Medical Basis

Cardiologists know that heart rate variability (HRV) is a well-established marker of mortality and sudden death shown to be attenuated in patients with coronary artery disease (CAD) even at rest. Based on this clinical evidence, HeartTrends was developed to provide an innovative modality with a high sensitivity for detection of myocardial ischemia at rest.


The diagnostic yield of the HeartTrends test has now been established and reported in peer-reviewed journals [9],[10]. Clinical studies show HeartTrends sensitivity (77%) compared with standard exercise stress testing relating both to subsequent coronary angiography. The negative predictive value for ruling out myocardial ischemia was 98%. While your actual measurements may differ – and may even be lower-- HeartTrends offers a new, additional “risk factor” for enhanced patient diagnosis.


The heart rate of individuals displays beat-to-beat variations that result from fluctuations in autonomic nervous system activity at the sinus node. Heart rate variability (HRV) decreases under situations of stress, either emotional or physical, whereas it increases with rest. HRV is considered a noninvasive marker of autonomic nervous system function.[1],[2] Over the past decade, low HRV has been shown to have prognostic value in patients with myocardial infarction [3]. In the general population low HRV is associated with death[4],[5] and, as evidenced in the Framingham Heart Study, with the risk of cardiac events [6],[7].


Several studies have shown that there is significant association between reduced HRV and incident coronary artery disease (CAD)[6],[7] suggesting that the imbalance of sympathetic and parasympathetic activity is associated with increased risk of CAD. These findings provide support for the hypothesis that correlates reduced parasympathetic activity to newly diagnosed CAD in the general population.


Recent clinical trial data indicates that the HRV analysis incorporated in the HeartTrends device[8] is a highly sensitive, noninvasive tool that aids in the detection of myocardial ischemia in subjects without known prior CAD, thereby providing an important new diagnostic tool for this population [9-13].

[1]  Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996; 93:1043-1065.

[2]  Hayano J, Sakakibara Y, Yamada A. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol. 1991; 67:199-204.

[3]  Bigger JT, et al. The ability of several short term measures of RR variability to predict mortality after myocardial infarction. Circulation. 1993; 88:927-934.

[4]  Tsuji H, Venditti FJ, et al. Reduced heart rate variability and mortality risk in an elderly cohort: the Framingham Heart Study. Circulation. 1994; 90:878-883.

[5]  Dekker JM, et al. Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men: the Zutphen Study. Am J Epidemiol. 1997; 145:899-908.


[6]  Tsuji H, et al. Impact of reduced heart rate variability on risk for cardiac events: The Framingham Heart Study. Circulation. 1996; 94:2850-2855.


[7]  Liao D, et al. Cardiac autonomic function and incident coronary heart disease: a population-based case-cohort study: the ARIC Study. Am J Epidemiol. 1997; 145:696–706.


[8]  Rozen G, et al. Multipole Analysis of Heart Rate Variability as a Predictor of Imminent Ventricular Arrhythmias in ICD Patients. Pacing Clin. Electrophysiol. 2013 36(11):1342-7.


[9] Oieru D, et al. A Novel Heart Rate Variability Algorithm for Detection of Significant Coronary Artery Disease – Pilot Data from a Prospective Clinical Trial. IMAJ 2015 17:161-165.


[10]  Goldkorn I, et al. Comparison of the Usefulness of Heart Rate Variability vs. Exercise Stress Testing for the Detection of Myocardial Ischemia in Patients Without Known Coronary Artery Disease. Am. J. Cardiology 2015. 115:1518-1522.

[11] Heart Rate Variability for Risk Assessment of Myocardial Ischemia in Patients Without Known Coronary Artery Disease: The HRV-DETECT Study. Ilan Goldenberg, Ronen Goldkorn, et al. J. Am. Heart Assoc. 2019, 8:e01454

[12] Joergensen RM et al. Heart Rate Variability Density Analysis (Dyx) and Prediction of Long-Term Mortality after Acute Myocardial Infarction. Ann Noninvasive Electrocardiol 2016;21(1):60–68.

[13]  Clinical US National Institute of Health (  -- search for ‘HeartTrends’).


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