Mitral valve dysplasia is a rare congenital etiology of primary mitral valve regurgitation. It can cause severe chronic mitral regurgitation, which may eventually lead to left atrial and ventricular dilation and dysfunction. Left ventricular non-compaction is a relatively rare cardiomyopathy that overlaps with hypertrophic and dilated cardiomyopathy. It can also lead to left or right ventricular dysfunction and failure. Papillary muscle hypertrophy may be a subtype of, or an early expression of, hypertrophic cardiomyopathy. Herein, we present a 42-year-old woman with a rare coexistence of mitral valve dysplasia, non-compaction left ventricular cardiomyopathy, and papillary muscle hypertrophy.

Heart failure remains a major cause of morbidity and mortality that is associated with myocardial changes in metabolism, contractile function, and molecular remodeling. Cardiomyopathies comprise a diverse group of disorders that can be triggered by various external and internal stressors. This review aims to cover the underlying molecular mechanism driving heart failure progression, at the level of alternative splicing.

Cardiovascular disease remains the leading cause of global mortality. Understanding its complexity requires dissecting the heart's cellular landscape. Here we present HeartMap, a comprehensive single-nucleus RNA sequencing atlas of the adult human heart. This resource integrates data from nine studies, encompassing over 2.4 million nuclei, 209 individuals, eight anatomical regions and seven disease and healthy states. After rigorous data harmonization and method comparison of batch correction methods, we characterized transcriptional diversity across 14 cell types. To demonstrate the utility of HeartMap, we identified robust disease-associated gene signatures in dilated cardiomyopathy by comparing multiple studies. Notably, we identified distinct activated fibroblast populations, enriched for COL22A1 or TNC, that display variable prevalence across cardiomyopathies. HeartMap provides a valuable tool for exploring cardiac disease at the single-cell level, facilitating both fundamental research and potential therapeutic development.

Infantile dilated cardiomyopathy (DCM) associated with left bundle branch block (LBBB) is a rare but life-threatening condition, especially when severe heart failure is present. Identifying effective solutions to improve the prognosis is crucial.

Hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM) represent the most frequent structural heart disorders. Due to the complexity of their diagnosis and the frequent occurrence of sudden cardiac death as the first manifestation, these diseases impose a relevant socio-economic burden, highlighting the urgent need for novel disease-specific biomarkers. Here, we assess the potential of microRNAs (miRNAs) as non-invasive predictors for HCM, ACM, and DCM. Electronic databases were systematically searched using relevant keywords pertaining to the disorders and miRNAs. To minimize spurious associations, only studies reporting the area under the curve (AUC) and including healthy controls were taken into account, resulting in the selection of 19 papers for further analyses. miR-29a-3p, miR-185-5p, and miR-454-3p were found overexpressed in HCM, ACM, and DCM, respectively, across different studies. Assessment of the correlation between circulating miRNA levels and cardiac features or genetic background failed to detect consistent profiles among different studies. Thus, further investigations employing consistent approaches and larger cohorts are required to validate the clinical utility of circulating miRNAs as non-invasive biomarkers for these structural cardiomyopathies.Systematic review registration PROSPERO CRD42023330236.

Background: Risk stratification in non-ischemic dilated cardiomyopathy (DCM) remains challenging because left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) do not fully capture the underlying myocardial substrate. Septal native T1 mapping provides a quantitative assessment of diffuse myocardial abnormalities and may contribute to myocardial tissue characterization within a multiparametric CMR framework. Methods: This retrospective single-center study included 45 consecutive patients with non-ischemic DCM referred for clinically indicated CMR at Perrino Hospital, Brindisi, Italy, between November 2023 and November 2025. All examinations were performed using a standardized CMR protocol including cine imaging, LGE, and native T1 mapping on a 1.5-T Siemens Healthineers scanner. Septal native T1 was used as the primary mapping parameter because of its established reproducibility and robustness for myocardial tissue characterization. Patients were followed for a composite endpoint including all-cause mortality, major ventricular arrhythmic events, appropriate ICD therapy, and hospitalization for heart failure. Endpoint coding was verified, and all analyses were performed using the final validated dataset. Results: During a median follow-up of 15 months, 14 patients (31.1%) experienced the composite endpoint. Patients with events had lower LVEF (27.1 ± 7.8% vs. 48.3 ± 10.5%; p < 0.001), higher LVEDVi (142.6 ± 28.5 vs. 110.6 ± 23.4 mL/m2; p = 0.001), and higher septal native T1 values among patients with available T1 measurements (1047.5 ± 25.0 vs. 1031.5 ± 24.3 ms; p = 0.065). ROC analysis identified a septal native T1 threshold of 1042 ms for prediction of the composite endpoint, with an exploratory AUC of 0.70. Event-free survival was lower in patients with septal native T1 ≥ 1042 ms. Given the limited number of events, all regression and hierarchical analyses should be interpreted as exploratory and hypothesis-generating. Conclusions: Higher septal native T1 values were observed in patients experiencing adverse clinical outcomes; however, native T1 was not independently associated with the composite endpoint in exploratory Cox regression analyses.

Cardiomyopathies are traditionally classified by structural and genetic phenotypes, but emerging evidence highlights chronic myocardial inflammation as a pivotal driver of disease progression across different etiologies. This review synthesizes the current literature on the cellular and molecular inflammatory mechanisms underlying hypertrophic cardiomyopathy, Anderson-Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy. Across these distinct conditions, endogenous triggers such as metabolic substrates, misfolded amyloid fibrils, mechanical stress, or viral genomes act as damage-associated molecular patterns. These stimuli activate innate and adaptive immune cascades, notably the Toll-like receptors, the NF-κB pathway, and the NLRP3 inflammasome. This immune activation establishes a pro-inflammatory microenvironment that promotes fibroblast reprogramming, myocardial edema, and progressive fibrotic or fibro-fatty remodeling. Inflammation is an active, core pathophysiological mechanism rather than a passive secondary bystander in cardiomyopathies. Recognizing these shared immune pathways provides a framework for improved risk stratification and highlights the potential for targeted immunomodulatory therapies to alter disease trajectories.

Autosomal dominant kidney hypomagnesemia with RRAGD variants (ADKH-RRAGD) is a hereditary disorder characterized by kidney tubulopathy and dilated cardiomyopathy (DCM). RagD, encoded by the RRAGD gene, is a small GTPase involved in activating the mechanistic target of rapamycin complex 1 (mTORC1) by amino acids. Although several gain-of-function variants in the RRAGD gene have been identified, their contributions to DCM remain unclear. Here, we hypothesize that these RRAGD variants induce mTORC1 overactivation, thereby contributing to the manifestation of DCM. To investigate this, we established T-REx HeLa cell lines that overexpress the RRAGD p.(Ser76Leu) or the wild-type (WT) variant to assess the effects on mTORC1 signaling. Additionally, we developed the first cellular model of ADKH-RRAGD utilizing genetically edited human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express the mutated variant. Our data indicate that the RRAGD p.(Ser76Leu) variant maintains the phosphorylation of mTORC1 targets (i.e., S6K, 4E-BP1, and TFEB) during amino acid starvation, in contrast to RRAGD WT in T-REx HeLa cells. The pharmacological inhibition of mTOR with Torin1 reversed these changes. In 2D-cultured RRAGDWT/p.(Ser76Leu) hiPSC-CMs, mTORC1 remained responsive to amino acid starvation. Results from bulk RNA sequencing showed an upregulation of pathways associated with cytoskeletal organization and a downregulation of muscle development in RRAGDWT/p.(Ser76Leu) hiPSC-CMs. Moreover, a prolonged duration of Ca2+ transients was observed in the mutant cardiomyocytes. Altogether, our data demonstrate that gain-of-function variants in RRAGD cause mTORC1 activation in T-REx HeLa cells. Consequently, cardiomyocytes develop impaired intracellular Ca2+ clearance and activation of transcriptional programs, suggesting dedifferentiation.

Coxsackievirus B3 is a primary cause of viral myocarditis, with ≈20% of cases progressing to dilated cardiomyopathy. Despite its clinical significance, therapeutic strategies remain limited. The pathogenesis of coxsackievirus B3-induced myocarditis is complex, centered on the virus's ability to hijack the myocardial microenvironment, which is composed of various cell types and their interactions, influencing disease progression and outcomes. This review comprehensively summarizes the changes in fibroblasts, endothelial cells, mast cells, monocytes/macrophages, neutrophils, dendritic cells, natural killer cells, and lymphocytes within the myocardial microenvironment during coxsackievirus B3 infection, highlighting their critical roles in disease development. Additionally, it provides an overview of recent findings on potential therapeutic approaches targeting the myocardial microenvironment. Targeted regulation of cellular functions, key molecular pathway intervention, intelligent delivery system development, and noninvasive biomarker identification, combined with organoid and artificial intelligence technologies, pave the way for precision therapy and diagnosis centered on myocardial microenvironment remodeling.