The management of myocarditis.
ABSTRACT Despite considerable advances in our understanding of myocarditis pathogenesis, the clinical management of myocarditis has changed relatively little in the last few years. This review aims to help bridge the widening gap between recent mechanistic insights, which are largely derived from animal models, and their potential impact on disease burden. We illustrate the pathogenetic mechanisms that are prime targets for novel therapeutic interventions. Pathway and pathogen-specific molecular diagnostic tests have expanded the role for endomyocardial biopsy. State of the art cardiac magnetic resonance imaging can now provide non-invasive tissue characterization and localize inflammatory infiltrates but imaging techniques are misleading if infectious agents are involved. We emphasize the gaps in our current clinical knowledge, particularly with respect to aetiology-based therapy, and suggest opportunities for high impact, translational investigations.
Article: Virus Detection and Semi-Quantitation in Explanted Heart Tissues of Idiopathic Dilated Cardiomyopathy Adult Patients using PCR coupled with Mass Spectometry Analysis.[show abstract] [hide abstract]
ABSTRACT: Viral detection in heart tissues has become a central issue for the diagnosis and the pathogenesis exploration of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses were detected and semi-quantified for the first time using a new technology based on PCR assays coupled to mass spectrometry analysis (PCR-MS) and in comparison by referenced real-time PCR ((RT)-qPCR) assays in 67 explanted heart samples of 31 IDCM adult patients. PCR-MS identified single or mixed Enterovirus (EV) and Parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas (RT)-qPCR assays identified viral infections in 26 (38.8%) samples corresponding to 16 (51.6%) of the patients. PCR-MS results correlated well with EV and PVB19 detection by (RT)-qPCR assays (kappa tests= 0.85 [0.72-1.00; 95%] and 0.82 [0.66-0.99; 95%], respectively). Levels of EV RNA (median value=550 [178-3200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median value= 486 [80-1157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and were correlated with those obtained by (RT)-qPCR assays (r(2)=0.57 P=0.002 and r(2)=0.64, P<0.001, for EV and PVB19 respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology that was capable to simultaneously identify 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semi-quantify common virus in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.Journal of clinical microbiology 05/2013; · 4.16 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: The transcription factor signal transducer and activator of transcription 3 (STAT3) is an important mediator of the inflammatory process. We investigated the role of STAT3 in viral myocarditis and its possible role in the development to dilated cardiomyopathy. We used STAT3-deficent mice with a cardiomyocyte-restricted knockout and induced a viral myocarditis using Coxsackievirus B3 (CVB3) which induced a severe inflammation during the acute phase of the viral myocarditis. A complete virus clearance and an attenuated inflammation were examined in both groups WT and STAT3 KO mice 4 weeks after infection, but the cardiac function in STAT3 KO mice was significantly decreased in contrast to the infected WT mice. Interestingly, an increased expression of collagen I was detected in STAT3 KO mice compared to WT mice 4 weeks after CVB3 infection. Furthermore, the matrix degradation was reduced in STAT3 KO mice which might be an explanation for the observed matrix deposition. Consequently, we here demonstrate the protective function of STAT3 in CVB3-induced myocarditis. Since the cardiomyocyte-restricted knockout leads to an increased fibrosis, it can be assumed that STAT3 signalling in cardiomyocytes protects the heart against increased fibrosis through paracrine effects.Cardiology research and practice. 01/2012; 2012:437623.
[show abstract] [hide abstract]
ABSTRACT: Myocarditis is defined as acute inflammation of the myocardium, usually following a non-specific flu-like illness, and encompasses a wide range of clinical presentations ranging from mild or subclinical disease to heart failure. We report a 12-day-old healthy full-term neonate who presented with abrupt onset of congestive cardiac failure (CCF) following a viral prodrome. Examination revealed persistent sinus tachycardia, lymphocytosis, gross cardiomegaly, nonspecific electrocardiogram changes with echocardiography showing Swiss cheese ventricular septal defect (VSD). VSD alone very rarely presents as early-onset cardiac failure in the absence of other precipitating factors like anemia, sepsis, hypoglycemia etc. Myocarditis, however, can mimic VSD and can present as fulminant cardiac failure in an otherwise healthy newborn. Myocarditis is usually diagnosed based on circumstantial evidence such as a recent viral infection and the sudden onset of cardiac dysfunction while ruling out other diagnostic possibilities. Elevated troponin T level is one of the most crucial noninvasive diagnostic modalities. Several trials have concluded that levels >0.055 ng/ml are statistically significant for diagnosing myocarditis in children. In our case an abrupt onset of cardiac failure following a viral prodrome and markedly elevated cardiac troponin T without sepsis and in the presence of normal coronary anatomy clinched the diagnosis of myocarditis. An early and aggressive treatment for CCF along with regular long-term follow-up plays a key role in the management of myocarditis. Role of high-dose Intravenous immunoglobulin in myocarditis has been studied by many trials with different outcomes. This is the first case report showing coexistence of VSD with myocarditis in a neonate presenting as early-onset acute cardiac failure. The report highlights the importance of screening for myocarditis in all previously normal babies presenting primarily with cardiogenic symptoms even if a structural heart disease is coexistent early in life. A simplified algorithm for work-up of CCF in a neonate is proposed.Journal of Postgraduate Medicine 04/2012; 58(2):147-9. · 1.26 Impact Factor