Modern clinical genetics in cardiology.

Advances in molecular genetics during the past decades led to seminal discoveries in the genetic basis of cardiovascular diseases, resulting in a new understanding of their pathogenesis, determinants of natural history and more recently paved the way for innovative therapies. A significant gap, however, exists between the rapidly increasing knowledge, especially of cardiovascular Mendelian disorders, and the medical applications in daily practice. This paper will focus on the practical issues the cardiologist may be faced with when suspecting a Mendelian disorder.

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Meat intake in relation to composition and function of gut microbiota.

Objective: Meat intake is suggested to affect gut microbiome composition and the risk of chronic diseases. We aimed to identify meat-associated gut microbiome features and their association with host factors.

Design: Gut microbiota species were profiled by deep shotgun metagenomics sequencing in 9669 individuals.

CRISPR detection of cardiac tumor-associated microRNAs.

As multiple imaging modalities cannot reliably diagnose cardiac tumors, the molecular approach offers alternative ways to detect rare ones. One such molecular approach is CRISPR-based diagnostics (CRISPR-Dx). CRISPR-Dx enables visual readout, portable diagnostics, and rapid and multiplex detection of nucleic acids such as microRNA (miRNA).

Molecular Stratification of Light-Chain Cardiac Amyloidosis With F-Florbetapir and Ga-FAPI-04 for Enhanced Prognostic Precision.

Background: Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.

Objectives: This prospective study aimed to delineate the molecular phenotypes of AL cardiac amyloidosis (AL-CA) by characterizing fibro-amyloid deposition using F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor-04 (Ga-FAPI-04) positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.

Deep Neural Network Analysis of the 12-Lead Electrocardiogram Distinguishes Patients With Congenital Long QT Syndrome From Patients With Acquired QT Prolongation.

Objective: To test whether an artificial intelligence (AI) deep neural network (DNN)-derived analysis of the 12-lead electrocardiogram (ECG) can distinguish patients with long QT syndrome (LQTS) from those with acquired QT prolongation.

Methods: The study cohort included all patients with genetically confirmed LQTS evaluated in the Windland Smith Rice Genetic Heart Rhythm Clinic and controls from Mayo Clinic's ECG data vault comprising more than 2.5 million patients.

Quantifying DNA Lesions and Circulating Free DNA: Diagnostic Marker for Electropathology and Clinical Stage of AF.

Background: Atrial fibrillation (AF) persistence is associated with molecular remodeling that fuels electrical conduction abnormalities in atrial tissue. Previous research revealed DNA damage as a molecular driver of AF.

Objectives: This study sought to explore the diagnostic value of DNA damage in atrial tissue and blood samples as an indicator of the prevalence of electrical conduction abnormalities and stage of AF.

Noninvasive Imaging of Immune Cell Activity in Myocardial Infarction Phases Using Tc-HYNIC-mAb SPECT/CT.

Acute myocardial infarction (MI) remains a leading cause of mortality worldwide, with inflammatory and reparative phases playing critical roles in disease progression. Currently, there is a pressing need for imaging techniques to monitor immune cell infiltration and inflammation activity during these phases. We developed a novel probe, Tc-HYNIC-mAb, utilizing a monoclonal antibody that targets the voltage-gated potassium channel 1.

CAR/CSACI Practice Guidance for Contrast Media Hypersensitivity.

Contrast media, including iodinated contrast media and gadolinium-based contrast agents, are commonly administered pharmaceuticals with excellent safety profiles. However, a minority of the population may experience a hypersensitivity reaction following intravenous administration. Hypersensitivity reactions can be immediate or delayed, and range from mild, such as urticaria, to severe, including anaphylaxis.

Impact of Wood Smoke Exposure on Aortic Valve Mineralization: Microvesicles as Mineral Conveyors in Patients with Coronary Stenosis.

Aortic valve calcification results from degenerative processes associated with several pathologies. These processes are influenced by age, chronic inflammation, and high concentrations of phosphate ions in the plasma, which contribute to induce mineralization in the aortic valve and deterioration of cardiovascular health. Environmental factors, such as wood smoke that emits harmful and carcinogenic pollutants, carbon monoxide (CO), and nitrogen oxide (NO), as well as other reactive compounds may also be implicated.

Cangrelor in Patients Undergoing Percutaneous Coronary Intervention After Out-of-Hospital Cardiac Arrest.

: Cangrelor provides rapid platelet inhibition, making it a potential option for out-of-hospital cardiac arrest (OHCA) survivors undergoing percutaneous coronary intervention (PCI). However, clinical data on its use after OHCA are limited. This study investigates in-hospital outcomes of cangrelor use in this population.

Association Between Serum Folate Concentrations and 10-Year Stroke Risk in a Prospective Community Cohort: Mediation and Interaction Analyses.

The relationship between folate concentrations and stroke risk remains unestablished, and the mediation effect of homocysteine (Hcy) and interaction effect of methylenetetrahydrofolate reductase () gene polymorphism has yet to be investigated. This cohort study involved 4903 subjects derived from a Chinese community population. The association between folate and first stroke was examined in Cox proportional hazard regression models.

Differential Inhibition by Cenobamate of Canonical Human Nav1.5 Ion Channels and Several Point Mutants.

Cenobamate is a new and highly effective antiseizure compound used for the treatment of adults with focal onset seizures and particularly for epilepsy resistant to other antiepileptic drugs. It acts on multiple targets, as it is a positive allosteric activator of γ-aminobutyric acid type A (GABA) receptors and an inhibitor of neuronal sodium channels, particularly of the late or persistent Na current. We recently evidenced the inhibitory effects of cenobamate on the peak and late current component of the human cardiac isoform hNav1.

Atherosclerosis and the Bidirectional Relationship Between Cancer and Cardiovascular Disease: From Bench to Bedside, Part 2 Management.

The first part of this review highlighted the evolving landscape of atherosclerosis, noting emerging cardiometabolic risk factors, the growing impact of exposomes, and social determinants of health. The prominent role of atherosclerosis in the bidirectional relationship between cardiovascular disease and cancer was also discussed. In this second part, we examine the complex interplay between multimorbid cardio-oncologic patients, cardiometabolic risk factors, and the harmful environments that lend a "syndemic" nature to these chronic diseases.

Prolonged Hypoxia in Rat Living Myocardial Slices Affects Function, Expression, and Structure.

Ischemic heart disease is the leading cause of death worldwide. Reduced oxygen supply and myocardial hypoxia lead to tissue damage and impairment of the heart function. To the best of our knowledge, the primary functional effects of hypoxia in the multicellular model of living myocardial slices (LMSs) have not been investigated so far.

Atrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets.

Atrial fibrosis is a hallmark of atrial cardiomyopathy and plays a pivotal role in the pathogenesis of atrial fibrillation (AF), contributing to its onset and progression. The mechanisms underlying atrial fibrosis are multifaceted, involving stretch-induced fibroblast activation, oxidative stress, inflammation, and coagulation pathways. Variations in fibrosis types-reactive and replacement fibrosis-are influenced by patient-specific factors such as age, sex, and comorbidities, complicating therapeutic approaches.

From Molecular to Radionuclide and Pharmacological Aspects in Transthyretin Cardiac Amyloidosis.

Amyloidosis is a rare pathology characterized by protein deposits in various organs and tissues. Cardiac amyloidosis (CA) can be caused by various protein deposits, but transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) are the most frequent pathologies. Protein misfolding can be induced by several factors such as oxidative stress, genetic mutations, aging, chronic inflammation, and neoplastic disorders.

The Molecular Basis of Asthma Exacerbations Triggered by Viral Infections: The Role of Specific miRNAs.

Viral respiratory infections are a significant clinical problem among the pediatric population and are one of the leading causes of hospitalization. Most often, upper respiratory tract infections are self-limiting. Still, those that involve the lower respiratory tract are usually associated with asthma exacerbations, leading to worsening or even the initiation of the disease.

Unusual Genomic and Biochemical Features of sp. nov-A Novel Bacterial Species Isolated from Anthill Soil.

The black garden ant () is a widely distributed species across Europe, North America, and North Africa, playing a pivotal role in ecological processes within its diverse habitats. However, the microbiome associated with remains poorly investigated. In the present study, we isolated a novel species, , from the soil of the anthill.

Nuclear Magnetic Resonance (NMR)-Based Lipidomics Reveal the Association of Altered Red Blood Cell (RBC) Membrane Lipidome with the Presence and the Severity of Coronary Artery Stenosis.

Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide despite significant improvements in diagnostic modalities. Emerging evidence suggests that erythrocytes, or red blood cells (RBCs), are one of the most important contributors to the events implicated in atherosclerosis, although the molecular mechanisms behind it are under investigation. We used NMR-based lipidomic technology to investigate the RBC lipidome in patients with CHD compared to those with normal coronary arteries (NCAs), all angiographically documented, and its correlation with coronary artery stenosis.

Prevalence and functional impact of chronotropic incompetence in amyloid cardiomyopathy: a multicentre analysis.

Background: Little evidence is available about heart rate (HR) response to exercise as well as its relationship with functional capacity in amyloid cardiomyopathy. Then, in a multicentre cohort of patients with amyloid cardiomyopathy, we investigated the prevalence of chronotropic incompetence (CI) and its relationships with cardiopulmonary exercise testing (CPET) variables.

Methods: Data from 172 outpatients with amyloid cardiomyopathy who performed a maximal CPET and who had no significant rhythm disorders were analysed.

Hypoxia inducible factor-dependent upregulation of Agrp in glomus type I cells of the carotid body.

Agouti-related peptide (AgRP) is a well-established potent orexigenic peptide primarily expressed in hypothalamic neurons. Nevertheless, the expression and functional significance of extrahypothalamic AgRP remain poorly understood. In this study, utilizing histological and molecular biology techniques, we have identified a significant expression of Agrp mRNA and AgRP peptide production in glomus type I cells within the mouse carotid body (CB).

Rnd3 Ameliorates Diabetic Cardiac Microvascular Injury via Facilitating Trim40-mediated Rock1 Ubiquitination.

Diabetic microvascular dysfunction is evidenced by disrupted endothelial cell junctions and increased microvascular permeability. However, effective strategies against these injuries remain scarce. In this study, the type 2 diabetes mouse model was established by high-fat diet combined with streptozotocin injection in Rnd3 endothelial- specific transgenic and knockout mice.