Peter Zimetbaum

A Critical Appraisal of Implantable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac Death

The indications for implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac death have rapidly expanded over the past 10 years. Clinical trial data have quickly been implemented into guidelines without critical reassessment of the strengths and limitations of the evidence. ICD therapy has inherent risks including infection, unnecessary shocks, potential for proarrhythmia, device malfunction, highly publicized manufacturer advisories, and procedural complications, which can adversely affect morbidity and quality of life. A reappraisal of the benefits and potential hazards of ICD therapy will enable physicians to a have a more mutually informed and balanced dialogue with their patients.

Electrocardiographic Predictors of Arrhythmic Death and Total Mortality in the Multicenter Unsustained Tachycardia Trial

Background—Stratifiers of sudden and total mortality risk are needed to optimally target preventive therapies in patients with coronary artery disease and impaired ventricular function. We assessed the prognostic significance of ECG markers of conduction abnormalities and left ventricular hypertrophy in the Multicenter Unsustained Tachycardia Trial (MUSTT). Methods and Results—We analyzed the ECGs of 1638 patients from MUSTT who did not receive antiarrhythmic therapy (antiarrhythmic medication or implantable cardioverter-defibrillator). After adjustment for other significant factors, left bundle-branch block and intraventricular conduction delay were associated with a 50% increase in the risk of both arrhythmic and total mortality. Right bundle-branch block was not associated with arrhythmic or total mortality. Left ventricular hypertrophy was the only ECG predictor of arrhythmic (hazard ratio, 1.35; 95% CI, 1.08 to 1.69) but not total mortality. Conclusions—In patients with coronary artery disease, depressed left ventricular function, and nonsustained ventricular tachycardia, QRS prolongation resulting from left bundle-branch block or intraventricular conduction delay but not right bundle-branch block provided prognostic information about the risk of arrhythmic and total mortality independently of electrophysiological evaluation and ejection fraction. Left ventricular hypertrophy was associated with increased arrhythmic but not total mortality.

Characteristics of heart failure patients associated with good and poor response to cardiac resynchronization therapy: a PROSPECT (Predictors of Response to CRT) sub-analysis

AIMS Predictors of Response to Cardiac Resynchronization Therapy (CRT) (PROSPECT) was the first large-scale, multicentre clinical trial that evaluated the ability of several echocardiographic measures of mechanical dyssynchrony to predict response to CRT. Since response to CRT may be defined as a spectrum and likely influenced by many factors, this sub-analysis aimed to investigate the relationship between baseline characteristics and measures of response to CRT. METHODS AND RESULTS A total of 286 patients were grouped according to relative reduction in left ventricular end-systolic volume (LVESV) after 6 months of CRT: super-responders (reduction in LVESV > or =30%), responders (reduction in LVESV 15-29%), non-responders (reduction in LVESV 0-14%), and negative responders (increase in LVESV). In addition, three subgroups were formed according to clinical and/or echocardiographic response: +/+ responders (clinical improvement and a reduction in LVESV > or =15%), +/- responders (clinical improvement or a reduction in LVESV > or =15%), and -/- responders (no clinical improvement and no reduction in LVESV > or =15%). Differences in clinical and echocardiographic baseline characteristics between these subgroups were analysed. Super-responders were more frequently females, had non-ischaemic heart failure (HF), and had a wider QRS complex and more extensive mechanical dyssynchrony at baseline. Conversely, negative responders were more frequently in New York Heart Association class IV and had a history of ventricular tachycardia (VT). Combined positive responders after CRT (+/+ responders) had more non-ischaemic aetiology, more extensive mechanical dyssynchrony at baseline, and no history of VT. CONCLUSION Sub-analysis of data from PROSPECT showed that gender, aetiology of HF, QRS duration, severity of HF, a history of VT, and the presence of baseline mechanical dyssynchrony influence clinical and/or LV reverse remodelling after CRT. Although integration of information about these characteristics would improve patient selection and counselling for CRT, further randomized controlled trials are necessary prior to changing the current guidelines regarding patient selection for CRT.

Hybrid Pharmacologic and Ablative Therapy: A Novel and Effective Approach for the Management of Atrial Fibrillation

Hybrid Therapy for Atrial Fibrillation. Introduction: Maintenance of sinus rhythm in patients with recurrent atrial fibrillation is often difficult to achieve with pharmacologic therapy. Complex catheter ablative procedures are being developed, but efficacy and safety issues remain to be clarified. We hypothesized that combined pharmacologic and simple ablative therapies in a targeted subset of patients will improve success in the treatment of atrial fibrillation.

Plasma lipids and lipoproteins and the incidence of cardiovascular disease in the very elderly. The Bronx Aging Study.

The Bronx Aging Study is a 10-year prospective investigation of very elderly volunteers (mean age at study entry, 79 years; range, 75-85 years) designed to assess risk factors for dementia and coronary and cerebrovascular (stroke) diseases. Entry criteria included the absence of terminal illness and dementia. All subjects (n = 350) included in this report had at least two lipid and lipoprotein determinations. Overall, more than one third of subjects showed at least a 10% change in lipid and lipoprotein levels between the initial and final measurements. Moreover, mean levels for women were consistently different than those for men, and because of this finding subjects were classified into potential-risk categories based on the changes observed by using their sex-specific lipid and lipoprotein distributions. The incidences of cardiovascular disease, dementia, and death were compared between risk groups. Proportional-hazards analysis showed that in men a consistently low high density lipoprotein cholesterol level (less than or equal to 30 mg/dl) was independently associated with the development of myocardial infarction (p = 0.006), cardiovascular disease (p = 0.002), or death (p = 0.002). For women, however, a consistently elevated low density lipoprotein cholesterol level (greater than or equal to 171 mg/dl) was associated with myocardial infarction (p = 0.032). Thus, low high density lipoprotein cholesterol remains a powerful predictor of coronary heart disease risk for men even into old age, while elevated low density lipoprotein cholesterol continues to play a role in the development of myocardial infarction in women. The findings suggest that an unfavorable lipoprotein profile increases the risk of cardiovascular morbidity and mortality even at advanced ages for both men and women.

Cost-Effectiveness of Radiofrequency Catheter Ablation Compared With Antiarrhythmic Drug Therapy for Paroxysmal Atrial Fibrillation

Background—Radiofrequency catheter ablation (RFA) has emerged as an important treatment strategy for atrial fibrillation (AF). The potential cost-effectiveness of RFA for AF, relative to antiarrhythmic drug (AAD) therapy, has not been fully explored from a US perspective. Methods and Results—We constructed a Markov disease simulation model for a hypothetical cohort of patients with drug-refractory paroxysmal AF, treated either with RFA with/without AAD or AAD alone. Costs and quality-adjusted life-years were projected over 5 years. Model inputs were drawn from published clinical trial and registry data, from new registry and trial data analysis, and from data prospectively collected from patients with AF treated with RFA at our institution. We assumed no benefit from ablation on stroke, heart failure or death, but did estimate changes in quality-adjusted life expectancy using data from several AF cohorts. In the base case scenario, cumulative costs with the RFA and AAD strategies were

Antiarrhythmic Drug Therapy for Atrial Fibrillation

26 584 and

Cardiovascular magnetic resonance characterization of mitral valve prolapse.

19 898, respectively. Over 5 years, quality-adjusted life expectancy was 3.51 quality-adjusted life-years with RFA versus 3.38 for the AAD group. The incremental cost-effectiveness ratio for RFA versus AAD was thus

Ambulatory Arrhythmia Monitoring Choosing the Right Device

51 431 per quality-adjusted life-year. Model results were most sensitive to time horizon, the relative utility weights of successful ablation versus unsuccessful drug therapy, and to the cost of an ablation procedure. Conclusions—RFA with/without AAD for symptomatic, drug-refractory paroxysmal AF appears to be reasonably cost-effective compared with AAD therapy alone from the perspective of the US health care system, based on improved quality of life and avoidance of future health care costs.

The Evolving Role of Ambulatory Arrhythmia Monitoring in General Clinical Practice

Antiarrhythmic medications have been available for nearly 100 years and remain a mainstay in the management of atrial fibrillation (AF). Goals of therapy with the use of these drugs include a reduction in the frequency and duration of episodes of arrhythmia as well an emerging goal of reducing mortality and hospitalizations associated with AF. The use of these drugs has been limited by both proarrhythmic and noncardiovascular toxicities as well as often modest antiarrhythmic efficacy. Despite these limitations, antiarrhythmic drugs remain widely prescribed for the management of symptomatic AF, and a host of new antiarrhythmic drugs are in various stages of clinical development. This review will focus primarily on antiarrhythmic drug use in patients with AF in the absence of significant structural heart disease or congestive heart failure. A multitude of studies have evaluated the health-related outcomes associated with a strategy of rate compared with rhythm control in patients with AF.1–5 These studies, which included primarily patients aged ≥60 years with at least 1 risk factor for stroke, failed to demonstrate a mortality benefit associated with a rhythm control strategy. This equivalence in outcome was in part related to toxicities associated with antiarrhythmic drug therapy as well as excess stroke risk in patients in whom anticoagulation was discontinued.6 Important groups of patients, including younger individuals without thromboembolic risk factors and the elderly (>80 years), were excluded from these trials, but the results were nonetheless applicable to a large percentage of the AF population. As a likely consequence of these landmark studies, rates of AF-associated hospitalization, cardioversion, and antiarrhythmic drug use plateaued or fell in the years after their publication.7 This trend has been reversed in the latter part of this decade, with an increase in rhythm control strategies driven largely by increased rates of AF …