Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin

Int J Cardiol. 2020 Oct 1:316:280-284. doi: 10.1016/j.ijcard.2020.05.036. Epub 2020 May 19.

Abstract

Background: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established.

Methods: We performed 12‑lead ECGs and 12‑lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control.

Results: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4). No patients showed "R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability.

Conclusion: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.

Keywords: COVID-19; Coronavirus; Severe acute respiratory syndrome; Sudden death; Ventricular arrhythmia.

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Azithromycin* / administration & dosage
  • Azithromycin* / adverse effects
  • Betacoronavirus / isolation & purification
  • COVID-19
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / physiopathology
  • Death, Sudden, Cardiac / etiology
  • Death, Sudden, Cardiac / prevention & control
  • Drug Monitoring / methods
  • Electrocardiography / methods*
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Hydroxychloroquine* / administration & dosage
  • Hydroxychloroquine* / adverse effects
  • Long QT Syndrome* / chemically induced
  • Long QT Syndrome* / complications
  • Long QT Syndrome* / diagnosis
  • Male
  • Middle Aged
  • Outcome and Process Assessment, Health Care
  • Pandemics*
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / physiopathology
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • Hydroxychloroquine
  • Azithromycin