Endothelial dysfunction in patients with heart failure: Relationship to disease severity

Background: Heart failure is associated with abnormal endothelium-dependent vasodilation. However, the relationship of this abnormality to heart failure severity has not been well defined. Methods and Results: We used strain-gauge plethysmography to assess forearm blood flow (FBF) responses to endothelium-dependent, endothelium-independent, and reactive hyperemic stimuli in normal subjects (n = 29) and in patients with mild (n = 26) and severe (n = 41) heart failure. FBF responses to intra-arterial methacholine (0.3, 1.5, 3.0 mu g/min) were significantly (P <.005) and similarly reduced in patients with mild (2.8 +/- 0.4, 5.9 +/- 0.7, and 7.7 +/- 1.1 mL/min/dL) and severe (2.7 +/- 0.4, 5.4 +/- 0.7, and 6.9 +/- 0.9) heart failure compared with normal subjects (4.5 +/- 0.4, 9.4 +/- 1.0, and 12.0 +/- 1.1). FBF responses to nitroprusside (1, 5, 10 mu g/min) were significantly reduced in mild (2.4 +/- 0.3, 6.7 +/- 1.1, and 11.9 +/- 2.0, P <.05) and severe (1.9 +/- 0.2, 5.1 +/- 0.5, and 7.3 +/- 0.9, P <.001) heart failure groups compared with normal subjects (3.8 +/- 0.5, 10.8 +/- 1.2, and 14.9 +/- 1.2). However, FBF responses were reduced to a greater extent (P <.001) in mild heart failure compared with severe heart failure. Peak reactive hyperemia was significantly impaired only in severe heart failure. There was no correlation between methacholine responses and ejection fraction, maximum oxygen consumption, wedge pressure, or serum norepinephrine. Conclusion: Impaired endothelium-dependent vasodilation is present and near maximum in mild heart failure. Endothelial dysfunction may be an early finding in human heart failure.