key: cord-1006218-bcynpexm
authors: Bursi, Francesca; Santangelo, Gloria; Sansalone, Dario; Valli, Federica; Vella, Anna Maria; Toriello, Filippo; Barbieri, Andrea; Carugo, Stefano
title: Prognostic utility of quantitative offline 2D‐echocardiography in hospitalized patients with COVID‐19 disease
date: 2020-09-22
journal: Echocardiography
DOI: 10.1111/echo.14869
sha: 0eb7c4b00dfcf4d04b8775e2c6e29609b4b71696
doc_id: 1006218
cord_uid: bcynpexm

PURPOSE: To assess the prognostic utility of quantitative 2D‐echocardiography, including strain, in patients with COVID‐19 disease. METHODS: COVID‐19‐infected patients admitted to the San Paolo University Hospital of Milan that underwent a clinically indicated echocardiographic examination were included in the study. To limit contamination, all measurements were performed offline. Quantitative measurements were obtained by an operator blinded to the clinical data. RESULTS: Among the 49 patients, nonsurvivors (33%) had worse respiratory parameters, index of multiorgan failure, and worse markers of lung involvement. Right ventricular (RV) dysfunction (as assessed by conventional and 2‐dimensional speckle tracking) was a common finding and a powerful independent predictor of mortality. At the ROC curve analyses, RV free wall longitudinal strain (LS) showed an AUC 0.77 ± 0.08 in predicting death, P = .008, and global RV LS (RV‐GLS) showed an AUC 0.79 ± 0.04, P = .004. This association remained significant after correction for age (OR = 1.16, 95%CI 1.01–1.34, P = .029 for RV free wall LS and OR = 1.20, 95%CI 1.01–1.42, P = .033 for RV‐GLS), for oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen (OR = 1.28, 95%CI 1.04–1.57, P = .021 for RV free wall‐LS and OR = 1.30, 95%CI 1.04–1.62, P = .020 for RV‐GLS) and for the severity of pulmonary involvement measured by a computed tomography lung score (OR = 1.27, 95%CI 1.02–1.19, P = .034 for RV free wall LS and OR = 1.30, 95%CI 1.04–1.63, P = .022 for RV‐GLS). CONCLUSIONS: In patients hospitalized with COVID‐19, offline quantitative 2D‐echocardiographic assessment of cardiac function is feasible. Parameters of RV function are frequently abnormal and have an independent prognostic value over markers of lung involvement.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new human coronavirus causing the ongoing coronavirus disease which started in December 2019 in Wuhan, China, and rapidly spread to all continents. The World Health Organization (WHO) declared the outbreak to be a pandemic on March 11, 2020. 1 Clinical presentation ranges from asymptomatic to acute respiratory distress syndrome (ARDS) that can lead to death. 2 Patients with concomitant cardiac diseases have an extremely poor prognosis, 3, 4 and SARS-CoV-2 may cause direct acute and chronic damage to the cardiovascular system. 5 Echocardiography may provide useful information, especially in critical care patients, because it can be performed quickly at the bedside. However, the recommendations relating to the use of echocardiography in the COVID-19 pandemic must be considered only as expert suggestions due to the lack of evidence-based scientific outcome data. To date, there is no means to predict the impact of the virus on patient outcome probably because the pathophysiology of COVID-19 remains unexplained. We aimed to assess the prognostic utility of quantitative 2D-echocardiography, including strain analysis, in hospitalized patients with confirmed COVID-19 disease. Baseline clinical characteristics, laboratory, radiological, and instrumental data as well as therapy were obtained by review of electronic medical records. We collected arterial blood gases analysis, type of ventilation and setting, and vital parameters at the time of the echocardiographic examination.

These data were used to calculate the sequential organ failure assessment (SOFA) score. 7 ARDS was defined by applying Berlin criteria. 8 Creatinine kinase, high-sensitivity troponin, N-terminal pro-brain natriuretic peptide (NT-proBNP), transaminases, C-reactive protein, lactic dehydrogenase, and procalcitonin were collected at the peak level. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the glomerular filtration rate (eGFR). 9 Computed tomography (CT) reports and images were reviewed to evaluate the presence of typical COVID-19 features. A semiquantitative lung total severity score was calculated according to Chung at al. Each of the five lung lobes was assessed for degree of involvement and classified as none (0%), minimal (1%-25%), mild (26%-50%), moderate (51%-75%), or severe (76%-100%) with a score 0-4 for each segment. The overall lung "total severity score" was reached by summing the five lobe scores (ranging from 0 to 20) with higher values indicating a greater alteration of lung parenchyma. 10 In-hospital death was the outcome. The final follow-up date was June 19, 2020.

According to international societies, during the COVID-19 pandemic to reduce the risk of contamination and consumption of personal protective equipment (PPE), examinations were performed only if they provide clinical benefit taking into account patient characteristics, blood test abnormalities, and hemodynamic stability. [11] [12] [13] The echocardiograms were performed at the bedside, with patients in the left lateral decubitus position when possible, but mostly in supine or sitting position with a machine dedicated to COVID-19- 

Values are expressed as means ± SD, in case of highly skewed variables as median (25 th -75th percentile) or as percentages for categorical variables. Differences between groups were analyzed using independent sample t test, Mann-Whitney test, chi-square test or

Fisher's exact test as appropriate. Correlations between variables were evaluated with the Pearson coefficients.

To evaluate the prognostic accuracy of the RV echocardiographic indexes, receiver operating characteristic (ROC) curves were constructed and the area under the curve was calculated; sensitivity and specificity were calculated using standard definitions. Logistic regression analysis was used to calculate the risk of death of RV function parameters, and data are presented as odds ratios (OR) and 95%

confidence intervals (CI). Multivariable logistic regression analyses were performed to examine the prognostic role of RV dysfunction independent of markers of severity of pulmonary involvement. The reproducibility was measured using Bland-Altman analysis. Analyses were performed using the Statistical Package for the Social Sciences (SPSS Inc, Chicago, Illinois) version 23, and a two-sided value of P < .05 was considered as statistically significant.

We enrolled 49 patients, 31 (63.3%) men, mean age 65.7 ± 12.6 years, 6 were Hispanic, and the remainder Caucasian. Table 1 patients, in the remainder it confirmed a known cardiac condition (16%) or did not reveal any cardiac abnormality (61%).

During a mean hospital stay of 30 ± 17 days, 16 (33%) patients died. Table 1 shows the characteristics of the entire population and survivors vs nonsurvivors. Nonsurvivors showed worse respiratory parameters and worse index of multiorgan failure. At the CT, they presented worse calculated lung severity score, higher prevalence of crazy paving pattern, and microvascular dilation. In 10 randomly selected and blindly analyzed studies, Bland-Altman analysis demonstrated good intra-and inter-observer agreement, with a small bias not significantly different from zero.

For free wall LS, mean differences ± 2 SDs were −0.5 ± 1.5% and 0.8 ± 2.2%, for intra-and inter-observer agreement, respectively.

For RV-GLS, mean differences ± 2 SDs were −0.1 ± 0.7% and −0.3 ± 1.7%, for intra-and inter-observer agreement, respectively. Abbreviations: CT = computed tomography; FiO2 = fraction of inspired oxygen; PaO2 = oxygen partial pressure at arterial gas analysis; RV = right ventricular; RV-GLS = right ventricular global longitudinal strain; SOFA = sequential organ failure assessment; TAPSE = tricuspidal annular plane systolic excursion.

quantitative 2D speckle tracking was feasible even though difficult acoustic windows were common in this challenging clinical setting, (b) RV dysfunction was a common finding, and (c) RV strain and TAPSE were associated with higher mortality, with a substantial independent prognostic value over markers of severity of pulmonary involvement.

In the present investigation, RV function was assessed by conventional parameters and using 2D speckle tracking. This technique, which has the advantage of being almost angle-independent and less affected by ventricular morphology, 17 This is in keeping with albeit slightly lower than previous data in similar settings demonstrating that RV strain was feasible in 94% of mechanically ventilated ARDS patients, even though difficult acoustic windows were common. 19 These findings have important potential clinical implications considering that some patients with COVID-19 at high risk might need a comprehensive examination and sometimes echocardiographic surveillance. 3 Emerging evidence suggests that cardiovascular complications represent a significant threat in COVID-19 beyond respiratory disease, but the pathophysiology remains incompletely understood.

with underlying cardiac diseases do not have sufficient reserve capacity to compensate. Hence, several reports indicate that patients with severe COVID-19 have often an elevated troponin, but unfortunately, echocardiographic data were not reported for most of these patients. 20 Of note, in our study, the conventional and strain indices of RV dysfunction, which were frequently altered, were correlated neither with respiratory parameters nor with the CT severity score.

This is in keeping with the hypothesis that SARS-CoV-2 is capable of causing multiple organ failure through various mechanisms. 21 Indeed, SARS-CoV-2 can directly infect the heart leading to immune cell recruitment and myocarditis 22 and impact the microvasculature via its effects on angiotensin-converting enzyme 2, triggering microvascular obstruction and tissue ischemia. 23 Importantly, pro-inflammatory cytokines upregulated in patients with severe COVID-19 21 have the potential to trigger cardiomyocyte dysfunction and cardiac depression as already well described in other inflammatory conditions such as sepsis. 24 33 but also to tailor follow-up subsequently.

The study has the inherent limitations of a retrospective analysis with a relatively limited sample size. However, the majority of the existing analyses, in COVID-19-infected patients, are based on retrospective and often single-center series. We analyzed only patients who were hospitalized with COVID-19 during the period of highest mortality and morbidity peak in our region and in whom the echocardiogram was deemed necessary for clinical reasons to better allocate available resources 34 (8.4% of total COVID-19 hospitalized patients). Therefore, our findings may not apply to populations in other areas or milder forms of COVID-19. We acknowledge that our analysis was limited to a short follow-up analysis as we examined in-hospital mortality.

Troponin and NT-proBNP were available only in a subgroup of patients; therefore, we could not examine their association with echocardiographic data.

Due to intervendor variability in 2D strain measurement algorithms, our results apply only to the strain software used in our study.

In our population, conventional measures of RV overload like PASP and TAPSE/PASP were measurable in a small percentage of subjects. Therefore, given the logistical challenges in the setting of this outbreak with limited cardiac catheterization laboratory availability, the true prevalence of RV pressure overload and ventriculoarterial coupling in this setting may be underreported.

Our data demonstrated that in hospitalized patients with COVID-19 undergoing a clinically indicated echocardiography examination, offline quantitative 2D-echocardiographic assessment of cardiac function is a valuable tool for physicians and can help understand the characteristics of cardiac involvement. RV systolic dysfunction especially 2D speckle tracking parameters were associated with increased mortality with substantial independent prognostic value beyond respiratory disease.

Additional larger studies are needed to explain the potential mechanistic relationships between RV dysfunction and COVID-19

outcomes.

The authors acknowledge the "Centro di Ricerca Aldo Ravelli" for supporting the study. We specify that they did not have any role in the design or conduct of the study, the collection, management, analysis or interpretation of the data, the preparation of the manuscript, or the decision to publish.

None.

The data underlying this article will be shared on reasonable request to the corresponding author.

https://orcid.org/0000-0001-6632-3871

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Prognostic utility of quantitative offline 2D-echocardiography in hospitalized patients with COVID-19 disease