Evaluating the Effect of Estimating Renal Function With the CKD-EPI 2021 Equation on the ABCD-GENE Score for Clopidogrel Response Prediction.

The ABCD-GENE score was developed to predict poor response to clopidogrel and includes Age, Body mass index, Chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m), Diabetes, and CYP2C19 GENE variants; a score ≥ 10 is predictive of reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). Estimation of GFR without a race variable via the CKD-EPI Scr 2021 equation is now recommended.

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy.

Beta-blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g.

Omega-3 fatty acids in the treatment of heart failure.

Omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) have garnered increased attention as a therapeutic option in cardiovascular disease. Most of the research to date has focused on their lipid altering effects and clinical benefits in patients with coronary artery disease, however, there are data supporting their use in the treatment of heart failure. We review the mechanisms through which Ω-3 PUFAs exert their positive effects on the cardiovascular system and highlight the observational and treatment studies that assessed their effects in patients with heart failure.

Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

Background: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.

Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.

Background: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear.

Methods: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects.

Using Omics to Identify Novel Therapeutic Targets in Heart Failure.

Omics refers to the measurement and analysis of the totality of molecules or biological processes involved within an organism. Examples of omics data include genomics, transcriptomics, epigenomics, proteomics, metabolomics, and more. In this review, we present the available literature reporting omics data on heart failure that can inform the development of novel treatments or innovative treatment strategies for this disease.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

Background: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

Effectiveness of Clopidogrel vs Alternative P2Y Inhibitors Based on the ABCD-GENE Score.

Background: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear.

Objectives: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI).

Methods: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y inhibitor treatment were included.

Estimating preferences and willingness to pay for pharmacogenetic testing in populations who are medically underserved: a discrete choice experiment.

The implementation of pharmacogenetic (PGx) testing may contribute to health disparities if access to testing is inequitable, as medically underserved patients are prescribed higher rates of drugs with PGx guidelines and often experience the benefits of emerging health technologies last. Limited research has evaluated potential implementation of PGx testing in populations who are medically underserved and none have evaluated their preferences regarding PGx test characteristics and cost. Our study endeavored to assess the willingness to pay for PGx testing and key PGx test preferences in a nationwide cohort of medically underserved respondents.

Feasibility of preemptive pharmacogenetic testing and improvement of medication treatment satisfaction among medically underserved patients.

Previous findings suggest that medically underserved patients are prescribed medications with pharmacogenetic (PGx) guidelines at a high frequency. Thus, underserved patients may especially benefit from PGx testing, but little evidence exists regarding the effect of testing in this population. This pilot study aimed to generate key feasibility data and explore clinical outcomes of PGx implementation in underserved populations.

An Introductory Tutorial on Cardiovascular Pharmacogenetics for Healthcare Providers.

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information.

Pharmacist-guided pharmacogenetic service lowered warfarin-related hospitalizations.

The authors aimed to assess outcomes with a pharmacogenetic (PGx)-informed, pharmacist-guided, personalized consult service for warfarin dosing. This retrospective cohort study included patients admitted with thromboembolic events. Eligible subjects received either PGx-informed (n = 389) or historical non-PGx pharmacist-guided warfarin dosing (Hx; n = 308) before hospital discharge.

Exploring perceptions, knowledge, and attitudes regarding pharmacogenetic testing in the medically underserved.

Pharmacogenetic testing may hold promise in addressing health disparities, as medically underserved patients appear to be prescribed medications with pharmacogenetic guidelines at higher rates. While routine clinical implementation of testing in medically underserved populations has not yet been achieved, using patient perspectives to inform implementation should increase the likelihood of success. The aim of this study was to assess the perceptions, knowledge, and attitudes regarding pharmacogenetic testing in medically underserved patients.

Patients' Perspectives of Factors That Influence Pharmacogenetic Testing Uptake: Enhancing Patient Counseling and Results Dissemination.

Patient preferences for pharmacogenetic (PGx) counseling, testing and results dissemination are not well-established, especially in medically underserved Black and Latino populations. The aim of this study was to capture the preferences of Black and Latino patients who received PGx testing to ascertain: (1) factors enhancing their willingness to do testing and (2) preferences for the dissemination of results. Using the constant comparative method, we thematically analyzed interviews with 13 patients from medically underserved populations who had undergone PGx testing.

Evaluation of Potential Racial Disparities in CYP2C19-Guided P2Y Inhibitor Prescribing After Percutaneous Coronary Intervention.

Black patients suffer worse outcomes after percutaneous coronary intervention (PCI) than White patients. Inequities in antiplatelet prescribing may contribute to this health disparity. We compared P2Y inhibitor prescribing by race following CYP2C19 genotyping to guide antiplatelet therapy selection after PCI.

Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease.

Background: Ischemic coronary heart disease (IHD) is the leading cause of death worldwide. Genetic variation is presumed to be a major factor underlying sex differences for IHD events, including mortality. The purpose of this study was to identify sex-specific candidate genes associated with all-cause mortality among people diagnosed with coronary artery disease (CAD).

Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention in Diverse Clinical Settings.

Background Studies have demonstrated increased risk of major atherothrombotic events in loss-of-function (LOF) variant carriers versus non-carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of -guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included.

Changing from mandatory to optional genotyping results in higher acceptance of pharmacist-guided warfarin dosing.

We evaluated the clinical acceptance and feasibility of a pharmacist-guided personalized consult service following its transition from a mandatory (mPGx) to optional (oPGx) // genotyping for warfarin. A total of 1105 patients were included. Clinical acceptance and feasibility outcomes were analyzed using bivariate and multivariable analyses.

β1-receptor polymorphisms and junctional ectopic tachycardia in children after cardiac surgery.

Junctional ectopic tachycardia (JET) is a potentially life-threatening postoperative arrhythmia in children with specific congenital heart defects and can contribute significantly to postoperative morbidity for at-risk populations. In adults, β1-adrenergic receptor (ADRB1) and β2-adrenergic receptor (ADRB2) genotypes have been associated with increased risk for arrhythmias. However, their association with arrhythmia risk in children is unknown.

Genetic polymorphisms in ADRB2 and ADRB1 are associated with differential survival in heart failure patients taking β-blockers.

Single nucleotide polymorphisms (SNPs) have been associated with differential beta-blocker (BB) effects on heart rate, blood pressure, and left ventricular ejection fraction in various patient populations. This study aimed to determine if SNPs previously associated with BB response are also associated with differential survival in heart failure (HF) patients receiving BBs. HF patient data were derived from electronic health records and the Social Security Death Index.

NR3C2 genotype is associated with response to spironolactone in diastolic heart failure patients from the Aldo-DHF trial.

Study Objective: This study aimed to determine if variants in NR3C2, which codes the target protein of spironolactone, or CYP11B2, which is involved in aldosterone synthesis, were associated with spironolactone response, focused on the primary end point of diastolic function (E/e'), in Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) participants.

Design: Post-hoc genetic analysis.

Data Source: Data and samples were derived from the multi-center, randomized, double-blind, placebo-controlled Aldo-DHF trial.

Cox-sMBPLS: An Algorithm for Disease Survival Prediction and Multi-Omics Module Discovery Incorporating -Regulatory Quantitative Effects.

Background: The development of high-throughput techniques has enabled profiling a large number of biomolecules across a number of molecular compartments. The challenge then becomes to integrate such multimodal Omics data to gain insights into biological processes and disease onset and progression mechanisms. Further, given the high dimensionality of such data, incorporating prior biological information on interactions between molecular compartments when developing statistical models for data integration is beneficial, especially in settings involving a small number of samples.

Multisite investigation of strategies for the clinical implementation of pre-emptive pharmacogenetic testing.

Purpose: The increased availability of clinical pharmacogenetic (PGx) guidelines and decreasing costs for genetic testing have slowly led to increased utilization of PGx testing in clinical practice. Pre-emptive PGx testing, where testing is performed in advance of drug prescribing, is one means to ensure results are available at the time of prescribing decisions. However, the most efficient and effective methods to clinically implement this strategy remain unclear.