Practice Patterns of Cardiovascular Magnetic Resonance Use in the Diagnosis of Pediatric Myocarditis: A Survey-Based Study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is used to diagnose myocarditis in adults and children based on the original Lake Louise Criteria (LLC) and more recently the revised LLC. The major change included in the revised LLC was the incorporation of parametric mapping, which significantly increases the sensitivity and specificity of diagnosis. Subsequently, scientific statements have recommended the use of parametric mapping in the diagnosis of myocarditis in children. However, there are some challenges to parametric mapping that are unique to the pediatric population. Our goal is to characterize clinical CMR and parametric mapping practice patterns for diagnosis of myocarditis in pediatric centers. METHODS: The Cardiovascular Magnetic Resonance Evaluation in Return to Athletes for Myocarditis in COVID-19 and Immunization Consortium created a REDCap survey to evaluate clinical practice patterns for diagnosis of myocarditis in pediatrics. This survey was distributed to the Society for Cardiovascular Magnetic Resonance community. RESULTS: 59 responses from 51 centers were received, with only one response from each center being utilized. Only 35% of centers (37% of North America, 31% of international) reported using CMR routinely in all patients with a suspicion for myocarditis. Diagnostic uncertainty was noted as the most important reason for CMR, while cost was noted as the least important consideration. The majority of centers reported using the revised LLC (37/51, 72%) compared to original LLC (7/51, 14%) or a hybrid criteria (6/51, 12%). When looking at the use of parametric mapping, only 5/47 (11%) for T1 mapping and 11/49 (22%) for T2 mapping reported having scanner-specific pediatric normative data. CONCLUSION: Routine CMR imaging for diagnosis of myocarditis in pediatrics is infrequently performed at surveyed centers despite the focus on a group of non-invasive cardiac imagers. While the majority reported using parametric mapping, few centers reporting having pediatric scanner-specific normative data. This highlights an important gap in the utilization of CMR that may aid in the diagnosis of myocardial disease.

Infarct-like versus Non-Infarct-like Clinical Presentation of Acute Myocarditis: Comparison of Cardiac Magnetic Resonance (CMR) Findings.

BACKGROUND: The clinical presentation of acute myocarditis (AM) is widely variable, ranging from a subclinical disease to an infarct-like syndrome. Cardiac magnetic resonance (CMR) has become the reference non-invasive diagnostic tool for suspected AM, allowing the identification of the various hallmarks of myocardial inflammation (edema, fibrosis, and hyperemia). The aim of the study was to investigate any differences in morphological, functional, and tissue characterization CMR parameters between infarct-like AM in patients with unobstructed coronary arteries and non-infarct-like AM, diagnosed according to the original Lake-Louise Criteria (LLC); Methods: We retrospectively selected 39 patients diagnosed with AM according to LLC, divided into 2 groups according to the clinical presentation: infarct-like in group 1 patients and non-infarct-like in group 2 patients. CMR morphologic, functional, and tissue characterization parameters were analyzed and compared. RESULTS: In group 1, CMR tissue characterization parameters were mainly altereda in septal location with mesocardial myocardial involvement; in group 2, CMR tissue characterization parameters were mainly altered in a lateral location with subepicardial myocardial involvement mainly at the mid-cavity. No significant differences in morphological or functional parameters were observed between the two study groups. CONCLUSIONS: Our results showed differences in the localization and distribution of myocardial tissue damage assessed by CMR among forms of AM accompanied by an infarct-like clinical presentation compared with non-infarct-like presentations of AM. The mechanisms underlying the different preferential sites of damage observed in our study are not known, and we do not exclude the possibility of their prognostic implications.

Cardiac magnetic resonance feature tracking myocardial strain analysis in suspected acute myocarditis: diagnostic value and association with severity of myocardial injury.

BACKGROUND: Albeit that cardiac magnetic resonance feature tracking (CMR-FT) has enabled quantitative assessment of global myocardial strain in the diagnosis of suspected acute myocarditis, the cardiac segmental dysfunction remains understudied. The aim of the present study was using CMR-FT to assess the global and segmental dysfunction of the myocardium for diagnosis of suspected acute myocarditis. METHODS: Forty-seven patients with suspected acute myocarditis (divided into impaired and preserved left ventricular ejection fraction [LVEF] groups) and 39 healthy controls (HCs) were studied. A total of 752 segments were divided into three subgroups, including segments with non-involvement (SNi), segments with edema (SE), and segments with both edema and late gadolinium enhancement (SE+LGE). 272 healthy segments served as the control group (SHCs). RESULTS: Compared with HCs, patients with preserved LVEF showed impaired global circumferential strain (GCS) and global longitudinal strain (GLS). Segmental strain analysis showed that the peak radial strain (PRS), peak circumferential strain (PCS), and peak longitudinal strain (PLS) values significantly reduced in SE+LGE compared with SHCs, SNi, SE. PCS significantly reduced in SNi (-15.3 ± 5.8% vs. -20.3 ± 6.4%, p < 0.001) and SE (-15.2 ± 5.6% vs. -20.3 ± 6.4%, p < 0.001), compared with SHCs. The area under the curve (AUC) values of GLS (0.723) and GCS (0.710) were higher than that of global peak radial strain (0.657) in the diagnosis of acute myocarditis, but the difference was not statistically significant. Adding the Lake Louise Criteria to the model resulted in a further increase in diagnostic performance. CONCLUSIONS: Global and segmental myocardial strain were impaired in patients with suspected acute myocarditis, even in the edema or relatively non-involved regions. CMR-FT may serve as an incremental tool for assessment of cardiac dysfunction and provide important additional imaging-evidence for distinguishing the different severity of myocardial injury in myocarditis.

Pediatric Myocarditis.

Myocarditis is a condition caused by acute or chronic inflammation of the cardiac myocytes, resulting in associated myocardial edema and myocardial injury or necrosis. The exact incidence is unknown, but is likely underestimated, with more mild cases going unreported. Diagnosis and appropriate management are paramount in pediatric myocarditis, as it remains a recognized cause of sudden cardiac death in children and athletes. Myocarditis in children is most often caused by a viral or infectious etiology. In addition, there are now two highly recognized etiologies related to Coronavirus disease of 2019 (COVID-19) infection and the COVID-19 mRNA vaccine. The clinic presentation of children with myocarditis can range from asymptomatic to critically ill. Related to severe acute respiratory syndrome-Coronavirus 2 (SARs-CoV-2), children are at greater risk of developing myocarditis secondary to COVID-19 compared to the mRNA COVID-19 vaccine. Diagnosis of myocarditis typically includes laboratory testing, electrocardiography (ECG), chest X-ray, and additional non-invasive imaging studies with echocardiogram typically being the first-line imaging modality. While the reference standard for diagnosing myocarditis was previously endomyocardial biopsy, with the new revised Lake Louise Criteria, cardiac magnetic resonance (CMR) has emerged as an integral non-invasive imaging tool to assist in the diagnosis. CMR remains critical, as it allows for assessment of ventricular function and tissue characterization, with newer techniques, such as myocardial strain, to help guide management both acutely and long term.

Contrast-enhanced cine MR sequences in the assessment of myocardial hyperemia in acute myocarditis: can they help? A feasibility study.

The study was designed to assess the accuracy of contrast-enhanced balanced steady-state free precession (cine-SSFP) CMR imaging sequences to exhibit myocardial hyperemia in acute myocarditis, which has for a long time been investigated in some centers using early gadolinium enhancement (EGE) sequence. Contrast-enhanced cine-SSFP (CESSFP) sequences were compared to precontrast cine-SSFP sequences to calculate the early cine-contrast enhancement in 36 consecutive patients with acute myocarditis and 36 controls matched for age and gender. Four-chamber views images were obtained in each subject before and after gadolinium injection. Absolute and relative left ventricular myocardial enhancement of the overall myocardium, then separately of the lateral wall and interventricular septum was analyzed in telediastole. Myocarditis patients displayed higher cine-SSFP absolute enhancement than controls (overall left ventricular myocardium 2.38 ± 0.33 vs 1.84 ± 0.31; lateral wall 2.45 ± 0.35 vs 1.83 ± 0.32; and septum 2.26 ± 0.29 vs 1.82 ± 0.29, p < 0.0001 for all). Less significant differences were observed for the relative enhancement (p < 0.05 for all). Using ROC curves, the optimal threshold value of absolute enhancement to diagnose acute myocarditis was 2.05 (sensitivity: 86%; specificity: 81%). Given the simplicity of use, contrast-enhanced cine-SSFP sequences should be used as an additional diagnostic tool to detect hyperemia in acute myocarditis patients.

Comparing the findings and diagnostic sensitivity of cardiovascular magnetic resonance in biopsy confirmed acute myocarditis with infarct-like vs. heart failure presentation.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the reference imaging modality in providing a non-invasive diagnosis of acute myocarditis (AM), as it allows for the detection of myocardial injury associated with AM. However, the diagnostic sensitivity and pattern of CMR findings appear to differ according to clinical presentation. METHODS: This is a retrospective cross-sectional study. Consecutive adult patients presenting to a single tertiary centre in South Africa between August 2017 and January 2022 with AM confirmed on endomyocardial biopsy (EMB) were enrolled. Patients with infarct-like symptoms, defined as those presenting primarily with chest pain syndrome with associated ST-T wave changes on electrocardiogram, or heart failure (HF) symptoms, defined as clinical signs and symptoms of HF without significant chest discomfort, were compared using contrasted CMR and parametric techniques with EMB confirmation of AM as diagnostic gold standard. RESULTS: Forty-one patients were identified including 23 (56%) with infarct-like symptoms and 18 (44%) with HF symptoms. On CMR, the infarct-like group had significantly higher ejection fractions of both ventricles (LVEF 55.3 ± 15.3% vs. 34.4 ± 13.5%, p < 0.001; RVEF 57.3 ± 10.9% vs. 42.9 ± 18.2%, p = 0.008), without significant differences in end diastolic volumes (LVEDVI 82.7 ± 30.3 ml/m2 vs. 103.4 ± 35.9 ml/m2, p = 0.06; RVEDVI 73.7 ± 22.1 ml/m2 vs. 83.9 ± 29.9 ml/m2, p = 0.25). Myocardial oedema was detected more frequently on T2-weighted imaging (91.3% vs. 61.1%, p = 0.03) and in more myocardial segments [3.0 (IQR 2.0-4.0) vs. 1.0 (IQR 0-1.0), p = 0.003] in the infarct-like group. Despite the absence of a significant statistical difference in the prevalence of late gadolinium enhancement (LGE) between the two groups (95.7% vs. 72.2%, p = 0.07), the infarct-like group had LGE detectable in significantly more ventricular segments [4.5 (IQR 2.3-6.0) vs. 2.0 (IQR 0-3.3), p = 0.02] and in a different distribution. The sensitivity of the original Lake Louise Criteria (LLC) was 91.3% in infarct-like patients and 55.6% in HF patients. When the updated LLC, which included the use of parametric myocardial mapping techniques, were applied, the sensitivity improved to 95.7% and 72.2% respectively. CONCLUSION: The pattern of CMR findings and its diagnostic sensitivity appears to differ in AM patients presenting with infarct-like and HF symptoms. Although the sensitivity of the LLC improved with the addition of parametric mapping in the HF group, it remained lower than that of the infarct-like group, and suggests that EMB should be considered earlier in the course of patients with clinically suspected AM presenting with HF.

Comprehensive Cardiac Magnetic Resonance to Detect Subacute Myocarditis.

(1) Background: Compared to acute myocarditis in the initial phase, detection of subacute myocarditis with cardiac magnetic resonance (CMR) parameters can be challenging due to a lower degree of myocardial inflammation compared to the acute phase. (2) Objectives: To systematically evaluate non-invasive CMR imaging parameters in acute and subacute myocarditis. (3) Methods: 48 patients (age 37 (IQR 28−55) years; 52% female) with clinically suspected myocarditis were consecutively included. Patients with onset of symptoms ≤2 weeks prior to 1.5T CMR were assigned to the acute group (n = 25, 52%), patients with symptom duration >2 to 6 weeks were assigned to the subacute group (n = 23, 48%). CMR protocol comprised morphology, function, 3D-strain, late gadolinium enhancement (LGE) imaging and mapping (T1, ECV, T2). (4) Results: Highest diagnostic performance in the detection of subacute myocarditis was achieved by ECV evaluation either as single parameter or in combination with T1 mapping (applying a segmental or global increase of native T1 > 1015 ms and ECV > 28%), sensitivity 96% and accuracy 91%. Compared to subacute myocarditis, acute myocarditis demonstrated higher prevalence and extent of LGE (AUC 0.76) and increased T2 (AUC 0.66). (5) Conclusions: A comprehensive CMR approach allows reliable diagnosis of clinically suspected subacute myocarditis. Thereby, ECV alone or in combination with native T1 mapping indicated the best performance for diagnosing subacute myocarditis. Acute vs. subacute myocarditis is difficult to discriminate by CMR alone, due to chronological connection and overlap of pathologic findings.

Multiparametric Cardiovascular Magnetic Resonance Approach in Diagnosing, Monitoring, and Prognostication of Myocarditis.

Myocarditis represents the entity of an inflamed myocardium and is a diagnostic challenge caused by its heterogeneous presentation. Contemporary noninvasive evaluation of patients with clinically suspected myocarditis using cardiac magnetic resonance (CMR) includes dimensions and function of the heart chambers, conventional T2-weighted imaging, late gadolinium enhancement, novel T1 and T2 mapping, and extracellular volume fraction calculation. CMR feature-tracking, texture analysis, and artificial intelligence emerge as potential modern techniques to further improve diagnosis and prognostication in this clinical setting. This review describes the evidence surrounding different CMR methods and image postprocessing methods and highlights their values for clinical decision making, monitoring, and risk stratification across stages of this condition.

Patterns of cardiovascular magnetic resonance inflammation in acute myocarditis from South Asia and Middle East.

Background: Cardiovascular magnetic resonance (CMR) is the test of choice for diagnosis and risk stratification of myocardial inflammation in acute viral myocarditis. The objective of this study was to assess patterns of CMR inflammation in a cohort of acute myocarditis patients from Northern Africa, Asia, and the Middle East using unsupervised machine learning. Methods: A total of 169 racially and ethnically diverse adults ( ≥ 18 years of age) with CMR confirmed acute myocarditis were studied. The primary outcome was a combined clinical endpoint of cardiac death, arrhythmia, and dilated cardiomyopathy. Machine learning was used for exploratory analysis to identify patterns of CMR inflammation. Results: Our cohort was diverse with 25% from Northern Africa, 33% from Southern Asia, and 28% from Western Asia/the Middle East. Twelve patients met the combined clinical endpoint - 3 had arrythmia, 8 had dilated cardiomyopathy, and 1 died. Patients who met the combined endpoint had increased anterior (p = 0.034) and septal (p = 0.042) late gadolinium enhancement (LGE). Multivariable logistic regression, adjusted for age, gender, and BMI, found that patients from Southern Asia (p = 0.041) and the Middle East (p = 0.043) were independently associated with lateral LGE. Unsupervised machine learning and factor analysis identified two distinct CMR patterns of inflammation, one with increased LGE and the other with increased myocardial T1/T2. Conclusions: We found that anteroseptal inflammation is associated with worsened outcomes. Using machine learning, we identified two patterns of myocardial inflammation in acute myocarditis from CMR in a racially and ethnically diverse group of patients from Southern Asia, Northern Africa, and the Middle East.

Case report: From monkeypox pharyngitis to myopericarditis and atypical skin lesions.

Background: A global outbreak of the human monkeypox virus (HMPXV), first identified in May 2022, was declared a health emergency of international concern on 23 July 2022. Before the global outbreak, monkeypox cases were mostly confined to central and west African countries, where this virus is prevalent. Close contact, mainly sexual contact, is supposed to be the main route of transmission, and it is remarkable that the incidence is higher in men who have sexual relationships with other men. Case summary: A 40-year-old Caucasian man arrived at the emergency department complaining of oppressive epigastric pain extending to the chest after a diagnosis of pharyngitis, which was suspected to be caused by the human monkeypox virus. Based on the clinical symptoms, physical examination, serum cardiac biomarkers, and electrocardiographic findings, he was diagnosed with myopericarditis. The real-time PCR for human monkeypox in skin lesions, urine, plasma, and the oropharyngeal swab was positive. The peak of troponin I was 20.6 ng/ml, and the electrocardiogram showed an upward concavity in the ST segment in diffuse leads, which was in agreement with the previous diagnosis. The presence of edema, subepicardial, and myocardial late gadolinium enhancement, and increased values on T1 mapping in the cardiac MRI were in agreement with the diagnosis of myopericarditis. Antiviral treatment with tecovirimat was started with excellent tolerability. After 6 days, the patient recovered and was discharged. Discussion: To our knowledge, this is one of the first reported cases of myopericarditis due to human monkeypox infection, which was confirmed by a cardiac MRI following modified Lake Louise criteria. The short span between the onset of the mucocutaneous symptoms and the myocardial damage suggests a pathogenic association. Furthermore, the active viral replication in plasma samples and the negative results on real-time PCR for other viruses support this clinical association.

Multiparametric Cardiovascular Magnetic Resonance in Acute Myocarditis: Comparison of 2009 and 2018 Lake Louise Criteria With Endomyocardial Biopsy Confirmation.

Background: Cardiac magnetic resonance (CMR) has been shown to improve the diagnosis of myocarditis, but no systematic comparison of this technique is currently available. The purpose of this study was to compare the 2009 and 2018 Lake Louise Criteria (LLC) for the diagnosis of acute myocarditis using 3.0 T MRI with endomyocardial biopsy (EMB) as a reference and to provide the cutoff values for multiparametric CMR techniques. Methods: A total of 73 patients (32 ± 14 years, 71.2% men) with clinically suspected myocarditis undergoing EMB and CMR with 3.0 T were enrolled in the study. Patients were divided into two groups according to EMB results (EMB-positive and -negative groups). The CMR protocol consisted of cine-SSFP, T2 STIR, T2 mapping, early and late gadolinium enhancement (EGE, LGE), and pre- and post-contrast T1 mapping. Their potential diagnostic ability was assessed with receiver operating characteristic curves. Results: The myocardial T1 and T2 relaxation times were significantly higher in the EMB-positive group than in the EMB-negative group. Optimal cutoff values were 1,228 ms for T1 relaxation times and 58.5 ms for T2 relaxation times with sensitivities of 86.0 and 83.7% and specificities of 93.3 and 93.3%, respectively. The 2018 LLC had a better diagnostic performance than the 2009 LLC in terms of sensitivity, specificity, positive predictive value, and negative predictive value. T1 mapping + T2 mapping had the largest area under the curve (0.95) compared to other single or combined parameters (2018 LLC: 0.91; 2009 LLC: 0.76; T2 ratio: 0.71; EGEr: 0.67; LGE: 0.73; ). The diagnostic accuracy for the 2018 LLC was the highest (91.8%), followed by T1 mapping (89.0%) and T2 mapping (87.7%). Conclusion: Emerging technologies such as T1/ T2 mapping have significantly improved the diagnostic performance of CMR for the diagnosis of acute myocarditis. The 2018 LLC provided the overall best diagnostic performance in acute myocarditis compared to other single standard CMR parameters or combined parameters. There was no significant gain when 2018LLC is combined with the EGE sequence.

Multiparametric cardiac magnetic resonance imaging in pediatric and adolescent patients with acute myocarditis.

BACKGROUND: The diagnostic value of cardiac magnetic resonance imaging (MRI) employing the 2018 Lake Louise criteria in pediatric and adolescent patients with acute myocarditis is undefined. OBJECTIVE: To evaluate the diagnostic value of the Lake Louise criteria in pediatric and adolescent patients with suspected acute myocarditis and to show the utility of cardiac MRI for follow-up in this patient cohort. MATERIALS AND METHODS: Forty-three patients (age range: 8-21 years) with suspected acute myocarditis and 13 control patients who underwent cardiac MRI were retrospectively analyzed. T2-weighted and late gadolinium enhancement imaging were performed in all patients. T1 and T2 mapping were available in 26/43 patients (60%). The Lake Louise criteria were assessed. In 27/43 patients (63%), cardiac MRI follow-up was available. Receiver operating characteristic analysis, Pearson's correlation coefficient and paired Student's t-test were used for statistical analysis. RESULTS: In the total cohort, the Lake Louise criteria achieved a sensitivity of 86% (95% confidence interval [CI]: 72-95%) and a specificity of 100% (95% CI: 79-100%) for the diagnosis of acute myocarditis. In the subgroup of patients with available mapping parameters, the diagnostic performance of the Lake Louise criteria was higher when mapping parameters were implemented into the score (area under the receiver operating characteristic curve: 0.944 vs. 0.870; P=0.033). T2 relaxation times were higher in patients with admission to the intermediate care unit and were associated with the length of intermediate care unit stay (r=0.879, P=0.049). Cardiac MRI markers of active inflammation decreased on follow-up examinations (e.g., T1 relaxation times: 1,032±39 ms vs. 975±33 ms, P<0.001; T2 relaxation times: 58±5 ms vs. 54±5 ms, P=0.003). CONCLUSION: The Lake Louise criteria have a high diagnostic performance for the diagnosis of acute myocarditis and are a valuable tool for follow-up in pediatric and adolescent patients. The mapping techniques enhance the diagnostic performance of the 2018 Lake Louise criteria.

The potential role of plasma miR-155 and miR-206 as circulatory biomarkers in inflammatory cardiomyopathy.

AIMS: Establishing a diagnosis of inflammatory cardiomyopathy (iCMP) by non-invasive means remains challenging despite advances in cardiac magnetic resonance imaging. Previous studies suggested the involvement of microRNAs in the pathogenesis of iCMP. We examined the association of a predefined set of circulatory microRNAs with clinical characteristics of iCMP and evaluated their diagnostic performance in suspected iCMP. METHODS AND RESULTS: Eighty-nine patients with clinical suspicion of iCMP were included in the analysis. All patients underwent cardiac catheterization with left ventricular endomyocardial biopsy, echocardiography, and cardiac magnetic resonance imaging applying the Lake Louise criteria (LLC). Plasma levels of miR-21, miR-126, miR-133a, miR-146b, miR-155, and miR-206 were determined using real-time polymerase chain reaction. Based on immunohistological findings on endomyocardial biopsy, iCMP was diagnosed in 67% of study participants (n = 60). Plasma levels of miR-155 and miR-206 were significantly increased in patients with iCMP as compared with patients with dilated cardiomyopathy (P = 0.008 and P = 0.009, respectively). In receiver operating characteristic curve analysis, miR-155 and miR-206 demonstrated superior diagnostic performance for iCMP (0.68 and 0.67, respectively) compared with LLC [area under the curve (AUC) 0.60], Troponin T (AUC 0.51), and N-terminal pro-brain natriuretic peptide (AUC 0.51). While baseline miR-155 and miR-206 plasma levels were predictive for biopsy-proven iCMP (odds ratio = 2.61, 95% confidence interval = 1.28-5.31, P = 0.008 and odds ratio = 2.65, 95% confidence interval = 1.27-5.52, P = 0.009) on univariate logistic regression analysis, the presence of positive LLC, high baseline C-reactive protein, or presence of clinical symptoms and signs of viral infection failed to predict iCMP (P > 0.05, respectively). CONCLUSIONS: The present data suggest that plasma levels of miR-206 and miR-155 are potential novel biomarkers for confirming the diagnosis of iCMP.

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis.

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. CONCLUSIONS: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.

Use of the new Lake Louise Criteria improves CMR detection of atypical forms of acute myocarditis.

The purpose of our study was to compare diagnostic performance of old and new Lake Louise Criteria (oLLC and nLLC) among different clinical presentations: infarct-like (IL), cardiomyopathic (CM) and arrhythmic (AR). 102 patients with clinical suspicion of acute myocarditis underwent cardiac magnetic resonance (CMR) on a 1.5 T scanner. Protocol included cine-SSFP, T2-weighted STIR, T2 mapping, early and late gadolinium enhancement and T1 mapping acquired before and after gadolinium administration. The degree of agreement has been calculated with Cohen's K test. 42 patients also underwent endomyocardial biopsy (EMB). IL onset was present in 54/102 patients, CM in 28/102 and AR in 20/102. nLLC were positive in 58.3% of the patients, while oLLC in 37.9%, k = 0.57 (IC: 0.428-0.713). The degree of agreement between nLLC and oLLC was 0.49 (IC: 0.111-0.876) for AR onset (nLLC positive in 35% vs oLLC in 15%), 0.25 (IC: 0.035-0.459) for CM pattern (nLLC positive in 60.7% vs oLLC 17.9%) and 0.73 (IC: 0.543-0.912) for IL presentation (nLLC positive in 66.7% vs oLLC in 57.4%). Diagnostic accuracy was 75% for both nLLC and oLLC among IL onset, and 41.6% for oLLC vs 66.7% for nLLC, as regards CM clinical presentation. nLLC have improved diagnostic performance of CMR for the diagnosis of acute myocarditis, in particular for atypical clinical presentation.

COVID-19 vs. Classical Myocarditis Associated Myocardial Injury Evaluated by Cardiac Magnetic Resonance and Endomyocardial Biopsy.

Background: Despite the ongoing global pandemic, the impact of COVID-19 on cardiac structure and function is still not completely understood. Myocarditis is a rare but potentially serious complication of other viral infections with variable recovery, and is, in some cases, associated with long-term cardiac remodeling and functional impairment. Aim: To assess myocardial injury in patients who recently recovered from an acute SARS-CoV-2 infection with advanced cardiac magnetic resonance imaging (CMR) and endomyocardial biopsy (EMB). Methods: In total, 32 patients with persistent cardiac symptoms after a COVID-19 infection, 22 patients with acute classic myocarditis not related to COVID-19, and 16 healthy volunteers were included in this study and underwent a comprehensive baseline CMR scan. Of these, 10 patients post COVID-19 and 13 with non-COVID-19 myocarditis underwent a follow-up scan. In 10 of the post-COVID-19 and 15 of the non-COVID-19 patients with myocarditis endomyocardial biopsy (EMB) with histological, immunohistological, and molecular analysis was performed. Results: In total, 10 (31%) patients with COVID-19 showed evidence of myocardial injury, eight (25%) presented with myocardial oedema, eight (25%) exhibited global or regional systolic left ventricular (LV) dysfunction, and nine (28%) exhibited impaired right ventricular (RV) function. However, only three (9%) of COVID-19 patients fulfilled updated CMR-Lake Louise criteria (LLC) for acute myocarditis. Regarding EMB, none of the COVID-19 patients but 87% of the non-COVID-19 patients with myocarditis presented histological findings in keeping with acute or chronic inflammation. COVID-19 patients with severe disease on the WHO scale presented with reduced biventricular longitudinal function, increased RV mass, and longer native T1 times compared with those with only mild or moderate disease. Conclusions: In our cohort, CMR and EMB findings revealed that SARS-CoV-2 infection was associated with relatively mild but variable cardiac involvement. More symptomatic COVID-19 patients and those with higher clinical care demands were more likely to exhibit chronic inflammation and impaired cardiac function compared to patients with milder forms of the disease.

The Doubled-Edged Sword of T1-Mapping in Systemic Sclerosis-A Comparison with Infectious Myocarditis Using Cardiovascular Magnetic Resonance.

AIMS: T1-mapping is considered a surrogate marker of acute myocardial inflammation. However, in diffuse cutaneous systemic sclerosis (dcSSc) this might be confounded by coexisting myocardial fibrosis. We hypothesized that T1-based indices should not by themselves be considered as indicators of myocardial inflammation in dcSSc patients. METHODS/RESULTS: A cohort of 59 dcSSc and 34 infectious myocarditis patients was prospectively evaluated using a 1.5-Tesla system for an indication of suspected myocardial inflammation and was compared with 31 healthy controls. Collectively, 33 (97%) and 57 (98%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. However, 33 (97%) and 45 (76%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. T2-signal ratio was significantly higher in myocarditis patients compared with dcSSc patients (2.5 (0.6) vs. 2.1 (0.4), p < 0.001). Early gadolinium enhancement, late gadolinium enhancement and T2-mapping did not differ significantly between groups. However, both native T1-mapping and extracellular volume fraction were significantly lower in myocarditis compared with dcSSc patients (1051.0 (1027.0, 1099.0) vs. 1120.0 (1065.0, 1170.0), p < 0.001 and 28.0 (26.0, 30.0) vs. 31.5 (30.0, 33.0), p < 0.001, respectively). The original Lake Louise criteria (LLc) were positive in 34 (100%) myocarditis and 40 (69%) dcSSc patients, while the updated LLc were positive in 32 (94%) and 44 (76%) patients, respectively. Both criteria had good agreement with greater but nonsignificant discordance in dcSSc patients. CONCLUSIONS: ~25% of dcSSc patients with suspected myocardial inflammation had no CMR evidence of acute inflammatory processes. T1-based indices should not be used by themselves as surrogates of acute myocardial inflammation in dcSSc patients.

Diagnostic and prognostic value of cardiac magnetic resonance in acute myocarditis: a systematic review and meta-analysis.

While diagnostic criteria were elaborated for acute myocarditis using cardiac magnetic resonance (CMR) in 2009, studies have since examined the yield of traditional and novel CMR parameters to achieve greater accuracy and to predict clinical outcomes. The purpose of this systematic review and meta-analysis was to determine the diagnostic and prognostic value of CMR parameters for acute myocarditis. MEDLINE and EMBASE were systematically searched for original studies that reported CMR parameters in adult patients suspected of acute myocarditis. Each CMR parameter's binary prevalence, mean value and standard deviation were extracted. Parameters were meta-analyzed using a random-effects model to generate standardized mean differences. After screening 1492 abstracts, 53 studies were included encompassing 2823 myocarditis patients and 803 controls. Pooled standardized mean differences between myocarditis patients and controls were: T2 mapping time 2.26 (95% CI 1.50-3.02), extracellular volume 1.64 (95% CI 0.87-2.42), LGE percentage 1.30 (95% CI 0.95-1.64), T1 mapping time 1.18 (95% CI 0.35-2.01), T2 ratio 1.17 (95% CI 0.80-1.54), and EGE ratio 0.93 (95% CI 0.66-1.19). Prolonged T1 mapping time had the highest sensitivity (82%), pericardial effusion had the highest specificity (99%). Baseline LV dysfunction and the presence of LGE were predictive of major adverse cardiac events. The results support integration of parametric mapping criteria in the diagnostic criteria for myocarditis. The presence of baseline LV dysfunction and LGE predict patients at higher risk of adverse events.

State of the art: Evaluation and prognostication of myocarditis using cardiac MRI.

Myocarditis encompasses both primary and secondary processes causing inflammation of the myocardium. Viral infections are a common secondary cause of myocarditis with important clinical relevance. Viral myocarditis has a varied clinical presentation, potentially resulting in significant morbidity and mortality. Acutely, systolic dysfunction and sudden cardiac death may ensue; chronically, myocarditis may result in a dilated cardiomyopathy requiring heart transplantation. Myocarditis is thought to be one of the most common causes of myocardial infarction with nonobstructive coronary arteries (MINOCA), with important consequences for cardiovascular outcomes. Patients with myocarditis are currently underdiagnosed. Cardiac MRI has evolved as the noninvasive test of choice, with cardiac MRI-specific diagnostic requirements defined in the Lake Louise Criteria (LLC). Detecting the presence of tissue edema, hyperemia, and necrosis in both acute and chronic stages form the foundation of the LLC. Cardiac MR for chronic myocarditis (greater than 8 weeks from symptom onset) has decreased sensitivity for diagnosis. Emerging sequences such as T1 and T2 parametric maps provide tissue characterization regarding inflammation without reliance on reference tissue, overcoming limitations of the LLC. Beyond diagnostic criteria, these imaging techniques have proven useful in further characterizing the diseased tissue, prognostication, and clinical decision-making. This review describes the utility and evolving use of cardiac MRI in clinical practice. Level of Evidence: 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2018;47:1061-1071.