key: cord-348155-otcg3lgh
authors: Mahmoud-Elsayed, Hani M.; Moody, William E.; Bradlow, William M.; Khan-Kheil, Ayisha M.; Hudsmith, Lucy E.; Steeds, Richard P.
title: Echocardiographic Findings in Covid-19 Pneumonia
date: 2020-05-28
journal: Can J Cardiol
DOI: 10.1016/j.cjca.2020.05.030
sha: 
doc_id: 348155
cord_uid: otcg3lgh

The aim of this study was to characterize the echocardiographic phenotype of patients with Covid-19 pneumonia and its relation to biomarkers. Seventy-four patients (59±13 years, 78% male) admitted with Covid-19 were included after referral for transthoracic echocardiography (TTE) as part of routine care. A level 1 British Society of Echocardiography TTE assessed chamber size and function, valvular disease and likelihood of pulmonary hypertension. The chief abnormalities were right ventricular (RV) dilatation (41%) and RV dysfunction (27%). RV impairment was associated with increased D-dimer and CRP levels. In contrast, left ventricular (LV) function was hyper-dynamic or normal in most (89%) patients.

A detailed description of the echocardiographic findings in Covid-19 pneumonia and its relation to prognostic biomarkers is lacking. In this series of consecutive patients admitted to a busy quarternary referral center with a high burden of Covid-19, the major findings were of right ventricular (RV) dilatation associated with impaired radial but preserved longitudinal RV systolic function. Reduced RV function was associated with elevated levels of D-dimer and C-reactive protein.

The aim of this study was to characterize the echocardiographic phenotype of patients with Covid-19 pneumonia and its relation to biomarkers. Seventy-four patients (59±13 years, 78% male) admitted with Covid-19 were included after referral for transthoracic echocardiography (TTE) as part of routine care. A level 1 British Society of Echocardiography TTE assessed chamber size and function, valvular disease and likelihood of pulmonary hypertension. The chief abnormalities were right ventricular (RV) dilatation (41%) and RV dysfunction (27%).

RV impairment was associated with increased D-dimer and CRP levels. In contrast, left ventricular (LV) function was hyper-dynamic or normal in most (89%) patients.

In the face of the coronavirus disease 2019 (Covid-19) pandemic, Birmingham has emerged as an epicenter within the United Kingdom. This has led to increasing demand for transthoracic echocardiography (TTE) in critically-ill patients being considered for mechanical ventilation and/or circulatory support. Although cardiac biomarkers such as highsensitivity troponin are emerging as strong predictors of outcome in Covid-19, there are only limited data on echocardiographic findings in these patients. A description of the echocardiographic phenotype and its relation to biomarkers and outcomes is therefore warranted. The aim of this study was to characterize the transthoracic echocardiography (TTE) findings in consecutive patients admitted with proven Covid-19 pneumonia.

This retrospective observational cohort study includes adults 18 years of age or older with Covid-19 pneumonia who underwent TTE between March 22 and April 17, 2020, at a 1215bed quaternary referral center. All cases were confirmed through reverse-transcriptasepolymerase-chain-reaction assays performed on nasopharyngeal swabs and had pulmonary infiltrates on chest radiograph. Patients were referred for TTE at the discretion of the clinician responsible for the patient's care, with one of the following indications: chest pain, arrhythmia, abnormal electrocardiogram changes, or haemodynamic instability. In order to minimise the risk of unnecessary exposure to Covid-19 on our echocardiographers, each 

Baseline demographics, risk factors, clinical, laboratory and echocardiographic characteristics are presented in Table 1 . The mean age was 59 ± 13 years, 78% were males and 72% white. Most patients had severe type 1 respiratory failure (PaO2 <8 kPa or <60mmHg) requiring mechanical ventilation (82%), with over half (58%) requiring vasopressor support (norepinephrine) during admission.

The median time between admission and echocardiography was 5 days (interquartile range 3 -10 days). While left ventricular (LV) systolic function was hyper-dynamic or normal in most cases (89%), the RV was dilated in 41%, and impaired in 27%. RV systolic dysfunction was associated with pulmonary embolism (20%). The median time between echocardiography and the peak levels of D-dimer, C-reactive protein (CRP) and highsensitivity cardiac Troponin I (HS Tn) was 3 days (IQR 1 -5 days). RV systolic dysfunction (assessed by fractional area change) was significantly associated with elevated D-dimer (ρ = -0.34, p = 0.003) and CRP (r =,-0.23 p = 0.045) but was not related to HS Tn (Figure 1) . RV size and function was not related to use of vasopressors or mechanical ventilation. Those patients with RV dysfunction on mechanical ventilation, had lower mean PO2/FiO2 ratio (a marker of ARDS severity), and higher mean FiO2 and positive end-expiratory pressure;

although results did not meet statistical significance. No patient had more than mild regurgitation and none had any degree of valvular stenosis.

Twenty-three patients (31%) underwent repeat echocardiography after a median interval of 8 days (IQR 3 -20 days). Across the cohort, there were no significant differences in LV or RV size and function compared with the baseline study.

At the time of submission, 28 patients (38%) have died, of whom 14 (41%) had a RV abnormality (13 dilated, 7 impaired), while only 2 (7%) had LV impairment. To date, 15 (20%) have been discharged.

In patients with COVID-19 pneumonia, RV dilatation and dysfunction is common and its presence is associated with a pro-thrombotic, inflammatory state reflected in elevated Ddimer and CRP levels. In contrast, LV size is normal and LV function is hyperdynamic in most, while significant valvular abnormalities, either primary or secondary, are absent.

Visual RV assessment has highlighted many subjects displaying marked reduction in radial RV systolic function but relative preservation of longitudinal shortening. This likely explains the discrepancy between the objective TAPSE and FAC measurements among patients with reduced RV function. Indeed, many patients exhibited the McConnell sign (exemplar case, Supplementary Video), which involves severe free wall hypokinesia or akinesia with apical sparing. This sign is not specific for acute pulmonary embolus (especially in patients on mechanical ventilation) and we believe in most Covid-19 subjects this could instead represent acute cor pulmonale secondary to ARDS. While this study has not demonstrated a link between mechanical ventilation and the presence of RV dysfunction and pulmonary hypertension, identification of RV impairment may prompt physicians to limit positive end-expiratory pressure and avoid hypercapnic acidosis, which could otherwise adversely affect RV performance by inducing pulmonary arteriolar vasoconstriction and increased RV afterload.

Echocardiography might also be used to help identify which patients with Covid-19 could benefit from therapeutic anticoagulation; although there is no current consensus, it was used empirically to good effect in Wuhan patients with very high D-dimer levels. 4 Prospective randomized trials may be warranted to determine whether TTE guided systemic anticoagulation confers survival benefit in hospitalized patients with Covid-19. 5 Acute myocarditis causing severe LV dysfunction has also been reported in Covid-19, 6 but based on our cohort, there is a low prevalence of LV impairment despite the ubiquitous presence of bilateral lung infiltrates on chest radiograph.

There are limitations to this study. As a retrospective observational cohort study, it is inevitably subject to selection bias. TTE was restricted to those patients with Covid-19 pneumonia with elevated HS Tn for safety reasons; these findings are not, therefore, generalizable to the many asymptomatic or pauci-symptomatic individuals with Covid-19.

Furthermore, only those patients with positive reverse-transcriptase-polymerase-chainreaction assays for Covid-19 were included and we acknowledge that the limited sensitivity of this assay (~70%) means that those patients with false negative nasopharyngeal swab results undergoing echocardiography were excluded. We acknowledge that echocardiographic estimation of pulmonary hypertension is challenging in critically ill patients and the studies that validated this approach did not include patients on mechanical ventilation; however, TTE was performed according to current appropriate guidelines.

Finally, not all patients underwent CT pulmonary angiography and it is conceivable, therefore, that a proportion of patients with RV dysfunction had undiagnosed thromboembolic disease.

In conclusion, RV dilatation and dysfunction is common in patients with Covid-19 pneumonia and elevated HS Tn. In contrast, the LV is seldom impaired and more often hyperdynamic. Hemoglobin (mean ± SD) g/L Platelets (median (IQR)) -/mm³ White cell count (median (IQR)) -/mm³ Neutrophils (median (IQR)) -/mm³ Lymphocytes (mean ± SD) -/mm³ Neutrophil-to-Lymphocyte ratio (median (IQR)) 128 ± 24 226 (172 -287) 9 (7 -13) 7.4 (5.2 -11.6) 0.97 ± 0.53 9.0 (5. 2 

Minimum Dataset for a Level 1 Echocardiogram: A guideline protocol from the British Society of Echocardiography

Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

The normality of distribution for continuous variables was determined using the Kolmogorov-Smirnov test. Variables not normally distributed were log-transformed. Baseline data were analysed using independent samples Student t, Chi-square or where appropriate, Fisher exact tests.