Continuous Low-Dose Infusion of Human Atrial Natriuretic Peptide in Patients With Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting: The NU-HIT (Nihon University working group study of low-dose Human ANP Infusion Therapy during cardiac surgery) for Left Ventricular Dysfunction

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Continuous low-dose infusion of human atrial natriuretic peptide (hANP) in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) inhibits the renin-angiotensin-aldosterone system and compensates for the adverse effects of CPB. We examined the influence of hANP infusion on cardiac and renal function in patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). The subjects were 133 patients who underwent CABG and had a pre-operative ejection fraction < or =35%. They were randomized to receive 0.02 microg/kg/min of hANP from the initiation of CPB (hANP group) or placebo (saline) infusion. Early post-operative mortality did not show a significant difference between the 2 groups, but perioperative complications were significantly less frequent in the hANP group (p = 0.015). Long-term all-cause mortality showed no difference, but the cardiac death-free rate at 5 or 8 years post-operatively was 98.5% in the hANP group and 85.5% in the placebo group (p = 0.0285). Post-operative ejection fraction was significantly larger and the post-operative brain natriuretic peptide level was significantly lower in the hANP group. Serum creatinine was significantly lower in the hANP group than the placebo group at 1 month, 6 months, and 1 year post-operatively, whereas the estimated glomerular filtration rate was significantly higher in the hANP group at these times. In patients with left ventricular dysfunction undergoing CABG, hANP showed renal- and cardio-protective effects and reduced post-operative complications. It also improved the long-term prognosis. We suggest that hANP should be considered as part of perioperative management of patients with cardiac dysfunction undergoing cardiac surgery. (NU-HIT trial for LVD; UMIN000001652).