QT-prolongation in patients with severe COVID-19 is multicausal and not limited to anti-SARS-CoV-2 drugs

We read with interest the article published by Zaballos et al. investigating QT prolongation in 77 patients with severe SARS-CoV-2 infection admitted to the intensive care unit (ICU) over a 3-month period.¹ The authors found that 56% of patients had QT prolongation, 44% had some type of arrhythmia, and 21% had atrial arrhythmia.¹ Overall mortality was 53%, with no difference between patients with and without QT prolongation,¹ and it was concluded that the high proportion of ICU COVID-19 patients with QT prolongation could be due to elevated cardiac biomarkers, viral myocarditis, and concomitant use of medications in the ICU.¹ The study is impressive, but raises some questions.

First, the authors only included anti-SARS-CoV-2 medication in their analysis, but not the other drugs that the 77 enrolled patients received in addition to this therapy, some of which could also have caused QT prolongation.² Furthermore, the authors fail to mention how many of their patients presented other risk factors for QT prolongation, such as female gender, age >65 years, heart failure, ventricular hypertrophy, myocardial infarction, recent conversion from atrial fibrillation, liver or kidney failure, hypothyroidism, family history of sudden cardiac death, diabetes, electrolyte imbalance, bradycardia, and congenital long-QT syndrome.³

Second, echocardiography was not performed. Since patients with QT prolongation are significantly more likely to present pro-brain natriuretic peptide (pro-BNP) >5000 pg/mL than patients with normal QT,¹ it is important to know how many of the enrolled patients presented heart failure or systolic dysfunction. In addition, it is important to rule out myocardial infarction, because troponin levels were higher in patients with QT prolongation than in those without.

Since patients with QT prolongation are more likely to present elevated troponin, and Takotsubo syndrome (TTS), which resembles myocardial infarction and has been reported as a cardiac complication of SARS-CoV-2 infections,⁴ it is important to know whether patients with elevated troponin have had TTS, myocardial infarction, angina chest pain, or renal insufficiency.

We disagree with the authors’ statement in the results section that there were no significant differences in demographics and clinical parameters.¹ Table 1 of the study shows that there were significantly more men than women with QT prolongation¹; therefore, the difference in the prevalence of QT prolongation in men (65%) vs women (30%) could be due to the smaller number of women included in the study.

In summary, this interesting study has limitations that call into question the results and their interpretation. Clarifying these weaknesses would strengthen the conclusions and could improve the study. QT prolongation, a common finding in ICU patients with COVID-19, is not only caused by QT-prolonging anti-SARS-CoV-2 medications, but also by several other factors.

Statement of ethics

The study was approved by the institutional review board.

Data availability statement

Data that support the findings of the study are available from the corresponding author.

Funding

No funding was received.

Author contribution

JF: design, literature search, discussion, first draft, critical comments, final approval.

Disclosures

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Compliance with ethics guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.