Search Results (309)

Background/Objectives: Cardiac arrhythmias are among the leading causes of sudden cardiac death (SCD). Pathogenic variants in potassium channel genes play a key role in inherited arrhythmia syndromes, yet their contribution in Central Asian populations remains poorly characterized. Methods: We performed targeted next-generation sequencing (NGS) using a 96-gene custom Haloplex panel in 79 Kazakhstani patients with clinically diagnosed arrhythmias, including atrioventricular block, sick sinus syndrome, and atrial fibrillation. Detected variants in potassium channel genes were classified according to ACMG guidelines and correlated with clinical phenotypes. Results: A total of 52 variants were identified across 11 potassium channel genes. Two likely pathogenic variants (KCNH2 p.Cys66Gly and p.Arg176Trp) and six variants of uncertain significance (VUS) in KCNQ1, KCNE2, KCNE3, and KCNJ8 were detected. Two novel previously unreported variants were found in KCNE5 and KCND3. Patients harboring pathogenic variants commonly presented with early-onset arrhythmias or a positive family history of cardiovascular disease. Carriers of KCNH2 variants exhibited mild QT prolongation and recurrent syncope. Conclusions: This is the first genetic study of potassium channel gene mutations in Kazakhstani patients with cardiac arrhythmias. The detection of pathogenic and novel variants highlights the clinical utility of integrating genetic testing into diagnostic and management pathways for arrhythmia syndromes. Population-specific genomic data are essential for improving risk stratification, guiding medication safety, and enabling cascade family screening in Central Asia. Full article

Deleterious variants in SCN5A lead to a wide clinical spectrum that includes pathologies characterized by life-threatening cardiac events (CEs). In the pediatric population, early identification, management, and risk stratification of these pathologies are the main current challenges. This study analyzed a Spanish pediatric cohort (≤18 years) carrying rare SCN5A variants to explore genotype–phenotype correlations. A retrospective descriptive cohort study, including clinical, demographic, and genetic data of probands and their relatives, was conducted. Out of 100 children studied, 69 had definitively deleterious SCN5A variants (26 females, 38%; median age: 3 years, IQR 1–12). The main diagnoses were isolated Brugada syndrome (BrS) (31; 45%); isolated long QT syndrome type 3 (LQT3) (5; 7%); isolated progressive cardiac conduction disease (PCCD) (1; 2%); isolated familial atrial fibrillation (1; 2%); overlapping phenotypes (7; 10%) including: BrS-PCCD (2; 2.8%); BrS-LQT3 (1; 1.4%); premature ventricular contraction-dilated cardiomyopathy (1; 1.4%); BrS-LQT3-PCCD (1; 1.4%); BrS-PCCD-sick sinus syndrome (SSS) (1; 1.4%) and BrS-PCCD-SSS-familial atrial fibrillation (1; 1.4%). Of them, 13 (19%) patients presented with CEs (cardiogenic syncope, ventricular tachycardia/fibrillation, sudden cardiac arrest/death, and appropriate implantable cardio defibrillator shock). These findings underscore the utility of genetic testing for early diagnosis, risk stratification, and personalized management, enhancing preventive strategies for CE prevention in pediatrics. Full article

Dravet Syndrome (DS) is a severe genetic epileptic encephalopathy caused by mutations in the SCN1A gene that encodes the voltage-gated sodium channel (Na_V1.1) subunit alpha. DS is characterized by intractable seizures, progressive developmental delay, cognitive impairment, and high mortality due to sudden unexpected death in epilepsy (SUDEP). SUDEP is mediated by respiratory dysfunction, but the exact molecular underpinnings are unclear. Though hippocampal metabolic alterations have been reported in DS mice, such changes in brain regions controlling breathing have not been studied. We used Scn1a^A1783V/WT DS mice to study temporal alterations in the brain metabolome, including analysis of brainstem and forebrain regions. Glycolytic and pentose phosphate pathway intermediates were significantly elevated in the brainstem of DS mice during the period of enhanced susceptibility to mortality (post-natal days P20–30). In older P40–P50 mice, mitochondrial aconitate and the antioxidant glutathione were significantly elevated in the brainstem. Single-nuclei RNA sequencing (snRNA seq) and proteomic analyses revealed alterations in genes associated with neurotransmission, cellular respiration, and protein translation, as well as reorganization of protein kinase-mediated pathways that are specific to the brainstem. These findings suggest that there are widespread metabolic changes in the brainstem of DS mice. Full article

Background and Objectives: Obstructive Sleep Apnea–Hypopnea Syndrome (OSAHS) is associated with increased cardiovascular risk, particularly in hypertensive patients. Heart rate variability (HRV) and QTc interval are noninvasive markers of autonomic function and ventricular repolarization, respectively, but their relationship with OSAHS severity remains unclear. To investigate whether the severity of OSAHS influences standard HRV and QTc parameters in hypertensive patients with moderate or severe OSAHS. Materials and Methods: This prospective study included 110 hypertensive patients with moderate (AHI 15–29.9/h, n = 37) or severe (AHI ≥ 30/h, n = 73) OSAHS. All patients underwent full-night respiratory polygraphy and 24-h Holter ECG monitoring. HRV indices (SDNN, SDANN, SDNNi, RMSSD, SDSD) and QTc interval were analyzed. Associations with OSAHS parameters and nocturnal hypoxemia were assessed using partial correlation and multivariate models, adjusted for obesity, diabetes mellitus, metabolic syndrome, and beta-blocker use. Results: Patients with severe OSAHS had higher body weight and neck circumference, and a higher prevalence of diabetes and obesity compared to those with moderate OSAHS. HRV and QTc parameters did not differ significantly between groups. Notably, reduced SDNN was independently associated with the percentage of time spent with oxygen saturation below 90% (TST90%, p = 0.003) and mean oxygen saturation (p = 0.003), indicating autonomic imbalance. QTc prolongation (≥450 ms in men, ≥460 ms in women) was present in 9.6% of patients but was not directly related to OSAHS severity. Conclusions: Hypertensive patients with OSAHS have a high cardiovascular risk burden and frequent autonomic dysfunction. Nocturnal hypoxemia is independently associated with impaired HRV, reflecting sympathetic predominance. QTc prolongation appears to be influenced by additional comorbidities rather than OSAHS severity alone. Full article

The accuracy of machine learning models in plant disease detection significantly relies on large volumes of knowledge-based labeled data; the acquisition of annotation remains a significant bottleneck in domain-specific research such as plant disease detection. While unsupervised learning alleviates the need for labeled data, its effectiveness is constrained by the intrinsic separability of feature clusters. These limitations underscore the need for approaches that enable supervised early disease detection without extensive annotation. To this end, we propose a self-supervised learning (SSL) framework for the early detection of soybean’s sudden death syndrome (SDS) using hyperspectral data acquired from an unmanned aerial vehicle (UAV). The methodology employs a novel distance-based spectral pairing technique that derives intermediate labels directly from the data. In addition, we introduce an adapted contrastive loss function designed to improve cluster separability and reinforce discriminative feature learning. The proposed approach yields an 11% accuracy gain over agglomerative hierarchical clustering and attains both classification accuracy and F1 score of 0.92, matching supervised baselines. Reflectance frequency analysis further demonstrates robustness to label noise, highlighting its suitability in label-scarce settings. Full article

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of acute coronary syndrome, characterized by the development of a false lumen within the coronary arterial wall, leading to narrowing or complete occlusion of the true lumen. This underrecognized condition accounts for a substantial proportion of sudden cardiac death (SCD), particularly among young, otherwise healthy women. Macroscopically, SCAD is defined by intramural hematoma and focal thickening of the arterial wall, while histological examination demonstrates separation of the tunica media, elastic fiber degeneration, and variable inflammatory infiltrates. Proposed pathogenic mechanisms include primary intimal tear and primary intramural hematoma, frequently associated with predisposing conditions such as fibromuscular dysplasia, connective tissue disorders, and specific hormonal states. In cases of myocardial infarction, the myocardium exhibits acute ischemic necrosis and early hypoperfusion injury. Postmortem diagnosis requires meticulous coronary dissection, adjunctive histochemical and immunohistochemical staining, and, when indicated, molecular autopsy (MA). The purpose of this review is to provide an updated synthesis of current knowledge on SCAD as a cause of SCD, integrating pathogenetic, morphological, and genetic perspectives, and to emphasize the role of MA as both a diagnostic and preventive tool. Full article

RASopathies are a heterogeneous group of genetic syndromes caused by germline mutations in genes encoding proteins of the RAS/MAPK pathway, which are essential in the regulation of cell proliferation, differentiation and survival. Although characterized by common phenotypic manifestations such as craniofacial dysmorphism, congenital heart defects, and growth retardation, an aspect of great clinical relevance is the increased risk of sudden cardiac death, especially in relation to hypertrophic cardiomyopathy (HCM) and ventricular arrhythmias. Pathogenic variants in genes such as RAF1, RIT1, PTPN11, BRAF and SHOC2 have been associated with phenotypes with increased incidence of HCM, sometimes with early onset and a rapidly evolving course. The literature highlights the importance of early identification of patients at risk; however, specific surveillance protocols and follow-up strategies are defined in expert guidelines. This literature review aims to provide an updated overview of the main RASopathies with cardiac involvement, highlighting the genotype-phenotype correlations, the pathogenic mechanisms underlying sudden cardiac death, and current diagnosis, monitoring, and prevention strategies. The aim is to promote greater clinical awareness and encourage a multidisciplinary approach aimed at reducing mortality in these rare genetic conditions. Full article

Dogs are classified according to their total cephalic index into three biotypes: dolichocephalic, mesocephalic, and brachycephalic. The latter has emerged due to the deliberate selection of extreme phenotypic traits during breeding, which has intensified the expression of associated conformational defects and led to several medical disorders. The Brachycephalic Obstructive Airway Syndrome (BOAS) is a respiratory condition directly linked to these conformational traits. Dogs affected by BOAS present a wide range of clinical signs, including respiratory noise, exercise intolerance, syncope episodes, or even sudden death. This study aimed to evaluate craniofacial anatomical differences and similarities among dogs of different cephalic biotypes (dolichocephalic, mesocephalic, and brachycephalic) and to determine how two exercise tolerance tests—a 6 min walk and a 1000 m walk—influence physiological parameters. Eighty dogs from different breeds were included and classified according to their biotype. Morphometric data from the head, body, and limbs were obtained. Additionally, physiological parameters, including heart rate, respiratory rate, blood pressure, oxygen saturation, and rectal temperature, were evaluated before and after the tolerance tests. The results indicated that dogs tolerated both exercise tests. Dolichocephalic and mesocephalic dogs showed a greater tolerance to or greater respiratory adaptation during walking. Despite the brachycephalic biotype, a wide dispersion at a distance of 1000 m, indicating that those with a higher BOAS grade did not require emergency medical assistance during the tests. However, evidence of rostral shortening (<38 mm), together with facial foreshortening and measurements ≥ 20 mm for necks, chest circumference, and nasal fold, suggested a higher risk of airway obstruction in brachycephalic dogs diagnosed with BOAS grades 2 and 3 compared to dolichocephalic and mesocephalic dogs. This anatomical conformation was associated with significant alterations in physiological parameters including heart rate, respiratory rate, oxygen saturation below 90%, and temperature, which did not return to baseline values 10 min post-exercise. This showed significant differences between the biotypes in the distance in the 1000 m test (H = 11.74; p = 0.0028) and between the subdivisions (p = 0.0389), where G3 covered less distance than G2 (699.1 m vs. 932.77 m. These findings suggest that extreme brachycephalic conformation impairs the respiratory function and leads to thermoregulatory inefficiency, potentially compromising the animals’ survival under physical stress. Moreover, the application of safe walking tests and non-invasive morphometric measurements is suggested to facilitate prompt diagnosis of BOAS. Full article

Background: Thyrotoxicosis is a systemic condition with well-documented cardiovascular effects, but its role as a precipitant of acute coronary syndromes (ACS) is often overlooked. This review summarizes clinical cases and original studies from the last 20 years, describing ACS triggered by thyrotoxicosis. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Embase for reports published between 2004–2025. Only case reports and original articles were included. Data extracted included demographics, ECG findings, angiography results, thyroid function, etiology of hyperthyroidism, and outcomes. Results: A total of 35 cases were identified. The mean age was in the fourth decade of life, with a female predominance (57%, 20 out of 35). More than half of the patients presented with ST-segment elevation myocardial infarction (STEMI) or STEMI equivalents (21 out of 35; 60%). Electrocardiographic abnormalities most often involved anterior or inferior leads. Coronary angiography revealed normal vessels or diffuse vasospasm in 18 cases (51%), while thrombotic occlusion was observed in 4 cases (11%), spontaneous dissection in 2 cases (6%), and myocardial bridging in 3 cases (9%). The leading cause of thyrotoxicosis was Graves’ disease (≈65%), followed by painless thyroiditis, iatrogenic causes, and gestational hyperthyroidism. Thyroid storm was reported in approximately 20% of cases and was associated with malignant ventricular arrhythmias or sudden cardiac death. Conclusions: Thyrotoxicosis should be recognized as a rare but important trigger of ACS, especially in young patients without traditional risk factors. Pathophysiological mechanisms include coronary vasospasm, increased myocardial oxygen demand, and hypercoagulability. Early recognition may prevent unnecessary revascularization and optimize outcomes through integrated endocrine and cardiac management. Full article

Background: Dilated cardiomyopathy (DCM) and long QT syndrome (LQTS) are genetically heterogeneous cardiac disorders that contribute significantly to morbidity and sudden cardiac death. Although they are typically considered distinct entities, co-occurrence within families has been increasingly recognized, complicating diagnosis and genetic counseling. Identifying shared genetic determinants may provide insights into overlapping disease mechanisms. Methods: We investigated a multi-generational family in which several members presented with features of both DCM and LQTS. Exome sequencing was performed to identify potential disease-causing variants, and candidate findings were validated by Sanger sequencing. In silico prediction tools and evolutionary conservation analysis were used to assess the pathogenic potential of the identified variant. Results: We identified a novel heterozygous missense variant in the CRYAB gene, c.368G>A (p.Arg123Gln). This variant is located in a highly conserved region critical for protein function and was consistently predicted to be deleterious across multiple computational algorithms. Segregation analysis demonstrated co-occurrence of the variant with disease phenotypes in affected family members. Clinically, several carriers exhibited overlapping features of both DCM and prolonged QT interval, suggesting a dual cardiac phenotype associated with this mutation. Conclusions: Our findings expand the phenotypic spectrum associated with CRYAB mutations, linking them to a combined presentation of dilated cardiomyopathy and long QT syndrome. This underscores the importance of including CRYAB in comprehensive gene panels for inherited cardiac disorders and highlights the need for integrated clinical and genetic evaluation in families presenting with complex cardiac phenotypes. Full article

Sudden Infant Death Syndrome (SIDS) is one of the leading causes of postnatal mortality, with the prone sleeping position identified as a critical risk factor. This article presents the design, implementation, and validation of a low-cost embedded system for unobtrusive, real-time monitoring of infant posture. The system acquires data from a pressure mat on which the infant rests, converting the pressure matrix into an image representing the postural imprint. A Convolutional Neural Network (CNN) has been trained to classify these images and distinguish between prone and supine positions with high accuracy. The trained model was optimized and deployed in a data acquisition and processing system (DAQ) based on the Raspberry Pi platform, enabling local and autonomous inference. To prevent false positives, the system activates a visual and audible alarm upon detection of a sustained risk position, alongside remote notifications via the MQTT protocol. The results demonstrate that the prototype is capable of reliably and continuously identifying the infant’s posture when used by people who are not technology experts. We conclude that it is feasible to develop an autonomous, accessible, and effective monitoring system that can serve as a support tool for caregivers and as a technological basis for new strategies in SIDS prevention. Full article

Anomalous origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital coronary anomaly with an estimated incidence of 1 in 300,000 live births. While commonly diagnosed in infancy, adult presentations are exceedingly rare and pose significant diagnostic challenges. Delayed diagnosis may result in progressive myocardial ischemia, heart failure, arrhythmias, or sudden cardiac death. Surgical correction is the definitive treatment, with the goal of restoring a dual coronary artery system and preventing irreversible myocardial damage. We present the case of a 30-year-old male with a prior history of non–ST-elevation myocardial infarction who was referred for evaluation of exertional angina and symptoms of heart failure. Transthoracic echocardiography revealed a dilated left ventricle with an ejection fraction (LVEF) of 35%. Coronary angiography and cardiac MDCT identified an anomalous origin of the left circumflex artery (LCx) from the right pulmonary artery (RPA) and a coronary–pulmonary artery fistula involving the LAD. The patient underwent successful surgical correction with reimplantation of the LCx into the ascending aorta. Postoperative recovery was uneventful. At 3-month follow-up the patient was symptom-free, though echocardiography revealed persistent LV dilation and reduced LVEF, necessitating continued pharmacologic therapy and monitoring. This case highlights the importance of maintaining a high index of suspicion for ALCAPA in adult patients with unexplained cardiomyopathy or ischemic symptoms. Early diagnosis and surgical intervention remain crucial for improving long-term outcomes and preventing life-threatening complications. Full article

Cannabis is one of the most studied psychoactive substances due to its increasing prevalence and evolving legal status. Of particular concern is the rising consumption among young individuals, where excessive use may disrupt reproductive processes and pose long-term health risks to offspring. This narrative review examines the effects of cannabis use on male and female reproductive health, including its impact on male fertility, the female reproductive system, placental function, and prenatal and postnatal outcomes, as well as fetal development. A nonsystematic review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases in November 2024. After screening titles and abstracts and the full-text analysis, 64 studies were included in this narrative review. In men, cannabinoids can interfere with spermatogenesis, reduce sperm motility and quality, and lower testosterone levels, as demonstrated in clinical and experimental studies. In women, cannabinoid-induced disorders include negative effects on ovarian follicle maturation, ovulation, placental function, and prenatal development. Prenatal exposure to cannabis is associated with the risk of reduced birth weight, birth defects, sudden infant death syndrome (SIDS) or lactation problems due to the penetration of cannabis metabolites into breast milk. The findings highlight the potential negative effects of cannabis on reproductive health and fetal development. Given these risks, individuals attempting to conceive, and pregnant women should be advised against cannabis use. Greater awareness is needed among healthcare professionals and the public regarding the reproductive risks associated with cannabis consumption. While the evidence on teratogenic effects is not always conclusive, caution should be exercised, and further research is essential to deepen the understanding of these effects. Full article

Background and Objectives: Obstructive sleep apnea syndrome (OSAS) and heart failure (HF) frequently coexist, amplifying cardiovascular risk through mechanisms involving chronic inflammation and autonomic dysfunction. This study investigates the impact of systemic inflammation, measured by the systemic immune-inflammation index (SII), and OSAS severity, assessed by the apnea–hypopnea index (AHI), on myocardial repolarization heterogeneity in patients with both conditions. Materials and Methods: In this retrospective study, 160 patients with HF and polysomnography-confirmed OSAS (AHI ≥ 5 events/h) were evaluated between January 2018 and November 2024. Patients were stratified by QT dispersion (QTd < 40 ms vs. ≥40 ms) to assess electrical heterogeneity. SII was calculated from neutrophil, platelet, and lymphocyte counts, and electrocardiographic markers (QTd, frontal QRS-T angle, T wave peak-to-end interval [TPEI]) were measured. Logistic regression and receiver operating characteristic (ROC) analyses were used to identify predictors of repolarization heterogeneity and ventricular arrhythmias. Results: Patients with QTd ≥ 40 ms (n = 78) exhibited higher SII (p < 0.001) and AHI (p < 0.001) compared to those with QTd < 40 ms (n = 82). SII and AHI independently predicted increased QTd in multivariate analysis (p = 0.01 and p < 0.001, respectively). ROC analysis identified SII ≥ 625.4 (sensitivity 73.1%, specificity 72%) and AHI ≥ 22.4 (sensitivity 79.5%, specificity 79.3%) as optimal cut-offs for predicting repolarization heterogeneity. SII, QTd, and TPEI were significantly associated with ventricular arrhythmias (p < 0.05). Patients with moderate-to-severe OSAS (AHI ≥ 15) had higher rates of ventricular tachyarrhythmias (17.8% vs. 5.7%, p = 0.03) and sudden cardiac death (9.3% vs. 1.9%, p = 0.05). Conclusions: Elevated SII and AHI are independent predictors of myocardial repolarization heterogeneity in patients with HF and OSAS, contributing to increased arrhythmic risk. These findings highlight the potential use of SII and AHI as accessible biomarkers for risk stratification, particularly in patients with a preserved ejection fraction, and underscore the need for targeted interventions to mitigate inflammation and OSAS severity. Full article

This study investigates the genetic background of pediatric-onset cardiac channelopathies, a rare group of genetic disorders causing arrhythmias and sometimes sudden death, whose genetic background remains partially unknown. The research analyzed 59 pediatric patients (<18 years of age) diagnosed with different channelopathies (LQTS, BrS, CPVT, SQTS, and conduction disorders), along with 40 of their family members, using Next-Generation Sequencing (NGS) after genetic counseling. A causative genetic variant was found in 47% of cases, mainly in the KCNQ1 (42%), RYR2 (16%), CACNA1C (10%), and SCN5A (10%) genes. Notably, a de novo large deletion in KCNH2 was detected in an LQTS patient, and a pathogenic CALM1 variant was identified in a child. A compound heterozygous KCNQ1 was consistent with Jervell and Lange-Nielsen syndrome. In light of these data, genetic testing is crucial for diagnosis, prognosis, and treatment planning; cascade screening allowed early risk identification and preventive interventions for family members. Expanding NGS technologies and research on new candidate genes may enhance personalized therapies in the future. Full article