BACKGROUND:There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. METHODS AND RESULTS:Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months.LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes.CONCLUSIONS: This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. Cardiac Magnetic Resonance Imaging in Myocarditis is a common cardiac disease of varying degree of severity. [1][2][3][4][5] Clinical presentation may range from mild symptoms to severe heart failure and ventricular arrhythmias. 6,7 Myocarditis has been reported in up to 25% of young adults presenting with sudden death. [8][9][10][11][12] As of today, there is a major unmet need to accurately diagnose patients with myocarditis and to identify individuals at highest risk for adverse cardiovascular events. One known indicator of poor outcome is persistent late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR). 13,14 Although cardiac enzymes and inflammatory markers may be elevated in acute myocarditis, 3,7,15,16 their role in predicting disease progression remains unknown. Transcriptomic biomarkers derived from a single endomyocardial biopsy have recently demonstrated promising results as highly accurate diagnostic test for lymphocytic myocarditis. 17,18 However, endomyocardial biopsy is an invasive procedure with the risk of complications and the limitation of sampling error. [19][20][21][22] Furthermore, it can only be performed in experienced centers. Therefore, its use is limit...

Background Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. Methods In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58–77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. Results In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02–5.45], OR0.68[0.59–0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55–0.75], DM OR1.47[1.26–1.72], CKD OR1.61[1.32–1.97], COPD OR1.30[1.07–1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. Conclusions Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. Trial registration CAPACITY-COVID (NCT04325412)

ObjectiveClinical data on the effect of non-steroidal anti-inflammatory drugs (NSAIDs) in myopericarditis are limited. Since NSAIDs are standard therapy in pericarditis, we retrospectively investigated their safety in myopericarditis.MethodsIn a retrospective case-control study, we identified 60 patients with myopericarditis from September 2010 to August 2017. Diagnosis was based on clinical criteria, elevated high-sensitivity troponin T and cardiac magnetic resonance imaging (CMR). All patients received standard heart failure therapy if indicated. Twenty-nine patients (62%) received NSAIDs (acetylsalicylic acid: n=7, average daily dose =1300 mg or ibuprofen: n=22, average daily dose =1500 mg) for an average duration of 4 weeks. To create two cohorts with similar baseline conditions, 15 patients were excluded. Three months after diagnosis, 29 patients were re-evaluated by CMR to measure late gadolinium enhancement (LGE).ResultsBaseline characteristics of those treated with or without NSAIDs were similar. Mean age was 34 (±13) years, 6 (13%) were women. Mean left ventricular ejection fraction (LVEF) was 56% (±5). 82 % of the patients (14 of 17) treated with NSAIDs experienced a decrease in LGE at 3 months, while it was only 58 % (7 of 12) of those without NSAIDs (p=0.15). At 12-month follow-up, one of the patients treated without NSAIDs experienced polymorphic ventricular tachycardia (VT) with cardiac arrest, while one of the patients with NSAIDs experienced non-sustained VT.ConclusionsThis is the first case-control study demonstrating that NSAIDs are safe in patients with myopericarditis and preserved LVEF. Our data suggest that this drug class should be tested prospectively in a large randomised clinical trial.

Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Methods and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P &lt; 0.018) particularly for severe (New York Heart Association class III/IV) heart failure (aRR 1.41, 95% CI 1.20–1.64; P &lt; 0.018). None of the other heart disease subtypes, including ischaemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in &lt;1% of patients. Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.

BACKGROUND: Systematic work-up of patients with myocardial infarction and non-obstructive coronary artery disease (MINOCA) using cardiac magnetic resonance imaging (CMR) led to a more than six-fold increase in the detection rate of myocarditis. In this study, we expanded on our prior two-year analysis by including preceding and subsequent years.METHODS: We performed a retrospective chart review of patients with angina-like symptoms and elevated highsensitivity troponin T (TnT-hs ≥14 ng/l) but without significant coronary artery disease, from 2011 to 2017. Patients underwent CMR to test for myocarditis. From 2011 to 2015, only patients with elevated TnT-hs, no significant coronary artery disease and moderate to high clinical likelihood of suffering from myocarditis, underwent CMR. In 2016 and 2017, CMR images were obtained from all patients with MINOCA, independent of the clinical likelihood that patients were suffering from myocarditis. RESULTS: A total of 556 patients who underwent CMR (70.5% male, 57 ± 17 years, with an average left ventricular ejection fraction of 51 ± 15%) qualified for inclusion in this study's analysis. From 2011 to 2015, 240 CMR examinations were performed, with the number increasing to 316 between 2016 and 2017. In total, myocarditis was diagnosed in 76 out of the 556 patients (13.7%). Between 2011 and 2015, the detection rate of myocarditis was 12.7 per 100,000 hospitalisations and increased 4.9-fold (p <0.0001), to 62.5 per 100,000 hospitalisations, between 2016 and 2017. CONCLUSION: A novel diagnostic algorithm led to an average 4.9-fold increase in the rate of myocarditis detection in our hospital over the two subsequent years. This highlights that myocarditis continues to be underdiag-nosed when CMR is not systematically used in patients with MINOCA.