Prognostic Value of Left Ventricular Global Longitudinal Strain in COVID-19.

The novel severe acute respiratory syndrome coronavirus 2019 (COVID-19) was declared a global pandemic by the World Health Organization on March 11, 2020. Reports have noted right ventricular longitudinal strain to be a strong predictor of mortality in patients with COVID-19. Although left ventricular global longitudinal strain (GLS) has been well validated as a prognostic cardiovascular marker, the utility of left ventricular GLS in risk stratification of COVID-19 remains unknown. We assessed the association of left ventricle GLS in patients with COVID-19.

Between March 16, 2020 and May 21, 2020, we reviewed 35 consecutive patients with laboratory confirmed diagnosed COVID-19 within the University Hospital Health System who underwent echocardiography. We excluded echocardiograms performed more than 10 days prior to and 21 days after COVID19 confirmation. We performed retrospective 2D strain analysis using EchoInsight software (Epsilon Imaging). Strain curves were manually examined and segments with poor strain curve quality were excluded. We followed patients for all-cause mortality, through linkage with state death files. Association between GLS and mortality was assessed using Kaplan-Meier survival analysis and Cox regression, using two follow-up times (time since echocardiogram and time since COVID19 confirmation). Cox models were adjusted for age and left ventricular ejection fraction. This study was approved by the institutional review board at University Hospitals.

A total of 31 patients were included in the final analysis (3 were excluded due to poor windows, and 1 was incompatible with the software). A total of 92 segments from 23 patients were excluded due to poor windows. The median time from COVID-19 confirmation to echocardiogram was 3 (1 to 7) days. Median age was 64 (60 to 71), Left Ventricular Ejection Fraction 57.5% (47.5 to 60), median GLS −11.8 (−14.7 to −10.2). At a median follow-up of 38 (26 to 49) days from COVID-19 and 29 (23 to 34) days from TTE, 8 patients died. Mortality by tertiles are shown in Figure 1 . For each 1% increase (less negative) in GLS was associated with increased mortality (Hazard ratio [HR] 1.52; 95% confidence interval [CI]: 1.10 to 2.11, p = 0.013 from COVID19; HR 1.39 (1.10 to 1.75), p = 0.006 from echocardiogram). After adjusting for age and LV ejection fraction, the association between GLS and mortality was unchanged (HR 1.39; 95% CI: 1.11 to 1.76, p = 0.005 from COVID19; HR 1.54; 95% CI: 1.10 to 2.15, p = 0.011 from echocardiogram).

Figure 1

Central Illustration: Model 1 comparing tertile of global longitudinal strain (GLS) and mortality by days since COVID-19 diagnosis as adjusted for ejection fraction (EF) and age. Model 2 comparing tertile of GLS and mortality by days since echocardiogram diagnosis as adjusted for age and EF.

Thus, we observed significantly increased mortality with decrease (less negative) in left ventricular GLS in patients with COVID-19. This is congruent with prior literature of left ventricular strain as a more powerful predictor of all cause death than visual ejection fraction even when adjusted for multiple confounders. Our study extends these results to patients with the severe acute respiratory syndrome coronavirus 2019 (COVID-19). Potential mechanisms to explain these results, besides specific direct tissue invasion, COVID-19 frequently leads to cytokine storm contributing to multisystem organ dysfunction/failure. Cytokine storm and cardiomyocyte oxidative stress has been linked to impaired global longitudinal strain on echocardiography.

Although limited by the small sample size, observational nature, unobserved confounding variables, and lack of metrics to further classify illness severity, our findings suggest that left ventricular GLS may be associated with mortality in patients with COVID-19. The potential utility of strain echocardiography in the COVID-19 population needs to be further explored.