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Common atrial fibrillation risk alleles at 4q25 predict recurrence after catheter-based atrial fibrillation ablation

BACKGROUND Common single nucleotide polymorphisms at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical atrial fibrillation (AF). Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5%-30% of AF cases. OBJECTIVE To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. METHODS Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years; 71% men; 89% typical AF) between 2004 and 2011. The primary end point was time to recurrence of any nonsinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF). RESULTS Two-hundred atrial tachycardia, atrial flutter, or AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76; 95% confidence interval [CI] 0.6-0.95; P = .016) compared with wild type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio 0.79; 95% CI 0.62-0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio 0.61; 95% CI 0.37-1.0; P = .037). CONCLUSIONS Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of patients with predominately typical AF. Our findings suggest that the rs2200733 polymorphism may hold promise as an objectively measured patient characteristic that can be used as a clinical tool for selecting patients for AF ablation.

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.

Relation of morbid obesity and female gender to risk of procedural complications in patients undergoing atrial fibrillation ablation.

Obese patients with atrial fibrillation (AF) are frequently treated with AF ablation. We sought to examine whether a body mass index (BMI) threshold exists beyond which the odds of experiencing a complication from AF ablation increases. All patients enrolled in the Vanderbilt AF Registry who underwent catheter-based AF ablation from May 1999 to February 2012 were included. Major complications were recorded. Morbid obesity was defined as a BMI >40 kg/m(2) and examined in multivariable analysis. A total of 35 complications (6.8%) occurred in 512 ablations. Morbidly obese patients experienced a greater rate of complications (6 of 42, 14.3%) than the nonmorbidly obese (29 of 470, 6.2%; p = 0.046). Using a discrete BMI cutoff, the odds of complications increased 3.1-fold in those with morbid obesity (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.1 to 8.4, p = 0.03) and 2.1-fold for female gender (OR 2.1, 95% CI 1.04 to 4.38, p = 0.04). With BMI as a continuous variable, the odds of complications increased by 5% per 1 unit increase in BMI (OR 1.05, 95% CI 1.0 to 1.11, p = 0.05), and the increase for female gender was 2.2-fold (OR 2.2, 95% CI 1.1 to 4.6, p = 0.03). In conclusion, morbid obesity represents a BMI threshold above which the odds of complications with AF ablation increase significantly. The increase in complications appears to be driven primarily by events in women, suggesting that morbidly obese women are a special population when considering AF ablation.

Cardiovascular Effects of Noncardiovascular Drugs

Most drugs are not used to treat heart disease. However, such “noncardiovascular” medications can often have cardiovascular effects. In this review, we discuss some cardiovascular manifestations of drugs used for noncardiovascular indications. We discuss these in the text according to the manifestations with which patients present; selected drugs are listed in Table 1 by their indication/drug class. The same medication may appear in different sections, reflecting the varied cardiovascular consequences of a particular drug. We also discuss cardiovascular effects of noncardiovascular drugs that arise indirectly from drug interactions that cause an increase or decrease in the concentration of a cardiovascular drug. View this table: Table 1. Selected Noncardiovascular Drugs With Cardiovascular Effects by Indication/Drug Class ### Atrial Fibrillation Most reports of atrial fibrillation (AF) induced by noncardiovascular drugs are case reports, and because AF is so common, it is difficult to determine whether the association is causal or incidental. The ability to reproduce AF with drug rechallenges supports causality, as does a mechanistic rationale. Table 1 lists drugs with a well-established association with AF. After numerous case reports of the onset of AF after pulse methylprednisolone, van der Hooft et al1 conducted a nested case-control study in the Rotterdam study that comprised almost 8000 adults. They found that high-dose corticosteroid use (≥7.5 mg prednisone equivalents) was associated with a significantly increased risk of new-onset AF (odds ratio [OR]=6.1; 95% confidence interval [CI], 3.9 to 9.4) but that low-dose corticosteroid use was not associated with AF (OR=1.4; 95% CI, 0.7 to 2.8). This increase in AF risk was seen with all indications for high-dose corticosteroids. It has been postulated that high-dose corticosteroids might mediate cellular potassium efflux and that this may in turn predispose to arrhythmia.2 There is concern that bisphosphonates may increase the risk of serious AF (AF resulting in hospitalization or disability or …

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.

Arrhythmogenic Munchausen syndrome culminating in caffeine-induced ventricular tachycardia.

We report a patient with numerous abnormal electrocardiograms (ECGs) in both inpatient and outpatient settings. Our patient both simulated and stimulated her arrhythmias with an ECG rhythm generator and intentional caffeine intoxication. To our knowledge, this is the first report of caffeine overdose for arrhythmogenesis.

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