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
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.