Percutaneous Chemical Ablation of Cardiac Nerves Shows Promise in Treating A-fib

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Adding ethanol infusion to radiofrequency catheter ablation in patients with persistent atrial fibrillation (A-fib) eliminates parasympathetic responses as well as A-fib inducibility, according to results of a small study published online February 18, 2014, in the Journal of the American College of Cardiology. The findings suggest the possibility of a new endovascular route for therapies targeting the intrinsic cardiac nerves.

The results were first presented at the Heart Rhythm Society’s Annual Scientific Sessions (2011) in San Francisco, CA.  

Researchers led by Miguel Valderrábano, MD, of Houston Methodist Hospital (Houston, TX), enrolled patients undergoing de novo or repeat catheter ablation for A-fib. Patients were administered up to four 1-mL ethanol infusions over 2 minutes through the Vein of Marshall (VOM). Three-dimensional maps of the left atrial geometry and regional bipolar voltage amplitude were performed at baseline and after VOM ethanol administration.

The study included 2 protocols. In the first, 8 patients who received a prior catheter ablation procedure underwent synchronized high-frequency stimulation (30 pulses, 100 Hz). In the second protocol, 32 patients undergoing catheter ablation for the first time and 40 patients undergoing a repeat procedure received high-frequency stimulation in bursts (5-10 seconds, 33 Hz).

Because parasympathetic responses were unable to be assessed in the first protocol (synchronized stimulation), it was abandoned in favor of the burst method. With the latter protocol, parasympathetic responses were found in 100% of patients undergoing catheter ablation for the first time and in 75% of those undergoing a repeat procedure.

Following ethanol infusion, 13 patients remained in sustained A-fib and thus inducibility could not be tested with repeat high-frequency stimulation. In the other 27 patients, A-fib, or any atrial arrhythmia, remained noninducible via VOM stimulation in 100% of patients, indicating that parasympathetic responses had been eliminated by ethanol injection.

Ethanol infusion was not associated with any acute complications.

A New Therapeutic Target?

According to the study authors, the VOM contains intrinsic cardiac nerves that connect with the AV node and can trigger A-fib. Giving the ethanol infusion through the VOM appears to be an effective means of eliminating parasympathetic responses and induction of A-fib, they conclude.

“These findings support the feasibility of VOM cannulation as a percutaneous technique for endovascular delivery of [intrinsic cardiac nerve]-targeted therapies,” they write.

Dr. Valderrábano and colleagues add that this method is attractive because local toxicity of ethanol is limited to tissues in direct contact with it, thus sparing neighboring structures such as the esophagus. They also suggest that the technique “directly addresses mechanistic sources of [A-fib] located in the VOM, including ectopic triggers.”  Furthermore, they say an important implication of the study is that the VOM can be used as a vascular route to deliver therapies targeting intrinsic cardiac nerves.

Promising, but Obstacles Remain

In an accompanying editorial, Kalyanam Shivkumar, MD, PhD, of the UCLA Cardiac Arrhythmia Center (Los Angeles, CA), says new approaches to the treatment of A-fib are critical given the high rate of suboptimal A-fib ablations, which often result in need for repeat procedures.

According to Dr. Shivkumar, the study capitalizes on an improved understanding of the link between the autonomic nervous system and A-fib and provides evidence that targeted ablation of the intrinsic cardiac nerve may be a promising tool in the therapeutic armamentarium against A-fib.

However, he observes, published evidence suggests that ablation of nerves that input to the intrinsic cardiac nerves results in only short-term reductions in the occurrence of A-fib. Importantly, Dr. Shivkumar also points to the clinical reality “that the VOM is absent or too small to be cannulated in some patients, potentially increasing procedure time.” Yet another drawback, he adds, is that therapies targeting the intrinsic cardiac nerves have the potential to create further instability in the neural network, thus exacerbating the risk of arrhythmias.

Study Details

In first-time ablation patients (n = 32), mean age was 63 ± 8 years and 9 were female. In repeat- ablation patients (n = 40), mean age was 64 ± 9 years and 12 were female.

Fluoroscopy and procedure times required to complete the VOM component of the procedure were 9.6 ± 5.2 min and 62.5 ± 12.5 min, respectively.

1. Báez-Escudero JL, Keida T, Dave AS, et al. Ethanol infusion in the vein of Marshall leads to parasympathetic denervation of the human left atrium: implications for atrial fibrillation. J Am Coll Cardiol. 2014;Epub ahead of print.

2. Rajendran PS, Buch E, Shivkumar K. Marshaling the autonomic nervous system for treatment of atrial fibrillation [editorial]. J Am Coll Cardiol. 2014;Epub ahead of print.

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