ABSTRACT
Heterogeneity in the incidence of postoperative atrial fibrillation (POAF) following heart surgery implies that underlying genetic and/or physiological factors impart a higher risk of this complication to certain patients. Glutathione peroxidase-4 (GPx4) is a vital selenoenzyme responsible for neutralizing lipid peroxides, mediators of oxidative stress known to contribute to postoperative arrhythmogenesis. Here, we sought to determine whether GPX4 single nucleotide variants are associated with POAF, and whether any of these variants are linked with altered GPX4 enzyme content or activity in myocardial tissue. Sequencing analysis was performed across the GPX4 coding region within chromosome 19 from a cohort of patients (N = 189) undergoing elective coronary artery bypass graft (−/+ valve) surgery. GPx4 enzyme content and activity were also analyzed in matching samples of atrial myocardium from these patients. Incidence of POAF was 25% in this cohort. Five GPX4 variants were associated with POAF risk (permutated p ≤ 0.05), and eight variants associated with altered myocardial GPx4 content and activity (p < 0.05). One of these variants (rs713041) is a well-known modifier of cardiovascular disease risk. Collectively, these findings suggest GPX4 variants are potential risk modifiers and/or predictors of POAF. Moreover, they illustrate a genotype−phenotype link with this selenoenzyme, which will inform future mechanistic studies.
ABSTRACT
BACKGROUND: Opioid abuse is a significant cause of morbidity and mortality in the United States, and injection drug use (IDU) is a common form of opioid abuse. IDU is a major risk factor for infections including infective endocarditis (IE). OBJECTIVES: To determine the prevalence of opioid abuse among patients with IE in both patient problem lists and diagnostic codes and describe underlying patient characteristics. METHODS: A retrospective chart review from 1-1-2010 to 11-19-2018 of a large academic medical center's patients with documented IE was performed. Demographic, comorbidity, opioid prescription data and records of drug abuse in both the patient's problem list and ICD9/10 codes were recorded. RESULTS: Of the 796 patients with documented IE, 105 patients (13.2%) had opioid abuse or related IDU in their problem list, but only 22 received an ICD-9/10 code associated with drug abuse. IE patients with opioid abuse were generally younger (43.6 vs 61.7 years [P < 0.001]), had fewer chronic comorbidities, and were prescribed opioids more often (86.7% vs 53.8% [P < 0.001]). CONCLUSIONS: Opioid abuse and IDU are commonly recorded in the problem list of patients with IE, but opioid abuse is frequently not listed as a diagnosis in administrative billing codes.
