Jonathan S. Steinberg

A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias

BACKGROUND Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias. They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs, but the relative efficacy of these two treatment strategies is unknown. METHODS To address this issue, we conducted a randomized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia. Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms, along with a left ventricular ejection fraction of 0.40 or less. One group of patients was treated with implantation of a cardioverter-defibrillator; the other received class III antiarrhythmic drugs, primarily amiodarone at empirically determined doses. Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years. Of 1016 patients (45 percent of whom had ventricular fibrillation, and 55 percent ventricular tachycardia), 507 were randomly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy. The primary end point was overall mortality. RESULTS Follow-up was complete for 1013 patients (99.7 percent). Overall survival was greater with the implantable defibrillator, with unadjusted estimates of 89.3 percent, as compared with 82.3 percent in the antiarrhythmic-drug group at one year, 81.6 percent versus 74.7 percent at two years, and 75.4 percent versus 64.1 percent at three years (P<0.02). The corresponding reductions in mortality (with 95 percent confidence limits) with the implantable defibrillator were 39+/-20 percent, 27+/-21 percent, and 31+/-21 percent CONCLUSIONS Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms, the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival.

Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria.

BACKGROUND In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. METHODS AND RESULTS Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. CONCLUSIONS The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. Clinical Trial Registration clinicaltrials.gov Identifier: NCT00024505.

Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria

Background— In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims—the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. Methods and Results— Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. Conclusions— The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00024505.

Inappropriate Implantable Cardioverter-Defibrillator Shocks in MADIT II : Frequency, Mechanisms, Predictors, and Survival Impact

OBJECTIVES This study sought to identify the incidence and outcome related to inappropriate implantable cardioverter-defibrillator (ICD) shocks, that is, those for nonventricular arrhythmias. BACKGROUND The MADIT (Multicenter Automatic Defibrillator Implantation Trial) II showed that prophylactic ICD implantation improves survival in post-myocardial infarction patients with reduced ejection fraction. Inappropriate ICD shocks are common adverse consequences that may impair quality of life. METHODS Stored ICD electrograms from all shock episodes were adjudicated centrally. An inappropriate shock episode was defined as an episode during which 1 or more inappropriate shocks occurred; another inappropriate ICD episode occurring within 5 min was not counted. Programmed parameters for patients with and without inappropriate shocks were compared. RESULTS One or more inappropriate shocks occurred in 83 (11.5%) of the 719 MADIT II ICD patients. Inappropriate shock episodes constituted 184 of the 590 total shock episodes (31.2%). Smoking, prior atrial fibrillation, diastolic hypertension, and antecedent appropriate shock predicted inappropriate shock occurrence. Atrial fibrillation was the most common trigger for inappropriate shock (44%), followed by supraventricular tachycardia (36%), and then abnormal sensing (20%). The stability detection algorithm was programmed less frequently in patients receiving inappropriate shocks (17% vs. 36%, p = 0.030), whereas other programming parameters did not differ significantly from those without inappropriate shocks. Importantly, patients with inappropriate shocks had a greater likelihood of all-cause mortality in follow-up (hazard ratio 2.29, p = 0.025). CONCLUSIONS Inappropriate ICD shocks occurred commonly in the MADIT II study, and were associated with increased risk of all-cause mortality.

Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting--a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society.

Echocardiography plays an evolving and important role in the care of heart failure patients treated with biventricular pacing, or cardiac resynchronization therapy (CRT). Numerous recent published reports have utilized echocardiographic techniques to potentially aide in patient selection for CRT prior to implantation and to optimized device settings afterwards. However, no ideal approach has yet been found. This consensus report evaluates the contemporary applications of echocardiography for CRT including relative strengths and technical limitations of several techniques and proposes guidelines regarding current and possible future clinical applications. Principal methods advised to qualify abnormalities in regional ventricular activation, known as dyssynchrony, include longitudinal velocities by color-coded tissue Doppler and the difference in left ventricular to right ventricular ejection using routine pulsed Doppler, or interventricular mechanical delay. Supplemental measures of radial dynamics which may be of additive value include septal-to-posterior wall delay using M-mode in patients with non-ischemic disease with technically high quality data, or using speckle tracking radial strain. A simplified post-CRT screening for atrioventricular optimization using Doppler mitral inflow velocities is also proposed. Since this is rapidly changing field with new information being added frequently, future modification and refinements in approach are anticipated to continue.

A Randomized Comparison of Pulmonary Vein Isolation With Versus Without Concomitant Renal Artery Denervation in Patients With Refractory Symptomatic Atrial Fibrillation and Resistant Hypertension

OBJECTIVES The aim of this prospective randomized study was to assess the impact of renal artery denervation in patients with a history of refractory atrial fibrillation (AF) and drug-resistant hypertension who were referred for pulmonary vein isolation (PVI). BACKGROUND Hypertension is the most common cardiovascular condition responsible for the development and maintenance of AF. Treating drug-resistant hypertension with renal denervation has been reported to control blood pressure, but any effect on AF is unknown. METHODS Patients with a history of symptomatic paroxysmal or persistent AF refractory to ≥2 antiarrhythmic drugs and drug-resistant hypertension (systolic blood pressure >160 mm Hg despite triple drug therapy) were eligible for enrolment. Consenting patients were randomized to PVI only or PVI with renal artery denervation. All patients were followed ≥1 year to assess maintenance of sinus rhythm and to monitor changes in blood pressure. RESULTS Twenty-seven patients were enrolled, and 14 were randomized to PVI only, and 13 were randomized to PVI with renal artery denervation. At the end of the follow-up, significant reductions in systolic (from 181 ± 7 to 156 ± 5, p < 0.001) and diastolic blood pressure (from 97 ± 6 to 87 ± 4, p < 0.001) were observed in patients treated with PVI with renal denervation without significant change in the PVI only group. Nine of the 13 patients (69%) treated with PVI with renal denervation were AF-free at the 12-month post-ablation follow-up examination versus 4 (29%) of the 14 patients in the PVI-only group (p = 0.033). CONCLUSIONS Renal artery denervation reduces systolic and diastolic blood pressure in patients with drug-resistant hypertension and reduces AF recurrences when combined with PVI.

The clinical implications of cumulative right ventricular pacing in the multicenter automatic defibrillator trial II.

Introduction: This study was designed to assess whether right ventricular pacing in the implantable cardioverter defibrillator (ICD) arm of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II was associated with an unfavorable outcome.

Value of the P-wave signal-averaged ECG for predicting atrial fibrillation after cardiac surgery.

BackgroundAtrial fibrillation (AF) is a commonly encountered arrhythmia in clinical practice, and it occurs rquently after cardiac surgery. The P-wave signal-averaged (SA) ECG noninvasively detects atrial conduction delay. Prior studies have described greater P-wave prolongation in patients with a history of AF, but prospective studies have not been performed. Methods and Resuls. Consecutive patients undergoing cardiac surgery were enrolled. The P-wave SAECG was recorded before surgery from three orthogonal leads using a sinus P-wave template and a cross-correlation function. The averaged P wave was filtered with a least-squares-fit filter and combined into a vector magnitude, and total P-wave duration was measured. Patients were observed after cardiac surgery for the development ofAF. One hundred thirty patients were enrolled, and 33 (25%) developed AF 2.6±2.0 days after surgery. Patients with AF more often had left ventricular hypertrophy on ECG (P<.05) and had a lower ejection fraction (P<.05). The P-wave duration on the SAECG was significantly longer in the AF patients than in those without AF: 152±18 versus 139±17 milliseconds (P<.001). An SAECG P-wave duration >140 milliseconds predicted AF with sensitivity of 77%, specificity of 55%, positive predictive accuracy of 37%, and negative predictive accuracy of 87%. The likelihood of experiencing AF was increased 3.9-fold if the SAECG P-wave duration was prolonged. P-wave SAECG results were independent of other clinical variables by multivariate analysis. ConclusionsThe P-wave duration recorded with the SAECG is a potent, accurate, and independent predictor of AF after cardiac surgery.

Analysis of Cause-Specific Mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study

Background—Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. This report describes the cause-specific modes of death in the AFFIRM treatment groups. Methods and Results—All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee, and a mode of death was assigned. In AFFIRM, 2033 patients were randomized to a rhythm-control strategy and 2027 patients to a rate-control strategy. During a mean follow-up of 3.5 years, there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients (P = 0.07). In the rhythm-control group, 129 patients (9%) died of a cardiac cause, and in the rate-control group, 130 patients (10%) died (P = 0.95). Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths. The numbers of vascular deaths were similar in the 2 groups: 35 (3%) in the rhythm-control group and 37 (3%) in the rate-control group (P = 0.82). There were no differences in the rates of ischemic stroke and central nervous system hemorrhage. In the rhythm-control group, there were 169 noncardiovascular deaths (47.5% of the total number of deaths), whereas in the rate-control arm, there were 113 noncardiovascular deaths (36.5% of the total number of deaths) (P = 0.0008). Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths. Conclusions—Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate.

Cardiac resynchronization therapy is more effective in women than in men: the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) trial.

OBJECTIVES The purpose of this study was to investigate the factors related to sex-specific outcomes for death and heart failure events in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) trial. BACKGROUND In the MADIT-CRT trial, women seemed to achieve a better result from resynchronization therapy than men. METHODS All 1,820 patients (453 female and 1,367 male) enrolled in the MADIT-CRT trial were included in this sex-specific outcome analysis that compared the effect of cardiac resynchronization therapy with defibrillator (CRT-D) relative to implanted cardioverter-defibrillator (ICD) on death or heart failure (whichever came first), heart failure only, and death at any time. RESULTS Female patients were more likely to have nonischemic cardiomyopathy and left bundle branch block and less likely to have renal dysfunction than male patients. Overall, female patients had a better result from CRT-D therapy than male patients, with a significant 69% reduction in death or heart failure (hazard ratio: 0.31, p < 0.001) and 70% reduction in heart failure alone (hazard ratio: 0.30, p < 0.001). Women had a significant 72% reduction in all-cause mortality in the total population (hazard ratio: 0.28, p = 0.02) and significant 82% and 78% reductions in mortality in those with QRS ≥ 150 ms and with left bundle branch block conduction disturbance, respectively, with sex-by-treatment interactions for mortality reduction significant at p < 0.05 in each of these 3 patient groups. These beneficial CRT-D effects among women were associated with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men. CONCLUSIONS Women in the MADIT-CRT trial obtained significantly greater reductions in death or heart failure (whichever came first), heart failure alone, and all-cause mortality with CRT-D therapy than men, with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men. (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).