Background-We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF). We also have reported that SCN1B is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel ␤-subunit genes SCN1B-SCN4B contribute to AF susceptibility. Methods and Results-Screening for mutations in the 4 ␤-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant ␤-subunits on SCN5A mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 mutation carriers, the ECGs showed saddleback-type ST-segment elevation in the right precordial leads. Transcripts encoding both SCN1B and SCN2B were detected in human atrium and ventricle. In heterologous expression studies using Chinese hamster ovary cells, the mutant ␤1-or ␤2-subunits reduced SCN5A-mediated current and altered channel gating compared with coexpression of wild-type subunits. Conclusions-Loss of function mutations in sodium channel ␤-subunits were identified in patients with AF and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility. (Circ Arrhythmia Electrophysiol. 2009;2:268-275.)

Objective To explore gender differences in real-world outcomes after catheter ablation of atrial fibrillation (AF). Background Compared to men, women with AF have greater thromboembolic risk and tend to be more symptomatic. Catheter ablation is generally more effective than antiarrhythmic drug therapy alone. However, there is limited data on the influence of gender on AF ablation outcomes. Methods We analyzed medical claims of 45 million United States patients enrolled in a variety of employee-sponsored and fee-for-service plans. We identified patients who underwent an AF ablation from 2007 to 2011 and evaluated 30-day safety and one-year effectiveness outcomes. Results Of the 21,091 patients who underwent an AF ablation, 7,460 (29%) were female. Women, compared to men, were older (62±11 vs. 58±11 years), had higher CHADS2 (1.2±1.1 vs. 1.0±1.0), higher CHA2DS2-VASc (2.9±1.5 vs. 1.6±1.4), and higher Charlson comorbidity index scores (1.2±1.3 vs. 1.0±1.2)(p<0.001 for all). Following ablation, women had higher risk of 30-day complications of hemorrhage (2.7 vs. 2.0%,p<0.001) and tamponade (3.8 vs. 2.9%,p<0.001). In multivariable analyses, women were more likely to have a re-hospitalization for AF (adjusted HR 1.12,p=0.009), but less likely to have repeat AF ablation (adjusted HR 0.92,p=0.04) or cardioversion (adjusted HR 0.75,p<0.001). Conclusion Women have increased hospitalization rates after AF ablation and are more likely to have a procedural complication. Despite the higher rate of hospital admissions for AF after ablation, women were less likely to undergo repeat ablation or cardioversion. These data call for greater examination of barriers and facilitators to sustain rhythm control strategies in women.

Objectives This study aimed to evaluate the cost-effectiveness of the CardioMems device in patients with chronic heart failure. Background The CardioMems device, an implantable pulmonary artery pressure monitor, was shown to reduce heart failure hospitalizations and improve quality of life in the CHAMPION trial. Methods We developed a Markov model to determine the hospitalization, survival, quality of life, cost, and incremental cost-effectiveness ratio of CardioMems implantation compared with usual care among a CHAMPION trial cohort of heart failure patients. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare reimbursement. We performed subgroup analyses of preserved and reduced ejection fraction and an exploratory analysis in a lower-risk cohort based on the CHARM trials. Results CardioMems reduced lifetime hospitalizations (2.18 versus 3.12), increased QALYs (2.74 versus 2.46) and increased costs ($176,648 versus $156,569), yielding a cost of $71,462 per QALY gained and $48,054 per life-year gained. The cost per QALY gained was $82,301 in patients with reduced ejection fraction and $47,768 in those with preserved ejection fraction. In the lower-risk CHARM cohort, the device would need to reduce heart failure hospitalizations by 41% in order to cost less than $100,000 per QALY gained. The cost-effectiveness was most sensitive to the device’s durability. Conclusion In populations similar to the CHAMPION trial, the CardioMems device is cost-effective if the trial effectiveness is sustained over long periods. Post-marketing surveillance data on durability will further clarify its value.

Objective To evaluate warfarin prescription, quality of International Normalized Ratio (INR) monitoring, and of INR control in patients with atrial fibrillation (AF) and chronic kidney disease. Methods We performed a retrospective cohort study of patients with newly diagnosed AF in the Veterans Administration (VA) health care system. We evaluated anticoagulation prescription, INR monitoring intensity, and time in and outside INR therapeutic range (TTR) stratified by chronic kidney disease severity (CKD). Results Of 123,188 patients with newly diagnosed AF, use of warfarin decreased with increasing severity of CKD (57.2% to 46.4%), although it was higher among patients on dialysis (62.3%). Although INR monitoring intensity was similar across CKD strata, the proportion with TTR ≥ 60% decreased with CKD severity, with only 21% of patients on dialysis achieving TTR ≥ 60%. After multivariate adjustment, the magnitude of TTR reduction increased with CKD severity. Patients on dialysis had the highest time markedly out of range with INR <1.5 or INR >3.5 (30%); 12% of INR time was > 3.5, and low TTR persisted for up to three years. Conclusions There is a wide variation in anticoagulation prescription based on CKD severity. Patients with moderate to severe CKD, including dialysis, have substantially reduced TTR, despite comparable INR monitoring intensity. These findings have implications for more intensive warfarin management strategies in CKD or alternative therapies such as direct oral anticoagulants.