Biomarkers Show Limited Utility in Guiding Early TAVR Timing for Asymptomatic Severe AS: EARLY TAVR Trial

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By Joseph Kim on

Key Takeaways:

  1. Elevated baseline NT-proBNP and hs-cTnT levels were associated with higher cardiovascular event rates, but did not predict greater relative benefit from early TAVR compared to clinical surveillance.
  2. The EARLY TAVR trial supports early intervention across the spectrum of biomarker concentrations in asymptomatic severe AS.

This pre-specified biomarker analysis of the EARLY TAVR trial (NCT03042104), presented at the American College of Cardiology Annual Scientific Session (ACC.25) and published simultaneously in Circulation, evaluated the role of baseline cardiac biomarkers—N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT)—in guiding the timing of transcatheter aortic valve replacement (TAVR) in asymptomatic patients with severe aortic stenosis (AS). Although elevated biomarker levels were associated with increased cardiovascular risk, they demonstrated limited utility in identifying patients who derived greater relative benefit from early TAVR compared to clinical surveillance.

This secondary analysis involved 798 patients randomized to early TAVR (n=398) or clinical surveillance (n=400). Patients were stratified by baseline NT-proBNP and hs-cTnT levels. Higher baseline levels of NT-proBNP (>median, 222 pg/mL) and elevated hs-cTnT (>15 ng/L) were significantly associated with increased risk of death or heart failure hospitalization at two years: NT-proBNP >222 pg/mL (hazard ratio [HR] 2.96; 95% CI, 1.87–4.69; p<0.001) and hs-cTnT >15 ng/L (HR 3.27; 95% CI, 2.04–5.24; p<0.001).

However, early TAVR provided similar or greater relative benefit compared to surveillance irrespective of baseline biomarker status. For patients with NT-proBNP ≤222 pg/mL, early TAVR significantly reduced the composite endpoint of death, stroke, or unplanned cardiovascular hospitalization compared to surveillance (HR 0.39; 95% CI, 0.23–0.64; p<0.001). Among patients with NT-proBNP >222 pg/mL, early TAVR also showed benefit but to a lesser degree (HR 0.71; 95% CI, 0.50–1.00; p=0.05; interaction p=0.06). Similarly, in patients with normal hs-cTnT levels (≤15 ng/L), early TAVR markedly reduced the composite endpoint compared with surveillance (HR 0.45; 95% CI, 0.29–0.69; p<0.001). Among patients with elevated hs-cTnT (>15 ng/L), the benefit was attenuated (HR 0.66; 95% CI, 0.44–0.98; p=0.04), with significant interaction (interaction p=0.04), indicating a greater relative benefit of early TAVR among patients with normal cardiac troponin.

Absolute risk reductions, however, were numerically larger among patients with higher baseline biomarkers due to higher overall event rates. Despite these differences, early TAVR consistently showed benefit across all biomarker levels, challenging guideline recommendations emphasizing biomarker thresholds to guide intervention timing.

Lead investigator Dr. Brian Lindman emphasized, “Our findings suggest limited value for single measurements of biomarkers to guide the timing of TAVR in asymptomatic patients. While biomarkers reflect higher risk, the relative benefit of early intervention appears consistent across biomarker levels.”