| Summary: | It has been recognized that heart rate variability (HRV), defined as the fluctuation of ventricular response intervals in atrial fibrillation (AFib) patients, is not completely random, and its nonlinear characteristics, such as multiscale entropy (MSE), contain clinically significant information. We investigated the relationship between ischemic stroke risk and HRV with a large number of stroke-naïve AFib patients (628 patients), focusing on those who had never developed an ischemic/hemorrhagic stroke before the heart rate measurement. The <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>CHA</mi></mrow><mn>2</mn></msub><msub><mrow><mi>DS</mi></mrow><mn>2</mn></msub><mo>−</mo><mi>VASc</mi></mrow></semantics></math></inline-formula> score was calculated from the baseline clinical characteristics, while the HRV analysis was made from the recording of morning, afternoon, and evening. Subsequently, we performed Kaplan–Meier method and cumulative incidence function with mortality as a competing risk to estimate the survival time function. We found that patients with sample entropy (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>S</mi><mi>E</mi><mrow><mrow><mo>(</mo><mi>s</mi><mo>)</mo></mrow></mrow></msubsup></mrow></semantics></math></inline-formula>) <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>≥</mo></semantics></math></inline-formula> 0.68 at 210 s had a significantly higher risk of an ischemic stroke occurrence in the morning recording. Meanwhile, the afternoon recording showed that those with <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>S</mi><mi>E</mi><mrow><mrow><mo>(</mo><mi>s</mi><mo>)</mo></mrow></mrow></msubsup></mrow></semantics></math></inline-formula> <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>≥</mo></semantics></math></inline-formula> 0.76 at 240 s and <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>S</mi><mi>E</mi><mrow><mrow><mo>(</mo><mi>s</mi><mo>)</mo></mrow></mrow></msubsup></mrow></semantics></math></inline-formula> <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>≥</mo></semantics></math></inline-formula> 0.78 at 270 s had a significantly lower risk of ischemic stroke occurrence. Therefore, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>S</mi><mi>E</mi><mrow><mrow><mo>(</mo><mi>s</mi><mo>)</mo></mrow></mrow></msubsup></mrow></semantics></math></inline-formula> at 210 s (morning) and 240 s ≤ s ≤ 270 s (afternoon) demonstrated a statistically significant predictive value for ischemic stroke in stroke-naïve AFib patients.
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