Echocardiographic Correlates of In-Hospital Death in Patients with Acute COVID-19 Infection: The World Alliance Societies of Echocardiography (WASE-COVID) Study

Abstract

Background: The novel severe acute respiratory syndrome coronavirus-2 virus, which has led to the global coronavirus disease-2019 (COVID-19) pandemic is known to adversely affect the cardiovascular system through multiple mechanisms. In this international, multicenter study conducted by the World Alliance Societies of Echocardiography, we aim to determine the clinical and echocardiographic phenotype of acute cardiac disease in COVID-19 patients, to explore phenotypic differences in different geographic regions across the world, and to identify parameters associated with in-hospital mortality.

Methods: We studied 870 patients with acute COVID-19 infection from 13 medical centers in four world regions (Asia, Europe, United States, Latin America) who had undergone transthoracic echocardiograms. Clinical and laboratory data were collected, including patient outcomes. Anonymized echocardiograms were analyzed with automated, machine learning-derived algorithms to calculate left ventricular (LV) volumes, ejection fraction, and LV longitudinal strain (LS). Right-sided echocardiographic parameters that were measured included right ventricular (RV) LS, RV free-wall strain (FWS), and RV basal diameter. Multivariate regression analysis was performed to identify clinical and echocardiographic parameters associated with in-hospital mortality.

Results: Significant regional differences were noted in terms of patient comorbidities, severity of illness, clinical biomarkers, and LV and RV echocardiographic metrics. Overall in-hospital mortality was 21.6%. Parameters associated with mortality in a multivariate analysis were age (odds ratio [OR] = 1.12 [1.05, 1.22], P = .003), previous lung disease (OR = 7.32 [1.56, 42.2], P = .015), LVLS (OR = 1.18 [1.05, 1.36], P = .012), lactic dehydrogenase (OR = 6.17 [1.74, 28.7], P = .009), and RVFWS (OR = 1.14 [1.04, 1.26], P = .007).

Conclusions: Left ventricular dysfunction is noted in approximately 20% and RV dysfunction in approximately 30% of patients with acute COVID-19 illness and portend a poor prognosis. Age at presentation, previous lung disease, lactic dehydrogenase, LVLS, and RVFWS were independently associated with in-hospital mortality. Regional differences in cardiac phenotype highlight the significant differences in patient acuity as well as echocardiographic utilization in different parts of the world.

Keywords: COVID-19; Echocardiography; International; Mortality; Strain; WASE.

Figure 1

Temporal trends in study enrollment in each of the four world regions. In the early months of the pandemic (January-February), the majority of COVID-19 admissions occurred in Asia, followed shortly thereafter by Europe and the United States (March-May), and finally Latin America (May-September).

Figure 2

Regional differences in heart and lung disease. (A) Regional differences in rates of heart disease among COVID-19 patients who underwent echocardiograms, with the highest rates observed in the United States (73.8%), followed by Latin America (68.1%), Europe (55.2%), and Asia (46.9%). (B) Regional differences in rates of lung disease among COVID-19 patients who underwent echocardiograms, with the highest rates observed in the United States (36.9%), followed by Latin America (11.8%), Europe (17.7%), and Asia (3.9%). Data are shown as a pie chart depicting percentage of patients with heart and lung disease, respectively, in each world region.

Figure 3

Regional differences in biomarkers. Violin plots depicting regional differences in LDH (A), BNP (B), and D-dimer (C) biomarkers. In all cases, the highest values were observed in the United States, followed by Europe, Latin America, and then Asia, with ranges depicted in the plots above. Central dots and lines represent mean ± SD. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 compared with United States.

Figure 4

Regional differences in LVEF, LVLS, RVFWS, and RVBD. Violin plots depicting regional differences in LVEF (A), LVLS (B), RVFWS (C), and RVBDs (D). Better functional average values were observed in Asia, followed by Europe, Latin America, and the United States. Central dots and lines represent means ± SD. Widths of the plots are directly proportionate to the number of cases. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 compared with United States.

Figure 5

Regional differences in in-hospital mortality. Pie chart demonstrating in-hospital mortality rates in different geographic regions (11% in Asia, 19% in Europe, 27% in Latin America, and 26% in the United States).