Background: Heart failure is associated with abnormal endothelium-dependent
vasodilation. However, the relationship of this abnormality to heart failu
re 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-independe
nt, and reactive hyperemic stimuli in normal subjects (n = 29) and in patie
nts 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 <.00
1) 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 fai
lure. There was no correlation between methacholine responses and ejection
fraction, maximum oxygen consumption, wedge pressure, or serum norepinephri
ne.
Conclusion: Impaired endothelium-dependent vasodilation is present and near
maximum in mild heart failure. Endothelial dysfunction may be an early fin
ding in human heart failure.