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

Tschöpe, Carsten; Linthout, Sophie Van; Jäger, Sebastian; Arndt, R; Trippel, Tobias Daniel; Müller, Irene; Elsanhoury, Ahmed; Rutschow, Susanne; Anker, Stefan D.; Schultheiß, Heinz Peter; Pauschinger, Matthias; Spillmann, Frank; Pappritz, Kathleen

doi:10.1002/ehf2.12887

Cited by 14 publications

(12 citation statements)

References 72 publications

(127 reference statements)

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“…Evidence shows that early blockade (starting at the acute phase of CVB3 infection) of the mineralocorticoid receptor with eplerenone has pleiotropic effects, including immunomodulatory, anti-oxidative and anti-apoptotic effects, and prevents adverse cardiac remodelling and dysfunction without affecting viral load in the heart in a mouse model of persistent viral myocarditis 287 . This finding suggests that eplerenone is an ideal candidate as an acute treatment of myocarditis, together with HF treatment.…”

Section: Therapymentioning

confidence: 99%

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

et al. 2020

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Inflammatory cardiomyopathy is defined as myocarditis in association with cardiac dysfunction and ventricular remodelling 1,2. Despite extensive research and improved diagnosis and understanding of the pathogenesis of inflammatory cardiomyopathy, this disorder is still associated with a poor prognosis when complicated by left ventricular (LV) dysfunction, heart failure (HF) or arrhythmia 3. Furthermore, fulminant myocarditis, a rare, sudden and severe cardiac inflammation, is one of the main causes of cardiogenic shock in young adults 4,5. Prompt diagnosis and specific treatment strategies are needed to reduce mortality and the need for heart transplantation in these patients 4,5. Many questions remain unanswered regarding the pathogenesis of inflammatory cardiomyopathy and the role of the viral infection, the immune system, the host genetic background and the environment in disease progression and prognosis. These gaps in knowledge highlight the need for advanced experimental systems that can better model the human immune system and the need to improve the characterization and classification of the patients, for example, with the use of phenomapping and phenomics, which involve detailed evaluation of immune status, viral presence and/or other biomarkers. In this Review, we discuss the available evidence and identify the gaps in our understanding of the pathogenesis, diagnosis, treatment and prognosis of myocarditis and inflammatory cardiomyopathy, appraise the available animal and cell models of these conditions and propose future directions for the field. We discuss the role

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Section: Therapymentioning

confidence: 99%

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

et al. 2020

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“…On the contrary, the role of CMR in detecting myocardial inflammation is increasingly recognized and evolving. However, currently used conventional diagnostic CMR approaches for diagnosing myocarditis [63], known as the original Lake Louise Criteria (based on T1 and T2-weighted imaging, and LGE), are lacking sensitivity in the detection of myocarditis. Although, LGE, if present, have typical patterns for the identification of viral myocarditis, in the situation of diffuse myocardial injury, the diagnostic accuracy of LGE is limited.…”

Section: Early Detection Of Residual Myocardial Injury In Covid-19 Pamentioning

confidence: 99%

COVID-19 myocarditis and prospective heart failure burden

Shchendrygina

Nagel

Püntmann

et al. 2020

Expert Review of Cardiovascular Therapy

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Introduction: COVID-19 is causing considerable morbidity and mortality worldwide. Serious respiratory complications aside, the heart is also frequently involved. The mechanisms and the extent of the myocardial injury, along with the short and long-term cardiovascular (CV) outcomes in COVID-19 survivors remain unclear. Areas covered: myocardial injury has been found in a considerable proportion of hospitalized COVID-19 patients and is associated with a worse prognosis. The late onset of CV complications with myocarditis-like changes revealed by CMR has been reported in COVID-19 survivors. Previous observational studies on viral myocarditis provide evidence of a significant incomplete recovery with residual dysfunction and remodeling of left ventricle. Incomplete recovery is thought to be the result of persistent myocardial inflammation due to a post-viral autoimmune response. Considering the significant inflammatory nature of COVID-19, COVID-19 survivors may be at risk of developing persistent residual myocardial injury, the sequelae of which are unclear. Expert commentary: COVID-19 is an emerging threat for the heart. The extent of CV injury, along with the short and long-term sequelae, requires further investigation. The early detection of residual myocardial changes in COVID-19 survivors is of utmost importance in order to identify those patients at risk of CV complication development.

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“…Spironolactone and eplerenone block ICAM-1 and CTGF transcription by inhibiting SGK1 and NF-κB, which allows the inhibition of mesangial fibrosis and glomerulonephritis [ 130 ]. Eplerenone in mice with viral myocarditis reduces the presence of monocytes/macrophages, oxidative stress, and the risk of cardiac fibrosis [ 131 ]. Spironolactone and eplerenone in rats reduce the concentration of reactive oxygen intermediates (ROIs) and CRP, which are increased by aldosterone [ 132 ].…”

Section: Resultsmentioning

confidence: 99%

“…Presence of monocytes/macrophages, oxidative stress, and the risk of cardiac fibrosis in viral myocarditis [ 131 ].…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory Potential of Diuretics

Bryniarski

Nazimek

Marcinkiewicz

2021

Biology

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In this review, diuretics and their immunomodulatory functions are described. The effects on the immune response of this group of drugs are reported in patients suffering from hypertension and under experimental conditions involving animal models and cell line studies. The pathogenesis of hypertension is strongly connected to chronic inflammation. The vast majority of diuretics modulate the immune response, changing it in favor of the anti-inflammatory response, but depending on the drug, these effects may differ. This topic is significantly important in medical practice regarding the treatment of patients who have coexisting diseases with chronic inflammatory pathogenesis, including hypertension or chronic heart failure. In patients with metabolic syndrome, allergies, or autoimmune disorders, the anti-inflammatory effect is favorable, because of the overstimulation of their immune system. Otherwise, in the geriatric population, it is important to find the proper anti- and pro-inflammatory balance to avoid an enhancement of immune response suppression, which can result in reducing the risk of serious infections that can occur due to the age-diminished function of the immune system. This article is intended to facilitate the selection of an antihypertensive drug that depends on the patient’s immune situation.

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

Cited by 14 publications

References 72 publications

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

COVID-19 myocarditis and prospective heart failure burden

Immunomodulatory Potential of Diuretics

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