Concurrent use of quinidine and disopyramide: evaluation of serum concentrations and electrocardiographic effects

The effects of concurrent disopyramide phosphate and quinidine sulfate therapy were studied in 16 normal healthy adults. No adverse effects serious enough to warrant discontinuation of therapy were observed. There was a small but significant increase in disopyramide serum concentration when concurrent quinidine therapy was given and a small decrease in quinidine serum concentration when disopyramide was added. No significant change in elimination half-life was seen for either drug. Both drugs produced prolongation of the corrected QT interval. This QT prolongation was greater for quinidine than for disopyramide.     

Echocardiographic detection of right ventricular hypertrophy

M-mode echocardiographic right ventricular wall thickness (RVW) and diastolic right ventricular internal diameter (RVID), when above the accepted normal range (RVW less than or equal to 5 mm, RVID less than or equal to 26 mm), are frequently used clinically to predict the presence of right ventricular hypertrophy. RVID was compared to anatomic right ventricular mass (RVM) in 27 patients and to RVW in 13 patients to determine their accuracy for predicting right ventricular hypertrophy (RVM greater than 65 gm). When increased, both measurements were specific for right ventricular hypertrophy. The specificity for RVW above 5 mm was 100% and for RVID greater than 26 mm was 79%. Neither was a sensitive indicator of hypertrophy. Only 36% of those with anatomic right ventricular hypertrophy had an echocardiographically dilated ventricle, and 67% had a thickened free wall. Neither measurement proved to be an accurate predictor of RVM, with a correlation for RVW of 0.56 and for diastolic RVID of 0.19.     

Effect of propafenone in patients with stable ventricular arrhythmias

Thirty patients with clinically significant ventricular ectopy were treated with propafenone, a new potent antiarrhythmic agent with membrane stabilizing action. Patients had a minimum mean of greater than 30 ventricular premature beats per hour documented by continuous 48-hour ambulatory ECG recording. Twenty-five patients qualified as responders, defined as greater than 85% reduction of ventricular ectopy compared to baseline, and completed a double-blind placebo-crossover phase. Significant reduction in single ventricular ectopy per hour, paired ventricular ectopy per hour, and ventricular tachycardia beats per hour were observed. Almost total abolition of ventricular tachycardia and paired ventricular ectopy was achieved. Side effects were minimal and well tolerated. A significant prolongation of the PR interval occurred. QRS prolongation and prolongation of the corrected QT interval was observed in some patients, with new left bundle branch block developing in two patients. Long-term efficacy and safety studies will be necessary to determine the ultimate role of this new agent in the selection of antiarrhythmic therapy, but these inital results are encouraging.     

Digoxin uptake into peripheral autonomic cardiac nerves: Possible mechanism of digitalis-induced antiarrhythmic and toxic electrophysiologic actions

It is generally accepted that certain cardiac rhythm disturbances are due to imbalances between the sympathetic and parasympathetic nervous systems. We have provided evidence that digoxin is concentrated in the peripheral nervous system of the heart as well as in the central nervous system. Previous findings have indicated that cardiac glycosides may directly or indirectly affect autonomic neurotransmitters. Therefore the uptake of digoxin into the peripheral cardiac nervous system may play an important role in both the antiarrhythmic and toxic electrophysiologic actions of digoxin.     

Comparison of the size of the arterial vascular bed to the right ventricular mass in patients with chronic obstructive pulmonary disease.

Hearts from patients dying with severe chronic obstructive pulmonary disease were examined for right ventricular mass and coronary arterial vascular bed size. Normal hearts obtained from patients dying of other causes were also examined for comparison. The relationship between the size of the vascular bed and ventricular mass was examined and a definite but low correlation was found. Severe obstructive coronary artery disease was excluded, and chronic hypoxemia did not alter the results. The arterial vascular bed supplying the right ventricle of male patients with severe chronic obstructive pulmonary disease appears to undergo a compensatory increase in size as the ventricular mass enlarges, but this is highly variable and incomplete.     

Histamine provocation of clinical coronary artery spasm: Implications concerning pathogenesis of variant angina pectoris

Twelve patients with nonexertional chest pain and nonobstructive fixed coronary disease (< 50% luminal diameter narrowing) were given histamine to investigate the potential role (coronary artery H₁ receptor agonism) of the endogenous agent in producing coronary artery spasm (CAS). Histamine, at intravenous dose of 0.5 to 1.0 μg/kg/min, provoked CAS in four patients. In six patients neither histamine nor ergonovine provoked spasm, and these patients were considered by chronic follow-up evaluation to have noncardiac etiology for their chest pain syndrome. In one patient CAS was provoked with ergonovine but not by histamine, and one ergonovine-positive patient had an equivocally positive histamine result. Pretreatment with cimetidine (H₂ receptor antagonism) was necessary to avoid unpleasant side effects of histamine. Thus these observations indicate that histamine should be included among the specific agents capable of inducing CAS and provide new insight concerning the mechanism(s) causing variant angina pectoris.     

Application and safety of outpatient ergonovine testing in accurately detecting coronary spasm in patients with possible variant angina

We analyzed the results of 61 consecutive outpatient ergonovine provocation tests to determine the safety and efficacy of such outpatient testing for detecting coronary artery spasm (CAS). Criteria for outpatient testing included: clinical history suggestive of variant angina, noncritical coronary artery disease documented by coronary arteriography, normal exercise treadmill test, no symptomatic arrhythmias, and no history of recent myocardial infarction. All antianginal medications were tapered and stopped. Ergonovine maleate was given as a bolus at 3-minute intervals in consecutive doses of 0.05, 0.10, and 0.25 mg. A positive test was defined as chest pain accompanied by > 0.1 mV ST segment elevation on 12-lead ECG. If pain and ST-segment elevation occurred, intravenous and sublingual nitroglycerin were immediately administered for rellef of myocardial ischemia. Of the 61 patients studied, 10 had positive tests; there were no complications. Follow-up of the 51 patients with negative studies has not revealed cardiac etiology for their chest pain. We conclude that outpatient ergonovine testing is a safe and accurate diagnostic test for identifying CAS in a highly selected population of patients with possible variant angina when performed under carefully controlled conditions.     

Latent defects of atrioventricular conduction in right coronary artery disease

The purpose of this study was to investigate the occurrence of latent defects in AV conduction in patients with right coronary artery disease. Twenty-two patients with greater than 50 per cent obstruction of the right coronary artery and a predominant right coronary artery system or pattern were studied with His bundle electrograms and determinations were made of the functional refractory period of the AV node and the point at which AV Wenckebach developed during rapid atrial pacing with a fixed cycle length. The patients were studied prior to or at least six months after the onset of clinical or electrocardiographic evidence of acute infarction. Similar measurements were made in eighteen control subjects with less than 50 per cent occlusion of the right coronary artery. The results showed significant prolongation of the functional refractory period (467 ± 63 msec. for patients with right coronary disease versus 408 ± 43 msec. in the control group; P <0.01) and earlier development of atrioventricular Wenckebach during rapid atrial pacing (143 ± 22 BPM in the coronary obstruction group versus 172 ± 19 BPM in the control group; P<0.01) in patients with significant disease of the right coronary artery when compared to the control group. Although all patients were found to have resting intervals on the His bundle electrogram within normal limits, the group with right coronary obstruction had slightly longer values for the resting P-H interval (122 ± 19 msec. versus 101 ± 31 msec. in the control group; P<0.05). This study establishes that latent defects in atrioventricular conduction exist in patients with significant disease of the right coronary artery in the absence of acute infarction.     

The correlation of metabolic and ultrastructural changes in emetine myocardial toxicity

Emetine exerts a specific effect on mitochondrial function and structure. Its action is to inhibit oxidative phosphorylation as measured by mitochondrial oxygen consumption, ADP:O ratio, and the respiratory control ratio. Our observations corelate documented specific structural abnormality with a metabolic change. These results probably account for some of the cardiotoxicity known to result from administration of emetine.     

The long-term suppression of ventricular arrhythmia by oral acebutolol in patients with coronary artery disease

The short-term efficacy of oral acebutolol was evaluated in 20 patients with coronary artery disease and frequent premature ventricular contractions (PVCs) by serial 24-hour Holter monitoring before and while the patients were receiving an average daily dose of 1,100 mg. of acebutolol for four weeks. Fifty-five percent of the 20 patients showed a greater than 70% PVC reduction from baseline values. The only serious side effect during short-term therapy was mild, reversible cardiac decompensation in one patient. The long-term safety and continued efficacy of acebutolol was then evaluated over the next 11 months in nine of the 11 patients showing greater than 70% PVC reduction at four weeks. Two-thirds of these nine patients continued to show greater than 80% PVC reduction from baseline values at 12 months. One patient developed alopecia during long-term therapy. The majority of patients not responding well to acebutolol at four weeks had an actual increase in PVCs on acebutolol therapy. We conclude that acebutolol produces long-term, effective reduction in PVCs without serious toxicity in the majority of patients with ventricular ectopy. However, this drug appears to either produce an excellent response or no response with regard to PVC control in most instances.     

Three-vessel coronary artery spasm in a patient with variant angina and normal coronary arteries

Variant angina with two or more electrocardiographic or angiographic localizations has seldom been reported [1-4]. We present a case of variant angina pectoris and normal coronary arteries with three different and independent electrocardiographic localizations.     

The reliability of coronary angiogram interpretation: an angiographic-pathologic correlation with a comparison of radiographic views.

This prospective study correlates premortem coronary angiographic interpretation with pathologic findings including the use of postmortem coronary angiograms. The reliability of a single radiographic view, left anterior oblique or right anterior oblique, or combined views (left anterior oblique plus right anterior oblique) was examined. The most reliable interpretation, the combined view, has a specificity of 93 per cent, but sensitivity is less at 61 per cent. Using a single view enhances diagnosis (sensitivity), but it leads to overestimation more frequently (decreased specificity). Proximal segments of the coronary arteries are prone to a significant per cent of false positive readings. The most accurate assessment of the anterior descending coronary artery system occurs with the use of the right anterior oblique with multiple views. Less routine use of the left anterior oblique view with increased use of the hemiaxial view is suggested for the angiography of the left coronary artery. Initial cusp injections of the right coronary artery may avoid a high per cent of false positive readings in the proximal segment.     

Randomized double-blind comparison of nifedipine and isosorbide dinitrate therapy in variant angina pectoris due to coronary artery spasm

Twelve patients were entered prospectively into a randomized double-blind study comparing the efficacy of nifedipine and isosorbide dinitrate (ISDN) in the treatment of variant angina pectoris due to coronary artery spasm. Using the diary technique, both anginal episodes and nitroglycerin tablets consumed were recorded during the pretrial, no drug period, and both active drug phases. During the baseline pretrial period, an average of 1.1 anginal episodes/day occurred with reduction to 0.28/day during nifedipine treatment and 0.39/day during ISDN treatment. Headache was the major side effect during ISDN treatment, occurring in 9 of 11 (81%) patients; and nonheart failure related pedal edema during nifedipine treatment, occurring in 4 of 12 (33%) patients. Intolerable side effects necessitating cessation of treatment occurred in two patients during nifedipine treatment and in three patients during ISDN treatment. Patients preferred nifedipine over ISDN because of increased efficacy and fewer uncomfortable side effects. We conclude that both nifedipine and ISDN are effective therapy for coronary spasm, but that nifedipine was more effective and was preferred by the majority of patients.     

Atrioventricular conduction patterns in patients with paroxysmal supraventricular tachycardia.

Atrioventricular conduction patterns suggestive of dual A-V nodal pathways have been reported in patients with and without a history of paroxysmal A-V nodal re-entrant tachycardia (PSVT). The purpose of this study was to determine whether significant association exists between this conduction pattern and the occurrence of PSVT in man. The pattern of A-V conduction was evaluated at similar pacing rates in 13 patients with documented PSVT and 135 patients with PSVT. Patients without PSVT were divided into groups with normal PR intervals (106 patients), PR intervals of 120 msec. or less (12 patients), and PR intervals of 200 msec. or greater (17 patients). Evidence of dual A-V nodal pathways was found in seven of 13 patients with PSVT and nine of 135 patients without PSVT, including eight of 106 patients with normal PR intervals, none of 12 patients with short PR intervals, and one of 17 patients with PR intervals of 200 msec. or greater. The incidence of dual A-V nodal pathways was significantly greater (P less than 0.01) in patients with PSVT when compared with all other groups. In two of four patients with PSVT, propranolol was found to unmask evidence of dual pathways; no evidence of dual pathways was produced by propranolol in 23 patients without PSVT. The data show that the pattern of dual A-V nodal pathways is common only in patients with PSVT and is significantly less frequent in patients without PSVT regardless of the presence of short or long PR intervals. The results of this study establish a strong association between this conduction pattern and the occurrence of PSVT in man.     

Myocardial infarction in patients with coronary artery spasm demonstrated by angiography

Twelve cases of myocardial infarction (MI) were documented in 11 of 39 patients who had coronary artery spasm (CAS) that was observed by angiography either before MI (3 patients), after MI (5 patients), or both before and after MI (3 patients). MI corresponded in location to sites of ECG changes of myocardial ischemia during spontaneous angina pectoris in 7 of 7 patients and to the region of myocardium supplied by the vessel in which CAS was observed by angiography in each patient. MI occurred in the distribution of the right coronary artery in 8 patients and of the left coronary artery in 4 patients. Of 12 vessels that supplled infarcted regions of myocardium, 7 vessels had ≥50% diameter fixed coronary artery narrowing (CAN), but the remaining 5 vessels had minimal (10%) or no fixed CAN. In those patients who were studied after MI, coronary angiography demonstrated that only 3 of 9 vessels in the distribution of infarcted regions of myocardium were completely occluded. Clinical follow-up for an average of 1.3 years after MI showed that 7 patients continued to have chest pain, 2 patients were asymptomatic, and 2 patients died suddenly 9 weeks and 1 year, respectively, after MI. Therefore, among our patients with CAS demonstrated by angiography, Mis (1) were frequent (28%), (2) occurred in the distribution of observed coronary spasm, (3) were frequently (5 of 12 arteries) in the distribution of vessels having minimal or no fixed narrowing, and (4) were often (6 of 9 arteries) in the distribution of vessels that were demonstrated to be patent after MI.