Indications and clinical impact of genetic testing for cardiac diseases have increased significantly over the past years. The aim of this physician-based EHRA survey was to assess current clinical practice and access to genetic testing for cardiac diseases across ESC countries and to evaluate adherence to the 2022 EHRA/HRS/APHRS/LAHRS Expert Consensus Statement on genetic testing. An online questionnaire composed of 28 questions was submitted to the EHRA Research Network and European Reference Network GUARD-Heart healthcare partners and promoted via dedicated social media channels. There were 357 respondents from 69 countries, 40% working in a hospital setting with a cardiac genetic service and/or a dedicated clinic focusing on inherited cardiac diseases and 27% with an onsite genetic laboratory. No genetic testing or low annual rate (<10/y) was declared by 39% of respondents. The majority of respondents (78%) declared issues or limitations to genetic testing access in their clinical practice. The main reasons for not providing or limited access to genetic testing were no availability of dedicated unit or genetic laboratory (35%) or reimbursement issues (25%). The most frequently reported indication for genetic testing was diagnostic purpose (55%). Most respondents (92%) declared offering genetic testing preceded by genetic counselling and 42% regular multidisciplinary evaluations for patients with cardiac genetic diseases. The perceived value of genetic testing in the diagnostic, prognostic, and therapeutic assessment was variable (67%, 39%, and 29%, respectively) and primarily based on the specific inherited disease. The majority of respondents recommended cascade genetic testing for the first-degree family members in case of pathogenic/likely pathogenic (P/LP) variant in the proband. This survey highlights a significant heterogeneity of genetic testing access and provision and issues attributable to the availability of dedicated unit/genetic laboratory and reimbursement. However, adequate adherence to indications in the current recommendations for genetic testing in patients with cardiac diseases was observed.

Objective: To investigate the value of myocardium scar area in predicting adverse cardiovascular events (MACEs) after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM). Methods: The first part of this study was a retrospective study. Patients diagnosed with ICM and undergoing CABG surgery at Beijing Anzhen Hospital, Capital Medical University from January 2017 to December 2022 were enrolled as the discovery cohort. All patients underwent cardiac magnetic resonance-late gadolinium enhancement (CMR-LGE) before surgery. According to the occurrence of postoperative MACEs, the patients were divided into MACEs group and MACEs-free group. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. The primary endpoint was postoperative MACEs. Univariate and multifactor regression analyses were used to analyze the risk factors for MACEs. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy and optimal cut-off value of myocardial scar area for endpoint events. The second part of this study was a prospective study. Patients with ICM who received CABG at Beijing Anzhen Hospital, Capital Medical University from January 2023 to June 2023 were enrolled as a validation cohort, and were divided into MACEs group and MACEs-free group according to whether MACEs occurred after surgery. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. Verify the reliability of the cut-off value obtained by ROC curve in the validation cohort. Results: A total of 120 patients with ICM (30 patients in MACEs group and 90 patients in MACEs-free group), aged (61.6±8.7) years, including 93 males, were included in the discovery cohort. A total of 22 ICM patients (5 patients in MACEs group and 17 patients in MACEs-free group), aged (59.5±8.2) years, including 18 males, were included in the validation cohort. Multivariate Cox regression showed that myocardial scar area (HR=1.258, 95%CI 1.096-1.444, P=0.001) was an independent risk factor for the primary endpoint event. The area under ROC curve of myocardial scar area for predicting postoperative MACEs was 0.90 (95%CI 0.83-0.95), and myocardial scar area≥36.0% was the optimal cut-off value for predicting postoperative MACEs, and its sensitivity, specificity and accuracy were 96.7%, 72.2% and 78.3%, respectively. In the validation cohort, the sensitivity, specificity and accuracy of myocardial scar area in predicting postoperative MACEs in patients with ICM after CABG were 80.0%, 82.4% and 81.8%, respectively. Conclusion: Myocardial scar area is an independent risk factor for MACEs after CABG in patients with ICM, and myocardial scar area≥36.0% is the optimal cut-off value for predicting MACEs after CABG. Myocardial scar area can help to identify patients at high risk of surgery and provide a basis for risk stratification of patients.
目的： 探讨心肌瘢痕面积预测缺血性心肌病患者冠状动脉旁路移植（CABG）术后发生不良心血管事件（MACEs）的价值。 方法： 本研究第1部分为回顾性研究，入选2017年1月至2022年12月在首都医科大学附属北京安贞医院诊断为缺血性心肌病并接受CABG手术治疗的患者作为发现队列，入选患者术前均行心脏磁共振-延迟钆强化检查，根据术后是否发生MACEs分为MACEs组和无MACEs组。收集并比较两组患者术前临床及影像资料、术中及术后相关资料。主要终点为术后发生MACEs。采用单因素和多因素回归分析影响缺血性心肌病患者CABG术后发生MACEs的相关危险因素，构建受试者工作特征（ROC）曲线，评估心肌瘢痕面积对终点事件的预测效能和最佳临界值。本研究第2部分为前瞻性研究，入选2023年1至6月在首都医科大学附属北京安贞医院接受CABG的缺血性心肌病患者作为验证队列，根据术后是否发生MACEs分为MACEs组和无MACEs组，收集并比较两组患者术前临床及影像资料、术中及术后相关资料。在验证队列中验证ROC曲线获得界值的可靠性。 结果： 发现队列共纳入120例缺血性心肌病患者（MACEs组30例，无MACEs组90例），年龄（61.6±8.7）岁，男性93例。验证队列共纳入22例缺血性心肌病患者（MACEs组5例，无MACEs组17例），年龄（59.5±8.2）岁，男性18例。多因素Cox回归示心肌瘢痕面积（HR=1.258，95%CI：1.096~1.444，P=0.001）是主要终点事件的独立危险因素。心肌瘢痕面积预测术后发生MACEs的ROC曲线下面积为0.90（95%CI：0.83~0.95），心肌瘢痕面积≥36.0%是预测术后发生MACEs的最佳临界值，其敏感度、特异度和准确度分别为96.7%、72.2%和78.3%。在验证队列中，心肌瘢痕面积预测缺血性心肌病患者CABG术后发生MACEs的敏感度、特异度和准确度分别为 80.0%，82.4%和81.8%。 结论： 心肌瘢痕面积是缺血性心肌病患者CABG术后是否发生MACEs的独立危险因素，心肌瘢痕面积≥36.0%是预测CABG术后是否发生MACEs的最佳临界值。该指标有助于识别手术高危患者，为患者危险分层提供依据。.

A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin\'s lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge.

OBJECTIVE: To describe the epidemiological, clinical, paraclinical, therapeutic and evolutionary characteristics of of peripartum cardiomyopathy (PPCM) in the internal medicine department of the Zinder National Hospital (ZNH).
METHODS: This was a descriptive cross-sectional study carried out from 2018 to 2022 at the ZNH Department of Internal Medicine. Included were all patients admitted for PPCM who met National Heart Blood and Lung Institute criteria. The data collected was analyzed using Excel and EPI INFO v7.
RESULTS: We had collected 100 cases of PPCM out of a total of 8706 hospitalized patients, i.e. a hospital prevalence of 1.14%. The mean age of the patients was 27.9 years ± 7.4 [17-45]. The majority of patients were from underprivileged social strata (n=64). The risk factors for PMPC found were essentially hot bath (n=66), home birth (n=40), natron porridge (n=35) and multiparity (n=57). Cardiac symptomatology appeared postpartum in 56% of patients. Dyspnea was the main symptom in 98% of cases. The physical signs were dominated by the functional systolic murmur (66%). Three quarters (75%) of the patients had congestive heart failure. Electrocardiographic signs were dominated by left ventricular hypertrophy (n=65). Cardiomegaly was present in 94% of patients. Left ventricular ejection fraction was altered in all patients. Impaired renal function was found in 31% of patients. Management was based on a low-sodium diet tripod, diuretics and converting enzyme inhibitors. Two cases of death were recorded.
CONCLUSIONS: PPCM is common in the Zinder region. It affects young women with several risk factors and is revealed by signs of congestive heart failure. For a better understanding of this still poorly elucidated condition, it is necessary to pursue research efforts.

Cardiomyopathy is the predominant defect in Barth syndrome (BTHS) and is caused by a mutation of the X-linked Tafazzin (TAZ) gene, which encodes an enzyme responsible for remodeling mitochondrial cardiolipin. Despite the known importance of mitochondrial dysfunction in BTHS, how specific TAZ mutations cause diverse BTHS heart phenotypes remains poorly understood. We generated a patient-tailored CRISPR/Cas9 knock-in mouse allele (TazPM) that phenocopies BTHS clinical traits. As TazPM males express a stable mutant protein, we assessed cardiac metabolic dysfunction and mitochondrial changes and identified temporally altered cardioprotective signaling effectors. Specifically, juvenile TazPM males exhibit mild left ventricular dilation in systole but have unaltered fatty acid/amino acid metabolism and normal adenosine triphosphate (ATP). This occurs in concert with a hyperactive p53 pathway, elevation of cardioprotective antioxidant pathways, and induced autophagy-mediated early senescence in juvenile TazPM hearts. However, adult TazPM males exhibit chronic heart failure with reduced growth and ejection fraction, cardiac fibrosis, reduced ATP, and suppressed fatty acid/amino acid metabolism. This biphasic changeover from a mild-to-severe heart phenotype coincides with p53 suppression, downregulation of cardioprotective antioxidant pathways, and the onset of terminal senescence in adult TazPM hearts. Herein, we report a BTHS genotype/phenotype correlation and reveal that absent Taz acyltransferase function is sufficient to drive progressive cardiomyopathy.

BACKGROUND: The adverse effects of a Western diet on obesity and diabetes among reproductive-aged women pose a significant threat to the cardiovascular health of their offspring. Given the crucial role of glutathione metabolism and glutathione-related antioxidant defense systems in cardiovascular diseases through scavenging ROS and maintaining redox homeostasis, further exploration of their specific influence is imperative to develop therapeutic strategies for cardiomyopathy induced by a maternal Western diet.
METHODS: We developed a prenatal maternal Western diet exposure model in C57/B6 mice to investigate cardiac morphology and function through histological analysis and echocardiography. RNA sequencing and analysis were utilized to elucidate the mechanisms underlying the impact of a maternal Western diet and N-acetylcysteine treatment on cardiomyopathy. Additionally, ELISAs, transmission electron microscopy, and flow cytometry were employed to assess the antioxidant defense system and mitochondrial ROS levels in progenitor cardiomyocytes.
RESULTS: N-acetylcysteine significantly mitigated cardiomyocyte hypertrophy, myocardial interstitial fibrosis, collagen type I accumulation, and left ventricular remodeling induced by a maternal Western diet, particularly in male offspring. Furthermore, N-acetylcysteine reversed the increase in apoptosis and the increase in the β/α-MyHC ratio in the myocardium of offspring that results from a maternal Western diet. RNA sequencing and GSEA revealed that the beneficial effects of N-acetylcysteine were linked to its ability to modulate oxidative phosphorylation pathways. Additionally, N-acetylcysteine treatment during pregnancy can markedly elevate glutathione levels, augment glutathione peroxidase (GPx) activity, and mitigate the accumulation of mitochondrial ROS caused by a maternal Western diet.
CONCLUSIONS: N-acetylcysteine mitigated cardiomyopathy induced by a maternal Western diet by bolstering glutathione synthesis and enhancing GPx activity, thereby scavenging mitochondrial ROS and modulating oxidative phosphorylation pathways.

Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac disorder characterized by the gradual replacement of cardiomyocytes with fibrous and adipose tissue, leading to ventricular wall thinning, chamber dilation, arrhythmias, and sudden cardiac death. Despite advances in treatment, disease management remains challenging. Animal models, particularly mice and zebrafish, have become invaluable tools for understanding AC\'s pathophysiology and testing potential therapies. Mice models, although useful for scientific research, cannot fully replicate the complexity of the human AC. However, they have provided valuable insights into gene involvement, signalling pathways, and disease progression. Zebrafish offer a promising alternative to mammalian models, despite the phylogenetic distance, due to their economic and genetic advantages. By combining animal models with in vitro studies, researchers can comprehensively understand AC, paving the way for more effective treatments and interventions for patients and improving their quality of life and prognosis.

UNASSIGNED: The study aimed to investigate the pathogenesis of sepsis-induced cardiomyopathy, a leading cause of mortality in septic patients. Transcriptome data from cecal ligation and puncture-induced septic mice were analyzed at different time points (24, 48, and 72 hours) using GSE171546 data. Through weighted gene co-expression network analysis, time series, and differential expression analyses, key time-series differentially expressed genes were identified. In addition, single-cell sequencing data (GSE207363) were used for both differential and pseudotime analyses to pinpoint differentially expressed genes specific to endothelial cells. The study highlighted Spock2, S100a9, S100a8, and Xdh as differential genes specific to endothelial cells in a time-dependent manner. Immunofluorescence validation confirmed the increased expression of SPOCK2 in the endothelial cells of cecal ligation and puncture-induced septic mice. Furthermore, in vitrostudies showed that deletion of Spock2 significantly increased LPS-induced apoptosis and necrosis in human umbilical vein endothelial cells. In conclusion, SPOCK2 expression was increased in septic cardiac endothelial cells and LPS-induced human umbilical vein endothelial cells and may play a protective role.

UNASSIGNED: Sepsis is characterized as a systemic inflammatory response syndrome resulting from infection, leading to the development of multiple organ dysfunction syndrome. Sepsis-induced cardiomyopathy (SICM) is a frequently encountered condition in clinical settings. Mesenchymal stem cells (MSCs) possess inherent immunomodulatory and anti-inflammatory attributes, rendering them a promising therapeutic approach to reestablish the equilibrium between anti-inflammatory and proinflammatory systems in septic patients. Consequently, MSCs are frequently employed in clinical investigations. In this study, the author established a mouse SICM model through cecal ligation and puncture and administered MSCs through the tail vein. Following successful modeling, the myocardial function and histopathological changes were detected by echocardiography, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, enzyme-linked immunosorbent assay,, and other experiments. As a result, MSCs demonstrated the ability to enhance myocardial function, promote cardiac tissue repair, suppress inflammatory response, reduce levels of myocardial injury markers, and mitigate oxidative stress. In addition, transcriptome and proteome analyses were conducted. Through differential expression analysis, functional enrichment analysis, and multiomics association analysis, it was revealed that the transcriptional factors nuclear receptor subfamily 1 (NR1D2) and target gene lipocalin 2 (LCN2) played key roles in mediating the effects of MSCs on SICM. JASPAR website and ChIP-qPCR experiment were used to predict and confirm the targeting relationship between them. Subsequent cell coculture experiments and a series of experiments confirmed that MSCs attenuated cardiomyocyte injury by downregulating the expression of NR1D2 and its downstream target gene LCN2. In conclusion, MSCs alleviate mice SICM through inhibiting NR1D2/LCN2 pathway.

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