Predictors of QT Interval Prolongation in Critically-ill Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine

  1. Frederico Scuotto
  2. Rogério Marra
  3. Lilian Leite de Almeida
  4. Mariana Santa Rita Soares
  5. Gabriela Kurita Silva
  6. Luiz Carlos Paul
  7. Guilherme Drummond Fenelon Costa
  8. Cláudio Cirenza

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Abstract

Background

Hydroxychloroquine (HCQ) has been described as a potential treatment for SARS-CoV-2 infection. However, there are safety concerns regarding its QT interval and pro-arrhythmic effects.

Objective

This trial aimed to determine the predictors of QT interval prolongation and pro-arrhythmic effects in patients hospitalized for SARS-CoV-2 infection and receiving HCQ.

Methods

We performed a retrospective observational study of 45 critically-ill patients hospitalized because of SARS-CoV-2 infection and treated with 800 mg of HCQ at day 1 and 400 mg on days 2–5. Clinical aspects and outcomes, basal and final corrected QT (QTc) interval, and the incidence of arrhythmias and arrhythmogenic death were observed. Independent predictors of QTc prolongation were identified using multivariable logistic regression analysis. QT interval prolongation was considered substantial at final QTc ≥ 480 ms.

Results

The mean age was 60.9 ± 16.67 years and 28 (62.2%) patients were men. Basal QTc was 442 ± 28 ms, and the final QTc interval was 458 ± 34 ms, for a mean QTc interval variation of 15 ± 11 ms. There was no arrhythmogenic death. The need for hemodialysis remained a statistically significant predictor of QT interval enlargement (odds ratio, 10.34; 95% confidence interval, 1.04 – 102.18; p = 0.045).

Conclusions

HCQ promotes mild to moderate QT interval prolongation. The risk of QT interval prolongation is higher among patients with acute renal failure requiring hemodialysis.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.26.20239418: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The study was submitted to the hospital’s ethics committee and approved.
    Consent: Since the study was retrospective and observational, no informed consent was required.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line AuthenticationAuthentication: Electrocardiogram Analysis: For the electrocardiogram (ECG) parameters, values from the baseline ECG, including heart rate (HR), QRS duration, and morphology as well as measured and corrected QT (QTc) interval, were collected for each patient before the treatment.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Our study has several limitations. First, this was a retrospective observational trial, with a non-randomized sample of patients. The treatment was not homogeneous between the patients, and 17.8% of patients were treated only with HCQ without azithromycin. Moreover, the sample size, although large enough to demonstrate hemodialysis as a predictor of QTc lengthening, was not large enough to show that acute renal failure and elevated creatinine levels are also statistically significant predictors, despite the fact that it can be inferred, reaching nearly significance. Furthermore, the inability to measure the final QTc interval in five patients might also affect the outcomes, given the reduced sample size. The ECG review by only one electrophysiologist might also have contributed to measuring bias. Lastly, we did not assess serum drug concentrations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.11.26.20239418v1 on medRxiv