Heart rate fragmentation as a marker of altered global autonomic nervous system activity: a novel predictor of atrial fibrillation occurrence in the general population
Authors: Guichard J B , Pichot V , Hupin D , Celle S , Da Costa A , Barthelemy J C , Roche F 
Published: October 2022

Abstract

Background
The dysfunction of the autonomic nervous system (ANS) plays an important role in the initiation and maintenance of atrial fibrillation (AF). However, the meaning of high heart rate variability (HRV) in predicting AF is still under debate due to conflicting results in population-based studies. Short-term HRV is conceptually attributed to vagal tone modulation. But recent data suggest that a component of short-term HRV, called heart rate fragmentation, is related to ANS breakdown. On the other hand, parasympathetic activity could be assess by a novel metric, the deceleration capacity (DC).

Objective
To assess predictive capacity of novel HRV-derived metrics, whether fragmentation indices or parameters of vagal tone, regarding the occurrence of AF in general population during long-term follow-up.

Methods
A cohort study was designed to prospectively assess the predictive value of ANS activity level among a healthy retired French population, regarding cardiovascular events and mortality. 1011 subjects aged 65 were enrolled in the study from 2000 to 2002. The enrolled population had no history of AF and a low cardiovascular risk. A median follow-up of 17.8 years (16.0–18.5) was managed. HRV data were acquired by 24-h Holter electrocardiogram (ECG) monitoring at baseline and assessed by frequency domain and time domain methods. Heart rate fragmentation using the percentage of inflection points (PIP), and assessment of specific parasympathetic activity using DC were then calculated. The study outcome was the onset of AF during follow-up, defined as a standard 12-lead ECG or Holter recording with ≥30 s of AF.

Results
AF was diagnosed in 123 patients along the 18-year follow-up, representing a cumulative incidence of 13.4%. Using univariate analysis (Figure 1A), a higher percentage of NN intervals that differ by more than 50 ms from the previous interval (pnn50) and root mean square differences of successive NN intervals (RMSSD) were associated with AF onset (p&lt;0.01). A lower ratio of low-frequency and high-frequency component (LF/HF) was the only frequency-domain parameter found to predict the AF occurrence (p&lt;0.01). The occurrence of AF was predicted by a higher PIP (p&lt;0.01) and lower DC (p&lt;0.01). Through multivariate analysis using clinical parameters that reached statistical significance in univariate analysis (Figure 1B), higher PIP was found as an independent predictor of AF occurrence (HR=2.1, 95% CI: 1.1–3.9, p=0.02), as well as male gender (HR=2.1, 95% CI: 1.1–3.9, p=0.02), and non-sustained supraventricular tachycardia (HR=2.1, 95% CI: 1.1–3.9, p=0.02).

Conclusion
(see Figure 2) Elevated PIP, a marker of heart rate fragmentation secondary to impaired ANS activity, is an independent predictor of the onset of AF in the healthy general population. Therefore, high HRV associated to AF occurrence could be the consequence of general ANS impairment rather than increased parasympathetic activity.

Funding Acknowledgement
Type of funding sources: None.