Introduction

Infection with SARS-CoV2, the virus causing coronavirus disease 2019 (COVID-19) is associated with several cardiac complications stemming from myocardial injury including acute coronary syndrome, myocarditis, heart failure, and arrhythmias. Even when patients are in the convalescent stage or have recovered from COVID-19, they may demonstrate ongoing evidence of cardiac injury.

Synopsis

In a recent multicenter, case-control study from the United Kingdom by Kotecha et al,¹ 148 COVID-19 survivors with evidence of myocardial injury by elevated high sensitivity troponin (hs-cTn) during their index hospitalization underwent multiparametric cardiovascular magnetic resonance (CMR) (native T1 and T2 mapping, late gadolinium enhancement [LGE], and adenosine stress perfusion in a subset) to evaluate for prevalence, patterns, and extent of myocardial injury by imaging. Participants underwent CMR imaging within 2 months following hospital admission to specifically evaluate for myocardial dysfunction, ischemia/infarction, and cardiac inflammation and/or fibrosis.

Most patients included in the study were male (70%), half were Caucasian, and the median age was 64 years. Among the cases, there was a high prevalence of cardiovascular risk factors (7% had prior myocardial infarction [MI], 12% had prior coronary revascularization, 57% were hypertensive, 34% had diabetes, 46% were hypercholesterolemic, and 24% were smokers).  About one third of patients required admission to the intensive care unit. Patients with either no troponin testing or a negative hs-cTn were excluded from the study.

In terms of CMR findings, LV ejection fraction (LVEF) was largely within normal limits (~67%) and was not significantly different between the COVID-19 survivors and two control groups (40 healthy volunteers and 40 matched patients scanned pre-COVID-19). However, there were 17 patients with reduced LVEF (13 with LVEF 35%-55%, 4 with LVEF <35%) and of those, 9 were due to prior myocardial infarction. Cardiac abnormalities were detected in 54% of patients on CMR and were classified as ischemic (infarction by LGE or inducibility by adenosine) in 22%, non-ischemic (myocarditis-like) in 26% and dual pathology in 9%. Notably, of the patients with an ischemic pattern on CMR, 66% had no prior history of ischemic heart disease although the majority (95%) had at least one cardiovascular risk factor.

In the patients with myocarditis-like pattern, about one third had evidence of active myocarditis and two thirds demonstrated a healed myocarditis pattern on CMR. There was no association between hs-cTn level and CMR diagnosis of myocarditis, indicating discordance between laboratory and imaging evidence of cardiac injury. Lastly, of those without any cardiac abnormalities, 10 had pulmonary embolism found on computed tomography pulmonary angiogram which could explain hs-cTn elevations in a subset. Taken together, the different abnormal cardiac imaging patterns detected on CMR suggest varying mechanisms of cardiac injury including MI, myocarditis, and inducible ischemia in the setting of acute illness.

COVID-19 Related Myocarditis

Myocarditis is a known complication of other viral illnesses including influenza; however, the true prevalence of myocarditis in COVID-19 is currently unknown.² In a meta-analysis of COVID-19 autopsy studies, histopathologic evidence of lymphocytic myocarditis was infrequent (~1.4%).³ However, other cardiovascular histopathologic findings were fairly common such as intravascular thrombi, inflammation, or intraluminal megakaryocytes, which could explain the abnormal CMR findings reported in COVID-19. Given the relatively high rate of acute cardiac complications, there is concern for persistent longer-term effects of myocardial injury.

Cardiovascular MR can be useful to identify etiology of injury, risk stratify patients and monitor the progression of myocardial disease found on initial imaging, and potentially guide follow-up and therapy over time. As such, several prior imaging studies have shed light on the extent of cardiac involvement of COVID-19 in the convalescent phase. Prior CMR studies revealed a relatively high prevalence of cardiac injury (50-75%) within three months of recovery, the majority consisting of changes consistent with global myocardial inflammation, edema, and interstitial fibrosis.^4,5

In the present study, most of the patients had no wall motion abnormalities or reduced ejection fraction, which is a favorable prognostic sign in myocarditis of non-COVID-19 etiology. However, a significant minority of recovered patients had evidence of ongoing cardiac inflammation on CMR, and this group may require continued follow-up to evaluate for progression to fibrosis and cardiomyopathy.⁶ As confirmed in this study, systemic illness with COVID-19 can also cause elevated troponin due to type II myocardial infarction⁷ and unmask cardiovascular disease in vulnerable patients,⁸ such as those with comorbid conditions (e.g., obesity, diabetes, hypertension) and those with no prior cardiac history.

Conclusion

The prevalence, pathophysiology and long-term prognostic significance of acute COVID-19 related myocardial injury as defined by acute troponin elevation remains unclear. Studies such as that reported by Kotecha et al. add to the growing literature regarding subacute sequelae of acute myocardial injury in patients recovering from severe COVID-19 using comprehensive multiparametric CMR to better define functional and structural myocardial abnormalities within a few months of diagnosis. The current study represents the largest CMR effort to date with a rigorously performed imaging protocol, inclusion of appropriate control groups, and multicenter enrollment of an ethnically diverse cohort of high risk COVID-19 survivors, most at risk for long-term sequelae of myocardial injury. Limitations of the study include selection bias by inclusion of only those surviving beyond hospital discharge and electing to present for follow-up CMR study, lack of a control group of hospitalized COVID-19 patients without troponin elevations, and lack of pre-hospitalization CMR studies for comparison.

While the reported prevalence of abnormal CMR findings is lower than previous publications of individuals with less severe COVID-19 disease,^4,5 it highlights the need for additional longer-term studies to examine the progression and prognostic significance of the observed CMR abnormalities, particularly among those with findings suggesting active myocarditis. The current study further underscores the important contribution of ischemic injury/infarction, particularly among older patients with cardiovascular risk factors, likely resulting from supply-demand mismatch due to critical illness. Also needed are studies that can better address the extent to which the imaging findings represent indirect myocardial injury due to myocardial inflammation, endothelial dysfunction, and/or cytokine storm versus direct myocyte necrosis specific to COVID-19 infection.

References

1. Kotecha T, Knight DS, Razvi Y, et al. Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance. Eur Heart J 2021;42:1866-78.
2. Shchendrygina A, Nagel E, Puntmann VO, Valbuena-Lopez S. COVID-19 myocarditis and prospective heart failure burden. Expert Rev Cardiovasc Ther 2021;19:5-14.
3. Halushka MK, Vander Heide RS. Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 post-mortem examinations. Cardiovasc Pathol 2021;50:107300.
4. Puntmann VO, Carerj ML, Wieter I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:1265-73.
5. Huang L, Zhao P, Tang D, et al. Cardiac involvement in patients recovered from COVID-2019 identified using magnetic resonance imaging. JACC Cardiovasc Imaging 2020;13:2330-39.
6. Schellhorn P, Klingel K, Burgstahler C. Return to sports after COVID-19 infection. Eur Heart J 2020;41:4382-84.
7. Perrone MA, Bernardini S. The assessment of high sensitivity cardiac troponin in patients with COVID-19: a multicenter study. IJC Heart Vasc 2021;32:100715.
8. Tschöpe C, Sherif M , Anker MS, et al. COVID‐19‐convalescence phase unmasks a silent myocardial infarction due to coronary plaque rupture. ESC Heart Fail 2021;Jan 08:[Epub ahead of print].

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, COVID-19 Hub, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Vascular Medicine, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Interventions and ACS, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Hypertension

Keywords: Dyslipidemias, Gadolinium, Cardiovascular Diseases, Control Groups, Contrast Media, COVID-19, SARS-CoV-2, Myocarditis, Troponin, Case-Control Studies, Prognosis, Critical Illness, Acute Coronary Syndrome, Patient Discharge, Prevalence, Follow-Up Studies, Influenza, Human, Adenosine, Acute Disease, Healthy Volunteers, Cytokines, Stroke Volume, Megakaryocytes, Severe Acute Respiratory Syndrome, Risk Factors, Myocardial Infarction, Heart Failure, Arrhythmias, Cardiac, Hypertension, Fibrosis, Fibrosis, Diabetes Mellitus, Ischemia, Magnetic Resonance Spectroscopy, Edema, Pulmonary Embolism, Angiography, Infarction, Perfusion, Muscle Cells, Intensive Care Units, Tomography, Hospitals, Obesity

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