Screening for Atrial Fibrillation (AF) by handheld single-lead ECG and risk of all-cause mortality stratified by non-AF cardiovascular disease

Abstract

Abstract Purpose Screening for Atrial fibrillation (AF) has been suggested as a strategy to increase early detection of silent AF. We aimed to evaluate all-cause mortality between patients with screen-detected and clinically-diagnosed AF, and the effect of oral anticoagulation therapy (OAC) on mortality. Methods We prospectively enrolled and performed AF screening using handheld single-lead ECG(AliveCor) on consecutive patients who attended medical outpatient clinics during December 2014 and December 2017. Repeat screening was performed among patients who had >1 clinic visits. All participants were divided into 5 cohorts: (i) previously known AF at baseline (kAF); (ii) initial screen-detected AF (S1-AF); (iii) subsequent screen-detected AF (FU-sAF); (iv) clinically-diagnosed AF during follow-up (FU-cAF); and (v) no AF. Risk of all-cause mortality was estimated by adjusted hazard ratio (HR) using COX proportional hazards regression, adjusting for age, gender, co-morbidities, concurrent chronic use of medications including OAC, with AF detection or clinical diagnosis and OAC therapy handled as time-varying variable. Subgroup analysis was conducted to identify heterogeneity of effect across with or without non-AF cardiovascular disease (CVD). Results Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had previously kAF, 1.9% (n=223) S1-AF, 0.6% (n=71) FU-sAF, 7.3% (n=867) FU-cAF, and 71.6% (n=8,559) no AF. During a median FU duration of 6.8(IQR: 5.2-8.1) years, patients with kAF (HR=1.8(1.6-2.0)), S1-AF (HR=1.6(1.3-1.9)) and FU-cAF (HR=1.6(1.4-1.8)) were at higher risk of all-cause mortality, compared to individuals without AF, whereas FU-sAF (HR=1.0(0.7-1.4)) had similar low risk of death as no AF. Heterogeneity of effect was detected in subgroup analysis. Among patients without non-AF CVD, FU-sAF (HR=6.0(1.8-19.8)) and FU-cAF (HR=4.7(3.3-6.7)) were at markedly higher risk of all-cause mortality. DOAC (HR=0.57(0.38-0.87)) but not VKA (HR=0.72(0.43-1.15) reduced mortality. However, in patients with CVD other than AF, risk of FU-sAF (HR=1.1(0.8-1.6)) decreased to as low as individuals without AF (P for interaction =0.0039).Both DOAC (HR=0.51(0.46-0.58)) and VKA (HR=0.87(0.78-0.98) were beneficial. Conclusion Likely delayed AF detection suggested by groups of FU-cAF and FU-sAF may be associated with significant rise in risk of mortality among patients without non-AF CVD. The effect diminished when non-AF CVD as potential competing risk existed. The role of VKA in reducing all-cause mortality warrants more studies.