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

Autores de INCLIVA

• Patricia Palau Sampio

  Autor

• Anna Mireia Mollar Fernandez

  Autor

• 

  Francisco Javier Chorro Gascó

  Autor

• 

  Juan Sanchis Fores

  Autor

• 

  Julio Nuñez Villota

  Autor

Participantes ajenos a INCLIVA

• Reese-Petersen, Alexander Lynge
• Dominguez, Eloy
• Ramon, Jose Maria
• Lopez, Laura

Grupos y Plataformas de I+D+i

• Grupo de investigación en Cardiología Clínica

  

  Leading Researcher

  Juan Sanchis Fores

• Grupo de Investigación en Electrofisiología cardiaca experimental

  

  Leading Researcher

  Antonio M. Alberola Aguilar

• Grupo de Investigación en Insuficiencia Cardiaca

  

  Established Researcher

  Julio Nuñez Villota

Abstract

Serum levels of matrix metalloproteinase-12 cleaved fragment of titin (TIM), a novel circulatory biomarker specific for cardiac titin degradation, has emerged as a potential biomarker in cardiovascular diseases. In this work, we aimed to evaluate the association between TIM and maximal functional 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 patients enrolled 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-HF patients. The independent association between TIM and pp-peakVO2 was evaluated by multivariate linear regression analysis. Results. The mean age of the sample was 73.8 ± 8.7 years, 56.5% were females, 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 912 pg/mL (302-1826). pp-peakVO2 was significant and inversely correlated with TIM (r= -41, p = .005). In multivariate analysis, after adjusting for NYHA class, hypertension, body mass index, and glomerular filtration rate, higher TIM was significantly associated with lower pp-peak VO2 (p = .029). Conclusions. In this sample of stable and symptomatic HFpEF patients, higher serum levels of TIM identified patients with worse functional status.

Keywords

• Titin degradation; functional capacity; heart failure with preserved ejection fraction