Three-Year Survival after Transcatheter Aortic Valve Replacement: Findings from the Marshfield Aortic Valve Experience (MAVE) Study.

Background: Transcatheter aortic valve replacement (TAVR) is a rapidly evolving treatment for severe aortic stenosis. However, uncertainties exist for optimal valve selection as there are few long-term studies comparing patient survival by valve type.Objective: We hypothesized that self-expandable valves (SEV) would provide a survival advantage over balloon expandable valves (BEV), as SEV continue to expand and might better accommodate to the anatomy of the aortic valve over time.Methods: We examined outcomes according to valve type from a rural tertiary referral center between 2012 and 2017.Results: Out of 269 patients, 77 deaths (28.6%) occurred over the study period with 6 deaths by 1 month post-TAVR and 37 deaths by 1 year post-TAVR. The median observation time for survivors was 21.5 months. The probability of survival at 3 years was 60.7% and 61.9% for patients who underwent treatment with SEV and BEV, respectively. There was no statistically significant difference in overall patient survival with or without adjustment for factors such as age, sex, race, and aortic valve area. Additionally, in a secondary analysis restricted to those patients treated in later years (2015-2017) survival among patients with BEV appeared superior (HR=0.456, P=0.015).Conclusion: Patients who underwent TAVR at a rural medical center with SEV showed similar survival compared to those who received a BEV. Superior survival was observed among those who received BEV versus SEV between 2015 and 2017.

Left bundle branch block and the evolving role of QRS morphology in selection of patients for cardiac resynchronization.

BACKGROUND: The clinical significance of left bundle branch block (LBBB) has recently expanded with the discovery of a strong association with better outcomes in patients receiving cardiac resynchronization therapy. METHODS: Several milestones have contributed to the current understanding on the role of LBBB in clinical practice. RESULT: Sunao Tawara described the arrangement of components of what he called the cardiac conduction system from the atrioventricular node to the terminal Purkinje fibers that connect to the working myocardium, and his hypotheses on how it functions remain current. Mauricio Rosenbaum and colleagues developed the bifascicular model of the left-sided conduction system that explains the characteristic electrocardiographic changes associated with propagation disturbances in its components. Andrés Ricardo Pérez-Riera and others have disputed the bifascicular model as oversimplified and have emphasized the role of the left septal fascicle. Marcelo Elizari and colleagues have explained the importance of masquerading bundle branch block. Elena Sgarbossa and colleagues developed a scheme to recognize ST elevation myocardial infarction in patients with left bundle branch block which remains current after more than 20 years. Enrique Cabrera and others identified electrocardiographic signs of remote myocardial infarction. CONCLUSION: Substantial progress has been made in the understanding of LBBB, yet its role in clinical practice continues to evolve and important gaps remain to which research should be directed.

The changing epidemiology of ventricular arrhythmias.

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.

Prevalence and mortality of patients with myocardial infarction and reduced left ventricular ejection fraction in a defined community: relation to the second multicenter automatic defibrillator implantation trial.

OBJECTIVES: We compared characteristics and mortality of patients from a community population meeting enrollment criteria of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT II) to those of the MADIT II subjects. BACKGROUND: MADIT II showed that implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with myocardial infarction (MI) and low left ventricular ejection fraction (LVEF)

Patients with recently diagnosed nonischemic cardiomyopathy benefit from implantable cardioverter-defibrillators.

OBJECTIVES: This study sought to determine whether the time from diagnosis to randomization was related to outcome in a clinical trial of implantable cardioverter-defibrillator (ICD) insertion in nonischemic cardiomyopathy. BACKGROUND: Whether the duration of nonischemic cardiomyopathy is related to arrhythmic risk and the possible benefit of ICD insertion is unknown. METHODS: The Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial randomized 458 patients with nonischemic dilated cardiomyopathy and a left ventricular ejection fraction <36% to receive standard medical therapy with or without an ICD. Patients were randomized regardless of the duration of known cardiomyopathy as long as a reversible cause of left ventricular dysfunction was not present. Patients were divided into recently and remotely diagnosed nonischemic cardiomyopathy groups based on the time from diagnosis of cardiomyopathy to randomization. To categorize patients, cut points of three and nine months were used. RESULTS: Patients with recently diagnosed cardiomyopathy who received an ICD had better survival than those treated with standard therapy at both cut points. This difference in survival was significant at three months (p < 0.05) and was borderline significant at nine months (p = 0.058). Patients with remotely diagnosed cardiomyopathy did not have a significant survival benefit with ICD insertion, but there were no significant differences between ICD benefit in the recent and remote diagnosis groups (p = 0.17 and 0.25). CONCLUSIONS: Patients who have a recent cardiomyopathy diagnosis do not have any less ICD benefit than those with a remote diagnosis. Thus, ICD therapy should be considered in such patients as soon as they are identified as long as a reversible cause of left ventricular dysfunction is excluded.

Sudden cardiac death unresponsive to implantable defibrillator therapy: an urgent target for clinicians, industry and government.

A major expansion in utilization of implantable cardioverter-defibrillators (ICDs) is anticipated based on the results of randomized clinical trials (RCT) that demonstrate increased survival in a sizable population of patients with reduced left ventricular function. However, if RCT accurately reflect clinical practice, then a substantial proportion of patients will die suddenly despite ICD implantation. ICD-unresponsive sudden cardiac death (SCD) has been recognized since the initial ICD experience. Yet, despite 25 years of technical advances, the frequency of ICD-unresponsive SCD has not declined. Pooled analysis of RCT indicates a crude rate of ICD-unresponsive SCD of 5%. This may not cause alarm in an average practice, but it comprises about 30% of cardiac deaths. Meta-analyses of RCT show that ICD therapy is associated with a relative risk reduction of SCD of approximately 60%, far less than the greater than 90% efficacy that many expect. The suboptimal performance of ICD therapy accounts for the failure of some RCT to achieve statistically significant effects on survival. The number of patients with ICD-unresponsive SCD is highly correlated with the number of cardiac deaths among control patients as well as ICD recipients. Otherwise, no definite patterns have emerged that clearly distinguish this mode of demise from other modes of cardiac death. Retrospective post-hoc analyses have not revealed distinguishing characteristics of patients with ICD-unresponsive SCD with respect to clinical variables, pre-terminal symptoms or to the setting of the terminal event. Despite advanced storage capabilities of implanted devices, almost no information has become available from RCT regarding the terminal rhythm or the response of the ICD. These observations have implications for clinical management and research. Candidates for ICD implantation based on RCT should be accurately informed about the residual risk of SCD. Investigators seeking to identify populations likely to benefit from ICD therapy based on SCD incidence should recognize that a significant fraction may not respond to ICD therapy. Reducing the incidence of ICD-unresponsive SCD would substantially improve survival and cost-effectiveness related to ICD therapy. Close cooperation between clinicians, investigators and representatives of industry and government is urgently needed to develop strategies to identify patients prone to ICD-unresponsive SCD, to determine its mechanisms and to develop methods of prevention and treatment.

Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Patients with nonischemic dilated cardiomyopathy are at substantial risk for sudden death from cardiac causes. However, the value of prophylactic implantation of an implantable cardioverter-defibrillator (ICD) to prevent sudden death in such patients is unknown. METHODS: We enrolled 458 patients with nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less than 36 percent, and premature ventricular complexes or nonsustained ventricular tachycardia. A total of 229 patients were randomly assigned to receive standard medical therapy, and 229 to receive standard medical therapy plus a single-chamber ICD. RESULTS: Patients were followed for a mean (+/-SD) of 29.0+/-14.4 months. The mean left ventricular ejection fraction was 21 percent. The vast majority of patients were treated with angiotensin-converting-enzyme (ACE) inhibitors (86 percent) and beta-blockers (85 percent). There were 68 deaths: 28 in the ICD group, as compared with 40 in the standard-therapy group (hazard ratio, 0.65; 95 percent confidence interval, 0.40 to 1.06; P=0.08). The mortality rate at two years was 14.1 percent in the standard-therapy group (annual mortality rate, 7 percent) and 7.9 percent in the ICD group. There were 17 sudden deaths from arrhythmia: 3 in the ICD group, as compared with 14 in the standard-therapy group (hazard ratio, 0.20; 95 percent confidence interval, 0.06 to 0.71; P=0.006). CONCLUSIONS: In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause.

Sympathetic nervous system activity and ventricular tachyarrhythmias: recent advances.

Sympathetic nervous system activity (SNSA) is believed to participate in the genesis of ventricular tachyarrhythmias (VTA) but understanding has been impeded by the number and complexity of effects and the paucity of data from humans. New information from studies of genetic disorders, animal models, and spontaneous human arrhythmias indicates the importance of the temporal pattern of SNSA in arrhythmia development. The proarrhythmic effects of short-term elevations of SNSA are exemplified by genetic disorders and include enhancement of early and delayed afterdepolarizations and increased dispersion of repolarization. The role of long-term elevations of SNSA is suggested by animal models of enhanced SNSA signaling that results in apoptosis, hypertrophy, and fibrosis, and sympathetic nerve sprouting caused by infusion of nerve growth factor. Processes that overlap short- and long-term effects are suggested by changes in R-R interval variability (RRV) that precede VTA in patients by several hours. SNSA-mediated alterations in gene expression of ion channels may account for some intermediate-term effects. The propensity for VTA is highest when short-, intermediate, and long-term changes are superimposed. Because the proarrhythmic effects are related to the duration and intensity of SNSA, normal regulatory processes such as parasympathetic activity that inhibits SNSA, and oscillations that continuously vary the intensity of SNSA may provide vital antiarrhythmic protection that is lost in severe heart failure and other disorders. These observations may have therapeutic implications. The recommended use of beta-adrenergic receptor blockers to achieve a constant level of inhibition does not take into account the temporal patterns and regional heterogeneity of SNSA, the proarrhythmic effects of alpha-adrenergic receptor stimulation, or the potential proarrhythmic effects of beta-adrenergic receptor blockade. Further research is needed to determine if other approaches to SNSA modulation can enhance the antiarrhythmic effects.