Pathogenesis, Diagnosis and Treatment of Cardiomyopathy and Cardiac Arrhythmias (2nd Edition)

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 485

Special Issue Editor


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Guest Editor
Division of Cardiology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea
Interests: atrial functional study; cryoablation technique for AF; arrhythmogenesis and inflammation in patients with AF; 3D-guided VT ablation; ventricular arrhythmia; VPC and hemodynamics; VPC and stroke
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Special Issue Information

Dear Colleagues,

Arrhythmias significantly contribute to increased morbidity and mortality, and cardiomyopathies (CM) are the leading cause of syncope and sudden cardiac death (SCD) in young people. Electrocardiographic findings and arrhythmias are closely related to cardiomyopathies. Both may be an early indication of a specific diagnosis or are the consequence of structural changes in a heart with myocardial fibrosis and decreased contractility. The spectrum of arrhythmias ranges from bradyarrhythmia to atrial and/or ventricular premature beats to atrial tachyarrhythmia and/or life-threatening ventricular arrhythmia. Atrial fibrillation (AF) represents the most common arrhythmia and is associated with an increased risk of cardio-thromboembolic events, heart failure and mortality in patients with CM, and there is growing evidence for atrial fibrillation ablation in an era of steadily increasing catheter ablation in patients with atrial fibrillation without CM. SCD prevention plays an important role in the new recommendations. These guidelines include five Class I indications for intracardiac defibrillator (ICD) treatment for CM as secondary preventions and are consistent with the 2022 ESC Guidelines for ventricular arrhythmia patient management and SCD prevention. This extends previously established individualized decision-making concepts and supports individual management and risk stratification by etiology. Recommendations for genetic testing have increased, and the guidelines acknowledge the growing evidence for specific high-risk genotypes, regardless of left ventricular morphology and function. For example, this includes a Class I recommendation for genetic testing in all patients who meet the diagnostic criteria for CM and serial genetic testing of relatives if there is a possibility of pathologic variants in the index patient. Alongside genetic testing, the role of cardiac MRI has increased in recent years, but randomized trials to guide ICD therapy are still lacking. Therefore, most guidelines emphasize the importance of an etiology-based, tailored, individualized management approach that integrates the patient’s medical history, electrocardiogram (ECG) and echocardiography, CMR, laboratory analyses, genetics and electrophysiological studies.

The scope of this Special Issue encompasses various aspects of cardiomyopathy and cardiac arrhythmias, including but not limited to:

  • The identification and characterization of underlying mechanisms and genetic factors contributing to cardiomyopathy and cardiac arrhythmias.
  • Advances in diagnostic modalities, such as innovative imaging techniques, molecular markers, genetics and electrophysiological studies.
  • Evaluation of novel therapeutic strategies and pharmacological interventions.

Dr. Sung Il Im
Guest Editor

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Keywords

  • arrhythmia
  • cardiomyopathy
  • pathogenesis
  • diagnosis

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Research

22 pages, 3303 KiB  
Article
Disparate Molecular Properties of Two Hypertrophic Cardiomyopathy-Associated cMyBP-C Mutants Reveal Distinct Pathogenic Mechanisms Beyond Haploinsufficiency
by Angelos Thanassoulas, Emna Riguene, Maria Theodoridou, Laila Barrak, Hamad Almaraghi, Mohammed Hussain, Sahar Isa Da’as, Mohamed A. Elrayess, F. Anthony Lai and Michail Nomikos
Biomedicines 2025, 13(5), 1010; https://doi.org/10.3390/biomedicines13051010 - 22 Apr 2025
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Abstract
Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder marked by abnormal thickening of the left ventricular myocardium, often leading to arrhythmias and heart failure. Mutations in sarcomeric protein genes, particularly MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), are [...] Read more.
Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder marked by abnormal thickening of the left ventricular myocardium, often leading to arrhythmias and heart failure. Mutations in sarcomeric protein genes, particularly MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), are major contributors to HCM pathogenesis. This study aims to investigate the structural and functional effects of two HCM-associated missense mutations, p.S236G and p.E334K, located within the C0–C2 domains of cMyBP-C. Methods: Following in silico analysis, a bacterial expression system was applied, enabling the discrete C0–C2 domains of wild-type (cMyBP-CWT) and mutant (cMyBP-CS236G and cMyBP-CE334K) cMyBP-C proteins to be expressed and purified as recombinant proteins. Structural and stability changes were assessed using circular dichroism (CD), differential scanning calorimetry (DSC), and chemical denaturation assays. Functional impact on actin binding was also evaluated in vitro. Results: CD analysis revealed altered secondary structure in both mutants compared to the wild-type protein. Thermal and chemical stability assays indicated increased stability in the cMyBP-CE334K mutant, suggesting that it exhibits a more rigid conformation. This increased rigidity corresponded with a significant reduction in the actin-binding affinity relative to the wild-type protein. Conclusions: Our findings demonstrate specific detrimental effects of the p.E334K mutation and underscore the importance of understanding the structural and functional consequences of HCM-associated mutations to assist the development of targeted therapeutic strategies. Full article
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