Plasma Tenascin-C: a prognostic biomarker in heart failure with preserved ejection fraction

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

Keywords:

• Tenascin-C
• interstitial fibrosis
• biomarkers
• heart failure with preserved ejection fraction
• inflammation
• prognosis

Acknowledgements

The authors thank the CMR radiographers at Glenfield Hospital for image acquisition and Bristol Myers Squibb for facilitating plasma biomarker analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data relevant to this study can be made available to readers following a reasonable request in writing to the corresponding author on behalf of the NIHR Leicester Cardiovascular Biomedical Research Centre in keeping with the guidance for governance of the study.

Additional information

Funding

This work was supported by the National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre under overall project Grant [IRS_BRU_0211_20033] and the John and Lucille Van Geest Foundation. Dr Daniel Chan was supported by the British Heart Foundation [grant number FS/15/10/31223]. Professor Gerry McCann was supported by NIHR Research Fellowships [grant numbers PDF-2011-0451 and CDF 2014-07-045].