In a cohort of healthy subjects undergoing smallpox vaccination, new-onset chest pain, dyspnoea, or palpitations occurred in 10.6% of the cases, as compared to 2.6% in subjects undergoing another vaccination. Importantly, an active survey of these subjects, including high-sensitive troponin testing, revealed that myocarditis was 60 times more frequent than clinically suspected.
Aside from clinically mild cases, myocarditis can present with symptoms and findings of acute heart failure or MI. In patients with MI and non-obstructed coronary arteries (MINOCA), myocarditis occurred in 33% of cases and was the single most frequent underlying cause for MINOCA.
Myocarditis can result in myocardial scars, which themselves may introduce a risk for cardiovascular events. In a recent study, myocardial scarring consistent with myocarditis was found in 25% of survivors of sudden cardiac death, and the presence and extent of such scars predicted outcome . However, in the setting of subepicardial LV scar, a differential diagnosis of other conditions, including hereditary forms of cardiomyopathy, needs to be considered. Neither the clinical presentation nor findings obtained by standard techniques, such as ECG or echocardiography, are specific for non-ischaemic myocardial inflammation, and thus CMR plays an important role in patients with suspected myocarditis. In turn, myocarditis is one of the most frequent indications for CMR scans.
Since the introduction of non-invasive in vivo tissue characterization by CMR, the awareness and understanding of clinicians of the impact of myocardial
involvement in systemic diseases have increased significantly. CMR is indicated in patients with symptoms and findings suggestive of myocardial injury of unknown aetiology. In patients with heart failure, it may act as a gatekeeper for the need of endomyocardial biopsy (EMB). Diagnostic targets of CMR in patients with suspected myocardial inflammation are myocardial oedema, inflammation-induced hyperaemia, and myocardial scarring in a non-ischaemic regional distribution pattern, and a standard protocol, known as the Lake Louise criteria, has been proposed.
Imaging in Myocarditis
Given the invasive nature of EMBs, non-invasive methods to assess for myocarditis play an essential role in the diagnosis of suspected myocarditis, although EMB remains the gold standard to achieve the aetiopathogenetic diagnosis. As stated in the recommendations of the ESC, CMR may be considered in clinically stable patients. However, CMR cannot differentiate between virus persistence and autoimmune inflammation and thus cannot replace EMB for certain therapeutic decision- making. In cases with acute heart failure or other life-threatening presentations, EMB should not be delayed by any other diagnostic procedure . Echocardiography remains an essential, and often the first-line, imaging modality to assess suspected cases; however, it suffers from a lack of sensitivity to identify myocarditis in cases without overt LV dysfunction , with a low specificity in distinguishing acute from chronic, as well as non-ischaemic from ischaemic forms of, cardiac disease. In the past, nuclear medicine imaging with 67-gallium and 111-indium has been described as a useful technique to identify acute myocarditis, but it is rarely used in contemporary clinical practice. FDG-PET has been compared to CMR with good diagnostic agreement but suffers from radiation exposure, limited availability, and relative poor spatial resolution. CMR, with its superior capabilities in myocardial tissue characterization, compared to other cardiac imaging modalities, in addition to excellent functional and morphological visualization, plays an eminent role in the non-invasive diagnosis of myocarditis. Suspected myocarditis is a top indication (>30% when including cardiomyopathies) for CMR . Tissue abnormalities related to inflammation, such as oedema, hyperaemia
and capillary leak, and myocyte necrosis, can be detected by CMR using T2-weighted imaging, EGE, and LGE, respectively. In addition, CMR can detect associated pericardial effusions and ventricular dysfunction as supportive information, and follow LV mass regression over time with the resolution of oedema. The Lake Louise Consensus Criteria (2009) recommends using a combination of any two out of the three tissue characterization techniques to increase the confidence in detecting acute myocarditis. Novel techniques, such as T1-mapping, ECV mapping, and T2-mapping, are emerging as promising methods to evaluate myocarditis.
The Lake Louise Criteria
Include T2-weighted, EGE, and LGE imaging. Cine imaging using SSFP sequences should also be performed for functional analysis and identification of any associated pericardial effusion. Most of the sequences used are well established in MR systems and standardized in recent recommendations, from image acquisition to final reporting.
T2-weighted imaging is typically acquired using black blood spin echo techniques with flow and fat suppression. Body coils or surface coils with signal intensity correction algorithms should be used to minimize hardware-derived signal inhomogeneity. Maximizing LV coverage will increase the diagnostic yield, and at least three short-axis slices should be obtained, with careful adjustments for heart rate variability which might hamper correct interpretation of signal intensities. Findings suspicious of focal oedema should be confirmed in at least one orthogonal plane.
Pre- and Post-contrast EGE Imaging
Pre- and post-contrast EGE imaging is obtained using T1-weighted, free-breathing black blood fast spin echo sequences in short-axis or axial views (the latter with more robust image quality). As for dark blood T2-weighted images, body coils are preferable. Spatial saturation bands over the atria and using four averages will improve the SNR. Post-contrast images should be acquired within the first minute after gadolinium injection (0.1 mmol/kg) at the same slice positions and using the same parameter prescriptions
as for the pre-contrast images.
Currently, these two components of the Lake Louise Criteria are not employed by all centres for a number of reasons, including the local ability to implement the methods, availability of expertise, and inconsistent image quality of T2-weighted and EGE images.
LGE imaging should be obtained using an inversion recovery GRE sequence, about 10 minutes after gadolinium administration (0.1 mmol/kg). As for all LGE imaging, optimization of the inversion time for myocardial nulling is essential. To increase the sensitivity for detecting disease, acquisition of a full short-axis stack, as well as long-axis views, should be performed. Findings of focal injury should be confirmed in at least one orthogonal plane.
Reporting of the results for assessment of myocarditis should include the description of the presence or absence of the assessed criteria.
The diagnosis of myocarditis using CMR requires multiple CMR techniques that provide overlapping, as well as complementary, information to increase diagnostic confidence.
The true gold standard of myocarditis for the validation of CMR imaging techniques is whole- heart histopathology for direct comparison to imaging findings, although this type of data is difficult to obtain for in vivo human subjects. EMB is problematic as a gold standard for validation of CMR diagnostic performance due to its sampling error and inability to rule out small areas of focal myocarditis, although it may have a role in selected clinical settings for therapeutic decision-making. The availability of imaging (echo, CMR, electrovoltage mapping)- guided EMB can increase its diagnostic sensitivity. Novel mapping methods are now available to add to the repertoire of tissue characterization techniques that are sensitive to various pathophysiologic changes that occur in myocarditis. In the future, it may be feasible to prescribe simplified and gadolinium-free CMR protocols, which can shorten scan times and obviate the need for contrast agent administration. As further evidence and experience accumulate, revised CMR imaging protocols are expected to increase the confidence and efficiency in the non-invasive diagnosis of myocarditis.