Supplementary Material for: Comparative Prognostic Value of Four Urinary Biomarkers for Cardiovascular and Renal Outcomes After Transcatheter Aortic Valve Implantation

Introduction: Renal risk stratification after transcatheter aortic valve implantation (TAVI) remains anchored to filtration metrics such as serum creatinine and estimated glomerular filtration rate (eGFR). These indices may not capture early tubular injury, which is clinically relevant in older TAVI populations. We therefore investigated whether four urinary biomarkers—N-acetyl-β-D-glucosaminidase (NAG), liver-type fatty acid–binding protein (L-FABP), β2-microglobulin, and α1-microglobulin—measured the day after TAVI, are associated with subsequent cardio-renal outcomes.
Methods: We enrolled 191 consecutive patients undergoing TAVI in a single-center cohort within the LAPLACE-TAVI registry (February 2016–December 2019). Spot urine collected 12–18 hours post-procedure was assayed for four urinary markers. The primary endpoint was a 24-month composite of all-cause death or first heart-failure hospitalization; a renal composite used contemporary surrogate criteria. Multivariable Cox models adjusted for clinical covariates including eGFR. Biomarkers were examined using cohort medians as prespecified cut points.
Results: Median follow-up was 1.8 years (interquartile range [IQR] 1.1–2.0); the primary endpoint occurred in 27/191 (14.1%). NAG showed no correlation with eGFR (r = −0.03, p = 0.68), whereas β2-microglobulin and α1-microglobulin correlated inversely with eGFR (r = −0.27, p = 0.002; r = −0.34, p < 0.001); L-FABP was not correlated (r = −0.09, p = 0.21). Patients above the cohort median for NAG (6.8 IU/L) experienced higher 2-year event rates, with early separation of Kaplan–Meier curves (log-rank p = 0.02). In adjusted models, both high NAG (hazard ratio [HR] 2.63, 95% confidence interval (CI) 1.17–6.46; p = 0.02) and high L-FABP (HR 2.48, 95% CI 1.08–6.16; p = 0.03) remained independently associated with the primary endpoint, whereas β2-microglobulin and α1-microglobulin were not. Creatinine and eGFR were comparable across NAG strata; renal composite events were higher in the high-NAG group but did not reach statistical significance.
Conclusion: A single urinary NAG and L-FABP measurement within 24 hours post TAVI identified increased 2-year risk of death or heart-failure hospitalization despite preserved filtration indices. Although limited by sample size and single-center design, these pilot data support external validation and the evaluation of biomarker-guided surveillance and reno-protective strategies following TAVI.