Post-COVID postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia: prevalence, overlap and clinical characteristics

Background Postural orthostatic tachycardia syndrome (POTS) and inappropriate sinus tachycardia (IST) are tachycardic phenotypes of cardiovascular dysautonomia following COVID-19 found in one third of highly symptomatic long COVID patients. Their prevalence and differential characteristics are poorly studied. Purpose To characterize and compare clinical and hemodynamic profiles among patients with long COVID who were diagnosed with POTS and IST. Methods Patients with symptomatic post-COVID tachycardia referred to the tertiary diagnostic center were examined by head-up tilt and/or active standing, 24-hour ECG monitoring, and classified as POTS, IST or POTS+IST (dual pathology). Data on comorbidities, clinical examinations, exercise ECG, 6-minute walk test, symptoms, and medications were collected. Categorical variables were compared using chi-square or Fisher’s exact test, and continuous variables were analyzed with ANOVA or Kruskal-Wallis tests, with appropriate post-hoc corrections. Results Of 369 referred patients, 270 (73%) were diagnosed with POTS (n=147, mean age 38±10 years, female 86%), IST (n=41, mean age 45±12 years, female 90%), or dual pathology (n=82, mean age 39±13 years, female 88%; Figure 1). Hypertension was more frequent in IST (37%) than in dual pathology (21%) and POTS (10%; p<0.001). Presyncope/syncope occurred in 70% of dual pathology patients, 59% of POTS, and 46% of IST patients (p=0.04). Cognitive impairment was most frequently reported in POTS patients (80%), followed by dual pathology (77%) and IST (54%; p=0.003) patients. Nausea was more prevalent in patients with dual pathology (63%) and POTS (63%) compared to IST (37%; p=0.006). Resting systolic blood pressure was higher in patients with dual pathology (124±18 mmHg) and IST (124±12 mmHg) compared to patients with POTS (117±14 mmHg; p=0.001). Functional capacity, measured by exercise ECG and six-minute walk test (POTS: 430±162 m, IST: 461±162 m, dual pathology: 421±130 m; p=0.221; normal value: ≥600 m) was similarly reduced across all groups. No significant difference was observed regarding self-reported symptom burden according to Malmö POTS Symptom Score (POTS: 61±20 points; IST: 61±24 points; dual pathology: 66±22 points; p=0.901). Conclusions IST exhibits distinct clinical and hemodynamic profiles with higher proportion of hypertension, higher resting systolic blood pressure and lower maximal heart rate on standing, whereas POTS and dual pathology exhibit higher rates of presyncope, cognitive impairment, and nausea. Furthermore, by only focusing on POTS, one might miss the 15% of patients diagnosed with only IST. These findings highlight the heterogeneity of post-COVID tachycardia phenotypes, underscoring the need for tailored diagnostic and therapeutic approaches.