Breathing rate and heart rate as confounding factors in measuring T wave alternans and morphological variability in ECG Author: Ismail Sadiq1, Erick A Perez-Alday2, Amit J Shah3, Gari D Clifford2,4 Affiliation: <sup>1</sup> Department of Electrical &amp; Computer Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America. <sup>2</sup> Department of Biomedical Informatics, Emory University, Atlanta, GA, United States of America. <sup>3</sup> Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States of America. <sup>4</sup> Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States of America. Conference/Journal: Physiol Meas Date published: 2021 Feb 6 Other: Volume ID: 42 , Issue ID: 1 , Pages: 015002 , Special Notes: doi: 10.1088/1361-6579/abd237. , Word Count: 266 Objective: High morphological variability magnitude (MVM) and microvolt T wave alternans (TWA) within an electrocardiogram (ECG) signifies increased electrical instability and risk of sudden cardiac death. However, the influence of breathing rate (BR), heart rate (HR), and signal-to-noise ratio (SNR) is unknown and may inflate measured values. Approach: We synthesize ECGs with morphologies derived from the Physikalisch-Technische Bundesanstalt Database. We calculate MVM and TWA at varying BRs, HRs and SNRs. We compare the MVM and TWA of signal with versus without breathing at varying HRs and SNRs. We then quantify the percentage of MVM and TWA estimates affected by BR and HR in a healthy population and assess the effect of removing these affected estimates on a method for classifying individuals with and without post-traumatic stress disorder (PTSD). Main results: For signals with high SNR (>15 dB), MVM is significantly increased when BRs are > 9 respirations/minute (rpm) and HRs are < 100 beats/minute (bpm). Increased TWAs are detected for HR/BR pairs of 60/15, 60/30 and 120/30 bpm/rpm. For 18 healthy participants, 8.33% of TWA windows and 66.76% of MVM windows are affected by BR and HR. On average, the number of windows with TWA elevations > 47 μV decreases by 23% after excluding regions with significant BR and HR effect. Adding HR and BR to a morphological variability feature increases the classification performance by 6% for individuals with and without PTSD. Significance: Physiological BR and HR significantly increase MVM and TWA , indicating that BR and HR should be considered separately as confounders. The code for this work has been released as part of an open-source toolbox. PMID: 33296886 PMCID: PMC9201765 DOI: 10.1088/1361-6579/abd237