There is a growing evidence of cardiovascular complications in coronavirus disease 2019 (COVID-19) patients. As evidence accumulated of COVID-19 mediated inflammatory effects on the myocardium, substantial attention has been directed towards cardiovascular imaging modalities that facilitate this diagnosis. Cardiac magnetic resonance imaging (CMRI) is the gold standard for the detection of structural and functional myocardial alterations and its role in identifying patients with COVID-19 mediated cardiac injury is growing. Despite its utility in the diagnosis of myocardial injury in this population, CMRI’s impact on patient management is still evolving. This review provides a framework for the use of CMRI in diagnosis and management of COVID-19 patients from the perspective of a cardiologist. We review the role of CMRI in the management of both the acutely and remotely COVID-19 infected patient. We discuss patient selection for this imaging modality; T1, T2, and late gadolinium enhancement imaging techniques; and previously described CMRI findings in other cardiomyopathies with potential implications in COVID-19 recovered patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, continues to spread across the United States (US) and globally. As of January 21, 2021, the US reported over 23 million confirmed cases of COVID-19 as well as over 400000 COVID-19 related mortalities[1]. It has been previously reported that COVID-19 patients often have complications involving acute myocardial injury. These injuries are the most frequently reported cardiovascular abnormality in COVID-19, and occur in approximately 8%-12% of all patients[2]. Other cardiovascular effects of COVID-19 include endothelial damage, systolic heart failure, and arrhythmias[3]. Proposed mechanisms for cardiac injury include those mediated by systemic inflammation, direct viral attack on cardiomyocytes, myocardial interstitial fibrosis, overactive cytokine and interferon immune response, coronary plaque destabilization, and hypoxia[4,5].

Myocarditis is an increasingly recognized complication of COVID-19[6]. While endomyocardial biopsy remains the gold standard for tissue diagnosis, this procedure is invasive, characterized by potential serious complications and may be impractical in certain patient populations. Non-invasive imaging modalities, however, provide a safe alternative to aid in the diagnosis and management of myocarditis. While echocardiography possesses distinct advantages including low cost, accessibility, and faster interpretation times that may be beneficial in resource-scarce settings, many patients with early or mild myocarditis may have a normal echocardiogram[7]. Computed tomography (CT) modalities lack high quality myocardial tissue characterization that is essential for the diagnosis of myocarditis while exposing patients to significant amounts of radiation and contrast materials. Nuclear imaging is another potential modality to aid in the diagnosis of myocarditis, but lacks the spatial resolution to distinguish mid or epicardial myocardial perfusion defects (myocarditis) from subendocardial perfusion defects (ischemic) with significant partial volume effect and hence limited diagnostic accuracy[7].

Cardiovascular magnetic resonance imaging (CMRI) techniques remain the preferred modality for assessing patients with suspected myocarditis. CMRI provides detailed anatomical visualization, tissue-level analysis, safety, quantitative accuracy, and inter-observer consistency[7,8]. CMRI techniques are not without their limitations. These include higher cost when compared to echocardiography, longer exam times, and reliance on imaging interpretation by readers specifically trained in this discipline. Despite these limitations, CMRI remains the preferred imaging modality in the assessment of COVID-19 patients suspected of myocarditis and has the potential of playing a pivotal role in early diagnosis COVID-19-related cardiac injury. Finally, CMRI has the unique ability to evaluate subclinical and chronic cardiac involvement following COVID-19 infection.

CMRI represents the gold standard for the noninvasive cardiac tissue characterization, detection of acute and chronic myocardial changes, and myocardial viability[9-12]. This volumetric and functional assessment utility has expanded its indications for not only diagnostic purposes, but also treatment guidance and patient follow-up as is currently being investigated in those patients with COVID-19 related acute myocarditis[13]. CMRI is also currently used to risk stratify patients with ischemic heart disease and myocarditis, assess precise ejection fraction, quantify scar tissue, and predict location of re-entrant circuits within the scar to guide catheter ablation[14]. The future of CMRI continues to grow with the incorporation of artificial intelligence, post-processing techniques and development of new MR sequences such as T1 and T2 mapping[13].

Late gadolinium enhancement

Late gadolinium enhancement (LGE) imaging techniques involves the use of gadolinium as a contrast agent to identify heterogeneity within myocardial tissue. LGE imaging represents a cornerstone of CMRI as it is used to define chronic myocardial fibrosis and necrosis caused by ischemia as well as myocardial fibrosis frequently present in non-ischemic dilated cardiomyopathy. Damaged cardiac tissue has a slower gadolinium washout time than healthy tissue, which allows for not only identification of myocardial scarring, but also its quantification[11,12,18]. LGE images of COVID-19 patients suspected of myocardial involvement revealed enhancement at the left ventricular base, suggestive of myocarditis (Figure 1).

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Figure 1  Delayed cardiac magnetic resonance image obtained after Gd administration showing patchy late Gd enhancement in the mid-myocardium of the basal inferolateral and mid anteroseptal walls consistent with prior myocarditis in patient who recovered from coronavirus disease 2019.

Renal function should be assessed prior to the use of LGE as its use is relatively contraindicated for patients with significant renal impairment, although new generation Gadolinium agents seem to be safer to use[14,16,19]. Current guidelines proposed by the European Society of Cardiology, American Heart Association (AHA) and American College of Cardiology indicate the use of CMRI for diagnosis and management of coronary artery disease and cardiomyopathies, with a class I recommendation for suspected infiltrative causes[13,14,20].

Although data regarding CMRI characteristics of COVID-19 myocarditis is limited to case reports and series, a small study did compare 8 patients with COVID-19 myocarditis to 8 patients with non-COVID-19 myocarditis and 12 healthy patients[21]. Patients with suspected acute COVID-19 myocarditis (with elevated troponin and CRP) were found to have a pattern of diffuse myocardial edema detected as diffuse globally higher T1 and T2 myocardial relaxation times. Comparatively1, the patients with non-COVID-19 myocarditis had a more focal disease with prolonged T1 and T2 relaxation times and more visible myocardial edema and LGE lesions. It was also noted that skeletal muscle T1 was elevated in COVID-19 myocarditis patients, which impacted the T2 ratio to not be elevated significantly. Severe wall-motion abnormalities due to stress-induced cardiomyopathy and small pericardial effusions were also detected as CMRI enhancements in the COVID-19 myocarditis group[21].

Although the role of CMRI in the diagnosis of COVID-19 related cardiac injury is accepted, its practical utilization in both the inpatient and outpatient venues faces challenges in this continuously expanding patient population. In an effort to address these concerns, the Society of Cardiovascular Magnetic Resonance (SCMR) created specific guidelines treating the use of CMRI in COVID-19 patients[39,40]. These treatment guidelines cover a variety of imaging settings, including the acutely ill patient suspected of having acute COVID-19 related myocardial injury. In these instances, the SCMR recommends a short imaging protocol of 10-15 minutes for patients with active COVID-19 infection and a poor functional status[16]. CMRI can be performed on ventilated patients through special guidelines but is highly discouraged unless absolutely clinically necessary[39]. A holistic approach is recommended with the safety of patients and healthcare workers in mind and the use of clinical judgement to suspect acute myocardial injury[39]. If used in an inpatient setting, a dedicated CMRI scanner should be established when possible to limit the spread of COVID-19[16]. In most circumstances, CMRI should be postponed until after resolution of the patient’s contagious state and performed in an outpatient setting[27,39]. Once completed, further cardiovascular recommendations may be made based upon imaging findings. Given the breadth of patients affected by COVID-19, it is possible to detect preexisting and undiagnosed cardiac abnormalities and/or true COVID-19 related injury. Consequently, cardiovascular specialists must adopt a tailored approach to the treatment of these patients in light of their clinical circumstances. For example, patients with cardiomyopathy detected on CMRI may be candidates for consultation by a dedicated congestive heart failure treatment team[41].

Due to the novelty of the COVID-19 pandemic, there is a lack of consensus on how to manage the long-term cardiac effects of COVID-19. The high prevalence and disease burden of the COVID-19 pandemic and the constraints it’s placed on healthcare resources make the determination of CMRI guidelines a difficult healthcare decision with ethical dimensions. Our center recommends using a risk stratification method to determine if a CMRI is needed for each individual patient (Table 2). High risk individuals include patients who have an abnormal echocardiogram, abnormal electrocardiogram (EKG), positive troponin levels, or history of myocarditis, myocardial infarction, or non-obstructive coronary artery disease. These patients should receive a CMRI if available.

While suspicion of myocarditis can be determined based on biomarkers, EKG, and echocardiography, these tests may not be sufficient to determine the true etiology of cardiac involvement. EKG manifestations of myocarditis vary considerably and most commonly involve sinus tachycardia and nonspecific T wave and ST segment changes[42]. Echocardiography may demonstrate increased wall thickness and hyperechogenicity but more often than not provide inconclusive findings[43]. These tests provide little use in differentiating myocarditis from similarly presenting processes such as myocardial infarction or pulmonary embolus. If the aforementioned workup does not point towards a definitive diagnosis of myocarditis, CMRI may be indicated to provide direct tissue characterization, assess cardiac function indirectly based on the degree of inflammation present, and produce the confidence necessary to establish the diagnosis of myocarditis[42,44,45]. In addition, contrast-enhanced MRI may be a useful, noninvasive tool for long-term follow-up of patients with acute myocarditis and provide more accurate data on predicting outcome. A small study of 16 patients with myocarditis found that contrast enhancement ratio at 4 wk after disease onset was predictive of long-term outcomes[12].

Patients who are asymptomatic or have negative labs or normal echocardiogram findings are low priority for receiving CMRI. While post-COVID-19 asymptomatic myocardial involvement has been documented in the literature as mentioned above, this group of individuals with no symptoms should forgo CMRI at this time unless symptoms arise due to constraints on healthcare resources amidst the pandemic.

There is, however, a large gray area between these patient extremes. Athletes, for example, are a unique patient population as they are at higher risk of sudden cardiac death if they resume vigorous exercise with signs of myocarditis[32]. While there is disagreement in the approach of these patients, we believe clinicians should defer to the 2015 AHA Return to Play guidelines[32]. If there are any abnormalities on imaging, athletes should sit out from play with repeat imaging likely warranted in three to six months[32]. Reintroduction to play can take place gradually if biomarkers and EKG findings normalize and imaging shows no active inflammation[32]. At this time, it is unclear if resolution of myocarditis-related LGE is necessary for athletes to resume competition, so physicians should continue to use clinical judgment in their assessment of these patients. The Big Ten Athletics organization has taken the lead on evaluating their collegiate athletes following COVID-19 infection by creating a Big Ten Cardiac Registry[46]. Every student-athlete who tests positive undergoes cardiac testing involving EKG, biomarkers, echocardiogram, and CMRI to thoroughly evaluate cardiac structure and function[46]. This cautious approach is ideal but may not be practical for resource-scarce areas across the country, highlighting the importance of center-specific guidelines. It should be emphasized that determining appropriate imaging guidelines is an ongoing process that should utilize new findings as they are brought forward.

While athletes make up a unique subset of patients, the general public also stands to benefit from CMR imaging as indicated in Table 2.

There are significant practical limitations regarding the use of CMRI in COVID-19 patients. In addition to limited availability at the global scale, CMRI represents a more expensive and time-consuming imaging modality when compared to conventional alternatives such as echocardiography. Additionally, consistent interpretation of CMRI images is vital to the widespread applicability of CMRI prognostic data[30]. This may be difficult to achieve considering many medical providers do not have access to the imaging modality itself or to cardiac imaging specialists who can accurately interpret the acquired images[47]. The lack of easy access to CMRI imaging creates the potential for selection bias in studies reporting CMRI results. These limitations must be taken into consideration during the creation of imaging guidelines of COVID-19 patients worldwide. Actively contagious COVID-19 patients with suspected cardiac involvement pose a unique challenge to clinicians. In order to reduce COVID-19 spread, CMR imaging may not be appropriate in COVID-19 patients who are actively contagious, thus placing a limitation on CMRI use in the early stage of COVID-19 infection[16]. Finally, it should also be noted that the CMRI studies conducted on COVID-19 patients discussed above all lack a pre-infection CMRI for comparison. Therefore, although unlikely, it is feasible that some included patients may have had preexisting changes detectable by CMRI following an unrelated COVID-19 infection. The lack of internal control limits the applicability of these research findings; nevertheless, the reported prevalence of myocardial abnormalities detected in these studies appears higher than that encountered both in clinical practice and the literature and thus deserves consideration.

The COVID-19 pandemic has created an unprecedented quest to obtain and synthesize data in a brief amount of time. A major topic, and one that is of particular concern, is the cardiovascular effects seen both acutely and in the chronic setting. Myocardial injury secondary to COVID-19 and the use of CMRI is an evolving subject. A systematic review of the literature, while limited, yields important insights into the use of CMRI.

In regards to active COVID-19 infection with concern for acute myocardial injury, CMRI has a more limited role. CMRI should be used in the acute setting when the findings will alter management and treatment strategies. Additionally, CMRI is able to aid in the diagnosis of myocardial infarction, RV strain in pulmonary embolism, and Takatsubo cardiomyopathy[34]. Given the infectious nature of the coronavirus, the risk of exposure and transmission of COVID-19 to healthcare workers should be kept in mind. CMRI should be performed cautiously or postponed unless they alter the treatment and management of patients in a time-critical manner.

Although CMRI usage will be constricted the general population vastly due to cost and availability limitations, we suspect a major use of CMRI moving forward will be in athletes who have recovered from COVID-19. This is due to the increased risk of adverse events including sudden cardiac death for this specific population. As demonstrated by Phelan et al[30], CMRI is recommended in athletes if clinical concern is elevated, despite normal or unremarkable biomarkers and/or Echocardiogram and EKG. Additionally, Rink et al[46] has created an athlete registry and will be performing CMRI on every student athlete that has recovered from COVID-19. As high school, collegiate, and professional sports begin their seasons, much consideration and caution will be present in those athletes who have recovered from COVID-19. Given what we know about evidence of LGE and associated ventricular events, indications for withholding athletes from competitive sport may certainly arise.

As a relatively new imaging modality with ongoing research, guidelines regarding CMRI use continue to evolve as new techniques and advances emerge. The role of CMRI in the diagnosis of COVID-19 related illness is evolving as well. Small studies have demonstrated the presence of cardiac injury even in minimally or asymptomatic COVID-19 patients. While the long-term sequelae of COVID-19 mediated cardiac disease is unknown, the diagnostic yield of CMRI places it squarely in the forefront of imaging strategies for this growing patient population. While factors such as availability and cost may limit the widespread adoption of CMRI, its use in selected populations such as competitive athletes remain important. Further studies examining the prognostic utility of CMRI findings in the recovered COVID-19 population appears warranted.