Efficacy on resynchronization and longitudinal contractile function comparing His-bundle pacing with conventional biventricular pacing: a substudy to the His-alternative study.

AIMS: His-bundle pacing has emerged as a novel method to deliver cardiac resynchronization therapy (CRT). However, there are no data comparing conventional biventricular (BiV)-CRT with His-CRT with regard to effects on mechanical dyssynchrony and longitudinal contractile function. METHODS AND RESULTS: Patients with symptomatic heart failure, left ventricular ejection fraction ≤ 35%, and left bundle branch block (LBBB) by strict ECG criteria were randomized 1:1 to His-CRT or BiV-CRT. Two-dimensional strain echocardiography was performed prior to CRT implantation and at 6 months after implantation. Differences in changes in mechanical dyssynchrony (standard deviation of time-to-peak in 12 midventricular and basal segments) and regional longitudinal strain in the six left ventricular walls were compared between the BiV-CRT and His-CRT groups.In the on-treatment analysis, 31 received BiV-CRT and 19 His-CRT. In both groups, mechanical dyssynchrony was significantly reduced after 6 months [BiV group from 120 ms (±45) to 63 ms (±22), P < 0.001, and His group from 116 ms (±54) to 49 ms (±11), P < 0.001] but no significant differences in changes could be demonstrated between groups [-9.0 ms (-36; 18), P = 0.50]. Global longitudinal strain (GLS) improved in both groups [BiV group from -9.1% (±2.7) to -10.7% (±2.6), P = 0.02, and His group from -8.6% (±2.1) to -11.1% (±2.0), P < 0.001], but no significant differences in changes could be demonstrated from baseline to follow-up [-0.9% (-2.4; -0.6), P = 0.25] between groups. There were no regional differences between groups. CONCLUSION: In heart failure, patients with LBBB, BiV-CRT, and His-CRT have comparable effects with regard to improvements in mechanical dyssynchrony and longitudinal contractile function.

High plasma 25-hydroxyvitamin D and high risk of nonmelanoma skin cancer: a Mendelian randomization study of 97 849 individuals.

BACKGROUND: High plasma 25-hydroxyvitamin D [25(OH)D] concentration has been associated observationally with a high risk of nonmelanoma skin cancer (NMSC), whereas many studies suggest that vitamin D could have a protective effect against cancer. The true association between vitamin D and risk of skin cancer remains unclear. OBJECTIVES: To test the hypothesis that genetically high plasma 25(OH)D protects against NMSC. METHODS: We included 103 084 individuals from the Danish general population, of whom 35 298 had plasma 25(OH)D measured and 97 849 were genotyped for four genetic variants near DHCR7 and CYP2R1 associated with 25(OH)D concentrations. We tested the association between plasma 25(OH)D levels and NMSC observationally and between genetically determined 25(OH)D levels and NMSC, using an instrumental variable approach. RESULTS: Multivariate-adjusted hazard ratios of NMSC were 3·27 [95% confidence interval (CI) 2·22-4·84] for plasma 25(OH)D ≥ 50 nmol L-1 vs. < 25 nmol L-1 . Genetic variants around DHCR7 and CYP2R1 were associated with up to 8·2 nmol L-1 higher 25(OH)D concentrations (F = 314). The odds ratio (OR) for a genetically determined 20 nmol L-1 higher plasma 25(OH)D was 1·11 (95% CI 0·91-1·35) for NMSC, with a corresponding observational multivariable adjusted OR of 1·13 (95% CI 1·10-1·17). CONCLUSIONS: Genetically determined high 25(OH)D levels did not appear to protect against NMSC, whereas high plasma 25(OH)D concentrations were associated with an observational high risk of NMSC. Thus, the observational association likely reflects confounding by sun exposure rather than causality.