Juan Carlos Estrada

Variation in the 4q25 Chromosomal Locus Predicts Atrial Fibrillation after Coronary Artery Bypass Graft Surgery

Background— Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery. Methods and Results— Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0×10−4 to 3.4×10−6). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. Conclusions— In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons.

Clinical use of and future perspectives on antiarrhythmic drugs.

Cardiac arrhythmias are associated with significant morbidity and mortality. Antiarrhythmic drug therapy was traditionally the mainstay of arrhythmia treatment; however, the limited efficacy and proarrhythmic potential of conventional antiarrhythmic drugs has generated interest in new approaches to the treatment of arrhythmias. Over the last decade, there has been improved characterization of the molecular pathways that culminate in arrhythmias. By analyzing mechanisms that increase susceptibility to arrhythmias in individuals with genetic syndromes, it might be possible to not only improve current therapies but also to develop novel approaches to treat and prevent common arrhythmias.

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.

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.

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.

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

USE OF DABIGATRAN ETEXILATE TO PREVENT STROKE AND THROMBOEMBOLISM IN PATIENTS UNDERGOING LEFT ATRIAL CATHETER ABLATION PROCEDURES FOR PAROXYSMAL OR PERSISTENT (NON-PERMANENT) ATRIAL FIBRILLATION AND LEFT ATRIAL FLUTTER

Background: Optimal dosing of dabigatran in patients undergoing left atrial (LA) ablation procedures for atrial fibrillation (AF) or LA flutter is unknown. Retrospective data suggest increased bleeding risk with continuous dabigatran, and increased embolic risk when interrupted. We sought to confirm

Twinkling artifact associated with guidewire placement.

July 2015 • Volume 121 • Number 1 www.anesthesia-analgesia.org 69 A 68-year-old man with atrial fibrillation presented for elective pulmonary vein isolation via cryoablation. He underwent general anesthesia and transesophageal echocardiography probe placement (IE33 X7-2t xMATRIX array probe connected to a Philips CX50 ultrasound system, Philips Healthcare, Andover, MA) for assessment of left atrial appendage thrombus and guidance of interatrial septal puncture for placement of a left atrial ablation catheter. While assessing the interatrial septum for a patent foramen ovale using color-flow Doppler, the electrophysiologist passed a superstiff 0.032-inch guidewire (St. Jude Medical, St. Paul, MN) from the right femoral vein through the right atrium into the superior vena cava to position the transseptal guiding introducer (St. Jude Medical). During this time, the echocardiographer identified the sudden appearance of a high-velocity, left-to-right flow pattern (Fig. 1; Supplemental Digital Content, Videos 1 and 2, http:// links.lww.com/AA/B84, http://links.lww.com/AA/B85). This flow seemed to originate from the interatrial septum, although a patent foramen ovale by color-flow Doppler had not been previously identified. Further interrogation of the interatrial septum in different echocardiographic planes revealed no defect but intermittent identification of a twinkling artifact. The twinkling artifact demonstrated brilliant rapid alternating hues with a flame-like appearance, just distal to the location of the guidewire. Increasing the Nyquist limit did not appear to significantly diminish this artifact. Removing the guidewire before positioning the transseptal guiding introducer in the fossa ovalis resulted in the disappearance of this artifact. An uneventful atrial septal puncture was performed and the introducer advanced into the left atrium.