B-Type natriuretic peptide in low-flow, low-gradient aortic stenosis - Relationship to hemodynamics and clinical outcome: Results from the multicenter truly or pseudo-severe aortic stenosis (TOPAS) study

Background-The prognostic value of B-type natriuretic peptide (BNP) is unknown in low-flow, low-gradient aortic stenosis ( AS). We sought to evaluate the relationship between AS and rest, stress hemodynamics, and clinical outcome. Methods and Results-BNP was measured in 69 patients with low-flow AS (indexed effective orifice area < 0.6 cm(2)/m(2), mean gradient <= 40 mm Hg, left ventricular ejection fraction <= 40%). All patients underwent dobutamine stress echocardiography and were classified as truly severe or pseudosevere AS by their projected effective orifice area at normal flow rate of 250 mL/s (effective orifice area <= 1.0 cm(2) or > 1.0 cm(2)). BNP was inversely related to ejection fraction at rest (Spearman correlation coefficient r(s)=-0.59, P < 0.0001) and at peak stress ( r(s) =- 0.51, P < 0.0001), effective orifice area at rest (r(s)=-0.50, P < 0.0001) and at peak stress ( r(s)=-0.46, P = 0.0002), and mean transvalvular flow (r(s)=- 0.31, P = 0.01). BNP was directly related to valvular resistance (r(s) = 0.42, P = 0.0006) and wall motion score index (r(s)= 0.36, P=0.004). BNP was higher in 29 patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a strong predictor of outcome. In the total cohort, cumulative 1-year survival of patients with BNP >= 550 pg/ mL was only 47 +/- 9% versus 97 +/- 3% with BNP < 550 (P < 0.0001). In 29 patients who underwent valve replacement, postoperative 1-year survival was also markedly lower in patients with BNP >= 550 pg/mL (53 +/- 13% versus 92 +/- 7%). Conclusions-BNP is significantly higher in truly severe than pseudosevere low- gradient AS and predicts survival of the whole cohort and in patients undergoing valve replacement.