Alan L. Saroff

Premature Atrial Stimulation as a Key to the Understanding of Sinoatrial Conduction in Man: Presentation of Data and Critical Review of the Literature

Since recording potentials directly from the sinoatrial node (SAN) is not yet possible, the electrophysiologic evaluation of this structure in intact human subjects must be accomplished with indirect technics. Two technics have been used to study SAN function in man: premature atrial stimulation (PAS) and rapid atrial pacing. Recent discussions of data using these technics have emphasized their role in determining SAN automaticity, but their role in evaluating conduction from atrium to SAN or SAN to atrium has not been fully explored. Using the technic of PAS, we have studied five patients with sinus bradycardia and symptoms of dizziness or syncope. Our analysis of the results obtained from these studies discloses the unique ability of this technic to evaluate conduction into and out of the SAN. An atrial premature depolarization (APD) elicited late in atrial diastole is followed by a compensatory pause (nonreset of the SAN pacemaker). An APD elicited earlier in atrial diastole is followed by a pause that is less than compensatory (SAN reset). From these responses estimates of sinoatrial conduction time were made. In one patient reset was never seen, suggesting markedly prolonged sinoatrial conduction. With these results in mind, the literature was reviewed and an alternate interpretation posed for existing data. PAS is not only a means of determining SAN automaticity, but also a very useful means of unmasking sinoatrial conduction abnormalities.

Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction.

Twenty patients of mean age 66.2 years, with suspected sinus node dysfunction, underwent extensive electrophysiologic study. Sinus bradycardia (18), sinus pauses (3), and sinoatrial block (1) were identified in their ECGs prior to study. Also 11 patients had some abnormality of atrioventricular nodal and/or intraventricular conduction prior to study. At the time of electrophysiological study, 10/20 patients (50%) had a mean cycle length exceeding 1000 msec, and mean P-V interval exceeded 210 msec in 7/20 (35%). The estimated “sinoatrial conduction time” exceeded 215 msec in 6/16 (38%) patients. The maximum first escape cycle following pacing at six different rates exceeded a value equal to 1.3 X the mean value of the control cycle length + 101 msec (slope of regression line + Y intercept + I SDd in 13/19 (68%) patients. Nineteen patients received I mg atropine intravenously and mean cycle length decreased by 19%, from 891 ± 175.8 msec to 718 ± 182.9 msec. Graded infusion of isoproterenol was employed in 19 patients; four patients required an infusion rate greater than 28.3 ng/kg/min to produce a 20% decrease in spontaneous sinus cycle length. These data would indicate that a variety of interventions are required to characterize the disturbance of sinus node automaticity and sinoatrial conduction in patients with sinus node dysfunction.

The antiarrhythmic effect of nortriptyline in cardiac patients with ventricular premature depolarizations

The effect of nortriptyline against ventricular arrhythmias was determined in 16 cardiac patients with 30 or more ventricular premature depolarizations per hour. Nortriptyline was administered orally, 0.5 mg/kg body weight per day, and increased by 0.5 mg/kg per day every third day until ventricular premature depolarizations were suppressed (greater than or equal to 80%), adverse effects occurred or a total daily dose of 3.5 mg/kg per day was given. Each patient had daily 24 hour continuous electrocardiograms, 12 lead standard electrocardiograms and physical examination; blood pressure was measured in the supine and standing position four times a day. Each patient also had radionuclide angiography at rest to measure ejection fraction before and at the effective or maximal dose. Thirteen patients (81%) had an antiarrhythmic response and 11 met the study criterion of at least 80% improvement. Doses ranged from 50 to 200 mg/day (mean 111 +/- 45), steady state plasma concentration ranged from 46 to 410 ng/ml (mean 153 +/- 96) and half-life of elimination of nortriptyline was 4 to 22 hours (mean 13 +/- 4). Administration of nortriptyline did not depress mean ejection fraction (before 42 +/- 12%, after 41 +/- 12%); it was associated with an orthostatic decrease in systolic blood pressure (mean -13 +/- 13 mm Hg). Nortriptyline is an effective antiarrhythmic agent which may be given twice a day even in patients with impaired ventricular function.

Physical activity participation among Caribbean Hispanic women living in New York: relation to education, income, and age.

BACKGROUND Inadequate participation in physical activity is a serious public health issue in the United States, with significant disparities among population groups. In particular, there is a scarcity of information about physical activity among Caribbean Hispanics, a group on the rise. METHODS Our goal was to accumulate data on physical activity among Caribbean Hispanic women living in New York and determine the relation between physical activity and age, marital status, education, income, primary language, and children in the household. To this end, a survey adapted from the National Health Interview Survey of the National Center for Health Statistics assessing type, frequency, and duration of physical activity was administered. RESULTS There were 318 self-identified Hispanic women who participated. Total activity time, mean 385 +/- 26 minutes, and education (r = 0.14, p < 0.01) were significantly related. Women who had attended some college had greater total activity time than those with some high school education (p = 0.046) or < 8th grade education (p = 0.022). Walking as a form of transportation was the most frequent pursuit, 285 +/- 21 minutes. Age (r = -0.34, p < 0.001) and education (r = 0.25, p < 0.001) correlated with nonwalking activity time (leisure time). Nonwalking activity times were greater in younger, that is, 18-29 years (p < 0.001) and college-educated women (p < 0.001). Physical activity recommendations were met by 11%; and 17% reported no physical activity. CONCLUSIONS Among Caribbean Hispanic women living in New York City, the current recommendations for physical activity are met by 11%, and physical activity and education are significantly related. Our observation that education is a critical factor related to physical activity suggests that programs to address the promotion of a physically active lifestyle are needed.

Desmethylimipramine and imipramine on left ventricular function and the ECG: a randomized crossover design

Sixteen severely depressed patients participated in a double-blind randomized, crossover study to compare the effects of desmethylimipramine and imipramine on left ventricular function and the electrocardiogram. Following a drug-free week, patients had 3 weeks of therapy each with desmethylimipramine and imipramine. During each treatment period systolic time intervals, echocardiograms and high-fidelity electrocardiograms were recorded. There was no difference between desmethylimipramine and imipramine on (1) systolic time intervals, (2) shortening fraction or mean velocity of circumferential shortening, or (3) the electrocardiogram. There was a difference between the drug-free period and desmethylimipramine or imipramine on the PEPc (P less than 0.05) and the PEP/LVET ratio (P less than 0.05); on the R-R (P less than 0.05), PR (P less than 0.05), QRS (P less than 0.05), and QTc (P less than 0.05) intervals; but no difference on the LVETc or shortening fraction or the mean velocity of circumferential shortening. Drugs such as desmethylimipramine and imipramine which prolong intraventricular conduction can probably be expected to prolong the PEP and PEP/LVET. For this reason systolic time intervals have limitations in assessing myocardial function and the echocardiogram more reliably estimates myocardial performance in patients receiving tricyclic antidepressants.

Cardiovascular effects of doxepin in cardiac patients with ventricular arrhythmias

The effect of doxepin on ventricular arrhythmias, the ECG, and left ventricular function was evaluated in 10 cardiac patients with symptoms with frequent ventricular premature depolarizations in a dose‐ranging protocol. Four patients (40%) had ≥80% ventricular premature depolarization suppression; four of eight with pairs and four of six with ventricular tachycardia had ≥90% suppression. The mean maximal doxepin dose was 115 ± 41 mg/day; mean nadir total doxepin concentration was 61 ± 48 ng/ml and mean nadir total desmethyldoxepin concentration was 51 ± 42 ng/ml. Doxepin increased the heart rate and the PR, QRS, and QTc intervals of the surface ECG (P not significant). There was no significant change in resting mean left ventricular ejection fraction with doxepin: 41% ± 15% vs. 43% ± 19% (P not significant). Complaints of sedation (eight patients) limited dose ranging and tolerance to the drug. Although doxepin suppressed ventricular premature depolarizations in four patients, marked sedation limits its usefulness for primary treatment of arrhythmias in this population.

Effect of indecainide in patients with left ventricular dysfunction

Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had ≥30 ventricular premature complexes/hour, moderate‐to‐marked left ventricular dysfunction, and mean ejection fraction 34% ± 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until ≥80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed ≥80% in nine patients (p < 0.05) and ventricular tachycardia episodes were completely suppressed in five of eight patients. The effective or maximal mean daily indecainide dose was 191 ± 32 mg; half of the responders achieved efficacy at serum drug concentration ≥600 ng/ml. Serum drug concentration was directly related to gender (r = 0.78, p < 0.04) and inversely related to creatinine clearance (r = 0.74, p < 0.05) and ejection fraction (r = 0.71, p < 0.02). Indecainide prolonged mean PR and QRS intervals (p < 0.05) but not QT or QTc. There was a linear relation between percent change in PR (r =0.80, p <0.001) and QRS (r = 0.66, p <0.001) intervals and serum drug concentration. After starting or increasing the dose, careful observation of patients with decreased renal function or reduced ejection fraction should be exercised because they attain higher drug concentration than normal subjects.

Indecainide compared with quinidine for chronic stable ventricular arrhythmias secondary to coronary artery disease or to cardiomyopathy

Indecainide, a new type Ic antiarrhythmic agent, and quinidine sulfate were compared in a randomized double-blind parallel study. Cardiac patients with greater than or equal to 30 ventricular premature complexes per hour hour received indecainide, 50 mg, or quinidine, 200 mg every 6 hours, and the doses were increased until more than 80% suppression was noted, adverse effects occurred or a maximal dose of 100 mg of indecainide or 400 mg of quinidine given every 6 hours. Efficacy was achieved in 8 of 10 taking indecainide (p less than 0.05) and 7 of 9 taking quinidine (p less than 0.05). At least 90% of episodes of ventricular tachycardia were suppressed in 4 of 7 patients taking indecainide and 1 of 4 taking quinidine. No adverse effects were observed in the 7 patients who responded to indecainide and the 4 who responded quinidine, resulting in short-term efficacy without adverse effects in 7 patients (70%) taking indecainide and 4 (44%) taking quinidine. The effective or maximal mean daily indecainide and quinidine doses were 190 +/- 32 mg and 1,022 +/- 291 mg, respectively; mean trough indecainide and quinidine concentrations were 617 +/- 247 ng/ml and 3.3 +/- 1.4 micrograms/ml, respectively. Indecainide prolonged mean PR and QRS intervals (p less than 0.05), but not QT and QTc intervals. Quinidine did not change PR or QRS intervals but prolonged QTc interval (p less than 0.05). During dosing, 1 patient discontinued indecainide treatment because of nausea; 3 discontinued quinidine because of gastrointestinal complaints.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiarrhythmic Effect of Lorcainide in Patients Taking Digoxin

To assess the antiarrhythmic effect of lorcainide and determine whether there is a pharmacokinetic interaction between lorcainide and digoxin, 12 patients with frequent premature ventricular depolarizations (PVDs) who were taking digoxin were treated with lorcainide. During a placebo period, serum digoxin concentration was measured for three days; plasma lorcainide concentration, a 12‐lead electrocardiogram (ECG), and a 24‐hour continuous ECG were measured on the day before the patients began lorcainide and repeated on days 3, 7, and 14 of treatment Lorcainide was given 100 mg bid or 100 mg tid. Lorcainide did not suppress group mean PVDs per hour, pairs, or ventricular tachycardia. Only four patients (33%) responded with ≥ 80% suppression of PVDs. Mean ejection fraction for responders was 46 ± 6%, and for nonresponders it was 28 ± 9% (P < .01). There was no significant pharmacokinetic interaction between lorcainide and digoxin. Mean digoxin concentration did not change after lorcainide administration; two patients had ≥ 50% increase in serum digoxin concentration. Patients with heart failure or reduced ejection fraction define a subset who have unpredictable effects from lorcainide, including a reduced antiarrhythmic effect.