Neurohumoral changes in patients with left ventricular dysfunction following acute myocardial infarction and the effect of nitrate therapy : A randomized, double-blind, placebo-controlled long-term study

Background: Several neurohumoral mechanisms involved in cardiovascular regulation are activated in the failing heart, but only limited information is available regarding the influence of long-term nitrate therapy. Materials and Methods: This was a double-blind, randomized comparison of isosorbide-5-mononitrate (IS-5-MN), 60 mg given orally, once daily for 11 months to patients (n = 47) with left ventricular (LV) dysfunction following acute myocardial infarction (AMI). Forty-five patients received placebo. All patients received ramipril. Plasma natriuretic peptides (atrial [ANP] and brain [BNP] natriuretic peptide), epinephrine, norepinephrine (NEP1), antidiuretic hormone, aldosterone (Aldo), renin activity (PRA), substance P, neuropeptide Y-like immunoreactivity, calcitonin gene-related peptide, and vasoactive intestinal peptide were measured at baseline and at the end of the treatment period. Clinical, echocardiographic, and hemodynamic data were also obtained. Results and Conclusions: Chronic nitrate therapy does not significantly affect the neurohumoral status in patients with LV dysfunction after AMI, apart from a decrease in ANP. Some hormones are more closely associated with diastolic dysfunction/increased volume load (ANP and BNP) and others are more closely associated with systolic dysfunction (PRA, NEPI, Aldo). There is a temporal dissociation of these 2 groups of hormones 1 year post infarction: ANP and BNP decrease, whereas NEPI and Aldo show a slight increase. BNP levels do not reflect all important pathophysiologic mechanisms in heart failure. Consequently, the use of other neuro-hormonal factors than BNP for monitoring of heart failure therapy should be explored.