key: cord-0813145-be1lta30
authors: Krishna, Hema; Ryu, Alexander J.; Scott, Christopher G.; Mandale, Deepa R.; Naqvi, Tasneem Z.; Pellikka, Patricia A.
title: Cardiac Abnormalities in COVID-19 and Relationship to Outcome
date: 2021-01-19
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2021.01.006
sha: 014321745ef08f57a03379785ae7167e958057d9
doc_id: 813145
cord_uid: be1lta30

Objective To characterize the clinical and transthoracic echocardiographic features and 30-day outcomes of hospitalized patients with COVID-19. Methods Retrospective cohort study that included 179 consecutive inpatients with COVID-19 who underwent clinically indicated transthoracic echocardiography at 10 sites in the Mayo Clinic Health System between March 10 and August 5, 2020. Echocardiography was performed at bedside by cardiac sonographers according to an abbreviated protocol. Echocardiographic results, demographics, laboratory findings, and clinical outcomes were analysed. Results Of the 179 patients, age 59.8± 16.9 years and 108 (60%) men, events within 30 days occurred in 70 (39%) patients including prolonged hospitalization in 43 (24%) and death in 27 (15%). Echocardiographic abnormalities included left ventricular ejection fraction < 50% in 29 (16%), regional wall motion abnormalities in 26 (15%), and right ventricular systolic pressure (RVSP) >35 mm Hg in 44 (25%). Myocardial injury, defined as the presence of significant troponin elevation accompanied by new ventricular dysfunction or electrocardiographic abnormalities, was present in 13 (7%). Prior echocardiography was available in 36 (20%) and pre-existing abnormalities were seen in 28 (78%) of these. In a multivariable age-adjusted model, AUC 0.81, prior cardiovascular disease, troponin, D-dimer, and RVSP were related to events at 30 days. Conclusion Bedside Doppler assessment of RVSP appears promising for short-term risk stratification in hospitalized COVID-19 patients undergoing clinically indicated echocardiography. Pre-existing echocardiographic abnormalities were common; caution should be exercised in attributing such abnormalities to the COVID-19 infection in this comorbid patient population.

COVID-19 is a rapidly evolving emergency with frequent cardiovascular involvement. A high risk of mortality has been reported amongst hospitalized COVID-19 patients with pre-existing coronary artery disease and among those who develop acute cardiac injury 1, 2 . However, to date, the impact of cardiac involvement on short-term outcome in the setting of COVID-19 is incompletely understood.

Echocardiography is widely utilized in the bedside evaluation of patients with COVID-19, and echocardiographic abnormalities have commonly been detected 3, 4 . Cardiac manifestations have included myocardial injury from acute coronary syndromes, myocarditis, and takotsubo cardiomyopathy 3 . Adverse right ventricular remodelling 5, 6 and abnormal right ventricular longitudinal strain 7 are among the frequently described abnormalities in patients with COVID-19 and have been related to increased mortality. However, some of the echocardiographic findings in COVID-19 patients may have been pre-existent, not unlikely in a group of patients who frequently have comorbidities.

To protect sonography staff and patients, cardiac imaging protocols have been abbreviated in the era of COVID-19. Bedside echocardiograms have been focused to assessing ventricular size and systolic function, the presence of left ventricular regional wall motion abnormalities, and the presence of hemodynamically significant valvular heart disease or a pericardial effusion [8] [9] [10] .

However, these modifications to a standard comprehensive echocardiographic examination may limit the utility of echocardiography in clinical risk stratification.

The current study was undertaken to characterize the clinical and echocardiographic features and 30 day outcomes of hospitalized patients with COVID-19 in whom echocardiography was J o u r n a l P r e -p r o o f clinically indicated. We hypothesized that besides clinical characteristics and laboratory values, echocardiographic findings would be independently associated with short-term outcome.

Patient population: This study was approved by the institutional review board and conducted among consecutive inpatients with a diagnosis of COVID-19 who underwent clinically indicated transthoracic echocardiography at 10 sites in the Mayo Clinic Health System between March 10 and August 5, 2020. The first available transthoracic echocardiogram performed after hospital admission for COVID-19 was included. Clinical information was abstracted from the medical record. Inpatient laboratory values closest to the time of the echocardiogram were recorded.

Echocardiography: Echocardiography was performed by registered cardiac sonographers at the patient's bedside using full-sized ultrasound systems (Vivid E9, GE Healthcare, Chicago, IL; EPIQ, Philips, Cambridge, MA). An abbreviated protocol was used to minimize staff contact with the patient. The focused study was directed toward evaluating biventricular function, detecting pericardial effusion, assessing pulmonary artery systolic pressure when feasible, and screening for significant valvular stenosis or regurgitation using 2-dimensional imaging and color Doppler 11 . Additional image acquisition and analysis, including measurement of global longitudinal strain, tricuspid annulus systolic excursion or tissue Doppler s', quantification of valvular heart lesions (proximal isovelocity surface area, multi-window Pedof transducer assessment, constriction/ restriction, and left or right ventricular strain) were performed only when clinically relevant and feasible. Sonographer staff entered the patient's room with contrast available in case this was necessary for assessment of ventricular function and regional wall motion.

Detailed retrospective review of the echocardiographic images, including side-by-side comparison with any echocardiogram prior to the diagnosis of COVID-19 but within 5 years, was performed by experienced level 3 echocardiographers, blinded to clinical information and outcome. Right ventricular size and systolic function were assessed in multiple views and by Doppler method when available. Left ventricular volumes were traced in the apical views when feasible. In some cases, a view or measurement was missing, precluding comparison of that variable for the 2 studies; the number in which comparison was possible is indicated in the results for each measurement comparison.

Outcomes: Thirty-day outcome was obtained by retrospective review of the electronic medical record to assess patient management and events during hospitalization, including prolonged (≥21 days) hospitalization 12 or death. Myocardial injury was also recorded and described, defined as the presence of significant elevation in high-sensitivity cardiac troponin 13 accompanied by either new or presumed new ventricular dysfunction or electrocardiographic abnormalities consistent with myocardial injury, but was not included as the outcome as echocardiographic evidence of injury was part of the definition.

Analysis: Continuous variables were expressed as mean (SD) or median (intraquartile range, IQR) according to data distribution and compared using the Student t test or Wilcoxon rank sum test, as appropriate. Categorical data, presented as number and percentages, were compared using х² test. Univariate and multivariable logistic regression analyses were performed to identify clinical and echocardiographic predictors of events at 30 days, including the composite of prolonged hospitalization or death. In multivariable models, missing values were imputed using median values and missing value indicator variables were added to these models to account for the imputation. Separate sensitivity analyses were conducted using imputed values from the 1 st and 3 rd quartiles and similar results were found.

There were 179 inpatients with COVID-19 who underwent transthoracic echocardiography during the study; echocardiograms for 110 (61%) were performed in the intensive care unit. The Baseline clinical characteristics, presenting symptoms, and baseline laboratory values for patients with and without the 30 day endpoint are shown on Table 1 . Other characteristics included cardiac device leads in 8 (4%), and prior congenital heart disease repair in 2 (1%).

Hemodynamic and echocardiographic characteristics according to the presence of an endpoint are shown in Table 2 . Echocardiographic abnormalities included left ventricular ejection fraction < 50% in 29 (16%), regional wall motion abnormalities in 26 (15%), global dysfunction Prior echocardiography was available in 36 (20%) patients; these exams were performed at a median of 8 (IQR 3, 30) months previously. Among these patients, pre-existing abnormalities were present in 28 (78%) and included left ventricular ejection fraction <50% in 4 (11%) and regional wall motion abnormalities in 9 (25%). Of the 29 patients with ejection fraction <50% following COVID-19 infection, pre-existing ejection fraction <50% was present in 4 of the 6 with prior studies. Additionally, 12 of the 26 patients with regional wall motion abnormalities following COVID-19 infection had prior TTEs; 7 of these 12 patients had new or worsened (Table 2 ).

Thirteen (7%) patients sustained acute myocardial injury; clinical features are detailed on Table   3 . Clinical diagnoses included myocarditis, non ST-elevation myocardial infarction, global ventricular dysfunction following resuscitated cardiac arrest, and stress cardiomyopathy. The left heart was also impacted, through processes clinically felt to represent ischemia/infarction, inflammatory or viral myocarditis, and stress cardiomyopathy. Left ventricular ejection fraction was more often <50% among individuals meeting the endpoint (27% versus 9%, P=.001). Though only 5% of patients with COVID-19 infection had a severely reduced left ventricular ejection fraction, 15% demonstrated regional wall motion abnormalities. However, few studies have incorporated pre-COVID-19 echocardiographic data to better understand the rate of left ventricular dysfunction attributable to COVID-19 itself, rather than simply an unmasking of baseline abnormalities in a population with a high incidence of comorbidities. We found a high prevalence (78%) of prior echocardiographic abnormalities among 20% of patients who had undergone an echocardiogram prior to the onset of COVID-19.

Among the 29 patients with reduced ejection fraction <50%, pre-existing low ejection fraction was known to be present in 4 of the 7 with baseline studies. Of the 26 patients with regional wall motion abnormalities, 12 had prior TTEs; 7 had either new or worsened regional wall motion abnormalities and the remaining 5 had no change.

The abbreviated echocardiographic imaging protocol instead of a standard comprehensive echocardiographic examination may have resulted in failure to recognize echocardiographic abnormalities in some patients in our cohort. Despite this and unlike prior studies, volumetric assessment of left ventricular size and systolic function was performed in 70% of our patients.

Quantitative assessment of right ventricular function was performed in 50 (28%) patients. Only 32% of the echocardiograms in the present series were performed using an ultrasound image enhancing agent; a higher prevalence of wall motion abnormalities may have been identified with more widespread use of these agents.

Limitations: Data collection was retrospective and obtained via electronic health record extraction. It was therefore subject to reporting and ascertainment bias. Patient selection for echocardiographic assessment was based on clinical judgment and not performed in a systematic manner; this likely predisposes our study towards overestimating the frequency of abnormalities.

Only 21% of patients had baseline TTE studies for comparison. Interim development or resolution of echocardiographic abnormalities may have skewed our comparative assessment of these data. Measurement of biomarkers was performed according to clinical judgment rather than systematically. Incorporation of newer therapeutic agents and methods found effective in various publications during the study period may have influenced our results. The scope of this study was limited to 30-day outcomes.

Long term impact of COVID-19 infection on cardiac outcomes remains to be prospectively investigated. Bedside Doppler assessment of RVSP appears promising for risk stratification and this variable should be measured in patients with COVID-19 undergoing clinically indicated echocardiography.

Conclusion: This study found that bedside Doppler assessment of RVSP may be a useful predictive tool for short-term risk stratification of hospitalized COVID-19 patients undergoing .02 # Troponin imputed using median in adjustment model. Model also includes indicator variable for imputation. *Troponin, RVSP, and D-dimer imputed using median in model. Model also includes indicator variables for imputation.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Coronavirus Disease 2019 (COVID-19) and Cardiac Injury-Reply

Global evaluation of echocardiography in patients with COVID-19

Spectrum of Cardiac Manifestations in COVID-19: A Systematic Echocardiographic Study

Prognostic Utility of Right Ventricular Remodeling Over Conventional Risk Stratification in Patients With COVID-19

The Right Ventricle: A Target in COVID-19 Cardiac Insult

Prognostic Value of Right Ventricular Longitudinal Strain in Patients With COVID-19

ASE Statement on Point-of-Care Ultrasound during the 2019 Novel Coronavirus Pandemic

ASE Statement on Protection of Patients and Echocardiography Service Providers During the 2019 Novel Coronavirus Outbreak: Endorsed by the American College of Cardiology

COVID-19 pandemic and cardiac imaging: EACVI recommendations on precautions, indications, prioritization, and protection for patients and healthcare personnel

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

Trends in Prolonged Hospitalizations in the United States from 2001 to 2012: A Longitudinal Cohort Study

Using High-Sensitivity Cardiac Troponin T for Acute Cardiac Care

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)

Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations

Characterization of Myocardial Injury in Patients With COVID-19

Moderately enlarged 9 (8) 8 (12) Severely enlarged 2 (2) 0 (0) GLS global longitudinal strain, LV left ventricular, LVEF left ventricular ejection fraction, RV right ventricular, RVSP right ventricular systolic pressure, RWMSI regional wall motion score index * indicates the number of patients for whom this comparison could be made when it was less than the total of 36 with a prior TTE