Matrix metalloproteinase-12 cleaved fragment of titin as a predictor offunctional capacity in patients with heart failure and preserved ejection fraction

Abstract

Objectives.Serum levels of matrix metalloproteinase-12 cleaved fragment of titin (TIM), a novel circula-tory biomarker specific for cardiac titin degradation, has emerged as a potential biomarker in cardio-vascular diseases. In this work, we aimed to evaluate the association between TIM and maximalfunctional capacity assessed by the percentage of predicted peak exercise oxygen uptake (pp-peakVO2) in patients with heart failure and preserved ejection fraction (HFpEF).Design.In this post-hoc study, we included 46 stable symptomatic (New York Heart Association II-III) HFpEF patientsenrolled in the TRAINING-HF study (NCT02638961). pp-peak-VO2 was calculated from baseline values.Baseline circulating levels of TIM were measured by competitive ELISA in serum from the TRAINING-HFpatients. The independent association between TIM and pp-peakVO2 was evaluated by multivariatelinear regression analysis.Results.The mean age of the sample was 73.8 ±8.7 years, 56.5% werefemales, and 76.1% were on NYHA II. The medians of pp-peakVO2 and TIM were 60.9% (50.4–69.3),and 130.1 ng/mL (98.1–159.5), respectively. The median of NT-proBNP was 912pg/mL (302–1826). pp-peakVO2 was significant and inversely correlated with TIM (r¼ 41,p¼.005). In multivariate analysis,after adjusting for NYHA class, hypertension, body mass index, and glomerular filtration rate, higherTIM was significantly associated with lower pp-peak VO2 (p¼.029).Conclusions.In this sample of sta-ble and symptomatic HFpEF patients, higher serum levels of TIM identified patients with worse func-tional status.