Abstract 17254: Diabetes Mellitus Significantly Impacts Left Ventricular Myocardial Structure and Function in Aortic Stenosis Before Valve Replacement
Purpose: Diabetes mellitus (DM) is an independent risk factor for progression of aortic valve stenosis (AS) and significantly impacts longterm outcome after valve replacement. High incidence of residual heart failure may account for this prognosis. We aimed to assess the impact of DM on diastolic (dys)function of AS patients.
Methods: Patients with severe isolated AS (n=46) and AS plus type-II diabetes patients (AS-DM+, n=16) with preserved left ventricular (LV) ejection fraction and no clinical or angiographic signs of coronary artery disease were studied. Doppler echocardiographic data was used to compare in vivo LV function. Biopsies were used to assess fibrosis, cardiomyocyte hypertrophy (MyD), advanced glycation endproducts (AGEs) and phosphorylation of myofilamentary proteins. Cardiomyocytes were also isolated and permeabilized to measure active force (Factive), resting force (Fpassive) and calcium sensitivity (pCa50).
Results: In isolated AS, LV deceleration time and end-diastolic pressure were augmented and the latter significantly correlated with increased fibrosis (r=0.40, p=0.04) and MyD (r=0.60, p<0.001). In AS-DM+ patients, diastolic dysfunction was exacerbated in comparison with isolated AS, as fibrosis, cardiomyocytes hypertrophy and AGEs were further increased and Fpassive significantly rose. Furthermore, AS-DM+ patients presented with a higher PKA-induced drop of pCa50, which was correlated with higher levels of PKA-induced phosphorylation of Troponin I.
Conclusions: We characterized the diastolic disturbances associated with AS chronic pressure overload alone and in the presence of diabetes. DM exacerbates the existing diastolic dysfunction of AS patients through extracellular matrix alterations (fibrosis and AGEs), Fpassive raise and PKA-mediated hyperphosphorylation status of troponin I. This study highlights the need for earlier therapeutic interventions in order to prevent the faster progression of diastolic dysfunction in diabetic AS patients.
- © 2010 by American Heart Association, Inc.