Felicitas Escher

Charité Universitätsmedizin Berlin | Charité · Medical Department, Division of Cardiology

Objective Inflammatory cardiomyopathy is characterised by inflammatory infiltrates leading to cardiac injury, left ventricular (LV) dilatation and reduced LV ejection fraction (LVEF). Several viral pathogens and autoimmune phenomena may cause cardiac inflammation. The effects of the gain of function FOXO3A single-nucleotide polymorphism (SNP) rs122...

Open in new tabDownload slide Pathological mechanisms of viral and postinfectious autoimmunity in myocarditis and inflammatory cardiomyopathy. A genetic predisposition is supposed for persistence of virus and/or inflammation. Advanced diagnostics including endomyocardial biopsies are essential for a pathologically-proven diagnosis as the basis for...

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential re...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DZHK Ernst und Berta Grimmke Stiftung Background Myocarditis is an inflammatory disease of the myocardium indicated by mononuclear cell infiltration. It is predominantly caused by infectious agents such as coxsackievirus B3 (CVB3). Esp...

SCN5A was considered an exclusively cardiac expressed ion channel but discovered to also act as a novel innate immune sensor. We report on a young SCN5A variant carrier with recurrent ventricular fibrillation and massive myocardial inflammation whose peculiar clinical course is highly suggestive of such a dual role of SCN5A. (Level of Difficulty: A...

Human parvovirus B19 (B19V) is the predominant virus currently detected in endomyocardial biopsies (EMBs). Recent findings indicate that, specifically, transcriptionally active B19V with detectable viral RNA is of prognostic relevance in inflammatory viral cardiomyopathy. We aimed to evaluate B19V replicative status (viral RNA) and beneficial effec...

Treatment of hypertension-mediated cardiac damage with left ventricular (LV) hypertrophy (LVH) and heart failure remains challenging. To identify novel targets, we performed comparative transcriptome analysis between genetic models derived from stroke-prone spontaneously hypertensive rats (SHRSP). Here, we identified carboxypeptidase X 2 (Cpxm2) as...

Parvovirus B19 (B19V) is the predominant cardiotropic virus currently found in endomyocardial biopsies (EMBs). However, direct evidence showing a causal relationship between B19V and progression of inflammatory cardiomyopathy are still missing. The aim of this study was to analyze the impact of transcriptionally active cardiotropic B19V infection d...

Plasminogen activator inhibitor-1 (PAI-1) has a cardioprotective function in mice by repressing cardiac fibrosis through TGF-β and plasminogen-mediated pathways. In addition it is known to be involved in the recruitment and polarization of monocytes/macrophages towards a M2 phenotype in cancer. Here, we investigated the expression of PAI-1 in human...

The diagnosis of acute and chronic myocarditis remains a challenge for clinicians. Characterization of this disease has been hampered by its diverse etiologies and heterogeneous clinical presentations. Most cases of myocarditis are caused by infectious agents. Despite successful research in the last few years, the pathophysiology of viral myocardit...

Aims: Cardiac involvement in COVID-19 is associated with adverse outcome. However, it is unclear whether cell specific consequences are associated with cardiac SARS-CoV-2 infection. Therefore, we investigated heart tissue utilizing in situ hybridization, immunohistochemistry and RNA-sequencing in consecutive autopsy cases to quantify virus load an...

Background/Introduction Preclinical data indicate that plasminogen activator inhibitor-1 (PAI-1) is cardioprotective by repressing cardiac fibrosis through TGF-β and plasminogen mediated pathways. In addition it is linked to the recruitment and polarization of non-classical M2 macrophages in cancer. Purpose The role of cardiac PAI-1 in fibrogenesi...

Background Cardiac amyloidosis (CA) is increasingly recognized as an underlying cause of heart failure with preserved ejection fraction (HFpEF), associated with high morbidity and mortality. However, most studies, solely investigated the prevalence of CA in special subgroups including HFpEF and severe aortic valve disease. Purpose With the present...

Infection of the heart muscle with cardiotropic viruses is one of the major etiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy (DCM) is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Ad...

Aims Acute cellular rejection (ACR) following heart transplantation (HTX) is associated with long-term graft loss and increased mortality. Disturbed mitochondrial bioenergetics have been identified as pathophysiological drivers in heart failure, but their role in ACR remains unclear. We aimed to prove functional disturbances of myocardial bioenerge...

Funding Acknowledgements Type of funding sources: None. Background/Introduction People living with human immunodeficiency virus (HIV, PLWH) are at increased risk of cardiovascular disease (CVD). HIV infection and accelerated traditional risk factors due to highly-active antiretroviral therapy (HAART) are proposed mechanisms for increased rate of he...

Human parvovirus B19 (B19V) is the predominant cardiotropic virus associated with dilated inflammatory cardiomyopathy (DCMi). Transcriptionally active cardiotropic B19V infection is clinically relevant and triggers adverse long-term mortality. During the study; we evaluated whether antiviral treatment with the nucleoside analogue telbivudine (LTD)...

Objectives The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART). Background PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared wit...

Background: Cardiac function can be influenced by liver cirrhosis and should be thoroughly evaluated before liver transplantation. We investigated left ventricular (LV) and, for the first time, left atrial (LA) strain and strain rate in end-stage liver cirrhosis patients of different etiologies. Methods: This retrospective, cross-sectional study...

Inflammatory cardiomyopathy diagnosed by endomyocardial biopsy (EMB) is common in non-ischemic heart failure (HF) and might be associated with adverse outcome. We aimed to identify markers predicting myocardial inflammation in HF. We screened 517 patients with symptomatic non-ischemic HF who underwent EMB; 397 patients (median age 54 [IQR 43/64], 2...

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has reached pandemic levels. Cardiovascular complications in COVID-19 have been reported frequently, however evidence for a causal relationship has not been established. This report describes the detection of SA...

Background Analyses in hospitalized patients and small autopsy series suggest that severe SARS-CoV-2 infection may affect the heart. We investigated heart tissue by in situ hybridization, immunohistochemistry and RNA sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19. Methods Left ventri...

Erythroparvovirus (B19V) genomes have been detected in various organs of infected individuals including endothelial cells of the heart muscle. However, the role of B19V as a causative pathogen of myocardial damage is still unknown. The majority of reports focus on the presence of viral DNA ignoring proof of viral RNAs as important markers for viral...

Aims MicroRNAs (miRNAs) might be used as prospective biomarkers for the identification of unexplained heart failure caused by a viral and/or inflammatory process. The aim of this study was to identify and to evaluate prognostic miRNAs in serum of patients with inflammatory heart diseases diagnosed by endomyocardial biopsies. Methods and results Af...

Background Human erythroparvovirus-1 (B19V) is the most frequently found virus in endomyocardial biopsies (EMBs). Recent studies have detected B19V genomes in various organs of symptomatic and asymptomatic individuals including endothelial cells of the heart muscle. Accordingly, B19V as a causative pathogen of myocardial damage has been questioned....

Aims: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim o...

Aims The purpose of this retrospective single‐centre study was to evaluate the non‐invasive detection of endomyocardial biopsy (EMB)‐established chronic myocardial inflammation in patients with heart failure with reduced ejection fraction (HFrEF) using T1 and T2 mapping. Methods and results The study population consisted of 52 retrospectively iden...

Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. Objective To evaluate the presence of myocardial injury in unselected patients recently...

Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown. Objective To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infecti...

Aims Since December 2019, the novel coronavirus SARS‐CoV‐2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID‐19 have been reported. SARS‐CoV‐2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechani...

Background Variants of the desmosomal protein desmoplakin are associated with arrhythmogenic cardiomyopathy, an important cause of ventricular arrhythmias in children and young adults. Disease penetrance of desmoplakin variants is incomplete and variant carriers may display noncardiac, dermatologic phenotypes. We describe a novel cardiac phenotype...

Aims: Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non-advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non...

Aims: Inflammation is a key driver of atherosclerosis and myocardial infarction (MI), and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) have been implicated in inflammation control. To obtain further information on the possible role of lncRNAs in the context of atherosclerosis, we obtained comprehensive transcriptome maps of...

Cardiac amyloidosis is associated with very high morbidity and mortality. Only if treated early, cardiac amyloidosis responds well to therapy, and early recognition with a full differential diagnostic workup including multimodality imaging is therefore critical at first presentation. Closely meshed clinical monitoring and imaging are indispensable...

Background Idiopathic giant cell myocarditis (IGCM) diagnostics is based on differential patterns of inflammatory cell infiltration, and multinucleated giant cells (GCs) in histological sections of endomyocardial biopsies (EMBs). However, the sampling error is high for the detection of focally GCs by histopathology. We report on a clinical evaluati...

Background Arrhythmogenic cardiomyopathy (AC) is an important cause of ventricular arrhythmias in children and young adults. AC is associated with mutation of desmosomal proteins, however, cardiac disease penetrance is incomplete and the clinical course varies widely without recognizable exogenous or epi/genetic co-factors. Importantly, DSP mutatio...

Background Myocarditis is defined by inflammatory involvement of the myocardium, either histologically by evidence of myocardial necrosis and cellular infiltration on endomyocardial biopsy (EMB), or non-invasively by presence of myocardial oedema using tissue mapping with cardiovascular magnetic resonance (CMR). Objective: to undertake intra-indivi...

Background Plasminogen activator inhibitor type-1 (PAI-1) is an important inhibitor of the fibrinolytic pathway and an acute phase reactant in response to inflammatory cytokines, resulting in thrombosis, arteriosclerosis, and tissue fibrosis. It has been identified as a potential biomarker for coronary artery disease and metabolic syndrom. However,...

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structura...

Myocarditis is an inflammatory condition of the myocardium causing dilated cardiomyopathy and threatening arrhythmias. It typically results from cardiotropic viral infection followed by an inflammatory destruction of the myocardium. Characterization of myocarditis has been hampered by its heterogeneous clinical presentations and diverse aetiologies...

The present research evaluated right ventricular (RV) structure, function and mechanics in the cancer patients before initiation of chemo- or radiotherapy, and the association between cancer and decreased RV longitudinal strain. This retrospective investigation included 101 chemo- and radiotherapy-naïve patients with solid cancer and 38 age- and ge...

Background: Enteroviral cardiomyopathy is a life-threatening disease, and detection of enterovirus (EV) RNA in the initial endomyocardial biopsy is associated with adverse prognosis and increased mortality. Some patients with EV infection may spontaneously eliminate the virus and recover, whereas those with virus persistence deteriorate and progre...

Aims: Foxo3 is a transcription factor involved in cell metabolism, survival, and inflammatory disease. However, mechanistic insight in Foxo3 effects is still limited. Here, we investigated the role of Foxo3 on natural killer (NK) cell responses and its effects in viral myocarditis. Methods and results: Effects of Foxo3 on viral load and immune r...

Aims: To evaluate the influence of endomyocardial biopsy (EMB)-proven intramyocardial inflammation on mortality in patients with cardiac transthyretin amyloid (ATTR) or amyloid light-chain (AL) amyloidosis. Methods and results: We included 54 consecutive patients (mean age 68.83 ± 9.59 years; 45 men) with EMB-proven cardiac amyloidosis. We follo...

Table S1. Primer Used to Test the Presence of Viral Genome Figure S1. Regression analysis of perforin‐positive cells vs CD8‐positive T cells in a subgroup of 230 patients.

Background: Human parvovirus B19 (B19V) infection and damage of circulating angiogenic cells (CAC) results in dysfunctional endogenous vascular repair (DEVR) with secondary end-organ damage. Trafficking of CAC is regulated by SDF-1α and the respective receptor CXCR4. We thus tested the hypothesis of a deregulated CXCR4/SDF-1α axis in symptomatic B...

Background The authors analyzed the effects of perforin‐dependent infiltration on long‐term mortality in patients with inflammatory cardiomyopathy (CMi). We previously demonstrated that left ventricular function deteriorates and progresses to substantial cardiac dysfunction in patients with perforin‐positive cardiac cell infiltration. Methods and...

Aims: Hepatitis C virus (HCV) has been associated with cardiomyopathies. Former anti-HCV therapies employing interferon could have serious side effects in patients with advanced heart failure since interferon may adversely impact upon cardiac function. We, therefore, examined whether the novel, interferon-free and highly virus-selective anti-HCV c...

Background . Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods . We infected C...

Aim To analyze the long-term outcome after immunosuppressive treatment of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy (CMi). Methods and results We investigated 114 patients with endomyocardial biopsy (EMB)-proven virus-negative chronic myocarditis or CMi, who were treated with prednisone and azathioprine for 6 m...

Background: Chronic viral infections of the heart are considered one antecedent event leading to progressive dysfunction of the myocardium, often with an impaired prognosis due to a virus- or immune-mediated myocardial injury. Symptomatic treatment does not influence the viral cause of heart failure, and the effect of antiviral treatment has not b...

List of undetectable miRNAs in different tissues and body fluids

MicroRNAs (miRNAs) can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples (tissue, serum, peripheral blood mononuclear cells or other body fluids) differ significantly even in the same patient and therefore have th...

Quadricuspid aortic valve (QAV) is a rare congenital cardiac defect. Aortic regurgitation is the predominant hemodynamically relevant abnormality in patients with QAV, and the main reason for patients requiring valve surgery. Calcific valve disease of the left heart valves is classified as 'low embolic risk' according to current guidelines. However...

We report the case of a 17‐year‐old female patient with known hypertrophic cardiomyopathy and a Wolff‐Parkinson‐White syndrome. She came to our department for further evaluation of a new diagnosed dilated cardiomyopathy characterized by an enlargement of the left ventricle and a fall in ejection fraction. Clinically, she complained about atypical c...

Based on the definition in the European Society of Cardiology statement, myocarditis is an inflammatory disease of the myocardium diagnosed by established histological, immunological, and immunohistochemical criteria, whereas inflammatory cardiomyopathy is myocarditis in association with cardiac dysfunction. Actual incidences of myocarditis and CMi...

Die Herzinsuffizienz (HI) ist nach wie vor eines der kardiologischen Themen mit höchster Relevanz, da die Inzidenz der Erkrankung steigt und die Morbidität und Mortalität der Patienten deutlich erhöht ist. Außerdem stellt die Herzinsuffizienz auch ein bedeutsames gesundheitsökonomisches Problem dar. Angesichts der schlechten Prognose, der eingeschr...

Myocarditis is an inflammatory disease of the cardiac muscle caused by myocardial infiltration of immunocompetent cells following any kind of cardiac injury. Myocarditis is a challenging diagnosis due to the heterogeneity of clinical presentations. It can be caused by infections, drugs, toxic substances, and autoimmune diseases. Chronic inflammator...