NEW YORK (Reuters Health) – Patients with left ventricular (LV) dysfunction should receive human atrial natriuretic peptide (hANP) infusions during coronary artery bypass graft (CABG) surgery, Japanese researchers say.

When given from the start of cardiopulmonary bypass, hANP protects the kidneys and heart, reduces the incidence of postoperative complications, and improves long-term outcomes, according to their paper in the April 27th Journal of the American College of Cardiology.

In the randomized NU-HIT trial for LVD, Dr. Akira Sezai from Nihon University School of Medicine, Tokyo, and colleagues administered either hANP or placebo to 133 patients with LV dysfunction undergoing CABG. The researchers point out that the starting dose of hANP was only 0.02 mcg/kg/min – much lower than the starting dose of 0.1 mcg/kg/min that’s given to patients with acute heart failure. Infusion at the initial dose continued until patients could take oral medication, at which point the dose was dropped to 0.01 mcg/kg/min and then discontinued 12 hours later.

The 68 patients in the treatment group received hANP in a continuous infusion for a mean of 2.8 days. The 65 patients in the control group received saline infusions for a mean 3.4 days.

Compared to the control group, the hANP group had significantly shorter mean stays in the ICU (3.6 vs 4.4 days, p = 0.039) and in the hospital (13.7 vs 19.3 days, p = 0.043). The hANP group also had a significantly lower incidence of postoperative complications (5.9% vs 15.4%, p = 0.015) and fewer arrhythmia episodes (14 vs 33, p = 0.0003).

There were no significant differences between the groups in 30-day and 180-day mortality, and overall survival rates did not differ significantly at 2, 5, and 8 years.

However, the rate of freedom from cardiac death was higher in treated patients vs controls (p = 0.028) at 2 years (98.5% vs 92.3%), 5 years (98.5% vs 85.5%), and 8 years (98.5% vs 85.5%).

Cardiac event-free rates were also significantly higher in the hANP group at those follow-up points.

Among the secondary endpoints, the treated group had a significantly greater mean LV ejection fraction and a significantly lower brain natriuretic peptide level than the control group as late as 1 year postoperatively.

Moreover, serum creatinine levels were significantly lower and estimated glomerular filtration rates were significantly higher in the hANP group at 1 month, 6 months, and 1 year.

“Even though hANP was only administered for a few days in the acute stage, a potent cardio- and renal-protective effect was demonstrated in long-term,” Dr. Sezai told Reuters Health by email.

Dr. Sezai believes hANP is compensating for the adverse effects of cardiopulmonary bypass. He pointed out that hANP is most effective in severely ill patients, such as those with chronic kidney disease, left ventricular dysfunction, acute myocardial dysfunction, thoracic aortic surgery, severe valve disease, or a ventricular assist device.

“I routinely provide hANP therapy for patients with left ventricular dysfunction undergoing CABG, valve surgery, and aortic surgery in my institute,” Dr. Sezai said.

Reference:
J Am Coll Cardiol 2010;55:1844-1851.