CMR findings in patients referred for suspected myocarditis following mRNA-based COVID vaccination compared with pre-COVID myocarditis referrals: A single-centre observational study.

Background: Vaccination is considered the key to overcome the COVID pandemic. For the first time mRNA-based vaccinations are used in humans. Case series suggested an increased risk of myocarditis after vaccination. This study sought to describe CMR findings in patients with suspected mRNA-vaccine associated myocarditis. Methods: A total of 33 consecutive patients referred for CMR work-up of suspected myocarditis associated with mRNA-based vaccination were included. A historical cohort of 135 consecutive patients referred for suspected myocarditis in the pre-COVID era served as control group. All patients underwent multi-parametric CMR including CINE and late gadolinium enhancement (LGE) imaging as well as parametric T1/T2 mapping of the left ventricular myocardium. Results: Patients referred for suspected vaccination-related myocarditis were more often female (55 % vs 32 %, p = 0.015) and demonstrated smaller LV dimensions as well as a better LV function compared to patients of the control group. CMR revealed a lower prevalence of non-ischemic LGE in patients with suspected vaccination-myocarditis (6 % vs 22 %, p = 0.04). However, among patients without LGE we observed a higher prevalence of an abnormal T1/T2 mapping result in patients with suspected vaccination-myocarditis compared to the control group (45 % vs 18 %, p = 0.010). Conclusion: In this small single-centre study, compared to myocarditis referrals in the pre-COVID era, patients currently referred for CMR work-up of suspected mRNA-vaccination-associated myocarditis demonstrated lower prevalence of LGE but higher prevalence of abnormal T1/T2 mapping. These hypothesis-generating observations may point towards a rather subtle myocardial damage and support the routine use of T1/T2 mapping in this indication.

TRoponin of Unknown origin in STroke evaluated by multi-component cardiac Magnetic resonance Imaging - The TRUST-MI study.

Aims: Increased high-sensitive cardiac troponin I (hs-cTnI) levels are common in patients with acute ischemic stroke. However, only a minority demonstrates culprit lesions on coronary angiography, suggesting other mechanisms, e.g., inflammation, as underlying cause of myocardial damage. Late Gadolinium Enhancement (LGE)-cardiac magnetic resonance (CMR) with mapping techniques [T1, T2, extracellular volume (ECV)] allow the detection of both focal and diffuse myocardial abnormalities. We investigated the prevalence of culprit lesions by coronary angiography and myocardial tissue abnormalities by a comprehensive CMR protocol in troponin-positive stroke patients. Methods and results: Patients with troponin-positive acute ischemic stroke and no history of coronary artery disease were prospectively enrolled. Coronary angiography and CMR (LGE, T1 + T2 mapping, ECV) were performed within the first days of the acute stroke. Twenty-five troponin-positive patients (mean age 62 years, 44% females) were included. 2 patients (8%) had culprit lesions on coronary angiography and underwent percutaneous coronary intervention. 13 patients (52%) demonstrated LGE: (i) n = 4 ischemic, (ii) n = 4 non-ischemic, and (iii) n = 5 ischemic AND non-ischemic. In the 12 LGE-negative patients, mapping revealed diffuse myocardial damage in additional 9 (75%) patients, with a high prevalence of increased T2 values. Conclusions: Our data show a low prevalence of culprit lesions in troponin-positive stroke patients. However, > 50% of the patients demonstrated myocardial scars (ischemic + non-ischemic) by LGE-CMR. Mapping revealed additional myocardial abnormalities (mostly inflammatory) in the majority of LGE-negative patients. Therefore, a comprehensive CMR protocol gives important insights in the etiology of troponin which might have implications for the further work-up of troponin-positive stroke patients.

Cost-Minimization Analysis for Cardiac Revascularization in 12 Health Care Systems Based on the EuroCMR/SPINS Registries.

OBJECTIVES: The aim of this study was to compare the costs of a noninvasive cardiac magnetic resonance (CMR)-guided strategy versus 2 invasive strategies with and without fractional flow reserve (FFR). BACKGROUND: Coronary artery disease (CAD) is a major contributor to the public health burden. Stress perfusion CMR has excellent accuracy to detect CAD. International guidelines recommend as a first step noninvasive testing of patients in stable condition with known or suspected CAD. However, nonadherence in routine clinical practice is high. METHODS: In the EuroCMR (European Cardiovascular Magnetic Resonance) registry (n = 3,647, 59 centers, 18 countries) and the U.S.-based SPINS (Stress-CMR Perfusion Imaging in the United States) registry (n = 2,349, 13 centers, 11 states), costs were calculated for 12 health care systems (8 in Europe, the United States, 2 in Latin America, and 1 in Asia). Costs included diagnostic examinations (CMR and x-ray coronary angiography [CXA] with and without FFR), revascularizations, and complications during 1-year follow-up. Seven subgroup analyses covered low- to high-risk cohorts. Patients with ischemia-positive CMR underwent CXA and revascularization at the treating physician's discretion (CMR+CXA strategy). In the hypothetical invasive CXA+FFR strategy, costs were calculated for initial CXA and FFR in vessels with ≥50% stenoses, assuming the same proportion of revascularizations and complications as with the CMR+CXA strategy and FFR-positive rates as given in the published research. In the CXA-only strategy, costs included CXA and revascularizations of ≥50% stenoses. RESULTS: Consistent cost savings were observed for the CMR+CXA strategy compared with the CXA+FFR strategy in all 12 health care systems, ranging from 42% ± 20% and 52% ± 15% in low-risk EuroCMR and SPINS patients with atypical chest pain, respectively, to 31% ± 16% in high-risk SPINS patients with known CAD (P < 0.0001 vs 0 in all groups). Cost savings were even higher compared with CXA only, at 63% ± 11%, 73% ± 6%, and 52% ± 9%, respectively (P < 0.0001 vs 0 in all groups). CONCLUSIONS: In 12 health care systems, a CMR+CXA strategy yielded consistent moderate to high cost savings compared with a hypothetical CXA+FFR strategy over the entire spectrum of risk. Cost savings were consistently high compared with CXA only for all risk groups.

Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis.

OBJECTIVES: The purpose of this study was to investigate the diagnostic value of simultaneous hybrid cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection and differentiation of active (aCS) from chronic (cCS) cardiac sarcoidosis. BACKGROUND: Late gadolinium enhancement (LGE) CMR and FDG-PET are both established imaging techniques for the detection of CS. However, there are limited data regarding the value of a comprehensive simultaneous hybrid CMR/FDG-PET imaging approach that includes CMR mapping techniques. METHODS: Forty-three patients with biopsy-proven extracardiac sarcoidosis (median age: 48 years, interquartile range: 37-57 years, 65% male) were prospectively enrolled for evaluation of suspected CS. After dietary preparation for suppression of myocardial glucose metabolism, patients were evaluated on a 3-T hybrid PET/MR scanner. The CMR protocol included T1 and T2 mapping, myocardial function, and LGE imaging. We assumed aCS if PET and CMR (ie, LGE or T1/T2 mapping) were both positive (PET+/CMR+), cCS if PET was negative but CMR was positive (PET-/CMR+), and no CS if patients were CMR negative regardless of PET findings. RESULTS: Among the 43 patients, myocardial glucose uptake was suppressed successfully in 36 (84%). Hybrid CMR/FDG-PET revealed aCS in 13 patients (36%), cCS in 5 (14%), and no CS in 18 (50%). LGE was present in 14 patients (39%); T1 mapping was abnormal in 10 (27%) and T2 mapping abnormal in 2 (6%). CS was diagnosed based on abnormal T1 mapping in 4 out of 18 CS patients (22%) who were LGE negative. PET FDG uptake was present in 17 (47%) patients. CONCLUSIONS: Comprehensive simultaneous hybrid CMR/FDG-PET imaging is useful for the detection of CS and provides additional value for identifying active disease. Our results may have implications for enhanced diagnosis as well as improved identification of patients with aCS in whom anti-inflammatory therapy may be most beneficial.

Myocardial mechanics in dilated cardiomyopathy: prognostic value of left ventricular torsion and strain.

BACKGROUND: Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT). METHODS: CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome. RESULTS: GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p < 0.001). The primary endpoint occurred in 59 (18.7%) patients [median follow-up 4.2 (2.0-5.6) years]. In the univariate analyses all strain parameters showed a significant prognostic value (p < 0.05). In the multivariate model, LV strain parameters, particularly GLS provided an incremental prognostic value compared to established CMR parameters like LV ejection fraction and late gadolinium enhancement. A scoring model including six categorical variables of standard CMR and strain parameters differentiated further risk subgroups. CONCLUSION: LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.

Coronary artery spasm and impaired myocardial perfusion in patients with ANOCA: Predictors from a multimodality study using stress CMR and acetylcholine testing.

BACKGROUND: Functional coronary disorders such as coronary spasm and microvascular dysfunction (including microvascular spasm and impaired microvascular dilatation) are frequent findings among patients with angina and non-obstructed coronary arteries (ANOCA). In this study, we investigated a potential association of coronary spasm and myocardial perfusion abnormalities as well as predictors of such functional coronary disorders in ANOCA patients using a multimodality diagnostic strategy including adenosine stress CMR and intracoronary acetylcholine testing. METHODS: We enrolled 129 patients with ANOCA who underwent acetylcholine testing and adenosine stress perfusion CMR. Patients were allocated to 3 groups according to their spasm testing result with regard to standardized COVADIS criteria: 1) epicardial spasm, 2) microvascular spasm, and 3) no spasm. The myocardial perfusion reserve index (MPRI) was semiquantitatively determined from adenosine stress perfusion CMR. Multivariate regression analyses were performed to identify predictors of coronary functional disorders. RESULTS: Patients with epicardial spasm had lower MPRI than patients without, whereas MPRI was preserved in patients with microvascular spasm. Multivariate analyses revealed age, previous myocardial infarction, LVEF and epicardial spasm as independent predictors of diminished MPRI, whereas previous PCI was associated with epicardial spasm, and female sex was a strong predictor of microvascular spasm. CONCLUSIONS: Our results demonstrate coexistence of different functional coronary disorder endotypes involving the macro- and microvascular level of the coronary circulation in patients with ANOCA. We demonstrate that epicardial spasm is associated with diminished myocardial perfusion reserve and report further predictors of coronary functional disorders.

Quality assurance of quantitative cardiac T1-mapping in multicenter clinical trials - A T1 phantom program from the hypertrophic cardiomyopathy registry (HCMR) study.

BACKGROUND: Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials. PURPOSE: To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use. METHODS: MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites. RESULTS: T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R2 > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions. CONCLUSIONS: The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials.

Myocarditis in athletes: A clinical perspective.

Myocarditis is an important cause of arrhythmias and sudden cardiac death (SCD) in both physically active individuals and athletes. Elite athletes seem to have an increased risk for viral infection and subsequent myocarditis due to increased exposure to pathogens (worldwide traveling/international competition) or impaired immune system (continuing training during infections/resuming training early thereafter, strenuous exercise training or competition, and exercising in extreme weather conditions). Initial clinical presentation is variable, but athletes characteristically express non-specific symptoms of fatigue, muscle soreness, increased heart rate at rest, as well as during exercise and reduced overall exercise capacity. Beyond resting electrocardiogram (ECG), cardiac biomarkers, echocardiography, and 24-hour Holter ECG, diagnostic work-up should include cardiac magnetic resonance imaging (CMR) assessing inflammation, oedema, and fibrosis by late gadolinium enhancement (LGE), respectively, as these measures are crucial for prognosis and sports eligibility. For patients with insufficient cardiac recovery, endomyocardial biopsy is recommended to clarify differential diagnoses and initiate specific treatment options. In uncomplicated cases with normal left ventricular function during acute phase and absent LGE, eligibility for sports can be attested to three months after clinical recovery. In those with persistent pathological findings, even after six months, the risk for SCD remains increased and resuming exercise beyond recreational activities can only be recommended individually based on course of disease, left ventricular function, arrhythmias, pattern of LGE in CMR, as well as intensity and volume of exercise performed during training and competition. For all athletes, follow-up examination should be performed yearly.

Long-term risk of sudden cardiac death in hypertrophic cardiomyopathy: a cardiac magnetic resonance outcome study.

AIMS: Sudden cardiac death (SCD) is an appalling complication of hypertrophic cardiomyopathy (HCM). There is an ongoing discussion about the optimal SCD risk stratification strategy since established SCD risk models have suboptimal discriminative power. The aim of this study was to evaluate the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for SCD risk stratification compared to the European Society of Cardiology (ESC) SCD risk score and traditional risk factors in an >10-year follow-up. METHODS AND RESULTS: Two hundred and twenty consecutive patients with HCM and LGE-CMR were enrolled. Follow-up data were available in 203 patients (median age 58 years, 61% male) after a median follow-up period of 10.4 years. LGE was present in 70% of patients with a median LGE amount of 1.6%, the median ESC 5-year SCD risk score was 1.84. In the overall cohort, SCD rates were 2.3% at 5 years, 4.8% at 10 years, and 15.7% at 15 years, independent from established risk models. An LGE amount of >5% left ventricular (LV) mass portends the highest risk for SCD with SCD prevalences of 5.5% at 5 years, 13.0% at 10 years, and 33.3% at 15 years. Conversely, patients with no or ≤5% LGE of LV mass have favourable prognosis. CONCLUSIONS: LGE-CMR in HCM patients allows effective 10-year SCD risk stratification beyond established risk factors. LGE amount might be added to established risk models to improve its discriminatory power. Specifically, patients with >5% LGE should be carefully monitored and might be adequate candidates for primary prevention implantable cardioverter-defibrillator during the clinical long-term course.

Diagnostic value of cardiovascular magnetic resonance in comparison to endomyocardial biopsy in cardiac amyloidosis: a multi-centre study.

BACKGROUND: Cardiac amyloidosis (CA) is an infiltrative disease characterised by accumulation of amyloid deposits in the extracellular space of the myocardium-comprising transthyretin (ATTR) and light chain (AL) amyloidosis as the most frequent subtypes. Histopathological proof of amyloid deposits by endomyocardial biopsy (EMB) is the gold standard for diagnosis of CA. Cardiovascular magnetic resonance (CMR) allows non-invasive workup of suspected CA. We conducted a multi-centre study to assess the diagnostic value of CMR in comparison to EMB for the diagnosis of CA. METHODS: We studied N = 160 patients characterised by symptoms of heart failure and presence of left ventricular (LV) hypertrophy of unknown origin who presented to specialised cardiomyopathy centres in Germany and underwent further diagnostic workup by both CMR and EMB. If CA was diagnosed, additional subtyping based on EMB specimens and monoclonal protein studies in serum was performed. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as native and post-contrast T1-mapping (in a subgroup)-allowing to measure extracellular volume fraction (ECV) of the myocardium. RESULTS: An EMB-based diagnosis of CA was made in N = 120 patients (CA group) whereas N = 40 patients demonstrated other diagnoses (CONTROL group). In the CA group, N = 114 (95%) patients showed a characteristic pattern of LGE indicative of CA. In the CONTROL group, only 1/40 (2%) patient showed a "false-positive" LGE pattern suggestive of CA. In the CA group, there was no patient with elevated T1-/ECV-values without a characteristic pattern of LGE indicative of CA. LGE-CMR showed a sensitivity of 95% and a specificity of 98% for the diagnosis of CA. The combination of a characteristic LGE pattern indicating CA with unremarkable monoclonal protein studies resulted in the diagnosis of ATTR-CA (confirmed by EMB) with a specificity of 98% [95%-confidence interval (CI) 92-100%] and a positive predictive value (PPV) of 99% (95%-CI 92-100%), respectively. The EMB-associated risk of complications was 3.13% in this study-without any detrimental or persistent complications. CONCLUSION: Non-invasive CMR shows an excellent diagnostic accuracy and yield regarding CA. When combined with monoclonal protein studies, CMR can differentiate ATTR from AL with high accuracy and predictive value. However, invasive EMB remains a safe invasive gold-standard and allows to differentiate CA from other cardiomyopathies that can also cause LV hypertrophy.

Left Ventricular Hypertrabeculation Is Not Associated With Cardiovascular Morbity or Mortality: Insights From the Eurocmr Registry.

Aim: Left ventricular non-compaction (LVNC) is perceived as a rare high-risk cardiomyopathy characterized by excess left ventricular (LV) trabeculation. However, there is increasing evidence contesting the clinical significance of LV hyper-trabeculation and the existence of LVNC as a distinct cardiomyopathy. The aim of this study is to assess the association of LV trabeculation extent with cardiovascular morbidity and all-cause mortality in patients undergoing clinical cardiac magnetic resonance (CMR) scans across 57 European centers from the EuroCMR registry. Methods and Results: We studied 822 randomly selected cases from the EuroCMR registry. Image acquisition was according to international guidelines. We manually segmented images for LV chamber quantification and measurement of LV trabeculation (as per Petersen criteria). We report the association between LV trabeculation extent and important cardiovascular morbidities (stroke, atrial fibrillation, heart failure) and all-cause mortality prospectively recorded over 404 ± 82 days of follow-up. Maximal non-compaction to compaction ratio (NC/C) was mean (standard deviation) 1.81 ± 0.67, from these, 17% were above the threshold for hyper-trabeculation (NC/C > 2.3). LV trabeculation extent was not associated with increased risk of the defined outcomes (morbidities, mortality, LV CMR indices) in the whole cohort, or in sub-analyses of individuals without ischaemic heart disease, or those with NC/C > 2.3. Conclusion: Among 882 patients undergoing clinical CMR, excess LV trabeculation was not associated with a range of important cardiovascular morbidities or all-cause mortality over ~12 months of prospective follow-up. These findings suggest that LV hyper-trabeculation alone is not an indicator for worse cardiovascular prognosis.