Heart Rate Variability for the Detection of Myocardial Ischemia in Subjects Without Known Coronary Artery Disease: The HRV-DETECT Study

Background:Detecting significant coronary artery disease (CAD) in the general population is complex and relies on combined assessment of traditional CAD risk factors and noninvasive testing. Exercise stress testing (EST) is commonly used for CAD assessment but is not recommended for screening due to limited sensitivity. Accordingly,additional noninvasive modalities are necessary for CAD screening. Heart rate variability (HRV) values were shown to be low in CAD patients and to predict of cardiovascular mortality and sudden cardiac death.

Hypothesis:We hypothesized that a CAD-specific HRV algorithm can be used to improve detection of subclinical or early ischemia in subjects without known CAD.

Methods:Between 2014 and 2018 we prospectively enrolled 1043 subjects with low to intermediate pretest probability for CAD were screened for myocardial ischemia in tertiary medical centers in the US and Israel. Subjects underwent one-hour Holter testing, with immediate HRV analysis using the HeartTrends DyDx algorithm, followed by exercise stress echocardiography (eSE: N=612) or exercise myocardial perfusion imaging (eMPI: N=431). Follow-up continued through May 2019. The primary endpoint was the presence of myocardial ischemia detected by eSE or eMPI.

Results:Mean age was 61 years and 38% were women. Myocardial ischemia was detected in 66 (6.3%) study subjects. After adjustment for CAD risk factors and EST results, low HRV (2-fold increased likelihood for myocardial ischemia (OR=2.11 [95% CI 1.47-2.95]; p<0.001). Furthermore, each single unit reduction in HRV was associated with a significant 52% (p=0.01) increased likelihood for myocardial ischemia. Adding HRV to traditional CAD risk factors improved the pretest probability for myocardial ischemia (Figure).

Conclusions:HRV-DETECT is the largest prospective international clinical study to evaluate the association of HRV with the risk of myocardial ischemia and cardiovascular events in individuals without known CAD.We have shown that short-term HRV testing can be used as a novel digital-health modality for enhanced risk assessment in this population (NCT01657006).