Immunosuppressive Therapy Improves Both Short- and Long-Term Prognosis in Patients With Virus-Negative Nonfulminant Inflammatory Cardiomyopathy

Merken, Jort J.; Hazebroek, Mark; Paassen, Pieter van; Verdonschot, Job A.J.; Empel, Vanessa van; Knackstedt, Christian; Hamid, Myrurgia Abdul; Seiler, Michael P.; Kolb, Julian; Hoermann, Philipp; Ensinger, Christian; Rocca, Hans‐Peter Brunner‐La; Poelzl, Gerhard; Heymans, Stéphane

doi:10.1161/circheartfailure.117.004228

Cited by 79 publications

(96 citation statements)

References 29 publications

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“…In 2013, the ESC proposed an alternative criteria based on the inflammatory cell type determined by immunostaining defining an abnormal inflammatory infiltrate as follows: “≥14 leucocytes/mm 2 including up to 4 monocytes/mm 2 with the presence of CD3‐positive T lymphocytes ≥7 cells/mm 2 ”. Merken et al reported that immunosuppressive therapy improved the long‐term outcomes of patients with virus‐free inflammatory cardiomyopathy basically defined by this criteria.…”

Section: Diagnosis Of Chronic Myocarditismentioning

confidence: 99%

“…Since it has been reported that ongoing viral replication has negative prognostic implications and that virus‐positive patients are less likely to respond to immunosuppression compared with patients who do not exhibit viral replication, the lack of response to immunosuppressive therapy has been explained in part by the absence of viral genome detection in early trials. The current consensus is that myocarditis patients with biopsy‐proven viral clearance by PCR may benefit from immunosuppressive agents such as predonisone and azathioprine . Large randomized trials of immunosuppressive therapies with predonisone and azathioprine targeted at virus‐negative chronic lymphocytic myocarditis are underway …”

Section: Future Directionsmentioning

confidence: 99%

“…The benefit of inhibiting IL‐1β was suggested by recent results in patients with myocardial infarction in the Canakinumab Anti‐inflammatory Thrombosis Outcome Study (CANTOS) . In addition, for viral myocarditis patients, nonspecific anti‐inflammatory therapy with NSAIDs or low‐dosage steroids has not been recommended owing to the risk of hampering viral clearance …”

Section: Future Directionsmentioning

confidence: 99%

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Inflammation in myocardial disease: From myocarditis to dilated cardiomyopathy

Imanaka‐Yoshida

2019

Pathology International

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Dilated cardiomyopathy (DCM) is a heterogeneous group of myocardial diseases clinically defined by the presence of left ventricular dilatation and contractile dysfunction. Among various causes of DCM, a progression from viral myocarditis to DCM has long been hypothesized. Supporting this possibility, studies by endomyocardial biopsy, the only method to obtain a definite diagnosis of myocarditis at present, have provided evidence of inflammation in the myocardium in DCM patients. A number of experimental studies have elucidated a cell‐mediated autoimmune mechanism triggered by viral infection in the progression of myocarditis to DCM. In addition, the important role of inflammation in the pathogenesis of heart failure has been recognized, and many terms including myocarditis, inflammatory cardiomyopathy, and inflammatory DCM have been used for myocardial diseases associated with inflammation. This review discusses the pathophysiology of inflammation in the myocardium, and refers to diagnosis and treatment based on these concepts.

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Section: Diagnosis Of Chronic Myocarditismentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

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Inflammation in myocardial disease: From myocarditis to dilated cardiomyopathy

Imanaka‐Yoshida

2019

Pathology International

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“…However, differences in patient selection and study design, as well as focus on LVEF as primary endpoint on relative short follow-up durations, have led to contradicting results. A recent retrospective analysis by Merken and colleagues revealed a potential beneficial effect of immunosuppression in patients with myocarditis [85]. A prospective multicenter trial using azathioprine and prednisone is currently ongoing (NCT01877746).…”

Section: Current Therapy and Future Directionsmentioning

confidence: 99%

Autoimmunity in Acute Myocarditis: How Immunopathogenesis Steers New Directions for Diagnosis and Treatment

et al. 2020

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Purpose of Review Over the last decade, myocarditis has been increasingly recognized as common cause of sudden cardiac death in young adults and heart failure overall. The purpose of this review is to discuss hypothesis of development of non-infectious myocarditis, to provide a description of the immunopathogenesis and the most common mechanisms of autoimmunity in myocarditis, and to provide an update on therapeutic options. Recent Findings A new entity of myocarditis is immune checkpoint inhibitor (ICI) induced myocarditis. ICIs are used in advanced cancer to "disinhibit" the immune system and make it more aggressive in fighting cancer. This novel drug class has doubled life expectancy in metastatic melanoma and significantly increased progression free survival in advanced non-small-cell lung cancer, but comes with a risk of autoimmune diseases such as myocarditis resulting from an overly aggressive immune system. Summary Myocarditis is an inflammatory disease of the heart with major public health impact. Thorough understanding of its immunopathogenesis is crucial for accurate diagnosis and effective treatment.

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“…There has been inconsistency in the effect of immunosuppression treatment. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] A recent systematic review 17 showed that recent two randomised controlled trials (RCTs) with a combination therapy of prednisolone plus azathioprine demonstrated improvement in LVEF. In addition, a large propensity-matched registry data has demonstrated for the first time prognostic improvement with the combination therapy.…”

Section: Introductionmentioning

confidence: 99%

Prednisone and azathioprine in patients with inflammatory cardiomyopathy: systematic review and meta‐analysis

et al. 2020

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Aims Chronic non-viral myocarditis, also called inflammatory cardiomyopathy, can be treated with immune suppression on tops of optimal medical therapy (OMT) for heart failure, using a combination of prednisolone and azathioprine (IPA). However, there has been inconsistency in the effects of immunosuppression treatment. This meta-analysis is the first to evaluate all available data of the effect of this treatment on left ventricular ejection fraction (LVEF) and the combined clinical endpoint of cardiovascular mortality and/or heart transplantation-free survival. Methods and results All trials with using IPA vs. OMT in this syndrome were searched using OVID Medline and ClinicalTrials. gov, following the PRISMA guidelines. Missing data were retrieved after contacting the corresponding authors. All data was reviewed and analysed using and standard meta-analysis methods. A random effect model was used to pool the effect sizes. A total of four trials (three randomised controlled trials and one propensity-matched retrospective registry) including 369 patients were identified. IPA on top of OMT did not improve LVEF [mean difference 9.9% (95% confidence interval À1.8, 21.7)] with significant heterogeneity. When we limited our pooled estimate to the published studies only, significant LVEF improvement by IPA was observed [14% (1.4, 26.6)]. No cardiovascular mortality benefit was observed with the intervention [risk ratio 0.34 (0.08, 1.51)]. Conclusions At the moment, there is insufficient evidence supporting functional and prognostic benefits of IPA added to OMT in virus negative inflammatory positive cardiomyopathy. Further adequate-powered well-designed prospective RCTs should be warranted to explore the potential effects of adding immunosuppressive therapy to OMT.

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Immunosuppressive Therapy Improves Both Short- and Long-Term Prognosis in Patients With Virus-Negative Nonfulminant Inflammatory Cardiomyopathy

Abstract: To conclude, this study suggests that immunosuppressive therapy in infl-CMP patients results in an improved heart transplantation-free survival as compared with standard heart failure therapy alone, underscoring the urgent need for a large prospective multicenter trial.

Cited by 79 publications

References 29 publications

Inflammation in myocardial disease: From myocarditis to dilated cardiomyopathy

Inflammation in myocardial disease: From myocarditis to dilated cardiomyopathy

Autoimmunity in Acute Myocarditis: How Immunopathogenesis Steers New Directions for Diagnosis and Treatment

Prednisone and azathioprine in patients with inflammatory cardiomyopathy: systematic review and meta‐analysis

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