QT Interval Prolongation Under Hydroxychloroquine/Azithromycin Association for Inpatients With SARS-CoV-2 Lower Respiratory Tract Infection

Abstract

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24^th to April 20^th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.

Figure 1

Twelve‐lead electrocardiogram of a 55 years‐old female patient presenting a significantly prolonged QTc interval (590 ms), under current psychotropics medication.

Figure 2

Corresponding CT‐scan image of the same patient with typical pulmonary lesions of COVID‐19 lower respiratory tract infection with a NEWS score initially calculated at 9 on admission.

Figure 3

Graph showing the evolution of the QTc from baseline to day 2, with the combined therapy (Hydroxychloroquine/Azithromycin).

Figure 4

Graph showing delta QTc variations in the 71 patients treated with the HCQ/AZT association (manual measurements with Bazett’s correction).

Figure 5

Bland‐Altman plot comparing automated corrected QT generated by ECG machine and manually (Bazett’s correction). LOA, limits of agreement.

Figure 6

Bland‐Altman plot comparing automated corrected QT generated by ECG machine and manually (Fridericia’s correction). LOA, limits of agreement.