Ethanol infusion in the vein of Marshall leads to parasympathetic denervation of the human left atrium: implications for atrial fibrillation

Abstract

Objectives: This study sought to determine whether ethanol infusion in the vein of Marshall (VOM) can ablate intrinsic cardiac nerves (ICN).

Background: ICN cluster around the left atrial epicardium and are implicated in the genesis of atrial fibrillation (AF).

Methods: Patients undergoing catheter AF ablation underwent adjunctive ethanol injection in the VOM. A multipolar catheter was introduced in the VOM and used for high-frequency stimulation (HFS), either as HFS with P-wave synchronized (SynchHFS), 30 pulses, 100 Hz (n = 8) or as HFS with 3 to 10 s bursts (BurstHFS), 33 Hz (n = 72) at 25 mA for 1-ms duration. Atrioventricular (AV) nodal conduction slowing (asystole >2 s or R-R interval prolongation >50%) and AF inducibility were assessed before and after VOM ethanol infusion. Up to 4 1-ml infusions of 98% ethanol were delivered via an angioplasty balloon in the VOM.

Results: SynchHFS induced AF in 8 of 8 patients. In 4 of 8 AF initiated spontaneously without VOM capture. No parasympathetic responses were elicited by SynchHFS. BurstHFS was performed in 32 patients undergoing de novo AF ablation (Group 1) and 40 patients undergoing repeat ablation (Group 2). Parasympathetic responses were found in all 32 Group 1 patients and in 75% of Group 2 patients. After VOM ethanol infusion, parasympathetic responses were abolished in all patients (both groups). There were no acute complications related to VOM ethanol infusion.

Conclusions: The VOM contains ICN that connect with the AV node and can trigger AF. Retrograde ethanol infusion in the VOM reliably eliminates local ICN responses. The VOM is a vascular route for ICN-targeting therapies.

Keywords: atrial fibrillation; ethanol; intrinsic cardiac nerves; vein of Marshall.

Figure 1. Results summary

a. SyncHFS protocol. b. BurstHFS protocol. See text for details.

Figure 2. Example of P-wave-synchronized high frequency stimulation (SynchHFS) inducing AF without atrial capture, and abolition of AF induction after VOM ethanol

a. At baseline (Pre-ethanol), 30 stimuli at 100 Hz following the P wave (sHFS) did not capture the atrium. After a sinus beat, AF ensues, with the first arising from the VOM location. b. After VOM ethanol infusion, SynchHFS fails to induce AF. c. Procedural sequence: Right anterior oblique fluoroscopic views of the intracardiac catheters. Top panel, a quadripolar catheter is inserted in the VOM for baseline HFS and VOM signal recording. Mid panel, an angioplasty balloon is inserted in the VOM for selective angiograms and ethanol infusion. Botton panel, repeat quadripolar catheter insertion in the VOM for post-ethanol HFS. CS: coronary sinus; HRA: high right atrium, LIPV: left inferior pulmonary vein; VOM: vein of Marshall; p, proximal; d, distal.

Figure 3. Asystolic response to BurstHFS in a patient undergoing de novo AF ablation (Group 1)

a. Procedural sequence from left to right. Right anterior oblique views. A quadripolar 1.7F catheter is inserted in the VOM, identified by nonselective contrast injection through the LIMA angiographic guide in the coronary sinus. Baseline HFS is performed. Next, an angioplasty balloon is inserted for VOM venogram and ethanol infusion at up to 4 locations, from distal to proximal. Finally, repeat insertion of the quadripolar catheter for HFS is done. b. Pre-ethanol response to BurstHFS. Surface electrocardiogram and coronary sinus (CS) signals are shown. BurstHFS leads to asystole of 5.7 s and induction of AF. c. After ethanol infusion, BurstHFS fails to induce parasympathetic responses or AF.

Figure 4. Bradycardic (RR prolongation) response to BurstHFS in a patient undergoing de novo AF ablation (Group 1)

a. Catheter location in right anterior oblique view. A septal occluder device is also present. b. Pre- and post-ethanol recordings. AF had been previously induced, and significant RR prolongation is induced by BurstHFS. Such response is abolished after ethanol injection.

Figure 5. Asystolic response to BurstHFS in a patient undergoing repeat AF ablation (Group 2)

a. Catheter location in right anterior oblique view. b. Pre- and post-ethanol recordings. AF had been previously induced, and a 5.35 s asystole is induced by BurstHFS. Such response is abolished after ethanol injection.

Figure 6. Bradycardic (RR prolongation) response to BurstHFS in a patient undergoing repeat AF ablation (Group 2)

a. Catheter location in right anterior oblique view. b. Pre- and post-ethanol recordings. AF had been previously induced, and significant RR prolongation is induced by BurstHFS. Such response is abolished after ethanol injection.

Figure 7. VOM electrograms and endocardial bipolar voltage maps before and after VOM ethanol infusion

a. De novo ablation (group 1). b. Repeat ablation (group 2). VOM signals are abolished and a large endocardial low-voltage area is created by ethanol.