Genetic mechanisms underlying arrhythmogenic mitral valve prolapse: Current and future perspectives.

Mitral valve prolapse (MVP) is a heart valve disease that is often familial, affecting 2%-3% of the general population. MVP with or without mitral regurgitation can be associated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). Research on familial MVP has specifically focused on genetic factors, which may explain the heritable component of the disease estimated to be present in 20%-35%. Furthermore, the structural and electrophysiological substrates underlying SCD/ventricular arrhythmia risk in MVP have been studied postmortem and in the electrophysiology laboratory, respectively. Understanding how familial MVP and rhythm disorders are related may help patients with MVP by individualizing risk and working to develop effective management strategies. This contemporary, state-of-the-art, expert review focuses on genetic factors and familial components that underlie MVP and arrhythmia and encapsulates clinical, genetic, and electrophysiological issues that should be the objectives of future research.

Implantable loop recorder for augmenting detection of new-onset atrial fibrillation after typical atrial flutter ablation.

BACKGROUND: Patients with typical atrial flutter (AFL) undergoing successful cavotricuspid isthmus ablation remain at risk for future development of new-onset atrial fibrillation (AF). Conventional monitoring (CM) techniques have shown AF incidence rates of 18%-50% in these patients. OBJECTIVES: To evaluate whether continuous monitoring using implantable loop recorders (ILRs) would enhance AF detection in this patient population. METHODS: Veteran patients undergoing AFL ablation between 2002 and 2019 who completed at least 6 months of follow-up after the ablation procedure were included. We compared new-onset AF detection between those who underwent CM and those who received ILRs immediately following AFL ablation. RESULTS: A total of 217 patients (age: 66 ± 9 years; all male) participated. CM was used in 172 (79%) and ILR in 45 (21%) patients. Median follow-up duration after ablation was 4.1 years. Seventy-nine patients (36%) developed new-onset AF, which was detected by CM in 51 and ILR in 28 (30% vs 62%, respectively, P < .001). AF detection occurred at 7.7 months (IQR: 4.7-17.5) after AFL ablation in the ILR group vs 41 months (IQR: 23-72) in the CM group (P < .001). Eleven patients (5%) experienced cerebrovascular events (all in the CM group) and only 4 of these patients (36%) were on long-term anticoagulation. CONCLUSION: Patients undergoing AFL ablation remain at an increased risk of developing new-onset AF, which is detected sooner and more frequently by ILR than by CM. Improving AF detection may allow optimization of rhythm management strategies and anticoagulation in this patient population.

Ischemic ventricular tachycardia: Multimodality imaging in precision ablation guidance.

Radiofrequency ablation is commonly performed in the management of incessant ventricular tachycardias. Pre-procedural planning using different imaging modalities including cardiac computed tomography and cardiac magnetic resonance plays an integral role in understanding the anatomy and potential origin of the arrhythmias to guide successful targeted ablation.

Advancements in Imaging for Atrial Fibrillation Ablation: Is There a Potential to Improve Procedural Outcomes?

Since the introduction of atrial fibrillation (AF) ablation in the 1990s, the procedure has continuously evolved, with gradual improvements in outcomes and safety. Recent technological advancements include the introduction of contact force catheters and high-resolution electroanatomical mapping systems, while imaging modalities including transesophageal echocardiography and fluoroscopy have become integral parts of AF ablation procedures. Further, intraprocedural intracardiac echocardiography and the integration of cardiac magnetic resonance and computed tomography images with electroanatomical mapping have shown promise to improve procedural outcomes by reducing radiation exposure and procedural times. However, available data on procedural utility and the reduction in AF recurrence rates associated with these modalities are mixed. This review therefore aims to discuss the current common imaging modalities used in AF ablation and their potential impact on outcomes. In particular, imaging is discussed with respect to the important information it offers before, during, and after the procedure. Perspectives on the future of imaging in AF ablation are also shared.

Cardiac Magnetic Resonance as a Tool to Assess Dyssynchrony.

Cardiac resynchronization therapy (CRT) improves cardiac mechanics and quality of life in many patients with evidence of electromechanical cardiac dyssynchrony. However, up to 30% of patients receiving CRT do not respond to therapy. The mediator for poor response likely varies among patients; however, careful evaluation of mechanical dyssynchrony may inform management strategies. In this article, some of the methods and supporting evidence for dyssynchrony assessment with MRI as a predictor for CRT response are presented. The case is made for pre-implant assessment with MRI because of its ability to characterize scar, coronary venous distribution, and regional strain patterns.

Reversal of Pacing-Induced Cardiomyopathy Following Cardiac Resynchronization Therapy.

OBJECTIVES: This study sought to determine the extent, time course, and predictors of improvement following cardiac resynchronization therapy (CRT) upgrade among pacing-induced cardiomyopathy (PICM) patients. BACKGROUND: PICM is an important cause of heart failure in patients exposed to frequent right ventricular (RV) pacing. CRT may reverse PICM. METHODS: We retrospectively studied 1,279 consecutive patients undergoing CRT procedures between 2003 and 2016. Patients undergoing CRT upgrade from a dual-chamber or single-chamber ventricular pacemaker for PICM were included. PICM was defined as decrease of ≥10% in left ventricular ejection fraction (LVEF), resulting in LVEF <50% among patients experiencing ≥20% RV pacing without an alternative cause of cardiomyopathy. Severe PICM was defined as pre-upgrade LVEF ≤35%. Clinical, electrocardiographic, and echocardiographic characteristics associated with both the extent of LVEF recovery and with post-upgrade LVEF of >35% among those with severe PICM were identified. RESULTS: Of 69 PICM patients, LVEF improved from 29.3% to 45.3% over a median 7.0 months. Of 54 patients with severe PICM, 39 (72.2%) improved to LVEF >35% over a median 7.0 months. Most improvement occurred within the first 3 months, although improvement continued over the remainder of the first year. In linear regression, narrower native QRS was associated with greater LVEF improvement following CRT upgrade (+2.00% per 10-ms decrease; p = 0.05). CONCLUSIONS: CRT is highly efficacious in reversing PICM, with 72% of severe PICM patients achieving LVEF >35% and most of the improvement occurring within 1 year. These data support initial upgrade to a CRT pacemaker with consideration of further upgrade to CRT defibrillator after 1 year if LVEF remains ≤35%.

Analysis of the interactions between the C-terminal cytoplasmic domains of KCNQ1 and KCNE1 channel subunits.

Ion channel subunits encoded by KCNQ1 and KCNE1 produce the slowly activating K+ current (IKs) that plays a central role in myocardial repolarization. The KCNQ1 alpha-subunit and the KCNE1 beta-subunit assemble with their membrane-spanning segments interacting, resulting in transformation of channel activation kinetics. We recently reported a functional interaction involving C-terminal portions of the two subunits with ensuing regulation of channel deactivation. In the present study, we provide evidence characterizing a physical interaction between the KCNQ1-CT (KCNE1 C-terminus) and the KCNE1-CT (KCNE1 C-terminus). When expressed in cultured cells, the KCNE1-CT co-localized with KCNQ1, co-immunoprecipitated with KCNQ1 and perturbed deactivation kinetics of the KCNQ1 currents. Purified KCNQ1-CT and KCNE1-CT physically interacted in pull-down experiments, indicating a direct association. Deletion analysis of KCNQ1-CT indicated that the KCNE1-CT binds to a KCNQ1 region just after the last transmembrane segment, but N-terminal to the tetramerization domain. SPR (surface plasmon resonance) corroborated the pull-down results, showing that the most proximal region (KCNQ1 amino acids 349-438) contributed most to the bimolecular interaction with a dissociation constant of approximately 4 microM. LQT (long QT) mutants of the KCNE1-CT, D76N and W87F, retained binding to the KCNQ1-CT with comparable affinity, indicating that these disease-causing mutations do not alter channel behaviour by disruption of the association. Several LQT mutations involving the KCNQ1-CT, however, showed various effects on KCNQ1/KCNE1 association. Our results indicate that the KCNQ1-CT and the KCNE1-CT comprise an independent interaction domain that may play a role in IKs channel regulation that is potentially affected in some LQTS (LQT syndrome) mutations.