Voltage-sensitive dyes were used to stain intact perfused hearts and to simultaneously measure optical action potentials (APs) from 124 sites on the epicardium. Patterns of electrical depolarization (activation) and repolarization (recovery) along the surface of the heart were determined from the upstrokes and repolarization phases of optical APs. Standard surface extracellular techniques can detect electrical activation but not the recovery or the duration of APs. The optical recordings were previously shown to be equivalent to intracellular electrode measurements (Salama and Morad, Science Wash. DC 191: 485-487, 1976) and now reveal that AP durations are heterogeneous throughout the epicardium, with durations increasing from the base to the apex of the ventricles. In hearts beating under normal sinus rhythm, the direction and conduction velocity of the activation waves could be altered by electrical stimulation. The normal heterogeneities in AP durations became more pronounced in the presence of the Ca2+-entry blocker, verapamil. The local metabolic state of the tissue was also monitored optically through its intrinsic NADH fluorescence measured from 124 separate regions on the heart. The time course and extent of metabolic injury caused by general anoxia or by a local ischemia induced by a coronary ligation was monitored through maps of NADH fluorescence. The present technique makes it possible to correlate changes in the metabolic state of the muscle with detailed changes in patterns of electrical activity and thus provides a powerful new tool to study fundamental aspects of normal and abnormal cardiac rhythm.

Compared to procainamide in an animal arrhythmic model, the antiarrhythmic potency of the N-acetylated metabolite of procainamide (NAPA) was 92% with respect to dose and 70% with respect to plasma level. The antiarrhythmic effects of combinations of the drugs were additive. Measurements of procainamide and NAPA plasma levels needed to suppress ventricular extrasystoles suggested that both compounds are nearly equipotent in patients as well. The average plasma level required for arrhythmia control in these patients was equivalent to 5.1 mcg/ml procainamide. Since patients on long-term procainamide therapy have plasma concentrations of NAPA that are usually comparable to, and occasionally greater than, their procainamide levels, dose regiments based on procainamide levels alone need revision to include consideration of the levels of this metabolite.

The actuarial incidence and pattern of occurrence of shocks were analyzed in 65 patients after implantation of the automatic implantable cardioverter defibrillator. During a mean follow-up of 25 +/- 21 months only one patient died suddenly, and this patient had a nonfunctioning device at the time of death. The long-term actuarial risk of death from any cause in the patients who received appropriate shocks was not significantly different than for the entire group. The 1- and 4-year cumulative risk of receiving any shock was 51 +/- 7% and 81 +/- 11%; of receiving an appropriate shock was 33 +/- 7% and 64 +/- 10%; of receiving a spurious shock was 17 +/- 5% and 21 +/- 6%; and of receiving an "indeterminate" shock was 19 +/- 6% and 52 +/- 10%. In 14 patients who were followed for 24 months without receiving an appropriate shock, the actuarial risk of receiving an appropriate shock was 29 +/- 14% during the next 24 months. The mean number of shocks delivered during appropriate episodes was 1.6 +/- 0.9, which was significantly lower than the mean of 4.0 +/- 2.0 shocks during spurious episodes (P less than 0.02). The mean number of shocks during indeterminate episodes was 1.7 +/- 1.5. Our data confirms the efficacy of the implantable defibrillator in preventing sudden death. The majority of patients with this device receive appropriate shocks during long-term follow-up, and the cumulative incidence of appropriate shocks increases steadily for at least 4 years. In contrast, the cumulative incidence of spurious shocks plateaus at about 12 months. Our data suggests that many "indeterminate" shocks actually appear to be appropriate.

No abstract

The ability of the automatic implantable cardioverter-defibrillator to prolong overall survival, particularly in patients with significantly depressed cardiac function, has not been well documented. Of 119 patients who received the implantable defibrillator in this institution, 40 had a left ventricular ejection fraction less than 30% (Group A) and 79 had an ejection fraction greater than or equal to 30% (Group B). For each group, cumulative survival was compared with the projected survival if the implantable defibrillator had not been used. Projected survival was based on the assumption that the first appropriate shock would have resulted in death without the defibrillator. For Group A, the 3 year cumulative survival rate was 67 +/- 12% versus a projected survival rate of 6 +/- 15% (p less than 0.001). For Group B, the 3 year cumulative survival rate was 96 +/- 3% versus a projected survival rate of 46 +/- 8% (p less than 0.001). Both the cumulative and projected survival rates for patients in Group A were significantly worse than for patients in Group B (p less than 0.01). The projected survival rates for both Groups A and B were comparable with the observed survival rate in similar patients treated without the implantable defibrillator. In summary, the implantable cardioverter-defibrillator significantly prolonged overall survival, even in patients with poor cardiac function. The technique of estimating projected survival appears to allow a realistic estimate of the reduction in mortality achieved by the defibrillator.