特発性拡張型心筋症

BACKGROUND: Grain-free diets have been potentially linked to dilated cardiomyopathy (DCM) in several studies in dogs, although the underlying mechanisms for this potential link, if present, are unclear. Additionally, some studies have found no association between grain-free diets and DCM in dogs. Unfortunately, many of these studies were limited by the validity of owner-reported diet information. Furthermore, the effect of grain-free diets on other cardiac conditions in dogs is even less studied. OBJECTIVES: To assess the validity of owner-reported grain-free diet status information, and to model the potential effect of grain-free diet exposures over the first several years of Dog Aging Project data collection. METHODS: The validity of owner-reported grain-free status of the diet was evaluated by comparing owner-reported grain-free diet status to the ingredients. Several regression analyses were performed, accounting for likely confounding factors identified with a directed acyclic graph (DAG), to measure the effect of owner-reported grain-free diet status on all cardiac diagnoses. General linear mixed-effects models and general linear regression models were used with similar results. RESULTS: There was a large misclassification error in the diets reported to be grain-free. In spite of this, modelling methods anticipate that any bias introduced into an effect estimate would be very small. Several modelling methods failed to find a statistically significant association between grain-free status of the diet and any cardiac diagnosis. When including incident-only cases in a linear model with confounders, the odds ratio for the effect of grain-free diet status on any new cardiac diagnosis was 1.05 (0.91-1.21, p value 0.52), suggesting no effect. CONCLUSIONS: The findings suggested that the potential effect of grain-free feeding on all owner-reported new diagnoses of any cardiac disease within this dataset is likely minimal or absent.

Hypertrophic cardiomyopathy (HCM) is marked by asymmetric cardiac wall thickening, hypercontractility, diastolic dysfunction, and fibrosis. Pathogenic sarcomere gene variants cause HCM, but comparable abnormalities occur in patients with unexplained disease, albeit with fewer adverse events. To investigate stage- and genotype-specific disease mechanisms, we performed single-nucleus RNA sequencing of cardiac tissues from 47 patients with HCM, spanning obstructive HCM with preserved systolic function and end-stage HCM, and compared them with nonfailing donor and dilated cardiomyopathy hearts. We identified transcriptional programs associated with cardiomyocyte hypertrophy, fibrosis, and vascular remodeling. Pathogenic variant-positive early-stage HCM samples showed reduced cardiomyocyte abundance and expansion of a proarrhythmogenic cardiomyocyte state. We identified proline-rich 16 (PRR16) as a cardiomyocyte growth-associated gene in HCM and validated its increased expression by RNA in situ hybridization and in a human induced pluripotent stem cell-derived cardiomyocyte HCM model. In HCM samples, fibroblast compositional shifts were associated with profibrotic activation and adverse extracellular matrix remodeling, accompanied by reduced collagen IV (COL4A1/COL4A2) expression and ultrastructural basement membrane abnormalities. HCM samples also exhibited extensive vascular alterations, including shifts in endothelial cell subpopulations, reduced pericyte abundance suggestive of microvascular dysfunction, and increased lymphangiogenic vascular endothelial growth factor C signaling. Unsupervised and supervised machine learning approaches distinguished HCM from dilated cardiomyopathy and accurately predicted genotype status in early-stage HCM from cell type-resolved transcriptional profiles, revealing widespread genotype-driven remodeling. Together, our findings uncover multicellular, genotype-associated remodeling programs in HCM, providing insight into mechanisms underlying arrhythmia, fibrosis, microvascular dysfunction, and heart failure progression.

BACKGROUND: Fast monomorphic ventricular tachycardia (VT) in non-ischemic and inherited cardiomyopathies is frequently treated as an imminently shock-requiring rhythm. Yet ventricular rate is an imperfect surrogate for tachycardia mechanism. When VT remains regular, monomorphic, and sustained by an organized reentrant circuit with an accessible excitable gap, antitachycardia pacing (ATP) may terminate even very rapid episodes without high-energy shock delivery. CASE SERIES: We report five patients with distinct non-ischemic arrhythmogenic substrates in whom fast sustained monomorphic VT (≥188 beats/min; tachycardia cycle length ≤320 ms), including very fast/VF-zone events >250 beats/min, was successfully terminated by ATP. The phenotypes comprised LMNA cardiomyopathy with conduction disease and septal fibrosis; TTN truncating variant-associated dilated cardiomyopathy with VT at approximately 260 beats/min; δ-sarcoglycan-associated dilated cardiomyopathy with clustered VT/electrical storm; severe non-ischemic cardiomyopathy with left bundle branch block, CRT-D implantation, and circumferential ring-like fibrosis, followed by 27 early post-implant VT episodes all terminated by ATP; and hypertrophic cardiomyopathy with an apical left ventricular aneurysm and diffuse late gadolinium enhancement, complicated by shock-free electrical storm. Several episodes were asymptomatic or initially attributed to atrial arrhythmia, whereas device interrogation documented sustained VT requiring therapy. DISCUSSION: Across these heterogeneous non-ischemic substrates, the unifying electrophysiological phenotype was fast, regular, monomorphic VT that remained susceptible to termination by ATP. The series illustrates how ATP response reflects the interaction among circuit organization, scar architecture, tachycardia cycle length, pacing-vector access, detection-zone design, and ATP programming. These observations complement randomized evidence supporting ATP for fast VT and contemporary shock-minimizing ICD programming, including PainFREE Rx II, PITAGORA ICD, MADIT-RIT, ADVANCE III, and APPRAISE ATP. CONCLUSION: Fast VT in non-ischemic cardiomyopathy should not be considered intrinsically shock-dependent. When the tachycardia is sustained, regular, monomorphic, and electrophysiologically organized, ATP may successfully terminate even very rapid episodes while preserving defibrillation as back-up therapy. The key clinical implication is that ventricular rate, although relevant to risk assessment and therapy, is an imperfect surrogate for ATP susceptibility and should not alone dictate device-programming strategy.

BACKGROUND: Mechanisms underlying cardiac manifestations of immune-mediated congenital complete heart block (CCHB) remain unclear. Dilated cardiomyopathy (DCM) in immune-mediated CCHB has been associated with RV pacing, whereas reports of LV pacing-associated DCM are lacking. CASE SUMMARY: A girl with immune-mediated CCHB showed endocardial fibroelastosis (EFE) at 20 weeks of gestation before heart block developed at 22 weeks. After LV basal-lateral pacing, she developed DCM with LV dyssynchrony. Cardiac resynchronization therapy (CRT) improved LV function and induced reverse remodeling. CONCLUSIONS: Myocardial injury may precede conduction system involvement in immune-mediated CCHB. Subclinical immune-mediated myocardial vulnerability and pacing-related dyssynchrony may contribute to DCM progression.

Genetic testing for dilated and arrhythmogenic cardiomyopathies (DCM, ACM) is increasingly important as it can refine diagnosis, inform risk stratification, and enable cascade screening. However, its clinical application remains challenging due to variable penetrance, phenotypic overlap, and marked genetic heterogeneity. This review provides a practical framework for the use of genetic testing in DCM and ACM. We outline a stepwise approach to clinical phenotyping and patient selection, review the principles of genetic testing and result interpretation, and summarize key pre- and post-test counseling considerations. We also highlight clinically important genotypes with implications for prognosis, arrhythmic risk, decisions regarding implantable cardioverter-defibrillator (ICD) implantation, family screening, and lifestyle counseling. Finally, we discuss the two-hit model that determines disease expressivity, emerging targeted therapies, and future directions in precision care.