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BACKGROUND: Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Multiple identified mutations in nexilin (NEXN) have been suggested to be linked with severe DCM. However, the exact association between multiple mutations of Nexn and DCM remains unclear. Moreover, it is critical for the development of precise and effective therapeutics in treatments of DCM. RESULTS: In our study, Nexn global knockout mice and mice carrying human equivalent G645del mutation are studied using functional gene rescue assays. AAV-mediated gene delivery is conducted through systemic intravenous injections at the neonatal stage. Heart tissues are analyzed by immunoblots, and functions are assessed by echocardiography. Here, we identify functional components of Nexilin and demonstrate that exogenous introduction could rescue the cardiac function and extend the lifespan of Nexn knockout mouse models. Similar therapeutic effects are also obtained in G645del mice, providing a promising intervention for future clinical therapeutics. CONCLUSIONS: In summary, we demonstrated that a single injection of AAV-Nexn was capable to restore the functions of cardiomyocytes and extended the lifespan of Nexn knockout and G645del mice. Our study represented a long-term gene replacement therapy for DCM that potentially covers all forms of loss-of-function mutations in NEXN.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes. METHODS AND RESULTS: We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p =

Variants in RNA binding motif protein 20 (RBM20) are causative in a severe form of dilated cardiomyopathy referred to as RBM20 cardiomyopathy, yet the mechanisms are unclear. Moreover, the reason(s) for phenotypic heterogeneity in carriers with different pathogenic variants are similarly opaque. To gain insight, we carried out multi-omics analysis, including the first analysis of gene expression changes at the protein level, of mice carrying two different pathogenic variants in the RBM20 nuclear localization signal (NLS). Direct comparison of the phenotypes confirmed greater premature morality in S639G variant carrying mice compared to mice with the S637A variant despite similar cardiac remodeling and dysfunction. Analysis of differentially spliced genes uncovered alterations in the splicing of both RBM20 target genes and non-target genes, including several genes previously implicated in arrhythmia. Global proteomics analysis found that a greater number of proteins were differentially expressed in the hearts of Rbm20 S639G mice relative to WT than in Rbm20 S637A versus WT. Gene ontology analysis suggested greater mitochondrial dysfunction in Rbm20 S639G mice, although direct comparison of protein expression in the hearts of Rbm20 S639G versus Rbm20 S637A mice failed to identify any significant differences. Similarly, few differences were found by direct comparison of gene expression at the transcript level in Rbm20 S639G and Rbm20 S637A despite greater coverage. Our data provide a comprehensive overview of gene splicing and expression differences associated with pathogenic variants in RBM20, as well as insights into the molecular underpinnings of phenotypic heterogeneity associated with different dilated cardiomyopathy-associated variants. [Display omitted] • Disparate RBM20 NLS variants causes distinct disease phenotypes. • S639G variant causes greater premature mortality compared to S637. • DSGs in Rbm20 S639G versus Rbm20 S637A included genes linked to arrhythmia. • Unique Rbm20 S639G DEPs implicate mitochondrial dysfunction in phenotype differences. • First protein-level and multi-omics characterization in RBM20 cardiomyopathy. [ABSTRACT FROM AUTHOR]

Summary: Evidence suggests an association between obesity and the risk for cardiomyopathy development; however, robust evidence is still lacking. In this study we sought to explore the relationship of obesity with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and possible interactions with sex using large‐scale epidemiological real‐world data. We analysed data from the Nationwide Inpatient Sample of US hospitalisations for the years 2015–2019. There were a total of 46 934 admissions with diagnosis of HCM and 170 924 with DCM. There was a significant interaction between cardiomyopathies' diagnosis with sex and age subgroups; the rates of both DCM and HCM increased with age (p <.001 for both); DCM diagnosis was significantly higher in males compared with females (0.85% vs. 0.35%, p <.001). After adjustment for age, sex, race and presence of arterial hypertension there was a significant stepwise positive association between obesity and the population rates of both cardiomyopathy subtypes. For hospitalised patients with a body mass index (BMI) ≥30 kg/m2 there was an odds ratio (OR) of 1.68 (95% CI: 1.55–1.81, p <.001) for HCM and OR = 1.82 (95% CI: 1.79–1.84, p <.001) for DCM. More importantly, the positive relationship between a cardiomyopathy diagnosis (HCM or DCM) with increasing BMI was driven by the male sex (p <.001 for both) and it was non‐significant in females. The findings from this nationwide observational analysis support a sexual dimorphism in the relationship between obesity and HCM or DCM, which should be further investigated. [ABSTRACT FROM AUTHOR]

Background: Dilated cardiomyopathy (DCM) presents with diverse clinical courses, hardly predictable solely by the left ventricular (LV) ejection fraction (EF). Longitudinal strain (LS) offers distinct information from LVEF and exhibits various distribution patterns. This study aimed to evaluate the clinical significance of LS distribution patterns in DCM. Methods: We studied 139 patients with DCM (LVEF ≤ 35%) who were admitted for heart failure (HF). LS distribution was assessed using a bull's eye map and the relative apical LS index (RapLSI), calculated by dividing apical LS by the sum of basal and mid-LS values. We evaluated the associations of LS distribution with cardiac events (cardiac death, LV assist device implantation, or HF hospitalization) and LV reverse remodeling (LVRR), as indicated by subsequent LVEF changes. Results: Twenty six (19%) and 29 (21%) patients exhibited a pattern of relatively apical impaired or preserved LS (defined by RapLSI < 0.25 or > 0.75, signifying a 50% decrease or increase in apical LS compared to other segments), and the remaining patients exhibited a scattered/homogeneously impaired LS pattern. The proportion of new-onset heart failure and LVEF differed between the three groups. During the median 595-day follow-up, patients with relatively-impaired apical LS had a higher rate of cardiac events (both log-rank p < 0.05) and a lower incidence of LVRR (both p < 0.01) compared to patients with other patterns. RapLSI was significantly associated with cardiac event rates after adjusting for age, sex, and new-onset HF or global LS. Conclusion: DCM patients with reduced EF and distinct distribution patterns of impaired LS experienced different outcomes. [ABSTRACT FROM AUTHOR]

Background: Integration of artificial intelligence enhances precision, yielding dependable evaluations of left ventricular volumes and ejection fraction despite image quality variations. Commercial software like HeartModelAI provides fully automated 3DE quantification, simplifying the measurement of left chamber volumes and ejection fraction. In this manuscript, we present a cross-sectional study to assess and compare the diagnostic accuracy of automated 3D echocardiography (HeartModelAI) to the standard Cardiac Magnetic Resonance Imaging in patients with dilated cardiomyopathy. Methods: In this cross-sectional study, 30 patients with dilated cardiomyopathy referring to the Tehran Heart Center with cardiac magnetic resonance imaging and comprehensive 3D transthoracic echocardiography within 24 h were included. All 3D volume analysis was performed with fully automated quantification software (HeartModelAI) using 3D images of 2,3, and 4-chamber views at the end of systole and diastole. Results: Excellent Inter- and Intra-observer correlation coefficient was reported for HeartModelAI software for all indexes. HeartModelAI displayed a remarkable correlation with cardiac magnetic resonance for left ventricular end-systolic volume index (r = 0.918 and r = 0.911); nevertheless, it underestimated left ventricular end-systolic volume index and left ventricular end-diastolic volume index. Conversely, ejection fraction, stroke volume, and left ventricular mass were overestimated. It was found that manual contour correction can enhance the accuracy of automated model estimations, particularly concerning EF in participants needing correction. Conclusion: HeartModelAI software emerges as a rapid and viable imaging approach for evaluating the left ventricle's structure and function. In our study, LV volumes assessed by HeartModelAI demonstrated strong correlations with cardiac magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Excess lipid accumulation in the heart is associated with lipotoxicity and cardiac dysfunction due to excessive fatty acid oxidation. Peroxisome proliferator-activated receptor gamma (PPARγ) modulates the expression of key molecules involved in the FA metabolic pathway. Cardiomyocyte-specific overexpression of PPARγ causes dilated cardiomyopathy associated with lipotoxicity in mice. miR-130b-3p has been shown to be downregulated in the plasma of idiopathic dilated cardiomyopathy patients, but its role in modulating cardiomyocyte lipotoxicity via PPARγ remains unclear. Our objective was to investigate the protective role of miR-130b-3p against palmitate-induced lipotoxicity in cardiomyocytes through the modulation of the PPARγ signaling pathway. Human cardiomyoblasts were treated with palmitate. Intracellular lipid accumulation and expression of PPARγ and its downstream targets (CD36, FABP3, CAV1, VLDLR) were analyzed. Mitochondrial oxidative stress was assessed via MitoTracker Green and Redox Sensor Red staining and expression of CPT1B and SOD2. Endoplasmic reticulum stress and apoptosis were determined by examining GRP78, ATF6, XBP1s, CHOP, and caspase-3 expression. miR-130b-3p overexpression was achieved using transfection methods, and its effect on these parameters was evaluated. Luciferase assays were used to confirm PPARγ as a direct target of miR-130b-3p. Palmitate treatment led to increased lipid accumulation and upregulation of PPARγ and its downstream targets in human cardiomyoblasts. Palmitate also increased mitochondrial oxidative stress, endoplasmic reticulum stress and apoptosis. miR-130b-3p overexpression reduced PPARγ expression and its downstream signaling, alleviated mitochondrial oxidative stress and decreased endoplasmic reticulum stress and apoptosis in palmitate-stimulated cardiomyoblasts. Luciferase assays confirmed PPARγ as a direct target of miR-130b-3p. Our findings suggest that miR-130b-3p plays a protective role against palmitate-induced lipotoxicity in cardiomyocytes by modulating the PPARγ signaling pathway. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a myocardial disorder resulting in a substantial decline in cardiac function and potentially leading to heart failure. This research combines bioinformatics analysis with empirical validation to explore the roles and mechanisms of miR-214 in DCM. Using the DEseq2 R package, a total of 125 differentially expressed circulating miRNAs (DE c-miRNAs) and 784 DE genes (DEGs) were identified. Cross-analysis between target genes of DE c-miRNAs and DEGs identified 124 common genes, and protein-protein interaction analysis of common genes identified 11 hub genes. Twelve DE c-miRNAs were further verified by quantifying their levels in the serum of DCM patients and healthy individuals. miR-214 levels were significantly decreased in serum from DCM patients, positively correlated with left ventricular ejection fraction and left ventricular fractional shortening. Further analysis showed that miR-214 directly targets and negatively regulates phosphodiesterase 5 A (PDE5A). Elevated PDE5A expression reduced cGMP levels; however, using sildenafil, a PDE5A inhibitor, reversed this effect, substantiating the regulatory mechanism of miR-214 on cGMP via PDE5A. These results provide new potential targets for the diagnosis and treatment of DCM. [ABSTRACT FROM AUTHOR]

Skeletal muscle actin (ACTA1) mutations are a prevalent cause of skeletal myopathies consistent with ACTA1's high expression in skeletal muscle. Rare de novo mutations in ACTA1 associated with combined cardiac and skeletal myopathies have been reported, but ACTA1 represents only ~20% of the total actin pool in cardiomyocytes, making its role in cardiomyopathy controversial. Here we demonstrate how a mutation in an actin isoform expressed at low levels in cardiomyocytes can cause cardiomyopathy by focusing on a unique ACTA1 variant, R256H. We previously identified this variant in a family with dilated cardiomyopathy, who had reduced systolic function without clinical skeletal myopathy. Using a battery of multiscale biophysical tools, we show that R256H has potent effects on ACTA1 function at the molecular scale and in human cardiomyocytes. Importantly, we demonstrate that R256H acts in a dominant manner, where the incorporation of small amounts of mutant protein into thin filaments is sufficient to disrupt molecular contractility, and that this effect is dependent on the presence of troponin and tropomyosin. To understand the structural basis of this change in regulation, we resolved a structure of R256H filaments using cryoelectron microscopy, and we see alterations in actin's structure that have the potential to disrupt interactions with tropomyosin. Finally, we show that ACTA1R256H/+ human-induced pluripotent stem cell cardiomyocytes demonstrate reduced contractility and sarcomeric organization. Taken together, we demonstrate that R256H has multiple effects on ACTA1 function that are sufficient to cause reduced contractility and establish a likely causative relationship between ACTA1 R256H and clinical cardiomyopathy. [ABSTRACT FROM AUTHOR]

Key Points: Question: Are cardiac magnetic resonance imaging–derived measurements associated with adverse outcomes in nonischemic dilated cardiomyopathy (NIDCM)? Findings: In this meta-analysis of 103 studies comprising 29 687 patients with NIDCM, late gadolinium enhancement (LGE) presence and extent were consistently associated with arrhythmic, nonarrhythmic, and mortality end points, whereas left ventricular ejection fraction (LVEF) was not significantly associated with mortality and arrhythmia. Higher native T1 relaxation times were associated with arrhythmic end points and major adverse cardiac events. Due to insufficient data, a pooled analysis could not be conducted for the measurements of native T1 relaxation times, extracellular volume fraction, and global longitudinal strain concerning mortality end points. Meaning: The presence and extent of LGE were associated with adverse clinical outcomes, whereas LVEF was not associated with mortality and arrhythmic end points in NIDCM. Importance: Accurate risk stratification of nonischemic dilated cardiomyopathy (NIDCM) remains challenging. Objective: To evaluate the association of cardiac magnetic resonance (CMR) imaging–derived measurements with clinical outcomes in NIDCM. Data Sources: MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection databases were systematically searched for articles from January 2005 to April 2023. Study Selection: Prospective and retrospective nonrandomized diagnostic studies reporting on the association between CMR imaging–derived measurements and adverse clinical outcomes in NIDCM were deemed eligible. Data Extraction and Synthesis: Prespecified items related to patient population, CMR imaging measurements, and clinical outcomes were extracted at the study level by 2 independent reviewers. Random-effects models were fitted using restricted maximum likelihood estimation and the method of Hartung, Knapp, Sidik, and Jonkman. Main Outcomes and Measures: All-cause mortality, cardiovascular mortality, arrhythmic events, heart failure events, and major adverse cardiac events (MACE). Results: A total of 103 studies including 29 687 patients with NIDCM were analyzed. Late gadolinium enhancement (LGE) presence and extent (per 1%) were associated with higher all-cause mortality (hazard ratio [HR], 1.81 [95% CI, 1.60-2.04]; P <.001 and HR, 1.07 [95% CI, 1.02-1.12]; P =.02, respectively), cardiovascular mortality (HR, 2.43 [95% CI, 2.13-2.78]; P <.001 and HR, 1.15 [95% CI, 1.07-1.24]; P =.01), arrhythmic events (HR, 2.69 [95% CI, 2.20-3.30]; P <.001 and HR, 1.07 [95% CI, 1.03-1.12]; P =.004) and heart failure events (HR, 1.98 [95% CI, 1.73-2.27]; P <.001 and HR, 1.06 [95% CI, 1.01-1.10]; P =.02). Left ventricular ejection fraction (LVEF) (per 1%) was not associated with all-cause mortality (HR, 0.99 [95% CI, 0.97-1.02]; P =.47), cardiovascular mortality (HR, 0.97 [95% CI, 0.94-1.00]; P =.05), or arrhythmic outcomes (HR, 0.99 [95% CI, 0.97-1.01]; P =.34). Lower risks for heart failure events (HR, 0.97 [95% CI, 0.95-0.98]; P =.002) and MACE (HR, 0.98 [95% CI, 0.96-0.99]; P <.001) were observed with higher LVEF. Higher native T1 relaxation times (per 10 ms) were associated with arrhythmic events (HR, 1.07 [95% CI, 1.01-1.14]; P =.04) and MACE (HR, 1.06 [95% CI, 1.01-1.11]; P =.03). Global longitudinal strain (GLS) (per 1%) was not associated with heart failure events (HR, 1.06 [95% CI, 0.95-1.18]; P =.15) or MACE (HR, 1.03 [95% CI, 0.94-1.14]; P =.43). Limited data precluded definitive analysis for native T1 relaxation times, GLS, and extracellular volume fraction (ECV) with respect to mortality outcomes. Conclusion: The presence and extent of LGE were associated with various adverse clinical outcomes, whereas LVEF was not significantly associated with mortality and arrhythmic end points in NIDCM. Risk stratification using native T1 relaxation times, extracellular volume fraction, and global longitudinal strain requires further evaluation. This meta-analysis investigates the association of various cardiac MRI–derived measurements with adverse clinical outcomes in patients with nonischemic dilated cardiomyopathy for the purpose of risk stratification. [ABSTRACT FROM AUTHOR]

Background: Stem cell therapy is the transplantation of human cells to aid the healing of damaged or wounded tissues and cells. Only a few small-scale trials have been conducted to investigate stem cell therapy for non-ischemic dilated cardiomyopathy (DCM). We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of stem cell therapy for DCM. Methods: A comprehensive search of the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, and ProQuest was conducted from their inception to June 30, 2024, to access randomized controlled trials (RCTs) that were centered on stem cell therapy for DCM. The primary outcome was left ventricular ejection fraction (LVEF), and the secondary outcomes included left ventricular end-diastolic dimension (LVEDD), left ventricular end-diastolic volume (LVEDV), 6-min walk test (6MWT), NYHA functional classification, quality of life (QoL) such as Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-brain natriuretic peptide (NT-proBNP), and VO2 peak. Moreover, major adverse cardiovascular events (MACEs) were also recorded. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of the included RCTs, and the certainty of the evidence was assessed using the GRADE method. Sensitivity analysis was taken into consideration to determine the stability of the results. This review was registered with PROSPERO (CRD42024568912). Results: Eleven RCTs involving 637 participants were included in the quantitative analysis. The results indicated that there was a significant increase in mean LVEF (MD = 4.84, 95% CI 3.25–6.42, P < 0.00001) and considerable decrease in LVEDV (MD = − 29.51, 95% CI − 58.07 to − 0.95, P = 0.04) and NT-proBNP (MD = − 737.55, 95% CI − 904.28 to − 570.82, P < 0.00001) in DCM patients treated with stem cell therapy compared with controls. Stem cell therapy was also related to the improvement in functional capacity, as evaluated by 6MWT (MD = 44.32, 95% CI 34.70 − 53.94, P < 0.00001) and NYHA functional classification (MD = − 0.63, 95% CI − 0.96 to − 0.30, P = 0.0002). It also had positive effects on improving QoL, including significantly decreasing MLHFQ score (MD = − 16.60, 95% CI − 26.57 to − 6.63, P = 0.001) and increasing the KCCQ score (MD = 14.76, 95% CI 7.76 − 21.76, P < 0.0001). No significant differences were observed in LVEDD, VO2 peak, and MACEs between the two groups. The GRADE analysis revealed that the evidence was graded from low to moderate. Sensitivity analysis of the results suggested that the results were stable. Conclusion: The systematic review and meta-analysis indicates that stem cell therapy may be an effective and safe approach to improve cardiac function and quality of life in DCM patients. Nevertheless, given the limitations of existing studies, larger well-designed RCTs are required to confirm and support our findings. [ABSTRACT FROM AUTHOR]

Background: Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening condition. Due to the scarcity of epidemiological data in North Africa, we conducted this study to assess the outcomes of PPCM in our region. Materials and methods: This monocentric retrospective cohort study involving all patients diagnosed with PPCM was conducted between January 2010 and December 2022. Results: Twenty-seven PPCM patients, with a median age of 33 years (Interquartile range (IQR) = 9), were included. 52% of patients were diagnosed during the postpartum period. Dyspnea New York Heart Association III/IV(NYHA III/IV) was the most common functional symptom (85%). The median left ventricle ejection fraction (LVEF) was 30% (IQR = 11%). Atrial fibrillation occurred in 11.1% of patients, thromboembolic complications occurred in 18.5%, Pulmonary edema occurred in 85% of patients and cardiogenic shock occurred in 14.8% of patients, with two patients requiring Extracorporeal Membrane Oxygenation (ECMO) support. The predominant mode of delivery was a cesarean Sect. (82% of patients), and the indication for a cesarean delivery was obstetrical in 59% of patients. Prematurity occurred in 36% of newborns, and intrauterine fetal death occurred in one pregnancy. The median follow-up was 24 months [6–144 months]. LVEF recovery was noted in 67% of patients. Bromocriptine was administered to six patients (22%), and none of these patients died and out of them, five patients recovered their LVEF (83%). The overall mortality rate during the follow-up period was 15%, comprising three in-hospital cardiac deaths and one occurring two years later due to refractory advanced heart failure. No significant differences were observed between LVEF recovery and LVEF non-recovery groups. Factors significantly associated with mortality were multiparity, poor antenatal care (ANC) attendance, thromboembolic events, cardiogenic shock, and Pulmonary edema. Five patients with LV recovery subsequently became pregnant, none experienced a relapse of PPCM. However, one of the descendants of a patient was diagnosed with dilated cardiomyopathy. Conclusion: This study revealed that the diagnosis of PPCM in our hospital is often delayed until symptoms become more advanced, resulting in high morbi-mortality. [ABSTRACT FROM AUTHOR]

Becker muscular dystrophy (BMD) is an X-linked disorder due to in-frame mutations in the DMD gene, leading to a less abundant and truncated dystrophin. BMD is less common and severe than Duchenne muscular dystrophy (DMD) as well as less investigated. To accelerate the search for innovative treatments, we developed a rat model of BMD by deleting the exons 45–47 of the Dmd gene. Here, we report a functional and histopathological evaluation of these rats during their first year of life, compared to DMD and control littermates. BMD rats exhibit moderate damage to locomotor and diaphragmatic muscles but suffer from a progressive cardiomyopathy. Single nuclei RNA-seq analysis of cardiac samples revealed shared transcriptomic abnormalities in BMD and DMD rats and highlighted an altered end-addressing of TMEM65 and Connexin-43 at the intercalated disc, along with electrocardiographic abnormalities. Our study documents the natural history of a translational preclinical model of BMD and reports a cellular mechanism for the cardiac dysfunction in BMD and DMD offering opportunities to further investigate the organization role of dystrophin in intercellular communication. Synopsis: This new genome-edited rat model of Becker muscular dystrophy (BMD) develops progressive heart failure with reduced ejection fraction and confirms the role of dystrophin in the organization of the cardiomyocyte intercalated discs. A rat model of BMD was created by deleting exons 45–47 of the Dmd gene. BMD rats exhibited moderate damage to locomotor and diaphragmatic muscles and developed progressive cardiomyopathy. Single nuclei RNA-seq of cardiac samples revealed shared transcriptomic abnormalities between BMD and DMD rats. Both BMD and DMD hearts exhibited mislocalized TMEM65 and Connexin 43 (Cx43) proteins from the intercalated discs (ICDs), leading to disrupted ICD structure and impaired electrical synchronization. Echocardiographic evaluation revealed progressive dilated cardiomyopathy in BMD rats, accompanied by reduced ejection and shortening fractions, demonstrating a cardiac morbid trajectory similar to that of DMD rats. This new genome-edited rat model of Becker muscular dystrophy (BMD) develops progressive heart failure with reduced ejection fraction and confirms the role of dystrophin in the organization of the cardiomyocyte intercalated discs. [ABSTRACT FROM AUTHOR]

D-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the hypercoagulable state of the body. The research aimed to analyze the value of D-dimer in the prognosis of patients with dilated cardiomyopathy (DCM). Patients admitted to our center for the first time with DCM were enrolled consecutively. The clinical characteristics variables were obtained from the electronic medical record system, and the prognostic information was obtained using telephone return visits and a review of repeated hospitalization records. Univariate and multivariate Cox regression was used to explore the association of D-dimer with all-cause mortality. Smooth curve fitting, threshold saturation effect analysis, and subgroup analysis were performed. Ultimately, 534 patients were included. After a follow-up of the enrolled patients, 485 patients obtained prognostic information, of which 159 died from all causes, and the main cause of death was heart failure (89/159), the sudden death accounted for about 17%. The independent positive association between D-dimer and all-cause mortality remained unchanged in both unadjusted and adjusted Cox regression models. In the fully adjusted model, each standard deviation increase in D-dimer was associated with a 14% increase in all-cause mortality (HR = 1.14; 95% CI: 1.02 ~ 1.27; P < 0.05). Curve fitting and threshold effect analysis showed an inflection point in the relationship between D-dimer and all-cause mortality (non-linear test: P = 0.03). When D-dimer was equal to 362ng/ml, HR = 1; and as the value increased, the risk of all-cause mortality increased by 34.7% for every 2-fold increase in D-dimer gradually (HR = 1.347; 95% CI: 1.069 ~ 1.697; P = 0.012). In subgroup analysis, D-dimer and BMI had a significant interaction on all-cause mortality, with a significantly increased risk of all-cause mortality in subjects with BMI ≥ 25 kg/m2 (HR = 1.99; 95% CI: 1.34 ~ 2.97; P < 0.01). The ROC curve showed that D-dimer was a good predictor of all-cause mortality, and the areas under the curve at 1-, 3-, and 5-year were 0.71, 0.64, and 0.59, respectively. In addition, D-dimer improved the predictive performance of the MAGGIC heart failure score in patients with DCM. D-dimer is not only independently associated with all-cause mortality in DCM patients, but also has good predictive value, suggesting that D-dimer may be an early and useful marker for improving the management of DCM patients. [ABSTRACT FROM AUTHOR]

The Ras-related GTP-binding protein D (RRAGD) gene plays a crucial role in cellular processes. Recently, RRAGD variants found in patients have been implicated in a novel disorder with kidney tubulopathy and dilated cardiomyopathy. Currently, the consequences of RRAGD variants at the organismal level are unknown. Therefore, this study investigated the impact of RRAGD variants on cardiac function using a zebrafish embryo model. Furthermore, the potential usage of rapamycin, an mTOR inhibitor, as a therapy was assessed in this model. Zebrafish embryos were injected with RRAGD p.S76L and p.P119R cRNA and the resulting heart phenotypes were studied. Our findings reveal that overexpression of RRAGD mutants resulted in decreased ventricular fractional shortening, ejection fraction, and pericardial swelling. In RRAGD S76L-injected embryos, lower survival and heartbeat were observed, whereas survival was unaffected in RRAGD P119R embryos. These observations were reversible following therapy with the mTOR inhibitor rapamycin. Moreover, no effects on electrolyte homeostasis were observed. Together, these findings indicate a crucial role of RRAGD in cardiac function. In the future, the molecular mechanisms by which RRAGD variants result in cardiac dysfunction and if the effects of rapamycin are specific for RRAGD-dependent cardiomyopathy should be studied in clinical studies. NEW & NOTEWORTHY: The resultant heart-associated phenotypes in the zebrafish embryos of this study serve as a valuable experimental model for this rare cardiomyopathy. Moreover, the potential therapeutic property of rapamycin in cardiac dysfunctions was highlighted, making this study a pivotal step toward prospective clinical applications. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as pivotal medications for heart failure, demonstrating remarkable cardiovascular benefits extending beyond their glucose-lowering effects. The unexpected cardiovascular advantages have intrigued and prompted the scientific community to delve into the mechanistic underpinnings of these novel actions. Preclinical studies have generated many mechanistic theories, ranging from their renal and extrarenal effects to potential direct actions on cardiac muscle cells, to elucidate the mechanisms linking these drugs to clinical cardiovascular outcomes. Despite the strengths and limitations of each theory, many await validation in human studies. Furthermore, whether SGLT2 inhibitors confer therapeutic benefits in specific subsets of cardiomyopathies akin to their efficacy in other heart failure populations remains unclear. By examining the shared pathological features between heart failure resulting from vascular diseases and other causes of cardiomyopathy, certain specific molecular actions of SGLT2 inhibitors (particularly those targeting cardiomyocytes) would support the concept that these medications will yield therapeutic benefits across a broad range of cardiomyopathies. This article aims to discuss the important mechanisms of SGLT2 inhibitors and their implications in hypertrophic and dilated cardiomyopathies. Furthermore, we offer insights into future research directions for SGLT2 inhibitor studies, which hold the potential to further elucidate the proposed biological mechanisms in greater detail. [ABSTRACT FROM AUTHOR]

Background: Restoring electrical synchrony with cardiac resynchronization therapy (CRT) reverses the heart failure phenotype developed by left-ventricular (LV) dyssynchrony. This study aimed to identify new predictors of response to LV-only fusion pacing CRT. Methods: A select group of patients with CRT-P indications received a right atrium (RA)/LV DDD pacing system. LV dyssynchrony was assessed via offline TDI timing focusing on the temporal difference between peak septal (E″T) and lateral wall (A"T) motion. CRT effectiveness was evaluated at each follow-up, involving the heart rate recovery index (HRRI) parameter (acceleration/deceleration time) derived from exercise testing along with the echocardiographic parameters. Patients were classified into super-responders (SR), responders (R), and non-responders (NR). Results: Baseline initial characteristics: 62 patients (35 male) aged 62 ± 11 y.o. with non-ischemic dilated cardiomyopathy (DCM). Ejection fraction (EF) 27 ± 5.2%; QRS 164 ± 18 ms; 29% had type III diastolic dysfunction (DD), 63% type II DD, and 8% type I DD. Average follow-up was 45 ± 19 months: 34% of patients were SR, 61% R, and 5% NR. The E″T decreased from 90 ± 20 ms to 25 ± 10 ms in SR, with a shorter deceleration time (DT) during exercise test compared to NR (109 ± 68 ms vs. 330 ± 30 ms; p < 0.0001). The responders present a higher HRRI (2.87 ± 1.47 vs. 0.98 ± 0.08; p = 0.03) compared to NR and a significantly decrease in E"T and A"T from 76 ± 13 ms to 51 ± 11 ms (p < 0.0001). Prolonged DT was associated with an accentuated LV dyssynchrony and nonoptimal response to CRT. Conclusions: The study identified new parameters for assessing responsiveness to LV-only fusion pacing CRT, which could improve candidate selection and CRT implementation. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field. [ABSTRACT FROM AUTHOR]

Background: Atrioventricular block (AVB) is common in the elderly and therefore considered to be a degenerative disease of the cardiac conduction system. However, there exist other etiologies contributing to AVB in young patients. This study aimed to determine the etiologies in patients aged before 60 years receiving their first pacemaker implantation for AVB in China. Methods and Results: Medical records and diagnostic tests of AVB patients were reviewed to identify the etiologies between 2010 and 2021 at Guangdong Provincial People's Hospital. Eight hundred and twenty‐six patients (median age 47 years; 47.9% males) were included. The etiologies were identified in 336 (40.7%) cases, including complications to cardiac surgery (n = 190 [23.0%]), myocarditis (n = 57 [6.9%]), myocardial infarction (n = 25 [3.0%]), complications to catheter‐based interventional procedures (n = 21 [2.5%]) and others (n = 43 [5.2%]). AVB caused by myocardial infarction was more common in men (5.8% vs. 0.5%, p <.001), while women received pacing treatment earlier (48 vs. 46 years, p =.019). Men were more likely to suffer from dilated cardiomyopathy (6.6% vs. 2.1%, p =.001) and atrial fibrillation/flutter (23.0% vs. 12.8%, p <.001). The number of first pacemaker implantation increased with age especially among patients with unclear etiologies. Conclusion: The etiology of AVB was only determined in approximately 40% of patients receiving their first pacemaker implantation aged before 60 years. The predominance of AVB with unknown etiology and potential gender differences warrants further studies. [ABSTRACT FROM AUTHOR]

Introduction: In children with myocarditis or dilated cardiomyopathy (DCM) on extracorporeal membrane oxygenation (ECMO) for cardiogenic shock, it is often necessary to decompress the left heart to minimize distension and promote myocardial recovery. We compare outcomes in those who underwent balloon atrial septostomy (BAS) versus direct left atrial (LA) drainage for left heart decompression in this population. Methods: Retrospective study of the Extracorporeal Life Support Organization (ELSO) multicenter registry of patients ≤ 18 years with myocarditis or DCM on ECMO who underwent LA decompression. Descriptive and univariate statistics assessed association of patient factors with decompression type. Multivariable logistic regression sought independent associations with outcomes. Results: 369 pediatric ECMO runs were identified. 52% myocarditis, 48% DCM, overall survival 74%. 65% underwent BAS and 35% LA drainage. Patient demographics including age, weight, gender, race/ethnicity, diagnosis, pre-ECMO pH, mean airway pressure, and arrest status were similar. 89% in the BAS group were peripherally cannulated onto ECMO, versus 3% in the LA drainage group (p <.001). On multivariable analysis, LA drainage (OR 3.96; 95% CI, 1.47-10.711; p =.007), renal complication (OR 2.37; 95% CI, 1.41-4.01; p =.001), cardiac complication (OR 3.14; 95% CI, 1.70-5.82; p <.001), and non-white race/ethnicity (OR 1.75; 95% CI, 1.04-2.94; p =.035) were associated with greater odds of mortality. There was a trend toward more episodes of pulmonary hemorrhage in BAS (n = 17) versus LA drainage group (n = 3), p =.08. Comparing only those with central cannulation, LA drainage group was more likely to be discontinued from ECMO due to recovery (72%) versus the BAS group (48%), p =.032. Conclusions: In children with myocarditis or DCM, there was a three times greater likelihood for mortality with LA drainage versus BAS for LA decompression. When adjusted for central cannulation groups only, there was better recovery in the LA drainage group and no difference in mortality. Further prospective evaluation is warranted. [ABSTRACT FROM AUTHOR]

The article explains the importance of assessing cardiac output for optimal vessel opacification in computed tomography for proper diagnoses. Topics discussed include different classifications of heart failure based on the sidedness and pumping abilities of the heart, determinants of cardiac output such as heartbeat, heart rate, preload, contractility and afterload, as well as Laplace's law of physiological wall stress and its effects on cardiac output.

Aims This study aimed to compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular death or non-fatal heart failure events in patients with non-ischaemic dilated cardiomyopathy (DCM). Methods and results CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm [median age 54 (interquartile range 44–64) years, 61% men, median left ventricular ejection fraction 42% (30–51%)] were analysed for measures of LA structure [LA maximum volume index (LAVImax) and LA minimum volume index (LAVImin)] and function (LA emptying fraction, LA reservoir strain, LA conduit strain (LACS), and LA booster strain]. Over a median follow-up of 7.4 years, 103 patients (18%) met the primary endpoint. Apart from LACS, each measure of LA structure and function was associated with the primary endpoint after adjusting for other important prognostic variables. The addition of each LA metric to a baseline model containing the same important prognostic covariates improved model discrimination, with LAVImin providing the greatest improvement [ C -statistic improvement: 0.702–0.738; χ 2 test comparing likelihood ratio P < 0.0001; categorical net reclassification index: 0.210 (95% CI 0.023–0.392)]. Patients in the highest tercile of LAVImin had similar event rates to those with persistent atrial fibrillation. Measures of LA strain did not enhance model discrimination above LA volumetric measures. Conclusion Measures of LA structure and function offer important prognostic information in patients with DCM and enhance the prediction of adverse outcomes. LA strain was not incremental to volumetric analysis for risk prediction. [ABSTRACT FROM AUTHOR]

Background: Canine dilated cardiomyopathy (DCM) is a disease of the myocardium classically characterised by progressive eccentric hypertrophy (dilation) and systolic dysfunction of typically the left ventricle; however, DCM can also manifest as electrical abnormalities resulting in arrhythmic forms of the disease. The aetiology is idiopathic and there is often a genetic basis, which explains its over‐representation in certain breeds. Preclinical DCM describes the usually protracted period where an individual dog experiences structural changes over several years, or an arrhythmia (in specific breeds) that meet criteria for diagnosis without outward clinical signs of disease. Detection of this phase is crucial to facilitate early intervention with medical treatment, close monitoring and prognostication. Clinical DCM describes progression to congestive heart failure; the management of this will be discussed in the second part of this series, to be published in a subsequent issue of In Practice. Aim of the article: This article discusses case selection for DCM screening, including the utility of cardiac biomarkers. It outlines the echocardiographic diagnostic criteria for preclinical DCM, as well as the identification of arrhythmias that may be primary in nature or associated with the presence of cardiac remodelling. The medical management of preclinical DCM and associated arrhythmias is also discussed. [ABSTRACT FROM AUTHOR]

Dilated cardiomyopathy (DCM) is a heart condition that causes enlarged and weakened left ventricles and affects the heart’s ability to pump blood effectively. Most genetic etiology still needs to be understood. Previously, we have used the known germline hereditary fusion genes (HFGs) to identify HFGs associated with multiple myeloma and leukemia. In this study, we have developed a statistical model to study fusion transcripts discovered from the left ventricles of 122 DCM patients and 252 GTEx (Genotype Tissue Expression) healthy controls to discover novel HFGs, ranging from 4% to 87.7%, and EFGs, ranging from 4% to 99.2%, associated with DCM. This discovery of numerous novel HFGs and EFGs associated with DCM provides first-hand evidence that DCM results from interactive developmental consequences between germline genetic and environmental abnormalities and paves the way for future research and diagnostic and therapeutic applications, instilling hope for the future of DCM treatment. [ABSTRACT FROM AUTHOR]

During the disease trajectory, patients with advanced heart failure are often hospitalised with a high probability of admission to the intensive care setting. Using a case study, this article explores the care given to a patient with decompensated heart failure in an intensive care unit (ICU). It will discuss the significance of holistic assessment and effective symptom management, in particular the research related to breathlessness management. The importance of effective communication within the ICU multidisciplinary team, including with the patient/family will be explored, as the ICU environment can often lead to communication breakdown, patients being unable to voice their wishes and over-medicalisation. The effectiveness of early involvement of the palliative care team in ICU will be examined, including the use of tools such advance care planning and a treatment escalation plan and whether use of these can enable a better patient and family experience at the end of life. The role of palliative care champions will be discussed. [ABSTRACT FROM AUTHOR]

Background : Altered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease. Methods: Mendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1567 plasma proteins and performed cis MR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways. Results: We identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p = 0.029) and DCM for acylcarnitines (p = 0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis. Conclusions: This study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development. [ABSTRACT FROM AUTHOR]

Background and objective: The aim of this study was to investigate potential hub genes for dilated cardiomyopathy (DCM). Methods: Five DCM-related microarray datasets were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were used for identification. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, disease ontology, gene ontology annotation and protein-protein interaction (PPI) network analysis were then performed, while a random forest was constructed to explore central genes. Artificial neural networks were used to compare with known genes and to develop new diagnostic models. 240 population blood samples were collected and expression of hub genes was verified in these samples using RT-PCR and demonstrated by Nomogram. Results: After differential analysis, 33 genes were statistically significant (adjusted P < 0.05). Functional enrichment of these differential genes resulted in 85 Gene Ontology (GO) functions identified and 6 pathways enriched for the KEGG pathway. PPI networks and molecular complex assays identified 10 hub genes (adjusted P < 0.05). Random forest identified SMOC2 and SFRP4 as the most important, followed by FCER1G and FRZB. NeuraHF models (SMOC2, SFRP4, FCER1G and FRZB) were selected by artificial neural network model and had better diagnostic efficacy for the onset of DCM, compared with the traditional KG-DCM models (MYH7, ACTC1, TTN and LMNA). Finally, SFRP4 and FRZB were expressed higher in DCM verified by RT-PCR and as a factor for DCM identified by Nomogram. Conclusions: We performed an integrated analysis and identified SFRP4 and FRZB as a new factor for DCM. But the exact mechanism still needs further experimental verification. [ABSTRACT FROM AUTHOR]

Correlation between echocardiographic and pathoanatomic variables and their prognostic value in murine cardiomyopathy models remain unknown. Using echocardiography, morphometrics, and survival monitoring, we characterized transgenic (TG) mice with dilated cardiomyopathy due to cardiac overexpression of β2‐adrenoceptors focusing on predicting heart failure (HF) risk and HF mortality. In 12‐month‐old non‐TG and TG mice, echocardiography was performed to determine left ventricular (LV) dimensions (d), wall thickness (h), and fractional shortening (FS). Animals were monitored for 3 months for survival. Organ weights and pathological events indicating left HF were determined. TG mice (n = 76) had reduced FS and enlarged LV, and 79% died of HF or likely arrhythmias during the follow‐up period while all non‐TG mice (n = 26) survived. These mice with left HF also had pulmonary congestion and hypertrophy/dilatation of the right ventricle (RV). Weights of lungs, RV, and atria were intercorrelated (r = 0.79–0.83) and also negatively correlated with FS × (h/d) index (r = −0.502 to −0.609). By FS × (h/d) tertiles, TG mice of low tertiles were identified with the highest mortality (96%) largely due to HF (76%). In conclusion, in aged cardiomyopathy mice a good correlation existed between echocardiographic and pathoanatomic variables. Echocardiography‐derived LV function and remodeling were useful in identifying a subgroup of TG mice with a high risk of HF and HF fatality. [ABSTRACT FROM AUTHOR]

ABSTRACT Malate is an important dicarboxylic acid produced from fumarate in the tricarboxylic acid cycle. Deficiencies of fumarate hydrolase (FH) and malate dehydrogenase (MDH), responsible for malate formation and metabolism, respectively, are known to cause recessive forms of neurodevelopmental disorders (NDDs). The malic enzyme isoforms, malic enzyme 1 (ME1) and 2 (ME2), are required for the conversion of malate to pyruvate. To date, there have been no reports linking deficiency of either malic enzyme isoforms to any Mendelian disease in humans. We report a patient presenting with NDD, subtle dysmorphic features, resolved dilated cardiomyopathy, and mild blood lactate elevation. Whole exome sequencing (WES) revealed a homozygous frameshift variant (c.1379_1380delTT, p.Phe460fs*22) in the malic enzyme 2 (ME2) gene resulting in truncated and unstable ME2 protein in vitro. Subsequent deletion of the yeast ortholog of human ME2 (hME2) resulted in growth arrest, which was rescued by overexpression of hME2, strongly supporting an important role of ME2 in mitochondrial function. Our results also support the pathogenicity and candidacy of the ME2 gene and variant in association with NDD. To our knowledge, this is the first report of a Mendelian human disease resulting from a biallelic variant in the ME encoding gene. Future studies are warranted to confirm ME2‐associated recessive NDD. [ABSTRACT FROM AUTHOR]

Titin-truncating variant (TTNtv) is the most common genetic cause of dilated cardiomyopathy (DCM). In the previous study, we found a novel heterozygous TTNtv c.13254T>G (p.Tyr4418Ter) associated with DCM, but lacking functional evidence. The purpose of this study is to demonstrate the pathogenicity of TTNtv c.13254T>G. We constructed a mouse model with TTNtv Y4370* on exon 45 by CRISPR/Cas9-mediated genome engineering to imitate the TTNtv. c.13254T>G. Transmission electron microscope (TEM), immunohistochemistry, western blot (WB), Transcriptome sequencing (RNA-seq), and tandem Mass Tag (TMT) proteome analysis were performed on the mutant (KO) and WT mice cardiac tissue. Multi-omics association analysis was performed to observe the damages of cardiac tissue, and changes of inflammatory factors and Titin protein. TEM results showed that TTNtv Y4370* may lead to broken myofibrils, sparse myofilament structure, and broken Z-line and H-zone in many places of cardiac tissue of KO mice. Immunohistochemistry showed a significant increase in cTnT and TNF-α expression level in KO mice cardiac tissue. RNA-seq and TMT proteome enrichment analysis further strengthened that TTNtv Y4370* led to cardiac injury and inflammatory response in KO mice. In summary, TTNtv c.13254T>G contributed to the cardiac injury, inflammatory response and construct alterations in mice, that is TTNtv c.13254T>G may cause DCM in mice. These functional evidence of TTNtv c.13254T>G have important significance for follow-up genetic research of DCM in human. [ABSTRACT FROM AUTHOR]

Aims: Evidence on the relative impact of diverse genetic backgrounds associated with non‐ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long‐term outcomes of different gene groups in DCM. Methods and results: Electronic databases were systematically screened to identify studies reporting prognostic data on pre‐specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta‐analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67–2.65), MVAEs (OR 1.86, 95% CI 1.52–2.26), and HFEs (OR 2.01, 95% CI 1.08–3.73) than genotype‐negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20–2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non‐LMNA and non‐desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv. Conclusions: Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM. [ABSTRACT FROM AUTHOR]

The clinical manifestations of ischemic cardiomyopathy (ICM) bear resemblance to dilated cardiomyopathy (DCM), yet their treatments and prognoses are quite different. Early differentiation between these conditions yields positive outcomes, but the gold standard (coronary angiography) is invasive. The potential use of ECG signals based on variational mode decomposition (VMD) as an alternative remains underexplored. An ECG dataset containing 87 subjects (44 DCM, 43 ICM) is pre-processed for denoising and heartbeat division. Firstly, the ECG signal is processed by empirical mode decomposition (EMD) and VMD. And then, five modes are determined by correlation analysis. Secondly, bispectral analysis is conducted on these modes, extracting corresponding bispectral and nonlinear features. Finally, the features are processed using five machine learning classification models, and a comparative assessment of their classification efficacy is facilitated. The results show that the technique proposed provides a better categorization for DCM and ICM using ECG signals compared to previous approaches, with a highest classification accuracy of 98.30%. Moreover, VMD consistently outperforms EMD under diverse conditions such as different modes, leads, and classifiers. The superiority of VMD on ECG analysis is verified. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report highlights dilated cardiomyopathy as a cardiovascular complication in autoimmune polyendocrine syndrome type 1 (APS‐1), emphasizing the need for early recognition and a multidisciplinary approach. Comprehensive care and regular follow‐up are crucial in managing these atypical presentations to optimize patient outcomes. APS‐1, also known as Whitaker syndrome, is characterized by a triad of mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. This rare autosomal recessive disorder results from mutations in the autoimmune regulator (AIRE) gene. Cardiovascular and pulmonary manifestations in APS‐1 are infrequently reported in the literature. We present a case of a 28‐year‐old male who presented with shortness of breath and pedal edema. Physical examination revealed alopecia, absence of eyebrows, hyperpigmentation on joints, oral candidiasis, and nail dystrophy. Echocardiography demonstrated dilated cardiomyopathy (DCM) and pericardial effusion. Chest x‐ray showed left‐sided pleural effusion. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, low parathyroid hormone (PTH), low cortisol, and high adrenocorticotropic hormone (ACTH) levels. The combination of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency confirmed the diagnosis of APS‐1. To the best of our knowledge, this is the first Pakistani and second worldwide reported case of APS‐1 presenting with such a combination of manifestations. Early recognition and multidisciplinary management are crucial for improving outcomes in these patients. [ABSTRACT FROM AUTHOR]

Background: Cardiomyopathy was an anatomic and pathologic diagnosis was associated with muscle or electrical dysfunction of the heart. The American Heart Association (AHA) defines cardiomyopathy as a heterogeneous group of diseases of the myocardium, usually with inappropriate ventricular hypertrophy or dilatation. This study aimed to evaluate for etiological factors of cardiomyopathy among hospitalized patients and to correlate the clinical findings with electrocardiographic and echocardiographic findings. Methods: A Cross-sectional study was conducted among 55 patients admitted with cardiomyopathy to the department of general medicine of the hospital for 18 months. All eligible patients had undergone relevant investigations including Echocardiogram, Doppler study, 12 lead electrocardiogram, chest radiogram and coronary angiogram whenever indicated and possible. Correlation of etiological factors with echocardiographic and electrocardiographic changes were done. Results: Out of 55 cases 90% of the cases were presented with complaints of dyspnea, 33% of them had chest pain, 25% had fatiguability and 20% had palpitations. Half of the cases had Idiopathic Dilated Cardiomyopathy (51%). The most common etiological factor of cardiomyopathy was Non ischemia (51%). Echocardiographic findings of the cases at the time of admission are <35% of Ejection fraction are seen among 71%.Echocardiogram revealed that both Mitral regurgitation and tricuspid regurgitation mostly seen among Idiopathic dilated cardiomyopathy. Left ventricular thrombus was seen in Idiopathic DCM and Diastolic dysfunction was seen mainly in Idiopathic DCM and highest LVEF was seen among HOCM and Least LVEF was seen among Alcoholic Cardiomyopathy. Conclusions: In the present study, the most common presenting symptoms were dyspnea, chest pain, fatiguability and palpitations. Half of the cases are of Idiopathic Dilated Cardiomyopathy followed by ischemic Dilated Cardiomyopathy. Two-dimensional echocardiography has been the most used, efficient and accessible technique for establishment of the diagnosis of cardiomyopathies. Limitations: current study was a cross-sectional study and sample size and sampling method was purposive which was why the generalisability of results were questionable. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic dilated cardiomyopathy (DCM) is a serious disease causing mitral regurgitation and contraction defects of the myocardium. Through mitral valve (MV) repair surgery, the clinical status of patients can be improved. Methods: Pediatric patients with DCM and mitral insufficiency who underwent mitral repair procedures between 2019 and 2023 were retrospectively investigated. The patients' demographic characteristics, preoperative and postoperative clinical conditions, and echocardiographic findings were compared. The techniques used in patient operations were examined. Similarly, data regarding the postoperative intensive care unit processes and mortality data of the patients were recorded. Results: Mitral repair was performed in 3 patients during the study period. The mean age of the patients was 4.66 months (±3.05) and body weight was 5.25 kg (±0.25). In the preoperative period, left ventricular ejection fraction decreased slightly in all patients [mean: 43.3% standard deviation (SD): ±2.8]. Although the preoperative and postoperative values of left ventricular end-diastolic diameter (LVEDd) and LVEDd Z-scores were above normal, respectively, they showed a decreasing trend after the operation. Although the mitral annulus diameters decreased slightly after the operation in all three patients, they remained high (mean: 17.6 mm SD: ±1.5). A significant decrease in MV insufficiency was observed in postoperative follow-ups after discharge (1st-2nd degree). Wooler annuloplasty and posterior valve pericardial patch augmentation were applied as the primary approach in all patients. The patients did not develop additional morbidities, and no mortality was observed during hospitalization. Conclusion: Successful surgical interventions to prevent mitral regurgitation in pediatric patients with DCM and mitral regurgitation, may improve the clinical status of these patients. [ABSTRACT FROM AUTHOR]

During a heart attack, ischemia causes losses of billions of cells; this is especially concerning given the minimal regenerative capability of cardiomyocytes (CMs). Heart remuscularization utilizing stem cells has improved cardiac outcomes despite little cell engraftment, thereby shifting focus to cell-free therapies. Consequently, we chose induced pluripotent stem cells (iPSCs) given their pluripotent nature, efficacy in previous studies, and easy obtainability from minimally invasive techniques. Nonetheless, using iPSC secretome-based therapies for treating injured CMs in a clinical setting is ill-understood. We hypothesized that the iPSC secretome, regardless of donor health, would improve cardiovascular outcomes in the CM model of ischemia–reperfusion (IR) injury. Episomal-generated iPSCs from healthy and dilated cardiomyopathy (DCM) donors, passaged 6–10 times, underwent 24 h incubation in serum-free media. Protein content of the secretome was analyzed by mass spectroscopy and used to treat AC16 immortalized CMs during 5 h reperfusion following 24 h of hypoxia. IPSC-derived secretome content, independent of donor health status, had elevated expression of proteins involved in cell survival pathways. In IR conditions, iPSC-derived secretome increased cell survival as measured by metabolic activity (p < 0.05), cell viability (p < 0.001), and maladaptive cellular remodelling (p = 0.052). Healthy donor-derived secretome contained increased expression of proteins related to calcium contractility compared to DCM donors. Congruently, only healthy donor-derived secretomes improved CM intracellular calcium concentrations (p < 0.01). Heretofore, secretome studies mainly investigated differences relating to cell type rather than donor health. Our work suggests that healthy donors provide more efficacious iPSC-derived secretome compared to DCM donors in the context of IR injury in human CMs. These findings illustrate that the regenerative potential of the iPSC secretome varies due to donor-specific differences. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Methods Conclusion Pilot studies indicate that immunoadsorption with subsequent IgG substitution (IA/IgG) induces beneficial effects in patients with dilated cardiomyopathy (DCM) and heart failure. This placebo‐controlled study investigates whether IA/IgG treatment enhances left ventricular (LV) systolic function as compared to a control group receiving pseudo‐treatment.This multicentre, randomized, double‐blind, parallel‐group trial aims to include 200 patients with heart failure due to DCM (LV ejection fraction [LVEF] <40%) on optimized guideline‐directed heart failure medication. Participants are randomly assigned in a 1:1 ratio to IA/IgG using protein‐A columns, or to pseudo‐immunoadsorption followed by an intravenous infusion without IgG. Follow‐up visits take place by telephone after 1 and 3 months and at the study centres after 6, 12 and 24 months. The primary efficacy endpoint is the change in LVEF from baseline to 6 months determined by contrast echocardiography, analysed at a core lab. In addition, LV end‐diastolic and end‐systolic volumes will be analysed as secondary endpoints over the entire study period to assess whether IA/IgG affects LV remodelling. As main secondary outcome, a composite of all‐cause death, cardiac resuscitation, hospitalization for heart failure, and need for cardiac surgery to improve myocardial pump function will be evaluated after 24 months. In addition, exploratory outcomes as well as safety endpoints related to the treatment will be assessed throughout the whole study period.IASO‐DCM is a randomized study which will provide comprehensive insights into the effects of immunoadsorption with subsequent IgG substitution in patients with DCM. [ABSTRACT FROM AUTHOR]

The heart is an organ with a low ability to renew and repair itself. MSCs have cell surface markers such as CD45−, CD34−, CD31−, CD4+, CD11a+, CD11b+, CD15+, CD18+, CD25+, CD49d+, CD50+, CD105+, CD73+, CD90+, CD9+, CD10+, CD106+, CD109+, CD127+, CD120a+, CD120b+, CD124+, CD126+, CD140a+, CD140b+, adherent properties and the ability to differentiate into cells such as adipocytes, osteoblasts and chondrocytes. Autogenic, allogeneic, normal, pretreated and genetically modified MSCs and secretomes are used in preclinical and clinical studies. MSCs and their secretomes (the total released molecules) generally have cardioprotective effects. Studies on cardiovascular diseases using MSCs and their secretomes include myocardial infraction/ischemia, fibrosis, hypertrophy, dilated cardiomyopathy and atherosclerosis. Stem cells or their secretomes used for this purpose are administered to the heart via intracoronary (Antegrade intracoronary and retrograde coronary venous injection), intramyocardial (Transendocardial and epicardial injection) and intravenous routes. The protective effects of MSCs and their secretomes on the heart are generally attributed to their differentiation into cardiomyocytes and endothelial cells, their immunomodulatory properties, paracrine effects, increasing blood vessel density, cardiac remodeling, and ejection fraction and decreasing apoptosis, the size of the wound, end-diastolic volume, end-systolic volume, ventricular myo-mass, fibrosis, matrix metalloproteins, and oxidative stress. The present review aims to assist researchers and physicians in selecting the appropriate cell type, secretomes, and technique to increase the chance of success in designing therapeutic strategies against cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Myopathy is a common manifestation in mitochondrial disorders, but the pathomechanisms are still insufficiently studied in children. Here, we report a severe, progressive mitochondrial myopathy in a four-year-old child, who died at eight years. He developed progressive loss of muscle strength with nocturnal hypoventilation and dilated cardiomyopathy. Skeletal muscle showed ragged red fibers and severe combined respiratory chain deficiency. Mitochondrial DNA sequencing revealed a novel m.5670A>G mutation in mitochondrial tRNAAsn (MTTN) with 88 % heteroplasmy in muscle. The proband also had systemic NAD+ deficiency but rescuing this with the NAD+ precursor niacin did not stop disease progression. Targeted metabolomics revealed an overall shift of metabolism towards controls after niacin supplementation, with normalized tryptophan metabolites and lipid-metabolic markers, but most amino acids did not respond to niacin therapy. To conclude, we report a new MTTN mutation, secondary NAD+ deficiency in childhood-onset mitochondrial myopathy with metabolic but meager clinical response to niacin supplementation. [ABSTRACT FROM AUTHOR]

Introduction and methods: Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in impaired glycogen breakdown in skeletal muscle. Despite being labelled as a "pure myopathy," cardiac involvement has been reported in some cases, including various cardiac abnormalities such as electrocardiographic changes, coronary artery disease, and cardiomyopathy. Here, we present a unique case of a 72-year-old man with GSD-V and both mitral valvulopathy and coronary artery disease, prompting a systematic review to explore the existing literature on cardiac comorbidities in McArdle disease. Results: Our systematic literature revision identified 7 case reports and 1 retrospective cohort study. The case reports described 7 GSD-V patients, averaging 54.3 years in age, mostly male (85.7%). Coronary artery disease was noted in 57.1% of cases, hypertrophic cardiomyopathy in 28.5%, severe aortic stenosis in 14.3%, and genetic dilated cardiomyopathy in one. In the retrospective cohort study, five out of 14 subjects (36%) had coronary artery disease. Discussion and conclusion: Despite McArdle disease primarily affecting skeletal muscle, cardiac involvement has been observed, especially coronary artery disease, the frequency of which was moreover found to be higher in McArdle patients than in the background population in a previous study from a European registry. Exaggerated cardiovascular responses during exercise and impaired glycolytic metabolism have been speculated as potential contributors. A comprehensive cardiological screening might be recommended for McArdle disease patients to detect and manage cardiac comorbidities. A multidisciplinary approach is crucial to effectively manage both neurological and cardiac aspects of the disease and improve patient outcomes. Further research is required to establish clearer pathophysiological links between McArdle disease and cardiac manifestations in order to clarify the existing findings. [ABSTRACT FROM AUTHOR]

We explored N6-methyladenosine (m6A) RNA methylation as one of the gene regulatory mechanisms in heart failure (HF) biology. Understanding the different physiological mechanisms will facilitate the prevention and individualized treatment of HF. The Gene Expression Omnibus (GEO) database served as the source of the data. In GSE116250, differential analysis between ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) and controls yielded differentially expressed m6A regulators. Differential analysis between HF and controls in GSE131296 identifies m6A-modified genes and then performs enrichment analysis. Protein–protein interaction (PPI) network analysis was performed for the differentially expressed ICM- or DCM-associated genes in GSE116250 and GSE55296, respectively. Finally, the diagnostic genes for ICM and DCM were predicted using receiver operating characteristic (ROC) curve. YTHDC1, HNRNPC and HNRNPA2B1 were significantly downregulated in GSE116250 in DCM and ICM compared with controls. A total of 195 genes were identified in GSE131296 as subject to m6A alteration. These genes may play a role in HF through the MAPK signaling pathway and p53 signaling pathway. PPI network analysis identified CCL5, CXCR4 and CCL2 as key genes for ICM and IL-6 as a key gene for DCM. Through ROC curves, we identified m6A-modified APLP1, KLF2 as potential diagnostic genes for ICM, and m6A-modified FGF7, FREM1 and C14orf132 as potential diagnostic genes for DCM. Our findings support m6A modifying mechanisms in HF etiology that contribute to the treatment of HF. Thus, our data suggest that m6A methylation may be an interesting target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Introduction: Myocarditis is an inflammatory disease of the myocardial layer of the heart that can be prone to dilation of chambers with presentation as heart failure secondary to dilated cardiomyopathy. Myocarditis can lead to remodeling and fibrosis that can affect the heart's relaxation-lusitropy and chronotropic function. The current techniques for identifying myocarditis, such as endomyocardial biopsy and imaging, are costly, and intrusive. The current literature aims to identify reliable, accurate, and prognostically educative biomarkers of myocarditis. Areas covered: This review covers the definition, clinical features, diagnostic markers, cardiac imaging, prognosis, and complications of myocarditis. PubMed, Embase, and the Cochrane data bank were searched from inception to 1 January 2024 for relevant articles. Expert opinion: By adopting these diagnostic and prognostic biomarkers, clinicians can have a better comprehension of the progression of the disease and provide early diagnosis and treatment for myocarditis. [ABSTRACT FROM AUTHOR]

Copyright of Archives of the Turkish Society of Cardiology / Türk Kardiyoloji Derneği Arşivi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Medizinische Klinik: Intensivmedizin & Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Integration of artificial intelligence enhances precision, yielding dependable evaluations of left ventricular volumes and ejection fraction despite image quality variations. Commercial software like HeartModelAI provides fully automated 3DE quantification, simplifying the measurement of left chamber volumes and ejection fraction. In this manuscript, we present a cross-sectional study to assess and compare the diagnostic accuracy of automated 3D echocardiography (HeartModelAI) to the standard Cardiac Magnetic Resonance Imaging in patients with dilated cardiomyopathy. Methods In this cross-sectional study, 30 patients with dilated cardiomyopathy referring to the Tehran Heart Center with cardiac magnetic resonance imaging and comprehensive 3D transthoracic echocardiography within 24 h were included. All 3D volume analysis was performed with fully automated quantification software (HeartModelAI) using 3D images of 2,3, and 4-chamber views at the end of systole and diastole. Results Excellent Inter- and Intra-observer correlation coefficient was reported for HeartModelAI software for all indexes. HeartModelAI displayed a remarkable correlation with cardiac magnetic resonance for left ventricular end-systolic volume index (r = 0.918 and r = 0.911); nevertheless, it underestimated left ventricular end-systolic volume index and left ventricular end-diastolic volume index. Conversely, ejection fraction, stroke volume, and left ventricular mass were overestimated. It was found that manual contour correction can enhance the accuracy of automated model estimations, particularly concerning EF in participants needing correction. Conclusion HeartModelAI software emerges as a rapid and viable imaging approach for evaluating the left ventricle’s structure and function. In our study, LV volumes assessed by HeartModelAI demonstrated strong correlations with cardiac magnetic resonance imaging.

Cui Xie,1 Yang Xiang,1 You Wu,1 Youen Zhang1,2 1Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 2Arteriosclerosis Cardiovascular Disease Clinical Medical Research Center of Hubei Province, Shiyan, Hubei, 442000, People’s Republic of ChinaCorrespondence: Youen Zhang, Email zye112@hotmail.comAbstract: We present a patient of a 46-year-old female patient was admitted to our hospital due to chest tightness and shortness of breath that lasted for over a month. Echocardiography revealed left-ventricle diameter (anteroposterior) of 54 mm, electrocardiogram showed sinus bradycardia, and QRS duration of 90 ms. The patient experienced no chest tightness or shortness of breath, and there was a marked improvement in exercise tolerance and quality of life after cardiac contractility modulation implantation.Keywords: heart failure, cardiac contractility modulation, dilated cardiomyopathy, ventricular remodeling

Abstract Dilated cardiomyopathy (DCM) is a myocardial disorder resulting in a substantial decline in cardiac function and potentially leading to heart failure. This research combines bioinformatics analysis with empirical validation to explore the roles and mechanisms of miR-214 in DCM. Using the DEseq2 R package, a total of 125 differentially expressed circulating miRNAs (DE c-miRNAs) and 784 DE genes (DEGs) were identified. Cross-analysis between target genes of DE c-miRNAs and DEGs identified 124 common genes, and protein-protein interaction analysis of common genes identified 11 hub genes. Twelve DE c-miRNAs were further verified by quantifying their levels in the serum of DCM patients and healthy individuals. miR-214 levels were significantly decreased in serum from DCM patients, positively correlated with left ventricular ejection fraction and left ventricular fractional shortening. Further analysis showed that miR-214 directly targets and negatively regulates phosphodiesterase 5 A (PDE5A). Elevated PDE5A expression reduced cGMP levels; however, using sildenafil, a PDE5A inhibitor, reversed this effect, substantiating the regulatory mechanism of miR-214 on cGMP via PDE5A. These results provide new potential targets for the diagnosis and treatment of DCM.

Abstract Background Stem cell therapy is the transplantation of human cells to aid the healing of damaged or wounded tissues and cells. Only a few small-scale trials have been conducted to investigate stem cell therapy for non-ischemic dilated cardiomyopathy (DCM). We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of stem cell therapy for DCM. Methods A comprehensive search of the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, and ProQuest was conducted from their inception to June 30, 2024, to access randomized controlled trials (RCTs) that were centered on stem cell therapy for DCM. The primary outcome was left ventricular ejection fraction (LVEF), and the secondary outcomes included left ventricular end-diastolic dimension (LVEDD), left ventricular end-diastolic volume (LVEDV), 6-min walk test (6MWT), NYHA functional classification, quality of life (QoL) such as Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-brain natriuretic peptide (NT-proBNP), and VO2 peak. Moreover, major adverse cardiovascular events (MACEs) were also recorded. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of the included RCTs, and the certainty of the evidence was assessed using the GRADE method. Sensitivity analysis was taken into consideration to determine the stability of the results. This review was registered with PROSPERO (CRD42024568912). Results Eleven RCTs involving 637 participants were included in the quantitative analysis. The results indicated that there was a significant increase in mean LVEF (MD = 4.84, 95% CI 3.25–6.42, P

Abstract D-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the hypercoagulable state of the body. The research aimed to analyze the value of D-dimer in the prognosis of patients with dilated cardiomyopathy (DCM). Patients admitted to our center for the first time with DCM were enrolled consecutively. The clinical characteristics variables were obtained from the electronic medical record system, and the prognostic information was obtained using telephone return visits and a review of repeated hospitalization records. Univariate and multivariate Cox regression was used to explore the association of D-dimer with all-cause mortality. Smooth curve fitting, threshold saturation effect analysis, and subgroup analysis were performed. Ultimately, 534 patients were included. After a follow-up of the enrolled patients, 485 patients obtained prognostic information, of which 159 died from all causes, and the main cause of death was heart failure (89/159), the sudden death accounted for about 17%. The independent positive association between D-dimer and all-cause mortality remained unchanged in both unadjusted and adjusted Cox regression models. In the fully adjusted model, each standard deviation increase in D-dimer was associated with a 14% increase in all-cause mortality (HR = 1.14; 95% CI: 1.02 ~ 1.27; P

Left ventricular thrombus (LVT) is a severe consequence that typically follows acute myocardial infarction (MI) and can occur in nonischemic cardiomyopathies. In patients who have experienced an ST-segment elevation acute myocardial infarction (STEMI), LVT is seen up to 15% of the time; for patients without an ischemic cardiomyopathy, it is only 2% to 36% of the time. According to Virchow's triad, the cornerstone of LVT formation includes endothelial injury, blood stasis, and hypercoagulability. However, LVT increases morbidity and mortality in patients with both ischemic and nonischemic cardiomyopathies by increasing the risk of stroke or systemic embolism. Studies on nonischemic etiology are limited, and the majority of LVT case series concentrate on ischemic cardiomyopathies. We present this case with the nonischemic cardiomyopathies caused by LVT. Specifically, the patient underwent coronary artery assessment using photon-counting computed tomography, which is among the most advanced systems worldwide.