Continuous daily assessment of multiple sclerosis disability using remote step count monitoring.

Disability measures in multiple sclerosis (MS) rely heavily on ambulatory function, and current metrics fail to capture potentially important variability in walking behavior. We sought to determine whether remote step count monitoring using a consumer-friendly accelerometer (Fitbit Flex) can enhance MS disability assessment. 99 adults with relapsing or progressive MS able to walk ≥2-min were prospectively recruited. At 4 weeks, study retention was 97% and median Fitbit use was 97% of days. Substudy validation resulted in high interclass correlations between Fitbit, ActiGraph and manual step count tally during a 2-minute walk test, and between Fitbit and ActiGraph (ICC = 0.76) during 7-day home monitoring. Over 4 weeks of continuous monitoring, daily steps were lower in progressive versus relapsing MS (mean difference 2546 steps, p < 0.01). Lower average daily step count was associated with greater disability on the Expanded Disability Status Scale (EDSS) (p < 0.001). Within each EDSS category, substantial variability in step count was apparent (i.e., EDSS = 6.0 range 1097-7152). Step count demonstrated moderate-strong correlations with other walking measures. Lower average daily step count is associated with greater MS disability and captures important variability in real-world walking activity otherwise masked by standard disability scales, including the EDSS. These results support remote step count monitoring as an exploratory outcome in MS trials.

Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Statin use is associated with lower risk of atrial fibrillation in women with coronary disease: the HERS trial.

OBJECTIVE: To determine the efficacy of statin treatment in atrial fibrillation (AF) prevention in women. DESIGN: Cohort study using data obtained in the Heart and Estrogen/Progestin Replacement Study (HERS). SETTING: Secondary analysis of a multicentre, randomised controlled clinical trial. PATIENTS: 2673 Postmenopausal women with coronary disease. MAIN OUTCOME MEASURES: AF prevalence at baseline and incident AF over a mean follow-up of 4.1 years. RESULTS: 88 Women with AF were identified: 29 at baseline and 59 during follow-up. Women with AF were significantly less likely to be taking a statin at study enrollment than those without AF (22% vs 37%, p = 0.003). Baseline statin use was associated with a 65% lower odds of having AF at baseline after controlling for age, race, history of myocardial infarction or revascularisation and history of heart failure (odds ratio 0.35, 95% confidence interval (CI) 0.13 to 0.93, p = 0.04). The risk of developing AF during the study among those free from AF at baseline, adjusted for the same covariates, was 55% less for those receiving statin treatment (hazard ratio 0.45, 95% CI 0.26 to 0.78, p = 0.004). CONCLUSIONS: Statin treatment is associated with a lower prevalence and incidence of AF after adjustment for potential confounders in postmenopausal women with coronary disease.

Antiarrhythmic agents in facilitating electrical cardioversion of atrial fibrillation and promoting maintenance of sinus rhythm.

Atrial fibrillation (AF) is a prevalent arrhythmia associated with significant morbidity and mortality. Electrical cardioversion of AF is a potentially definitive treatment, but as little as 67% of patients may be successfully cardioverted and, after normal sinus rhythm (NSR) is achieved, AF often recurs. Class IA, IC, and III antiarrhytmic agents are used for both facilitation of electrical cardioversion and subsequent maintenance of NSR. The mechanisms of these agents may be related to suppressing automaticity, prolonging the wavelength of reentrant wavelets, and preventing electrical remodeling. The possibility of proarrhythmia and other adverse effects complicates use of these drugs, and no large trials have been completed to elucidate definite indications. Several factors may predict failure with electrical cardioversion alone (duration of AF, atrial size, age, underlying disease, and factors that affect transthoracic impedance), calling for empiric pharmacotherapy to facilitate cardioversion. For this purpose, class IA agents hold some promise, evidence for class IC agents is conflicting, and class III agents are the most effective. Adverse effects are rare given the short course before cardioversion, but ibutilide, the most efficacious in this regard, may be proarrhythmic after only a single dose. In promoting maintenance of sinus rhythm, antiarrhythmics across the different classes have similar efficacies: NSR may be maintained in approximately 40-65% of patients compared to approximately 30-35% with placebo at 1 year. Amiodarone is distinct in its success, with approximately 60-80% of patients remaining in NSR. For all of these agents, long-term therapy may lead to proarrhythmia or other substantial adverse effects. Finally, a serial antiarrhythmic strategy may be effective, with maintenance of NSR and minimal adverse effects ultimately achieved by trial and error.