Cerebral Blood Flow, Endothelial Function In Patients With Coronary Artery Disease And Arterial Hypertension Receiving Ivabradine In Combination With Perindopril

2014 
Introduction: Myocardial fibrosis is a fundamental event in the development of cardiac failure, regardless of its aetiology. Diffuse myocardial fibrosis may be relevant in the pathogenesis of heart failure with a normal left ventricular (LV) ejection fraction (HFNEF), which accounts for up to half of all cases of heart failure and carries a comparable morbidity/mortality profile. The precise mechanism of LV diastolic dysfunction in the presence of myocardial fibrosis has not previously been established. Objectives: The purpose of this study was to utilise cardiac magnetic resonance (CMR) imaging and invasive LV pressure-volume (PV) measurements to explore the relationship between diffuse myocardial fibrosis and indices of diastolic performance in a cohort of cardiac transplant recipients. Methods: We performed CMR with T1 mapping and obtained invasive LV PV mea- surements via a conductance catheter in twenty cardiac transplant recipients at the time of clinically-indicated coronary angiography. Right heart catheterization was also performed. Results: Despite normal intra-cardiac pressures, both post-contrast myocardial T1 time and extracellular volume fraction correlated with b, the load-independent passive LV stiffness constant (r ¼ -0.71, p ¼ 0.001 and r ¼ 0.58, p ¼ 0.04, respectively). Following multivariate analysis, post-contrast myocardial T1 time remained the only independent predictor of b .N o significant associations were observed between myocardial T1 time and s, the active LV relaxation constant, or other load-dependent parameters of diastolic function. Conclusion: Diffuse myocardial fibrosis, assessed by post-contrast myocardial T1 time, correlates with invasively-determined LV stiffness in cardiac transplant recipients. In pa- tients with increased diffuse myocardial fibrosis, abnormal passive ventricular stiffness may be a major contributor to diastolic dysfunction. The ability to non-invasively evaluate diffuse myocardial fibrosis using T1 mapping in a variety of cardiomyopathies may enhance our understanding of the pathogenesis and natural history of these conditions, and enable the therapeutic trials of putative anti-fibrotic agents. Disclosure of Interest: None Declared Introduction: Apolipoprotein A-I (apoA-I) induction represents a novel approach to promoting the functionality of high-density lipoproteins (HDL). The impact of apoA-I induction on plaque composition is unknown. Objectives: To evaluate the impact of the apoA-I inducer, RVX-208, on plaque compo- sition using radiofrequency analysis of intravascular ultrasound (IVUS). Methods: 323 patients with angiographic coronary artery disease and low HDL-C levels were treated with RVX-208 100 mg twice daily or placebo (3:1 allocation) for 26 weeks. IVUS imaging was performed in matched coronary artery segment at baseline and at end of the study. Radiofrequency analysis of the IVUS signal was evaluated to determine the changes in fibrotic, fibrofatty, necrotic and calcific components of plaque imaged. Results: Compared with baseline, RVX-208 increased apoA-I by 12.8% (P<0.001) and HDL-C by 11.1% (P<0.001). This associated with reductions in percent atheroma volume by 0.40% (P¼0.08) and total atheroma volume by 4.2mm 3 (P<0.001). Compared with baseline, RVX-208 administration was associated with increases in the proportion of fibrous (P¼0.04), necrotic (P¼0.007) and calcifi c( P¼0.002) and a decrease in fibrofatty (P<0.001) material. The increase in necrotic material is often observed surrounding increasing calcium signal as an artifact on radiofrequency anal- ysis. The difference in change in fibrous components was significant compared with placebo. (Table)
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