Cardiomyopathy classification remains challenging due to their extraordinary clinical, morphological, and genetic heterogeneity. As diagnostic technologies evolve, so too must the frameworks by which we conceptualize and communicate these diseases. Since the 2008 ESC morphofunctional classification and the genotype-phenotype integrated MOGE(S) system proposed in 2013, substantial advances in imaging and genetics have prompted a revised 2023 ESC phenotype-first model. The five current phenotypes-dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and non-dilated left ventricular cardiomyopathy (NDLVC)-capture major morphological expressions but display extensive overlap, especially among DCM, ARVC, and NDLVC. This overlap underscores the need for dynamic, multiparametric diagnostic pathways and individualized interpretation.

Myocardial calcification is an uncommon complication associated with end-stage chronic kidney disease (CKD) in feline patients. This report describes the clinical and multimodal imaging features of metastatic calcification in a 10-year-old castrated male mixed-breed cat. The patient presented with dyspnea and anorexia, and was diagnosed with IRIS Stage 4 CKD. Laboratory findings revealed severe hyperphosphatemia and an elevated calcium-phosphorus product (CPP) of 135 mg[2]/dL[2], based on total calcium. This value significantly exceeds 70 mg[2]/dL[2], a threshold associated with a high probability of inducing soft tissue mineralization. Echocardiography revealed extensive hyperechoic foci with posterior acoustic shadowing in the interventricular septum and left ventricular wall. Functional assessment demonstrated a restrictive diastolic filling pattern, suggesting increased myocardial stiffness and congestive heart failure. Computed tomography (CT) further visualized systemic involvement, showing diffuse, amorphous calcifications (400-900 HU) in the myocardium, multifocal aortic wall, and extracardiac tissues. Despite intensive treatment with diuretics and renal support, the patient was euthanized eight days later due to progressive renal failure. This case illustrates that the interaction between metastatic calcification and uremic cardiomyopathy (UC) can result in refractory heart failure, underscoring the value of combined echocardiography and CT in evaluating end-stage renal disease.

Infiltrative cardiomyopathies, a subset of restrictive cardiomyopathies, are rare but clinically essential disorders often lead to heart failure, which is a major global health issue. Although interest in these conditions is growing, they remain poorly understood due to their low occurrence, vague clinical signs, and frequent underreporting. Advances in diagnosis have been made through multimodal imaging techniques-including cardiac magnetic resonance, nuclear imaging, and computed tomography-as well as genetic testing and new biomarkers for amyloidosis. However, a universal biomarker that applies across the entire range of infiltrative cardiomyopathies has yet to be identified. This review discusses albumin, a vital regulator of physiological balance, as a promising biomarker candidate. In this narrative review, we explore disease mechanisms, identify knowledge gaps in research, and suggest new connections to direct future studies and enhance diagnostic accuracy.

Physical activity (PA) is essential for the cardiovascular, emotional, and social health of all children and adolescents. However, for pediatric patients with cardiomyopathy, decades of risk-averse clinical guidance have resulted in widespread PA restriction due to fears of sudden cardiac death and disease progression. This has contributed to sedentary behavior, poor cardiorespiratory fitness, and increased risk of secondary cardiometabolic conditions in this population. However, emerging data challenge this restrictive paradigm, showing that the risk of sudden cardiac death may not be higher in some patients with cardiomyopathy who exercise than in those who are less active, and that participation in PA may also have a positive effect on reverse remodeling. This American Heart Association scientific statement provides an evidence-based framework for the promotion of PA in pediatric patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, or arrhythmogenic cardiomyopathy, as well as those with implantable cardioverter defibrillators; outlines the physical, social, and emotional benefits of PA for these children and adolescents; and provides updated risk stratification strategies, including the use of advanced imaging, exercise testing, and genotype-specific data. This scientific statement underscores the importance of shared decision-making tailored to developmental maturity and family goals and emphasizes the need for longitudinal surveillance as clinical phenotypes evolve. With individualized assessment and informed shared decision-making, most children and adolescents with cardiomyopathy can safely engage in PA, with important implications for long-term cardiometabolic and psychologic health.

Objective: To summarize the clinical phenotypes, genotypes, and treatment outcomes of restrictive cardiomyopathy (RCM) associated with FLNC gene variants in children. Methods: Case series study. The clinical data of 5 pediatric patients with FLNC gene variant-associated RCM who were admitted to the Department of Pediatrics, Peking University First Hospital, from January 2008 to October 2023, including clinical manifestations, laboratory examinations, echocardiographic findings, genetic testing results, as well as treatment and follow-up outcomes was retrospectively analyzed. Results: Among the 5 patients, there were 4 females and 1 male, with the age of onset ranging from 3 to 5 years. Three patients presented with heart failure symptoms as the initial manifestation, 1 patient with recurrent syncope, and 1 patient was diagnosed asymptomatically via family screening. At initial presentation, 4 patients were graded as class Ⅱ and 1 patient as class Ⅰ according to the modified Ross classification for pediatric heart failure. Three patients had concomitant myopathy, manifesting as decreased muscle strength, spinal deformity and other abnormalities. All 5 patients had electrocardiographic manifestations of conduction block to varying degrees, and 1 patient developed atrial flutter during follow-up. Echocardiography revealed an overlapping phenotype of RCM and hypertrophic cardiomyopathy in 2 patients. All genetic variants were located in the rod domain (ROD) of the FLNC gene. In terms of variant types, 4 patients were missense variants and 1 patient was deletion-insertion variant. The primary treatments included diuretics, β-blockers, and angiotensin-converting enzyme inhibitors. One patient underwent heart transplantation, 3 patients remained clinically stable, and 1 patient was lost to follow-up. Conclusions: FLNC-related RCM typically has an early age of onset, is frequently accompanied by myopathy, and may show conduction block on electrocardiography. Missense variants in the ROD are the predominant type of FLNC gene variant in this disease. Thus, early genetic screening and long-term multidisciplinary follow-up are warranted for affected patients.

Hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA) are major causes of myocardial thickening, yet they arise from distinct genetic, structural, and pathophysiological mechanisms. Differentiating these entities is clinically crucial, as management strategies and prognostic implications differ substantially. However, overlapping phenotypic features, particularly left ventricular hypertrophy, frequently complicate diagnosis. Recent advances in multimodality cardiac imaging have markedly improved the ability to distinguish HCM from CA through refined anatomical assessment and non-invasive tissue characterization. Echocardiography helps evaluate ventricular structure, diastolic function, and flow patterns. Asymmetric septal hypertrophy, dynamic left ventricular outflow tract (LVOT) obstruction, and systolic anterior motion (SAM) of the mitral valve are characteristic of HCM, while concentric wall thickening, biatrial enlargement, restrictive filling, and the "apical sparing" strain pattern point toward CA. Cardiac MRI adds further diagnostic value through tissue characterization. In HCM, late gadolinium enhancement (LGE) typically appears as patchy mid-wall or junctional fibrosis, whereas in CA it is diffuse, involving the subendocardium or the full wall thickness. Mapping parameters also help differentiate the two conditions: native T1 and ECV are mildly elevated in HCM but markedly increased in CA due to extensive extracellular amyloid deposition.

Glypican-4 (GPC-4), an endothelial cell surface protein, is released into the circulation in the context of ischemia, inflammation, neurohumoral activity, and shear stress. This study aimed to investigate the prognostic value of GPC-4 in chronic heart failure. GPC-4 concentrations were determined in two prospective cohorts: patients with chronic heart failure with reduced ejection fraction (HFrEF), and with transthyretin amyloid cardiomyopathy (ATTR-CM). Multivariable Cox regression analyses were adjusted for age, sex, estimated glomerular filtration rate, N-terminal B-type natriuretic peptide, and left ventricular ejection fraction. In HFrEF (n = 205, median age 66 years, 22% women), 58 patients (28%) died, 18 (9%) from cardiovascular cause, and 46 patients (22%) were hospitalized for worsening heart failure (WHF) during 4.2 years follow-up. In ATTR-CM (n = 121, median age 76 years, 12% women), 34 patients (28%) died, 12 (10%) from cardiovascular cause, and 32 patients (26%) had a WHF hospitalization during 2.2 years follow-up. Baseline GPC-4 (median [interquartile range]) levels were 1553 (1041, 1950) pg/ml in HFrEF, and 2071 (1579, 2893) pg/mL in ATTR-CM. In HFrEF, GPC-4 was independently associated with all-cause mortality (HR 1.69, 95%CI 1.22-2.32, p = 0.003) and cardiovascular mortality (HR 1.61, 95%CI 1.01-2.56, p = 0.045), but not with WHF hospitalizations. Conclusively, in ATTR-CM, GPC-4 independently predicted all-cause mortality (HR 1.96, 95%CI 1.12-3.44, p = 0.018), but not cardiovascular mortality and WHF hospitalizations. GPC-4 carries strong prognostic value for all-cause death in chronic heart failure across various etiologies, but not for heart-failure specific outcomes. Further studies are warranted to elucidate its value in cardiovascular disease. KEY MESSAGES : Glypican-4 rises with ischemia, inflammation, neurohumoral activity, and shear stress. Circulating glypican-4 predicts prognosis in chronic heart failure, regardless of cause. Glypican-4 predicted all-cause death in heart failure with reduced ejection fraction and restrictive cardiomyopathy, but not heart failure-specific outcomes.

Dilated cardiomyopathy (DCM) results from systolic dysfunction, while restrictive cardiomyopathy (RCM) is due to diastolic dysfunction. The diverse pathophysiology of primary DCM and RCM suggests distinct underlying genetic mechanisms. A well-established disease gene for DCM and RCM is cardiac troponin I3 (TNNI3), which causes dominant and recessively inherited forms. In children, bi-allelic truncating TNNI3 variants have typically been associated with DCM, and heterozygous missense TNNI3 variants are associated with RCM. We report a 2-year-old female with severe RCM that is genetically caused by a homozygous TNNI3 nonsense variant, c.406C>T (p.Arg136∗), which results in a more distal (C-terminal) truncation than most previously reported disease-associated nonsense variants. In myocardial biopsies of the patient, TNNI3 protein abundance was diminished, suggesting that residual TNNI3 function may underlie RCM, while TNNI3 absence causes DCM. The RCM in this patient was treatment refractory and resulted in a heart transplant at the age of 28 months. Overall, recessive TNNI3 protein truncation causes severe pediatric RCM, suggesting that the allelic status, type of genetic alteration, and length of TNNI3 protein truncation determine cardiomyopathy onset and subtype manifestation.