Potential Role of Device-Based Electrical Therapies in Atrial Fibrillation With Heart Failure

© 2024 HMP Global. All Rights Reserved.

Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of EP Lab Digest or HMP Global, their employees, and affiliates. 

Featured is the presentation entitled "Potential Role of Device-Based Electrical Therapies in AF With HF" by Stavros Stavrakis, MD, PhD, at the 2024 Western AF Symposium. 

Stavros Stavrakis, MD, PhD: Hello, everyone. Thank would like to thank Nassir for the kind invitation. It's my honor to present this session on the potential role of device-based electrical therapies in atrial fibrillation (AF) with heart failure (HF). I don't need to tell you that AF is a global epidemic. Prevalence and incidence and attributable mortality are increasing, and this is projected to increase even further with the epidemic of obesity and the aging population. 

There is a bidirectional relationship between AF and HF. About 20% of patients with AF develop HF during follow-up and about 10% of patients with HF develop AF. Incident or prevalent HF, whether it's HFrEF or HFpEF, are associated with worse outcomes, including mortality. There are a lot of different mechanisms of incident AF in HF, including myocardial fibrosis, neurohumoral activation, disruption in calcium metabolism, late atrial dilation, etc. One thing we’ve learned from basic science is there is something about the rhythmicity of ventricular contraction that is important. In this study, which I find very intriguing, they paced cardiomyocytes for 24 hours, either regularly or irregularly, and found there was a decrease in calcium transients in the cardiomyocytes with irregular pacing. There was also an increase in reactive oxygen species, etc, that made these cardiomyocytes more prone to developing HF. Does it matter? Yes, it does. This is data from PARADIGM-HF showing that development of AF is associated with worse outcomes, both the primary endpoint and HF hospitalization. The same trends are shown in patients with HFpEF. These are data from TOPCAT showing that patients with AF have consistently worse outcomes in HF. 

So, how do we manage AF in patients with HF? The guidelines say to first ablate. It's a class I recommendation in HFrEF and IIa recommendation in HFpEF. The cornerstone is pulmonary vein isolation (PVI), whether by cryo, radiofrequency, or pulsed field ablation. What happens if we cannot for some reason perform PVI, or the patient does not want PVI? Then, we have the option of atrioventricular (AV) node ablation with pacing. It's also in the guidelines. The question is, do we put in a cardiac resynchronization therapy (CRT) device, biventricular pacing device, or dual-chamber pacemaker? About 10 years ago, we performed a meta-analysis of the existing studies and showed that CRT, compared to dual-chamber pacemakers, decreases HF hospitalization but has no effect on all-cause mortality. A more recent study, APAF-CRT by Brignole et al, showed that AV node ablation plus CRT, compared to medical therapy, results in a decrease in mortality in these patients. More recently, with the advent of His bundle pacing or conduction system pacing, in this study, which was a crossover study comparing CRT versus His bundle pacing, there was a significant yet slight, about 4 percent, better improvement in ejection fraction with His bundle pacing compared to biventricular pacing. So, this is another alternative modality. Atrial anti-tachycardia pacing also results in better outcomes. 

I also want to bring up a different device-based therapy for AF, which is autonomic modulation, including baroreceptor activation therapy, renal denervation, and auricular non-invasive vagus nerve stimulation. So, in terms of baroreceptor activation, there is a small electrode that is placed on the carotid baroreceptors that activates the afferent vagal baroreceptors, increasing parasympathetic activity and decreasing sympathetic activity, which results in improved outcomes. Baroreceptor activation therapy has been FDA approved for patients with HFrEF. No specific data for AF, but in the subgroup analysis, which was prespecified, there was no difference in the outcomes, whether the patient had AF or not. So, that may be a potential therapy for patients with AF and HF. 

In the ERADICATE-AF trial, investigators showed that the addition of renal denervation to conventional PVI resulted in better outcomes in terms of recurrence of AF or atrial flutter. I want to point out that about three-quarters of the patients had HF, so that may be another device-based modality in these patients. This is from our data from the TREAT AF study showing that non-invasive tragus stimulation for 6 months reduced AF burden in patients with paroxysmal AF. The AF burden at 6 months was decreased significantly. In our patients, about 20% of them had HF. This was HFpEF, not HFrEF, because we excluded those patients. 

So, what evidence do we have for HFpEF? We performed another study specifically in patients with HFpEF, which showed that there was a significant decrease at 3 months in quality of life, global longitudinal strain by strain of echocardiography, and serum tumor necrosis factor alpha (TNF-α). Interestingly, we found a linear relationship between the improvement in TNF-α and the improvement in global longitudinal strain, suggesting that the two may be causally related. So, we have a lot of alternative modalities in select patients. 

In conclusion, I hope I have convinced you that AF and HF have an interactive relationship, one worsening the other. The ablate and pace option with CRT or conduction system pacing may be used when rate or rhythm control have failed. Autonomic modulation may play a role in select patients with AF and HF. Thank you.

The transcripts have been edited for clarity and length.