Heart Rate Variability in Hospitalized Patients with Suspected or Confirmed Diagnosis of COVID-19: A Retrospective Analysis in Comparison to Healthy Controls and in Relation to Proinflammatory Cytokines
Abstract
Objective: This study was designed to evaluate heart rate variability (HRV) in hospitalized patients with suspected or confirmed diagnosis of coronavirus disease-2019 (COVID-19) in comparison to healthy controls and in relation to proinflammatory cytokines.
Materials and Methods: A total of 115 subjects consisting of 3 subgroups (53 patients with confirmed diagnosis of COVID-19, 42 patients with suspected diagnosis of COVID-19 and 20 healthy controls) were included in this study. Data on patient demographics, inflammatory markers (C-reactive protein [CRP], D-Dimer, ferritin, procalcitonin) and the 24-h Holter monitoring parameters were recorded.
Results: None of the Holter monitoring parameters differed significantly between patients with suspected COVID-19 and those with confirmed COVID-19. In both suspected COVID-19 and confirmed COVID-19 groups, standard deviation of all NN intervals (SDNN, p<0.001 for each) and HRV triangular index (p<0.001 for each) values were significantly lower than the values in the control group, while the root mean square of differences between successive NN intervals (RMSSD, p<0.001 for each), low frequency (LF, p=0.001 and p<0.001, respectively), high frequency (HF, p<0.001 for each) and LF/HF ratio (p<0.001 for each) values were significantly higher than the values in the control group. Procalcitonin and SDNN values (r=0.227, p=0.044) were positively correlated.
Conclusion: Our findings revealed significant changes in both time-domain and frequency-domain parameters of HRV in COVID-19 patients, regardless of the viral load, in favor of autonomic nervous system dysfunction. Accordingly, our findings indicate the potential utility of HRV as a valuable clinical tool to monitor autonomic dysfunction in COVID-19 patients resulting from the underlying inflammatory process or the treatment side effects, aiding clinicians in early prediction of a cytokine storm, and in the triage, disease progress monitoring and treatment.
Keywords
COVID-19 heart rate variability time domain indices frequency-domain indices suspected diagnosis confirmed diagnosis proinflammatory cytokines COVID-19, heart rate variability, time domain indices, frequency-domain indices, suspected diagnosis, confirmed diagnosis, proinflammatory cytokines
References
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- Reference16 Shaffer, F, Ginsberg J.P, An overview of heart rate variability metrics and norms, Frontiers in Public Health, 2017, 5, 528.
- Reference17 Fairchild, D, Predictive monitoring for early detection of sepsis in neonatal ICU patients, Current Opinion in Pediatrics, 2013, 25, 172-179.
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COVID-19 şüpheli veya kesin tanısı ile yatışı yapılan hastalarda kalp hızı değişkenliği: Sağlıklı kontrollere göre ve proinflamatuvar sitokinler açısından bir retrospektif analiz
Abstract
Giriş ve Amaç: Bu çalışma, Koronavirüs hastalığı-2019 (COVID-19) şüpheli veya kesin tanısı ile yatışı yapılan hastalarda kalp hızı değişkenliğinin (KHD) sağlıklı kontrollerle kıyaslanması ve proinflamatuvar sitokinler bağlamında değerlendirilmesi amacı ile tasarlandı.
Gereç ve Yöntemler: Bu çalışmaya, 3 alt gruptan oluşan (53 kesin COVID-19 tanısı almış hasta, 42 şüpheli COVID-19 tanısı almış hasta ve 20 sağlıklı kontrol) toplam 115 denek dahil edildi. Hasta demografik özellikleri, inflamatuvar belirteçler (C-reaktif protein [CRP], D-Dimer, ferritin ve prokalsitonin) ve 24-saat Holter monitorizasyon parametrelerine ait veriler kaydedildi.
Bulgular: Holter monitorizayonu parametrelerinin hiçbiri, şüpheli ve kesin COVID-19 tanısına sahip gruplar arasında anlamlı fark göstermedi. Şüpheli ve kesin COVID-19 tanılı her iki grupta, bütün NN intervallerinin standart sapması (SDNN, her biri için p<0,001) ve KHD triangular indeksi (her biri için p<0,001) değerleri kontrol grubu değerlerine göre anlamlı olarak daha düşük iken, ardışık normal NN intervalleri arasındaki farkların karekökü (RMSSD, her biri için p<0,001), düşük frekans (LF, sırasıyla p=0,001 ve p<0.001), yüksek frekans (HF, her biri için p<0,001) ve LF/HF oranı (her biri için p<0,001) değerleri kontrol grubu değerlerine göre anlamlı olarak daha yüksek bulundu. Prokalsitonin ve SDNN değerleri arasında pozitif korelasyon mevcuttu (r=0,227, p=0,044).
Sonuç: Bulgularımız COVID-19 hastalarında KHD’nin hem zaman-bağımlı hem de frekans-bağımlı parametreler açısından önemli değişimler gösterdiğine ve bu değişimin viral yükten bağımsız olup, otonom sinir sistemi disfonksiyonu lehine olduğuna işaret etmektedir. Dolayısıyla bulgularımız, KHD’nin COVID-19 hastalarında altta yatan inflamatuvar sürece veya tedavi yan etkilerine bağlı gelişen otonom disfonksiyonun değerlendirilmesi açısından kullanışlı bir klinik araç olarak sitokin fırtınasının erken tahmini, tiraj, hastalık progresyonunun izlenmesi ve tedavi bakımından klinisyenlere yol gösterebileceği yönündedir.
Keywords
COVID-19; kalp hızı değişkenliği zaman-bağımlı indeksler frekans-bağımlı indeksler şüpheli tanı; kesin tanı; proinflamatuvar sitokinler
References
- Reference1 Perlman, S, Another decade, another coronavirus. The New England journal of medicine, 2020, 382(8), 760-762.
- Reference2 Wang, L, Wang, Y, Ye, D, Liu, Q, Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence, International journal of antimicrobial agents, 2020, 55(6), 105948.
- Reference3 Kwenandar, F, Japar, K.V, Damay, V, Hariyanto, T.I, Tanaka, M, Lugito, N.P.H, et al., Coronavirus disease 2019 and cardiovascular system: A narrative review, International Journal of Cardiology. Heart & Vasculature, 2020, 29, 100557.
- Reference4 Kaliyaperumal, D, Rk, K, Alagesan, M, Ramalingam, S, Characterization of cardiac autonomic function in COVID-19 using heart rate variability: a hospital based preliminary observational study, Journal of Basic and Clinical Physiology and Pharmacology, 2021, 32(3), 247-253.
- Reference5 Huang, C, Wang, Y, Li, X, Ren, L, Zhao, J, Hu, Y, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet (London, England), 2020, 395(10223), 497-506.
- Reference6 Xu, Z, Shi, L, Wang, Y, Zhang, J, Huang, L, Zhang, C, et al., Pathological findings of COVID-19 associated with acute respiratory distress syndrome, The Lancet. Respiratory medicine, 2020, 8(4), 420-422.
- Reference7 Aragón-Benedí, C, Oliver-Forniés, P, Galluccio, F, Yamak Altinpulluk, E, Ergonenc, T, El Sayed Allam, A, et al., Is the heart rate variability monitoring using the analgesia nociception index a predictor of illness severity and mortality in critically ill patients with COVID-19? A pilot study, PLoS One, 2021, 16(3), e0249128.
- Reference8 Gattinoni, L, Chiumello, D, Caironi, P, Busana, M, Romitti, F, Brazzi, L, et al., COVID-19 pneumonia: different respiratory treatments for different phenotypes?, Intensive Care Medicine, 2020, 46(6), 1099-1102.
- Reference9 Pavlov, V.A, Tracey, K.J, Neural regulation of immunity: molecular mechanisms and clinical translation, Nature Neuroscience, 2017, 20(2), 156-166.
- Reference10 Tufan, A, Avanoğlu Guler, A, Matucci-Cerinic, M, COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs, Turkish Journal of Medical Sciences, 2020, 50(SI-1), 620-632.
- Reference11 Guo, T, Fan, Y, Chen, M, Wu, X, Zhang, L, He, T, et al., Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19), JAMA cardiology, 2020, 5(7), 811-818.
- Reference12 Lazzerini, P.E, Boutjdir, M, Capecchi, P.L., COVID-19, Arrhythmic Risk, and Inflammation: Mind the Gap!, Circulation, 2020, 142(1), 7-9.
- Reference13 Kim, M.S, An, M.H, Kim, W.J, Hwang, T.H, Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis, PLoS Medicine, 2020, 17(12), e1003501.
- Reference14 Chary, M.A, Barbuto, A.F, Izadmehr, S, Hayes, B.D, Burns, M.M, COVID-19: Therapeutics and Their Toxicities, Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology, 2020, 16(3), 284-294.
- Reference15 Thayer, J.F, Yamamoto, S.S, Brosschot, J.F, The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors, International Journal of Cardiology, 2010, 141, 122-131.
- Reference16 Shaffer, F, Ginsberg J.P, An overview of heart rate variability metrics and norms, Frontiers in Public Health, 2017, 5, 528.
- Reference17 Fairchild, D, Predictive monitoring for early detection of sepsis in neonatal ICU patients, Current Opinion in Pediatrics, 2013, 25, 172-179.
- Reference18 Pavlov, V.A, Chavan, S.S, Tracey, K.J, Bioelectronic medicine: from preclinical studies on the inflammatory reflex to new approaches in disease diagnosis and treatment, Cold Spring Harbor Perspectives in Medicine, 2020, 10, a034140.
- Reference19 Drury, R.L, Jarczok, M, Owens, A, Thayer, J.F, Wireless Heart Rate Variability in Assessing Community COVID-19, Frontiers in Neuroscience, 2021, 15, 564159.
- Reference20 Bourdillon, N, Yazdani, S, Schmitt, L, Millet, G.P, Effects of COVID-19 lockdown on heart rate variability, PLoS One. 2020, 15(11), e0242303.
- Reference21 Hasty, F, García, G, Dávila, C.H, Wittels, S.H, Hendricks, S, Chong, S, Heart Rate Variability as a Possible Predictive Marker for Acute Inflammatory Response in COVID-19 Patients, Military Medicine, 2020, 186(1-2), e34-E38.
- Reference22 The Turkish Ministry of Health, Guidelines for the Management of Adults with COVID-19. https://covid19bilgi.saglik.gov.tr/depo/rehberler/COVID-19_Rehberi.pdf, 2020 (accessed 18.04.2021)
- Reference23 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, European Heart Journal, 1996, 17(3), 354-381.
- Reference24 Behbahani, S, Shahram, F, Electrocardiogram and heart rate variability assessment in patients with common autoimmune diseases: a methodological review, Turk Kardiyoloji Dernegi Arsivi : Turk Kardiyoloji Derneginin yayin organidir, 2020, 48(3), 312-327.
- Reference25 Malik, M, Camm, A.J, Components of heart rate variability -- What they really mean and what we really measure, The American Journal of Cardiology, 1993, 72, 821-822.
- Reference26 Das, G, Mukherjee, N, Ghosh, S, Neurological Insights of COVID-19 Pandemic, ACS chemical neuroscience, 2020, 11(9), 1206-1209.
- Reference27 Ahmad, S, Ramsay, T, Huebsch, L, Flanagan, S, McDiarmid, S, Batkin, I, et al., Continuous multi-parameter heart rate variability analysis heralds onset of sepsis in adults, PLoS One, 2009, 4(8), e6642.
- Reference28 Chen, W.L, Chen, J.H, Huang, C.C, Kuo, C.D, Huang, C.I, Lee, L.S, Heart rate variability measures as predictors of in-hospital mortality in ED patients with sepsis, The American Journal of Emergency Medicine, 2008, 26(4), 395-401.
- Reference29 Pontet, J, Contreras, P, Curbelo, A, Medina, J, Noveri, S, Bentancourt, S, et al., Heart rate variability as early marker of multiple organ dysfunction syndrome in septic patients, Journal of Critical Care, 2003; 18(3):156-163.
- Reference30 Chen, W.L, Tsai, T.H, Huang, C.C, Chen, J.H, Kuo, C.D. Heart rate variability predicts short-term outcome for successfully resuscitated patients with out-of-hospital cardiac arrest, Resuscitation, 2009, 80(10), 1114-1118.
- Reference31 Chen, I.C, Kor, C.T, Lin, C.H, Kuo, J, Tsai, J.Z, Ko, W.J, et al., High-frequency power of heart rate variability can predict the outcome of thoracic surgical patients with acute respiratory distress syndrome on admission to the intensive care unit: a prospective, single-centric, case-controlled study, BMC Anesthesiology, 2018, 18(1), 34.
- Reference32 Leitzke, M, Stefanovic, D, Meyer, J.J, Schimpf, S, Schönknecht, P. Autonomic balance determines the severity of COVID-19 courses, Bioelectronic Medicine, 2020, 6(1), 22.
- Reference33 Tracey, K.J. The inflammatory reflex, Nature, 2002, 420(6917), 853-859.
- Reference34 Pavlov, V.A, Wang, H, Czura, C.J, Friedman, S.G, Tracey, K.J. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation, Molecular Medicine (Cambridge, Mass.), 2003, 9(5-8), 125-134.
- Reference35 Baptista, A.F, Baltar, A, Okano, A.H, Moreira, A, Campos, A.C.P, Fernandes, A.M, et al., Applications of non-invasive neuromodulation for the management of disorders related to covid-19, Frontiers in Neurology, 2020, 11, 573718. Reference36 Farsalinos, K, Niaura, R, Le Houezec, J, Barbouni, A, Tsatsakis, A, Kouretas, D, et al., Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system, Toxicology Reports, 2020, 7:, 658-663.
- Reference37 Johnson, J.N, Ackerman, M.J, QTc: how long is too long?, British Journal of Sports Sedicine, 2009, 43(9), 657-662.
- Reference38 Woosley, R, Heise, C, Romero, K, QTdrugs list. https://www.crediblemeds.org/., 2020 (accessed 20.05.2021)
- Reference39 Vouri, S.M, Thai, T.N, Winterstein, A.G, An evaluation of co-use of chloroquine or hydroxychloroquine plus azithromycin on cardiac outcomes: A pharmacoepidemiological study to inform use during the COVID19 pandemic, Research in Social & Administrative Pharmacy: RSAP, 2021, 17(1), 2012-2017.
- Reference40 Chatre, C, Roubille, F, Vernhet, H, Jorgensen, C, Pers, Y.M, Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature, Drug Safety, 2018, 41(10), 919-931.
- Reference 41 Ozturk, T, Gurpinar, T, Balaban, C.I, Tuncok, Y, Potential interactions between increased cytokines in COVID-19 and drugs used to treat COVID-19, Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 2021, 8(1), 174-185.
- Reference 42 Williams, D.P, Koenig, J, Carnevali, L, Sgoifo A, Jarczok MN, Sternberg EM, et al., Heart rate variability and inflammation: A meta-analysis of human studies, Brain, Behavior, and Immunity, 2019, 80, 219-226.
Details
| Primary Language | English |
|---|---|
| Subjects | Cardiovascular Surgery |
| Journal Section | Araştırma Makalesi |
| Authors | |
| Publication Date | September 30, 2021 |
| Published in Issue | Year 2021 Volume: 8 Issue: 3 |
