Abstract 19068: Connective Tissue Growth Factor in Human Diastolic Heart Failure from the Taiwan Diastolic Heart Failure Registry and a Canine Model of Diastolic Dysfunction

Abstract

BACKGROUND: Diastolic heart failure (DHF) is characterized by myocardial interstitial fibrosis and left ventricular hypertrophy. The study investigated the association between connective tissue growth factor (CTGF) and DHF from animal model to clinical indices. METHODS: The participants of current study were enrolled from the Taiwan Diastolic Heart Failure Registry (TDHFR). 1284 patients were screened and a total of 125 patients with a diagnosis of DHF confirmed by echocardiography were recruited. The severity of DHF was decided according to tissue doppler imaging (E/e’). Soluble plasma levels of CTGF were measured in all subjects and the associations with diastolic function parameters were calculated. Canine model of DHF was induced by aortic banding. Hemodynamic and echocardiographic data were obtained before and after pressure loading (at baseline and after 2 weeks). Myocardium tissues were collected, and western blotting was used to detect the protein expression of CTGF for each dog. The correlation between CTGF, the severity of diastolic dysfunction and hemodynamic changes was then calculated. RESULTS: Patients with severe DHF presented significantly higher plasma CTGF levels than the controls. Significant correlation were found for plasma CTGF and E/e’ (r = 0.80, p<0.001) in advanced DHF patients (E/e’ >15). After 2 weeks in canine models, the protein expression of CTGF from LV myocardial tissue was significantly increased (p<0.01) compared with the controls (shame dogs). Moreover, the expression of CTGF paralleled the severity of LV diastolic dysfunction parameters (r= 0.70, p= 0.03 for E/e’) and hemodynamic changes (r= 0.75, p= 0.02). After adjusting the possible confounding factors for diastolic dysfunction, CTGF levels were associated with diastolic parameters both in human and canine models (Plasma CTGF, B=0.064, p<0.001; tissue CTGF, B= 9.87, p = 0.05). CONCLUSIONS: Both Plasma and myocardium CTGF levels had significant correlations to the severity of DHF. Our study offered the evidence to apply novel therapies for DHF patients aim to down-regulate the overexpression of CTGF.