1LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; 2Tirol Kliniken GmbH Kardiologie und Angiologie Innsbruck, Österreich
Background:
Atrial fibrillation (AF) is associated with increased morbidity and mortality. eBRAVE-AF was a siteless, randomized, controlled trial that showed that photoplethysmographic (PPG), smart-device based screening for AF significantly increased the detection rate of treatment-relevant AF, when compared to usual care. In this post-hoc analysis, we hypothesized that information derived from sequential PPG-measurements in individuals being in sinus rhythm, might be predictive for future AF- development and we aimed to develop a dynamic AF-risk score, based on demographic and PPG-derived data (PPGAF-score).
Methods:
In eBRAVE-AF, individuals who were free of AF at baseline were randomized to digital screening or usual care. For digital screening, participants used a certified app to screen for irregularities by means of PPG, and abnormal findings were confirmed by a 14-day external ECG loop recorder. The primary endpoint was newly diagnosed AF treated with oral anticoagulation (OAC) within 6 months after randomization. After 6 months, participants were invited to cross-over for a second study phase with reverse assignment. 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, which was dichotomized at the median value, (ii) the standard deviation (SD) of the HR between subsequent PPG-measurements, which was also dichotomized at the median value and (iii) the failure to demonstrate nocturnal HR reduction (day HR/night HR < 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 measurements and a median of 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 < 0.001), male sex (2.7; 95% CI 1.2–5.9;p = 0.017), HR < 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 < 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 > 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 < 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 > 0.22 was associated with a 7-fold increased risk for developing treatment-relevant AF. PPG recordings are easy to perform, readily available and might provide a valuable tool not only for diagnosing AF, but also for selecting high-risk individuals, who might benefit from intensified AF-screening.