The Quest for New Approaches in Myocarditis and Inflammatory Cardiomyopathy

Heymans, Stéphane; Eriksson, Urs; Lehtonen, Jukka; Cooper, Leslie T.

doi:10.1016/j.jacc.2016.09.937

Cited by 291 publications

(309 citation statements)

References 168 publications

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“…Viral myocarditis (VMC) is the most prevalent type of myocarditis, which often associates with sudden cardiac death and chronic dilated cardiomyopathy, especially in the young adults . One of the major viruses linked to VMC is the Coxsackievirus B3 (CVB3).…”

Section: Introductionmentioning

confidence: 99%

Fasudil exerts a cardio‐protective effect on mice with coxsackievirus B3‐induced acute viral myocarditis

Dai

Wang

Tai

et al. 2018

Cardiovascular Therapeutics

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Summary Aims To investigate whether there exists a cardio‐protective effect of Fasudil, a selective Rho kinase (ROCK) inhibitor, in an experimental murine model of acute viral myocarditis. Methods Male BALB/c mice were randomly assigned to three groups: control, myocarditis treated with placebo and myocarditis treated with Fasudil (n = 40 animals per group). Myocarditis was established by intraperitoneal injection with coxsackievirus B3 (CVB3). Twenty‐four hours after infection, Fasudil was intraperitoneally administered for 14 consecutive days. Twenty mice were randomly selected from each group to monitor a 14‐day survival rate. On day 7 and day 14, eight surviving mice from each group were sacrificed and their hearts and blood were obtained to perform serological and histological examinations. Expression of ROCKs, IL‐17, IL‐1b, TNFα, RORgt, and Foxp3 were quantified with RT‐PCR. Plasma levels of TNF alpha, IL‐1 beta, and IL‐17 were measured by ELISA. In addition, protein levels of IL‐17 and ROCK2 in cardiac tissues were analyzed with Western blot. Results Fasudil treatment significantly increased survival, attenuated myocardial necrotic lesions, reduced CVB3 replication and expression of ROCK2 and IL‐17 in the infected hearts. This treatment also imposed a T‐cell subpopulation shift, from Th17 to Treg, in cardiac tissues. Conclusions ROCK pathway inhibition was cardio‐protective in viral myocarditis with increased survival, decreased viral replication, and inflammatory response. These findings suggest that Fasudil might be a potential therapeutic agent for patients with viral myocarditis.

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Section: Introductionmentioning

confidence: 99%

Fasudil exerts a cardio‐protective effect on mice with coxsackievirus B3‐induced acute viral myocarditis

Dai

Wang

Tai

et al. 2018

Cardiovascular Therapeutics

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“…[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.…”

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confidence: 99%

Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up

Berg

Kottwitz

Baltensperger

et al. 2017

Circ: Heart Failure

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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...

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“…The transition from acute myocarditis to chronic dilated cardiomyopathy in human disease remains poorly understood. 11 In general, studies of adults with myocarditis published from eastern Asia 12 describe a higher rate of inotrope and mechanical circulatory support use than series from Western Europe and North America. It is not clear whether these clinical differences are related to subject selection or to differences in the biology of the disease across different populations.…”

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confidence: 99%