Cardiac Biomarkers in Patients with Asymptomatic Severe Aortic Stenosis: Analysis from the EARLY TAVR Trial.

Background: The EARLY TAVR trial demonstrated that early transcatheter aortic valve replacement (TAVR) intervention was superior to clinical surveillance (CS) with delayed TAVR in patients with asymptomatic, severe aortic stenosis (AS). Cardiac biomarkers are associated with maladaptive remodeling, symptom onset, and worse outcomes after TAVR. Whether elevated biomarkers identify asymptomatic patients more likely to benefit from early intervention is unknown.

Methods: A core laboratory measured N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT). Associations between biomarker levels and risk of the trial primary endpoint (death, stroke, or unplanned cardiovascular hospitalization) and other secondary endpoints were examined with Kaplan-Meier curves and Cox proportional hazard models. Interaction tests were performed to assess whether the treatment effect of early TAVR, compared with CS, differed according to biomarker levels.

Results: Among 901 patients randomized in EARLY TAVR, 798 (89%) had biospecimens measured (median NT-proBNP 287 [145, 601]; median hs-cTnT 14.6 [10.5, 21.0]). Higher levels of NT-proBNP and hs-cTnT were broadly associated with higher event rates for multiple endpoints. In general, there was no significant interaction between baseline biomarkers and treatment group with respect to any composite or individual endpoint examined, although trends broadly demonstrated a greater relative benefit of early TAVR at lower biomarker levels. There was a significant interaction between hs-cTnT and treatment group with respect to death or heart failure hospitalization (HFH) (interaction p=0.04) and HFH alone (interaction p=0.03) such that the relative benefit of early TAVR was greater for patients with normal, rather than elevated, levels of hs-cTnT at baseline. For some endpoints, higher baseline NT-proBNP was associated with numerically greater absolute risk reduction with early TAVR than lower NT-proBNP levels.

Conclusions: In patients with asymptomatic severe high gradient AS, higher NT-proBNP and hs-cTnT levels were broadly associated with higher event rates as expected. However, the relative benefit of an early TAVR strategy was consistent regardless of baseline biomarker levels and, contrary to our hypothesis, tended to be more pronounced in those with the lowest biomarker levels. These findings suggest limited value for single measurements of these biomarkers to guide the timing of TAVR in asymptomatic patients.