Search Results (372)

Objectives: Sudden cardiac death (SCD) is a leading cause of mortality, accounting for approximately 50% of all cardiovascular deaths and 20% of all-natural deaths in Western countries. In individuals over 50 years of age, coronary artery disease (CAD) is responsible for more than 80% of cases, whereas in younger subjects SCD is more frequently associated with non-ischemic myocardial diseases, including hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy (ACM), dilated cardiomyopathy (DCM), and myocarditis. Additional causes in young adults include coronary artery anomalies and primary arrhythmic disorders related to channelopathies. This study evaluated the diagnostic performance of post-mortem cardiac magnetic resonance imaging (PM-CMR) in identifying morphological substrates underlying SCD in formalin-fixed explanted hearts, with particular attention to the concordance between PM-CMR findings and autopsy results in cases of sudden coronary death. Material and Methods: We retrospectively reviewed 110 PM-CMR examinations from the Regional Register of Sudden Cardiac Death of Friuli-Venezia Giulia, of which 101 were included in the final analysis. Results: PM-CMR detected pathological findings in 60 hearts (59%), including acute ischemic lesions in 39 cases and other conditions, such as hypertrophic cardiomyopathy, chronic fibrotic ischemic changes, and adipose metaplasia in 21 cases. A good agreement between PM-CMR and autopsy findings was observed (Cohen’s kappa = 0.8). Conclusions: Overall, PM-CMR proved effective in identifying relevant morphological and signal alterations, supporting conventional autopsy. Despite some limitations, particularly in hyperacute ischemic lesions, PM-CMR appears to play a promising role in the diagnostic work-up of SCD and in supporting family screening programs for primary prevention. Full article

Background/Objectives: Hypertrophic cardiomyopathy (HCM) in childhood is associated with a risk of adverse cardiovascular events despite preserved left ventricular (LV) ejection fraction (EF). The aim of this study was to evaluate echocardiographic parameters of longitudinal LV systolic function and determine their relationship with cardiac magnetic resonance (CMR) findings and major adverse cardiovascular events (MACE) in children and adolescents with HCM. Methods: This single-centre prospective observational study enrolled 31 children and adolescents with HCM and preserved LV EF. Echocardiographic assessment included mitral annular plane systolic excursion (MAPSE), tissue Doppler mitral annulus systolic velocity (s′), mitral annular displacement index (MADI), and LV global longitudinal strain (GLS). Investigated CMR parameters encompassed LV mass, maximal wall thickness, and late gadolinium enhancement (LGE). Associations between echocardiographic and CMR findings were analyzed, and the discriminative value of longitudinal function parameters for MACE was assessed. Results: Impaired longitudinal systolic function was frequently detected in our cohort. Lower MAPSE and s′ z-scores were present in 61.3% of patients, reduced MADI in 96.8%, and reduced LV GLS in all subjects. Patients with MACE showed significantly lower MADI (p < 0.001) and worse LV GLS (p = 0.003). An exploratory LV GLS cut-off value of −12.1% showed discrimination for MACE in this cohort, with 75% sensitivity and 95.7% specificity. Echocardiographic parameters significantly correlated with CMR markers of hypertrophy and fibrosis, particularly LV GLS, which demonstrated the strongest associations with LV mass and the presence and extent of LGE. Conclusions: Echocardiographic parameters of longitudinal LV systolic function could contribute to closer clinical surveillance in children and adolescents with HCM. LV GLS may identify subtle myocardial dysfunction and provide exploratory prognostic information; however, its role in risk stratification requires prospective validation in larger pediatric HCM cohorts. Full article

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disorder and a major cause of heart failure (HF) and sudden cardiac death. Although sarcomeric gene mutations initiate the disease, increasing evidence identifies oxidative stress, mitochondrial dysfunction, and maladaptive nutrient signaling as key drivers of disease progression. Enhanced reactive oxygen species (ROS) production in HCM promotes energetic impairment, calcium mishandling, fibrosis, and the activation of pro-hypertrophic pathways, while disrupting protein quality control and endothelial function. Despite recent therapeutic advances, effective disease-modifying strategies targeting these molecular mechanisms remain limited. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), originally developed for type 2 diabetes, have demonstrated robust cardioprotective effects in HF independent of glycemic control. Beyond their renal actions, SGLT2i modulate myocardial metabolism, reduce oxidative stress, improve mitochondrial function, restore sodium and calcium homeostasis, and attenuate inflammation and maladaptive mTOR activation. Emerging preclinical and translational data suggest that these pleiotropic mechanisms may counteract key pathophysiological processes underlying HCM. This review summarizes the molecular interplay between oxidative stress and hypertrophic remodeling in HCM and explores the rationale for SGLT2 inhibition as a potential disease-modifying therapeutic strategy. Full article

Feline hypertrophic cardiomyopathy (HCM) is the most common cardiac disease in cats, causing morbidity and mortality. Recently, a variant in the Alström syndrome protein 1 (ALMS1) gene has been reported to be associated with HCM in Sphynx cats. However, information is limited on the prevalence and clinical significance of the ALMS1 p.G2462R variant in Sphynx cats in Thailand. Therefore, the objectives of this study were to determine the prevalence of the ALMS1 p.G2462R variant in Sphynx cats in Thailand and to assess its association with the clinical and echocardiographic features of feline HCM. A sample of 47 Sphynx cats was used based on specific inclusion and exclusion criteria. Clinical data, including sex, age, and body weight, together with echocardiographic assessments of the HCM phenotype and blood samples for ALMS1 genotyping, were collected from each enrolled cat. The prevalence of the ALMS1 p.G2462R variant was 44.68%, comprising 6.38% homozygous and 38.30% heterozygous mutations. Genotype frequencies were consistent with the Hardy–Weinberg equilibrium. However, no significant association was identified between the ALMS1 p.G2462R variant and echocardiographic parameters related to the HCM phenotype. In conclusion, within this population, the ALMS1 p.G2462R variant did not appear to play a primary role in the pathogenesis of HCM in Sphynx cats. Full article

Hypertrophic Cardiomyopathy Phenotype (HCM-Ph) is the most common group of myocardial disorders in cats. It has been the subject of research worldwide with prevalence rates ranging from 8% to 34%. However, there is no data available on its occurrence in Morocco. This study aimed to investigate the prevalence of HCM-Ph in apparently healthy cats in Morocco, describe the epidemiological and echocardiographic findings of affected cats and to compare patients in ACVIM stages B1 and B2. A total of 81 apparently healthy cats underwent echocardiographic screening. The overall prevalence of HCM-Ph was 9.88% (95% CI: 4.36–18.54%). The median age was four years (IQR 3.5–5.5) and a male overrepresentation (75%) was noted. Affected cats exhibited various echocardiographic patterns of left ventricular hypertrophy, normal left ventricular diameters, preserved fractional shortening and different degrees of left atrial enlargement. Cats in B2 stage were older and had more myocardial hypertrophy compared to cats in B1 stage, highlighting the potential role of wall thickness in clinical staging and risk assessment. Subclinical HCM-Ph is relatively common in apparently healthy cats in Morocco. Veterinarians should be aware of its clinical importance, as despite the fact that it presents no clinical signs, it can have fatal cardiovascular outcomes. Full article

Hypertrophic cardiomyopathy (HCM), with or without obstructive phenomena, remains underdiagnosed and undertreated. This condition often involves pathological changes in the mitral valve leaflets and apparatus, which can lead to relevant mitral regurgitation (MR). The mechanism of MR is mostly related to the systolic anterior motion (SAM) of the anterior mitral leaflet. The treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM) with persistent symptoms despite optimal pharmacological therapy includes septal myectomy or transcoronary ablation of septal hypertrophy (TASH). Percutaneous edge-to-edge repair of the mitral valve represents an innovative alternative therapy with promising results regarding clinical symptoms and echocardiographic findings. In this article, we provide a concise, critical overview of the current evidence on this technique in HOCM and delineate future perspectives and unresolved issues. Full article

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease, with macrophages playing a critical role in its pathological remodeling. Our study aims to investigate the molecular basis of HCM by analyzing macrophage-related gene expression at the single-cell level. Utilizing published scRNA-seq datasets (GSE181764 and GSE161921), we identified macrophages as the key cell cluster most associated with HCM. Integration with bulk RNA-seq data (GSE249925) and differential expression analysis revealed three hub genes: ASPN (asporin), F13A1 (Coagulation Factor XIII A Chain), and SORBS2 (Sorbin and SH3 domain-containing protein 2). Immune infiltration analysis showed significant decreases in multiple immune cell subsets in HCM patients, including neutrophil and macrophages. Intercellular communication analysis revealed an approximately 50% reduction in total interactions in HCM, accompanied by markedly weakened macrophage signaling reception and loss of regulatory pathways. Single-cell validation confirmed that F13A1 expression was predominantly restricted to macrophage clusters and significantly downregulated in HCM macrophages, demonstrating strong macrophage specificity and diagnostic potential. Furthermore, a LASSO-based diagnostic model incorporating three genes (IGFBP4, FOS, CTSC) exhibited high predictive performance, with validated accuracy in both training and external validation sets. Collectively, our findings shed light on the mechanisms underlying macrophage dysfunction in HCM and offer novel insights into the cellular and molecular dynamics. Full article

Background: Myocardial fibrosis is an important pathological feature of hypertrophic cardiomyopathy (HCM) and is associated with ventricular arrhythmias, disease progression, and adverse clinical outcomes. Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) is the reference non-invasive technique for myocardial fibrosis assessment; however, its availability may be limited. Global longitudinal strain (GLS) derived from transthoracic echocardiography (TTE) has emerged as a sensitive marker of myocardial dysfunction and may provide complementary information regarding myocardial involvement. Aim: The aim of our study was to evaluate the diagnostic value of transthoracic echocardiography (TTE) with 2D global longitudinal strain (GLS) to detect the degree of myocardial fibrosis (LGE) in patients with LV hypertrophy (LVH). Methods: A total of 95 consecutive patients referred for cardiovascular magnetic resonance (CMR) because of suspected hypertrophic cardiomyopathy or left ventricular hypertrophy were screened for eligibility. After applying exclusion criteria and excluding patients with alternative diagnoses or inadequate image quality, 83 patients were included in the final analysis. All the participants underwent both CMR and transthoracic echocardiography with GLS assessment. Results: The final study population included 83 patients (57.5 ± 13 years; 66% males). CMR confirmed HCM in 58 (70%) patients, including 23 with left ventricular outflow tract obstruction (LVOTO). The remaining patients demonstrated varying degrees of left ventricular hypertrophy that did not fulfill established diagnostic criteria for hypertrophic cardiomyopathy. Cardiovascular magnetic resonance studies (58 cases; 69%) showed a non-ischemic LGE in LV (23% of segments with LGE). GLS in patients with LGE was significantly lower than those without LGE (−13.9 ± 3.6 vs. −15.9 ± 2.7%, p = 0.01). The mean GLS was −14.52 ± 3.5% and showed a moderate positive correlation with the extent of myocardial fibrosis (LGE%LV; r = 0.45, p < 0.01). This relationship remained significant in multivariable regression analysis (standardized coefficient = 0.683; p < 0.05). Moreover, the transthoracic echocardiography GLS showed a significant association for LV LGE (−14.3%; AUC 0.658; p = 0.01, sensitivity 39%, specificity 90%) with a better diagnostic performance for LGE in more than four LV segments (−12.1%; AUC 0.867; p < 0.001, sensitivity 72%, specificity 87%). Conclusions: GLS was independently associated with myocardial fibrotic burden assessed by CMR. Although it cannot replace CMR for tissue characterization, GLS may provide adjunctive information and may help identify patients with greater fibrotic burden. Prospective studies are needed to validate its clinical utility. Full article

Background/Objectives: Guidelines for obstructive hypertrophic cardiomyopathy (HCM) recommend treatment with disopyramide as an add-on to beta-blockers or calcium-channel blockers when symptoms persist. Data pertaining to effective disopyramide use in practice beyond single-center experience are very limited. This study aimed to quantify disopyramide use in patients with obstructive HCM in England, France and Germany, before the availability of cardiac myosin inhibitors. Methods: This retrospective study used nationally representative databases from England (Clinical Practice Research Datalink and Hospital Episode Statistics, 2010–2019), France (National Healthcare Data System, 2012–2019) and Germany (German statutory health insurance, 2011–2019). Adults (18+) with obstructive HCM were included, based on diagnostic codes for obstructive HCM or any HCM with septal reduction therapy. Disopyramide usage was defined as ≥1 prescription for a patient in a calendar year. Results: Overall, 3730, 6823 and 1141 patients diagnosed with obstructive HCM were identified in the English, French and German databases, respectively. In England, disopyramide use ranged from 4.7% to 5.6% per year with use generally stable over time. The equivalent usage for France was 1.7% to 2.6% per year. As expected, no recorded reimbursed use was reported in Germany during the study period. Conclusions: Disopyramide use is very low in patients with obstructive HCM, possibly due to treatment-related issues, availability or lack of reimbursement. These barriers may drive the uptake of alternative guideline recommended therapies for obstructive HCM treatment. Full article

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous, involving more than 11 genes. Since HCM genetic testing was covered by Japan’s national health insurance in 2022, variant detection and the need for family-based intervention have increased, although funding is limited to symptomatic patients only. In this study, we evaluated institutional genetic testing outcomes, factors associated with pathogenic variants, and follow-up of at-risk relatives. Methods: We retrospectively analyzed individuals with confirmed or suspected HCM who underwent genetic testing between October 2022 and June 2025. Data regarding molecular results, family history of cardiomyopathy or sudden cardiac death in first-, second-, and third-degree relatives, and cascade screening were collected. Statistical analysis was performed using R version 2025.09.2 + 418. Results: Among 33 probands (median age, 54 years; 51% male), 13 individuals (39%) had pathogenic or likely pathogenic variants (PV or LPV), while six (18%) harbored variants of uncertain significance (VUS), and 14 (43%) yielded negative results. The PV or LPV cohort was significantly younger at the time of testing (median, 34 vs. 59 years; p = 0.008) and had a family history of PV or LPV (77% vs. 20%; p = 0.005). Only three relatives from two PV or LPV probands underwent cascade genetic screening; two tested positive and initiated targeted cardiac surveillance. Conclusions: Despite achieving actionable results, the restricted uptake of cascade screening highlights the need for improved communication and systemic support to facilitate family-based testing and precision medicine. Full article

Hypertrophic Cardiomyopathy (HCM) is one of the most common inherited cardiomyopathies and remains an important cause of ventricular arrhythmias and sudden cardiac death (SCD), particularly in younger individuals. Although the annual incidence of arrhythmic death is relatively low in contemporary cohorts, identifying those patients who may benefit from primary prevention with an implantable cardioverter-defibrillator (ICD) remains a major clinical challenge. Current risk stratification strategies rely on two principal paradigms. The European approach is centered on the HCM Risk-SCD score, whereas the American approach is mainly based on major clinical risk markers. Both strategies have important strengths and limitations, reflecting the persistent difficulty of accurately predicting arrhythmic events in such a heterogeneous disease. The HCM Risk-SCD score has demonstrated robust external validation and high specificity for identifying patients at higher risk, but it may fail to recognize some vulnerable individuals who remain below conventional treatment thresholds. For this reason, several additional risk modifiers have gained increasing relevance in contemporary practice. Among them, extensive late gadolinium enhancement, left ventricular systolic dysfunction, apical aneurysm, and clinically meaningful genetic findings may provide important incremental prognostic information beyond traditional models. Emerging disease-modifying therapies, in particular Mavacamten, may also influence future risk assessment. However, whether these improvements translate into a true reduction in SCD risk remains uncertain. Importantly, the decision to implant an ICD should not depend on numerical risk alone. It should arise from a process of shared decision-making integrating estimated risk, treatment burden, competing comorbidities, age, lifestyle, and patient values. In this context, the concept of an individualized threshold of “acceptable risk” becomes central. In conclusion, prevention of SCD in HCM is moving beyond conventional scores toward a personalized and dynamic framework in which predictive tools, advanced phenotyping, evolving therapies, clinical expertise, and patient preferences are combined to guide individualized care. Full article

Noonan syndrome (NS) is a paradigmatic rare, genetically heterogeneous, multisystem disorder belonging to the RASopathies family, caused by dysregulated RAS/MAPK signaling. It is characterized by distinctive craniofacial features, postnatal short stature, and a high prevalence of congenital cardiac defects, with pulmonary valve stenosis (PS) and hypertrophic cardiomyopathy (HCM) being the hallmark lesions. First described by Dr. Jacqueline Noonan in 1968, the molecular era began with the discovery of PTPN11 mutations in 2001, revolutionizing diagnosis, risk stratification, and understanding of pathogenesis. Strong genotype–phenotype correlations now guide prognosis and personalized management; for instance, RAF1 and RIT1 variants confer a high risk of severe, early-onset HCM, while PTPN11 is strongly linked to dysplastic PS. Cardiac involvement remains the central determinant of long-term outcomes, requiring continuous surveillance from the prenatal period through adulthood. Management is inherently multidisciplinary, addressing endocrine, hematologic, neurodevelopmental, and oncologic aspects. Recent consensus statements emphasize the critical need for structured transition from pediatric to adult care. Novelty arises from the potential of MEK inhibitors as targeted therapies for severe HCM and lymphatic complications. This review provides a comprehensive update on NS, integrating foundational clinical knowledge with contemporary molecular insights, advanced cardiologic management, and emerging frontiers in therapy and diagnostics, underscoring the necessity of a proactive, lifelong, and personalized care approach. Full article

Background/Objectives: Differentiating clinically suspected cardiac amyloidosis from hypertrophic cardiomyopathy (HCM) remains a significant clinical challenge, especially when contrast-enhanced imaging is contraindicated. This study evaluated the potential diagnostic utility of non-contrast cardiac MRI parameters, specifically native T1 and T2 mapping, as supportive indicators in this differential diagnosis. Methods: This retrospective single-center study included 20 patients with clinically suspected amyloidosis (based on combined clinical and echocardiographic assessment), 20 patients with HCM, and 20 healthy controls. Cine imaging and native T1/T2 mapping were analyzed. Myocardial, blood-pool, and liver T1/T2 values, along with morphological parameters, were recorded. N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin levels, when available, were documented retrospectively for descriptive purposes. Receiver operating characteristic (ROC) analyses were performed to assess the discriminatory performance of imaging parameters. Results: Patients in the suspected amyloidosis group demonstrated significantly higher myocardial, blood-pool, and liver T1 values, as well as higher myocardial T2 values, compared with both the HCM and control groups (p < 0.001). Myocardial T1 showed strong discriminatory performance for differentiating suspected amyloidosis from controls (cut-off 1061 ms, AUC = 0.975). In distinguishing suspected amyloidosis from HCM, blood-pool T1 (AUC = 0.900) and myocardial T1 (AUC = 0.938) provided the highest diagnostic performance. Additionally, elevated NT-proBNP (>1000 pg/mL in 93% of tested cases) and troponin levels were observed in the suspected amyloidosis group, consistent with increased myocardial stress. Conclusions: Native T1 and T2 mapping may offer valuable supportive information in differentiating clinically suspected amyloidosis from HCM on non-contrast MRI. Myocardial and blood-pool T1 values appear to provide complementary tissue characterization, which may be particularly useful when gadolinium administration or invasive procedures are not feasible. These findings suggest a role for non-contrast mapping in the diagnostic workup but require further validation in larger, biopsy-confirmed multicenter cohorts. Full article

Background: Genetic testing in hypertrophic cardiomyopathy (HCM) yields variable positivity rates. Identifying clinical predictors of positive genetic tests could improve pre-test counseling and refine expectations about diagnostic yield. Methods: We analyzed consecutive genotyped HCM probands from a contemporary multicenter cohort across four Italian tertiary centers. Genotype positivity was defined as the presence of ≥1 pathogenic or likely pathogenic variant (ACMG classes 4–5). Multivariable logistic regression identified predictors of genotype positivity. Sensitivity analyses assessed the incremental value of left atrial volume index (LAVI) ≥ 34 mL/m² and the mode of first clinical presentation. Results: Among 274 genotyped probands (median age at diagnosis 54 years; 62% male), 86 (31%) were genotype-positive (38% MYBPC3, 29% MYH7). Age at diagnosis <40 years (OR 2.38, 95%CI 1.26–4.51, p = 0.008), family history of sudden cardiac death/major ventricular arrhythmias (OR 2.34, 95%CI 1.16–4.84, p = 0.019) and family history of non-ischemic cardiomyopathy (OR 1.92, 95%CI 1.04–3.54, p = 0.038), were independently associated with genotype positivity whereas arterial hypertension was inversely associated (OR 0.42, 95%CI 0.23–0.77). Maximal left ventricular wall thickness > 20 mm and gender were not predictive of genotype positivity. Inclusion of LAVI modestly improved the model performance (AUC 0.769, p = 0.016, ΔAUC +0.024; DeLong p = 0.016) but without leading to meaningful patient reclassification. Conclusions: Genotype positivity in HCM links to earlier onset and family history; traditional severity markers and initial presentation may not independently suggest genetic causality. These findings may help shape a personalized approach to genetic counseling in HCM. Full article

The management of obstructive hypertrophic cardiomyopathy (HCM) has been transformed by the advent of cardiac myosin inhibitors (CMIs), such as mavacamten and aficamten. Unlike traditional pharmacotherapy, which primarily addresses symptoms, CMIs target the underlying mechanism of sarcomeric hypercontractility, offering significant reductions in left ventricular outflow tract (LVOT) gradients and improved functional capacity. This review evaluates the evolving role of CMIs in refining surgical candidate selection and postoperative care. Clinically, CMIs function as an in vivo “biological test” to distinguish between dynamic, functional obstruction—often manageable with medication—and fixed anatomical obstruction driven by complex septal or mitral substrates. While clinical trials demonstrate that CMIs can delay or prevent the need for SRT in a significant proportion of patients, surgery remains the definitive solution for those with dominant structural anomalies or drug intolerance. Consequently, the therapeutic paradigm is shifting from a binary “drugs or surgery” approach to a synergistic model. In this framework, CMIs optimize the identification of patients truly requiring structural myectomy while serving as a valuable adjunct for managing residual hypercontractility, ultimately facilitating a personalized, multidisciplinary approach to HCM treatment. Full article