Atrial arrhythmia in adults with sickle cell anemia: a missing link toward understanding and preventing strokes.

Although patients with homozygous sickle cell anemia (SCA) carry both significant left atrial (LA) remodeling and an increased risk of stroke, the prevalence of atrial arrhythmia (AA) has never been prospectively evaluated. The aim of this study was to identify the prevalence and predictors of atrial arrhythmia in SCA. From 2018 to 2022, consecutive adult patients with SCA were included in the DREPACOEUR prospective registry and referred to the physiology department for cardiac evaluation, including a 24-hour electrocardiogram monitoring (ECG-Holter).

Point of care CYP2C19 genotyping after percutaneous coronary intervention.

Loss-of-function CYP2C19 variants are associated with increased cumulative ischemic outcomes warranting CYP2C19 genotyping prior to clopidogrel administration. TAILOR-PCI was an international, multicenter (40 sites), prospective, randomized trial comparing rapid point of care (POC) genotype-guided vs. conventional anti-platelet therapy.

Technical Advances for the Clinical Genomic Evaluation of Sudden Cardiac Death: Verification of Next-Generation Sequencing Panels for Hereditary Cardiovascular Conditions Using Formalin-Fixed Paraffin-Embedded Tissues and Dried Blood Spots.

Background: Postmortem genetic testing for heritable cardiovascular (CV) disorders is often lacking because ideal specimens (ie, whole blood) are not retained routinely at autopsy. Formalin-fixed paraffin-embedded tissue (FFPET) is ubiquitously collected at autopsy, but DNA quality hampers its use with traditional sequencing methods. Targeted next-generation sequencing may offer the ability to circumvent such limitations, but a method has not been previously described.

Genetic variation in statin intolerance and a possible protective role for UGT1A1.

The etiology of statin intolerance is hypothesized to be due to genetic variants that impact statin disposition and clearance. We sought to determine whether genetic variants were associated to statin intolerance. The studied cohort consisted of hyperlipidemic participants (n = 90) clinically diagnosed with statin intolerance by a cardiologist and matched controls without statin intolerance.

Preemptive Pharmacogenomic Testing for Precision Medicine: A Comprehensive Analysis of Five Actionable Pharmacogenomic Genes Using Next-Generation DNA Sequencing and a Customized CYP2D6 Genotyping Cascade.

Significant barriers, such as lack of professional guidelines, specialized training for interpretation of pharmacogenomics (PGx) data, and insufficient evidence to support clinical utility, prevent preemptive PGx testing from being widely clinically implemented. The current study, as a pilot project for the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment Protocol, was designed to evaluate the impact of preemptive PGx and to optimize the workflow in the clinic setting. We used an 84-gene next-generation sequencing panel that included SLCO1B1, CYP2C19, CYP2C9, and VKORC1 together with a custom-designed CYP2D6 testing cascade to genotype the 1013 subjects in laboratories approved by the Clinical Laboratory Improvement Act.

Genetic and biochemical analyses in dyslipidemic patients undergoing LDL apheresis.

Objective: Familial hypercholesterolemia (FH) can be due to mutations in LDLR, PCSK9, and APOB. In phenotypically defined patients, a subset remains unresponsive to lipid-lowering therapies and requires low density-lipoprotein (LDL) apheresis treatment. In this pilot study, we examined the genotype/phenotype relationship in patients with dyslipidemia undergoing routine LDL apheresis.

Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing.

Long QT syndrome (LQTS) is a cardiac channelopathy associated with syncope, seizures, and sudden death. Approximately 75% of LQTS is due to mutations in genes encoding for 3 cardiac ion channel α-subunits (LQT1 to LQT3). However, traditional mutational analyses have limited detection capabilities for atypical mutations such as large gene rearrangements.

Relation of ADRB1, CYP2D6, and UGT1A1 polymorphisms with dose of, and response to, carvedilol or metoprolol therapy in patients with chronic heart failure.

The response to beta blockers in patients with heart failure could be associated with the genotype of drug-metabolizing enzymes and/or drug targets. The purpose of the present study was to determine whether specific genetic polymorphisms in ADRB1 (encoding the beta1-adrenergic receptor), CYP2D6, and UGT1A1 correlated with dose of, or response to, metoprolol or carvedilol treatment in patients with heart failure. A cohort of patients with heart failure (n = 93), characterized as responders or nonresponders to metoprolol (n = 19) or carvedilol (n = 74) therapy, was retrospectively identified.

LDLR promoter variant and exon 14 mutation on the same chromosome are associated with an unusually severe FH phenotype and treatment resistance.

Familial hypercholesterolemia (FH) is the most common form of autosomal-dominant hypercholesterolemia, and is caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Heterozygous FH is characterized by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular disease, whereas homozygous FH results in more severe LDL cholesterol elevation with death by 20 years of age. We present here the case of an African-American female FH patient presenting with a myocardial infarction at the age of 48, recurrent angina pectoris and numerous coronary artery stents.