Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19

Padilla, Sergio; Telenti, Guillermo; Guillén, Lucía; García, José Alberto; García-Abellán, Javier; Ding, Carolina; Mora, Antonia; García-Pachón, Eduardo; Gutiérrez, Félix; Masiá, Mar

BACKGROUND: We aimed to assess the risk of QT-corrected (QTc) interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. METHODS: Longitudinal, prospective cohort. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval exceeding 470 ms in men or 480 ms in women. Patients were treated under strict cardiac supervision. RESULTS: One hundred and five adults, 56% male and median (Q1, Q3) age of 69 (57, 79), were included. All received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/RTV). Concomitant medications classified as having risk of developing Torsades de Pointes (TdP) were simultaneously used in 81 (77%) patients. In 14 (13%) subjects, a moderate-to-severe QTc prolongation was observed, mostly at days 3-5 from baseline, with 6 (6%) of them developing severe prolongation (> 500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/RTV to HCQ/AZM did not significantly prolong the QTc. Multivariable Cox regression revealed that comedications with known risk of TdP (HR 11.28, 95%CI 1.08–117.41), higher neutrophil-to-lymphocyte ratio (HR 1.10, 95%CI 1.03-1.18 per unit increase) and higher serum HS-cardiac troponin I (HR 4.09, 95%CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. CONCLUSIONS: In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacologic therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically a higher neutrophil-to-lymphocyte ratio, are conditions under which QTc interval monitoring should be particularly careful.