Effect of Catheter Ablation With Vein of Marshall Ethanol Infusion vs Catheter Ablation Alone on Persistent Atrial Fibrillation

Abstract

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.

Efficacy and safety of ethanol infusion into the vein of Marshall for mitral isthmus ablation

“…Reported complications of VOM-EI include vascular access complications, pericardial effusion, pericarditis, VOM dissection and volume overload. 10,11,13 In our population of patients with intended VOM-EI, we observed pericardial effusion/pericarditis in four patients (18%) and VOM dissection in two (9%), all of which resolved without additional interventions. We performed echocardiography the day after VOM-EI in 86% of patients, irrespective of symptom status.…”

“…10 Other groups reported successful VOM-EI rates of 73.4-92%. 11,13,14 . Using the same approach, we successfully achieved VOM-EI in comparable 86% of cases.…”

Anatomical targets and expected outcomes of catheter‐based ablation of atrial fibrillation in 2020

“…Initial attempts were performed to modulate AF induction by parasympathetic responses elicited through high‐frequency stimulation in the ligament of Marshall, which were successfully abolished by ethanol injection (Table 3). 101 The first randomized controlled clinical trial in patients with persistent AF undergoing their first catheter ablation has recently reported that the 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 (49.2% vs. 38% after a single procedure) 102 . The MARS‐AF trial (vein of Marshall ethAnol for Recurrent perSistent AF) is another randomized controlled study currently on‐going in patients with persistent AF, including also patients with prior ablation.…”

“…In case of symptomatic persistent AF recurrences, it would be reasonable to move forward to a third step and target other anatomical regions that have been potentially associated with AF maintenance as mitral isthmus, cardiac ganglia, ligament of Marshall, atrial scar regions, and LAA (Figure 3B). In this context, point‐by‐point RF delivery still represents the most accredited strategy, 69,78,106,107,119,120 with the exception of the ligament of Marshall and the LAA, for which direct ethanol injection in the vein and cryoballoon ablation, 102,109 respectively, have shown to be an effective way to achieve rapid ablation of such regions.…”

Mapping and ablation of non‐pulmonary vein drivers of persistent atrial fibrillation: Has a STAR been born?

“…However, most of these initially‐promising strategies have failed to show benefit in multicenter randomized trials 1,7 . Furthermore, methods that have shown additional benefit over PVI in multicenter RCTs may raise the risk of procedural or postprocedure complications (as in the case of hybrid surgical ablation or left atrial appendage isolation) or require a different skillset while still leaving a relatively large proportion of patients with recurrence (vein of Marshall ethanol injection) 8–12 …”