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. 2025 Jun 23;41(3):e70119.
doi: 10.1002/joa3.70119. eCollection 2025 Jun.

Pulmonary vein isolation does not alter cardiovascular afferent autonomic reflexes in atrial fibrillation

Varun Malik  1 , Adrian D Elliott  1 , Gijo Thomas  1 , Bradley Pitman  1 , John L Fitzgerald  1 , Glenn D Young  1 , Leonard F Arnolda  1 , Dennis H Lau  1 , Prashanthan Sanders  1
Affiliations

Pulmonary vein isolation does not alter cardiovascular afferent autonomic reflexes in atrial fibrillation

Varun Malik et al. J Arrhythm. .

Abstract

Background: Pulmonary vein isolation (PVI) remains the cornerstone of atrial fibrillation (AF) ablation. We previously demonstrated abnormal cardiac volume-sensitive reflexes (whose receptors are co-located in veno-atrial tissue) in AF patients. Whether PVI disrupts afferent nerves is unknown.

Objectives: Evaluate whether PVI disrupts afferent volume-sensitive reflexes.

Methods: We consecutively studied autonomic reflexes in AF patients undergoing PVI, repeating the study post-PVI, if AF-free >6 months. We excluded patients with AF recurrence/procedural complications, allowing repeat procedures. We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR) continuously during low-level Lower Body Negative Pressure (LBNP), at 0, -20 and -40 mmHg (predominantly testing volume baroreceptors); Valsalva reflex (predominantly arterial baroreceptors); and Isometric Handgrip reflex (IHR, both). LBNP produces reflex vasoconstriction, evaluated from forearm blood flow (FBF ∝ 1/vascular resistance).

Results: 18 patients were studied pre-PVI; n = 9 completed both visits. Mean age was 64 ± 3 years (78% male); BMI 28 ± 1 kg/m2; LA size 37 ± 2 mL/m2; and left ventricular function 65 ± 3%. Despite alterations in heart rate variability (HRV), there was no difference in IHR, Valsalva, or LBNP responses pre- versus post-PVI. During LBNP, MAP decreased slightly both pre- (-1.6 ± 3%) and post-PVI (-2.8 ± 1.8%); p = .7. HR increased similarly (p = .7) pre- (10.6 ± 6.4%) and post-PVI (7.2 ± 1.5%). FBF response was unchanged (p = .8). Resting (arterial) baroreflex sensitivity was unaltered.

Conclusion: PVI does not impair cardiovascular reflexes involving afferent baroreceptors, suggesting HRV changes reflect efferent modulation or ablation adequacy rather than afferent disruption. Whether disrupting sino-atrial efferent nerves represents a marker of adequate ablation or influences PVI outcomes requires evaluation.

Keywords: Valsalva reflex; atrial fibrillation; autonomic nervous system; isometric handgrip reflex; lower body negative pressure.

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Conflict of interest statement

Dr. Dennis H. Lau reports that the University of Adelaide (UoA) has received on his behalf lecture and/or consulting fees from Abbott Medical, Biotronik, Medtronic, and Microport CRM. Dr. Prashanthan Sanders reports having served on the advisory board of Biosense‐Webster, Medtronic, Abbott, Boston Scientific, Pacemate, and CathRx. Dr. Prashanthan Sanders reports that the UoA has received on his behalf lecture and/or consulting fees from Medtronic, Abbott, Boston Scientific, and Pfizer. Dr. Prashanthan Sanders reports that the UoA has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, and Microport. All remaining authors have no conflicts.

Figures

FIGURE 1
FIGURE 1
CONSORT Diagram of patient recruitment and establishment of a cohort with completed pre‐ and post‐PVI visits (Visit 1 + 2), where PVI resulted in freedom from AF >6 months.
FIGURE 2
FIGURE 2
IHR hemodynamic responses were compared to their corresponding baseline value prior to IHR and were expressed as percentage change. Data ± SEM. MAP, Mean Arterial Pressure (mmHg) & HR, Heart rate (bpm). Pre and post comparisons for IHR; p < .05.
FIGURE 3
FIGURE 3
Valsalva phase II response was compared to each corresponding baseline value prior to Valsalva and was expressed as percentage change. Data ± SEM. MAP, Mean Arterial Pressure (mmHg) & HR, Heart rate (bpm). Pre and postcomparisons for Valsalva for Phase II (autonomic phase: IILATE – IIEARLY; p < .05).
FIGURE 4
FIGURE 4
LBNP. Forearm Blood Flow (FBF) response to LBNP—20 mmHg and—40 mmHg negative pressure. Expressed as percentage change from baseline. Data ± SEM. Pre and post CV comparisons; p < .05.
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