Drug-Drug Interaction Potential of Mavacamten with Midazolam: Combined Results from Clinical and Model-Based Studies.

Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single-center, open-label study in healthy participants.

Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.

Background And Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD.

Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]).

Effects of Omeprazole and Verapamil on the Pharmacokinetics, Safety, and Tolerability of Mavacamten: Two Drug-Drug Interaction Studies in Healthy Participants.

Two open-label, Phase 1 studies assessed the effects of omeprazole (a weak to moderate cytochrome P450 [CYP] 2C19 inhibitor) and verapamil (a moderate CYP3A4 inhibitor) on the pharmacokinetics, safety, and tolerability of mavacamten. In the omeprazole study, healthy participants received mavacamten 15 mg alone or with a 31-day course of omeprazole 20 mg once daily. In the verapamil study, healthy participants received mavacamten 25 mg alone or with a 28-day course of verapamil 240 mg once daily.

Drug-Drug Interaction Potential of Mavacamten with Oral Contraceptives: Results from a Clinical Pharmacokinetic Study and a Physiologically Based Pharmacokinetic Model.

Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and, as such, could reduce the exposure of the active components of oral contraceptives, ethinyl estradiol (EE) and norethindrone (NOR), where CYP3A4 is involved in metabolism. This study assessed if repeat doses of mavacamten led to a drug-drug interaction with EE and/or NOR. This was an open-label study in healthy women.

A Patient-Centered Model of Fast-Track Lung Cancer Diagnosis.

Introduction: Despite the increasing importance of digital resources in modern life over the past decades, little is known about the impact of internet-based solutions on patient's health. We aimed to study the potential benefit of a digital platform helping patients to deal with abnormal chest CT scan revealing possible lung cancer.

Methods: We set up a fast-track lung cancer diagnosis pathway through a secure online platform.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes.

Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial.

Importance: Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear.

Objective: To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET).

Allogeneic Cell Combination Therapy Ameliorates Chronic Kidney Disease-Induced Heart Failure with Preserved Ejection Fraction.

Background: Left ventricular hypertrophy and heart failure with preserved ejection fraction (HFpEF) are primary manifestations of the cardiorenal syndrome in patients with chronic kidney disease (CKD). Therapies that improve morbidity and mortality in HFpEF are lacking. Cell-based therapies promote cardiac repair in ischemic and non-ischemic cardiomyopathies.

Lung and heart-lung transplantation for children with PAH: Dramatic benefits from the implementation of a high-priority allocation program in France.

Purpose: Pulmonary arterial hypertension (PAH) is rare but remains fatal in infants and children despite the advance of targeted therapies. Lung transplantation (LTx), first performed in pediatric patients in the 1980s, is, with the Potts shunt, the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool, resulting-together with peculiarities of PAH in infants-in high waitlist mortality.

Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction.

Therapies for heart failure with preserved ejection fraction (HFpEF) are lacking. Growth hormone-releasing hormone agonists (GHRH-As) have salutary effects in ischemic and nonischemic heart failure animal models. Accordingly, we hypothesized that GHRH-A treatment ameliorates chronic kidney disease (CKD)-induced HFpEF in a large-animal model.

Lung transplantation for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by relentlessly progressive lung function impairment that is consistently fatal in the absence of lung transplantation, as no curative pharmacological treatment exists. The pace of progression varies across patients, and acute life-threatening exacerbations occur unpredictably, causing further sharp drops in lung function. Recently introduced antifibrotic agents slow the pace of disease progression and may improve survival but fail to stop the fibrotic process.

The impact of patient sex on the response to intramyocardial mesenchymal stem cell administration in patients with non-ischaemic dilated cardiomyopathy.

Aims: Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, the phenotypic presentation of patients with non-ischaemic dilated cardiomyopathy (NIDCM) differs between men and women. However, whether the response to mesenchymal stem cell (MSC) therapy is influenced by sex remains unknown.

Prevalence of Trachoma in Pakistan: Results of 42 Population-Based Prevalence Surveys from the Global Trachoma Mapping Project.

: Previous phases of trachoma mapping in Pakistan completed baseline surveys in 38 districts. To help guide national trachoma elimination planning, we set out to estimate trachoma prevalence in 43 suspected-endemic evaluation units (EUs) of 15 further districts.: We planned a population-based trachoma prevalence survey in each EU.

Atrial Fibrillation in the Elderly: The Role of Sub-Clinical Isolated Cardiac Amyloidosis.

Amyloid infiltration of the atrium is described in patients with valvular heart disease and is associated with an increased risk for atrial fibrillation(AF) while amyloid deposits in the ventricles is increasingly being diagnosed in patients with HFpEF. The role of amyloid deposits in patients with AF without valvular heart disease, which represents the most common form of AF globally, is undefined. In this study, we sought to assess the prevalence of sub-clinical isolated cardiac amyloidosis (ICA) at autopsy and the odds of AF in these patients.

Genetic determinants of responsiveness to mesenchymal stem cell injections in non-ischemic dilated cardiomyopathy.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness to MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial.

Methods: POSEIDON-DCM patients (n = 34) underwent genetic sequence analysis and deletion/duplication testing.

Impact of diastolic dysfunction on long-term mortality and quality of life after transcatheter aortic valve replacement.

Background: There is conflicting data as to whether diastolic dysfunction (DD) affects the prognosis of patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR).

Methods: Consecutive patients undergoing TAVR underwent assessment of DD with preoperative echocardiography and NT-pro BNP. Long-term survival was ascertained every 6 months by clinic visits or phone.

Intravascular Stem Cell Bioreactor for Prevention of Adverse Remodeling After Myocardial Infarction.

Background Prevention of adverse remodeling after myocardial infarction (MI) is an important goal of stem cell therapy. Clinical trial results vary, however, and poor cell retention and survival after delivery likely limit the opportunity to exert beneficial effects. To overcome these limitations, we built an implantable intravascular bioreactor (IBR) designed to protect contained cells from washout, dilution, and immune attack while allowing sustained release of beneficial paracrine factors.

Attenuation of frailty in older adults with mesenchymal stem cells.

Aging frailty is a syndrome characterized by a progressive decline in health and clinical symptoms of exhaustion, weight loss, a feeling of slowing down, and a decrease in functional capacity. The biological substrate for frailty is sarcopenia, which is potentiated by chronic inflammation and depletion or impairment of endogenous precursor and stem cells. Current interventions focus on interdisciplinary approaches which include nutritional supplementation, physical exercise, and cognitive intervention.

Prevalence of Trachoma in Kogi State, Nigeria: Results of four Local Government Area-Level Surveys from the Global Trachoma Mapping Project.

Purpose: To determine the prevalence of trachoma in four Local Government Areas (LGAs) of Kogi State, Nigeria.

Methods: In June 2014, we conducted population-based, cross-sectional surveys according to Global Trachoma Mapping Project (GTMP) protocols in selected LGAs of Kogi State. In each LGA, 25 clusters were selected with probability proportional to size.

Prevalence of and risk factors for trachoma in Kwara state, Nigeria: Results of eight population-based surveys from the Global Trachoma Mapping Project.

Purpose: To determine the prevalence of and risk factors for trachoma in selected local government areas (LGAs) of Kwara State, Nigeria.

Methodology: Population-based cross-sectional surveys were conducted in eight LGAs of Kwara State using Global Trachoma Mapping Project (GTMP) protocols. In each LGA, 25 villages were selected using probability-proportional-to-size sampling; 25 households were selected from each village using compact segment sampling.

Endobronchial ultrasound-guided fine-needle aspiration for pulmonary carcinomas genotyping: experience with 398 cases including rapid analysis in 43 cases.

Background: Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) of mediastinal lymph nodes is a minimally invasive and efficient tool for both diagnosis and staging of lung cancer. EBUS-FNA also permits tumor genotyping. However this critical datum for the therapeutic management is often long to obtain for metastatic patients with short life expectancy.

Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy.

Background: Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done.

Methods And Results: We conducted a subanalysis of 3 single-center, randomized, and blinded clinical trials: (1) TAC-HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON-DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy).