B-type Natriuretic Peptide for Cardio-Renal Decompensation Syndrome

Heart failure represents a growing epidemic in the United States. Recent figures reveal that almost 5 million people have heart failure in the U.S. alone, with an incidence (550,000 new diagnoses/year) that has increased up to threefold over the last 25 years. This growing incidence of heart failure is thought to be due to changing population demographics. Rates of major risk factors for the disease-diabetes mellitus, hypertension, and renal insufficiency--have all been steadily increasing.

Renal insufficiency causes particular difficulty for the management of heart failure. Most CHF patients have a significant degree of renal insufficiency - both because the risk factors for the two diseases are the same, but also because reduced cardiac output related to CHF leads to reduced glomerular filtration rate (GFR). Diuretics in escalating doses, a cornerstone of therapy for CHF exacerbations, can also lead to worsening renal function, a continued inability to achieve an adequate diuresis and toxicity from the agents given.

B-type Natriuretic Peptide (BNP) is a 32-amino acid peptide hormone secreted predominantly from the ventricles in response to increased pressure and volume. It has several actions in vivo, working as a diuretic, natriuretic and as a systemic pulmonary vasodilator. Natrecor is a recombinant peptide structurally identical to endogenous BNP, approved for the treatment of decompensated heart failure.

In the Vasodilation in the management of Acute Congestive Heart Failure (VMAC)trial, therapy with Natrecor resulted in improvements in pulmonary capillary wedge pressure seen within 15 minutes of starting the therapy; these improvements were significantly better than with intravenous nitroglycerine. Patients also reported a greater improvement in dyspnea with Natrecor therapy than with placebo. In a prior study, our group has demonstrated that prolonged Natrecor infusions result in improved hemodynamic parameters for Stage D heart failure patients awaiting heart transplantations.

Natrecor therapy holds theoretical value for patients with heart failure and concomitant renal insufficiency. Prior experimental work has demonstrated that BNP infusions can increase diuresis, natriuresis, and importantly, GFR in healthy subjects--all of which represent major objectives in the therapy of heart failure patients. Many have also reported the clinical experience that renal function was preserved, and diuresis/natriuresis more readily achieved in patients with heart failure exacerbations and renal insufficiency with the addition of Natrecor therapy. However, this potential use for Natrecor has not been rigorously tested.