Effortless Screening for Ischemia: Results from Clinical Trials and Real World Data

Noy Zelig Bilder, Professor Ilan Goldenberg, MD
Director, Department of Cardiology, Leviev Heart Center, Sheba Medical Center, Israel

Background: Low heart rate variability (HRV) has been shown to be associated with myocardial ischemia and increased risk for all-cause mortality as well as sudden cardiac death. We hypothesized that the novel HeartTrends HRV algorithm may be superior to conventional EST for the detection of myocardial ischemia in patients without known CAD.

Methods: Two ongoing prospective, large clinical multicenter trials (Mayo Clinic, Sheba, Rabin, and Shaarei Tzedek Medical Centers, Israel) have yielded 700 consecutive subjects at intermediate risk for CAD Subjects typically underwent one-hour ECG acquisition for HRV analysis, employing HeartTrends prior to an echo stress test (n=250) or exercise myocardial perfusion imaging (n=450). Interpretation of test results was blinded. Sensitivity, specificity, positive and negative predictive values were calculated for EST and the HeartTrends HRV analysis, using echo stress testing or exercise myocardial imaging as gold-standards for the detection of myocardial ischemia.

Results: Mean age of study subjects was 61 (±11.4) years, 41% female, 49% had hypertension, 56% dyslipidemia, 20% diabetes, and 48% had a family history of CAD. The sensitivity of the HeartTrends HRV algorithm for detecting myocardial ischemia was 70% as compared with only 36% shown for standard EST, with similar findings among those who underwent stress MPI and stress echo. Moreover, HeartTrends showed a negative predictive value of 96% for ruling out significant myocardial ischemia. Consistent with these findings, multivariate analysis showed that HeartTrends was associated with a relative incremental value of 4.2 (p<0.001) compared with EST for detection of myocardial ischemia. Results were consistent among patients who subsequently underwent coronary angiography, showing a significantly higher sensitivity associated with HRV compared with EST.

Conclusion: Our data demonstrate that a novel HeartTrends HRV algorithm provides superior sensitivity compared to conventional exercise stress testing for the noninvasive detection of myocardial ischemia in subjects at intermediate pretest risk for disease.