Plasma norepinephrine and atrial natriuretic peptide in heart failure: Influence of felodipine in the third vasodilator heart failure trial

Abstract

Background: Reflex activation of the sympathetic nervous system by short-acting dihydropyridine calcium channel antagonists has been reported to harm hypertensive patients. Different neurohormonal profiles and their response to treatment may influence the effectiveness of dihydropyridine vasodilator treatment of heart failure. Methods: Four hundred fifty men with left ventricular (LV) systolic dysfunction were administered standard heart failure treatment and felodipine extended release (ER) or placebo in the Vasodilator Heart Failure Trial III (V-HeFT III). Plasma norepinephrine (PNE) levels, atrial natriuretic peptide (ANP) levels, exercise capacity, LV ejection fraction (EF), cardiac dimensions and function, and arrhythmia frequency were measured. Hospital-free survival for baseline neurohormonal classes was assessed. Results: Distributions of ANP and PNE levels at baseline in patients with heart failure of ischemic and nonischemic causes were virtually identical. ANP levels at baseline were inversely related to LVEF ( r = −0.39; P = .0001), exercise duration ( r = −0.19; P = .0001), and peak oxygen consumption ( r = −0.27; P = .008) and directly related to LV ( r = 0.23; P = .0006) and right ventricular dilatation ( r = 0.23; P = .0008). The increase in ANP levels between baseline and 3 months ( P = .02) and 1 year ( P = .03) was significantly less in the felodipine-ER group than in the placebo group, but PNE levels did not differ between treatment groups. Hospital-free survival was directly related to baseline ANP ( P = .0002) and PNE levels( P = .004). All-cause mortality was related to baseline PNE levels ( P = .02) but not baseline ANP levels. Conclusion: Levels of ANP and PNE hormones are related to LV dysfunction, exercise performance, and hospital-free survival in heart failure and PNE levels are related to all-cause mortality. Treatment with felodipine ER did not adversely affect survival in any neurohormone subclass.