A Toolbox of Potential Immune-Related Therapies for Inflammatory Cardiomyopathy

Abstract

Myocarditis is a multifactorial disorder, characterized by an inflammatory reaction in the myocardium, predominantly triggered by infectious agents, but also by antigen mimicry or autoimmunity in susceptible individuals. Unless spontaneously resolved, a chronic inflammatory course concludes with cardiac muscle dysfunction portrayed by ventricular dilatation, clinically termed inflammatory cardiomyopathy (Infl-CM). Treatment strategies aim to resolve chronic inflammation and preserve cardiac function. Beside standard heart failure treatments, which only play a supportive role in this condition, systemic immunosuppressants are used to diminish inflammatory cell function at the cost of noxious side effects. To date, the treatment protocols are expert-based without large clinical evidence. This review describes concept and contemporary strategies to alleviate myocardial inflammation and sheds light on potential inflammatory targets in an evidence-based order.

Epicardial Fat Expansion in Diabetic and Obese Patients With Heart Failure and Preserved Ejection Fraction—A Specific HFpEF Phenotype

“…Inflammation is an important driver of HF, by which its role in the pathogenesis of HFrEF and HFpEF differs (133,134). Although it plays a pathological role in the EAT of obese patients (46), pharmacological treatment with anti-inflammatory agents like steroids (135) cannot be recommended in HF patients with DM and/or metabolic syndrome (136). Theoretically, several biological agents like interleukin (IL)-1 and IL-6 inhibitors can target EAT-induced myocardial inflammation (136).…”

“…Although it plays a pathological role in the EAT of obese patients (46), pharmacological treatment with anti-inflammatory agents like steroids (135) cannot be recommended in HF patients with DM and/or metabolic syndrome (136). Theoretically, several biological agents like interleukin (IL)-1 and IL-6 inhibitors can target EAT-induced myocardial inflammation (136). The small D-HARD study has demonstrated the beneficial effects of the competitive IL-1 receptor antagonist anakinra in HFpEF patients (137).…”

Modulation of the acute defence reaction by eplerenone prevents cardiac disease progression in viral myocarditis

“…A panel of different (anti‐)inflammatory and (anti‐)fibrotic network systems including macrophages, B and T cells, 8,16–18 platelets, 19 myofibroblasts, 20,21 cytokines, 22–24 chemokines, 25 damage‐associated molecular patterns, 26–30 soluble ST2, 31 lysyl oxidase‐like 2, 18 galectin‐3, 32 matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) 33,34 as well as aldosterone, 24,35 play a major role in the defence and healing process under these circumstances. For most of these potential targets, with the exception of aldosterone, no well‐established therapeutic strategies are available, and no direct translation into the clinic is possible 36 . In an animal study, aldosterone infusion has been shown to induce ventricular hypertrophy and interstitial fibrosis in both right and left ventricles 37 .…”

“…For most of these potential targets, with the exception of aldosterone, no well-established therapeutic strategies are available, and no direct translation into the clinic is possible. 36 In an animal study, aldosterone infusion has been shown to induce ventricular hypertrophy and interstitial fibrosis in both right and left ventricles. 37 Further studies have suggested that aldosterone-induced generation of reactive oxygen species and low-grade inflammation underlie aldosterone-induced cardiac fibrosis.…”

Current Perspectives on Inflammation in Cardiovascular Disease; from Biomarker to Therapy

“…The characteristic inflammatory reaction in myocarditis can, when progressed into a state of chronic inflammation, result in outward remodeling and loss of cardiac function, which is clinically referred to as inflammatory cardiomyopathy (Infl-CM). Elsanhoury and colleagues describe that Infl-CM remains an unmet medical need [8]. Several therapeutic targets, revealed by basic research, still lack translation to the patient.…”