David J. Wilber

IMPROVED SURVIVAL WITH AN IMPLANTED DEFIBRILLATOR IN PATIENTS WITH CORONARY DISEASE AT HIGH RISK FOR VENTRICULAR ARRHYTHMIA

BACKGROUND Unsustained ventricular tachycardia in patients with previous myocardial infarction and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent. We studied whether prophylactic therapy with an implanted cardioverter-defibrillator, as compared with conventional medical therapy, would improve survival in this high-risk group of patients. METHODS Over the course of five years, 196 patients in New York Heart Association functional class I, II, or III with prior myocardial infarction; a left ventricular ejection fraction < or = 0.35; a documented episode of asymptomatic unsustained ventricular tachycardia; and inducible, nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were randomly assigned to receive an implanted defibrillator (n = 95) or conventional medical therapy (n=101). We used a two-sided sequential design with death from any cause as the end point. RESULTS The base-line characteristics of the two treatment groups were similar. During an average follow-up of 27 months, there were 15 deaths in the defibrillator group (11 from cardiac causes) and 39 deaths in the conventional-therapy group (27 from cardiac causes) (hazard ratio for overall mortality, 0.46; 95 percent confidence interval, 0.26 to 0.82; P=0.009). There was no evidence that amiodarone, beta-blockers, or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio. CONCLUSIONS In patients with a prior myocardial infarction who are at high risk for ventricular tachyarrhythmia, prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy.

A comparison of T-wave alternans, signal averaged electrocardiography and programmed ventricular stimulation for arrhythmia risk stratification.

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.

Time Dependence of Mortality Risk and Defibrillator Benefit After Myocardial Infarction

Background—Prophylactic implantable defibrillators (ICDs) improve survival in patients with impaired ventricular function after myocardial infarction (MI), but it is uncertain whether mortality risk and survival benefit depend on the elapsed time from MI. Methods and Results—The Multicenter Automatic Defibrillator Implantation Trial II examined the impact of ICDs on survival in post-MI patients with ejection fractions ≤30%. In 1159 patients, mean time from most recent MI to enrollment was 81±78 months. Patients were randomized to an ICD (n=699) or conventional care (n=460) in a 3:2 ratio. Mortality rates (deaths per 100 person-years of follow-up) in both treatment groups were analyzed by time from MI divided into quartiles (<18, 18 to 59, 60 to 119, and ≥120 months). In conventional care patients, these rates increased as time from MI increased (7.8%, 8.4%, 11.6%, 14.0%; P =0.03). Mortality rates in ICD patients were consistently lower in each quartile and showed minimal increase over time (7.2%, 4.9%, 8.2%, 9.0%; P =0.19). Covariate-adjusted hazard ratios for risk of death associated with ICD therapy were 0.97 (95% CI, 0.51 to 1.81; P =0.92) for recent MI (<18 months) and 0.55 (95% CI, 0.39 to 0.78; P =0.001) for remote MI (≥18 months). Conclusions—Mortality risk in patients with ejection fractions ≤30% increases as a function of time from MI. The survival benefit associated with ICDs appears to be greater for remote MI and remains substantial for up to ≥15 years after MI.

Atrial Fibrillation After Radiofrequency Ablation of Type I Atrial Flutter Time to Onset, Determinants, and Clinical Course

BACKGROUND The occurrence of atrial fibrillation after ablation of type I atrial flutter remains an important clinical problem. To gain further insight into the pathogenesis and significance of postablation atrial fibrillation, we examined the time to onset, determinants, and clinical course of atrial fibrillation after ablation of type I flutter in a large patient cohort. METHODS AND RESULTS Of 110 consecutive patients with ablation of type I atrial flutter, atrial fibrillation was documented in 28 (25%) during a mean follow-up of 20.1+/-9.2 months (cumulative probability of 12% at 1 month, 23% at 1 year, and 30% at 2 years). Among 17 clinical and procedural variables, only a history of spontaneous atrial fibrillation (relative risk 3.9, 95% confidence intervals 1.8 to 8.8, P=0.001) and left ventricular ejection fraction <50% (relative risk 3.8, 95% confidence intervals 1.7 to 8.5, P=0.001) were significant and independent predictors of subsequent atrial fibrillation. The presence of both these characteristics identified a high-risk group with a 74% occurrence of atrial fibrillation. Patients with only 1 of these characteristics were at intermediate risk (20%), and those with neither characteristic were at lowest risk (10%). The determinants and clinical course of atrial fibrillation did not differ between an early (< or = 1 month) compared with a later onset. Atrial fibrillation was persistent and recurrent, requiring long-term therapy in 18 patients, including 12 of 19 (63%) with prior atrial fibrillation and left ventricular dysfunction. CONCLUSIONS Atrial fibrillation after type I flutter ablation is primarily determined by the presence of a preexisting structural and electrophysiological substrate. These data should be considered in planning postablation management. The persistent risk of atrial fibrillation in this population also suggests a potentially important role for atrial fibrillation as a trigger rather than a consequence of type I atrial flutter.

Atypical Atrial Flutter Originating in the Right Atrial Free Wall

BACKGROUND Data from experimental models of atrial flutter indicate that macro-reentrant circuits may be confined by anatomic and functional barriers remote from the tricuspid annulus-eustachian ridge atrial isthmus. Data characterizing the various forms of atypical atrial flutter in humans are limited. METHODS AND RESULTS In 6 of 160 consecutive patients referred for ablation of counterclockwise and/or clockwise typical atrial flutter, an additional atypical atrial flutter was mapped to the right atrial free wall. Five patients had no prior cardiac surgery. Incisional atrial tachycardia was excluded in the remaining patient. High-density electroanatomic maps of the reentrant circuit were obtained in 3 patients. Radiofrequency energy application from a discrete midlateral right atrial central line of conduction block to the inferior vena cava terminated and prevented the reinduction of atypical atrial flutter in each patient. Atrial flutter has not recurred in any patient (follow-up, 18+/-17 months; range, 3 to 40 months). CONCLUSIONS Atrial flutter can arise in the right atrial free wall. This form of atypical atrial flutter could account for spontaneous or inducible atrial flutter observed in patients referred for ablation and is eliminated with linear ablation directed at the inferolateral right atrium.

Clinical course and implantable cardioverter defibrillator therapy in postinfarction women with severe left ventricular dysfunction.

Background: There are limited data regarding implantable cardioverter defibrillator (ICD) therapy in postinfarction women with severe left ventricular dysfunction. The aim of this study was to evaluate the risk of cardiac events and effects of ICD therapy in women as compared to men enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II).

Multicenter Automatic Defibrillator Implantation Trial II (MADIT II): Design and Clinical Protocol

From the * C a r d i o ~ ~ Unit, D e p a r ~ n t of Medicine, **Depar~ent of Biostatistics , and ***Depar~en& of Communit~ and Preveentiwe Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York; ?Good Samaritan Hospital, Los Angeles, California; ftscripps Memorial Hospital, La J o b , California; ?##University Hospital, Mageburg, Germany; and the § C a r d i o ~ ~ Unit, U~wersity of Chicago, ~ ~ i c a g o , l~~inois

Conduction Properties of the Inferior Vena Cava‐Tricuspid Annular Isthmus in Patients with Typical Atrial Flutter

Conduction Properties of the Annular Isthmus. Introduction: A functional region of slow conduction located in the inferior right atrium has been postulated to be critical to the induction and maintenance of typical human atrial flutter. We reexamined the potential role of functional conduction delay in the annular isthmus between the tricuspid valve and the inferior vena cava; it is within this region that such delays have been postulated to occur, and where interruption of conduction by radiofrequency energy application has been shown to eliminate typical flutter.

Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentry Tachycardia Utilizing Nonfluoroscopic Electroanatomical Mapping

The advent of catheter ablation stimulated extensive research into anatomical localization of the pathways involved in atrioventricular nodal reentrant tachycardia(AVNRT). Conventional electrophysiological methods that attempt to correlate intracardiac electrograms with two‐dimensional fluoroscopic anatomy are limited by the relative inaccuracy and poor reproducibility of this technique, and the requirement for high levels of radiation exposure. A new method of nonfluoroscopic electroanatomical mapping utilizes magnetic field sensing with a specialized catheter to construct three‐dimensional electroanatomical endocardial maps of selected heart chambers with spatial resolution of < 1 mm. This system can be used in patients undergoing catheter ablation for AVNRT to create accurate maps of Kochs triangle and to guide application of radiofrequency energy. Initial experience in 14 patients suggests efficacy and safety comparable to conventional mapping and ablation techniques. Further evaluation may confirm the potential benefits of this system with respect to success rates, complications, procedure time, and radiation exposure.

What Can We Expect from Prophylactic Implantable Defibrillators

Death due to ventricular tachyarrhythmia (VT) remains an important public health problem; patients with prior myocardial infarction (MI) constitute the largest identifiable population for prophylactic interventions. Targeting of progressively higher-risk subgroups of post-MI survivors carries inevitable tradeoffs with respect to the global impact of interventions on overall mortality. Therapy with aspirin, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors comprise the benchmark against which all additional interventions, including implantable defibrillators, must be measured. Initial enthusiasm for empiric amiodarone therapy has been tempered by the limited benefit demonstrated in recent randomized trials. Trials of other class III antiarrhythmic drugs, including both d,l-sotalol and d-sotalol, have also failed to demonstrate survival benefit. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) demonstrated significantly improved survival associated with defibrillators in a small subgroup of post-MI survivors with a high short-term risk of death. The ultimate number and optimal criteria for selection of patients who may benefit from prophylactic defibrillator therapy after MI will undergo continued evolution as new data from current and ongoing trials become available.