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Investigations of the impact of ventricular arrhythmias in populations have focused primarily on two aspects, ventricular ectopic activity and sudden cardiac death (SCD). The observation that coronary heart disease (CHD) is an important background of death due to ventricular tachyarrhythmia (VTA) remains the dominant belief today. The evidence supports the principle that reduction of deaths due to VTA is multifactorial and results from improved primary prevention, treatment of CHD complications, and secondary prevention. Recent evidence for unfavorable trends for SCD and CHD mortality raises the specter of a reversal in the gains made against fatal VTA in recent decades.

Objectives: The goal of this study was to compare T-wave alternans (TWA), signal-averaged electrocardiography (SAECG) and programmed ventricular stimulation (EPS) for arrhythmia risk stratification in patients undergoing electrophysiology study., Background: Accurate identification of patients at increased risk for sustained ventricular arrhythmias is critical to prevent sudden cardiac death. T-wave alternans is a heart rate dependent measure of repolarization that correlates with arrhythmia vulnerability in animal and human studies. Signal-averaged electrocardiography and EPS are more established tests used for risk stratification., Methods: This was a prospective, multicenter trial of 313 patients in sinus rhythm who were undergoing electrophysiologic study. T-wave alternans, assessed with bicycle ergometry, and SAECG were measured before EPS. The primary end point was sudden cardiac death, sustained ventricular tachycardia, ventricular fibrillation or appropriate implantable defibrillator (ICD) therapy, and the secondary end point was any of these arrhythmias or all-cause mortality., Results: Kaplan-Meier survival analysis of the primary end point showed that TWA predicted events with a relative risk of 10.9, EPS had a relative risk of 7.1 and SAECG had a relative risk of 4.5. The relative risks for the secondary end point were 13.9, 4.7 and 3.3, respectively (p < 0.05). Multivariate analysis of 11 clinical parameters identified only TWA and EPS as independent predictors of events. In the prespecified subgroup with known or suspected ventricular arrhythmias, TWA predicted primary end points with a relative risk of 6.1 and secondary end points with a relative risk of 8.0., Conclusions: T-wave alternans is a strong independent predictor of spontaneous ventricular arrhythmias or death. It performed as well as programmed stimulation and better than SAECG in risk stratifying patients for life-threatening arrhythmias.

Detection of local electrical myocardial activation by means of extracellular recordings is often difficult in the presence of polyphasic electrograms. The purpose of this investigation was to compare the ability of several variables to distinguish unipolar deflections due to local activation from those due to nonlocal activity. A model of polyphasic deflections based on atrial recordings during reentrant tachycardia was used to facilitate distinction of local and distant activity by methods independent of the test variables. The performance of variables were assessed by comparing areas under receiver operating characteristic curves. Optimal thresholds of test variables were identified by maximizing statistics which corrected for the pretest probability of local activation. We found that the greatest negative first derivative of the unipolar potential discriminated between local and distant ventricular signals, but performed less well than the ratio of the first derivative to the potential for distinguishing between local atrial signals and distant ventricular signals. A linear combination of the potential and the ratio of the first derivative and the potential performed well for all groups of signals studied. We conclude that optimal criteria for detecting local activation depends on the characteristics of the population of signals and that a statistical approach can be used to identify optimal criteria for a given population.

Ninety-six patients with recurrent, drug-refractory tachyarrhythmias were treated with amiodarone for 8.0 +/- 7.5 months (range 1 day to 27 months): 77 for recurrent ventricular tachycardia or ventricular fibrillation (VT/VF), two for complex ventricular ectopy, and 17 for supraventricular tachyarrhythmias. The actuarial incidence of successful amiodarone therapy was 52 +/- 7% at 12 months and 28 +/- 9% at 24 months for patients with VT/VF. Neither patient with complex ventricular ectopy was successfully treated. Among the patients with supraventricular tachyarrhythmias, 64.7% were successfully treated for 7.7 +/- 7.6 months (range 1 to 22 months). Amiodarone toxicity occurred in 66 of 91 patients (72.5%) treated for more than 1 week. Fourteen patients had therapy-limiting toxicity. Of these 14, six had pulmonary toxicity, four had arrhythmia exacerbation, one had hepatitis, one had renal toxicity, one had rash, and one had erythema nodosum. The actuarial incidence of therapy-limiting side effects was 27 +/- 7% at 15 months. We conclude that amiodarone is useful in the treatment of refractory tachyarrhythmias but that the rate of efficacy in VT/VF is lower and the incidence of significant toxicity is higher than has been generally appreciated.

To evaluate vulnerability to ventricular arrhythmia induction, programmed electrical stimulation was performed in the operating room in 17 consecutive patients undergoing myotomy-myectomy for obstructive hypertrophic cardiomyopathy (HC). A control group of 5 patients undergoing coronary artery bypass grafting with normal left ventricular function and no previous myocardial infarction also was tested. Of the 17 patients with HC, 14 had inducible sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), 1 had inducible unsustained VT and the remaining 2 had less than 6 ventricular beats. In contrast, none of the 5 control patients had an inducible sustained ventricular arrhythmia, 1 had inducible unsustained VT, and the remaining 4 had less than 3 ventricular beats. The difference between the 2 groups with respect to induction of a sustained ventricular arrhythmia, unsustained VT or less than 6 ventricular beats was significant (p less than 0.001). It is concluded that patients with severe obstructive HC are unusually vulnerable to ventricular arrhythmia induction. This suggests that spontaneous ventricular tachyarrhythmias may be an important cause of sudden death in patients with HC.