Hypertension is the most common cardiovascular condition in recreational athletes, especially older (masters) athletes. The interacting effects of hypertension, cardiac adaptation to endurance training, and antihypertensive medications on exercise performance are complex and of relevance to athletes, trainers, and health care providers. Cardiac adaptations occur in response to aging and endurance training, and findings may overlap with pathologic cardiac remodeling.
View Article and Find Full Text PDFAims: Enalapril is a prodrug and needs to be activated by carboxylesterase 1 (CES1). A previous in vitro study demonstrated the CES1 genetic variant, G143E (rs71647871), significantly impaired enalapril activation. Two previous clinical studies examined the impact of G143E on single-dose enalapril PK (10 mg); however, the results were inconclusive.
View Article and Find Full Text PDFTrandolapril, an angiotensin-converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1-mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects.
View Article and Find Full Text PDFPurpose: To determine whether routine postprocedure chest radiography is indicated to exclude pneumothorax after outpatient right heart catheterization with or without endomyocardial biopsy.
Methods: This HIPAA-compliant retrospective quality improvement cohort study was approved by the institutional review board. All outpatients from January 1, 2010, to July 1, 2017, who underwent routine postprocedure chest radiography after right heart catheterization with or without endomyocardial biopsy formed the study population (n = 6,036).
Heart failure affects more than 6 million people in the United States and incurs a heavy toll in morbidity, mortality, and health care costs. It frequently coexists with other important disorders, including hypertension, coronary artery disease, diabetes, and obesity. Decades of clinical trials have shown that several medications and interventions are effective for improving outcomes; however, mortality and hospitalization rates remain high.
View Article and Find Full Text PDFBackground: Tricuspid regurgitation after cardiac transplantation is associated with worse clinical outcomes. This study sought to determine the association of donor tricuspid valve repair (dTVR) with outcomes after cardiac transplantation.
Methods: Patients who underwent cardiac transplantation between January 20, 2002, and December 31, 2016, were included.
Drug Metab Dispos
November 2017
Carboxylesterase 1 (CES1) is the predominant human hepatic hydrolase responsible for the metabolism of many clinically important medications. CES1 expression and activity vary markedly among individuals; and genetic variation is a major contributing factor to CES1 interindividual variability. In this study, we comprehensively examined the functions of nonsynonymous single nucleotide polymorphisms (nsSNPs) and haplotypes using transfected cell lines and individual human liver tissues.
View Article and Find Full Text PDFCentrifugal (CFG) and axial flow (AX) left ventricular assist devices have different hydrodynamic properties that may impact the effectiveness of left ventricular unloading. We sought to determine whether patients implanted with the HeartWare HVAD (CFG) and HeartMate II (AX) had a similar degree of hemodynamic support by comparing parameters measured using echocardiography and right heart catheterization. Using our prospectively collected database, we identified 268 patients implanted with the AX and 93 with the CFG.
View Article and Find Full Text PDFSacubitril was recently approved by the Food and Drug Administration for use in combination with valsartan for the treatment of patients with heart failure with reduced ejection fraction. As a prodrug, sacubitril must be metabolized (hydrolyzed) to its active metabolite sacubitrilat (LBQ657) to exert its intended therapeutic effects. Thus, understanding the determinants of sacubitril activation will lead to the improvement of sacubitril pharmacotherapy.
View Article and Find Full Text PDFThis review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology.
View Article and Find Full Text PDFIntroduction: Vitamin D deficiency has been associated with the development of myocardial hypertrophy and inflammation. These findings suggest that vitamin D status and vitamin D receptor (VDR) genomics may play a role in myocardial fibrosis. The aim of this pilot study was to determine the association between vitamin D levels, VDR polymorphisms, and biomarkers of left ventricular remodeling and hemodynamics.
View Article and Find Full Text PDFObjective: Obesity has been associated with superior outcomes in heart failure (HF) and acute coronary syndrome (ACS). Although patients with new-onset HF after ACS are at a high risk, they may receive less aggressive treatment. It is unknown whether treatment practices are biased by BMI.
View Article and Find Full Text PDFPurpose: Hypoalbuminemia is believed to decrease diuretic effectiveness and contribute to diuretic resistance that is observed in patients with nephrotic syndrome. Hypoalbuminemia is also seen in patients with acute decompensated heart failure (ADHF). However, the role of hypoalbuminemia on the effectiveness of continuous infusion diuretics in patients with ADHF is not known.
View Article and Find Full Text PDFThe bilirubin level has been associated with worse outcomes, but it has not been studied as a predictor for the mode of death in patients with systolic heart failure. The Prospective Randomized Amlodipine Evaluation Study (PRAISE) cohort (including New York Heart Association class IIIB-IV patients with left ventricular ejection fraction <30%, n = 1,135) was analyzed, divided by bilirubin level: ≤0.6 mg/dl, group 1; >0.
View Article and Find Full Text PDFObjectives: To determine whether risk for implantable cardioverter-defibrillator (ICD) therapy varies by body mass index (BMI) in systolic heart failure (HF).
Background: It is unknown whether obesity increases sudden death risk in patients with systolic HF.
Methods: Secondary analysis of patients with HF, left ventricular ejection fraction ≤0.
A 42-year-old woman with a history of cardiomyopathy and multiple ablation procedures for atrial tachycardia developed intra-atrial conduction block that mimicked atrioventricular (AV) nodal block during radiofrequency ablation at the cavotricuspid isthmus. She was treated with atrial pacing (from the coronary sinus), which overcame intra-atrial conduction block and resulted in AV nodal conduction.
View Article and Find Full Text PDFBackground: Previous studies have not extensively examined the association of hyperuricemia and adverse outcomes in systolic heart failure (HF) in relation to xanthine oxidase inhibitor therapy.
Methods: The Prospective Randomized Amlodipine Survival Evaluation study included New York Heart Association class IIIB or IV patients with left ventricular ejection fraction <30%. For analysis, the population was divided into uric acid quartiles among nonallopurinol users (2.
Aims: To determine the association between obesity and outcomes in post-acute myocardial infarction (AMI) patients with systolic heart failure (HF).
Methods And Results: Of the 6632 Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) participants, 6611 had data on baseline body mass index (BMI) and 6561 had BMI > or = 18.5 kg/m(2).
Several studies have suggested that obesity may be associated with a survival advantage in heart failure (HF). The duration of HF likely influences disease severity and may introduce lead-time bias into analyses of outcomes. The aim of this study was to analyze a cohort in which the exact time of HF onset could be determined: patients in the University of Michigan subset of the acute coronary syndromes (ACS) database of the Global Registry of Acute Coronary Events (GRACE) who developed new-onset HF (no history of HF and left ventricular ejection fraction