Objectives This study sought to determine how exercise influences penetrance of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) among patients with desmosomal mutations. Background ...Although animal models and anecdotal evidence suggest that exercise is a risk factor for ARVD/C, there have been no systematic human studies. Methods Eighty-seven carriers (46 male; mean age, 44 ± 18 years) were interviewed about regular physical activity from 10 years of age. The relationship of exercise with sustained ventricular arrhythmia (ventricular tachycardia/ventricular fibrillation VT/VF), stage C heart failure (HF), and meeting diagnostic criteria for ARVD/C (2010 Revised Task Force Criteria TFC) was studied. Results Symptoms developed in endurance athletes (N = 56) at a younger age (30.1 ± 13.0 years vs. 40.6 ± 21.1 years, p = 0.05); they were more likely to meet TFC at last follow-up (82% vs. 35%, p < 0.001) and have a lower lifetime survival free of VT/VF (p = 0.013) and HF (p = 0.004). Compared with those who did the least exercise per year (lowest quartile) before presentation, those in the second (odds ratio OR: 6.64, p = 0.013), third (OR: 16.7, p = 0.001), and top (OR: 25.3, p < 0.0001) quartiles were increasingly likely to meet TFC. Among 61 individuals who did not present with VT/VF, the 13 subjects experiencing a first VT/VF event over a mean follow-up of 8.4 ± 6.7 years were all endurance athletes (p = 0.002). Survival from a first VT/VF event was lowest among those who exercised most (top quartile) both before (p = 0.036) and after (p = 0.005) clinical presentation. Among individuals in the top quartile, a reduction in exercise decreased VT/VF risk (p = 0.04). Conclusions Endurance exercise and frequent exercise increase the risk of VT/VF, HF, and ARVD/C in desmosomal mutation carriers. These findings support exercise restriction for these patients.
Objectives The purpose of this study was to provide a systematic multicenter survey on the incidence and causes of death occurring in the setting of or as a consequence of catheter ablation (CA) of ...atrial fibrillation (AF). Background CA of AF is considered to be generally safe. However, serious complications, including death, have been reported. Methods Using a retrospective case series, data relevant to the incidence and cause of intra- and post-procedural death occurring in patients undergoing CA of AF between 1995 and 2006 were collected from 162 of 546 identified centers worldwide. Results Thirty-two deaths (0.98 per 1,000 patients) were reported during 45,115 procedures in 32,569 patients. Causes of deaths included tamponade in 8 patients (1 later than 30 days), stroke in 5 patients (2 later than 30 days), atrioesophageal fistula in 5 patients, and massive pneumonia in 2 patients. Myocardial infarction, intractable torsades de pointes, septicemia, sudden respiratory arrest, extrapericardial pulmonary vein (PV) perforation, occlusion of both lateral PVs, hemothorax, and anaphylaxis were reported to be responsible for 1 death each, while asphyxia from tracheal compression secondary to subclavian hematoma, intracranial bleeding, acute respiratory distress syndrome, and esophageal perforation from an intraoperative transesophageal echocardiographic probe were causes of 1 late death each. Conclusions Death is a complication of CA of AF, occurring in 1 of 1,000 patients. Knowledge of possible precipitating causes is key to operators and needs to be considered during decision making with patients.
Abstract Classically, the 3 pillars of atrial fibrillation (AF) management have included anticoagulation for prevention of thromboembolism, rhythm control, and rate control. In both prevention and ...management of AF, a growing body of evidence supports an increased role for comprehensive cardiac risk factor modification (RFM), herein defined as management of traditional modifiable cardiac risk factors, weight loss, and exercise. In this narrative review, we summarize the evidence demonstrating the importance of each facet of RFM in AF prevention and therapy. Additionally, we review emerging data on the importance of weight loss and cardiovascular exercise in prevention and management of AF.
The reported complication rate of catheter ablation of atrial fibrillation (AF) varies.
Our goal was to assess temporal trends and the effect of both institutional and individual operators' ...experience on the incidence of complications.
All patients undergoing AF ablation at Johns Hopkins Hospital between February 2001 and December 2010 were prospectively enrolled in a database. Major complications were defined as those that were life-threatening, resulted in permanent harm, required intervention, or significantly prolonged hospitalization.
Fifty-six major complications occurred in 1190 procedures (4.7%). The majority of complications were vascular (18; 1.5%), followed by pericardial tamponade (13; 1.1%) and cerebrovascular accident (12; 1.1%). No cases of death or atrioesophageal fistula occurred. The overall complication rate decreased from 11.1% in 2002 to 1.6% in 2010 (P <.05). On univariate analysis, demographic and clinical factors associated with the increased risk of complications were CHADS(2) score of ≥2 (hazard ratio HR = 2.5; 95% confidence interval CI = 1.4-4.4; P = .002), female gender (HR = 2.0; 95% CI = 1.2-3.5; P = .014), and age (HR = 1.03; 95% CI = 1.0-1.1; P = .042). Gender and CHADS(2) score of ≥2 remained independent predictors of complication on multivariable analysis.
The complication rate of catheter ablation of AF decreased with increased institutional experience. Female gender and CHADS(2) score of ≥2 are significant independent risk factors for complications and should be considered when referring patients for AF ablation.
Abstract Objectives The aims of this study were to: 1) use a novel method of late gadolinium enhancement (LGE) quantification that uses normalized intensity measures to confirm the association ...between LGE extent and atrial fibrillation (AF) recurrence following ablation; and 2) examine the presence of interaction and effect modification between LGE and AF persistence. Background Recurrent AF after catheter ablation has been reported to associate with the baseline extent of left atrial LGE on cardiac magnetic resonance. Traditional methods for measurement of intensity lack an objective threshold for quantification and interpatient comparisons of LGE. Methods The cohort included 165 participants (mean age 60.0 ± 10.2 years, 77% men, 57% with persistent AF) who underwent initial AF ablation. The association of baseline LGE extent with AF recurrence was examined using multivariable Cox proportional hazards models. Multiplicative and additive interactions between AF type and LGE extent were examined. Results During 10.2 ± 5.7 months of follow-up, 63 patients (38.2%) experienced AF recurrence. Baseline LGE extent was independently associated with AF recurrence after adjusting for confounders (hazard ratio: 1.5 per 10% increased LGE; p < 0.001). The hazard ratio for AF recurrence progressively increased as a function of LGE. The magnitude of association between LGE >35% and AF recurrence was greater among patients with persistent AF (hazard ratio: 6.5 p = 0.001 vs. 3.6 p = 0.001); however, there was no evidence for statistical interaction. Conclusions Regardless of AF persistence at baseline, participants with LGE ≤35% have favorable outcomes, whereas those with LGE >35% have a higher rate of AF recurrence in the first year after ablation. These findings suggest a role for: 1) patient selection for AF ablation using LGE extent; and 2) substrate modification in addition to pulmonary vein isolation in patients with LGE extent exceeding 35% of left atrial myocardium.
Objectives The aims of this study were to determine the spectrum and prevalence of “background genetic noise” in the arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) genetic test and ...to determine genetic associations that can guide the interpretation of a positive test result. Background ARVC is a potentially lethal genetic cardiovascular disorder characterized by myocyte loss and fibrofatty tissue replacement of the right ventricle. Genetic variation among the ARVC susceptibility genes has not been systematically examined, and little is known about the background noise associated with the ARVC genetic test. Methods Using direct deoxyribonucleic acid sequencing, the coding exons/splice junctions of PKP2 , DSP , DSG2 , DSC2 , and TMEM43 were genotyped for 93 probands diagnosed with ARVC from the Netherlands and 427 ostensibly healthy controls of various ethnicities. Eighty-two additional ARVC cases were obtained from published reports, and additional mutations were included from the ARVD/C Genetic Variants Database. Results The overall yield of mutations among ARVC cases was 58% versus 16% in controls. Radical mutations were hosted by 0.5% of control individuals versus 43% of ARVC cases, while 16% of controls hosted missense mutations versus a similar 21% of ARVC cases. Relative to controls, mutations in cases occurred more frequently in non-Caucasians, localized to the N-terminal regions of DSP and DSG2, and localized to highly conserved residues within PKP2 and DSG2. Conclusions This study is the first to comprehensively evaluate genetic variation in healthy controls for the ARVC susceptibility genes. Radical mutations are high-probability ARVC-associated mutations, whereas rare missense mutations should be interpreted in the context of race and ethnicity, mutation location, and sequence conservation.
Objectives The aim of this study was to define the genetic basis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Background Arrhythmogenic right ventricular cardiomyopathy, characterized ...by right ventricular fibrofatty replacement and arrhythmias, causes sudden death. Autosomal dominant inheritance, reduced penetrance, and 7 desmosome-encoding causative genes are known. The basis of low penetrance is poorly understood. Methods Arrhythmogenic right ventricular cardiomyopathy probands and family members were enrolled, blood was obtained, lymphoblastoid cell lines were immortalized, deoxyribonucleic acid was extracted, polymerase chain reaction (PCR) amplification of desmosome-encoding genes was performed, PCR products were sequenced, and diseased tissue samples were studied for intercellular junction protein distribution with confocal immunofluorescence microscopy and antibodies against key proteins. Results We identified 21 variants in plakophilin-2 ( PKP2 ) in 38 of 198 probands (19%), including missense, nonsense, splice site, and deletion/insertion mutations. Pedigrees showed wide intra-familial variability (severe early-onset disease to asymptomatic individuals). In 9 of 38 probands, PKP2 variants were identified that were encoded in trans (compound heterozygosity). The 38 probands hosting PKP2 variants were screened for other desmosomal genes mutations; second variants (digenic heterozygosity) were identified in 16 of 38 subjects with PKP2 variants (42%), including desmoplakin ( DSP ) (n = 6), desmoglein-2 ( DSG2 ) (n = 5), plakophilin-4 ( PKP4 ) (n = 1), and desmocollin-2 ( DSC2 ) (n = 1). Heterozygous mutations in non -PKP 2 desmosomal genes occurred in 14 of 198 subjects (7%), including DSP (n = 4), DSG2 (n = 5), DSC2 (n = 3), and junctional plakoglobin ( JUP ) (n = 2). All variants occurred in conserved regions; none was identified in 700 ethnic-matched control subjects. Immunohistochemical analysis demonstrated abnormalities of protein architecture. Conclusions These data suggest that the genetic basis of ARVC includes reduced penetrance with compound and digenic heterozygosity. Disturbed junctional cytoarchitecture in subjects with desmosomal mutations confirms that ARVC is a disease of the desmosome and cell junction.
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