PPGAF-score: a photoplethysmographic risk prediction tool for developing atrial fibrillation
Authors: Freyer L , Krasniqi A , Spielbichler P , Von Stuelpnagel L , Massberg S , Bauer A , Rizas K 
Published: October 2024

Abstract

Background
Digital screening for AF was recently shown to significantly increased the detection rate of treatment-relevant AF when compared to usual care. In this post-hoc analysis of the eBRAVE-AF trial, we hypothesized that information derived from sequential PPG-measurements in sinus rhythm might be predictive for future AF-development and we aimed to develop a dynamic AF-risk score (PPGAF-score).

Methods
In eBRAVE-AF, individuals who were free of AF were randomized to digital screening or usual care. For digital screening, participants screened for irregularities by means of PPG and abnormal findings were confirmed by a 14-day Holter-ECG. The primary endpoint was newly diagnosed AF treated with oral anticoagulation (OAC) within 6 months. After 6 months, participants were invited to a second, cross-over study phase. In this sub-study we identified participants who performed PPG-measurements both on day (8 am-6 pm) and at night (10 pm-6 am). PPGAF-score was calculated using the coefficients derived from Cox regression analysis. The multivariable model included age ≥ 65 years, sex and three PPG-derived parameters: (i) mean heart rate (HR) of each single PPG-measurement and (ii) the standard deviation (SD) of the HR between subsequent PPG-measurements, which were both dichotomized at the median value and (iii) the failure to demonstrate nocturnal HR reduction (day HR/night HR &lt; 1). PPGAF-score was dichotomized at the median value.

Results
Of the 2,436 participants included in this analysis, 1,208 (50%) were ≥ 65 years old and 776 (32%) participants were females. Cumulatively 186,551 PPG measurements were performed, corresponding to a median of 28 (IQR 23) daytime and 3 (IQR 5) nighttime measurements per participant. The median HR per measurement was 69 (IQR 11) bpm, the median SD of the HR was 6 (IQR 2) bpm, and 759 (31%) participants failed to show a nocturnal HR reduction. During a follow-up time of 12 months, 53 subjects reached the primary endpoint. Cox regression analysis showed that age ≥ 65 years (HR 3.6; 95% CI 1.9–7.0; p &lt; 0.001), male sex (2.7; 95% CI 1.2–5.9;p = 0.017), HR &lt; 69bpm (HR 1.9; 95% CI 1.1–3.5;p=0.028), SD of HR ≥ 6bpm (HR 2.2; 95% CI 1.2–4.0;p=0.011) and the failure to show nocturnal HR reduction (HR 3.2; 95% CI 1.9–5.5; p &lt; 0.001) were all independent predictors of the primary endpoint. PPGAF-score was calculated from the multivariable model. The median value was 0.22. PPGAF-score &gt; 0.22 compared to a risk score ≤ 0.22 was associated with a significantly higher risk for developing AF requiring OAC (HR 6.9, 95% CI 3.1–15.4;p &lt; 0.001; Figure 1).

Conclusion
Combining demographic and PPG-derived parameters, we developed a dynamic prediction tool for assessing the one-year risk of developing AF requiring OAC. A risk score of &gt; 0.22 was associated with a 7-fold increased risk for developing treatment-relevant AF. PPG recordings might provide a valuable tool not only for diagnosing AF, but also for selecting high-risk individuals.