Biomarker responses during and after treatment with nesiritide infusion in patients with decompensated chronic heart failure

Background: Objective methods to assess the adequacy of medication therapy for patients with advanced heart failure are lacking. Serial measurements of biomarkers might be beneficial. Therapy guided by N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be helpful because NT-proBNP should be lowered by therapies that decrease endogenous BNP secretion. Methods: NT-proBNP and BNP were measured in a nonconsecutive patient cohort receiving clinically indicated intravenous nesiritide. Blood samples were drawn before, at 6 and 24 h during, and at 6 h after infusion. A reduction in NT-proBNP was defined as a decrease from baseline during infusion ("infusion responders") of >3 SD of the variability of the assay measurement (∼20%). Patients with decreases >20% in both NT-pro BNP and BNP at 6 h post infusion were designated "biochemical responders". Results: Forty patients [27 males; mean (SE) age, 68 (2) years; mean (SE) left ventricular ejection fraction, 25 (1.4)%] were studied. All patients improved clinically. Overall, the changes in NT-proBNP were a 18 (4.6)% [mean (SE)] and 19.8% (median) decrease from baseline at 24 h of infusion and a 22 (6.0)% and 17.8% decrease at 6 h post infusion (P <0.001 compared with baseline). In a large number of patients, decreases in NT-proBNP were, however, within the variability of the assay. Subgroup analysis showed that 22 of 40 patients were infusion responders with a >20% decrease from baseline in NT-proBNP during nesiritide infusion, whereas only 12 patients were biochemical responders with >20% decreases from baseline postinfusion for both NT-proBNP and BNP. Conclusions: In this study, many patients had decreased NT-proBNP and BNP values after therapy with nesiritide, but the majority of patients did not demonstrate biochemically significant decreases in analytes despite a clinical response. Until we know more about the responses of natriuretic peptides to therapies such as nesiritide, a strategy of monitoring NT-proBNP and BNP to guide therapy cannot be universally advocated.