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Background Heart failure (HF) and atrial fibrillation (AF) often coexist; yet, outcomes of ablation in patients with AF and concomitant HF are limited. This analysis assessed outcomes of cryoablation in patients with AF and HF. Methods and Results The Cryo AF Global Registry is a prospective, multicenter registry of patients with AF who were treated with cryoballoon ablation according to routine practice at 56 sites in 26 countries. Patients with baseline New York Heart Association class I to III (HF cohort) were compared with patients without HF. Freedom from atrial arrhythmia recurrence ≥30 seconds, safety, and health care utilization over 12‐month follow‐up were analyzed. A total of 1303 patients (318 HF) were included. Patients with HF commonly had preserved left ventricular ejection fraction (81.6%), were more often women (45.6% versus 33.6%) with persistent AF (25.8% versus 14.3%), and had a larger left atrial diameter (4.4±0.9 versus 4.0±0.7 cm). Serious procedure‐related complications occurred in 4.1% of patients with HF and 2.6% of patients without HF (P=0.188). Freedom from atrial arrhythmia recurrence was not different between cohorts with either paroxysmal AF (84.2% [95% CI, 78.6–88.4] versus 86.8% [95% CI, 84.2–89.0]) or persistent AF (69.6% [95% CI, 58.1–78.5] versus 71.8% [95% CI, 63.2–78.7]) (P=0.319). After ablation, a reduction in AF‐related symptoms and antiarrhythmic drug use was observed in both cohorts (HF and no‐HF), and freedom from repeat ablation was not different between cohorts. Persistent AF and HF predicted a post‐ablation cardiovascular rehospitalization (P=0.032 and P=0.001, respectively). Conclusions Cryoablation to treat patients with AF is similarly effective at 12 months in patients with and without HF. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02752737.

BackgroundPopulation‐based studies suggest that genetic factors contribute to sudden cardiac death (SCD). Methods and ResultsIn the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy‐arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single‐nucleotide polymorphisms (SNPs) in 3 genes coding G‐protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter‐defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, a community‐based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11‐1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18‐2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26‐1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05‐1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10‐2.13]) genetic models. ConclusionsGNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community‐based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00478933.