Investigation of Autonomic Dysfunction Following COVID-19: the Role of Heart Rate Recovery Indices

Yıl 2024, Cilt: 14 Sayı: 3, 296 - 303, 31.12.2024

Metin Çoksevim , Mustafa Yenerçağ

Öz

Aim: COVID-19, caused by SARS-CoV-2, has been linked to longterm complications known as “long COVID,” including autonomic dysfunction. Heart rate recovery (HRR) following exercise is a widely used marker for assessing autonomic function. This study evaluated HRR in Long-Term COVID patients and its association with inflammatory markers.
Materials and Methods: This retrospective study included 152 participants: 76 Long-Covid patients and 76 controls. Heart rate recovery was measured at 1, 2, 3, 4, and 5 minutes post-exercise using the Bruce protocol. Baseline demographic data and inflammatory markers, including CRP, D-dimer, and ferritin, were collected. Correlation analysis was performed between HRR and these markers.
Results: Long-Covid patients had significantly elevated levels of CRP (14.6±2.3 mg/L vs. 3.3±2.5 mg/L), D-dimer (128.2±42.1 μg/ml vs. 21.1±9.7 μg/ml), and ferritin (277.5±146.8 ng/ml vs. 112.3±78.2 ng/ml) compared to controls (p <0.001). HRR1 and HRR2 were significantly reduced in post-COVID patients (22.4±7.4 vs. 29.0±8.0; 31.5±17.4 vs. 40.2±10.9; p <0.001). Heart rate recovery at 3, 4, and 5 minutes was also markedly lower. A moderate negative correlation was found between HRR2 and CRP (rs=-0.537), D-dimer (rs=-0.459), and ferritin (rs=-0.461) (p <0.001).
Conclusion: Long-Covid patients exhibited impaired HRR, indicating autonomic dysfunction, which correlated with elevated inflammatory markers. These findings highlight the importance of HRR as a marker for autonomic imbalance in Long-Covid, suggesting a need for further investigation into therapeutic strategies for autonomic dysfunction.

Anahtar Kelimeler

long COVID, heart rate recovery (HRR), autonomic dysfunction, inflammatory markers

Kaynakça

• 1. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. The lancet. 2020;395(10223):470–3.
• 2. Asarcikli LD, Hayiroglu Mİ, Osken A, Keskin K, Kolak Z, Aksu T. Heart rate variability and cardiac autonomic functions in post-COVID period. Journal of Interventional Cardiac Electrophysiology. 2022;63(3):715–21.
• 3. Gyöngyösi M, Alcaide P, Asselbergs FW, Brundel BJ, Camici GG, Martins PdC, et al. Long COVID and the cardiovascular system –elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases. Cardiovascular Research. 2023;119(2):336–56.
• 4. Shouman K, Vanichkachorn G, Cheshire WP, Suarez MD, Shelly S, Lamotte GJ, et al. Autonomic dysfunction following COVID-19 infection: an early experience. Clinical Autonomic Research. 2021;31:385–94.
• 5. Seibert FS, Stervbo U, Wiemers L, Skrzypczyk S, Hogeweg M, Bertram S, et al. Severity of neurological Long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors. Autoimmunity Reviews. 2023:103445.
• 6. Okutucu S, Karakulak UN, Aytemir K, Oto A. Heart rate recovery: a practical clinical indicator of abnormal cardiac autonomic function. Expert review of cardiovascular therapy. 2011;9(11):1417–30.
• 7. Fecchio RY, Brito L, Leicht AS, Forjaz CL, Peçanha T. Reproducibility of post-exercise heart rate recovery indices: A systematic review. Autonomic Neuroscience. 2019;221:102582.
• 8. Dani M, Dirksen A, Taraborrelli P, Torocastro M, Panagopoulos D, Sutton R, et al. Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies. Clinical Medicine. 2021;21(1):e63.
• 9. Lachman S, Terbraak MS, Limpens J, Jorstad H, Lucas C, op Reimer WS, et al. The prognostic value of heart rate recovery in patients with coronary artery disease: a systematic review and meta-analysis. American Heart Journal. 2018;199:163–9.
• 10. Qiu S, Cai X, Sun Z, Li L, Zuegel M, Steinacker JM, et al. Heart rate recovery and risk of cardiovascular events and all‐cause mortality: a meta‐analysis of prospective cohort studies. Journal of the American Heart Association. 2017;6(5):e005505.
• 11. https://www. who. int/publications/i/item/ WHOCCmlg, 2021 W--n-c--AJ. World Health Organization (2021) COVID-19 Clinical management: living guidance. 2021.
• 12. Health NIf, Excellence C. COVID-19 rapid guideline: managing the long-term effects of COVID-19: National Institute for Health and Care Excellence;2020.
• 13. Byun YH, Kim SY, Mok Y, Kim Y, Jee SH. Heart rate recovery and cancer risk: prospective cohort study. Asia Pacific Journal ofPublic Health. 2018;30(1):45–55.
• 14. Aneni E, Roberson LL, Shaharyar S, Blaha MJ, Agatston AA, Blumenthal RS, et al. Delayed heart rate recovery is strongly associated with early and late-stage prehypertension during exercise stress testing. American journal of hypertension. 2014;27(4):514–21.
• 15. Organization WH. “What is wrong with me?” Children face a frustrating lack of answers about long COVID. In: WHO/ Europe., editor. WHO/Europe https://wwwwhoint/europe (accessed 5 October 2023)2023.
• 16. Astin R, Banerjee A, Baker MR, Dani M, Ford E, Hull JH, et al. Long COVID. mechanisms, risk factors and recovery. Experimental physiology. 2023;108(1):12–27.
• 17. Clavario P, De Marzo V, Lotti R, Barbara C, Porcile A, Russo C, et al. Cardiopulmonary exercise testing in COVID-19 patients at 3 months follow-up. International journal of cardiology. 2021;340:113–8.
• 18. Jimeno-Almazán A, Pallarés JG, Buendía-Romero Á, Martínez- Cava A, Courel-Ibáñez J. Chronotropic incompetence in nonhospitalized patients with post-COVID-19 syndrome. Journal of Clinical Medicine. 2021;10(22):5434.
• 19. Ladlow P, O’Sullivan O, Houston A, Barker-Davies R, May S, Mills D, et al. Dysautonomia following COVID-19 is not associated with subjective limitations or symptoms but is associated with objective functional limitations. Heart Rhythm. 2022;19(4):613–20.
• 20. Pancar Yuksel E, Yuksel S, Yenercag M, Soylu K, Aydin F, Senturk N, et al. Impaired heart rate recovery indices in psoriasis patients. Med Sci Monit. 2014;20:350–4.
• 21. Huckstep OJ, Burchert H, Williamson W, Telles F, Tan CMJ, Bertagnolli M, et al. Impaired myocardial reserve underlies reduced exercise capacity and heart rate recovery in preterm-born young adults. Eur Heart J Cardiovasc Imaging. 2021;22(5):572–80.
• 22. Dewar A, Kass L, Stephens RCM, Tetlow N, Desai T. Heart Rate Recovery Assessed by Cardiopulmonary Exercise Testing in Patients with Cardiovascular Disease: Relationship with Prognosis. Int J Environ Res Public Health. 2023;20(6).
• 23. Karakayalı M, Artac I, Ilis D, Omar T, Altunova M, Guzel E, et al. Evaluation of Symptomatic and Asymptomatic Outpatients in the Post-COVID-19 Period With Electrocardiographic Ventricular Depolarization and Repolarization Parameters. International Journal of Cardiovascular Sciences. 2024;37:e20230105.
• 24. Karakayalı M, Artac I, Ilis D, Omar T, Rencuzogullari I, Karabag Y, et al. Evaluation of outpatients in the post-COVID-19 period in terms of autonomic dysfunction and silent ischemia. Cureus. 2023;15(6).