Inherited cardiovascular

PURPOSE OF REVIEW: Increases in the availability of genetic data and advances in the tools and methods for their analyses have enabled well-powered genetic association studies that have significantly enhanced our understanding of the genetic factors underlying both rare and common valve diseases. Valvular heart diseases, such as congenital valve malformations and degenerative valve lesions, increase the risk of heart failure, arrhythmias, and sudden death. In this review, we provide an updated overview of our current understanding of the genetic mechanisms underlying valvular heart diseases...

BACKGROUND: Familial hypercholesterolaemia (FH) warrants early diagnosis to prevent premature atherosclerotic cardiovascular disease (CVD). However, underdiagnosis and undertreatment of FH persist. This study aimed to assess the knowledge and practice of FH care among general practitioners (GPs) in the Netherlands. METHODS: An internationally standardised, online questionnaire was sent to Dutch GPs between February 2021 and July 2022. The survey assessed knowledge and awareness of FH, encompassing general familiarity, awareness of management guidelines, inheritance, prevalence, CVD risk, and clinical practice related to FH...

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally and is responsible for an estimated one-third of deaths as well as significant morbidity and health care utilisation. Technological and bioinformatic advances have facilitated the discovery of pathogenic germline variants for some specific CVDs, including familial hypercholesterolaemia, cardiomyopathies and arrhythmic syndromes. Use of these genetic tests for earlier disease identification is increasing due, in part, to decreasing costs, Medicare rebates, and consumer comfort with genetic testing...

OBJECTIVE: To explore the clinical characteristics of 1q21.1 microdeletion by using single nucleotide polymorphism microarrays (SNP array). METHODS: Eighteen cases of 1q21.1 microdeletion syndrome diagnosed at the Longgang District Maternal and Child Health Care Hospital of Shenzhen City from June 2017 to December 2022 were selected as the study subjects. Clinical data of the patients were collected. Results of chromosomal karyotyping and SNP assay were retrospectively analyzed...

BACKGROUND: Brugada syndrome (BrS) is a channelopathy that can lead to sudden cardiac death in the absence of structural heart disease. Patients with BrS can be asymptomatic or present with symptoms secondary to polymorphic ventricular tachycardia or ventricular fibrillation. Even though BrS can exhibit autosomal dominant inheritance, it is not easy to identify the phenotype and genotype in a family thoroughly. CASE: We report the case of a 20-year-old man with variants in SCN5A and RyR2 genes who was resuscitated from sudden cardiac death during sleep due to a ventricular fibrillation...

INTRODUCTION: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre. MATERIALS AND METHODS: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted...

PURPOSE OF REVIEW: Congenital heart disease (CHD) is the most frequently occurring birth defect. Majority of the earlier reviews focussed on the association of genetic factors with CHD. A few epidemiological studies provide convincing evidence for environmental factors in the causation of CHD. Although the multifactorial theory of gene-environment interaction is the prevailing explanation, explicit understanding of the biological mechanism(s) involved, remains obscure. Nonetheless, integration of all the information into one platform would enable us to better understand the collective risk implicated in CHD development...

INTRODUCTION: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in trauma patients, despite chemoprophylaxis. Statins have been shown capable of acting upon the endothelium. We hypothesized that statin therapy in the pre- or in-hospital settings leads to a decreased incidence of VTE. METHODS: We conducted a retrospective cohort study of injured patients who received statin therapy pre- or in-hospital. Adult, highest-level trauma activation patients admitted January 2018 - June 2022 were included...

BACKGROUND: Preimplantation genetic testing (PGT) is a reproductive technology that selects embryos without (familial) genetic variants. PGT has been applied in inherited cardiac disease and is included in the latest American Heart Association/American College of Cardiology guidelines. However, guidelines selecting eligible couples who will have the strongest risk reduction most from PGT are lacking. We developed an objective decision model to select eligibility for PGT and compared its results with those from a multidisciplinary team...

BACKGROUND: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD...

Maturity-onset diabetes of the young (MODY) is a spectrum of clinically heterogenous forms of monogenic diabetes mellitus characterized by autosomal dominant inheritance, onset at a young age, and absence of pancreatic islets autoimmunity. This rare form of hyperglycemia, with clinical features overlapping with type 1 and type 2 diabetes mellitus, has 14 subtypes with differences in prevalence and complications occurrence which tailor therapeutic approach. MODY phenotypes differ based on the gene involved, gene penetrance and expressivity...

INTRODUCTION: Loeys-Dietz syndrome (LDS) is a heritable disease that is the result of dysregulation of the transforming growth factor beta (TGFβ) pathway. The pathogenic variants associated with the condition are linked to aortic aneurysms and dissections along with other cardiovascular and non-cardiovascular abnormalities. LDS type III is associated with pathogenic variants in the SMAD3 gene responsible for signally in the TGFβ pathway. Most of the current knowledge of LDS stems from studies of LDS I and II patient with limited data on large cohorts of LDS III patients...

BACKGROUND: To realize the potential of genome engineering therapeutics, tractable strategies must be identified that balance personalized therapy with the need for off-the-shelf availability. We hypothesized that regional clustering of pathogenic variants can inform the design of rational prime editing therapeutics to treat the majority of genetic cardiovascular diseases with a limited number of reagents. METHODS: We collated 2435 high-confidence pathogenic/likely pathogenic (P/LP) variants in 82 cardiovascular disease genes from ClinVar...

SARS-CoV-2, responsible for the global COVID-19 pandemic, has manifested significant cardiovascular implications for the infected population. These cardiovascular repercussions not only linger beyond the initial phase of illness but have also been observed in individuals who remain asymptomatic. This extended and pervasive impact is often called the post-acute COVID-19 syndrome (PACS) or "Long COVID". With the number of confirmed global cases approaching an alarming 756 million, the multifaceted challenges of Long COVID are undeniable...

A female neonate born with normal Apgar scores at 38+2 weeks of gestational age unexpectedly passed away within less than 30 hours after birth. The situation mirrors her brother's earlier demise within 24 hours post-delivery, suggesting a possible genetic disorder. A gross examination revealed widespread cyanosis and distinct yellowish changes on the cardiac ventricles. Histopathological analysis disclosed lipid accumulation in the liver, heart, and kidney. Tandem mass spectrometry detected elevated levels of 10 amino acids and 14 carnitines in cardiac blood...

PURPOSE OF REVIEW: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition with potential for severe complications including sudden cardiac death. Early diagnosis allows appropriate risk stratification and prompt intervention to minimise the potential for adverse outcomes. The implications of poorly coordinated screening are significant, either missing relatives at high-risk or burdening low-risk individuals with a diagnosis associated with reduced life expectancy. We aim to guide clinicians through the diagnostic pathway through to novel treatment options...

Clopidogrel, is a standard treatment in the prevention of major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Clopidogrel response is highly variable, mainly due to the presence of polymorphisms in the genes involved in drug metabolism. The aim of this study was to evaluate the association between the presence of the ABCB1 C3435T and CYP2C19* 2 polymorphism and the clinical outcome in patients with CAD treated with clopidogrel. A total of 96 patients with CAD were included in the study...

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity...

INTRODUCTION: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model...

This editorial, comments on the article by Spartalis et al published in the recent issue of the World Journal of Cardiology . We here provide an outlook on potential ethical concerns related to the future application of gene therapy in the field of inherited arrhythmias. As monogenic diseases with no or few therapeutic options available through standard care, inherited arrhythmias are ideal candidates to gene therapy in their treatment. Patients with inherited arrhythmias typically have a poor quality of life, especially young people engaged in agonistic sports...