Abstract 12007: Association of Thrombin Generation with Left Ventricular Diastolic Dysfunction in Hypertensive Patients with Heart Failure with Preserved Ejection Fraction
Purpose: Thrombin is not only one of the key players in the coagulation cascade, but also has a role as a vasomotor regulator. In the heart, Protease-activated receptor-1 (PAR-1) which is the high-affinity receptor for thrombin, is expressed in cardiac fibroblasts and cardiomyocytes; in which there are some reports said to contribute to cardiac remodeling and hypertrophy (Circ 2007). Importantly, a recent study showed that PAR-1 expression was significantly increased in human end-stage heart failure and instigated cardiac remodeling (J Cell Mol Med, 2005). Yet there is no report regarding the impact of thrombin on cardiac diastolic dysfunction. In this study, we hypothesized that thrombin may participate in the development of cardiac remodeling and may be associated with left ventricular diastolic dysfunction (LVDD).
Methods: A total of 58 patients with hypertension (Control n=17, Heart failure with preserved ejection fraction (HFPEF) n=41) underwent cardiac magnetic resonance (CMR) and echocardiography to assess LVDD. Blood samples were taken to measure prothrombin F1+2 (F1+2), as a marker of thrombin generation, D-dimer, and BNP. As indices of LVDD, early: peak diastolic filling rate (PFR) and time to peak filling rate (T-PFR) were assessed by CMR. Images were acquired in contiguous 6-8 short-axis slices (1cm interval) through the LV, and the LV volumetric changes were analyzed. Deceleration time, E/A ratio, E/e’, and EF were measured using echocardiography. Relationship between F1+2 and these indices of LVDD were investigated using Spearman’s rank sum test.
Results: All patients had preserved LV systolic function (EF>40%). Among all parameters tested, F1+2 (median and interquartile range (IQR) = 206.5, 162.5-321.3 pmol/l vs 148.5, 119.78-177.8), E/e’ (12.5±0.7 vs 9.5±1.1) levels were greater, T-PFR (168.4±7.2 ms vs 136.4±10.7) were longer, and BNP levels were greater in HFPEF than in Control. Within HFPEF, F1+2 correlated significantly (p<0.05) with stroke volume-adjusted PFR (ρ=-0.43), T-PFR (ρ=0.54), E/e’ (ρ=0.54), and BNP (ρ=0.47), respectively. There was no significant correlation with E/A ratio and deceleration time.
Conclusions: Prothrombic state may participate in the impairment of LV early diastolic filling in patients with HFPEF.
- © 2012 by American Heart Association, Inc.