CORONARY PERFUSION:IMPACT OF FLOW DYNAMICS AND GEOMETRIC DESIGN OF TWO DIFFERENT AORTIC PROSTHESES OF SIMILAR SIZE

BackgroundAortic valve replacement leads to improvement of coronary flow but not to complete normalization. Coronary hypoperfusion contributes to higher left ventricular mass persistence, arrhythmias, congestive heart failure and sudden death. This prospective study compares 2 similarly sized aortic prostheses (mechanical and porcine) regarding coronary flow and hemodynamic performances in patients who underwent surgery for pure aortic stenosis.MethodsSixty patients having undergone aortic valve replacement for pure aortic stenosis with Medtronic Mosaic Ultra bioprosthesis 21 mm (n = 30) or St Jude Regent mechanical valve 19 mm (n = 30) were evaluated preoperatively and 12 months postoperatively comparing the coronary flow and the hemodynamic behavior. Echocardiography and cardiac positron emission tomography were performed at rest and during exercise or adenosine maximal stimulation, respectively.ResultsThe St Jude Regent mechanical valve, compared with the Medtronic Mosaic Ultra bioprosthesis, had reduced coronary flow reserve (2.1 ± 0.3 vs 2.3 ± 0.2; P = .003), less favorable systolic/diastolic time ratio (0.87 ± 0.02 vs 0.78 ± 0.03; P < .001), and higher mean transprosthetic gradient (46 ± 11 vs 38 ± 9; P = .003) during exercise. Multivariate analysis of impaired coronary reserve related indexed effective orifice area less than 0.65 cm/m2 (risk ratio [RR], 1.9; 95% confidence intervals [CI], 1.5-2.8; P < .001), mechanical valve (RR, 2.5; 95% CI, 1.7-3.3; P < .001), and systolic/diastolic time ratio greater than 0.75 (RR, 2.6; 95% CI, 1.8-3.8; P < .001), as well as high transprosthetic gradient (RR, 1.7; 95% CI, 1.3-2.4; P < .001) ) during exercise with coronary reserve less than 2.2.ConclusionsImprovement of coronary flow and reserve was more evident for bioprostheses than for mechanical valves. The bioprostheses demonstrated superior hemodynamics during exercise, which may have some impact on exercise capability during normal daily life

Large-scale association analyses identify host factors influencing human gut microbiome composition

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P <5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) <P <5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis

Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits

Genome-wide association studies (GWAS) have identified thousands of variants associated with complex traits, but their biological interpretation often remains unclear. Most of these variants overlap with expression QTLs, indicating their potential involvement in regulation of gene expression. Here, we propose a transcriptome-wide summary statistics-based Mendelian Randomization approach (TWMR) that uses multiple SNPs as instruments and multiple gene expression traits as exposures, simultaneously. Applied to 43 human phenotypes, it uncovers 3,913 putatively causal gene-trait associations, 36% of which have no genome-wide significant SNP nearby in previous GWAS. Using independent association summary statistics, we find that the majority of these loci were missed by GWAS due to power issues. Noteworthy among these links is educational attainment-associated BSCL2, known to carry mutations leading to a Mendelian form of encephalopathy. We also find pleiotropic causal effects suggestive of mechanistic connections. TWMR better accounts for pleiotropy and has the potential to identify biological mechanisms underlying complex traits