Characterization of Myocardial Injury in Patients With COVID-19

Gennaro Giustino, MD; Lori B. Croft, MD; Giulio G. Stefanini, MD, PHD; Renato Bragato, MD; Jeffrey J. Silbiger, MD; Marco Vicenzi, MD; Tatyana Danilov, MD; Nina Kukar, MD; Nada Shaban, MD; Annapoorna Kini, MD; Anton Camaj, MD, MS; Solomon W. Bienstock, MD; Eman R. Rashed, MD; Karishma Rahman, MD, PHD; Connor P. Oates, MD; Samantha Buckley, BS; Lindsay S. Elbaum, MD; Derya Arkonac, MD; Ryan Fiter, MD; Ranbir Singh, MD; Emily Li, MD; Victor Razuk, MD; Sam E. Robinson, MD; Michael Miller, MS; Benjamin Bier, MD; Valeria Donghi, MD; Marco Pisaniello, MD; Riccardo Mantovani, MD; Giuseppe Pinto, MD; Irene Rota, MD; Sara Baggio, MD; Mauro Chiarito, MD; Fabio Fazzari, MD; Ignazio Cusmano, MD; Mirko Curzi, MD; Richard Ro, MD; Waqas Malick, MD; Mazullah Kamran, MD; Roopa Kohli-Seth, MD; Adel M. Bassily-Marcus, MD; Eric Neibart, MD; Gregory Serrao, MD; Gila Perk, MD; Donna Mancini, MD; Vivek Y. Reddy, MD; Sean P. Pinney, MD; George Dangas, MD, PHD; Francesco Blasi, MD, PHD; Samin K. Sharma, MD; Roxana Mehran, MD; Gianluigi Condorelli, MD; Gregg W. Stone, MD; Valentin Fuster, MD, PHD; Stamatios Lerakis, MD, PHD; Martin E. Goldman, MD

Disclosures

J Am Coll Cardiol. 2020;76(18):2043-2055. 

In This Article

Results

Patient Characteristics

A total of 305 patients were included from March 2020 to May 2020 from 7 hospitals in New York City (United States) and Milan (Italy) (Supplemental Table 6). The demographics, clinical characteristics, and laboratory characteristics according to the presence of myocardial injury are shown in Table 1. Baseline medications are reported in Supplemental Table 7. Median age was 63 years and 67.2% were men. A total of 190 patients (62.6%) had biomarker evidence of myocardial injury of whom 118 had myocardial injury at the time of hospital admission and 72 developed myocardial injury during the hospitalization. The median time of in-hospital stay (to discharge, death, or still in the hospital) was 14 days (interquartile range [IQR]: 7 to 23 days). The median time to peak cardiac troponin elevation among patients presenting with normal cardiac troponin was 5 days (IQR: 1 to 12 days). Patients with myocardial injury were older and had a higher prevalence of hypertension, diabetes mellitus, and chronic kidney disease. In addition, patients with myocardial injury had higher levels of natriuretic peptides, inflammatory biomarkers (e.g., interleukin-6, C-reactive protein, ferritin), serum creatinine, coagulation biomarkers (e.g., D-dimer), and serum lactate (Table 1).

Electrocardiographic, Echocardiographic, and Angiographic Findings

As shown in Table 2, patients with myocardial injury more frequently had ST-segment elevation or depression at presentation and the most common ST-segment changes were regional (i.e., ascribed to a coronary artery distribution) compared with those without myocardial injury. The presence of conduction disturbances and low voltage were also more frequent in patients with myocardial injury. Among patients with myocardial injury and a normal ECG at presentation, 30.9% developed new ECG ischemic changes during the hospitalization.

The median number of days between admission and TTE evaluation was 4 days (IQR: 1 to 10 days). The presence of cardiac symptoms (e.g., chest pain or shortness of breath) and troponin elevations were the most common reasons for TTE (Supplemental Table 8). The range of echocardiographic abnormalities in patients with myocardial injury is provided in the Central Illustration. The median LV ejection fraction of the overall study cohort was 60% (IQR: 48% to 65%). Compared with patients without myocardial injury, those with myocardial injury had an increased prevalence of any versus no major echocardiographic abnormalities (63.2% vs. 21.7%; OR: 6.17; 95% CI: 3.62 to 10.51; p < 0.0001), including global LV dysfunction, regional LV wall motion abnormalities, grade II or III diastolic dysfunction, RV dysfunction, and pericardial effusions (Table 2). Patients with myocardial injury also had greater LV volumes, wall thickness, and left atrial volumes.

Central Illustration.

Spectrum of Echocardiographic Abnormalities in Patients With Biomarker Evidence of Myocardial Injury and Coronavirus Disease-2019
Among patients with coronavirus disease-2019 (COVID-19) who underwent transthoracic echocardiography (TTE), cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Cardiac structural abnormalities included right ventricular dysfunction, left ventricular (LV) wall motion abnormalities, global left ventricular dysfunction, diastolic dysfunction, and pericardial effusions.

The relationships among ECG changes, clinical presentation, and echocardiographic characteristics are reported in Table 3 and Supplemental Table 9. Patients with ST-segment changes more frequently had chest pain at the time of presentation and, among these patients, those with regional ST-segment changes had higher degrees of troponin elevations. Patients with regional ST-segment changes more frequently had wall motion abnormalities on echocardiography, conversely those with diffuse ST-segment changes more frequently had global LV dysfunction (including lower ejection fraction) and RV dysfunction.

Coronary angiography was performed in 11 patients; 8 had confirmed ACS (7 with total thrombotic occlusion of a major epicardial artery who required percutaneous coronary intervention) and 3 had normal coronary arteries. Compared with patients with other types of myocardial injury, those with confirmed ACS more frequently had chest pain at the time of clinical presentation, had higher troponin elevations, lower levels of peak D-dimer levels, and all had wall motion abnormalities on TTE (Supplemental Tables 10 and 11).

Myocardial Injury and In-hospital Outcomes

In-hospital treatments and outcomes are reported in Table 4. Among the entire study cohort of 305 patients, intensive care unit admission and mechanical ventilation were required in 43.9% and 34.5% of patients respectively, and in-hospital mortality occurred in 18.7%. Compared with patients without myocardial injury, those with myocardial injury had higher rates of in-hospital death (26.8% vs. 5.2%; p < 0.0001) (Figure 1A), intensive care unit admission, mechanical ventilation, ARDS, AKI, and cardiocirculatory shock. The rates of in-hospital mortality were 5.2%, 21.0%, and 31.2% among patients without myocardial injury with or without echocardiographic abnormalities, with myocardial injury but without echocardiographic abnormalities and with myocardial injury and echocardiographic abnormalities, respectively (trend adjusted OR: 2.27; 95% CI: 1.30 to 3.94; p = 0.004) (Figure 1B). As shown in Figure 2, by multivariable analysis, mortality was increased in patients with myocardial injury and echocardiographic abnormalities even after adjustment for other major complications of COVID-19 (adjusted OR: 3.87; 95% CI: 1.27 to 11.80) but not in patients without echocardiographic abnormalities (adjusted OR: 1.00; 95% CI: 0.27 to 3.71). Results were consistent using multivariable Cox regression models (Supplemental Table 12). In-hospital outcomes in patients with myocardial injury and major echocardiographic abnormalities are reported in Supplemental Table 13. Outcomes in patients with confirmed ACS versus other types of myocardial injury are shown in Supplemental Table 14.

Figure 1.

In-Hospital Mortality in Patients With COVID-19, Myocardial Injury, and Echocardiographic Abnormalities
Kaplan-Meier curves for all-cause mortality in patients with versus without myocardial injury (A) and in patients with versus without myocardial injury according to the presence or absence of major echocardiographic abnormalities (B). Includes wall motion abnormalities, global left ventricular dysfunction, diastolic dysfunction, right ventricular dysfunction, and presence of pericardial effusion. Event rates are censored at 20 days from hospital admission. TTE = transthoracic echocardiography.

Figure 2.

Independent Predictors of In-Hospital Death From Multivariable Logistic-Regression Analysis
Results are reported as odds ratios (ORs) and 95% confidence intervals (CIs). The following variables were included in the final model: age, sex, race, history of heart failure, acute respiratory distress syndrome, acute kidney injury stage II or III, cardiocirculatory shock, myocardial injury (with or without major echocardiographic abnormalities), and center identifier. *Includes wall motion abnormalities, global left ventricular dysfunction, diastolic dysfunction, right ventricular dysfunction, or presence of mild or more severe pericardial effusion.

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