Multiscale Entropy of the Heart Rate Variability for the Prediction of an Ischemic Stroke in Patients with Permanent Atrial Fibrillation

BACKGROUND: Atrial fibrillation (AF) is a significant risk factor for ischemic strokes, and making a robust risk stratification scheme would be important. Few studies have examined whether nonlinear dynamics of the heart rate could predict ischemic strokes in AF. We examined whether a novel complexity measurement of the heart rate variability called multiscale entropy (MSE) was a useful risk stratification measure of ischemic strokes in patients with permanent AF. METHODS AND RESULTS: We examined 173 consecutive patients (age 69±11 years) with permanent AF who underwent 24-hour Holter electrocardiography from April 2005 to December 2006. We assessed several frequency ranges of the MSE and CHA(2)DS(2)-VASc score (1 point for congestive heart failure, hypertension, diabetes, vascular disease, an age 65 to 74 years, and a female sex and 2 points for an age≥75 years and a stroke or transient ischemic attack). We found 22 (13%) incident ischemic strokes during a mean follow up of 3.8-years. The average value of the MSE in the very-low frequency subrange (90–300 s, MeanEn(VLF2)) was significantly higher in patients who developed ischemic strokes than in those who did not (0.68±0.15 vs. 0.60±0.14, P<0.01). There was no significant difference in the C-statistic between the CHA(2)DS(2)-VASc score and MeanEn(VLF2) (0.56; 95% confidence interval, 0.43–0.69 vs. 0.66; 95% confidence interval, 0.53–0.79). After an adjustment for the age, CHA(2)DS(2)-VASc score, and antithrombotic agent, a Cox hazard regression model revealed that the MeanEn(VLF2) was an independent predictor of an ischemic stroke (hazard ratio per 1-SD increment, 1.80; 95% confidence interval, 1.17–2.07, P<0.01). CONCLUSION: The MeanEn(VLF2) in 24-hour Holter electrocardiography is a useful risk stratification measure of ischemic strokes during the long-term follow-up in patients with permanent AF.