Heinz-Peter Schultheiss

Freie Universität Berlin | FUB · Medical School - Charité - Department 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...

Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractil...

Background Mitochondrial dysfunction is a driving factor in the development of heart failure (HF) and relates to poor cardiac function. Through elevated oxidative stress it is linked to myocardial inflammation. Both mechanisms promote the development of cardiac fibrosis, a key contributor to adverse outcomes in ischaemic and non-ischaemic HF. Diffe...

Background/Introduction With the growing prevalence of prediabetes in developed countries, complications of this predecessor of diabetes mellitus type 2 become increasingly important for medical research and practice. Prediabetes is defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and may also incorporate elevated h...

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...

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...

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...

Adenine nucleotide translocase 1 (ANT1) transfers ATP and ADP over the mitochondrial inner membrane and thus supplies the cell with energy. This study analyzed the role of ANT1 in the immune response of ischemic heart tissue. Ischemic ANT1 overexpressing hearts experienced a shift toward an anti-inflammatory immune response. The shift was character...

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)...

Chagas’ disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi , is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD....

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...

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis mea...

Type 2 Diabetes Mellitus (T2DM) is a major risk factor for chronic heart failure, even independent of coronary artery disease. Various underlying mechanisms worsening ventricular function in T2DM have been postulated based on data from animal studies, including mitochondrial abnormalities, alterations of Nuclear factor kappa-B (NfκB) expression, in...

Background: Viral genesis is the most common cause of myocarditis. COVID-19-associated myocarditis seems to be a notable extrapulmonary manifestation, which may result in the need for a different treatment. There has been no positive polymerase chain reaction (PCR) testing of SARS-CoV-2 in heart specimens, thus far. Case summary: A 48-year-old mal...

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...

Human herpesvirus 6A and 6B (HHV-6) can integrate into the germline, and as a result about 70 million people harbour the genome of one of these viruses in every cell of their body. Until now, it has been largely unknown if i) these integrations are ancient, ii) if they still occur, and iii) whether circulating virus strains differ from integrated o...

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: Left ventricular (LV) dysfunction in viral myocarditis is attributed to myocardial inflammation and fibrosis, inducing acute and long-time cardiac damage. Interventions are not established. On the basis of the link between inflammation, fibrosis, aldosterone, and extracellular matrix regulation, we aimed to investigate the effect of an early...

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...

Nuclear factor kappa-B (NFkB) has been postulated to induce cardiac fibrosis and dysfunction in heart failure and triggers inflammatory pathways. NFkB can be induced by damaged mitochondria. Its association with myocardial mitochondrial respiratory function in non-ischemic diabetes-related heart failure in humans is yet unclear. We hypothesized tha...

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 In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced...

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...

Our results indicate a new mechanism by which ANT1 influences cardioprotection. Our study shows for the first time, that ANT1 is involved in cardio protective HSP27 signaling. ANT1-OE supports HSP27 expression and secretion from cardiomyocytes. Secreted HSP27 stimulates TLR4 thereby inducing AKT signaling, ANT as well as its own intracellular synth...

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 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,...

To identify potential biomarkers supporting better phenotyping and to improve understanding of the pathophysiology of dilated cardiomyopathy (DCM), this study comparatively analyzed plasma protein profiles of DCM patients and individuals with low normal and normal left ventricular ejection fraction (LVEF) by mass spectrometry. After plasma depletio...

Background: Data concerning the effect of chronic right ventricular pacing in patients with normal left ventricular ejection fraction (LVEF%) are contradictory. The aim of this study is to evaluate the prevalence of pacing-induced cardiomyopathy (PICM) at midterm follow-up after permanent pacemaker implantation (PPM). Methods: A series of 170 pa...

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...

Aims: Human parvovirus B19 (B19V) infection directly induces apoptosis and modulates CXCR4 expression of infected marrow-derived circulating angiogenic cells (CACs). This leads to dysfunctional endogenous vascular repair. Treatment for B19V-associated disease is restricted to symptomatic treatment. Telbivudine, a thymidine analogue, established in...

The capacity of mitochondria in heart muscle cells to use oxygen to produce energy correlates with cardiac function. Julia Szendroedi at Heinrich-Heine University, Düsseldorf, Germany, and colleagues have established a technique to reliably evaluate mitochondrial energy metabolism in patients with or recovering from heart failure. They showed that...

Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s)ST2 predicts mortality from acute and chronic heart failure, but has not been studied...

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...

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...

Background: Despite improvements in immunosuppressive therapy, allograft rejection (AR) remains a major concern following heart transplantation (HTX), associated with graft loss and increased mortality. AR is currently detected histologically in surveillance endomyocardial biopsies (EMB) post HTX, which has been criticized for sampling error and in...

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...