drugs have hypotensive effects that are mediated by both cardiac and noncardiac actions. Dihydropyridine calcium blockers, such as nifedipine and nicardipine, are potent vascular smooth muscle relaxants that lower blood pressure by decreasing peripheral arteriolar resistance. Reflex tachycardia, however, may blunt the magnitude of their hypotensive effect, especially in patients with increased baroreflex sensitivity. Nondihydropyridine calcium blocker drugs, such as verapamil and diltiazem, exert their hypotensive action by both cardiac and peripheral circulatory mechanisms. These drugs also act as arteriolar vasodilators. In addition, they slow the heart rate by decreasing the automaticity of sinoatrial pacemaker cells in the heart. The combined negative chronotropic and vasodilatory actions are especially useful in hypertensive patients with baroreflex sensitivity who are prone to fast heart rates, and in hypertensive patients with associated coronary artery disease. Coronary heart disease patients with or without coexisting hypertension usually show reduction in systolic blood pressure (SBP) and heart rate (HR) both at rest and during submaximal exercise on the treadmill or bicycle. A reduced double product (SBP X HR) with submaximal exertion results in a decrease in cardiac work and correlates with enhanced exercise capacity and delay in onset of angina during exercise testing. In some patients with both hypertensive and coronary heart diseases and ventricular dysrhythmias emerging during exercise, verapamil may confer antiarrhythmic as well as antihypertensive and antianginal benefits. At present, calcium blocker drugs, which have an elimination half-life of 3 to 6 hours, must be given 3 times a day for effective antihypertensive control. However, a sustained-release formulation of verapamil with a half-life of 12 ± 6 hours shows great promise as a 2-times-a-day antianginal and antihypertensive drug.

The efficacy and safety of high-dose verapamil (480 mg/day) and diltiazem therapy (360 mg/day) were compared in separate cohorts of 26 and 20 patients, respectively. All patients had stable exertional angina and underwent an initial 6-week double-blind, placebo-controlled, randomized phase followed by a 12-month open-label period. Angina attacks were reduced by verapamil (6.3 +/- 7.5 to 2.5 +/- 4.1 attacks per week, p less than 0.001) and by diltiazem (9.2 +/- 7.5 to 3.0 +/- 3.1 attacks per week, p less than 0.001), while treadmill time increased with both verapamil (372 +/- 132 to 444 +/- 108 s, p less than 0.001) and diltiazem (412 +/- 175 to 536 +/- 164 s, p less than 0.001) during the short-term study. Both agents continued to show similar salutory effects at the end of one year. The beneficial effects of both drugs appeared to be related in part to a reduction of the rate-pressure product during submaximal exercise (12% by verapamil, 7% by diltiazem, both p less than 0.05). Adverse effects were few and consisted primarily of mild constipation in six patients taking verapamil, and pedal edema and transient flushing in 2 patients each using diltiazem. Thus, high-dose verapamil and diltiazem have similar beneficial effects and are safe for the long-term treatment of effort-related angina pectoris.

Our study in 10 patients with stable, exercise-related angina under a double-blind, placebo-controlled protocol correlated plasma verapamil levels after single oral doses of 120 and 240 mg and exercise performance. Plasma verapamil levels peaked at 2 hr in seven patients and 4 hr in three patients and declined thereafter, with a mean plasma t1/2 of 3.22 and 4.54 hr after the 120- and 240-mg dose. Despite the relatively short t1/2s, total exercise duration and time to onset of angina and S-T segment depression were longer than placebo values for 4 hr after the 120-mg dose and for 8 hr after the 240-mg dose. Percentage increase in treadmill time and log of plasma verapamil levels correlated. All patients with plasma levels above 100 ng/ml had at least a 50% increase in exercise duration. Thus measurement of plasma verapamil levels are useful in patients who fail to respond to a dose of verapamil. If the level is below 100 ng/ml, increasing the dose of verapamil may improve response.

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.

The long-term efficacy and safety of high-dose verapamil therapy (480 mg/day) was assessed in 26 patients with chronic stable angina pectoris during a 3-phase protocol: Phase 1--an initial, 6-week placebo-controlled, double-blind crossover assessment; Phase 2--an open label, 1-year follow-up; and Phase 3--a final drug withdrawal and rechallenge 10-week study. Three patients withdrew during Phase 2 (1 had hepatitis and 2 underwent coronary bypass surgery). Adverse effects during Phase 2 were mild, consisting of constipation (6 patients) and prolongation of the P-R interval (5 patients); however, no patient required alteration of the 480 mg/day dosage. At the end of Phase 2, 10 patients underwent the Phase 3 study, commencing with a 2-week period in which verapamil was either tapered gradually or abruptly discontinued. This was followed by an 8-week double-blind, placebo-controlled crossover rechallenge study with verapamil. The clinical and exercise responses to verapamil compared with placebo were similar during the Phase 3 protocol and the initial Phase 1 study (treadmill time increased by 55% and anginal attacks per week decreased by 63% during Phase 3, compared with a 28% increase and a 42% decrease, respectively, during Phase 1, p = not significant [NS]). Withdrawal of verapamil produced a similar return of anginal symptoms whether the drug was abruptly discontinued or its administration tapered. No patient had unstable angina pectoris or acute myocardial infarction. These investigations demonstrate that verapamil is safe and effective when evaluated after 1 year of continuous therapy using a dosage of 480 mg/day. There is no evidence of drug tachyphylaxis, nor does verapamil appear to cause an abrupt withdrawal syndrome in patients with chronic 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.