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      Heart rate variability as a marker of cardiovascular dysautonomia in post-COVID-19 syndrome using artificial intelligence

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          Abstract

          Introduction

          Cardiovascular dysautonomia comprising postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH) is one of the presentations in COVID-19 recovered subjects. We aim to determine the prevalence of cardiovascular dysautonomia in post COVID-19 patients and to evaluate an Artificial Intelligence (AI) model to identify time domain heart rate variability (HRV) measures most suitable for short term ECG in these subjects.

          Methods

          This observational study enrolled 92 recently COVID-19 recovered subjects who underwent measurement of heart rate and blood pressure response to standing up from supine position and a 12-lead ECG recording for 60 s period during supine paced breathing. Using feature extraction, ECG features including those of HRV (RMSSD and SDNN) were obtained. An AI model was constructed with ShAP AI interpretability to determine time domain HRV features representing post COVID-19 recovered state. In addition, 120 healthy volunteers were enrolled as controls.

          Results

          Cardiovascular dysautonomia was present in 15.21% (OH:13.04%; POTS:2.17%) . Patients with OH had significantly lower HRV and higher inflammatory markers. HRV (RMSSD) was significantly lower in post COVID-19 patients compared to healthy controls (13.9 ± 11.8 ms vs 19.9 ± 19.5 ms; P = 0.01) with inverse correlation between HRV and inflammatory markers. Multiple perceptron was best performing AI model with HRV(RMSSD) being the top time domain HRV feature distinguishing between COVID-19 recovered patients and healthy controls.

          Conclusion

          Present study showed that cardiovascular dysautonomia is common in COVID-19 recovered subjects with a significantly lower HRV compared to healthy controls. The AI model was able to distinguish between COVID-19 recovered patients and healthy controls.

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          Most cited references33

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          Is Open Access

          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            An Overview of Heart Rate Variability Metrics and Norms

            Healthy biological systems exhibit complex patterns of variability that can be described by mathematical chaos. Heart rate variability (HRV) consists of changes in the time intervals between consecutive heartbeats called interbeat intervals (IBIs). A healthy heart is not a metronome. The oscillations of a healthy heart are complex and constantly changing, which allow the cardiovascular system to rapidly adjust to sudden physical and psychological challenges to homeostasis. This article briefly reviews current perspectives on the mechanisms that generate 24 h, short-term (~5 min), and ultra-short-term (<5 min) HRV, the importance of HRV, and its implications for health and performance. The authors provide an overview of widely-used HRV time-domain, frequency-domain, and non-linear metrics. Time-domain indices quantify the amount of HRV observed during monitoring periods that may range from ~2 min to 24 h. Frequency-domain values calculate the absolute or relative amount of signal energy within component bands. Non-linear measurements quantify the unpredictability and complexity of a series of IBIs. The authors survey published normative values for clinical, healthy, and optimal performance populations. They stress the importance of measurement context, including recording period length, subject age, and sex, on baseline HRV values. They caution that 24 h, short-term, and ultra-short-term normative values are not interchangeable. They encourage professionals to supplement published norms with findings from their own specialized populations. Finally, the authors provide an overview of HRV assessment strategies for clinical and optimal performance interventions.
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              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.

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                Author and article information

                Journal
                Indian Pacing Electrophysiol J
                Indian Pacing Electrophysiol J
                Indian Pacing and Electrophysiology Journal
                Indian Heart Rhythm Society. Published by Elsevier B.V.
                0972-6292
                29 January 2022
                29 January 2022
                Affiliations
                [a ]Department of Cardiology, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research, Delhi, India
                [b ]Department of Pharmacology, Maulana Azad Medical College, Delhi, India
                [c ]SBILab, Department of ECE, IIIT, Delhi, India
                [d ]Senior Consultant Cardiologist and Director Cardiac Electrophysiology, Narayana Superspeciality Hospital, Gurugram, India
                Author notes
                []Corresponding author. Academic block Department of Cardiology, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research, Room no. 125, First floor, New Delhi, 110002, India.
                Article
                S0972-6292(22)00004-3
                10.1016/j.ipej.2022.01.004
                8800539
                35101582
                9ed706f0-f8bd-42ef-9935-da7953f868c8
                © 2022 Indian Heart Rhythm Society. Published by Elsevier B.V.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 15 August 2021
                : 29 December 2021
                : 20 January 2022
                Categories
                Article

                Cardiovascular Medicine
                artificial intelligence,autonomic nervous system,covid-19,heart rate variability,machine learning

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