In patients with NVAF at increased risk for stroke or bleeding who are candidates for chronic anticoagulation, LAAC resulted in improved rates of hemorrhagic stroke, cardiovascular/unexplained death, and nonprocedural bleeding compared to warfarin.

Atrial fibrillation (AF), the most common human cardiac arrhythmia, is associated with abnormal intracellular Ca 2+ handling. Diastolic Ca 2+ release from the sarcoplasmic reticulum via "leaky" ryanodine receptors (RyR2s) is hypothesized to contribute to arrhythmogenesis in AF, but the molecular mechanisms are incompletely understood. Here, we have shown that mice with a genetic gain-of-function defect in Ryr2 (which we termed Ryr2 R176Q/+ mice) did not exhibit spontaneous AF but that rapid atrial pacing unmasked an increased vulnerability to AF in these mice compared with wild-type mice.

The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience-based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.

IMPORTANCE Catheter ablation of persistent atrial fibrillation (AF) has limited success. Procedural strategies beyond pulmonary vein isolation have failed to consistently improve results. The vein of Marshall contains innervation and AF triggers that can be ablated by retrograde ethanol infusion. OBJECTIVE To determine whether vein of Marshall ethanol infusion could improve ablation results in persistent AF when added to catheter ablation. DESIGN, SETTING, AND PARTICIPANTS The Vein of Marshall Ethanol for Untreated Persistent AF (VENUS) trial was an investigator-initiated, National Institutes of Health-funded, randomized, single-blinded trial conducted in 12 centers in the United States. Patients (N = 350) with persistent AF referred for first ablation were enrolled from October 2013 through June 2018. Follow-up concluded in June 2019. INTERVENTIONS Patients were randomly assigned to catheter ablation alone (n = 158) or catheter ablation combined with vein of Marshall ethanol infusion (n = 185) in a 1:1.15 ratio to accommodate for 15% technical vein of Marshall ethanol infusion failures. MAIN OUTCOMES AND MEASURESThe primary outcome was freedom from AF or atrial tachycardia for longer than 30 seconds after a single procedure, without antiarrhythmic drugs, at both 6 and 12 months. Outcome assessment was blinded to randomization treatment. There were 12 secondary outcomes, including AF burden, freedom from AF after multiple procedures, perimitral block, and others. RESULTSOf the 343 randomized patients (mean [SD] age, 66.5 [9.7] years; 261 men), 316 (92.1%) completed the trial. Vein of Marshall ethanol was successfully delivered in 155 of 185 patients. At 6 and 12 months, the proportion of patients with freedom from AF/atrial tachycardia after a single procedure was 49.2% (91/185) in the catheter ablation combined with vein of Marshall ethanol infusion group compared with 38% (60/158) in the catheter ablation alone group (difference, 11.2% [95% CI, 0.8%-21.7%]; P = .04). Of the 12 secondary outcomes, 9 were not significantly different, but AF burden (zero burden in 78.3% vs 67.9%; difference, 10.4% [95% CI, 2.9%-17.9%]; P = .01), freedom from AF after multiple procedures (65.2% vs 53.8%; difference, 11.4% [95% CI, 0.6%-22.2%]; P = .04), and success achieving perimitral block (80.6% vs 51.3%; difference, 29.3% [95% CI, 19.3%-39.3%]; P < .001) were significantly improved in vein of Marshall-treated patients. Adverse events were similar between groups.CONCLUSIONS AND RELEVANCE Among patients with persistent AF, addition of vein of Marshall ethanol infusion to catheter ablation, compared with catheter ablation alone, increased the likelihood of remaining free of AF or atrial tachycardia at 6 and 12 months. Further research is needed to assess longer-term efficacy.

Background Treatment of perimitral flutter (PMF) requires bidirectional mitral isthmus (MI) block, which can be difficult with radiofrequency ablation (RFA). The vein of Marshall (VOM) is located within the MI. Objective To test whether VOM ethanol infusion could help achieve MI block. Methods Perimitral conduction was studied in patients undergoing ablation of atrial fibrillation (AF). Group 1 included 50 patients with a previous AF ablation undergoing repeat ablation, 30 of which had had MI ablation. Spontaneous (8/50) or inducible PMF (21/50) was confirmed by activation mapping. Group 2 included 21 patients undergoing de novo VOM ethanol infusion. The VOM was cannulated with a quadripolar catheter for pacing and with an angioplasty balloon to deliver up to four 1mL infusions of 98% ethanol. Voltage maps were created before and after VOM ethanol. Bidirectional MI block was verified by differential pacing. RFA times required to achieve it were assessed. Results In Group 1, VOM ethanol infusion acutely terminated PMF in 5/29 patients. RFA needed to achieve bidirectional MI block was 2.2±1.6 min. Presence of PMF or previous MI ablation did not affect RFA times. In Group 2, RFA needed to achieve bidirectional MI block was 2.0±1.6 min (p=NS). Five patients had bidirectional MI block achieved solely by VOM ethanol without RFA. In both groups, ablation after VOM ethanol was required in the annular aspect of the MI. There were no acute complications. Conclusion VOM ethanol infusion is useful in the treatment of PMF and assists in reliably achieving bidirectional MI block.