Structural Heart Abnormalities Research Articles

Aspirin reduces Ponatinib-induced cardiovascular toxic phenotypes and death in zebrafish

BackgroundPonatinib (Iclusig) is an oral tyrosine kinase BCR-ABL inhibitor for treating patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) who are resistant to the therapies with other tyrosine kinase inhibitors. However, adverse cardiovascular events caused by Ponatinib are a serious issue that affects patients' survival rates. Thus, it is necessary to search for candidate drugs to reduce the cardiovascular toxicity of Ponatinib. PurposeTo investigate the effects of Aspirin on Ponatinib-induced cardiovascular toxicity in zebrafish. MethodsAB strain of wild type zebrafish (Danio rerio), Tg (cmlc2: GFP) transgenic zebrafish, and Tg (gata1: dsRed) transgenic zebrafish were used as in vivo models to assess survival, blood flow, cardiac morphology, and function. Thrombus formation was detected using O-dianisidine staining. The transcriptome of zebrafish larvae treated with Ponatinib was assessed using RNA sequencing. ResultsPonatinib not only reduced survival rate but also caused cardiovascular toxic events such as pericardial edema, abnormal heart structure, low heart rate, and thrombosis. In addition, whole-body transcriptome analysis showed that Ponatinib up-regulated the expression of cyclooxygenase-1 (COX-1). Compared with other antithrombotic drugs, a COX-1 inhibitor Aspirin more effectively reduced ponatinib-induced cardiovascular toxicity events and improved the survival rate of zebrafish larvae. ConclusionOur findings suggest that Aspirin exhibits the potential to reduce Ponatinib-induced cardiovascular toxicity.

Unraveling the rationale and conducting a comprehensive assessment of AdipoRon (adiponectin receptor agonist) as a candidate drug for diabetic nephropathy and cardiomyopathy prevention and intervention-a systematic review.

Type 2 diabetes mellitus (T2DM) is a widespread chronic disease characterized by persistent hyperglycemia, leading to severe complications such as diabetic cardiomyopathy and nephropathy, significantly affecting patient health and quality of life. The complex mechanisms underlying these complications include chronic inflammation, oxidative stress, and metabolic dysregulation. Diabetic cardiomyopathy, marked by structural and functional heart abnormalities, and diabetic nephropathy, characterized by progressive kidney damage, are major contributors to the increased morbidity and mortality associated with T2DM. AdipoRon, a synthetic adiponectin receptor agonist, has shown potential in preclinical studies for mimicking the beneficial effects of endogenous adiponectin, reducing inflammation and oxidative stress, and improving lipid metabolism and mitochondrial function. This systematic review evaluates the therapeutic potential of AdipoRon, focusing on its impact on diabetic cardiomyopathy and nephropathy. Through a comprehensive literature search and analysis, we highlight AdipoRon's role in ameliorating cardiovascular and renal complications in various animal models and cellular systems. The findings underscore the urgent need for translational clinical studies to validate AdipoRon's efficacy and safety in human populations, aiming to advance this promising therapeutic approach from experimental models to clinical application, potentially offering new hope for improved management of diabetic complications.

Comparative Analysis of Decellularization Methods on Bovine Pericardium Scaffolds for Cardiac Tissue Engineering

Background: Congenital heart disease (CHD) involves structural heart abnormalities present since fetal development. Corrective surgery is often the ideal treatment, utilizing implants or scaffolds for tissue repair. However, repeated surgeries may be required due to declining function of grafts, leading to increased healthcare costs. Bovine pericardium is a promising scaffold material for tissue engineering due to its composition of collagen, glycosaminoglycans (GAGs), and proteoglycans. This study aimed to compare the effectiveness of bovine pericardium scaffolds using different decellularization methods: sodium dodecyl sulfate (SDS) and hydrogen peroxide (H2O2). Methods: An experimental study was conducted with bovine pericardium scaffolds divided into control and treatment groups. The treatment groups used decellularization with SDS (0.5%, 1%) and H2O2 (3%). Scaffolds were evaluated for tensile strength, strain, Young's modulus, and histological properties, including nuclear density, collagen density, and GAG content. Data were analyzed using statistical methods to compare the effectiveness of each decellularization technique. Results: Histological analysis revealed that all decellularized samples showed no nuclear density, while control samples displayed light nuclear density. Collagen density was light in scaffolds treated with SDS 0.5% and H2O2, while SDS 1% resulted in no collagen presence. GAG density was absent in SDS-treated samples and minimal in H2O2-treated samples. Tensile strength was highest in H2O2-treated scaffolds (24.01 N) and lowest in SDS 0.5%. SDS 1% showed the greatest tensile strain, while H2O2-treated scaffolds had the highest stiffness. Conclusion: The decellularization methods effectively removed cellular components from the bovine pericardium scaffolds, with varying impacts on the extracellular matrix. SDS 1% provided the most elastic scaffold, while H2O2 preserved tensile strength and stiffness. These findings suggest that the choice of decellularization method can be optimized based on the desired mechanical properties of the scaffold for cardiac tissue engineering applications. Further research is needed to evaluate the long-term performance of these scaffolds in clinical settings.

Recent Advances in the Management of Non-rheumatic Atrial Fibrillation: A Comprehensive Review.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia characterized by irregular atrial electrical activity, posing significant challenges to patient management and healthcare systems worldwide. Non-rheumatic AF, distinct from AF due to rheumatic heart disease, encompasses a spectrum of etiologies, including hypertension, coronary artery disease, and structural heart abnormalities. This review examines the latest advancements in managing non-rheumatic AF, encompassing diagnostic approaches, pharmacological therapies, and innovative non-pharmacological interventions. Diagnostic strategies ranging from traditional electrocardiography to advanced imaging modalities are explored alongside emerging biomarkers and wearable technologies facilitating early detection and management. Pharmacological management options, including novel anticoagulants and rhythm control agents, are evaluated in light of current guidelines and recent clinical trials. Non-pharmacological interventions, such as catheter ablation and device-based therapies, are discussed regarding their evolving techniques and outcomes. Special considerations for diverse patient populations, including elderly individuals and athletes, are addressed, emphasizing personalized approaches to optimize therapeutic outcomes. The review concludes with insights into future directions for AF management, highlighting promising avenues in gene therapy, regenerative medicine, and precision medicine approaches. By synthesizing recent research findings and clinical innovations, this review provides a comprehensive overview of the dynamic landscape of non-rheumatic AF management, offering insights for clinicians, researchers, and healthcare stakeholders.

Effect of obstructive sleep apnea on the severity of acute coronary syndrome

Objective: To investigate the effects of obstructive sleep apnea (OSA) on myocardial damage, coronary multi-vessel lesion and postoperative indexes in patients with acute coronary syndrome(ACS). Methods: The patients, admitted to the Second Affiliated Hospital of Soochow University from September 2022 to October 2023 due to chest tightness and pain, diagnosed with ACS and accompanied by emergency/elective percutaneous coronary intervention(PCI)at, were prospectively enrolled. Portable sleep monitor was used to monitor after stabilization of condition(postoperative day 2±1). The patients were divided into the OSA group (AHI≥15/h) and the control group (AHI<15/h) according to apnea-hypopnea index (AHI). The hematologic indices, echocardiographic parameters, coronary vascular scores and postoperative indicators between the groups were compared. Binary logistic regression model was used to analyze the risk factors for muti-vessel lesion in patients with ACS. Results: One hundred and four ACS patients who met the inclusion criteria were ultimately included, including 85 males (81.7%) and 19 females (18.3%), aged (57.3±10.8) years, of whom 48.1% (50/104) were complicated with OSA. Body mass index (BMI), prevalence of hypertension and diabetes, triglyceride (TG), glycosylated hemoglobin A1c (HbA1c) and D-dimer in the OSA group were higher than those in the control group (P<0.05). There were statistically significant differences in sleep parameters between the two groups (P<0.05). The patients in the OSA group exhibited higher troponin T (cTnT) [M(Q1,Q3),54.0 (9.3,343.8) ng/L vs 15.0 (7.8,38.8) ng/L, P<0.05], larger left atrial internal diameters [41.4 (39.3,45.2) mm vs 40.2 (37.1,42.0) mm, P<0.05], more diseased vessels [2 (1, 3) vs 1 (1, 2), P<0.001], a higher percentage of muti-vessel lesion[60.0%(30/50)vs 29.6%(16/54),P<0.05], and a higher incidence of cardiovascular complications during hospitalization[10.0%(5/50)vs 0(0/54), P=0.017]. The results of binary logistic regression analysis suggested that after adjusting for confounders, AHI (OR=1.035, 95%CI: 1.008-1.063, P=0.011) was independently associated with the development of muti-vessel lesion in patients with ACS. Conclusions: ACS patients with OSA suffer more severe myocardial damage, are more likely to develop structural abnormalities of left heart and multi-vessel lesion, and have a higher incidence of postoperative complications. High AHI is a risk factor for multi-vessel lesion in ACS patients.

Comparison of Age-Related Decline and Behavioral Validity in C57BL/6 and CB6F1 Mice.

Variability in physical resilience to aging prompts a comprehensive examination of underlying mechanisms across organs and individuals. We conducted a detailed exploration of behavioral and physiological differences between C57BL/6 and CB6F1 mice across various age groups. In behavioral assays, B6 mice displayed superior performance in rotarod tasks but higher anxiety while CB6F1 mice exhibited a decline in short-term memory with age. Grip strength, long-term memory, and voluntary wheel running declined similarly with age in both strains. Examining physiological phenotypes, B6 mice exhibited lower body fat percentages across ages compared to CB6F1 mice, though cataract severity worsened with age in both strains. Analysis of cardiac functions revealed differences between strains, with worsening left ventricular hypertrophy and structural heart abnormalities with age in CB6F1 mice along with higher blood pressure than B6. Lesion scores showed an age-related increase in heart, kidney, and liver lesions in both strains, while lung lesions worsened with age only in CB6F1 mice. This study underscores the validity of behavioral assays and geropathology assessment in reflecting age-related decline and emphasizes the importance of considering strain specificity when using mouse models to study human aging.

Cardiac arrhythmia in individuals with steroid sulfatase deficiency (X-linked ichthyosis): candidate anatomical and biochemical pathways.

Circulating steroids, including sex hormones, can affect cardiac development and function. In mammals, steroid sulfatase (STS) is the enzyme solely responsible for cleaving sulfate groups from various steroid molecules, thereby altering their activity and water solubility. Recent studies have indicated that Xp22.31 genetic deletions encompassing STS (associated with the rare dermatological condition X-linked ichthyosis), and common variants within the STS gene, are associated with a markedly elevated risk of cardiac arrhythmias, notably atrial fibrillation/flutter. Here, we consider emerging basic science and clinical findings which implicate structural heart abnormalities (notably septal defects) as a mediator of this heightened risk, and propose candidate cellular and biochemical mechanisms. Finally, we consider how the biological link between STS activity and heart structure/function might be investigated further and the clinical implications of work in this area.

Determining the recurrence rate of premature ventricular complexes and idiopathic ventricular tachycardia after radiofrequency catheter ablation with the help of designing a machine-learning model

Ventricular arrhythmias increase cardiovascular morbidity and mortality. Recurrent PVCs and IVT are generally considered benign in the absence of structural heart abnormalities. Artificial intelligence is a rapidly growing field. In recent years, medical professionals have shown great interest in the potential use of ML, an integral part of AI, in various disciplines, including diagnostic applications, decision-making, prognostic stratification, and solving complex pathophysiological aspects of diseases from these data at extraordinary complexity, scale, and acquisition rate. The aim of this study was to design an ML model to predict the probability of PVC and IVT recurrence after RF ablation.Data of patients were collected and manipulated using traditional analysis and various artificial intelligence models, namely MLP, Gradient Boosting Machines, Random Forest, and Logistic Regression.Hypertension, male sex, and the use of non-irrigate catheters were associated with less freedom from arrhythmia. All these results were obtained through traditional analytic methods, and according to AI, none of the variables had a clear effect on the recurrence of arrhythmia.Each AI model presents unique strengths and weaknesses, and further optimization and fine-tuning of these models are necessary to increase their clinical utility. By expanding the dataset, improved predictions can be fostered to ultimately increase the clinical utility of AI in predicting PVC erosion outcomes.

Экстрасистолия у пациентов с синдромом дисплазии соединительной ткани

The ventricular heart rhythm disturbances occurring in individuals with no structural heart abnormality are a pressing issue not only due to their significance, but also due to the lack of clear approaches to treatment of such patients. In actual clinical practice, the physician faces a number of unresolved problems related to both causes and treatment of premature heath beats. This issue requires further research aimed to determine the optimal tactics of management for the specific patient with premature heath beats.

Clinical features and risk factors for postoperative recurrence in patients with Cushing's syndrome of different etiologies

The clinical characteristics of Cushing’s syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.

Understanding the Risk Factors for Cardiac Arrest in Young Adults: A Systematic Review

Introduction: Cardiac arrest, once largely associated with older individuals, is increasingly affecting young adults, necessitating a deeper understanding of its risk factors in this demographic. Aim: To identify and analyse relevant literature to uncover the risk factors contributing to cardiac arrest among young adults. Materials and Methods: A comprehensive search of databases using specific keywords related to cardiac arrest, risk factors, and young adults was conducted. Out of 573 studies initially identified, 245 duplicates were removed, and 328 were screened based on eligibility criteria. After further assessment, 123 records were rejected, leaving 205 full-text papers for review. Ultimately, eight studies were included in the qualitative analysis. Results: The review highlighted modifiable lifestyle factors, cardiovascular conditions, genetic predisposition and environmental influences as significant contributors to cardiac arrest risk in young adults. Specifically, obesity, smoking, physical inactivity, and substance abuse emerged as prominent modifiable risk factors. Predisposing factors such as inherited cardiac conditions, structural heart abnormalities, and acquired cardiac disorders were also identified. Environmental factors, including air pollution and socioeconomic status, were found to play a role in shaping the risk profile of young adults. Conclusion: The review concludes by emphasising the importance of addressing modifiable risk factors and promoting cardiovascular health awareness to mitigate the incidence of cardiac arrest in young adults. By addressing these factors, healthcare providers can work towards reducing the burden of cardiac arrest and improving outcomes in this vulnerable population. The present systematic review provides valuable insights into the risk factors contributing to cardiac arrest in young adults and lays a foundation for evidence-based preventive measures.

Human Genetics of Cardiac Arrhythmias.

Inherited forms of cardiac arrhythmias mostly are rare diseases (prevalence <1:2000) and considered to be either "primary electrical heart disorders" due to the absence of structural heart abnormalities or "cardiac ion channel disorders" due to the myocellular structures involved. Precise knowledge of the electrocardiographic features of these diseases and their genetic classification will enable early disease recognition and prevention of cardiac events including sudden cardiac death.The genetic background of these diseases is complex and heterogeneous. In addition to the predominant "private character" of a mutation in each family, locus heterogeneity involving many ion channel genes for the same familial arrhythmia syndrome is typical. Founder pathogenic variants or mutational hot spots are uncommon. Moreover, phenotypes may vary and overlap even within the same family and mutation carriers. For the majority of arrhythmias, the clinical phenotype of an ion channel mutation is restricted to cardiac tissue, and therefore, the disease is nonsyndromic.Recent and innovative methods of parallel DNA analysis (so-called next-generation sequencing, NGS) will enhance further mutation and other variant detection as well as arrhythmia gene identification.

Contribution of Three-Dimensional Transesophageal Echocardiography in the Assessment of Atrial Septal Defects (ASD)

The article examines the contribution of real-time three-dimensional transesophageal echocardiography (3D TEE) in the assessment of ostium secundum atrial septal defects (ASD) in adults. 3D TEE provides a precise and comprehensive view of cardiac anatomy, enabling the evaluation of size, shape, and border quality of the ASD. In a series of 27 cases, 3D TEE demonstrated a strong correlation between 3D-measured ASD parameters and the size of the closure device required. This technique is crucial for accurate pre-interventional evaluation, enhancing the success and safety of percutaneous or surgical interventions for ostium secundum ASD. Three-dimensional transesophageal echocardiography represents a significant advancement in cardiovascular imaging for complex structural heart abnormalities.

The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress-Role of New Drugs, Flozins.

Heart failure (HF) is a multifactorial clinical syndrome involving many complex processes. The causes may be related to abnormal heart structure and/or function. Changes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and the natriuretic peptide system are important in the pathophysiology of HF. Dysregulation or overexpression of these processes leads to changes in cardiac preload and afterload, changes in the vascular system, peripheral vascular dysfunction and remodeling, and endothelial dysfunction. One of the important factors responsible for the development of heart failure at the cellular level is oxidative stress. This condition leads to deleterious cellular effects as increased levels of free radicals gradually disrupt the state of equilibrium, and, as a consequence, the internal antioxidant defense system is damaged. This review focuses on pharmacotherapy for chronic heart failure with regard to oxidation-reduction metabolism, with special attention paid to the latest group of drugs, SGLT2 inhibitors-an integral part of HF treatment. These drugs have been shown to have beneficial effects by protecting the antioxidant system at the cellular level.

Noonan syndrome: rhGH treatment and PTPN11 mutation.

To analyze the clinical data and genetic characteristics of Noonan syndrome, both the effect and side effects of recombinant human growth hormone (rhGH) treatment. We collected clinical data from 8 children with Noonan syndrome diagnosed from November 2017 to June 2021. The diagnosis was clarified by exome second-generation sequencing and parental PCR-NGS validation and interpretation of the preceding evidence, and growth hormone therapy was administered. Of the cases, four males and four females were seen for slow height growth and the median age at diagnosis was 8 years 7 months (1 year 7 months to 12 years 6 months). Here, 7 children were treated with rhGH. Compared to the pre-treatment period, the growth rate increased after rhGH treatment [3.7 ± 0.5 cm/year before treatment and 8.0 ± 1.0 cm/year after treatment, p < 0.01], with the maximum growth rate between 3 and 6 months of treatment and decreasing with the duration of treatment thereafter. The growth hormone treatment was discontinued and the orthopedic consultation was ordered with regular follow-up, which was considered to be related to the PTPN11 mutation. Noonan syndrome is characterized by slow growth, short stature, mental retardation, peculiar facial features, structural heart abnormalities and abnormal bone metabolism. and osteochondroma was found after case 2 rhGH treatment. Genetic examination is mostly caused by PTPN11 mutation. It is recommended to pay attention to bone metabolism abnormalities before growth hormone treatment, especially in children with PTPN11 mutations.

Automated T1 and T2 mapping segmentation on cardiovascular magnetic resonance imaging using deep learning.

Structural and functional heart abnormalities can be examined non-invasively with cardiac magnetic resonance imaging (CMR). Thanks to the development of MR devices, diagnostic scans can capture more and more relevant information about possible heart diseases. T1 and T2 mapping are such novel technology, providing tissue specific information even without the administration of contrast material. Artificial intelligence solutions based on deep learning have demonstrated state-of-the-art results in many application areas, including medical imaging. More specifically, automated tools applied at cine sequences have revolutionized volumetric CMR reporting in the past five years. Applying deep learning models to T1 and T2 mapping images can similarly improve the efficiency of post-processing pipelines and consequently facilitate diagnostic processes. In this paper, we introduce a deep learning model for myocardium segmentation trained on over 7,000 raw CMR images from 262 subjects of heterogeneous disease etiology. The data were labeled by three experts. As part of the evaluation, Dice score and Hausdorff distance among experts is calculated, and the expert consensus is compared with the model's predictions. Our deep learning method achieves 86% mean Dice score, while contours provided by three experts on the same data show 90% mean Dice score. The method's accuracy is consistent across epicardial and endocardial contours, and on basal, midventricular slices, with only 5% lower results on apical slices, which are often challenging even for experts. We trained and evaluated a deep learning based segmentation model on 262 heterogeneous CMR cases. Applying deep neural networks to T1 and T2 mapping could similarly improve diagnostic practices. Using the fine details of T1 and T2 mapping images and high-quality labels, the objective of this research is to approach human segmentation accuracy with deep learning.

The Efficacy of Ice Cubes in Patients with Heart Failure

ABSTRACT Heart failure (HF) as abnormal heart structure and function increases neurohormonal response and sympathetic activity resulting in a renin-angiotensin-aldosterone system (RAAS). Congestion as the result of RAAS, increase signs and symptoms of HF including thirst. Fluid restriction as the recommendation to reduce congestion is increased thirst in patients with HF. The purpose of this study is to evaluate the effectiveness of ice cubes on thirst intensity, thirst distress, hospitalization, and mortality in patients with HF. This research implied quasi-experimental research, with one group pre and post-design. The sample recruited was 13 samples from outpatients and inpatients of a general hospital in Jakarta. Diagnosis must be HF by the cardiologist, over 18 years old, and in stable condition. Thirst intensity was measured by a visual analog score of 0-100, thirst distress was measured by thirst distress scale-heart failure, hospitalization, and mortality were measured by asking the patients or the family. There is a significant difference in thirst intensity before and after intervention (p &lt; 0.05); and there is also a significant difference in thirst distress before and after intervention (p &lt; 0.05). However, no difference in hospitalization and mortality after the ice cubes intervention. It is important for healthcare professionals or families to apply ice cubes sucking in patients with HF. The inpatients' patients are the most important to use the ice cubes to reduce thirst intensity and thirst distress due to thirst is higher in hospitalized patients with HF. Keywords: Ice Cubes, Thirst, Heart Failure

Detecting heart failure using novel bio-signals and a knowledge enhanced neural network

BackgroundClinical decisions about Heart Failure (HF) are frequently based on measurements of left ventricular ejection fraction (LVEF), relying mainly on echocardiography measurements for evaluating structural and functional abnormalities of heart disease. As echocardiography is not available in primary care, this means that HF cannot be detected on initial patient presentation. Instead, physicians in primary care must rely on a clinical diagnosis that can take weeks, even months of costly testing and clinical visits. As a result, the opportunity for early detection of HF is lost. Methods and resultsThe standard 12-Lead ECG provides only limited diagnostic evidence for many common heart problems. ECG findings typically show low sensitivity for structural heart abnormalities and low specificity for function abnormalities, e.g., systolic dysfunction. As a result, structural and functional heart abnormalities are typically diagnosed by echocardiography in secondary care, effectively creating a diagnostic gap between primary and secondary care. This diagnostic gap was successfully reduced by an AI solution, the Cardio-HART™ (CHART), which uses Knowledge-enhanced Neural Networks to process novel bio-signals. Cardio-HART reached higher performance in prediction of HF when compared to the best ECG-based criteria: sensitivity increased from 53.5% to 82.8%, specificity from 85.1% to 86.9%, positive predictive value from 57.1% to 70.0%, the F-score from 56.4% to 72.2%, and area under curve from 0.79 to 0.91. The sensitivity of the HF-indicated findings is doubled by the AI compared to the best rule-based ECG-findings with a similar specificity level: from 38.6% to 71%. ConclusionUsing an AI solution to process ECG and novel bio-signals, the CHART algorithms are able to predict structural, functional, and valve abnormalities, effectively reducing this diagnostic gap, thereby allowing for the early detection of most common heart diseases and HF in primary care.

Prenatal genetic diagnosis for fetuses with anomalies revealed by fetal echocardiography

To carry out amniocyte karyotyping analysis and chromosomal microarray analysis (CMA) for women with anomalies revealed by fetal echocardiography. From January 2019 to December 2021, genetic testing was carried out for 205 fetuses including 97 with soft marker anomalies and 108 with structural heart abnormalities. Among these, 138 only had abnormal fetal echocardiography, whilst 38 and 29 were complicated with extracardiac soft marker anomalies and extracardiac structural malformation, respectively. No significant difference was detected in the detection rate of genetic anomalies between fetuses with heart-related soft markers and those with abnormal heart structures (P > 0.05). Compared with those with abnormal fetal echocardiography alone, the detection rates of chromosomal aneuploidies in those with abnormal extracardiac soft markers or abnormal extracardiac structures were significantly higher (P < 0.05). Twenty-eight chromosomal aneuploidies (including a rare mosaicism), 2 balanced translocations and 1 supernumerary marker chromosome were detected by karyotyping analysis. Twenty-seven aneuploidies, 19 copy number variations (CNVs) and 1 uniparental disomy were detected by CMA. Prenatal diagnosis has attached great importance to the suggestive role of fetal heart-related soft markers, and chromosomal aneuploidies are more common among fetuses with abnormal extracardiac soft markers and extracardiac structural abnormalities. Chromosomal Karyotyping is useful for the detection of balanced translocations and mosaicisms. CMA is helpful for the detection of CNVs. Identification of the genetic causes can facilitate genetic counseling for the affected couples.

68Ga-FAPI PET visualize heart failure: from mechanism to clinic.

Heart failure (HF) is a chronic progressive clinical syndrome associated with structural and/or functional heart abnormalities. Active fibroblasts and ventricular remodelling play an essential role in HF progression. 68Ga-labelled fibroblast activation protein (FAP) inhibitor (68Ga-FAPI) binds to FAP. This study aimed to examine the feasibility of using 68Ga-FAPI positron emission tomography (PET)/computed tomography (CT) to visualize changes in cardiac fibrosis and function over time in the HF setting. After establishing an isoproterenol (ISO)-induced HF rat model (14 consecutive days of intraperitoneal ISO injections), echocardiography and 68Ga-FAPI PET/CT were performed weekly in experimental and control groups. Rat hearts were examined weekly for biodistribution analysis; autoradiography; and haematoxylin and eosin, FAP immunofluorescence and Masson's trichrome staining analysis. Rat blood was sampled weekly for enzyme-linked immunosorbent assay analysis of various plasma indicators. A preliminary clinical study was also performed in seven HF patients who underwent both 13N-amino (NH3) perfusion and 68Ga-FAPI cardiac PET imaging. In the animal experiments, myocardial 68Ga-FAPI uptake, expression of FAP and myocardial contractility peaked on day 7 after the initial ISO injection. Only slight fibrotic changes were observed on histopathological examination. 68Ga-FAPI uptake and ventricular wall motion decreased over time as cardiac fibrosis and degree of myocardial injury gradually increased. In the human HF patient study, 68Ga-FAPI PET imaging identified varying degrees of 68Ga-FAPI uptake in the myocardium that did not precisely match with 13N-NH3 myocardial perfusion. As HF progresses, 68Ga-FAPI uptake is high in the early stages and then gradually decreases. Although preliminary, our findings suggest that 68Ga-FAPI PET can be used to demonstrate active myocardial fibrosis. Active myocardial FAP expression is followed by myocardial remodelling and fibrosis. Detection of early active FAP expression may assist treatment decision making in HF patients. NCT04982458.