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The preceding review indicates that silent myocardial ischemia has definite prognostic implications in both symptomatic and asymptomatic patients with coronary artery disease. Patients surviving an acute myocardial infarction are at a particularly high risk if they show evidence of myocardial ischemia. At present, many noninvasive diagnostic modalities are available to the physician for the evaluation of symptomatic and silent myocardial ischemia in such patients. Because as many as 30 per cent of patients may become asymptomatic after myocardial infarction, physicians must be aggressive in evaluating their patients for the presence of silent myocardial ischemia. The presence of silent ischemia would help identify those patients at high risk of postinfarction complications. Future use of currently available therapeutic modalities directed toward treatment of total ischemic burden on the myocardium may help lower morbidity and mortality in these patients by reducing the risk of subsequent cardiac events.

Calcium channel blockers have been postulated to be more effective as monotherapeutic antihypertensive agents in the elderly than in younger patients. To determine if a new dihydropyridine derivative, nitrendipine, is more effective in the elderly (older than 60 years) than in younger hypertensive subjects (younger than 60 years), nitrendipine was administered in a multicentered study to 21 elderly and 33 younger subjects with essential hypertension. After gradual discontinuation of previous antihypertensive therapy and 2 weeks of placebo, the daily dose of nitrendipine (10 to 40 mg) was titrated over 3 weeks to achieve a 10 mm Hg decrease in supine diastolic blood pressure (BP) for patients entering with 90 to 99 mm Hg. For patients entering with at least 100 mm Hg, the dose was titrated to diastolic BP no greater than 90 mm Hg. Titrated dose of nitrendipine was maintained for 4 additional weeks. Propranolol was added for "symptomatic" tachycardia. Nitrendipine reduced BP in 90% of patients completing all phases of the study (n = 49). The proportion of responders was 47% among the elderly and 44% among young subjects. Change in heart rate was similar in both groups (-0.1 +/- 9.9 and +2.9 +/- 8.8 beats/min, mean +/- standard deviation). Two elderly and 1 younger subject required addition of propranolol (difference not significant). There was no correlation between the age of patients and changes in supine systolic and diastolic BP or heart rate (r = 0.21, -0.15 and -0.21, respectively). Adverse effects occurred with equal frequency in older and younger subjects (19 of 21 vs 23 of 33 patients, difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-one of 496 (4%) patients with chronic bifascicular block, studied and followed prospectively, had block distal to the His bundle (BDH) induced by atrial pacing during initial electrophysiologic studies. In six, BDH was noted during pacing-induced atrioventricular (AV) nodal Wenckebach periods (at paced rates of 150--190 beats/min), with BDH in the short HH cycles after the AV nodal blocked P (lond cycle). The AH interval was normal in all six patients and HV was normal in four. None of the six patients has developed AV block during a mean follow-up of 5.33 +/- 0.48 years. In 15 patients, pacing-induced BDH was noted during intact AV nodal conduction (paced rate of 80--200 beats/min). The AH interval was prolonged in one, and HV was prolonged in 10 of the 15 patients. During a mean follow-up of 3.4 +/- 0.59 years, seven of these patients developed AV block, one had treadmill-provoked AV block, and two died suddenly (major morbid event in 10 of 15 patients). In conclusion, BDH induced by atrial pacing is an infrequent finding in patients with bifascicular block, and can be a functional as well as a pathologic response. The latter is associated with a high risk of major morbid events (AV block and sudden death).

Electrophysiologic studies have contributed significantly to the improved understanding of cardiac arrhythmias. Whereas previously treatment of these arrhythmias was largely empirical, electrophysiologic studies have paved the way for a scientific approach to evaluation and management of the patient with a potentially life-threatening problem.

The precise mechanism responsible for silent myocardial ischemia has not been established, but available data suggest that both an increase in oxygen demand and a decrease in coronary blood flow may be responsible. Studies indicate that more than 60 minutes of silent ischemia during 24-hour ambulatory electrocardiographic monitoring correlates with an increased incidence of myocardial infarction, cardiac death, and recurrent symptoms requiring coronary revascularization. Even in patients with shorter, repeated episodes of silent ischemia, small areas of subendocardial necrosis may develop that eventually lead to progressive left ventricular dysfunction, which increases the risk of subsequent mortality. Antianginal therapy, even though effective in control of symptoms, does not abolish silent ischemia. Further study of the pathogenesis of silent ischemia is needed before an effective treatment plan can be established.

The most appropriate treatment for a patient with angina pectoris depends on the underlying pathophysiologic process and whether any associated illness is present. Each patient's clinical history must be carefully reviewed so the hemodynamic process responsible for the clinical picture is understood. If symptoms are produced mostly by an increase in myocardial oxygen demand, efforts should be directed toward reducing the demand or improving coronary blood flow to meet the demand. If symptoms appear to occur secondary to vasospasm, treatment should be directed toward relief of spasm with potent vasodilating agents, such as calcium channel blockers. Most patients have a clinical picture consistent with mixed angina and may require combination therapy. Treatment of associated illnesses and the safety of pharmacologic agents used in their presence should be carefully considered. Finally, if treatment is to successfully reduce the incidence of serious cardiac events and prolong life, the goal of therapy should be relief of the total ischemic burden on the heart.

Electrophysiologic studies were done in 32 patients with aortic stenosis. In 24 patients with intact A-V conduction, A-H intervals ranged from 55 to 145 msec and were prolonged in two. Two had split His bundle potentials. The H-V intervals ranged from 25 to 94 msec and were prolonged in 12. The mean H-V interval was 63 +/- 2.6 msec in 12 patients with calcific aortic stenosis compared with 50 +/- 4.9 msec in 12 without calcification (P less than 0.05). The mean H-V in 10 patients with aortic gradients greater than 40 mm Hg was 62 +/- 5.6 msec compared with 47 +/- 3.1 msec in nine with gradients less than 40 (P less than 0.05). In patients with aortic stenosis and A-V block, the site of the block was distal to the His bundle in three and within the His bundle in five. All eight had calcified valves. Aortic stenosis was commonly associated with latent and manifest conduction disease in the His bundle and the trifascicular conduction system. Conduction disease was more extensive with calcified valves and greater valve obstruction.

The hemodynamic and antiarrhythmic interactions between nadolol and a commonly used class I antiarrhythmic agent, quinidine or procainamide, were evaluated in 18 patients with ventricular arrhythmias in a double-blind, parallel study. Patients qualified for entry into the study if their ventricular arrhythmias remained poorly controlled (greater than or equal to 10 ventricular premature complexes/hr) with the class I agent alone and they had a left ventricular ejection fraction greater than 30%. Patients received their usual therapeutic doses of quinidine or procainamide throughout the study, which consisted of 3 treatment periods; a 2-week placebo treatment period, a 2-week open-label oral nadolol dose titration period, during which the dosages of nadolol were gradually increased from 40 mg daily to a maximum tolerated dose up to 120 mg daily, and a 4-week randomized, parallel comparison period during which patients were treated with either a class I agent alone or a combination of a class I agent and nadolol. Left ventricular ejection fractions by radionuclide ventriculography and 24-hour ambulatory electrocardiographic (Holter) recordings were obtained at the end of each treatment period. A positive treatment response was defined as greater than or equal to 75% reduction in ventricular premature complex frequency. During the dose titration phase, combination therapy with nadolol (mean dose 94 mg daily) and class I agents produced a mean decrease in ventricular premature complexes of 79% (p less than 0.01), and a mean decrease in ventricular couplets of 95% (p less than 0.01). A positive response was observed in 57% of patients treated with nadolol plus a class I agent.(ABSTRACT TRUNCATED AT 250 WORDS)

One-hundred and five patients with hypertension received nitrendipine (10-40 mg/day) or hydralazine (50-200 mg/day) in a double-blind randomized design. Nitrendipine decreased supine blood pressure 15/10 mm Hg, and hydralazine decreased it 11/11 mm Hg. Standing blood pressure was decreased 15/12 mm Hg by nitrendipine and 12/11 mm Hg by hydralazine. Supine and standing heart rate rose significantly after both drugs. Blood pressure variation through one dosing interval increased 42% when hydralazine was given but was not altered by nitrendipine. Side-effects from the two drugs were similar in patients who completed the study, but six patients discontinued participation due to side-effects of hydralazine, while only one discontinued due to nitrendipine side-effects. Ten patients required propranolol for hydralazine side-effects, and only three required it for nitrendipine side-effects. Nitrendipine and hydralazine are equally effective as antihypertensive monotherapy in patients with mild to moderate hypertension for periods up to 7 weeks, but nitrendipine appears to be better tolerated.

Prolonged (greater than 152 msec) calculated sinoatrial conduction times (SACT) were found in 24 of 470 patients studied by the atrial extrastimulus technique, ranging from 155 to 220 msec (180+/-4.4; mean+/-SEM). There were 18 males and six females with ages of 29 to 85 (mean 65+/-2.6). Electrocardiographic monitoring revealed significant sinus or atrial dysrhythmias in 19 (79%) patients. Of these 19, 15 had persistent sinus bradycardia and/or sinoatrial block, three had sinus bradyarrhythmia with paroxysmal atrial tachycardia, and one had isolated atrial tachycardia. Additional electrophysiological evidence of sinus node or atrial dysfunction was present in 11 patients. Four patients needed permanent pacing during follow-up (mean follow-up period of 427+/-39 days) because of symptomatic bradyarrhythmia. Three patients died, none suddenly. In conclusion, prolonged calculated SACT was associated with a high incidence of electrocardiographic and electrophysiologic abnormalities of sinus node and/or atrium. Despite this, bradyarrhythmic morbidity was relatively low, suggesting that prolonged sinoatrial conduction time in the absence of symptoms is not an indication for prophylactic pacing.

Calcium (Ca(++)) plays an essential role in many cardiovascular physiologic processes. Electrophysiologic properties of the sinus and atrioventricular nodes greatly depend on Ca(++) ion influx. Also, Ca(++) is the main link for excitation-contraction coupling of the myocardium. Ca(++) channel blockers are a group of heterogeneous compounds that block the ionic influx of Ca(++) into the myocardial and vascular smooth muscle cells. Because Ca(++) plays a central role, it is not surprising that Ca(++) channel blockers can produce profound alterations in cardiovascular functions. Recently several studies have shown these agents to be useful in the treatment of supraventricular tachyarrhythmia, variant angina, chronic stable angina and hypertrophic cardiomyopathy. In the future they may be found useful in preserving myocardium during cardiopulmonary bypass, in limiting infarct size and in the treatment of hypertension and congestive heart failure.

Electrophysiological studies were conducted in 13 patients with normal sinus node function and 14 with sinus node dysfunction before and after intravenous lidocaine. Mean +/- SEM sinus cycle length significantly shortened from 810 +/- 34.3 to 774 +/- 34.3 msec in patients with normal sinus node (P less than 0.001) and from 1061 +/- 67.6 to 1016 +/- 64.5 msec in patients with sinus node dysfunction (P less than 0.025) after lidocaine. Mean sinus recovery time was 1027 +/- 49.4 before and 1026 +/- 52.5 msec after lidocaine in patients with normal sinus node (NS) and 1269 +/- 97.7 before and 1170 +/- 73.8 msec after lidocaine in patients with sinus node dysfunction (P less than 0.05). Mean calculated sinoatrial conduction time was 87 +/- 9.5 before and 90 +/- 9.2 msec after lidocaine in patients with normal sinus node (NS) and 80 +/- 10.3 before and 96 +/- 10.2 msec after lidocaine in patients with sinus node dysfunction (P less than 0.001). Mean atrial effective and functional refractory periods were not significantly changed with lidocaine. Thus lidocaine shortened sinus cycle length in both groups, without affecting atrial refractoriness. Lidocaine appeared to depress perinodal tissue only in patients with sinus node dysfunction. The abbreviation of sinus recovery time in patients with sinus node dysfunction could reflect increased sinus automaticity and/or increased perinodal refractoriness, allowing entrance block to occur. This mechanism may explain why sinus arrest has been noted in some patients during lidocaine administration.

Patients with CHF are commonly encountered in clinical practice. Cardiac arrhythmias, particularly complex ventricular premature contractions, often occur in these patients. The presence of ventricular tachyarrhythmia, especially ventricular tachycardia, denotes a poor prognosis. Patients with CHF already have a limited life span, and the presence of ventricular arrhythmia further increases an already high death rate. Although previous reports failed to show any significant effect of treatment on mortality in patients with CHF, results of recent studies are encouraging. Several reports have shown that treatment with angiotensin converting enzyme inhibitors and newer antiarrhythmic agents reduces the frequency of ventricular arrhythmia and decreases mortality. It is hoped that the results of these studies will be confirmed in well-controlled, large-scale, prospective trials.