Coronary artery disease (CAD) is the most common cause of death globally. To detect CAD noninvasively at an early stage before clinical symptoms occur is still nowadays challenging. Analysis of the variation of heartbeat interval (RRI) opens a new avenue for evaluating the functional change of cardiovascular system which is accepted to occur at the subclinical stage of CAD. In addition, systolic time interval (STI) and diastolic time interval (DTI) also show potential. There may be coupling in these electromechanical time series due to their physiological connection. However, to the best of our knowledge no publication has systematically investigated how can the coupling be measured and how it changes in CAD patients. In this study, we enrolled 39 CAD patients and 36 healthy subjects and for each subject the electrocardiogram (ECG) and photoplethysmography (PPG) signals were recorded simultaneously for 5 min. The RRI series, STI series, and DTI series were constructed, respectively. We used linear cross correlation (CC), coherence function (CF), as well as nonlinear mutual information (MI), cross conditional entropy (XCE), cross sample entropy (XSampEn), and cross fuzzy entropy (XFuzzyEn) to analyse the bivariate RRI-DTI coupling, RRI-STI coupling, and STI-DTI coupling, respectively. Our results suggest that the linear CC and CF generally have no significant difference between the two groups for all three types of bivariate coupling. The MI only shows weak change in RRI-DTI coupling. By comparison, the three entropy-based coupling measurements show significantly decreased coupling in CAD patients except XSampEn for RRI-DTI coupling (less significant) and XCE for STI-DTI and RRI-STI coupling (not significant). Additionally, the XFuzzyEn performs best as it was still significant if we further applied the Bonferroni correction in our statistical analysis. Our study indicates that the intrinsic electromechanical coupling is most probably nonlinear and can better be measured by nonlinear entropy-based measurements especially the XFuzzyEn. Besides, CAD patients are accompanied by a loss of electromechanical coupling. Our results suggest that cardiac electromechanical coupling may potentially serve as a noninvasive diagnostic tool for CAD.
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