Systemic endothelial dysfunction as an early predictor of adverse outcome in heart failure

Objective - Endothelial dysfunction is an early event in the natural progression of heart failure. Increased oxidative stress has been linked to impaired endothelial function and both may play a prognostic role. Methods and Results - Endothelium-dependent and endothelium-independent vasodilatation were determined in 289 patients with mild left ventricular dysfunction by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. Vascular effects of the coadministration of the antioxidant vitamin C at pharmacological doses ( 24 mg/min) were assessed. Occurrence of death, heart transplantation, and readmission with worsening heart failure were recorded as clinical outcome parameters during a follow-up period of 4.8 years. Patients experiencing adverse events ( n = 79) had lower vasodilator responses to acetylcholine ( P < 0.001) and to sodium nitroprusside ( P = 0.03) compared with patients without events. However, beneficial effects of vitamin C did not differ between both groups. Cox proportional hazards model demonstrated that age ( P = 0.001), renal function ( P = 0.001), and blunted acetylcholine-induced vasodilatation ( P = 0.007) remained independent predictors of adverse outcome. Conclusions - Impaired peripheral endothelial function independently predicts long-term adverse outcome in patients with early-stage heart failure. The findings suggest that assessment of peripheral endothelial function may represent an additional mean for risk stratification and therapy management in these patients.