Treating electrical storm : sympathetic blockade versus advanced cardiac life support-guided therapy.

BACKGROUND: Electrical storm (ES), defined as recurrent multiple ventricular fibrillation (VF) episodes, often occurs in patients with recent myocardial infarction. Because treating ES according to the Advanced Cardiac Life Support (ACLS) guidelines yields a poor outcome, we evaluated the efficacy of sympathetic blockade in treating ES patients and compared their outcome with that of patients treated according to the ACLS guidelines. METHODS AND RESULTS: Forty-nine patients (36 men, 13 women, mean age 57+/-10 years) who had ES associated with a recent myocardial infarction were separated into 2 groups. Patients in group 1 (n=27) received sympathetic blockade treatment: 6 left stellate ganglionic blockade, 7 esmolol, and 14 propranolol. Patients in group 2 (n=22) received antiarrhythmic medication as recommended by the ACLS guidelines. Patient characteristics were similar in the 2 groups. The 1-week mortality rate was higher in group 2: 18 (82%) of the 22 patients died, all of refractory VF; 6 (22%) of the 27 group 1 patients died, 3 of refractory VF (P<0.0001). Patients who survived the initial ES event did well over the 1-year follow-up period: Overall survival in group 1 was 67%, compared with 5% in group 2 (P<0.0001). CONCLUSIONS: Sympathetic blockade is superior to the antiarrhythmic therapy recommended by the ACLS guidelines in treating ES patients. Our study emphasizes the role of increased sympathetic activity in the genesis of ES. Sympathetic blockade-not class 1 antiarrhythmic drugs-should be the treatment of choice for ES.

Abolition of Holter monitor-detected silent myocardial ischemia after percutaneous transluminal coronary angioplasty.

Twenty-four hour Holter ambulatory electrocardiographic recordings were obtained before and after successful coronary angioplasty in 36 patients. Twenty-five patients had one vessel, 10 had two vessel and 1 had three vessel coronary artery disease. Holter monitor-detected myocardial ischemia, defined as ST segment depression or elevation greater than or equal to 1 mm, was present in 10 patients (28%). These 10 patients had a total of 39 ischemic episodes of 3 to 144 minutes' duration, with a total cumulative duration of 398 minutes. None of the 10 had Holter monitor-detected ischemia after successful angioplasty (p less than 0.01). Treadmill exercise duration increased by 29% after coronary angioplasty (p less than 0.01), and peak exercise heart rate-systolic blood pressure product increased by 27% (p less than 0.01). Thus, Holter monitor-detected myocardial ischemia is a relatively uncommon finding in patients with predominant single vessel coronary artery disease undergoing coronary angioplasty. When such ischemia is present, it is eliminated by successful coronary angioplasty.

Treatment of catecholamine-sensitive right ventricular tachycardia by endocardial catheter ablation.

Endocardial catheter ablation with direct current high voltage shocks was performed in a patient with recurrent syncope due to a catecholamine-sensitive ventricular tachycardia that was drug refractory and occurred in the absence of identifiable heart disease. Pace mapping and catheter activation mapping of the spontaneous and isoproterenol-induced ventricular tachycardia located the tachycardia origin in the right ventricular outflow tract. Ablation dramatically reduced spontaneous ventricular tachycardia and ectopic activity (from 50,000 to less than 100 ectopic beats/24 h). The patient has remained symptom free and without ventricular tachycardia recurrence for 3 years. These observations and review of previous studies suggest that catheter mapping can easily locate the arrhythmia focus in the right ventricular outflow tract and that catheter ablation can be performed at low risk. Catheter ablation is a viable option for the treatment of right ventricular catecholamine-sensitive tachycardias that are unresponsive to antiarrhythmic drugs.

Endothelium-dependent vasorelaxation is impaired in cocaine arteriopathy.

OBJECTIVES: This study sought to assess endothelium-dependent vasorelaxation in long-term users of cocaine. BACKGROUND: Cocaine use has been associated with myocardial infarction, stroke and intestinal infarction. Previously demonstrated effects of the drug, including increased heart rate and blood pressure and increased vascular tone, do not explain the sporadic nature of these vascular events or the occurrence of ischemia remote from acute administration. Abnormal endothelial function could contribute to focal vasospasm and thrombosis and predispose to premature atherosclerosis, all of which have been demonstrated in cocaine users with myocardial infarction. METHODS: Using plethysmography, we studied the change in forearm blood flow in response to intraarterial acetylcholine and nitroprusside in 10 long-term cocaine users and 13 control subjects of similar age who had not used cocaine; sample size was based on a 70% power to detect a 20% reduction in flow with acetylcholine between subjects and control subjects. Using graded doses of intracoronary acetylcholine (from 10(-9) to 10(-6) mol/liter), we studied a second group of 10 cocaine users with angiographically normal or near-normal arteries. RESULTS: Mean forearm blood flow during acetylcholine infusion was significantly lower in cocaine users than in control subjects (p = 0.02). During nitroprusside infusion, there was no difference (p = 0.2) between cocaine users and control subjects. Cigarette smoking did not explain the differences between cocaine users and control subjects. Acetylcholine elicited coronary vasoconstriction in 8 of 10 subjects. CONCLUSIONS: We conclude that endothelium-dependent vasorelaxation is impaired in long-term users of cocaine.

Electrophysiologic basis for the suppression by amiodarone of orthodromic supraventricular tachycardias complicating pre-excitation syndromes.

Ten patients with refractory recurrent supraventricular tachycardia were found by electrophysiologic study to have bypass tracts and orthodromic atrioventricular reentrant tachycardia. All had failed to respond to conventional antiarrhythmic therapy and were therefore treated with oral amiodarone (1,600 to 2,000 mg/day for 2 weeks, then 800 to 1,200 mg/day for another 2 weeks with subsequent 200 to 600 mg/day maintenance doses). During or after the fourth week of therapy, electrophysiologic study was repeated. In 9 of 10 patients, supraventricular tachycardia could not be reinduced by programmed stimulation. In the remaining patient, nonsustained supraventricular tachycardia (greater than 10 beats, lasting less than 30 seconds) with a slower basic cycle length than that during the control period was provoked. Significant increases in the effective refractory period of the accessory pathway in both the anterograde (+26%, p less than 0.05) and retrograde (+40%, p less than 0.02) directions were noted, the magnitude of change being independent of the control effective refractory period. There were also significant increases in the effective refractory period of the right atrium (+24%, p less than 0.01) and the right ventricle (+15%, p less than 0.01) during long-term therapy with amiodarone. Over a mean follow-up period of 20 months, symptomatic control of the arrhythmia occurred in all patients; in only one patient treatment with amiodarone could not be continued because of side effects. These data establish the electrophysiologic basis for the effectiveness of amiodarone in the prophylactic control of refractory paroxysmal supraventricular tachycardia complicating the bypass tract syndromes.

Severity of silent myocardial ischemia on ambulatory electrocardiographic monitoring in patients with stable angina pectoris: relation to prognostic determinants during exercise stress testing and coronary angiography.

The relation of silent ischemia in patients with stable angina to known predictors of severity of coronary disease on exercise stress testing and coronary angiography is poorly defined. This issue was therefore examined with use of Holter electrocardiographic (ECG) recordings, treadmill exercise tests and angiographic indexes in 102 patients (not taking antianginal therapy) and the results were compared with Holter and treadmill findings in 42 volunteers. A total of 159 ischemic episodes (90% silent) were identified during 2,503 h on Holter recording in 97 patients (mean duration per episode 22.7 +/- 147 min; range 1 to 234). Holter recordings had a 92% specificity and an 80% positive predictive value, but a sensitivity of only 37% and a negative predictive value of 27% for coronary disease. Sixty-three patients (Group I) had no ischemia on Holter recording, 22 (Group II) had a cumulative duration of 1 to 60 min/24 h and in 12 (Group III) ischemia exceeded 60 min/24 h. There was no significant correlation between cumulative ischemia duration on Holter recording and exercise duration or time to ST segment depression on treadmill exercise. In general, the greater the number of coronary vessels involved and the higher the proximal coronary artery stenosis score, the greater the likelihood of ischemia and the longer the cumulative ischemia duration on Holter recording. Irrespective of the severity of coronary disease, in about 25% of Holter recordings in each angiographic category there were no ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrioventricular block complicating amiodarone-induced hypothyroidism in a patient with pre-excitation and rate-dependent bilateral bundle branch block.

As a clinical entity atrioventricular (AV) block due to hypothyroidism is rare. Such a case induced by hypothyroidism complicating long-term therapy with amiodarone in a 45 year old woman with pre-excitation is presented. Electrophysiologic data obtained before and during thyroxine replacement therapy showed that hypothyroidism lengthens the effective refractory period of the atria, AV node, bypass tract and His-Purkinje system (that in the ventricle not being measured); this lengthening resembles the effects of long-term administration of amiodarone. These observations suggest that depressed thyroid function may be protective against arrhythmias but a patient with preexisting conduction system disease may develop AV block. The tendency to develop AV block in a patient who is euthyroid was reduced by bypass tract conduction. These findings are significant not only in monitoring amiodarone effects during chronic prophylactic drug therapy but also in providing further insight into the complex interrelation between the action of the drug and the thyroid hormones on cardiac muscle.

Prognostic significance of silent myocardial ischemia in patients with unstable angina.

Silent myocardial ischemia is common in unstable angina, but its prognostic significance is unknown. Fifty-two (42 with subsequent angiography) of 81 patients prospectively evaluated for unstable angina had ambulatory electrocardiographic (Holter) recordings analyzed by compact analog technique after they had received medical treatment (3 of the 52 had unanalyzable recordings and were excluded). From 1,103 hours of recordings, 298 ischemic episodes were identified, only 9% associated with angina. By Ridit analysis a significant correlation was found between the cumulative duration of transient myocardial ischemia and the number of diseased coronary vessels and indexes of proximal stenosis. During a 3 to 6 month follow-up period, there was one death and one patient was lost to follow-up among 20 patients without transient ischemia; in the group of 11 patients with a cumulative duration of transient ischemia less than 60 minutes/24 h, 7 were alive and well, 2 required coronary bypass surgery, 1 had coronary angioplasty for recurrence of angina and 1 was lost to follow-up. In the group of 18 patients with ischemia duration greater than 60 minutes/24 h, only 1 developed a stable angina pattern; 12 required coronary surgery (n = 11) or angioplasty (n = 1) and 5 developed myocardial infarction (2 died, 2 needed surgery for postinfarction angina and 1 recovered). A favorable clinical outcome occurred in only 6% of patients in the group with ischemia duration greater than 60 minutes/24 h; this rate was significantly lower (p less than 0.001) than that (70%) for the group with ischemia duration less than 60 minutes/24 h or that (95%) for the group without ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of indexes for myocardial ischemia: a comparison of exercise treadmill test, ambulatory electrocardiographic monitoring and symptoms of myocardial ischemia.

Fifty-four patients with chronic stable angina were studied to determine and compare weekly variability of indexes for the detection of myocardial ischemia. All patients underwent three single-blind placebo periods, each lasting 1 week. An exercise treadmill test, 24 h ambulatory electrocardiographic (Holter) monitoring (analyzed blindly) and an accurate diary of anginal attacks and nitroglycerin use were obtained at the end of each placebo period. An unbalanced, completely random component of variance analysis was used to calculate a component for within subject variability and a component for among subject variability. The coefficient of variation and percent variation (within subjects) of onset of chest pain during exercise were 19% and 30%, respectively; the corresponding values were 28% and 33% for onset of 1 mm ST depression, 15% and 15% for exercise duration, 44% and 27% for number of ischemic episodes/24 h, 56% and 43% for anginal frequency and 55% and 27% for nitroglycerin consumption, respectively. With use of this statistical method and variation within subjects, the change in the value of each variable necessary to exceed those attributable to spontaneous variation was determined. The trade-off between repeated measurements and number of subjects, the sample size estimated for planning studies and the minimal sample size for using various designs were also determined. Although the data indicate that all indexes for myocardial ischemia, both during exercise and during daily activity, vary considerably, but the exercise variables have less variability and are more reproducible.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications.

Administration of amiodarone (600 to 1,600 mg/day) to 28 patients during long-term digoxin therapy (0.25 +/- 0.05 mg/day) increased serum digoxin level from 0.97 +/- 0.45 to 1.98 +/- 0.84 ng/ml (p less than 0.001). Gastrointestinal side effects occurred in nine patients, central nervous system reactions occurred in five and cardiovascular reactions occurred in four. Pharmacokinetic studies in six patients with a 1 mg intravenous digoxin dose before and during amiodarone therapy increased serum digoxin level at 30 minutes from 8.59 +/- 1.68 to 10.07 +/- 1.70 ng/ml (p less than 0.05). Amiodarone caused a 31% prolongation of digoxin elimination half-life from 49.5 +/- 8.8 to 65.0 +/- 28.8 hours, but the increase in half-life was not statistically significant. Total body clearance was reduced significantly (29%, p less than 0.05) from 2.05 +/- 0.76 to 1.46 +/- 0.64 ml/min per kg. Nonrenal clearance also showed a significant decrease (33%, p less than 0.05) from 1.20 +/- 0.46 to 0.80 +/- 0.30 ml/min per kg. The renal clearance decreased by 22% and the volume of distribution decreased by 11% after amiodarone therapy, but these changes were not significant. The data show that the mechanism of digoxin-amiodarone interaction is multifactorial and emphasize the need for close monitoring of serum digoxin levels and clinical features during concurrent digoxin-amiodarone therapy.

Resetting of ventricular tachycardia: implications for localizing the area of slow conduction.

Analysis of local endocardial electrograms recorded during reentrant ventricular tachycardia does not provide direct information as to the participation of the recording site in the tachycardia circuit. To determine if programmed electrical stimulation at the recording site can assist in localizing areas of slow conduction that are participating in the tachycardia circuit, seven patients with sustained monomorphic ventricular tachycardia were studied. The cardiac cycle was scanned with single stimuli delivered during ventricular tachycardia at multiple endocardial sites. In four patients, an endocardial site was identified at which stimuli advanced the tachycardia with marked conduction delay and without alteration of the ventricular activation sequence, as indicated by a lack of change in the configuration of the QRS complex and endocardial electrograms distant from the stimulation site. This finding was seen only during stimulation at sites displaying abnormal electrograms and is consistent with premature depolarization of an area of slow conduction within the tachycardia focus by stimuli delivered at or near that area. Attempted endocardial catheter ablation at or adjacent to these sites in three patients was followed by persistent noninducibility of ventricular tachycardia in one patient, marked modification of the configuration and cycle length of inducible tachycardia in one patient and transient noninducibility of tachycardia in one patient. Programmed electrical stimulation during ventricular tachycardia at sites with abnormal electrograms may provide information about the proximity of the stimulation site to the tachycardia circuit.

Fractionated endocardial electrograms are associated with slow conduction in humans: evidence from pace-mapping.

Fractionated ventricular electrograms recorded during catheter mapping may arise from areas of asynchronous depolarization associated with slow conduction, the substrate for reentrant ventricular tachycardia, but can also be a nonspecific abnormality or even artifact. To determine whether fractionated sinus rhythm electrograms are associated with slow conduction in humans, the results of endocardial catheter mapping and pacing at 133 endocardial sites in 13 patients were analyzed. Eleven patients had sustained monomorphic ventricular tachycardia and two patients had old myocardial infarction without ventricular tachycardia. Functional evidence of slow conduction at the recording site was assessed by pacing at that site and measuring the interval between the stimulus artifact (S) and the onset of the QRS complex in the 12 lead electrocardiogram (ECG). During pacing at 89 of 90 sites without fractionated sinus rhythm electrograms, the S-QRS interval was less than 40 ms, a value consistent with rapid propagation of the stimulated wave front away from the pacing site. During pacing at 21 (49%) of 43 sites with fractionated sinus rhythm electrograms, the S-QRS interval was greater than 40 ms (range 40 to 140), consistent with slow conduction at the pacing site (p less than 0.001 versus nonfractionated sites). In 9 of the 11 patients with ventricular tachycardia analysis of the paced QRS configuration, electrograms during induced ventricular tachycardia or programmed stimulation during tachycardia suggested that a site with a long S-QRS interval during pacing was located at or near a ventricular tachycardia circuit. Therefore, fractionated sinus rhythm electrograms are often associated with slow conduction, which may be the substrate for reentrant ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperthyroxinemia with bradycardia and normal thyrotropin secretion after chronic amiodarone administration.

Pituitary-thyroid function was tested in 15 euthyroid patients before, during, and after long term oral treatment with amiodarone (2-n-butyl-3,4'-diethylaminoethoxy-3',5'-diiodobenzoylbenzofurane; 600-1200 mg daily), an iodine-containing potent antiarrhythmic drug. The drug caused increases in serum total T4, free T4, and rT3, with a concomitant decrease in T3. Baseline serum TSH was significantly higher after 1 week of drug treatment and returned to normal levels after 12 weeks of treatment. All patients receiving amiodarone had a slowing of their heart rate (P less than 0.01), and heart rate gradually increased 6 weeks after drug withdrawal, concurrent with the slow fall in T4 and rT3 levels. Amiodarone did not cross-react in the iodothyronine RIAs. The results suggest that amiodarone inhibits the peripheral conversion of T4 to T3 and may block the metabolic action of thyroid hormone in man.

Amiodarone kinetics after oral doses.

Amiodarone serum kinetics after single oral doses and after long-term therapy were investigated in patients with ventricular tachyarrhythmias. When amiodarone was given as a single oral dose (1400 to 1800 mg, n = 6), serum levels of amiodarone and its metabolite, measured by high-performance liquid chromatography, correlated (r = 0.69, P less than 0.01). Peak concentrations (amiodarone, 3 to 14 microgram/ml; metabolite, 0.7 microgram/ml) were attained in 4.9 +/- 1.2 hr. Using computer fits to the data, amiodarone mean elimination rate constant and half-life (t 1/2 e) were 0.128 +/- 0.063 hr-1 and 7.2 +/- 5.0 hr. In 12 patients given a mean dose of 1327 +/- 338 mg/day of amiodarone for 4.1 +/- 2.3 wk, mean serum amiodarone level was 3.84 +/- 2.92 microgram/ml (range 0.92 to 11.99); in three patients simultaneous determination of concentrations of amiodarone and its metabolite revealed that concentration of the latter was about 50% of that of the parent drug during long-term therapy. In four patients on maintenance therapy (400 to 800 mg/day, serum level 1.08 +/- 1.3 microgram/ml) drug was discontinued and serum amiodarone levels were determined serially. Serum drug disappearance followed a single exponential function with an elimination rate constant of 0.030 +/- 0.012 day-1 and t 1/2 e of 29 +/- 19 days. Our kinetic data are consistent with the long therapeutic amiodarone t 1/2 noted in the treatment of cardiac arrhythmias.

Effects of sotalol on ventricular tachycardia and fibrillation produced by programmed electrical stimulation: comparison with other antiarrhythmic agents.

Sotalol, a beta blocker, is now recognized as an important class III agent. The drug lengthens the action potential in most cardiac tissues without affecting conduction. Several studies have shown that sotalol is very effective in treating life-threatening arrhythmias. One hundred thirty-eight patients with inducible and clinically sustained tachycardia were retrospectively analyzed. With the use of the S1S2S3 stimulation protocol for ventricular tachycardia (VT) induction, sotalol prevented VT/ventricular fibrillation (VF) induction in 45% of the patients; other class I agents prevented VT/VF induction in only 15 to 22%. Data were also analyzed from a prospective multicenter study comparing sotalol with procainamide in suppressing sustained VT in 153 patients with symptomatic sustained VT/VF. With the use of the S1S2S3S4 stimulation protocol, sotalol prevented VT/VF induction in 35% of the patients, whereas procainamide prevented VT/VF induction in only 22% (difference not significant). When patients whose VT induced by the triple-stimuli protocol were excluded, sotalol prevented VT induction in 53%. These findings indicate that the antiarrhythmic effects of sotalol are comparable to those of class I agents in treating malignant arrhythmias. Although more data are needed on the comparative effects of sotalol, available data establish sotalol as an important addition to available antiarrhythmic agents.

Use of calcium antagonists for cardiac arrhythmias.

Calcium antagonists have emerged as a new class of antiarrhythmic agents for the control of certain supraventricular and ventricular arrhythmias. Electrophysiologically, these agents are heterogeneous but their main action is mediated through a depressant effect on the slow calcium channel in cardiac muscle, most readily demonstrated in isolated tissue preparations. In vivo, their actions are modulated by their reflex actions and by their interaction with the autonomic nervous system due to the noncompetitive adrenergic-blocking actions that some of the compounds exhibit. The major agents exerting antiarrhythmic actions are verapamil, diltiazem, gallopamil, tiapamil and bepridil; the dihydropyridines are devoid of electrophysiologic actions in vivo. Calcium antagonists prolong intranodal conduction time, lengthen the effective and functional refractory periods in the atrioventricular node but exert little or no effect on atrial, ventricular, His-Purkinje or bypass tract conduction or refractoriness (except in the case of bepridil, which has additional electrophysiologic properties). These effects form the basis of the clinical antiarrhythmic effects of this class of agents. The most striking action is the predictable and prompt termination of the reentrant supraventricular tachycardia by intravenous verapamil and diltiazem and the slowing of the ventricular response in atrial flutter and fibrillation. These agents may also be of value in the long-term control of ventricular response in atrial flutter and fibrillation; their role in multifocal atrial tachycardia and other ectopic tachycardias is less well defined. Calcium antagonists reverse ischemic ventricular arrhythmias caused by coronary artery spasm but exert little or no action in the usual forms of sustained ventricular tachyarrhythmias associated with severe structural heart disease. They are poor suppressants of ventricular premature complexes. Recent data have established their role in exercise-induced tachycardia occurring in the context of ischemic heart disease; they are also of value in ventricular tachycardia occurring in young patients who develop tachycardia with a right bundle branch block and left axis deviation morphology, an arrhythmia thought to be due to triggered automaticity.

Long-term antithrombotic treatment for atrial fibrillation.

Nonvalvular atrial fibrillation (AF) is the most common cardiac disorder causing stroke and systemic emboli. Recent clinical trials have clearly demonstrated the effects of antithrombotic treatment in preventing these devastating complications of AF. This review summarizes the salient findings of the first 5 published studies the Atrial Fibrillation, Aspirin, Anticoagulation Study (AFASAK) from Copenhagen, Denmark; the Boston Area Anticoagulation Trial for Atrial Fibrillation (BATAFF); the Canadian Atrial Fibrillation Anticoagulation study (CAFA); the Stroke Prevention in Non-rheumatic Atrial Fibrillation (SPINAF) study; and the Stroke Prevention in Atrial Fibrillation study (SPAF I) from the United States. These trials emphasize the unequivocal benefits of warfarin therapy compared with no treatment. SPAF II showed that aspirin is quite effective in younger patients (<75 years) who have no risk factors. The European Atrial Fibrillation Trial (EAFT) and SPAF III demonstrated that in older patients (>75 years) who had associated risk factors, warfarin therapy at the target international normalized ratio (INR) of 2-3, is the best treatment; however, a combination of low intensity fixed-dose warfarin and aspirin is ineffective. Thus, the guidelines recommended by the American College of Chest Physicians should be followed in treating patients with AF.

Second-generation calcium antagonists: search for greater selectivity and versatility.

Calcium antagonists have a variable specificity for cardiac and peripheral activity. Based on such activity, these compounds, new and old, can be classified into 4 categories. Type 1 agents, typified by verapamil, its congeners (tiapamil and gallopamil) and diltiazem, prolong atrioventricular nodal conduction and refractoriness with little effect on ventricular or atrial refractoriness. These actions, to a large extent, account for the antiarrhythmic properties of this type of calcium antagonists. Type 2 agents include nifedipine and other dihydropyridines. In vivo, these agents are devoid of electrophysiologic effects in usual doses and concentrations. They are potent peripheral vasodilators with some selectivity of action for different vascular beds; their overall hemodynamic effects are dominated by this peripheral vasodilatation and reflex augmentation of sympathetic reflexes. Type 3 agents are flunarizine and cinnarizine (piperazine derivatives); in vitro and vivo, they are potent dilators of peripheral vessels, with no corresponding calcium-blocking actions in the heart. Type 4 agents (perhexiline, lidoflazine and bepridil) have a broader pharmacologic profile; they block calcium fluxes in the heart, in the peripheral vessels or in both. They may inhibit the fast channel in the heart and have other electrophysiologic actions. A clear understanding of the varied pharmacologic properties of the different classes of calcium antagonists is likely to provide a rational basis for the use of the newer agents in clinical therapeutics.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium antagonists and beta blockers in the control of mild to moderate systemic hypertension, with particular reference to verapamil and propranolol.

The antianginal and antiarrhythmic role of calcium antagonists is well established. Recent preliminary studies have indicated that, like beta blockers, calcium antagonists may produce short- and long-term hypotensive effects in patients with mild to moderate essential hypertension. The pharmacologic properties of calcium antagonists provide a clear rationale for their use in the control of essential hypertension. The comparative hypotensive effects of verapamil (80 to 160 mg 3 times a day) and propranolol (40 to 120 mg 3 times a day) were evaluated over 4 weeks, preceded by a 4-week placebo phase, in a double-blind protocol in 17 patients with mild to moderate hypertension. Verapamil (n = 10) reduced the mean sitting systolic blood pressure by 10.7% (p less than 0.01) and standing by 7.6% (p less than 0.04). The corresponding data for propranolol (n = 7) were 4.8% (not significant) and 5% (p = 0.04). Verapamil reduced the sitting diastolic blood pressure by 10.8% (p less than 0.01), propranolol by 7.5% (p = 0.01); the standing diastolic blood pressure was reduced by 10.7% with verapamil (p less than 0.01) and by 8.6% (p = 0.01) with propranolol. With verapamil the mean heart rate fell from 77.60 +/- 8.42 to 70.20 +/- 4.85 beats/min (p = 0.03); with propranolol it fell from 76.85 +/- 6.91 to 66.29 +/- 4.54 beats/min (p less than 0.01). Although a trend towards a slightly greater hypotensive effect was apparent with verapamil compared with propranolol, the difference was not statistically significant. It is concluded that verapamil and propranolol exert comparable hypotensive potency in patients with mild to moderate hypertension.

Circadian variation in occurrence of transient overt and silent myocardial ischemia in chronic stable angina and comparison with Prinzmetal angina in men.

Circadian periodicity was examined in 68 patients with chronic stable angina and in 9 patients with Prinzmetal angina. The frequency and duration of transient ischemic episodes were determined from analysis of 1 or more 24-hour Holter recordings by the compact analog technique. Ninety percent of the episodes in both syndromes were silent; 80% of the episodes of Prinzmetal angina were associated with ST-segment elevation and all episodes of chronic stable angina had ST-segment depression. Ischemic episodes were shorter (3 +/- 2 vs 18 +/- 23 minutes, p less than 0.0005) but more frequent (21 +/- 18 vs 6 +/- 4 per 24 hours, p less than 0.0001) in patients with Prinzmetal angina than in those with chronic stable angina. In patients with chronic stable angina, both silent and painful episodes had a peak occurrence in the morning and early afternoon hours (between 8 AM and 3 PM); the fewest episodes were between 1 AM and 5 AM. This distribution was not random by chi-square test (p less than 0.001). Cosinor analysis of ischemic episodes periodicity showed the acrophase at 1 PM, which was not different from that (3 PM) of the circadian rhythmicity for heart rate. In case of Prinzmetal angina, the acrophase of heart rate changes was at 5 PM, but a clear periodicity in the distribution of the ischemic episodes was not found. These differences in the circadian periodicity may reflect differences in the mechanism of ischemia in chronic stable angina and in Prinzmetal angina and are likely to be of therapeutic significance.