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, 8 (24), e014540

Heart Rate Variability for Risk Assessment of Myocardial Ischemia in Patients Without Known Coronary Artery Disease: The HRV-DETECT (Heart Rate Variability for the Detection of Myocardial Ischemia) Study

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Heart Rate Variability for Risk Assessment of Myocardial Ischemia in Patients Without Known Coronary Artery Disease: The HRV-DETECT (Heart Rate Variability for the Detection of Myocardial Ischemia) Study

Ilan Goldenberg et al. J Am Heart Assoc.

Abstract

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. We hypothesized that a CAD-specific heart rate variability (HRV) algorithm can be used to improve detection of subclinical or early ischemia in patients without known CAD. Methods and Results Between 2014 and 2018 we prospectively enrolled 1043 patients with low to intermediate pretest probability for CAD who were screened for myocardial ischemia in tertiary medical centers in the United States and Israel. Patients underwent 1-hour Holter testing, with immediate HRV analysis using the HeartTrends DyDx algorithm, followed by exercise stress echocardiography (n=612) or exercise myocardial perfusion imaging (n=431). The threshold for low HRV was identified using receiver operating characteristic analysis based on sensitivity and specificity. The primary end point was the presence of myocardial ischemia detected by exercise stress echocardiography or exercise myocardial perfusion imaging. The mean age of patients was 61 years and 38% were women. Myocardial ischemia was detected in 66 (6.3%) patients. After adjustment for CAD risk factors and exercise stress testing results, low HRV was independently associated with a significant 2-fold increased likelihood for myocardial ischemia (odds ratio, 2.00; 95% CI, 1.41-2.89 [P=0.01]). Adding HRV to traditional CAD risk factors significantly improved the pretest probability for myocardial ischemia. Conclusions Our data from a large prospective international clinical study show that short-term HRV testing can be used as a novel digital-health modality for enhanced risk assessment in low- to intermediate-risk individuals without known CAD. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT01657006, NCT02201017).

Keywords: coronary artery disease; heart rate variability; risk prediction.

Figures

Figure 1
Figure 1
Flow diagram of the HRV‐DETECT (Heart Rate Variability for the Detection of Myocardial Ischemia) study design. CAD indicates coronary artery disease; EST, exercise stress test; HRV, heart rate variability; MPI, myocardial perfusion imaging.
Figure 2
Figure 2
Posttest probability for myocardial ischemia by heart rate variability (HRV). CAD indicates coronary artery disease.
Figure 3
Figure 3
Comparison of area under the curve (AUC) for coronary artery disease (CAD) risk factors before and after the addition of heart rate variability (HRV) by: (A) age; (B) diabetes mellitus; (C) family history of CAD; and (D) comparison of model 2 (CAD risk factors without HRV) and model 3 (CAD risk factor+HRV)*. *P values were assessed using Delong tests.
Figure 4
Figure 4
Comparison of area under the curve (AUC) for exercise stress test (EST) before and after the addition of heart rate variability (HRV).* *P values were assessed using Delong tests.

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