Vein of Marshall ethanol infusion for persistent atrial fibrillation: VENUS and MARS clinical trial design

Abstract

Background: Although pulmonary vein isolation (PVI) is effective in the treatment of paroxysmal atrial fibrillation (AF), its success rates in persistent AF are suboptimal. Ablation strategies to improve outcomes including additional lesions beyond PVI have not consistently shown benefit. Recurrence as perimitral flutter (PMF) is a common form of ablation failure. The vein of Marshall (VOM) contains myocardial connections and abundant sympathetic and parasympathetic innervation implicated in the genesis and maintenance of AF, and is anatomically co-localized with the mitral isthmus, the ablation target of PMF. VOM ethanol infusion is effective in targeting these arrhythmia substrates.

Objective: To test the safety and efficacy of VOM ethanol infusion when added to PVI in patients undergoing either de novo ablation of persistent AF or after a previous ablation failure.

Study design: VENUS-AF and MARS-AF are prospective, multicenter, randomized, controlled trials. VENUS-AF will enroll patients undergoing their first catheter ablation of persistent AF. MARS-AF will enroll patients undergoing ablation after previous ablation failure(s). Patients (n = 405) will be randomized to PVI alone or in combination with VOM ethanol infusion. The primary endpoints include procedural safety and freedom from AF or atrial tachycardia (AT) of more than 30 seconds on 30-day continuous event monitors at 6 and 12 months after randomization procedure (single-procedure success), off antiarrhythmic drugs. Key secondary endpoints include AF burden, freedom from AF/AT after repeat procedures and quality of life.

Conclusions: The VENUS-AF and MARS-AF will determine the safety and potential rhythm control benefit of VOM ethanol infusion when added to PVI in patients with persistent AF undergoing de novo or repeat ablation, respectively.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1.. VOM ethanol infusion procedure.

A, Contrast injection in the CS lumen through the sub-selector catheter with its tip close to the VOM, showing the VOM take-off and branching patterns outlined in B. C, selective venogram via an angioplasty balloon in a VOM branch. Collaterals fill LA veins in the LA roof (outlined in D).

Figure 2.. Tissue ablation by VOM ethanol.

A, Contrast injection in the CS showing the VOM take-off. B, VOM cannulation with angioplasty balloon. Contrast is injected prior to ethanol. A circular catheter is placed in the left inferior PV (LIPV). C-D, Voltage maps (scar in red, of 7 cm2) of the left atrium pre-and post-ethanol.

Figure 3.. Atrial denervation by VOM ethanol.

Parasympathetic innervation (histochemical staining) of the LA. Dotted line is the location of the VOM, coinciding with the left dorsal (LD) tract of vagal nerves, connected with neural plexi (insets). From indicated reference. B, VOM cannulation with a quadripolar catheter to perform high-frequency stimulation, indicated by the blue arrow in C and D, Electrograms during high-frequency stimulation in the VOM during on-going AF. Pre-ethanol infusion (C), atrioventricular block with asystole of 4.1 s is induced. Such response is abolished after ethanol infusion (D).

Figure 4.. Clinical trial design.

Patients with drug-refractory persistent AF undergoing their first (VENUS) or repeat (MARS) either PVAI alone or in combination with VOM ethanol infusion (VOM-PV).

Figure 5.

Efficacy boundaries at 33%, 66%, and 100% accrual of VENUS primary outcomes.