H. Leon Greene

Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.

BACKGROUND AND METHODS In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo. RESULTS Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty. CONCLUSIONS There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

ACC/AHA guidelines for ambulatory electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography): Developed in collaboration with the North American Society for Pacing and Electrophysiology

A meter drive circuit includes a signal input circuit through which an input signal is applied to a peak hold circuit for producing an output signal which indicates an instantaneous peak value of the input signal and which is held for a predetermined time, a sample and hold circuit for sampling the level of the output signal of the peak hold circuit, and holding the sampled level, and a signal level indicator connected to the sample and hold circuit to provide an indication of the sampled level.

A prospective randomized evaluation of biphasic versus monophasic waveform pulses on defibrillation efficacy in humans

Biphasic waveforms have been suggested as a superior waveform for ventricular defibrillation. To test this premise, a prospective randomized intraoperative evaluation of defibrillation efficacy of monophasic and biphasic waveform pulses was performed in 22 survivors of out of hospital ventricular fibrillation who were undergoing cardiac surgery for implantation of an automatic defibrillator. The initial waveform used in a patient for defibrillation testing, either monophasic or biphasic, was randomly selected. Subsequently, each patient served as his or her own control for defibrillation testing of the other waveform. The defibrillation threshold was defined as the lowest pulse amplitude that would effectively terminate ventricular fibrillation with a single discharge delivered 10 s after initiation of an episode of ventricular fibrillation induced with alternating current. Each defibrillation pulse was recorded oscilloscopically, and defibrillation pulse voltage, current, resistance and stored energy were measured. Fifteen (68%) of the 22 patients had a lower defibrillation threshold with the biphasic pulse, 3 (14%) had a lower threshold with the monophasic pulse and 4 (18%) had equal defibrillation thresholds (within 1.0 J) regardless of waveform. The mean leading edge defibrillation threshold voltage was 317 +/- 105 V when the monophasic pulse was used and 267 +/- 102 V (16% less) when the biphasic pulse was used (p = 0.008). Mean leading edge defibrillation threshold current was 7.9 +/- 3.7 A when the monophasic pulse was used and 6.8 +/- 3.8 A (14% less) when the biphasic pulse was used (p = 0.051).(ABSTRACT TRUNCATED AT 250 WORDS)

Classification of deaths after myocardial infarction as arrhythmic or nonarrhythmic (The Cardiac Arrhythmia Pilot Study)

The Cardiac Arrhythmia Pilot Study (CAPS) was a randomized, double-blind trial of antiarrhythmic drugs (encainide, flecainide, moricizine, imipramine and placebo) in 502 patients with at least 10 ventricular premature complexes/hour, 6 to 60 days after acute myocardial infarction. CAPS tested the feasibility of performing a larger study to determine if suppression of ventricular ectopic activity after acute myocardial infarction could improve survival. Patients in CAPS were followed for 1 year. All death or cardiac arrest events were evaluated by at least 2 investigators using a classification scheme that characterized the underlying mechanism as cardiac arrhythmic, cardiac nonarrhythmic or noncardiac. Forty-five patients (9%) died or had cardiac arrest during the 1-year follow-up, 29 (64%) within 1 hour from the onset of symptoms and 16 greater than 1 hour from the onset of symptoms. Twenty-three deaths (51%) were classified as arrhythmic, 19 (42%) as nonarrhythmic and 3 (7%) as noncardiac. Acute myocardial ischemia or infarction was associated with the death/cardiac arrest event in 16 patients (36%), 8 in the arrhythmic death group. Discrepancies in classification among reviewers were particularly common in patients with long-standing symptoms of congestive heart failure, in whom it was frequently difficult to identify the precise moment of the onset of symptoms in the death/cardiac arrest event. Using only the temporal relation of symptoms to categorize deaths or cardiac arrests, the mechanism of 12 (27%) of the 45 patients was in disagreement with the classification based on the Events Committee review. Classification of death as sudden or nonsudden is not equivalent to the classification of death as arrhythmic or nonarrhythmic.

Toxic and therapeutic effects of amiodarone in the treatment of cardiac arrhythmias

Amiodarone was used to treat cardiac arrhythmias that had been refractory to conventional medical therapy. The first 70 consecutive patients treated with amiodarone in this study had at least 6 months of follow-up (range 6 to 24, mean 11) and form the basis for this report. Sixty-six patients were treated for ventricular arrhythmias and four for supraventricular tachycardias. Amiodarone therapy consisted of a loading dose of 600 mg orally twice a day for 7 days, and 600 mg daily thereafter. Doses were reduced only if side effects occurred. Because of frequent side effects, the dose was reduced from 572 +/- 283 mg per day (mean +/- standard deviation) at 45 days to 372 +/- 174 mg per day at 6 months. With a mean follow-up of 11 months in the 54 patients who continued to take amiodarone, only 4 patients had ventricular fibrillation. Three additional patients experienced recurrent sustained ventricular tachycardia in long-term follow-up. All 70 patients had extensive clinical and laboratory evaluation in follow-up. Side effects were common, occurring in 93% of patients. Thirteen patients (19%) had to discontinue the medication because of severe side effects. Fifty-six patients had gastrointestinal side effects, most commonly constipation. All patients but 1 eventually developed corneal microdeposits, and 43 patients were symptomatic. Cardiovascular side effects were uncommon. Symptomatic pulmonary side effects occurred in seven patients, with unequivocal pulmonary toxicity occurring in five. Neurologic side effects, most commonly tremor and ataxia, occurred in 52 patients. Thyroid dysfunction occurred in 3 patients, and 32 patients had cutaneous abnormalities. Miscellaneous other side effects occurred in 32 patients. Amiodarone appears to be useful in the management of refractory arrhythmias. Because virtually all patients develop side effects when given a maintenance daily dose of 600 mg, lower maintenance doses should be used. It is unknown if the more severe side effects are dose-related. Amiodarone is difficult to administer because of its narrow toxic-therapeutic range and prolonged loading phase. More importantly, the first sign of antiarrhythmic failure may be manifest as sudden cardiac death.

The repetitive ventricular response in man. A predictor of sudden death.

We examined the value of cardiac pacing for assessing ventricular electrical instability and for predicting ventricular tachycardia and sudden death in 50 patients with refractory symptomatic ventricular tachycardia, 12 normal patients, and 48 survivors of a recent myocardial infarction. The repetitive ventricular response (two or more ventricular premature beats produced by a single ventricular pacing stimulus during control of heart rate with atrial pacing) was absent in all 12 normal patients but was present in 44 of the 50 patients (88 per cent) with recurrent ventricular tachycardia (P less than 0.001). Of the 48 survivors of myocardial infarction, 19 had repetitive ventricular responses. During the next 12 months 15 of these patients (79 per cent) had symptomatic ventricular tachycardia or sudden death, or both, as compared with four of 29 patients (14 per cent) who did not have repetitive ventricular responses (P less than 0.001). The repetitive ventricular response identifies patients with life-threatening ventricular instability, but it is still an investigational technic that should be used only with due precautions.

Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial

Introduction: The implantable cardioverter defibrillator (ICD) is commonly used to treat patients with documented sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Arrhythmia recurrence rates in these patients are high, but which patients will receive a therapy and the forms of arrhythmia recurrence (VT or VF) are poorly understood.

The CASCADE study: Randomized antiarrhythmic drug therapy in survivors of Cardiac Arrest in Seattle

The Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) study evaluated antiarrhythmic drug therapy in patients who had survived an episode of out-of-hospital ventricular fibrillation (VF) and who were thought to be at high risk for recurrence of VF. Therapy with empiric amiodarone was compared to therapy with other antiarrhythmic agents, guided by electrophysiologic testing and/or Holter recording. The study evaluated the endpoints of (1) cardiac death, (2) cardiac arrest from ventricular fibrillation with resuscitation, and (3) complete syncope followed by a shock from an automatic implanted defibrillator that restored consciousness. The study comprised 228 patients, 113 treated with amiodarone and 115 treated with conventional antiarrhythmic drug therapy. Most patients had coronary artery disease with a prior myocardial infarction, and one half of the population had a history of congestive heart failure. The mean left ventricular ejection fraction was 35%. Survival was better in patients treated with amiodarone than in patients treated with other antiarrhythmic agents. Patients treated with amiodarone were less likely to receive a shock from an implanted defibrillator, and syncope followed by a shock from a defibrillator was less common in patients treated with amiodarone. However, overall mortality was high, and side effects of therapy were common. Patients treated with amiodarone, even at the low doses used in this study, were still at risk for thyroid dysfunction (both hyperthyroidism and hypothyroidism) and for pulmonary toxicity.

Reversal by Phenylephrine of the Beneficial Effects of Intravenous Nitroglycerin in Patients with Acute Myocardial Infarction

Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.

Comparison of monophasic and biphasic defibrillating pulse waveforms for transthoracic cardioversion

All transthoracic defibrillators on the US market use nominally monophasic shock waveforms. However, biphasic waveforms have a lower defibrillation threshold than monophasic waveforms for transthoracic defibrillation of animals and for defibrillation of humans by implantable cardioverter defibrillators. The relative efficacies of Edmark monophasic and Gurvich biphasic transthoracic cardioversion waveforms (200 J into 50 omega) were compared for transthoracic cardioversion in 171 patients undergoing electrophysiologic study for evaluation of ventricular arrhythmias. Patients were randomized in a blinded fashion to receive either a monophasic or a biphasic waveform for the initial shock for conversion of induced ventricular arrhythmias (ventricular fibrillation [VF] = 53, monomorphic ventricular tachycardia [VT] = 80, polymorphic VT = 30, ventricular flutter = 8). Delivered energies for the Edmark and Gurvich waveforms were 215 +/- 11 and 171 +/- 11 J, respectively. There were no significant differences in patient characteristics, use of antiarrhythmic agents, arrhythmia cycle length, or duration of arrhythmia prior to shock for monophasic and biphasic waveform groups. The first shock for all arrhythmias was successful in 75 of 88 patients (85.2%) for the monophasic waveform compared with 81 of 83 patients (97.6%) for the biphasic waveform, p = 0.0054. The first shock for VF was successful in 22 of 28 patients (78.6%) for the monophasic waveform compared with 25 of 25 (100%) for the biphasic waveform, p = 0.0241. The Gurvich biphasic waveforms delivering a mean of 171 J were superior to Edmark monophasic waveforms delivering a mean of 215 J for transthoracic cardioversion of arrhythmias of short duration. This finding may have important implications for the development of future transthoracic defibrillators.