TY - JOUR
T1 - Effect of Catheter Ablation with Vein of Marshall Ethanol Infusion vs Catheter Ablation Alone on Persistent Atrial Fibrillation
T2 - The VENUS Randomized Clinical Trial
AU - Valderrábano, Miguel
AU - Peterson, Leif E.
AU - Swarup, Vijay
AU - Schurmann, Paul A.
AU - Makkar, Akash
AU - Doshi, Rahul N.
AU - Delurgio, David
AU - Athill, Charles A.
AU - Ellenbogen, Kenneth A.
AU - Natale, Andrea
AU - Koneru, Jayanthi
AU - Dave, Amish S.
AU - Giorgberidze, Irakli
AU - Afshar, Hamid
AU - Guthrie, Michelle L.
AU - Bunge, Raquel
AU - Morillo, Carlos A.
AU - Kleiman, Neal S.
N1 - Funding Information:
Conflict of Interest Disclosures: Dr Valderrábano reported serving as a consultant for Biosense Webster; a speaker for Boston Scientific; research support member for Circa Scientific; and consultant and speaker for Baylis Medical. Dr Swarup reported providing research and consulting services to Biosense Webster, Boston Scientific, and Abbott outside the submitted work. Dr Athill reported receiving grants and other funding from Methodist Hospital Research Institute during the conduct of the study and grants and personal fees from Boston Scientific and Abbott Laboratories; grants from Biosense Webster; and personal fees from Janssen Pharmaceutical and Zoll Medical outside the submitted work. Dr Natale reported receiving personal fees from Biosense Webster, Biotronik, Medtronic, Boston Scientific, and Abbott during the conduct of the study and outside the submitted work. Dr Dave reported serving as a consultant to Abbott outside the submitted work. Dr Bunge reported receiving grants from Houston Methodist Research Institute during the conduct of the study. Dr Morillo reported receiving personal fees from Medtronic and serving as a member of the steering
Funding Information:
Funding/Support: This study was funded by grant R01HL115003 from the National Institutes of Health/National Heart, Lung, and Blood Institute. Additional support came from Charles Burnett III and Lois and Carl Davis Centennial Chair endowments (Dr Valderrábano) and Houston Methodist Research Institute.
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/10/27
Y1 - 2020/10/27
N2 - 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 Measures: The 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.Results: Of 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.Trial Registration: ClinicalTrials.gov Identifier: NCT01898221.
AB - 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 Measures: The 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.Results: Of 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.Trial Registration: ClinicalTrials.gov Identifier: NCT01898221.
KW - Aged
KW - Atrial Fibrillation/therapy
KW - Catheter Ablation/methods
KW - Combined Modality Therapy/methods
KW - Ethanol/administration & dosage
KW - Female
KW - Humans
KW - Infusions, Intravenous/adverse effects
KW - Kaplan-Meier Estimate
KW - Male
KW - Single-Blind Method
KW - Tachycardia/therapy
KW - Treatment Outcome
KW - Vena Cava, Superior/embryology
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U2 - 10.1001/jama.2020.16195
DO - 10.1001/jama.2020.16195
M3 - Article
C2 - 33107945
AN - SCOPUS:85094931356
SN - 0098-7484
VL - 324
SP - 1620
EP - 1628
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 16
ER -