Jay A. Montgomery

Common Genetic Variants and Response to Atrial Fibrillation Ablation

Background—Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results—Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1–1.6]; P=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions—Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.

Cardiac sympathectomy for the management of ventricular arrhythmias refractory to catheter ablation

BACKGROUND Catheter ablation is now a mainstay of therapy for ventricular arrhythmias (VAs). However, there are scenarios where either physiological or anatomical factors make ablation less likely to be successful. OBJECTIVE The purpose of this study was to demonstrate that cardiac sympathetic denervation (CSD) may be an alternate therapy for patients with difficult-to-ablate VAs. METHODS We identified all patients referred for CSD at a single center for indications other than long QT syndrome and catecholaminergic polymorphic ventricular tachycardia who had failed catheter ablation. Medical records were reviewed for medical history, procedural details, and follow-up. RESULTS Seven cases of CSD were identified in patients who had failed prior catheter ablation or had disease not amenable to ablation. All patients had VAs refractory to antiarrhythmic drugs, with a median arrhythmia burden of 1 episode of sustained VA per month. There were no acute complications of sympathectomy. One of 7 patients (14%) underwent heart transplant. No patient had sustained VA after sympathectomy at a median follow-up of 7 months. CONCLUSION Because of anatomical and physiological constraints, many VAs remain refractory to catheter ablation and remain a significant challenge for the electrophysiologist. While CSD has been described as a therapy for long QT syndrome and catecholaminergic polymorphic ventricular tachycardia, data regarding its use in other cardiac conditions are sparse. This series illustrates that CSD may be a viable treatment option for patients with a variety of etiologies of VAs.

Feasibility of Defibrillation and Pacing without Transvenous Leads In A Combined Micra and S-Icd System Following Lead Extraction

A 70-year-old female with permanent atrial fibrillation and complete heart block with a permanent pacemaker placed in 2007, later upgraded to dual-chamber implantable cardioverter defibrillator (ICD) after a ventricular fibrillation arrest in 2012, was referred for lead extraction due to DF-4 Sprint Quattro ICD lead fracture. She had increasing heart failure symptoms with left ventricular ejection fraction of 50%, QRS duration 195 ms, and severe tricuspid regurgitation that by echocardiogram was potentially related to tethering of two leads to the tricuspid valve. Laser-assisted lead extraction was performed of the entire ICD system with temporary pacing support. A MICRA transcatheter pacemaker was then placed in the septum (Medtronic, Minneapolis, MN, USA), followed immediately by placement of a fully subcutaneous ICD (S-ICD) (Boston Scientific, Natick, MA, USA). (See Fig. 1) Notably, the patient passed S-ICD screening during continuous pacing through the MICRA transcatheter pacemaker in two of three vectors, while supine (successful

Measurement of diffuse ventricular fibrosis with myocardial T1 in patients with atrial fibrillation

Atrial fibrillation (AF) is associated with cardiac fibrosis, which can now be measured noninvasively using T1‐mapping with cardiac magnetic resonance imaging (CMRI). This study aimed to assess the impact of AF on ventricular T1 at the time of CMRI.

In‐hospital and one year outcomes with drug‐eluting versus bare metal stents in large native coronary arteries: A report from the evaluation of drug‐eluting stents and ischemic events registry

We sought to compare the clinical outcomes after perctuaneous coronary revascularization of large coronary arteries using drug‐eluting (DES) or bare‐metal (BMS) stents.

Non-pulmonary vein mediated atrial fibrillation: A novel sub-phenotype

Background Atrial fibrillation (AF) is a mechanistically heterogeneous disorder, and the ability to identify sub-phenotypes (“endophenotypes”) of AF would assist in the delivery of personalized medicine. We used the clinical response to pulmonary vein isolation (PVI) to identify a sub-group of patients with non-PV mediated AF and sought to define the clinical associations. Methods Subjects enrolled in the Vanderbilt AF Ablation Registry who underwent a repeat AF ablation due to arrhythmia recurrence were analyzed on the basis of PV reconnection. Subjects who had no PV reconnection were defined as “non-PV mediated AF”. A comparison group of subjects were identified who had AF that was treated with PVI-only and experienced no arrhythmia recurrence >12 months. They were considered a group enriched for “PV-mediated AF”. Univariate and multivariable binary logistic regression analysis was performed to investigate clinical associations between the PV and non-PV mediated AF groups. Results Two hundred and twenty nine subjects underwent repeat AF ablation and thirty three (14%) had no PV reconnection. They were compared with 91 subjects identified as having PV-mediated AF. Subjects with non-PV mediated AF were older (64 years [IQR 60,71] vs. 60 [52,67], P = 0.01), more likely to have non-paroxysmal AF (82% [N = 27] vs. 35% [N = 32], P<0.001), and had a larger left atrium (LA) (4.2cm [3.6,4.8] vs. 4.0 [3.3,4.4], P = 0.04). In univariate analysis, age (per decade: OR 1.56 [95% CI: 1.04 to 2.33], P = 0.03), LA size (per cm: OR 1.8 [1.06 to 3.21], P = 0.03) and non-paroxysmal AF (OR 8.3 [3.10 to 22.19], P<0.001) were all significantly associated with non-PV mediated AF. However, in multivariable analysis only non-paroxysmal AF was independently associated with non-PV mediated AF (OR 7.47 [95% CI 2.62 to 21.29], P<0.001), when adjusted for age (per decade: OR 1.25 [0.81 to 1.94], P = 0.31), male gender (OR 0.48 [0.18 to 1.28], P = 0.14), and LA size (per 1cm: 1.24 [0.65 to 2.33], P = 0.52). Conclusions Non-paroxysmal AF was the only clinical variable found to be independently associated with non-PV mediated AF. We demonstrated that analysis of AF ablation outcomes data can serve as a tool to successfully identify a sub-phenotype of subjects who have non-PV mediated AF. Clinical trial registration ClinicalTrials.gov ID # NCT02404415.

Apparent Failure to Sense during Temporary Pacing with a Permanent Pulse Generator

An 84-year-old woman with a history of atrial fibrillation, sinus node dysfunction, bileaflet mechanical mitral valve after endocarditis following a dental procedure, and ventricular fibrillation arrest with subsequent dual-chamber implantable cardioverter-defibrillator (ICD) placement in 2006 was transferred to our institution with a device pocket infection after an ICD generator change. The ICD generator was removed and all leads were extracted without complication. Because of underlying sinus bradycardia, a permanent pacemaker lead was implanted in the right atrium via the internal jugular vein and connected to a resterilized Medtronic InSync III Model 8042 cardiac resynchronization therapy (CRT) pacemaker generator (Medtronic Inc, Minneapolis, MN, USA) affixed to the external chest wall. The generator was programmed to AAI with a lower rate limit (LRL) of 60 beats/min and an atrial high rate (AHR) detection of 180 beats/min. Several days later, the arrhythmia service was asked to reassess the pacemaker system for malfunction when an electrocardiogram (ECG) showed what appeared to be atrial failure to sense and capture (Fig. 1). The ECG revealed atrial tachycardia with variable conduction to the ventricle as well as two premature ventricular complexes. Pacing spikes were seen marching through the ECG

Pulmonary Vein Sleeve Length and Association With Body Mass Index and Sex in Atrial Fibrillation

The pulmonary vein (PV) sleeves are extensions of left atrial tissue that cover the proximal surface of the PV adventitia. Despite the importance of the PV sleeves for atrial fibrillation (AF) pathogenesis and as a target of therapy, surprisingly little is known about the variability in their size

Association of Body Mass Index With Intracardiac Left Atrial Voltage in Patients With Atrial Fibrillation

Obesity is a global epidemic and the strongest clinical predictor for development of atrial fibrillation (AF) [(1)][1]. Obesity-related AF is emerging as a unique subgroup for which specific therapeutic strategies are being successfully developed [(2)][2]. Obesity contributes to a complex atrial

Extraction of looped transvenous pacing leads to reduce tricuspid regurgitation: MONTGOMERY et al.

Transvenous leads are a known source of iatrogenic tricuspid regurgitation. It is commonly held that extraction of chronic pacing and defibrillator leads will not reduce this, due to the inevitable trauma to the valve associated with the procedure. We demonstrate three cases of clinically significant reductions in tricuspid regurgitation after extraction of leads that were looped across the tricuspid valve.