Critical Concerns Regarding the Conclusions of Pulmonary Vein Isolation's Impact on Cardiovascular Autonomic Reflexes

Abstract

We have followed with great interest the research article by Malik et al., which investigates the impact of pulmonary vein isolation (PVI) on cardiovascular afferent autonomic reflexes in patients with atrial fibrillation [1]. Although we are pleased that the authors systematically conducted their study regarding the assessment of autonomic function, we would like to present to the authors some significant flaws in their final results that undermine the validity and generalizability of their conclusions.

The most important limitation of the study is its highly underpowered design, as only nine patients completed pre- and post-PVI assessments. Modern statistical practices in heart rate variability research suggest that a modest or large effect size ranges from 0.25 to 0.9. In contrast, a recommended sample size of 25–64 participants in each group should provide the study with a power of 80%–90% [2]. The size of the authors' sample lacks the statistical power to detect clinically significant changes in parameters of the autonomic nervous system.

The authors' conclusion that PVI does not have a direct impact on cardiovascular reflexes contradicts several other large-scale studies published over the last 5 years. The molecular markers related to CIRCA-DOSE examined 346 patients and found that PVI leads to meaningful, sustained changes in heart rate parameters [3]. Specifically, patients who did not demonstrate arrhythmia recurrence had significantly faster daytime heart rates (11 ± 11 vs. 8 ± 12 bpm, p = 0.001) and nighttime heart rates. The trial results essentially contradict the study's conclusion.

The authors acknowledge finding meaningful variations in the parameters of heart rate variability, which are associated with a reduction in total power (p = 0.03) and very low-frequency components (p = 0.03), but reject these as not being linked to afferent disruption. Such interpretation disagrees with what is known concerning physical physiology. According to several studies, significant correlations exist between baroreflex sensitivity and heart rate variability, with correlation coefficients ranging from 0.30 to 0.53 (p < 0.001–0.02) [4]. The variant of autonomic function proposed by the authors is based on a compartmentalized interpretation, which is not entirely consistent with the context of cardiovascular autonomic regulation being viewed as an integrated process.

Recent comparative findings on pulsed field ablation (PFA) versus thermal ablation studies also raise doubts about the study's conclusions. The ADVENT study subanalysis also demonstrated a marked variation in the autonomic effect between ablation modalities, with thermal ablation causing a greater increase in heart rate (+8.8 vs. +5.2 bpm at 12 months, p = 0.03) and decreased heart rate variability compared to PFA [5]. Such results indicate that thermal PVI can cause serious neural injuries, meaning that the study findings are inaccurate.

Increasing evidence from larger, well-powered studies consistently shows that PVI has significant effects on cardiac autonomic adjustment, and this can occur through numerous interventions beyond merely impeding effortless efferent flow. Clinical implications are substantial; autonomic modulation appears to be a reliable indicator of procedural success and long-term outcomes. We respectfully appeal to the authors to consider these limitations and suggest that future studies should be conducted using well-substantiated study designs and comprehensive autonomic assessment protocols. Extensive, multisite studies with real-time monitoring and biomarker evaluation, as well as intermodality comparisons, will be needed to settle the question of the autonomic consequences of PVI and their clinical relevance to the scientific community.

The authors have nothing to report.

The authors declare no conflicts of interest.