Search Results (91)

Catalpa bungei C. A. Mey, an economically and ecologically important tree species endemic to China, exhibits notable drought resistance; however, the spatial dynamics of its habitat under future climate change have not been thoroughly investigated. We employed a parameter-optimized MaxEnt modeling framework to project current and future suitable habitats for C. bungei under two Shared Socioeconomic Pathway scenarios, SSP126 (low-emission) and SSP585 (high-emission), based on CMIP6 climate data. We incorporated 126 spatially rarefied occurrence records and 22 environmental variables into a rigorous modeling workflow that included multicollinearity assessment and systematic variable screening. Parameter optimization was performed using the kuenm package in R version 4.2.3, and the best-performing model configuration was selected (Regularization Multiplier = 2.5; Feature Combination = LQT) based on the AICc, omission rate, and evaluation metrics (AUC, TSS, and Kappa). Model validation demonstrated robust predictive accuracy. Four primary environmental predictors obtained from WorldClim version 2.1—the minimum temperature of the coldest month (Bio6), annual precipitation (Bio12), maximum temperature of the warmest month (Bio5), and elevation—collectively explained over 90% of habitat suitability. Currently, the optimal habitats are concentrated in central and eastern China. By the 2090s, the total suitable habitats are projected to increase by approximately 4.25% under SSP126 and 18.92% under SSP585, coupled with a significant northwestward shift in the habitat centroid. Conversely, extremely suitable habitats are expected to markedly decline, particularly in southern China, due to escalating climatic stress. These findings highlight the need for adaptive afforestation planning and targeted conservation strategies to enhance the climate resilience of C. bungei under future climate change. Full article

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

Background/Objectives: Long QT Syndrome type 2 (LQT2) is a cardiac channelopathy linked to pathogenic variants in the KCNH2 gene, which encodes the Kv11.1 potassium channel, essential for cardiac repolarization. Variants affecting splice sites disrupt potassium ion flow, prolong QT interval, and increase the risk of arrhythmias and sudden cardiac death (SCD). Understanding genotype–phenotype correlations is key, given the variability of clinical manifestations even within families sharing the same variant. We aimed to evaluate new pathogenic variants by analyzing genotype–phenotype correlations in informative families. Methods: Genetic and clinical assessments were performed on index cases and family members carrying KCNH2 pathogenic variants, referred for genetic testing between 2010 and June 2023. The next-generation sequencing (NGS) of 210 cardiovascular-related genes was conducted. Clinical data, including demographic details, family history, arrhythmic events, electrocardiographic parameters, and treatments, were collected. Results: Among 390 patients (152 probands) tested for LQTS, only 2 KCNH2 variants had over 5 carriers. The detailed clinical information of 22 carriers of this KCNH2 p.Ser261fs. has already been reported by our research group. Moreover, we identified 12 carriers of the KCNH2 c.77-2del variant, predicted to disrupt a splice site and not previously reported. Segregation analysis showed its high penetrance, supporting its classification as pathogenic. Conclusions: The newly identified KCNH2 c.77-2del variant is a pathogenic, as strongly supported by the segregation analysis. Our findings underscore the importance of further research into splice site variants to enhance clinical management and genetic counseling for affected families. Full article

Background: Genetic testing for long QT syndrome (LQTS) is straightforward in many families; however, in severe and complex cases, a single disease-causing variant may not be enough to explain all clinical features. In such cases, the search for genetic modifiers may be beneficial for precise diagnosis and management. Case presentation: We describe a three-generational family affected with clinically heterogeneous LQTS type 3 and bradycardia in which a novel missense variant p.V642M in HCN4 was identified in addition to the known pathogenic variant p.E1784K in SCN5A. We performed the detailed clinical investigation of the family and a deep in silico analysis of the discovered variants, showing the causal role of a new HCN4 variant in sinus bradycardia and its possible contribution to the phenotypic heterogeneity of LQTS type 3. Conclusions: This case is the first description of a functional variant in HCN4 as a candidate modifier in LQTS type 3 and demonstrates the importance of analyzing additional genetic variations in families with complex LQTS phenotypes. Full article

Congenital long QT syndrome (LQTS) is a group of heritable conditions that are associated with cardiac repolarization abnormalities characterized by QT prolongation on electrocardiogram and the risk of life-threatening arrhythmias. The prenatal detection of LQTS presents significant challenges for clinicians, and a multidisciplinary approach is required for optimal prenatal and postnatal management. In this comprehensive literature review, we describe strategies for the fetal diagnosis of LQTS with variable initial presentation, genetic testing in suspected fetal LQTS, the utility of fetal magnetocardiography as an additional diagnostic tool, prenatal management, and postnatal treatment. We focus on a multidisciplinary team approach including fetal cardiology, adult and pediatric electrophysiology, neonatology, maternal–fetal medicine, and genetic counselors, all playing vital roles in the comprehensive prenatal management and orchestration of postnatal treatment to optimize neonatal outcomes. Full article

Background: Congenital long QT syndrome (LQTS) is a rare cardiac disorder caused by repolarization abnormalities in the myocardium that predisposes to ventricular arrhythmias and sudden cardiac death. Potassium channel-mediated LQT1 and LQT2 are the most common types of channelopathy. Recently, LQTS has been acknowledged as an electromechanical disease. Methods: A total of 87 genotyped LQT1/LQT2 patients underwent cardiac evaluation. A comparison between LQT1 and LQT2 electrical and mechanical parameters was performed. Results: LQT2 patients had worse electrical parameters at rest: a longer QTc interval (p = 0.007), a longer T_pe in lead V2 (p = 0.028) and in lead V5 (p < 0.001), and a higher T_pe/QT ratio in lead V2 (p = 0.011) and in lead V5 (p = 0.005). T_pe and T_pe/QT remained significantly higher in the LQT2 group after brisk standing. T_pe was longer in LQT2 patients compared with LQT1 patients during peak exercise (p = 0.007) and almost all recovery periods in lead V2 during EST. The mid-cavity myocardium mean radial contraction duration (CD) was longer in LQT2 patients (p = 0.02). LQT2 patients had a longer mean radial CD in mid-septal (p = 0.015), mid-inferior (p = 0.034), and mid-posterior (p = 0.044) segments. Conclusions: Potassium channel-mediated LQTS has different effects on cardiac electromechanics with a more pronounced impact on LQT2 patients. T_pe was more prominent in the LQT2 cohort, not only at rest and brisk standing but also during EST exercise and at recovery phases. The altered mean radial CD in the mid-cavity myocardium was also specific for LQT2 patients. Full article

Long QT syndrome (LQTS) presents a group of inheritable channelopathies with prolonged ventricular repolarization, leading to syncope, ventricular tachycardia, and sudden death. Differentiating LQTS genotypes is crucial for targeted management and treatment, yet conventional genetic testing remains costly and time-consuming. This study aims to improve the distinction between LQTS genotypes, particularly LQT3, through a novel electrocardiogram (ECG)-based approach. Patients with LQT3 are at elevated risk due to arrhythmia triggers associated with rest and sleep. Employing a database of genotyped long QT syndrome E-HOL-03-0480-013 ECG signals, we introduced two innovative parameterization techniques—area under the ECG curve and wave transformation into the unit circle—to classify LQT3 against LQT1 and LQT2 genotypes. Our methodology utilized single-lead ECG data with a 200 Hz sampling frequency. The support vector machine (SVM) model demonstrated the ability to discriminate LQT3 with a recall of 90% and a precision of 81%, achieving an F1-score of 0.85. This parameterization offers a potential substitute for genetic testing and is practical for low frequencies. These single-lead ECG data could enhance smartwatches’ functionality and similar cardiovascular monitoring applications. The results underscore the viability of ECG morphology-based genotype classification, promising a significant step towards streamlined diagnosis and improved patient care in LQTS. Full article

Background and Clinical Significance: Congenital LQTS is a life-threatening condition, resulting from a mutation of the gene encoding the cardiac ion channels, which results in prolongation of the ventricular action potential. Genetic screening of family members in symptomatic and asymptomatic patients is crucial for the prevention of sudden cardiac death. There are a number of detected mutations of congenital LQTS, of which the three forms LQT1, LQT2, and LQT3 are the best described. In addition to the described ECG morphology, the key triggers and treatment approach are described. This emphasizes even more the importance of timely screening of these patients, and the decision for therapy. It should be emphasized that the phenotypic manifestations significantly depend on the affected genes. The guidelines in the treatment approach are very clear, although it should be emphasized that beta blockers are the first and basic treatment therapy. The therapeutic choice is narrowed especially if they are not effective. Case Presentation: This is a case report of a young woman diagnosed with LQTS who was confirmed to have KCNH2 mutations through genetic analysis. The same mutation was also confirmed in her children. Changes in the therapeutic approach are described, and the use of beta blockers, depending on the symptoms and drug tolerance. Especially in the postpartum period, due to reduced progesterone levels, in this case, the patient was implanted with a cardioverter defibrillator. Conclusions: It should be emphasized that timely recognition is essential for early diagnosis, regular control, timely initiation of treatment, and prevention of adverse events. Full article

Inherited arrhythmia syndromes include several different diseases, as well as Brugada syndrome (BrS), long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and short QT syndrome (SQTS). They represent, together with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), an important cause of sudden cardiac death in the young. Most arrhythmia syndromes are inherited in an autosomal dominant manner, and genetic studies are suggested.: to report the spectrum of genetic variations and clinical phenotype in an Italian cohort with confirmed inherited arrhythmia syndromes and arrhythmogenic cardiomyopathy using whole-exome sequencing (WES). Patients with confirmed inherited arrhythmia syndromes and hereditary cardiomyopathy were recruited at the Cardiology Unit, University Polyclinic Hospital of Foggia, Italy and were included in this study. Genomic DNA samples were extracted from peripheral blood and conducted for WES. The variants were annotated using BaseSpace Variant Interpreter Annotation Engine 3.15.0.0 (Illumina). Reported variants were investigated using ClinVar, VarSome Franklin and a literature review. They were categorised agreeing to the criteria of the American College of Medical Genetics and Genomics. Overall, 62 patients were enrolled. Most of them had a clinical diagnosis of BrS (n 48, 77%). The remaining patients included in the present study had diagnosis of confirmed LQT (n 7, 11%), AR-DCM (n 4, 6.5%), ARVD (n 2, 3%), and SQT (n 1, 1.6%). Using the WES technique, 22 variants in 15 genes associated with Brugada syndrome were identified in 21 patients (34%). Among these, the SCN5A gene had the highest number of variants (6 variants, 27%), followed by KCNJ5 and CASQ2 (2 variants). Only one variant was identified in the remaining genes. In 27 patients with a clinical diagnosis of BrS, no gene variant was detected. In patients with confirmed LQT, SQT, 10 variants in 9 genes were identified. Among patients with ARVD and AR-DCM, 6 variants in 5 genes were found. Variants found in our cohort were classified as pathogenic (6), likely pathogenic (3), of uncertain significance (26), and benign (1). Two additional gene variants were classified as risk factors. In this study, 13 novel genetic variations were recognized to be associated with inherited arrhythmogenic cardiomyopathies. Our understanding of inherited arrhythmia syndromes continues to progress. The era of next-generation sequencing has advanced quickly, given new genetic evidence including pathogenicity, background genetic noise, and increased discovery of variants of uncertain significance. Although NGS study has some limits in finding the full genetic data of probands, large-scale gene sequencing can promptly be applied in real clinical practices, especially in inherited and possibly fatal arrhythmia syndromes. Full article

Background: Screening for cardiovascular disease (CVD) and its associated risk factors in childhood facilitates early detection and timely preventive interventions. However, limited data are available regarding screening tools and their diagnostic yield when applied in unselected pediatric populations. Aims: To evaluate the performance of a CVD screening program, based on history, 12-lead ECG and phonocardiography, applied in primary school children. Methods: The methods used were prospective study, with voluntary participation of third-grade primary school children in the region of Crete/Greece, over 6 years (2018–2024). Personal and family history were collected by using a standardized questionnaire and physical evaluation (including weight, height, blood pressure measurement), and cardiac auscultation (digital phonocardiography (PCG)) and 12-lead electrocardiogram (ECG) were recorded at local health stations (Phase I). Following expert verification of responses and obtained data, assisted by designated electronic health record with incorporated decision support algorithms (phase II), pediatric cardiology evaluation at the tertiary referral center followed (phase III). Results: A total of 944 children participated (boys 49.6%). A total of 790 (83.7%) had Phase I referral indication, confirmed in 311(32.9%) during Phase II evaluation. Adiposity (10.8%) and hypertension (3.2%) as risk factors for CVD were documented in 10.8% and 3.2% of the total population, respectively. During Phase III evaluations (n = 201), the majority (n = 132, 14% of total) of children were considered as having a further indication for evaluation by other pediatric subspecialties for their reported symptoms. Abnormal CVD findings were present in 69 (7.3%) of the study population, including minor/trivial structural heart disease in 23 (2.4%) and 17 (1.8%), respectively, referred due to abnormal cardiac auscultation, and ECG abnormalities in 29 (3%), of which 6 (0.6%) were considered potentially significant (including 1 case of genetically confirmed channelopathy-LQT syndrome). Conclusions: CVD screening programs in school children can be very helpful for the early detection of CVD risk factors and of their general health as well. Expert cardiac auscultation and 12-lead ECG allow for the detection of structural and arrhythmogenic heard disease, respectively. Further study is needed regarding performance of individual components, accuracy of interpretation (including computer assisted diagnosis) and cost-effectiveness, before large-scale application of CVD screening in unselected pediatric populations. Full article

Inherited cardiac channelopathies are major causes of sudden cardiac death (SCD) in young people. Genetic testing is focused on the identification of single-nucleotide variants (SNVs) by Next-Generation Sequencing (NGS). However, genetically elusive cases can carry copy number variants (CNVs), which need specific detection tools. We underlie the utility of identifying CNVs by investigating the literature data and internally analyzing cohorts with CNVs in KCNQ1, KCNH2, SCN5A, and RYR2. CNVs were reported in 119 patients from the literature and 21 from our cohort. Young patients with CNVs in KCNQ1 show a Long QT (LQT) phenotype > 480 ms and a higher frequency of syncope. None of them had SCD. All patients with CNV in KCNH2 had a positive phenotype for QT > 480 ms. CNVs in SCN5A were represented by the Brugada pattern, with major cardiac events mainly in males. Conversely, adult females show more supraventricular arrhythmias. RYR2-exon3 deletion showed a broader phenotype, including left ventricular non-compaction (LVNC) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Pediatric patients showed atrial arrhythmias and paroxysmal atrial fibrillation. Relatively higher syncope and SCA were observed in young females. The detection of CNVs can be of greater yield in two groups: familial channelopathies and patients with suspected Jervell and Lange-Nielsen syndrome or CPVT. The limited number of reported individuals makes it mandatory for multicentric studies to give future conclusive results. Full article

Genetic overdiagnosis of long QT syndrome (LQTS) becomes a critical concern due to the high clinical significance of DNA diagnosis. Current guidelines for LQTS genetic testing recommend a limited scope and strict referral based on the Schwartz score. Nevertheless, LQTS may be underdiagnosed in patients with borderline phenotypes. We aimed to evaluate the total yield of rare variants in cardiac genes in LQTS patients. The cohort of 82 patients with LQTS referral diagnosis underwent phenotyping, Schwartz score counting, and exome sequencing. We assessed known LQTS genes for diagnostics, as per guidelines, and a broader set of genes for research. Diagnostic testing yield reached 75% in index patients; all causal variants were found in KCNQ1, KCNH2, and SCN5A genes. Research testing of 248 heart-related genes achieved a 50% yield of molecular diagnosis in patients with a low Schwartz score (<3.5). In patients with LQTS-causing variants, each additional rare variant in heart-related genes added 0.94 points to the Schwartz score (p value = 0.04), reflecting the more severe disease in such patients than in those with causal variants but without additional findings. We conclude that the current LQTS genetic diagnosis framework is highly specific but may lack sensitivity for patients with a Schwartz score <3.5. Improving referral criteria for these patients could enhance DNA diagnosis. Also, our results suggest that additional variants in cardiac genes may affect the severity of the disease in the carriers of LQTS-causing variants, which may aid in identifying new modifier genes. Full article

This paper investigated a new speed regulator using an adaptive transitioning policy iteration learning technique for the variable reluctance motor (VRM) drive. A transitioning strategy is used in this unique scheme to handle the nonlinear behavior of the VRM by using a series of learning centers, each of which is an individual local learning controller at linear operational location that grows throughout the system’s nonlinear domain. This improved control technique based on an adaptive dynamic programming algorithm is developed to derive the prime solution of the infinite horizon linear quadratic tracker (LQT) issue for an unidentified dynamical configuration with a VRM drive. By formulating a policy iteration algorithm for VRM applications, the speed of the motor shows inside the machine model, and therefore the local centers are directly affected by the speed. Hence, when the speed of the rotor changes, the parameters of the local centers grid would be updated and tuned. Additionally, a multivariate transition algorithm has been adopted to provide a seamless transition between the Q-centers. Finally, simulation and experimental results are presented to confirm the suggested control scheme’s efficacy. Full article

In this paper, we introduce a control method for the linear quadratic tracking (LQT) problem with zero steady-state error. This is achieved by augmenting the original system with an additional state representing the integrated error between the reference and actual outputs. One of the main contributions of this paper is the integration of a linear quadratic integral component into a general LQT framework. In this framework, the reference trajectories are generated using a linear exogenous system. During a simulative implementation for the specific real-world system of a car-in-the-loop (CiL) test bench, we assumed that the ‘real’ system was completely known. Therefore, for model-based control, we could have a perfect model identical to the ‘real’ system. It became clear that for CiL, stable solutions cannot be achieved with a controller designed with a perfect model of the ‘real’ system. On the contrary, we show that a model trained via Bayesian optimization (BO) can facilitate a much larger set of stable controllers. It exhibited an improved control performance for CiL. To the best of the authors’ knowledge, this discovery is the first in the LQT-related literature, which is a further distinctive feature of this work. Full article

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20–40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening. Full article