Usefulness of the B-Type Natriuretic Peptides in Low Ejection Fraction, Low-Flow, Low-gradient Aortic Stenosis Results from the TOPAS Multicenter Prospective Cohort Study

Patients with low ejection fraction, low-flow, low-gradient (i.e. Classical low flow [CLF]) aortic stenosis (AS) have a dismal short-term outcome without aortic valve replacement (AVR) but high operative mortality. We hypothesized that brain natriuretic peptides (BNP/NT-proBNP) can risk stratify patients with CLF AS and may assist in clinical decision making. Patients with aortic valve area ≤1.2 cm², mean transvalvular gradient &lt;40 mmHg, and left ventricular ejection fraction &lt;50%, were prospectively recruited. BNP and/or NT-proBNP were measured at baseline. Among 234 patients (77[68-83] years, 76% males), BNP &gt;550 pg/ml or NT-proBNP &gt;1,600 pg/ml (85% and 93% sensitivity, respectively to correctly classify 1-year death) strongly predicted all-cause mortality (adjusted HR=2.53 [1.68-3.81], p&lt;0.001) outperforming flow reserve and baseline LVEF (all likelihood ratio p≤0.02). For both natriuretic peptides, spline curve analysis showed gradual increase in mortality with higher biomarkers levels, which was blunted by AVR. In a head-to-head comparison (n=104), NT-proBNP appeared to have superior incremental prognostic value than BNP (likelihood-ratio p&lt;0.001 vs. p=0.07). Baseline NT-proBNP ≥1,600 pg/ml or BNP ≥550 pg/ml, identified: i) a high-risk cohort with a dismal outcome under conservative management, but a markedly better survival associated with early AVR (adjusted HR=0.41[0.25-0.65], p&lt;0.001); and ii) a low-risk cohort with an excellent 1-year survival (94±4%) with conservative management or deferred AVR. : In patients with CLF AS, BNP/NT-proBNP have the potential to identify high-risk patients who may benefit from early AVR. NCT01835028. <b>HTTPS://CLINICALTRIALS.GOV/CT2/SHOW/NCT01835028</b>