An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiomyopathy that follows an autosomal dominant inheritance pattern. The majority of HCM cases can be attributed to mutation of the MYBPC3 gene, which encodes cMyBP-C, a crucial structural protein of the cardiac muscle. The manifestation of HCM's morphological, histological, and clinical symptoms is subject to the complex interplay of various determinants, including genetic mutation and environmental factors. Approximately half of MYBPC3 mutations give rise to truncated protein products, while the remaining mutations cause insertion/deletion, frameshift, or missense mutations of single amino acids. In addition, the onset of HCM may be attributed to disturbances in the protein and transcript quality control systems, namely, the ubiquitin-proteasome system and nonsense-mediated RNA dysfunctions. The aforementioned genetic modifications, which appear to be associated with unfavorable lifelong outcomes and are largely influenced by the type of mutation, exhibit a unique array of clinical manifestations ranging from asymptomatic to arrhythmic syncope and even sudden cardiac death. Although the current understanding of the MYBPC3 mutation does not comprehensively explain the varied phenotypic manifestations witnessed in patients with HCM, patients with pathogenic MYBPC3 mutations can exhibit an array of clinical manifestations ranging from asymptomatic to advanced heart failure and sudden cardiac death, leading to a higher rate of adverse clinical outcomes. This review focuses on MYBPC3 mutation and its characteristics as a prognostic determinant for disease onset and related clinical consequences in HCM.

Beyond Blood Sugar: How Left Atrium Strain Predicts Cardiac Outcomes in Type 2 Diabetes.

Speckle tracking echocardiography is an innovative imaging technique that evaluates myocardial motion, including the function of the left atrium (LA). The assessment of the left atrium's function across its dimensions can have diagnostic and prognostic roles in various cardiovascular conditions. Left atrial strain has been recognized as a valuable predictor of mortality and cardiovascular incidents in the general population across various conditions. For individuals with type 2 diabetes mellitus (T2DM), left atrial dysfunction, as gauged by speckle tracking echocardiography, appears particularly prognostic. Parameters such as peak atrial longitudinal strain (PALS) and left atrial stiffness have been linked with heightened risks of severe cardiovascular events, including atrial fibrillation (AF), heart failure (HF) hospitalizations, or mortality. Consequently, recognizing left atrial dysfunction early is crucial for accurate diagnosis, guiding treatment choices, comprehensive patient management, and prognosis evaluation. Using two-dimensional (2D) speckle tracking echocardiography, results from recent studies report that treatment with empagliflozin significantly enhanced LA function in patients with type 2 diabetes mellitus, improving left atrial strain (LAS) contraction and reservoir values. Furthermore, treatments with glucagon-like peptide-1 (GLP)-1 receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors were shown to improve LA reservoir strain more effectively than insulin alone, suggesting their potential in reducing cardiovascular complications in T2DM patients. This narrative review further addresses ongoing challenges and potential enhancements needed to boost the clinical value of left atrium strain, emphasizing its significance in managing and improving outcomes for diabetic patients.

Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin-angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition. A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.