ABSTRACT
There is an unmet need for accurate and practical screening to detect myocarditis. We sought to test the hypothesis that the extent of acute myocarditis, measured by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR), can be estimated based on routine blood markers. A total of 44 patients were diagnosed with acute myocarditis and included in this study. There was strong correlation between myoglobin and LGE (rs = 0.73 [95% CI 0.51; 0.87], p < 0.001), while correlation was weak between LGE and TnT-hs (rs = 0.37 [95% CI 0.09; 0.61], p = 0.01). Receiver operating curve (ROC) analysis determined myoglobin ≥ 87 µg/L as cutoff to identify myocarditis (92% sensitivity, 80% specificity). The data were reproduced in an established model of coxsackievirus B3 myocarditis in mice (n = 26). These data suggest that myoglobin is an accurate marker of acute myocarditis. Graphical Abstract Receiver operating curve analysis determined myoglobin ≥ 87 µg/L as cutoff to identify myocarditis and these data were reproduced in an established model of coxsackievirus B3 myocarditis in mice: CMRI, cardiac magnetic resonance imaging; Mb, myoglobin; LGE, late gadolinium enhancement; ROC, receiver operating curve analysis.
Subject(s)
Contrast Media/administration & dosage , Magnetic Resonance Imaging, Cine , Myocarditis/blood , Myocarditis/diagnostic imaging , Myoglobin/blood , Acute Disease , Adult , Animals , Biomarkers/blood , Coxsackievirus Infections/blood , Coxsackievirus Infections/diagnostic imaging , Coxsackievirus Infections/virology , Disease Models, Animal , Female , Humans , Male , Mice, Inbred BALB C , Middle Aged , Myocarditis/virology , Predictive Value of Tests , Reproducibility of Results , Retrospective StudiesABSTRACT
BACKGROUND: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood. METHODS: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13). RESULTS: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K. CONCLUSIONS: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , Myocarditis/virology , Virus Diseases/virology , Viruses/isolation & purification , Adult , Biopsy , DNA, Viral/genetics , DNA, Viral/isolation & purification , Female , Humans , Male , Middle Aged , Myocarditis/pathology , RNA, Viral/genetics , RNA, Viral/isolation & purification , Virus Diseases/diagnosis , Virus Diseases/genetics , Viruses/geneticsABSTRACT
Objective: Clinical 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. Methods: In 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). Results: Baseline 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. Conclusions: This 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.
ABSTRACT
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 high-sensitivity 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 underdiagnosed when CMR is not systematically used in patients with MINOCA.  .
Subject(s)
Coronary Artery Disease/diagnosis , Magnetic Resonance Imaging , Myocardial Infarction/diagnosis , Myocarditis/diagnostic imaging , Angina Pectoris/etiology , Female , Heart/physiopathology , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
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.