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From GWAS Hits to Treatment Targets
Genome-wide association (GWA) studies, as a prototype of large-scale OMICs studies, have advanced our understanding of the genetic basis of many common diseases. With respect to coronary artery disease (CAD) and cardiovascular risk factors, like lipids, blood pressure or BMI, they have identified hundreds of chromosomal loci that modulate disease risk. Despite their scientific success, GWA studies have been criticized for having failed so far in delivering diagnostically or therapeutically relevant products. However, the ability to achieve such goals has been strengthened recently by further layers of OMICs-based data, including large-scale transcriptomics data, and better annotation of regu...
Prognostic Impact and Diagnostic Value of Invasively Derived Hemodynamic Measures in Patients with Severe Aortic Stenosis Undergoing TAVI
Abstract: Background Ejection time (ET), acceleration time (AT) and time between left ventricular and aortic systolic pressure peaks (T-LVAo) might be of diagnostic and prognostic use in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Aim We aimed to assess the diagnostic value and prognostic impact of invasively measured ET, AT, and T-LVAo in patients undergoing TAVI. Methods A total of 1274 patients received invasive measurement of ET, AT and T-LVAo prior to TAVI. Anatomic AS severity was assessed by CT-derived aortic valve calcification density (AVCd). Impact on all-cause mortality was retrospectively analyzed. Results In multivariable linear regression, T-LVAo showed the strongest correlation with AVCd. No prognostic impact of T-LVAo was found according to uni- and multivariable analyses. In contrast, using an individual C-statistic derived cutoff (CD), patients with ET or AT ≥ CD showed lower mortality rates compared to patients with ET or AT CD (1-year mortality: ET ≥ vs. CD: 15.01vs. 33.1%, AT ≥ vs CD 16.3 vs. 26.5%, p
