Cardiomyopathies—from Basic Mechanisms to Novel Therapeutic Approaches

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 15768

Special Issue Editors


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Guest Editor
Department Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
Interests: cardiology; heart failure; peripartum cardiomyopathy; cardio-oncology

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Guest Editor
Department Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
Interests: cardiology; chronic heart failure; acute heart failure; peripartum cardiomyopathy; CVD in pregnancy

Special Issue Information

Dear Colleagues,

Cardiomyopathies are a highly heterogeneous group of diseases, characterized by structural and functional abnormalities in the heart muscle caused by various etiologies, including inherited and acquired cardiomyopathies. The clinical course of these myocardial diseases ranges from a few or no symptoms to symptomatic heart failure, cardiogenic shock, and sudden cardiac death. Non-ischemic cardiomyopathies can be broadly classified into dilated cardiomyopathies (DCM), hypertrophic cardiomyopathies (HCM), arrhythmogenic right ventricular cardiomyopathies (ARVC), restrictive cardiomyopathies (RCM), and unclassified cardiomyopathies.

In recent years, a large number of potential candidate genes and signaling pathways have been identified, which are involved in the pathogenesis of cardiomyopathies. Both phenotypic and pathogenic heterogeneity strongly suggest that individualized diagnostic and therapeutic approaches are needed in patient care.

Nevertheless, knowledge is lacking regarding pathogenesis and individualized treatment concepts. Therefore, new compounds, therapeutic strategies, and application methods such as organ- or cell-specific therapeutic strategies are required to treat the various forms of cardiomyopathies.

For this Special Issue, we encourage the submission of manuscripts on any aspects of molecular mechanisms, diagnosis, and treatment of cardiomyopathies, including experimental, translational, and clinical research. We accept reviews, short communications, methodology papers and full-size research papers with a focus on the following aspects:

  • Novel effective therapeutic and/or diagnostic strategies for a particular type of cardiomyopathy;
  • Approaches to better classify the phenotypes of a distinct cardiomyopathy;
  • New genes, pathomechanisms, and potential drug targets for a particular type of cardiomyopathy.

Dr. Melanie Ricke-Hoch
Dr. Tobias J. Pfeffer
Guest Editors

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Keywords

  • cardiomyopathy
  • heart failure
  • dilated cardiomyopathy
  • hypertrophic cardiomyopathy
  • peripartum cardiomyopathy
  • arrhythmogenic cardiomyopathy

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Published Papers (5 papers)

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Research

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17 pages, 2720 KiB  
Article
Endothelial Cell GATA2 Modulates the Cardiomyocyte Stress Response through the Regulation of Two Long Non-Coding RNAs
by Natali Froese, Malgorzata Szaroszyk, Mortimer Korf-Klingebiel, Katrin Koch, Jan D. Schmitto, Robert Geffers, Denise Hilfiker-Kleiner, Christian Riehle, Kai C. Wollert, Johann Bauersachs and Joerg Heineke
Biology 2022, 11(12), 1736; https://doi.org/10.3390/biology11121736 - 29 Nov 2022
Cited by 4 | Viewed by 2110
Abstract
Capillary endothelial cells modulate myocardial growth and function during pathological stress, but it is unknown how and whether this contributes to the development of heart failure. We found that the endothelial cell transcription factor GATA2 is downregulated in human failing myocardium. Endothelial GATA2 [...] Read more.
Capillary endothelial cells modulate myocardial growth and function during pathological stress, but it is unknown how and whether this contributes to the development of heart failure. We found that the endothelial cell transcription factor GATA2 is downregulated in human failing myocardium. Endothelial GATA2 knock-out (G2-EC-KO) mice develop heart failure and defective myocardial signal transduction during pressure overload, indicating that the GATA2 downregulation is maladaptive. Heart failure and perturbed signaling in G2-EC-KO mice could be induced by strong upregulation of two unknown, endothelial cell-derived long non-coding (lnc) RNAs (AK037972, AK038629, termed here GADLOR1 and 2). Mechanistically, the GADLOR1/2 lncRNAs transfer from endothelial cells to cardiomyocytes, where they block stress-induced signalling. Thereby, lncRNAs can contribute to disease as paracrine effectors of signal transduction and therefore might serve as therapeutic targets in the future. Full article
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12 pages, 1133 KiB  
Article
Neutrophile-Lymphocyte Ratio and Outcome in Takotsubo Syndrome
by David Zweiker, Edita Pogran, Laura Gargiulo, Ahmed Abd El-Razek, Ivan Lechner, Ivan Vosko, Stefan Rechberger, Heiko Bugger, Günter Christ, Diana Bonderman, Evelyn Kunschitz, Clara Czedik-Eysenberg, Antonia Roithinger, Valerie Weihs, Christoph C. Kaufmann, Andreas Zirlik, Axel Bauer, Bernhard Metzler, Thomas Lambert, Clemens Steinwender and Kurt Huberadd Show full author list remove Hide full author list
Biology 2022, 11(8), 1154; https://doi.org/10.3390/biology11081154 - 1 Aug 2022
Cited by 5 | Viewed by 2223
Abstract
Background: Takotsubo syndrome (TTS) is an important type of acute heart failure with significant risk of acute complications and death. In this analysis we sought to identify predictors for in-hospital clinical outcome in TTS patients and present long-term outcomes. Methods: In this analysis [...] Read more.
Background: Takotsubo syndrome (TTS) is an important type of acute heart failure with significant risk of acute complications and death. In this analysis we sought to identify predictors for in-hospital clinical outcome in TTS patients and present long-term outcomes. Methods: In this analysis from the Austrian national TTS registry, univariable and multivariable analyses were performed to identify significant predictors for severe in-hospital complications requiring immediate invasive treatment or leading to irreversible damage, such as cardiogenic shock, intubation, stroke, arrhythmias and death. Furthermore, the influence of independent predictors on long-term survival was evaluated. Results: A total of 338 patients (median age 72 years, 86.9% female) from six centers were included. Severe in-hospital complications occurred in 14.5% of patients. In multivariable analysis, high neutrophile-lymphocyte-ratio (NLR; OR 1.04 [95% CI 1.02–1.07], p = 0.009) and low LVEF (OR 0.92 [0.90–0.95] per %, p < 0.001) were significant predictors of severe in-hospital complications. Both the highest NLR tercile and the lowest LVEF tercile were significantly associated with reduced 5-year survival. Conclusions: Low LVEF and high NLR at admission were independently associated with increased in-hospital complications and reduced long-term survival in TTS patients. NLR is a new easy-to-measure tool to predict worse short- and long-term outcome after TTS. Full article
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14 pages, 1623 KiB  
Article
Magnetic Resonance Assessment of Ejection Fraction Versus Echocardiography for Cardioverter-Defibrillator Implantation Eligibility
by Călin Schiau, Daniel-Corneliu Leucuța, Sorin Marian Dudea and Simona Manole
Biology 2021, 10(11), 1108; https://doi.org/10.3390/biology10111108 - 27 Oct 2021
Cited by 1 | Viewed by 1668
Abstract
Background: The aim of this study was to investigate the potential impact of performing two-dimensional echocardiography (2DE) compared to cardiovascular magnetic resonance (CMR) for left ventricular ejection fraction (LVEF) on implantable cardioverter defibrillator (ICD) eligibility. Methods: A prospective cohort of 166 consecutive patients [...] Read more.
Background: The aim of this study was to investigate the potential impact of performing two-dimensional echocardiography (2DE) compared to cardiovascular magnetic resonance (CMR) for left ventricular ejection fraction (LVEF) on implantable cardioverter defibrillator (ICD) eligibility. Methods: A prospective cohort of 166 consecutive patients with nonischemic cardiomyopathy (NICM) was designed to compare transthoracic 2DE and CMR imaging. Results: Echocardiography measurements have important differences and large limits of agreement compared to CMR, especially when assessing ventricle volumes, and smaller but relevant differences when assessing LVEF. The agreement between CMR and 2DE regarding the identification of subjects with EF <= 35, respectively <= 30, and thus eligible for an ICD measured by Cohen’s Kappa was 0.78 (95% CI: 0.68–0.88), p < 0.001, respectively 0.65 (95% CI: 0.52–0.78), p < 0.001. The disagreement represented 7.9%/11.3% of the subjects who had EF < 35%/< 30% as observed by CMR, who would have been classified as eligible for an ICD, resulting in an additional need to use an ICD. Moreover, 2.6%/3.3% would have been deemed eligible by echocardiography for an ICD. Conclusions: These measurement problems result in incorrect assignments of eligibility that may have serious implications on the quality of life and the prevention of death events for patients assessed for eligibility of an ICD. Full article
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Review

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17 pages, 1537 KiB  
Review
Immune Checkpoint Inhibitor Associated Myocarditis and Cardiomyopathy: A Translational Review
by Dong Wang, Johann Bauersachs and Dominik Berliner
Biology 2023, 12(3), 472; https://doi.org/10.3390/biology12030472 - 20 Mar 2023
Cited by 11 | Viewed by 5606
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized oncology and transformed the treatment of various malignancies. By unleashing the natural immunological brake of the immune system, ICIs were initially considered an effective, gentle therapy with few side effects. However, accumulated clinical knowledge reveals that ICIs [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized oncology and transformed the treatment of various malignancies. By unleashing the natural immunological brake of the immune system, ICIs were initially considered an effective, gentle therapy with few side effects. However, accumulated clinical knowledge reveals that ICIs are associated with inflammation and tissue damage in multiple organs, leading to immune-related adverse effects (irAEs). Most irAEs involve the skin and gastrointestinal tract; however, cardiovascular involvement is associated with very high mortality rates, and its underlying pathomechanisms are poorly understood. Ranging from acute myocarditis to chronic cardiomyopathies, ICI-induced cardiotoxicity can present in various forms and entities. Revealing the inciting factors, understanding the pathogenesis, and identifying effective treatment strategies are needed to improve the care of tumor patients and our understanding of the immune and cardiovascular systems. Full article
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19 pages, 1252 KiB  
Review
Neuraminidases—Key Players in the Inflammatory Response after Pathophysiological Cardiac Stress and Potential New Therapeutic Targets in Cardiac Disease
by Maren Heimerl, Thomas Gausepohl, Julia H. Mueller and Melanie Ricke-Hoch
Biology 2022, 11(8), 1229; https://doi.org/10.3390/biology11081229 - 17 Aug 2022
Cited by 7 | Viewed by 3106
Abstract
Glycoproteins and glycolipids on the cell surfaces of vertebrates and higher invertebrates contain α-keto acid sugars called sialic acids, terminally attached to their glycan structures. The actual level of sialylation, regulated through enzymatic removal of the latter ones by NEU enzymes, highly affects [...] Read more.
Glycoproteins and glycolipids on the cell surfaces of vertebrates and higher invertebrates contain α-keto acid sugars called sialic acids, terminally attached to their glycan structures. The actual level of sialylation, regulated through enzymatic removal of the latter ones by NEU enzymes, highly affects protein-protein, cell-matrix and cell-cell interactions. Thus, their regulatory features affect a large number of different cell types, including those of the immune system. Research regarding NEUs within heart and vessels provides new insights of their involvement in the development of cardiovascular pathologies and identifies mechanisms on how inhibiting NEU enzymes can have a beneficial effect on cardiac remodelling and on a number of different cardiac diseases including CMs and atherosclerosis. In this regard, a multitude of clinical studies demonstrated the potential of N-acetylneuraminic acid (Neu5Ac) to serve as a biomarker following cardiac diseases. Anti-influenza drugs i.e., zanamivir and oseltamivir are viral NEU inhibitors, thus, they block the enzymatic activity of NEUs. When considering the improvement in cardiac function in several different cardiac disease animal models, which results from NEU reduction, the inhibition of NEU enzymes provides a new potential therapeutic treatment strategy to treat cardiac inflammatory pathologies, and thus, administrate cardioprotection. Full article
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