Ranolazine reduces atrial fibrillatory wave frequency.

AIMS: Antiarrhythmic medications for the treatment of atrial fibrillation (AF) have limited efficacy and rare but potentially life-threatening side effects. Ranolazine is an antianginal agent that may have antiarrhythmic activity in AF. METHODS AND RESULTS: Using the Duke Enterprise Data Unified Content Explorer database, we analysed a cohort of AF patients on ranolazine. Patients served as their own historic control. Electrocardiograms (ECGs) were analysed before and after ranolazine initiation to determine the effect of ranolazine on dominant frequency (DF), f-wave amplitude, and organizational index (OI). We identified 15 patients with ECGs in AF before and after ranolazine. Ranolazine was associated with lower DF by an average of 10% (5.10 ± 0.74 vs. 5.79 ± 0.96 Hz, P = 0.04) but not with changes in OI (0.47 ± 0.11 vs. 0.50 ± 0.12, P = 0.71) or amplitude (0.47 ± 0.43 vs. 0.41 ± 0.40 mV, P = 0.82). Ranolazine was also associated with lower DF in patients (n = 10) not on concomitant antiarrhythmic therapy (5.25 ± 0.78 vs. 6.03 ± 0.79 Hz, P = 0.04). CONCLUSION: Ranolazine is associated with lower AF DF but no change in OI or fibrillatory wave amplitude. Prospective trials are needed to evaluate ranolazine's potential as a novel antiarrhythmic drug for AF.

Arabidopsis has two functional orthologs of the yeast V-ATPase assembly factor Vma21p.

How individual protein subunits assemble into the higher order structure of a protein complex is not well understood. Four proteins dedicated to the assembly of the V(0) subcomplex of the V-adenosine triphosphatase (V-ATPase) in the endoplasmic reticulum (ER) have been identified in yeast, but their precise mode of molecular action remains to be identified. In contrast to the highly conserved subunits of the V-ATPase, orthologs of the yeast assembly factors are not easily identified based on sequence similarity. We show in this study that two ER-localized Arabidopsis proteins that share only 25% sequence identity with Vma21p can functionally replace this yeast assembly factor. Loss of AtVMA21a function in RNA interference seedlings caused impaired cell expansion and changes in Golgi morphology characteristic for plants with reduced V-ATPase activity, and we therefore conclude that AtVMA21a is the first V-ATPase assembly factor identified in a multicellular eukaryote. Moreover, VMA21p acts as a dedicated ER escort chaperone, a class of substrate-specific accessory proteins so far not identified in higher plants.

Left Atrial Appendage Electrical Isolation for Treatment of Recurrent Atrial Fibrillation: A Meta-Analysis.

OBJECTIVES: In this study, the authors sought to perform a meta-analysis of controlled studies assessing the relationship between left atrial appendage (LAA) electrical isolation (EI) and recurrent atrial fibrillation (AF). BACKGROUND: LAA triggers could play an important role in AF and can be treated with complete EI of the LAA via surgical or percutaneous approaches. METHODS: We conducted a meta-analysis of all controlled studies published as of November 21, 2016, assessing the relationship between left atrial appendage electrical isolation (LAAEI) and recurrent AF. The primary endpoint was atrial tachycardia (AT) or AF recurrence after the post-procedure blanking period. The association between LAAEI and AT/AF was estimated using random-effects modeling. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird method. RESULTS: We identified 7 studies including 1,037 patients; LAAEI was performed in 566 patients (55%). LAAEI was associated with a significantly lower rate of AT/AF recurrence in the primary analysis (OR: 0.38; 95% CI: 0.16 to 0.90; p = 0.02). The association between LAAEI and recurrent AT/AF was strongest in a sensitivity analysis restricted to studies of percutaneous LAAEI (OR: 0.22; 95% CI: 0.11 to 0.46; p < 0.001; 5 studies, n = 623). LAAEI was not associated with thromboembolism (OR: 0.50; 95% CI: 0.18 to 1.39; p = 0.18; 5 studies, n = 767), although these studies either incorporated LAA occlusion (3 studies, n = 552 patients) or follow-up echocardiography to assess LAA function (2 studies, n = 215 patients) to inform antithrombotic strategies. CONCLUSIONS: LAAEI is associated with a significant reduction in recurrent AT/AF. Randomized trials are required to confirm the efficacy and long-term safety of LAAEI and to determine the optimal concomitant antithrombotic strategy.