Prolonged QT predicts prognosis in COVID-19

Abstract

Background: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc).

Method: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19.

Results: Patients who died were older than survivors (82 vs 69.8 years, p < 0.001), more likely to have cancer (22.3% vs 13.1%, p = 0.034), dementia (25.6% vs 10.7%, p = 0.034) and ischemic heart disease (27.8% vs 10.7%, p < 0.001). Deceased patients exhibited higher levels of C-reactive protein (244.6 mg/L vs 146.5 mg/L, p < 0.01), troponin (1982.4 ng/L vs 413.4 ng/L, p = 0.017), with a significantly longer QTc interval (461.1 ms vs 449.3 ms, p = 0.007). Pre-COVID electrocardiograms were located for 172 patients; the QTc recorded on presentation with COVID-19 was longer than the prior measurement in both groups, but was more prolonged in the deceased group (448.4 ms vs 472.9 ms, pre-COVID vs COVID, p < 0.01). Multivariate Cox-regression analysis revealed age, C-reactive protein and prolonged QTc of >455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]).

Conclusion: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.

Keywords: COVID-19; Sars-Cov-2; electrocardiogram; mortality; prolonged QTc.

FIGURE 1

ECG example from the deceased group with QT measurements. a) Pre‐COVID and b) COVID admission ECG from a deceased patient. There is prolongation of the QTc with the COVID‐19 illness. The annotations demonstrate the QT interval and the R‐R interval used for correction [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Individual changes of the QTc. (A) There is an overall trend of prolonging QTc with the Covid‐19 infection. There was significant prolongation of the QTc from pre‐COVID measurement in the (B) deceased (p < 0.001) and the (C) survived patients (p < 0.001). The degree of prolongation was notably greater in the deceased patients [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Cox‐survival plot comparing mortality risk in QTc quartiles. In our cohort, a prolonged corrected QT‐interval in the fourth quartile (>469 ms) was associated with an increased risk of mortality when compared to the lower quartiles (p = 0.006, HR 1.98 [1.2‐3.2]) [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Kaplan‐Meier survival curve of patients with a prolonged QTc and normal QTc. At 6 weeks from the date of admission, the probability of survival in patients with a prolonged QTc (>455 ms male; >465 ms female) was significantly lower than those patients who had a normal QTc (p = 0.0027, HR 1.78 [1.2‐2.6]) [Color figure can be viewed at wileyonlinelibrary.com]