Allan M. Greenspan

Use of amiodarone in the treatment of persistent and paroxysmal atrial fibrillation resistant to quinidine therapy

The efficacy of amiodarone was assessed in 38 patients with atrial fibrillation resistant to quinidine and an effort made to identify factors correlated with amiodarone response. The study group included 29 patients with and 9 without organic heart disease and either persistent (n = 11) or paroxysmal (n = 27) atrial fibrillation. All patients were treated with amiodarone and followed up in a research clinic. Efficacy was classified as excellent (no recurrent symptomatic atrial fibrillation) in 15 (55%) of 27 patients with paroxysmal and 5 (45%) of 11 patients with persistent atrial fibrillation. Efficacy was poor (no effect on atrial fibrillation) in 5 (19%) of 27 patients with paroxysmal and 6 (55%) of 11 patients with persistent atrial fibrillation. Efficacy was good (amelioration but not total suppression) in 7 (26%) of 27 patients with paroxysmal atrial fibrillation. Efficacy was related to echocardiographic left atrial dimension, left ventricular ejection fraction and, in patients with persistent atrial fibrillation, the duration of the arrhythmia. During the follow-up period of 15 months (range 1 to 36), overall efficacy (considering response and toxicity) was 67% in the 27 patients with paroxysmal and 45% in the 11 patients with persistent atrial fibrillation. It is concluded that amiodarone offers an additional therapeutic alternative in quinidine-resistant atrial fibrillation and that certain clinical factors are correlated with amiodarone response.

Electrophysiologic testing in patients at high risk for sudden cardiac death. I. nonsustained ventricular tachycardia and abnormal ventricular function

Nonsustained ventricular tachycardia, although usually asymptomatic, is associated with a high risk of sudden cardiac death in patients with depressed left ventricular function. To test the vulnerability of such patients to symptomatic and potentially life-threatening arrhythmias, complete electrophysiologic studies were performed in 58 patients with clinically documented nonsustained ventricular tachycardia (greater than or equal to three complexes but less than 15 seconds of self-terminating ventricular tachycardia by 24 hour ambulatory electrocardiographic [Holter] or telemetric monitoring) and abnormal left ventricular function (ejection fraction less than 50% by radionuclide angiography). All patients had nonsustained ventricular tachycardia in the absence of antiarrhythmic drugs, acute ischemia, long QT syndrome, recent infarction or electrolyte abnormalities. The stimulation protocol for each patient included the introduction of single, double and triple ventricular extrastimuli at three cycle lengths (sinus, 600 and 450 ms) and two right ventricular sites (apex and outflow tract). A sustained ventricular tachyarrhythmia was induced in 23 patients (40%) and a nonsustained ventricular tachycardia in 14 patients (24%). Induction of sustained tachycardia correlated with the presence of akinesia or aneurysm, or both, by radionuclide angiography, but not with ejection fraction or presence or absence of coronary artery disease. These results indicate that: 1) patients with clinical nonsustained ventricular tachycardia and chronic left ventricular dysfunction have a high incidence of inducible sustained ventricular tachycardia or ventricular fibrillation; and 2) electrophysiologic testing may allow further substratification of risk of sudden cardiac death in high risk patients with nonsustained ventricular tachycardia.

Correlation between changes in R wave amplitude and left ventricular volume induced by rapid atrial pacing

To examine the Brody effect in humans, we studied 15 patients by means of coronary sinus pacing. We measured left ventricular (LV) volumes from the cardiac output (measured by the thermodilution technique) and LV ejection fraction (measured by radionuclide ventriculography). Pulmonary blood volume was determined by means of cardiac output and mean pulmonary transit time. In six patients, pacing was performed at two different rates, resulting in 21 pacing measurements. The heart rate increased with pacing from 73 +/- 11 to 119 +/- 19 bpm (mean +/- standard deviation, p less than 0.001). The end-diastolic volume (EDV) and the end-systolic volume (ESV) decreased with pacing (p less than 0.001 each). The R wave amplitude decreased with pacing (1.44 +/- 0.63 mV control vs 1.32 +/- 0.58 mV with pacing; p less than 0.01). R wave amplitude decreased in 19 of the 21 pacing studies (90%); EDV and ESV decreased in all 21 pacing studies, and pulmonary blood volume decreased in 14 of the 15 pacing studies (93%) performed in 11 patients. There was a significant correlation between the percentage of change in R wave amplitude with the percentage of change in EDV (r = 0.54, p less than 0.01) and with the percentage of change in ESV (r = 0.54, p less than 0.01). These results, therefore, validate Brodys hypothesis and indicate that changes in LV volumes affect the R wave amplitude.

Electrophysiology of esmolol

The electrophysiologic characteristics of esmolol were studied in 14 patients. Ten men and 4 women, mean age 57 years, were electrophysiologically evaluated at baseline, and also at 4 to 8 minutes after the administration of a maintenance infusion of esmolol. Plasma samples for esmolol blood levels were drawn at 10 minutes of the maintenance infusion, at the end of the maintenance infusion and 30 minutes after the maintenance infusion was discontinued. Results of this study showed that esmolol has typical beta-blocker electrophysiologic effects. Its major action was on sinus node function; it prolonged this basic sinus cycle length but had no significant effect on intrinsic automaticity as reflected by the corrected sinus node recovery time and sinoatrial conduction. Direct effects on atrioventricular (AV) nodal function were reflected by effects on AV nodal conduction and refractoriness. There was no direct effect on atrial function and, as expected, no effect on His-Purkinje or ventricular function. The intensity of esmolols electrophysiologic effects on sinus node function, AV nodal conduction and AH interval is comparable to those of other beta blockers.

Development of Congestive Heart Failure and Alterations in left Ventricular Function in Patients with Sustained Ventricular Tachyarrhythmias Treated with Amiodarone

The interaction between the efficacy and tolerance of amiodarone and the degree of left ventricular (LV) dysfunction was assessed in 126 patients with sustained ventricular tachyarrhythmias. In all patients radionuclide angiographic LV ejection fraction (EF) was measured before and after 8 to 12 months of amiodarone therapy. At baseline mean EF was 25 +/- 13% and 86 patients had an EF of 30% or less. In patients receiving amiodarone at steady state, there was a small but significant increase in EF (23 to 26%, p less than 0.05). Congestive heart failure (CHF) was present in 43 patients before amiodarone therapy. In 16 patients new (9 patients) or worsened (7 patients) CHF developed during the first year of amiodarone therapy. Development of CHF was not consistently related to a change in EF or heart rate. The clinical efficacy and tolerance of amiodarone were affected by the baseline EF and development of CHF. Efficacy and tolerance was 80% in patients with an EF of more than 30% and 60% in those with an EF of 30% or less. Among the 16 patients in whom new or worsened CHF developed, 6 (38%) died and 9 (56%) had recurrent ventricular tachyarrhythmias. Both baseline EF and development of CHF during amiodarone treatment significantly affect the prognosis in patients with ventricular tachyarrhythmias.

Combination Antiarrhythmic Drug Therapy For Ventricular Tachyarrhythmias

New antiarrhythmic drug regimens are constantly being sought because of the relatively low efficacy rates of standard antiarrhythmic agents in preventing induction of ventricular tachyarrhylhmias; the application of these agents is also limited due to serious or debilitating side‐effects. The combination of two antiarrhythmic agents with complimentary electrophysiologic activities and differing toxicities might offer significant advantages in overcoming the drawbacks of standard antiarrhythmic drug therapy. A knowledge of the pharmacodynamics of the major classes of antiarrhythmic agents will allow informed choices of drugs for use in combination therapy. Judging antiarrhythmic drug efficacy is a complex problem, requiring an understanding of (he influence of the arrhythmia monitoring technique. arrhythmia morphology and the response to previous drugs on drug efficacy rates, so that accurate comparisons of drug effectiveness can be made among different agents or combinations. A number of combination therapies have been tested for suppression of complex ventricular ectopy, nonsustained ventricular tachycardia and sustained ventricular tachycardia and ventricular fibrillation. The most successful combinations have been those using class IA and IB agents and class IA and II agents. In general, these combinations tend to show higher efficacy rates in suppressing all forms of ventricular ectopy and ventricular tachyarrhythmias, and usually have a lower incidence of toxic side‐effects compared with individual agents alone. On the basis of these initial results, it seems warranted to perform further studies to explore these combinations in larger populations and to test new combinations developed on the basis of pharmacodynamic principles.

The clinical electrophysiology of intravenous indecainide.

The electrophysiologic effects of indecainide, a new class IC antiarrhythmic agent, were assessed in 10 patients with left ventricular dysfunction and inducible sustained ventricular tachycardia. Indecainide was administered intravenously in a dose of 60 to 90 mg/kg at a rate of 12.5 to 15 micrograms/kg/min. Indecainide had no effect on sinus node function or atrial and ventricular effective refractory periods. The AH (106 +/- 13 vs 130 +/- 24 msec, p less than 0.002) and HV (57 +/- 7 vs 73 +/- 19 msec, p less than 0.001) intervals were significantly increased. The QRS duration increased (102 +/- 9 vs 120 +/- 13 msec, p less than 0.001); however, the JT duration did not change. Induction of ventricular tachycardia was prevented in 1 of 10 patients. In the remaining nine patients, the ventricular tachycardia cycle length was significantly prolonged (248 +/- 47 vs 320 +/- 71 msec, p less than 0.001). Indecainide significantly depressed intracardiac conduction at several sites.

A Comparative Study of the Electrophysiologic Effects of Striadyne, Adenosine Triphosphate and Adenosine in the Canine Heart

The chronotropic and dromotropic effects of the intra-atrial administration of 0.97, 1.93 and 2.90 microM/kg Striadyne, the pharmaceutical form of adenosine triphosphate (ATP) for clinical use, ATP, and adenosine, were compared in 13 anesthetized dogs. Striadyne, ATP and adenosine exerted transient dose-dependent negative chronotropic and dromotropic effects. There was no significant difference between the electrophysiologic effects of Striadyne and ATP which were significantly more pronounced than those of adenosine. Atropine (0.2 mg/kg) significantly attenuated the electrophysiologic effects of 2.90 microM/kg Stridyne and ATP but not those of adenosine. It is concluded that Striadyne and ATP have similar electrophysiologic effects which are more pronounced than those of adenosine mainly due to vagal involvement in their mechanism of action.

Determinants of hospital cost and length of stay for patients undergoing electrophysiologic testing

To assess the effects of various clinical factors in determining the cost and length of stay in patients undergoing electrophysiologic testing for cardiac arrhythmias, the hospital cost and length of stay data were reviewed in 222 consecutive inpatients who underwent electrophysiologic testing from January 1 to December 31, 1984. Admissions were classified as: primarily for treatment of arrhythmias (171 patients); primarily for treatment of arrhythmias but with serious concurrent illnesses that prolonged hospitalization (43 patients); or primarily for nonarrhythmic problems with electrophysiologic study an incidental part of hospitalization (8 patients). Based on allowable length of stay for the applicable DRGs, actual hospitalizations exceeded Medicare allowable length of stay by 50 to 500%. Retrospective review of hospital charts indicated that 3 clinical factors serve as effective markers in determining length of stay: need for amiodarone, induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), and presence of serious other medical problems that require stabilization before electrophysiologic testing. Our data indicate that 3 classes of patients can be identified: I. DRG A (45%)--those who did not have sustained VT or VF induced, did not require amiodarone and had no serious concurrent illnesses. The mean length of stay was 7.1 days. II. DRG B patients (21%)--those who had sustained VT or VF induced, but did not require amiodarone and had no serious concurrent illnesses. The mean length of stay was 13.7 days. III. DRG C patients (34%)--those who either had a serious concurrent illness or required amiodarone. The mean length of stay was 19.7 days. This classification schema might allow a more appropriate system for determining reimbursement.