Exercise Intolerance and Excessive Chronotropic Response Due to Possible Autonomic Dysfunction Post COVID-19 Infection

Introduction and Objectives: In patients with Post-Acute Sequelae of Coronavirus 2 infection (PASC), a post infectious autonomic dysfunction may be one of the underlying mechanisms. Patients often present with exercise intolerance and exaggerated heart rate response to exercise. We report a single centre experience of patients with PACS and suspected autonomic dysfunction. Methods: Forty-two patients evaluated in the Outpatient Cardiology Department with suspected PASC were included in the study. Patients complained of compromised exercise performance persisting >3 months after recovery from COVID-19 infection, compared to the pre-COVID-19 period. The patients were evaluated with 12-lead electrocardiogram, echocardiography, 24-hour ECG ambulatory monitoring and either exercise stress test or a 6-minute walk test. Results: All 42 patients demonstrated an exaggerated chronotropic response, defined as the inappropriate increase in heart rate before the 6th minute of exercise >100% of the age-predicted maximal heart rate value with reproduction of clinical symptoms. In addition, 24-hour ambulatory electrocardiography revealed an increased mean heart rate of 92 beats/minute and decreased mean standard deviation of sequential 5-minute N-N interval (SDNN) of 74.4 ms. Pharmaceutical treatment with b-blockers, ivabradine or both was administrated in 29 (69%) resulting in symptomatic improvement in 82.8% of those under treatment. However, residual symptoms persisted in 69% of patients after 3 months. Conclusions: In patients with “Post-acute COVID-19” syndrome, we found an excessive chronotropic response to exercise suggesting autonomic dysfunction as the underlying mechanism of symptoms. Treatment with beta blockers or ivabradine resulted in clinical improvement but a substantial proportion of patients remained symptomatic.