Search Results (190)

Variants in ELAC2, a gene encoding the mitochondrial RNase Z enzyme essential for mitochondrial tRNA processing, have been associated with severe pediatric-onset mitochondrial dysfunction, primarily presenting with developmental delay, hypertrophic cardiomyopathy (HCM), and lactic-acidosis. We hereby report the case of a 25-year-old young woman presenting with dilated cardiomyopathy (DCM) and peripheral sensorimotor polyneuropathy, harboring a homozygous variant in ELAC2. The same variant has been reported only once so far in a case of severe infantile-onset form of HCM and mitochondrial respiratory chain dysfunction, with in vitro data showing a moderate reduction in the RNase Z activity and supporting the current classification as C4 according to the American College of Medical Genetics (ACMG) criteria (PS3, PM2, PM3, PP4). Our extensive clinical, imaging, histological, and genetic investigations support a causal link between the identified variant and the patient’s phenotype, despite the fact that the latter might be considered atypical according to the current state of knowledge. A detailed review of the existing literature on ELAC2-related disease is also provided, highlighting the molecular mechanisms underlying tRNA maturation, mitochondrial dysfunction, and the variable phenotypic expression. Our case further expands the clinical spectrum of ELAC2-related cardiomyopathies to include a relatively late onset in young adulthood and underscores the importance of comprehensive genetic testing in unexplained cardiomyopathies with multisystem involvement. Full article

Background/Objectives: Anatomical and functional damage of the mitral valve (MV) apparatus in patients with dilated cardiomyopathy (DCM) is secondary to left ventricular (LV) injury, leading to functional mitral regurgitation (FMR). Real-time four-dimensional echocardiography (RT 4DE) is a useful imaging technique in different pathologies, including DCM. Left atrial (LA) strain, as measured by left atrium quantification software, is an accurate technique for evaluating increased filling pressure. The MV has a complex three-dimensional morphology and motion. Four-dimensional echocardiography (4DE) has revolutionized clinical imaging of the mitral valve apparatus. This study aims (1) to characterize the mitral annulus (MA) parameters in patients with DCM and advanced-stage heart failure (HF) according to etiology and (2) to find correlations between left atrial function and MA remodeling in this group of patients, using 4DE quantification software. Methods: A total of 82 patients with DCM and an LV ejection fraction ≤ 40% were recruited. Conventional 2DE and RT 4DE were conducted in DCM patients with a compensated phase of HF before discharge. The measured parameters were left atrial reservoir strain (LASr), annular area (AA), annular perimeter (AP), anteroposterior diameter (A-Pd), posteromedial to anterolateral diameter (PM-ALd), commissural distance (CD), interregional distance (ITD), annular height (AH), nonplanar angle (NPA), tenting height (TH), tenting area (TA), and tenting volume (TV). Results: Measured parameters revealed more advanced damage of LA and MA parameters in ischemic compared to nonischemic etiology. Univariate analysis identified AA, AP, A-Pd, PM-ALd, CD, ITD, TH, TA, and TV (p < 0.0001) as determinants of LASr. Including these parameters in a stepwise multivariate logistic regression, PM-ALd (p = 0.03), TH (p = 0.043), and TV (p = 0.0001) were the best predictors of LAsr in these patients. Conclusions: The results of this study revealed the correlation between LA function depression and MA remodeling in patients with DCM. Full article

Cardiac magnetic resonance imaging (CMRI) has become an indispensable tool in evaluating arrhythmic risk and guiding therapeutic decisions in patients with non-ischemic cardiomyopathies (NICMs), including dilated (DCM), hypertrophic (HCM), and arrhythmogenic cardiomyopathies (ACM). Both European and American guidelines have given an additive and different value of late gadolinium enhancement (LGE) in specific morpho-functional (hypertrophic, dilated, and arrhythmogenic) phenotypes. In particular, LGE plays a different weight in relation to different cardiomyopathies. In dilated cardiomyopathy, LGE is able to predict arrhythmic risk in relationship to the presence and localization (septal and/or ring like LGE). On the contrary, in HCM, LGE is related to increased risk of cardiac death according to the extent (LGE >15%), while in ACM, it has a greater role in the presence of fat infiltration associated with LGE. In this review, we aim to identify predictors of sudden cardiac death related to myocardial structural features seen in CMRI in cardiomyopathies, going beyond the sole assessment of left ventricular function and ejection fraction. Full article

Background: This study aimed to develop a predictive model to assess risk factors and prognoses in pediatric patients with dilated cardiomyopathy (DCM). Methods: A total of 233 pediatric patients with DCM who were hospitalized between January 2019 and June 2024 were enrolled. The children were followed up and categorized into two groups: the death/heart transplantation (D/HT) group and the non-D/HT group. Univariate and multivariate analyses identified risk factors. A nomogram model and a scoring system were developed. The performance of these models was evaluated using the H-L test, ROC analysis, and internal validation. Results: The results demonstrated that the age of onset, cardiac functional classification III–IV, moderate-to-severe mitral regurgitation, low voltage in limb leads on an ECG, and the need for vasoactive drugs are independent predictors of D/HT risk in children with DCM. A nomogram model was developed, achieving an AUC of 0.804 (95% CI: 0.734–0.874), a sensitivity of 80.3%, and a specificity of 66.7%. A scoring system was established: 1 point for age of onset, 10 points for cardiac functional classification III–IV, 2.5 points for moderate-to-severe mitral regurgitation, 4 points for low voltage in limb leads on an ECG, 3 points for the need for vasoactive drugs, or 0 points if none of these criteria were met. When the cumulative score was ≥ 13.25, the sensitivity and specificity increased to 68.9% and 73.9%, respectively. Conclusions: We developed both a nomogram and a scoring system model, which are capable of rapidly and accurately predicting the risk of D/HT in children with DCM. Full article

Background: Dilated Cardiomyopathy (DCM) is one of the leading causes of non-ischemic cardiomyopathy in the United States (US). The aim of our study is to analyze the general trends in DCM admissions between 2016 and 2021, and analyze social and healthcare disparities in terms of treatments and outcomes. Methods: National Inpatient Sample (NIS) data for the years 2016 to 2021 were used for the analysis. General population trends were analyzed. Normality of data distribution was tested using the Kolmogorov–Smirnov test and homogeneity was assessed using Levine’s test. One-way ANOVA was used after confirmation of normality of distribution to analyze social and healthcare disparities. Subgroup analysis was conducted, with the paired t-test for continuous variables and Fischer’s exact t-test for categorical variables to analyze statistical differences. Multivariate regression analysis was conducted to analyze the association of factors that were significant in the one-way ANOVA and paired t/chi square tests. A two-tailed p-value < 0.05 was used to determine statistical significance. Results: A total of 5262 admissions for DCM were observed between 2016 and 2021. A general declining trend was observed in the total number of DCM admissions, with a 33.51% decrease in total admissions in 2021 compared to 2016. All-cause in-hospital mortality remained stable across the years (between 3.5% and 4.5%). A total of 15.3% of admissions had CRT/ICD devices in place. A total of 425 patients (8.07%) for DCM underwent HT, and 214 admissions for DCM (4.06%) underwent LVAD placements between 2016 and 2021 In terms of interventions for DCM, namely Cardiac Resynchronization Therapy (CRT), Left Ventricular Assist Devices (LVADs) and Heart Transplantations (HTs), significant variance was observed in the mean age of the admissions with admissions over the mean age of 55 had lower number of interventions. Significant variance in terms of sex was observed for DCM admissions receiving HT, with lower rates observed for females. In terms of quarterly income, patients belonging to the lowest fourth quartile had higher rates of LVAD and HT compared to general DCM admissions. In the multivariate regression analysis, age at admission had significant association with lower chances of receiving LVADs and HT among DCM admissions, and significant association with higher chances of all-cause mortality during the hospital stay. Conclusions: A general declining trend in the total number of DCM admissions was observed between 2016 and 2021. Significant gender disparities were seen with lower rates of females with DCM receiving LVADs and HT. DCM admissions with mean age of 55 and above were found to have significantly lower rates of receiving LVADs and HT, and higher chances of all-cause mortality during the admission. Full article

Here, we present a unique case of the combination of two rare hereditary diseases—a familial form of dilated cardiomyopathy (DCM) and arterial calcification (AC)—in a 10-month-old boy. DCM was caused by a novel pathogenic nucleotide variant (NV) c.542G>T in the MYH7 gene, and AC was caused by biallelic nucleotide variants c.3421C>T and c.4015C>T in the ABCC6 gene. NVs were identified by the next-generation sequencing (NGS) of a broad panel of 404 genes potentially involved in cardiovascular disorders and subsequently validated by Sanger sequencing in the proband and his parents. Cardiologic examinations confirmed the familial nature of cardiomyopathy and the pathogenicity of variant c.542G>T in MYH7 gene. This case highlights the clinical utility of NGS in identifying complex co-existing hereditary conditions and emphasizes the need for the comprehensive genetic testing of patients with atypical clinical presentations. Full article

Background: The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated improved clinical outcomes in patients with advanced heart failure (HF). However, the influence of underlying HF etiology—ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM)—on post-implantation outcomes remains insufficiently characterized. Objectives: This paper aims to evaluate early postoperative outcomes following HM3 LVAD implantation in patients with ICM versus DCM and to identify the preoperative hemodynamic and clinical predictors of early mortality and hemodynamic instability. Methods: We conducted a retrospective single-center cohort study of 30 patients who underwent HM3 LVAD implantation between 2017 and 2024. Patients were stratified by HF etiology (ICM, n = 17; DCM, n = 13), and preoperative clinical, echocardiographic, and right heart catheterization data were analyzed. The primary endpoint was 30-day postoperative survival. Secondary endpoints included postoperative hemodynamic stability and the need for vasopressor support. Results: Non-survivors (n = 13) demonstrated elevated central venous pressure (>16.5 mmHg), mean right ventricular pressure (>31.5 mmHg), and pulmonary vascular resistance (>7.5 Wood units), in addition to higher preoperative creatinine levels and longer cardiopulmonary bypass times. Vasopressor requirement postoperatively was associated with elevated pre-implant systolic pulmonary artery pressure. Conclusions: Preoperative right-sided pressures and renal dysfunction are strong predictors of early mortality following HM3 LVAD implantation. Patients with ICM exhibit greater early left ventricular recovery compared to those with DCM. These findings underscore the importance of comprehensive and personalized preoperative risk stratification—particularly in patients with DCM and pulmonary hypertension—to optimize postoperative outcomes and guide patient selection for durable LVAD support. Full article

Background and Objectives: Nonischemic cardiomyopathies comprise a wide spectrum of heart muscle disorders characterized by different morphological, functional, and tissue abnormalities. Cardiovascular magnetic resonance (CMR) represents the gold standard imaging modality for assessing cardiac morphology, systolic function, and tissue characterization, thereby aiding in early diagnosis, precise phenotyping, and tailored treatment. The aim of this review is to provide an up-to-date overview of CMR techniques for studying myocardial perfusion and their applications to nonischemic cardiomyopathy, not only to rule out an underlying ischemic aetiology but also to investigate the pathophysiological characteristics of microcirculatory dysfunction in these patients. Materials and Methods: We performed a structured review of the literature focusing on first-pass gadolinium perfusion sequences, stress protocols, and emerging pixel-wise perfusion mapping approaches. Studies were selected to illustrate the methods for image acquisition, post-processing, and quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), as well as to highlight associations with clinical endpoints. Results: First-pass CMR perfusion imaging reliably detects diffuse and regional microvascular dysfunction across cardiomyopathies. Semi-quantitative parameters (e.g., upslope, MPRI) and quantitative MBF mapping (mL/g/min) have demonstrated that impaired perfusion correlates with disease severity, extent of fibrosis, and adverse outcomes, including heart failure hospitalization, arrhythmias, and mortality. Novel automated pixel-wise mapping enhances reproducibility and diagnostic accuracy, distinguishing coronary microvascular dysfunction from balanced three-vessel disease. Microvascular dysfunction—present in approximately 50–60% of dilated cardiomyopathy (DCM), 40–80% of hypertrophic cardiomyopathy (HCM), and >95% of cardiac amyloidosis (CA) patients—has emerged as a key driver of adverse outcomes. Perfusion defects appear early, often preceding overt hypertrophy or fibrosis, and provide incremental prognostic value beyond conventional CMR metrics. Conclusions: CMR represents a powerful tool for detecting myocardial perfusion abnormalities in nonischemic cardiomyopathies, improving phenotyping, risk stratification, and personalized management. Further standardization of quantitative perfusion techniques will facilitate broader clinical adoption. Full article

Background/Objectives: The mitochondrial unfolded protein response (UPRmt) is one of the mitochondrial quality control mechanisms that is responsible for reparation and removal of damaged proteins in mitochondria. Methods: Here we investigated the role of the UPRmt in the myocardium of humans with and without heart failure and in the cell culture model. Results: The analysis of myocardial samples by ELISA from patients with ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), as well as healthy donors, revealed a significantly reduced expression of the UPRmt proteins HSP10, CLPP, LONP1, OMA1, and SPG7 in patients with DCM and ICM. Furthermore, patients with DCM and ICM exhibited elevated levels of myocardial reactive oxygen species (ROS, tested by 4-hydroxynonenal) compared to controls, and a positive correlation between ROS production and mt-HSP70, OMA1, and SPG7 protein expression. The correlation analysis indicated a negative correlation between cardiomyocyte hypertrophy and the expression of several UPRmt genes. The inhibition of four tested UPRmt effector proteins exacerbated the injury of cultured cells under oxidative stress. The patients with ICM, DCM, or both, who showed lower myocardial expression of HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L, underwent heart transplantation or implantation of a left ventricular assist device earlier in life compared to those with the higher protein expression. Conclusions: In conclusion, our findings indicate that the reduced expression of several UPRmt effector proteins is associated with accelerated heart failure in patients, which, together with other results, indicates that impaired UPRmt may contribute to the pathogenesis of heart failure in humans. Full article

Secondary dilated cardiomyopathy (DCM) refers to left ventricular dilation and impaired systolic function arising from identifiable extrinsic causes, such as ischemia, hypertension, toxins, infections, systemic diseases, or metabolic disorders. Unlike primary DCM, which is predominantly genetic, secondary DCM represents a diverse spectrum of pathophysiological mechanisms linked to external insults on myocardial structure and function. The increasing prevalence of conditions such as alcohol use disorder, chemotherapy-induced cardiotoxicity, and viral myocarditis underscores the need for heightened awareness and early recognition of secondary DCM. A comprehensive analysis of clinical trial data and observational studies involving secondary dilative cardiomyopathy was conducted, with a focus on mortality, symptom relief, and major adverse events. A systematic literature review was performed using databases, including PubMed, Embase, and ClinicalTrials.gov, following PRISMA guidelines for study selection. Data were extracted on patient demographics, etiology of dilation, trial design, outcomes, and follow-up duration. Advances in diagnostic modalities have refined the ability to identify underlying causes of secondary DCM. For example, high-sensitivity troponin and cardiac magnetic resonance imaging are pivotal in diagnosing myocarditis and differentiating it from ischemic cardiomyopathy. Novel insights into toxin-induced cardiomyopathies, such as those related to anthracyclines and immune checkpoint inhibitors, have highlighted pathways of mitochondrial dysfunction and oxidative stress. Treatment strategies emphasize the management of the causing condition alongside standard heart failure therapies, including RAAS inhibitors and beta-blockers. Emerging therapies, such as myocardial recovery protocols in peripartum cardiomyopathy and immune-modulating treatments in myocarditis, are promising in reversing myocardial dysfunction. Secondary DCM encompasses a heterogeneous group of disorders that require a precise etiological diagnosis for effective management. Timely identification and treatment of the underlying cause, combined with optimized heart failure therapies, can significantly improve outcomes. Future research focuses on developing targeted therapies and exploring the role of biomarkers and precision medicine in tailoring treatment strategies for secondary DCM. Full article

We investigated the prevalence, clinical characteristics, and prognostic role of dilated cardiomyopathy (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC) in patients with transfusion-dependent β-thalassemia (β-TDT). We retrospectively included 415 β-TDT patients who underwent cardiovascular magnetic resonance to quantify myocardial iron overload (MIO) and biventricular function parameters and to detect replacement myocardial fibrosis. Demographic and laboratory parameters were comparable among patients with no overt cardiomyopathy (NOCM; n = 294), DCM (n = 12), and NDLVC (n = 109), while cardiac size and systolic function were significantly different. Compared to NOCM patients, DCM and NDLVC patients had a higher prevalence of MIO and replacement myocardial fibrosis. During a mean follow-up of 57.03 ± 18.01 months, cardiac complications occurred in 32 (7.7%) patients: 15 heart failures, 15 supraventricular arrhythmias, and 2 pulmonary hypertensions. Compared to the NOCM group, both the NDLVC and the DCM groups were associated with a significantly increased risk of cardiac complications (hazard ratio = 4.26 and 8.81, respectively). In the multivariate analysis, the independent predictive factors were age, MIO, and the presence of DCM and NDLVC versus the NOCM phenotype. In β-TDT, the detection of NDLVC and DCM phenotypes may hold value in predicting cardiac outcomes. Full article

There is no established detecting tool for hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). This study aimed to develop a deep-learning-based model for identifying HCM and DCM using standard 12-lead electrocardiogram (ECG) images. We obtained a cohort of patients with HCM (171 ECG images) or DCM (364 ECG images), confirmed by cardiovascular magnetic resonance (CMR) examinations, who underwent both ECG and CMR within 30 days at our institution. Age- and sex-matched healthy controls (2314 ECG images) were selected from our Health Check Center. A total of 2849 ECG images were processed via a fine-tuned ResNet50 architecture, with stratified five-fold cross-validation for model training, validation, and testing. The proposed model demonstrated strong performance in distinguishing DCM, achieving an area under the receiver operating curve (AUROC) of 0.996 and an area under the precision–recall curve (AUPRC) of 0.940. For the detection of HCM, the model also achieved an AUROC of 0.980 and an AUPRC of 0.953, respectively. The model prospectively exhibited stability in temporal validation. Furthermore, representative images of the Gradient-weighted Class Activation Mapping (Grad-CAM) technique analysis showed the regions corresponding to the anterior and anteroseptal leads were the most important areas for the prediction of HCM or DCM. This temporally validated fine-tuned ResNet50 model shows promise to inexpensively detect individuals with HCM or DCM. Full article

Multifocal ectopic Purkinje-related premature contractions (MEPPC) syndrome is a recently recognized rare form of arrhythmia involving the entire His–Purkinje system and often coinciding with dilated cardiomyopathy (DCM). Certain variants in the SCN5A gene may be linked to MEPPC syndrome. We present a case of a 32-year-old Caucasian female who exhibited a high burden of premature ventricular contractions (PVCs) and non-sustained episodes of ventricular tachycardia (NSVT) with an alternating QRS pattern, and who was resistant to traditional medical therapy and radiofrequency catheter ablation (RFCA), necessitating implantation of a cardioverter-defibrillator (ICD). A positive family history (father’s death at the age of 40 years) and the rapid deterioration of left ventricular function parameters echocardiographically during recurrent arrhythmic episodes raised concern about a potentially complex disease scenario. Genetic testing revealed a heterozygous variant of the SCN5A gene, c.2440C>T, p.(Arg814Trp), confirming the diagnosis of MEPPC syndrome. Treatment with a combination of class I antiarrhythmic drugs, flecainide and mexiletine, concomitant with beta blockers, led to symptomatic improvement, a reduction of PVCs (from 66 491 (44%) to 858 (1%)), and the restoration of left ventricular function (LV EF from 44% to 53%). A lack of defined diagnostic criteria hampers timely diagnosis, leading to ineffective interventions and delayed initiation of treatment with antiarrhythmic drugs. MEPPC patients remain at significant risk for severe heart failure and sudden cardiac death. Our clinical case report underscores the importance of accurate and timely diagnosis, which allows effective treatment with a combination of antiarrhythmic drugs and mitigates the risk associated with MEPPC syndrome. Full article

Acute heart failure (AHF) is a complex clinical syndrome characterized by the rapid or gradual onset of symptoms and/or signs of heart failure (HF), leading to an unplanned hospital admission or an emergency department visit. AHF is the leading cause of hospitalization in patients over 65 years, thus significantly impacting public health care. However, its prognosis remains poor with high rates of mortality and rehospitalization. Many pre-existing cardiac conditions can lead to AHF, but it can also arise de novo due to acute events. Therefore, understanding AHF etiology could improve patient management and outcomes. Cardiomyopathies (CMPs) are a heterogeneous group of heart muscle diseases, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), non-dilated cardiomyopathy (NDLVC), and arrhythmogenic right ventricular cardiomyopathy (ARVC), that frequently present with HF. Patients with CMPs are under-represented in AHF studies compared to other etiologies, and therefore therapeutic responses and prognoses remain unknown. In DCM, AHF represents the most frequent cause of death despite treatment improvements. Additionally, DCM is the first indication for heart transplant (HT) among young and middle-aged adults. In HCM, the progression to AHF is rare and more frequent in patients with concomitant severe left ventricle (LV) obstruction and hypertrophy or severe LV systolic dysfunction. HF is the natural evolution of patients with RCM and HF is associated with poor outcomes irrespective of RCM etiology. Furthermore, while the occurrence of AHF is rare among patients with ARVC, this condition in NDLVC patients is currently unknown. In this manuscript, we assessed the available evidence on AHF in patients with CMPs. Data on clinical presentation, therapeutic management, and clinical outcomes according to specific CMPs are limited. Future HF studies assessing the clinical presentation, treatment, and prognosis of specific CMPs are warranted. Full article

Dilated cardiomyopathy (DCM) is a significant contributor to heart failure (HF) in the pediatric population despite its lower incidence compared to adults. Method: We present a case-control study that investigates serum levels of Vitamin D, measured as 25-hydroxyvitamin D (25-OHD), in children diagnosed with DCM and explores the relationship between Vitamin D levels and left ventricular (LV) dimensions and systolic function. Results: Thirty patients (mean age: 10.61 ± 6.54 years) with DCM were included, with a control group of thirty-one matched healthy children. We found a high prevalence of 25-OHD deficiency (67%) in the DCM group, which was statistically significant compared to the control group (p < 0.05). Notably, a significant negative correlation was observed between 25-OHD levels and both LV end-diastolic diameter (LVEDD; r = −0.43, p < 0.01) and end-systolic diameter (LVESD; r = −0.46, p < 0.01). However, no significant correlation was found between Vitamin D levels and LV ejection fraction or shortening fraction. Conclusion: These findings emphasise the importance of assessing Vitamin D status in pediatric DCM patients and may suggest that Vitamin D supplementation can be beneficial in managing this condition through its potential effects on cardiac remodelling and function. Further research is warranted to clarify the underlying mechanisms and therapeutic implications. Full article