key: cord-0823635-ru725fbr
authors: Ammor, Othmane; Abdessamad, Ait Brik; Boussaadani, Badre El; Mahdi, Zainab; Najdi, Adil; Raissuni, Zainab
title: Hidroxicloroquina / cloroquina y azitromicina en pacientes con COVID-19: estudio prospectivo de parámetros eléctricos
date: 2020-09-11
journal: nan
DOI: 10.1016/j.rccl.2020.09.002
sha: 73a1c2fe0b46129ed2c038c629243f0369173a16
doc_id: 823635
cord_uid: ru725fbr

nan

This is a prospective observational study from Tangier University Hospital. All hospitalized patients with PCR-confirmed COVID-19 infection treated with chloroquine/hydroxychloroquine plus azithromycin were included from April 7 to May 6. PCR-confirmed COVID-19 patients were treated as follows: chloroquine (500 mg twice a day for 10 days) or hydroxychloroquine (200 mg 3 times a day, for 10 days) in combination with azithromycin (500 mg on day 1, then 250 mg a day from day 2 to 7). All data were collected, analyzed and verified by senior cardiologists. All patients had at least 3 electrocardiograms: on admission, on day 2, and at the end of treatment.

Continuous monitoring by telemetry in high-risk patients (intensive care unit patients, medical history of arrhythmia or heart disease) was performed. Two physicians analyzed all electrocardiograms, with rhythm analysis, heart rate calculation, and systematic search for Q waves of necroses, atrioventricular block, right/left bundle branch, ventricular extrasystoles, torsade de pointes and ventricular arrhythmia; PR, QRS, QT and QT corrected intervals were measured manually. The lead showing the longest QT interval was used. The QTc is calculated according to the Bazett formula whenever the heart rate was between 50-100 bpm and the rhythm was in regular sinus, and according to the FREDERICIA formula whenever the heart rate was below 50 bpm or above 100 bpm or the rhythm was irregular.

The prolongation was defined as QTc > 460 ms in women and > 450 ms in men, a severe prolongation was defined if QTc > 500 ms or QTc delta > 60 ms. 1 A total of 87 patients were treated with hydroxychloroquine/chloroquine plus azithromycin.

Clinical and demographic characteristics are summarized in Table1 Some monomorphic ventricular extrasystoles were noted, but no ventricular tachycardia or torsade de pointe was detected. A receiver operating characteristic (ROC) curve analysis was J o u r n a l P r e -p r o o f carried out to explore a QTc threshold at baseline for which there would be no risk of major QTc prolongation. There was no safety threshold for the initial QTc that allowed a safe prescription without ECG monitoring.

Chloroquine/hydroxychloroquine are related to type 1a antiarrhythmics and act as membrane stabilizers and cause QRS and QT prolongation. 2 The association induced mild QTc prolongation when given to young volunteers in good health.

In our study, the association of chloroquine/hydroxychloroquine and azithromycin induced significant QTc prolongation in 33 of 87 patients (38%), but a severe prolongation was noted in only 13 (15%) patients (QTc > 500 ms or delta QTc > 60ms). A significant QRS enlargement was noted, but no pathological prolongation was found (QRS > 120ms or delta QRS > 30%). Besides, no arrhythmic deaths have been reported in our series.

We found that the chloroquine group markedly increased QTc and QRS duration compared to the hydroxychloroquine group. Hydroxychloroquine seems to be safer. patients with prolonged QTc. 1 We observed that in our cohort there was no greater prolongation of the QT interval in women, and that age was the only factor implicated in this prolongation (> 48 years old).

Unfortunately, our study does not allow to suggest a safety threshold of the initial QTc for which there would be no major prolongation of the QTc, but we still believe that we can potentially suggest an early discharge with ambulatory follow-up for some selected patients, such as those younger, without cardiovascular risk factors or any other medication known to be associated with QTc prolongation.

An innovative approach has been described in a recent publication, proposing mobile cardiac outpatient telemetry for QTc and arrhythmia monitoring, and minimizing both health professionals' exposure and personal protective equipment use. 6 Moreover, this tool is not easily available in the majority of healthcare systems; other alternatives such as programs on smartwatches are currently under development for a better care optimizing. Our study has some limitations, a low sample size and a relatively young population; the results should be taken with caution and cannot be extrapolated. Kalaemia, mmol/L 4,7 (0.7) Glycemia, g/L 1,3 (0.8) Troponin I, ng/mL 9,9 (17.7)

Data are expressed as no. (%) or mean (± standard deviation).

BMI, body mass index; BP, blood pressure.

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)

Cardiotoxicity of antimalarial drugs

The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection

The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France

Inpatient Use of Ambulatory Telemetry Monitors for COVID-19

Patients Treated with Hydroxychloroquine and/or Azithromycin

FIGURE LEGENDS FIGURE 1: QTc after chloroquine/hydroxychloroquine treatment, at day 0, day 2 (D2) and end of treatment