Search Results (787)

Peripartum cardiomyopathy (PPCM) is a distinct condition that presents as heart failure (HF) in a woman who was previously healthy and has no prior cardiovascular issues. It results from idiopathic left ventricular (LV) dysfunction, characterized by a reduced LV ejection fraction below 45%. PPCM is a life-threatening condition with a high mortality rate (MR) that demands urgent treatment. Methods: This narrative review aims to define PPCM and its pathophysiology and conduct a scoping review of the latest data on the management of patients with peripartum cardiomyopathy during pregnancy and the postpartum period. Results: Currently, treatment follows standard HF protocols for reduced ejection fraction, with the possible addition of bromocriptine, and during pregnancy, medications that do not harm the fetus. Conclusions: Early, aggressive therapy is essential for a better prognosis, but managing PPCM can be challenging. Treatment of PPCM patients should be led by a team of highly qualified specialists, known as the Obstetric and Cardiac Care Team, comprising an obstetrician-perinatologist, an anesthesiologist, a cardiologist, and a cardiac intensive care specialist. Baseline left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) are the main prognostic factors. LVEF less than 30%, significant LV dilatation, LVEDD ≥ 6.0 cm, and right ventricular involvement are factors indicative of a poor prognosis. While pregnancy after PPCM is possible, it should be discouraged due to the significant risk of complications and even death. The most common causes of death in patients with PPCM are thromboembolic complications, severe HF, serious ventricular arrhythmias, cardiogenic shock, and sudden cardiac arrest. Full article

Background/Objectives: Infantile cardiomyopathy is a rare but often life-threatening condition in which monogenic causes are particularly relevant, especially when cardiac disease is preceded by hypotonia or multisystem involvement. Among sarcomeric genes, MYL2, encoding the ventricular regulatory myosin light chain, plays a critical role in myocardial contractility. However, biallelic MYL2-associated disease remains exceptionally rare, and its clinical spectrum is not fully defined. This study aims to describe a novel case and further delineate the phenotype of recessive MYL2-related cardiomyopathy. Methods: We report a male infant with congenital hypotonia and delayed motor development who underwent extensive metabolic, neuromuscular, and neuroimaging evaluation. Trio-based whole-exome sequencing was performed to identify a potential genetic etiology, followed by variant interpretation using standard bioinformatic and ACMG/AMP criteria. Results: The patient developed acute decompensated heart failure at approximately 10 months of age, with severe left ventricular systolic dysfunction and multiorgan failure, and died at 12 months despite maximal intensive care support. Whole-exome sequencing identified a homozygous MYL2 c.413T>A (p.Met138Lys) missense variant. The variant is absent or extremely rare in population databases, affects a highly conserved residue, is predicted to be deleterious by multiple in silico tools, and is compatible with autosomal recessive inheritance, with both parents confirmed as heterozygous carriers. In the context of a phenotype consistent with recessive MYL2-associated disease, these findings support a likely pathogenic interpretation. Conclusions: This case expands the allelic and phenotypic spectrum of recessive MYL2-associated cardiomyopathy and highlights the value of early genomic testing in infants with unexplained hypotonia and rapidly progressive cardiac dysfunction. Molecular diagnosis may aid in prognosis, clinical decision-making, and genetic counseling. Full article

Background and Clinical Significance: Patients with a left ventricular assist device (LVAD) are at risk of ventricular arrhythmias, which are generally hemodynamically tolerated if they occur. In such cases, patients may experience painful implantable cardioverter-defibrillator (ICD) shocks. Case Presentation: A 71-year-old patient with a history of dilated cardiomyopathy caused by a phospholamban (PLN) gain-of-function mutation, with a primary prevention ICD and an LVAD, presented with multiple ICD shocks which she experienced as painful and traumatic. She was found to have ongoing ventricular fibrillation with apparent hemodynamic stability. Conversion to sinus rhythm was achieved through intravenous administration of antiarrhythmic drugs followed by external defibrillation using stacked shocks. Due to the traumatic nature of the shocks, the shock function of the ICD was turned off. Nearly two months later, the patient presented for a second time and was again found to have ventricular fibrillation which had been present for at least six weeks. Conversion to sinus rhythm was unsuccessful and the patient was discharged to her home with an advanced care plan and her LVAD was deactivated. The patient died two months later. Conclusions: Patients with an LVAD can remain hemodynamically stable for prolonged periods of time during ventricular arrhythmias. ICD shocks are therefore mostly experienced as painful and even traumatic. Therefore, the routine use of ICD shock therapy in patients with an LVAD should be reconsidered. Adjustment of ICD programming to higher rates and longer detection may be warranted. Further investigation is warranted regarding a switch to devices with an alarm function rather than therapies for tachyarrhythmias. Full article

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by fibrofatty replacement of cardiomyocytes. The inflammatory episodes of ACM, known as the “hot phase”, can mimic acute myocarditis. It was seldom observed in a DES-associated ACM as a “hot-phase” presentation. Case Presentation: The proband, a 13-year-old female, initially presented with a series of clinical manifestations of fulminant myocarditis. Although recommendation-guided anti-immunotherapy had been provided, this patient still developed into an aggressive cardiomyopathy with biventricular dilation and severe systolic heart failure. Additionally, cardiac magnetic resonance demonstrated circumferential late gadolinium enhancement in left ventricular myocardium with diffuse fibrosis. Whole-exon sequencing identified a de novo missense variant, as c.335T>A (p.L112Q) of the DES gene, resulting in protein dysfunction. And a diagnosis of ACM due to a DES variant had been identified. Finally, this patient received heart transplantation, and biventricular fibrofatty infiltration was confirmed by pathological analysis. Conclusions: This case presented a de novo genetic variant that can induce severe and aggressive heart failure. This finding emphasizes the importance of comprehensive genetic analysis in patients suspected of having fulminant myocarditis, which would greatly benefit the precise clinical management and outcomes. Full article

Background: In end-stage liver disease (ESLD), cardiovascular changes are frequent and relate to the presence of hyperdynamic circulation. In 2019, diagnostic criteria for cirrhotic cardiomyopathy (CCM) were updated to include tissue Doppler and speckle tracking imaging in defining left ventricle (LV) systolic and diastolic dysfunction. Evaluation of diastolic function remains challenging, with frequent indeterminate cases and emerging evidence of worse prognosis. The aim of the present study was to evaluate the prevalence of LV systolic and diastolic dysfunction in cirrhosis, in correlation with liver disease severity and potential prognostic implications. Methods: We performed an observational, retrospective, non-randomized, single-center study that included 99 cirrhotic patients evaluated for liver transplant (LT) in a tertiary center. Liver disease severity and complications were analyzed with survival and echocardiography data to determine potential correlations with prognosis. For statistical analysis, IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA) was utilized. A two-sided p-value < 0.05 was considered statistically significant. Results: Left atrial (LA) volume index (r = 0.230, p = 0.022), LA reservoir strain (r = 0.291, p = 0.003), and LA contraction strain absolute value (r = 0.223, p = 0.027) positively correlated with the severity of liver disease expressed by MELD Na score. LA dilation (≥34 mL/m²) was the most common echocardiographic finding. It was present in 69.7% of patients, with one third having severe LA dilation (>45 mL/m²), which was associated with worse survival (log rank p = 0.019). LA contraction strain with an absolute value higher than 16% was also associated with worse survival (log rank p = 0.024). In multivariable Cox analysis, only MELD-Na and LA volume index remained independently associated with mortality. Diastolic dysfunction appeared more prevalent among the non-surviving patients irrespective of the diagnostic criteria used (p = 0.023 for American Society of Echocardiography 2016 criteria; p = 0.032 for CCM 2019 criteria). On binomial logistic regression, the presence of significant diastolic dysfunction (>grade 1) was associated with an increased probability of composite end-point of death or LT in the presence of liver disease severity confounders. The use of the LA stiffness index in discerning diastolic function in patients with standard inconclusive evaluation may warrant further investigation. Conclusions: Echocardiographic alterations, particularly LA enlargement, are associated with liver disease severity and clinical outcomes in ESLD. These findings are hypothesis-generating and suggest a potential role for echocardiography in risk stratification, warranting validation in larger prospective studies. Full article

Background/Objectives: The purpose of this study was to investigate the association between cardiovascular adverse drug events (ADEs) and the use of COVID-19 medicines. Methods: The analyses were conducted by leveraging pharmacovigilance data from the Food and Drug Authority (FDA) Adverse Event Reporting System (FAERS) and TriNetX electronic health records (EHRs). Transcriptomic data from human embryonic stem cell-derived cardiomyocytes (hESC-CMs) exposed to remdesivir were analyzed to provide supportive biological context for the observed cardiovascular safety signals. Results: Comparative analysis of three approved COVID-19 therapies revealed that COVID-19 patients treated with remdesivir had a higher risk of cardiovascular events than those treated with Paxlovid or REGEN-COV. FAERS analysis further indicated that bradycardia, hypotension, and cardiac arrest were the most frequently reported cardiovascular events associated with remdesivir, which was validated by propensity score-matched EHR data. These findings suggest an association between remdesivir exposure and increased cardiovascular ADEs relative to other COVID-19 therapies. Sex-stratified analysis using FAERS and EHR did not show strong sex-dependent patterns for remdesivir-associated cardiovascular ADEs. Age-stratified analyses of EHR data showed age-associated variation across the three cardiovascular ADEs. Bradycardia displayed a non-uniform pattern with higher prevalence in the youngest and oldest age groups, hypotension showed an overall age-associated increase, and cardiac arrest showed only a weak age-associated effect. Pathway enrichment analysis on transcriptomic data revealed that the “cGMP-PKG signaling pathway”, “dilated cardiomyopathy”, and “calcium signaling pathway” were enriched among genes up-regulated by remdesivir exposure. Conclusions: In summary, our integrated analysis of pharmacovigilance, EHR, and transcriptomic data provides convergent evidence for associations between remdesivir and cardiovascular ADEs and offers biological context into these associations. Full article

Background: Sudden cardiac death (SCD) is a major challenge in dilated (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC). Current management strategies, based on left ventricular ejection fraction (LVEF), the presence or extent of myocardial scar, and selected high-risk genetic variants, are insufficient to accurately identify patients at risk. Mechanical dispersion (MD), derived from speckle-tracking echocardiography, is a potential marker of arrhythmic risk that reflects variability in regional myocardial contraction timing. Aim: The purpose of this narrative review is to synthesize current evidence on the predictive role of MD for ventricular arrhythmias (VA) and SCD in DCM and NDLVC, with particular emphasis on its relationship to myocardial fibrosis (MF) and established echocardiographic markers. Results: Across prospective and retrospective cohorts of DCM patients, increased MD has consistently identified individuals at higher arrhythmic risk, often independently of LVEF and global longitudinal strain (GLS). Reported threshold values for risk prediction range from 50 ms to 90 ms, with hazard ratios confirming incremental prognostic accuracy. The relationship between MD and MF assessed by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) remains uncertain: some patients experience VA in the absence of LGE, while others display elevated MD despite no detectable focal MF, suggesting that additional mechanisms contribute to the arrhythmogenic substrate in DCM and NDLVC. Conclusions: MD may enhance SCD risk stratification in DCM and NDLVC by reflecting components of the arrhythmic substrate that are not detected by conventional markers. Full article

Background/Objectives: To establish a foundation for conserving and utilizing local frog germplasm resources in Zhejiang Province, for Quasipaa spinose, which has high commercial and nutritional value, a pan-genome analysis was performed. Methods: Herein, we characterized 405,263 SNPs for the giant spiny frog, Q. spinose, using the Illumina NovaSeq platform. Results: These loci were highly polymorphic in 59 individuals sampled from three different subpopulations, with 0.05 to 0.30 minor alleles per locus. The observed and expected heterozygosities were 0.2379 and 0.2683 (IBD), respectively. These polymorphic loci would be useful for assessing genetic diversity, population structure, gene flow, population assignment, and paternity in giant spiny frogs. Conclusions: Our investigation demonstrated that there are distinct genetic and evolutionary histories between Zhejiang and Jiangxi frogs. Phylogenetic inference effectively differentiated these three subpopulations based on their geographical origins, and the phylogenetic inference level of domesticated Zhejiang frogs was comparatively higher than that of the Jiangxi-derived population. Furthermore, by utilizing three selective signature methods, namely, Obs/Exp het, nucleotide diversity (Pi), and identical by state (IBS), across subpopulations, we concluded that these three breeds were from an identical population, and no genetic bottleneck occurred among these three lineages, in accordance with LD decay analysis. Finally, 2700 potential candidate genes were identified, including MAPK, calcium signaling pathway, Ras signaling pathway and regulation of actin cytoskeleton; we noted that the key genes associated with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy in humans beings and GnRH signaling pathway-related genes (i.e., CD80, IFNA, and KCNK1) were highly enriched, which could impact cardiac function through immune-associated genes. Full article

Cardiomyopathies comprise a heterogeneous group of myocardial disorders characterized by intrinsic structural and functional abnormalities that are not explained by secondary cardiovascular or systemic conditions. Although genetically determined cardiomyopathies have traditionally been interpreted within a Mendelian framework, this paradigm does not fully account for the marked variability in penetrance, expressivity, and clinical outcomes observed in affected individuals. Increasing evidence indicates that disease manifestation arises from a complex interplay between rare pathogenic variants, common genetic variation, epigenetic regulation, environmental factors, and stochastic molecular processes. This review focuses on hypertrophic and dilated cardiomyopathies, the most prevalent and extensively studied forms, and critically examines how epigenetic mechanisms, genetic modifiers, and molecular noise challenge classical pathophysiology concepts. We discuss how these factors contribute to phenotypic heterogeneity and influence disease severity, progression, and therapeutic response. Recognition of this multilayered genetic architecture has important clinical implications, supporting more refined risk stratification, improved genetic counseling, and the development of personalized and potentially variant-agnostic therapeutic strategies. Full article

Sudden cardiac death (SCD) is a major global health issue, defined as sudden natural death presumed to be of cardiac cause. While in the elderly SCD is commonly associated with coronary artery disease, in the younger population it is linked to inherited cardiomyopathies or channelopathies, even though SCD can remain unexplained even after a comprehensive autopsy in a substantial proportion of cases. In this context, genetic testing has gained importance, supported by the widespread availability of techniques such as next-generation and whole-exome/genome sequencing and their reduced costs. This state-of-the-art review summarizes the genetic bases of sudden cardiac death among cardiomyopathies, channelopathies and in sudden unexplained death presumed to be of arrhythmic cause. Among the structural causes, inherited cardiomyopathies such as hypertrophic, dilated, non-dilated left ventricular, arrhythmogenic right ventricular and restrictive ones represent major substrates for malignant ventricular arrhythmias mostly arising from variants in sarcomeric or desmosomal genes. Channelopathies (long or short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) are caused by variants in genes encoding cardiac ion channels and/or regulatory proteins, which equally predispose to high risk of life-threatening ventricular arrhythmias. In sudden arrhythmic death syndrome, with a structurally normal heart, post-mortem genetic testing (molecular autopsy) can uncover an underlying inherited condition. However, variants of uncertain significance are detected in more than half of the cases, underscoring the need for a multidisciplinary approach. Genetic testing also plays a key role in cascade screening of first-degree relatives. While monogenic variants drive risk in inherited cardiac disorders, emerging evidence suggests that polygenic contributions may modulate SCD susceptibility, highlighting future roles for polygenic risk scores in risk stratification. Full article

Pathological cardiac hypertrophy is a critical factor leading to cardiomyopathy and ultimately heart failure. While several signaling pathways controlling cardiac hypertrophy have been identified, the molecular mechanisms underlying their precise regulation remain incompletely understood. Strip1, a structural component of STRIPAK complexes, has been implicated in various cellular functions; however, its role in cardiomyocytes is uncharacterized. Here we identify Strip1 as a potent anti-hypertrophic factor, controlling cell size and the hypertrophic gene program in neonatal rat ventricular cardiomyocytes (NRVCMs). STRIP1 expression was found to be significantly reduced in human dilated and ischemic cardiomyopathies (DCM/ICM), as well as in murine stress model induced by transverse aortic constriction (TAC). In a knockdown model with morpholino-driven STRIP1 reduction in zebrafish in vivo, impaired cardiac function and heart failure–like features were observed. Interestingly, Strip1 localized to the nucleolus in NRVCMs, suggesting a putative nuclear/epigenetic role in cardiomyocytes. Furthermore, our data support association of Strip1 with cardiac STRIPAK complex, modulating kinase activities, including MST1/MST2 and MST4. Mechanistically, Strip1 appears to influence prohypertrophic signaling, including Hippo- and Calcineurin/NFAT-related pathways, which may contribute to pathological cardiac remodeling. Collectively, these findings establish Strip1 as an important modulator of cardiomyocyte hypertrophy and a potential therapeutic target for cardiomyopathy and heart failure. Full article

Background/Objectives: Right ventricular dysfunction is frequent in patients with dilated cardiomyopathy (DCM) and contributes significantly to prognosis. This study evaluated the prognostic value of echocardiography-determined surrogate parameters of right ventricular–arterial (RV–PA) coupling in patients with DCM. Methods: A total of 88 patients admitted between January 2019 to September 2023 were retrospectively and prospectively assessed and followed for a mean of 14 months. The primary endpoint was rehospitalization for decompensated heart failure (HF); the secondary endpoint was all-cause mortality. The parameters studied included TAPSE/PASP, RVFAC/PASP, RVFWLS/PASP, and RVEF/PASP. Results: In univariate analysis, all indices were associated with rehospitalization, but multivariate analysis retained only RVFWLS/PASP and RVEF/PASP as independent predictors. Optimal cut-offs were identified as 1.2 for RVEF/PASP (sensitivity 72%, specificity 80%) and 0.46 for RVFWLS/PASP (sensitivity 72%, specificity 76%). None of the parameters correlated significantly with all-cause mortality. Conclusions: These findings highlight the prognostic utility of non-invasively derived RV–PA coupling indices for rehospitalization risk stratification in DCM. Full article

Myocarditis is a complex inflammatory myocardial disease. Although traditionally regarded as exclusively immune-mediated, recent evidence highlights the significant role of underlying genetics on susceptibility, phenotypic variability, and long-term prognosis. This narrative review examines the evolving genetic architecture of myocarditis and its relationship to inherited cardiomyopathies, integrating mechanistic insights from molecular, imaging, and clinical studies. Variants in desmosomal genes such as desmoplakin (DSP) and plakophilin-2 (PKP2) are increasingly linked to recurrent myocarditis that may evolve into arrhythmogenic cardiomyopathy, supporting the concept of a genetically predisposed myocardium in which inflammatory stressors can act as triggers. Truncating variants in titin (TTN) and Filamin C (FLNC) are associated with fulminant or dilated phenotypes. Conversely, mutations in Lamin A/C (LMNA), Desmin (DES), and BCL2-Associated Athanogene 3 (BAG3) contribute to inflammatory myocardial remodeling and other forms of inherited cardiomyopathies. These findings collectively have the potential to redefine myocarditis as an inflammatory disorder influenced by genetic factors. Furthermore, advancements in genetic testing and multi-omics approaches show promise in enhancing diagnostic accuracy and informing management strategies. Full article

Background/Objectives: Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are common cardiomyopathies associated with heart failure. Electrocardiogram (ECG) screening before an echocardiogram could help streamline diagnosis, particularly in rural areas. Prior ECG–machine learning (ML) studies do not use open-source data when studying cardiomyopathy, and very few proprietary studies directly compare HCM and DCM or address ECG differences within obstructive (HOCM) and non-obstructive HCM (HNCM). Methods: Standard and vectorcardiogram-derived (VCG) ECG features were extracted from the MIMIC-IV-ECG database. The final cohort comprised 599 patients (HCM = 208 [HOCM = 99, HNCM = 53, unknown = 56]; DCM = 391 [ischemic cardiomyopathy with left ventricular dilation = 250, non-ischemic = 141]). Logistic regression (LR) and extreme gradient boosting (XGBoost) with five-fold cross-validation separated HCM from ischemic cardiomyopathy with left ventricular dilation (DCM-I) and non-ischemic DCM (DCM-NI), and HOCM from HNCM. Results: Using the area under the receiver-operating-characteristic curve (AUC-ROC) as the performance metric, LR achieved high discrimination of HCM from DCM-I (0.92) and DCM-NI (0.90). However, differentiating HOCM from HNCM proved more difficult (XGBoost = 0.81; LR = 0.75). Both DCM subtypes (especially ischemic) showed lower QRS amplitudes and right-posterior ventricular gradient orientation; HCM displayed higher amplitudes and larger, more complex T-loops. Within HCM, HOCM had stronger leftward electrical activity and more dipolar to non-dipolar QRS energy after singular value decomposition. Conclusions: Using only open-access data, we demonstrate an interpretable ECG-based pipeline that discriminates cardiomyopathy and highlights distinct features. While detecting obstruction remains difficult, ECG features provide measurable separation, supporting possible diagnostic screening and offering a reproducible framework for future studies. Full article

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and heart transplantation and is characterized by marked clinical and etiological heterogeneity. Recent studies have expanded the understanding of DCM from a predominantly monogenic disorder to a multifactorial disease shaped by genetic susceptibility and acquired or environmental “second hits”. Beyond rare pathogenic variants, emerging evidence highlights the contribution of clonal hematopoiesis of indeterminate potential to inflammation-driven adverse cardiac remodeling and disease progression. These secondary modifiers interact with pre-existing genetic backgrounds to amplify shared downstream pathways. In parallel, advances in mechanism-informed therapies are increasingly translating these insights into clinical practice. Beyond guideline-directed medical and device therapy, emerging approaches targeting specific molecular pathways, including sarcomeric modulators, inflammatory signaling, and gene- or cell-based interventions, illustrate a shift toward more personalized and stage-specific management of DCM and heart failure. This review aims to provide an updated overview of recent advances in the molecular mechanisms and diagnosis underlying DCM and discuss their implications for current and emerging therapeutic strategies. Full article