Heart Rate n-Variability (HRnV) and Its Application to Risk Stratification of Chest Pain Patients in the Emergency Department

Background: Chest pain is one of the most common complaints among patients presenting to the emergency department (ED). Causes of chest pain can be benign or life threatening, making its accurate risk stratification a critical issue in the ED. In addition to the use of established clinical scores, some studies attempted to create predictive models with heart rate variability (HRV). In this study, we proposed heart rate n-variability (HRnV), an alternative representation of beat-to-beat-variation in electrocardiogram (ECG) and investigated its association with major adverse cardiac events (MACE) for ED patients with chest pain. Methods: We conducted a retrospective analysis of data collected from the ED of a Singapore tertiary hospital between September 2010 and July 2015. Patients >20 years old who presented to the ED with chief complaint of chest pain were conveniently recruited. Five to six-minute single-lead (lead II) ECGs, demographics, medical history, troponin, and other required variables were collected. We developed the HRnV-Calc software to calculate the HRnV parameters. The primary outcome was 30-day MACE, including all-cause death, acute myocardial infarction, and revascularization. Univariable and multivariable logistic regression analyses were conducted to investigate individual risk factors, and to develop a HRnV prediction model, respectively. The receiver operating characteristic (ROC) analysis was performed to compare the HRnV model against other clinical scores in predicting 30-day MACE. Results: A total of 795 patients were included in the analysis, of which 247 (31%) had MACE within 30 days. The MACE group was older and had a higher proportion of male patients. Twenty-one conventional HRV and 115 HRnV parameters were calculated. In univariable analysis, eleven HRV parameters and 48 HRnV parameters were significantly associated with 30-day MACE. The stepwise logistic regression selected 16 predictors to construct a multivariable prediction model, which consisted of one HRV, seven HRnV parameters, troponin, ST segment changes, and several other factors. The HRnV model outperformed several clinical scores in the ROC analysis (area under the ROC curve of 0.917). Conclusions: The novel HRnV representation demonstrated its value of augmenting HRV and traditional risk factors in designing a robust risk stratification tool for patients with chest pain at the ED.