Atrial Fibrillation and Clonal Hematopoiesis in TET2 and ASXL1.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP) may contribute to the risk of atrial fibrillation (AF) through its association with inflammation and cardiac remodeling. Objective: To determine whether CHIP was associated with AF, inflammatory and cardiac biomarkers, and cardiac structural changes. Design, Setting, and Participants: This was a population-based, prospective cohort study in participants of the Atherosclerosis Risk in Communities (ARIC) study and UK Biobank (UKB) cohort. Samples were collected and echocardiography was performed from 2011 to 2013 in the ARIC cohort, and samples were collected from 2006 to 2010 in the UKB cohort. Included in this study were adults without hematologic malignancies, mitral valve stenosis, or previous mitral valve procedure from both the ARIC and UKB cohorts; additionally, participants without hypertrophic cardiomyopathy and congenital heart disease from the UKB cohort were also included. Data analysis was completed in 2023. Exposures: CHIP (variant allele frequency [VAF] ≥2%), common gene-specific CHIP subtypes (DNMT3A, TET2, ASXL1), large CHIP (VAF ≥10%), inflammatory and cardiac biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], IL-18, high-sensitivity troponin T [hs-TnT] and hs-TnI, N-terminal pro-B-type natriuretic peptide), and echocardiographic indices. Main Outcome Measure: Incident AF. Results: A total of 199 982 adults were included in this study. In ARIC participants (4131 [2.1%]; mean [SD] age, 76 [5] years; 2449 female [59%]; 1682 male [41%]; 935 Black [23%] and 3196 White [77%]), 1019 had any CHIP (24.7%), and 478 had large CHIP (11.6%). In UKB participants (195 851 [97.9%]; mean [SD] age, 56 [8] years; 108 370 female [55%]; 87 481 male [45%]; 3154 Black [2%], 183 747 White [94%], and 7971 other race [4%]), 11 328 had any CHIP (5.8%), and 5189 had large CHIP (2.6%). ARIC participants were followed up for a median (IQR) period of 7.0 (5.3-7.7) years, and UKB participants were followed up for a median (IQR) period of 12.2 (11.3-13.0) years. Meta-analyzed hazard ratios for AF were 1.12 (95% CI, 1.01-1.25; P = .04) for participants with vs without large CHIP, 1.29 (95% CI, 1.05-1.59; P = .02) for those with vs without large TET2 CHIP (seen in 1340 of 197 209 [0.67%]), and 1.45 (95% CI, 1.02-2.07; P = .04) for those with vs without large ASXL1 CHIP (seen in 314 of 197 209 [0.16%]). Large TET2 CHIP was associated with higher IL-6 levels. Additionally, large ASXL1 was associated with higher hs-TnT level and increased left ventricular mass index. Conclusions and Relevance: Large TET2 and ASXL1, but not DNMT3A, CHIP was associated with higher IL-6 level, indices of cardiac remodeling, and increased risk for AF. Future research is needed to elaborate on the mechanisms driving the associations and to investigate potential interventions to reduce the risk.

Association of Glutathione S-Transferase theta 1 and mu 1 Genes Polymorphisms with the Susceptibility of Myocardial Infarction in Bangladesh.

BACKGROUND: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide. Oxidative stress plays a vital role in the pathogenesis of atherosclerosis leading to myocardial infarction and Glutathione S-transferases (GSTs) act as detoxifying enzymes to reduce oxidative stress. The aim of the present study was to investigate the associations of the GST (T1 & M1) gene polymorphism with the susceptibility of myocardial infarction in the Bangladeshi population. METHODS: A case-control study on 100 cardiac patients with MI and 150 control subjects was conducted. The genotyping of GST (T1 & M1) gene was done using conventional Polymerase Chain Reaction. RESULTS: The percentage of GSTM1 genotypes was significantly (p< 0.01) lower in patients compared to control subjects while the GSTT1 genotypes were not significantly different between the study subjects. The individual with GSTM1 null allele was at 2.5-fold increased risk {odds ratio (OR)= 2.5; 95 % confidence interval (95 % CI)= 1.4 to 4.3; p< 0.01} of experiencing MI while individual with either GSTM1 or GSTT1 genotypes was at lower risk. In the case of GST M1 and GST T1 combined genotype, patients having both null genotypes for GST M1 and GST T1 gene showed significantly (p< 0.01) higher risk of experiencing MI when compared to control subjects (OR= 3.5; 95% CI= 1.7-7.2; p< 0.001). CONCLUSION: Thus our recent study suggested that GSTM1 alone and GSTM1 and T1 in combination augments the risk of MI in Bangladeshi population.

A novel software program for detection of potential air emboli during cardiac surgery.

BACKGROUND: Risks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time. FINDINGS: We created a software algorithm ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation", or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface. CONCLUSIONS: While monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.