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

Discussion

In the present multicenter international study, patients with COVID-19 and myocardial injury had a higher prevalence of ECG and echocardiographic abnormalities than did patients without myocardial injury. The echocardiographic abnormalities were diverse and included global LV dysfunction, regional wall motion abnormalities, diastolic dysfunction, RV dysfunction, and pericardial effusions, among others (Central Illustration). Myocardial injury was independently associated with increased risk of in-hospital mortality after adjustment for other major in-hospital complications of COVID-19 including ARDS, cardiocirculatory shock, and AKI, but only in patients with major abnormalities detected on TTE. Finally, we identified substantial differences in clinical and echocardiographic characteristics between patients with confirmed ACS on cardiac catheterization and those with other types of myocardial injury.

COVID-19 is a global pandemic responsible for significant morbidity, mortality, and health care costs.[1] A significant proportion of patients presenting with COVID-19 infection requiring hospitalization have evidence of myocardial injury based on serum cardiac troponin elevations, with an incidence ranging from 7% to 40%.[2–11] In most prior studies, cardiac injury has been associated with increased risk of in-hospital complications and mortality.[2–11] However, the underlying mechanisms of myocardial injury in patients with COVID-19 remain poorly understood because prior studies have not included cardiovascular imaging data and troponin elevations per se do not differentiate between etiologies of myocardial damage.

In the present study, we comprehensively characterized the structural and functional cardiac abnormalities of patients with COVID-19 infection and biomarker evidence of myocardial injury with the use of TTE. Consistent with prior reports, patients with myocardial injury had higher levels of inflammatory and coagulation biomarkers.[2,3] On TTE, most patients with myocardial injury had preserved LV function, and the LV ejection fraction was <50% in only 35% of patients. Nonetheless, patients with cardiac injury had a substantially greater prevalence of LV, RV, and pericardial abnormalities. Higher degrees of diastolic dysfunction were also more frequent in patients with myocardial injury, possibly reflecting the higher prevalence of hypertension and chronic kidney disease among these patients. ST-segment changes on the 12-lead ECG appeared to identify 2 different patterns of myocardial injury, with diffuse ST-segment changes associated with global biventricular dysfunction (possibly reflecting a diffuse myocardial inflammatory damage) and regional ST-segment changes associated with regional wall motion abnormalities (possibly reflecting regional ischemic damage of the myocardium due to macro- or microvascular thrombosis). Therefore, ECG and echocardiographic abnormalities in the context of the appropriate clinical scenario may help differentiate across the different etiologies of myocardial injury in COVID-19.

By multivariable analysis, myocardial injury in patients with major echocardiographic abnormalities was strongly associated with increased risk for in-hospital mortality, even after correcting for other major COVID-19–related complications such as ARDS, AKI, and cardiocirculatory shock (which themselves were also independent predictors of mortality). Conversely, myocardial injury without major echocardiographic abnormalities was not a significant predictor of increased mortality. Thus, TTE in patients with troponin-positive COVID-19 syndromes provides useful prognostic information. The association between myocardial injury and mortality (especially in those with echocardiographic abnormalities) is likely multifactorial and possibly both correlative and causative in nature. First, myocardial injury seems to correlate with the severity of the clinical manifestations of COVID-19 and may identify patients with worse baseline clinical status. Second, COVID-19 has been shown to broadly affect the cardiovascular system.[18] Proposed mechanisms include cytokine-mediated myocardial damage, oxygen supply-demand imbalance, microvascular and macrovascular thrombosis, endothelial damage, and possibly direct viral invasion of the myocardium.[9] It is therefore possible that the cardiac damage resulting from COVID-19, through direct or indirect pathways, contributes to the poor prognosis observed in certain patients.

Acute myocardial infarction is a leading cause of death worldwide and a treatable and recognizable cause of irreversible cardiac damage.[19] However, a reduction in the incidence of hospital admissions for ACS (especially ST-segment elevation myocardial infarction) has been described around the world.[14] In our study, cardiac catheterization was performed only in 11 of 305 patients (3.6%), and of those 11 patients, 8 (72.7%) had confirmed ACS and 3 had normal coronary arteries. Patients with confirmed ACS compared with other causes of troponin elevation had a different clinical profile from patients with other causes of myocardial injury, including more frequent chest pain at the time of clinical presentation, more ECG changes, lower levels of inflammatory biomarkers, and all had regional wall motion abnormalities on TTE. For example, 100% of patients with ACS had regional wall motion abnormalities, compared with 20% of troponin-positive patients without confirmed ACS. Therefore, in the appropriate clinical scenario, TTE (or a point-of-care ultrasound) may be considered among patients with COVID-19 infection and biomarker evidence of myocardial injury to potentially identify those who might benefit from expedited invasive management.

Study Limitations

Data collection was retrospective and used manual electronic health record extraction from multiple institutions. Therefore, it is subject to both reporting and ascertainment bias. Our sample size is modest but nonetheless represents one of the largest studies to date evaluating the association between myocardial injury and functional and structural cardiac assessment using echocardiography in patients with COVID-19. We did not include cardiac magnetic resonance imaging data, and only a small number of patients underwent cardiac catheterization. However, extensive cardiovascular work-up in patients with COVID-19 is often challenging due to both their clinical status and efforts to mitigate exposure risk of health care workers. There was no systematic basis on which patients were selected to undergo TTE evaluation. In fact, it is likely that only patients that were perceived to be at higher risk on clinical grounds underwent TTE. Also, echocardiograms were all interpreted locally and not centrally by an echocardiographic core laboratory. Finally, our study is limited to in-hospital outcomes; the long-term cardiovascular sequelae in patients with troponin-positive COVID-19 with and without echocardiographic abnormalities warrants future prospective investigation.

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