Abstract 3752: Vascular Responses to Acetylcholine, Nitroglycerin, Non-Selective NOS Inhibitor and Selective iNOS Inhibitor in the Forearm and Outcome in Patients with Heart Failure
The relationship between the impaired endothelial function and prognosis in patients with heart failure remains controversial. In the present study, we prospectively researched the prognosis in 54 patients with chronic heart failure due to dilated cardiomyopathy in whom forearm blood flow (FBF) responses to acetylcholine (ACh), nitroglycerin (TNG), a non-selective NOS inhibitor (LNMMA) and a selective iNOS inhibitor (Amn: aminoguanidine) were examined using plethysmography. FBF was measured in both arms during infusion of graded doses of ACh (3.75, 7.5, 15 μg/min), TNG (12.5, 25, 50 μg/min), Amn (2.5, 5, 10, 20 μmol/min), and LNMMA (2.5, 5, 10, 20 μmol/min).
Results: During the mean follow-up period of 4.8 years, 18 patients were admitted to hospital by reason of worsening heart failure, and 6 of those died in hospital. Patients experiencing adverse events had a lower vasodilator response to ACh (p=0.009) and TNG (p=0.04) compared with patients without events. Amn significantly decreased FBF (24±15 %, p<0.001) in patients with events, but did not in patients without events (2±3 %, p=0.62). FBF responses to LNMMA did not differ between the two patient groups. Kaplan-Meier analyses with log-rank test revealed significance in depressed FBF response to ACh (less than median value 160% ) (p=0.04) and greater response to Amn (more than median value 10.8 %) (p<0.001), and multivariate Cox proportional-hazards model analyses showed significance in FBF response to Amn (adjusted hazard ratio 10.1, p<0.001).
Conclusion: Greater vasodilator response to Amn, suggesting activation of iNOS in peripheral vessels, closely related to pathophysiology of heart failure with poor outcome.