Plasma Tenascin-C: a prognostic biomarker in heart failure with preserved ejection fraction
Prathap Kanagala, Jayanth R. Arnold, Jamal Nasir Khan, Anvesha Singh, Gaurav S. Gulsin, Daniel C. S. Chan, Adrian S. H. Cheng, Jing Yang, Zhuyin Li, Pankaj Gupta, Iain Squire, Gerry P McCann, Leong L. Ng
Abstract
Introduction Tenascin-C is a marker of interstitial fibrosis. We assessed whether plasma Tenascin-C differed between heart failure with preserved ejection fraction (HFpEF) and asymptomatic controls and related to clinical outcomes.Materials and Methods Prospective, observational study of 172 age- and sex-matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, males 50%) who underwent phenotyping with 20 plasma biomarkers, echocardiography, cardiac MRI and 6-minute-walk-testing. The primary endpoint was the composite of all-cause death/HF hospitalisation.Results Tenascin-C was higher in HFpEF compared to controls (13.7 [10.8–17.3] vs (11.1 [8.9–12.9] ng/ml, p < 0.0001). Tenascin-C correlated positively with markers of clinical severity (NYHA, E/E’, BNP) and plasma biomarkers reflecting interstitial fibrosis (ST-2, Galectin-3, GDF-15, TIMP-1, TIMP-4, MMP-2, MMP-3, MMP-7, MMP-8), cardiomyocyte stress (BNP, NTpro-ANP), inflammation (MPO, hs-CRP, TNFR-1, IL6) and renal dysfunction (urea, cystatin-C, NGAL); p < 0.05 for all.During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations). In multivariable Cox regression analysis, Tenascin-C (adjusted hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.305–2.360; p < 0.0001) and indexed extracellular volume (HR 1.465, CI 1.019–2.106; p = 0.039) were independently associated with adverse outcomes.Conclusions In HFpEF, plasma Tenascin-C is higher compared to age- and sex-matched controls and a strong predictor of adverse outcomes. Trial registration: ClinicalTrials.gov: NCT03050593