The Role of Myocardial Fibrosis and Bioenergetic Dysfunction in Heart Failure Prognosis: A Study Protocol

Introduction The blockage of the renin-angiotensin-aldosterone and sympathetic nervous systems is fundamental in heart failure (HF) treatment; nonetheless, other mechanisms related to myocardial fibrosis and bioenergetic dysfunction also have a relevant role in the genesis and progression of this syndrome. We aim to stratify the short-term outcome of patients hospitalized with acute decompensated heart failure (ADHF) in New York Heart Association (NYHA) class III or IV based on myocardial fibrosis biomarkers galectin-3 (Gal-3), suppression of tumorigenicity 2 (ST2) and growth differentiation factor15 (GDF-15), and bioenergetic dysfunction markers (absolute iron deficiency and functional iron deficiency). Secondary endpoints were evaluation of short-term prognosis through early HF readmission and all-cause mortality (up to 90 days after hospital discharge), annual heart failure readmission and all-cause mortality, and annual risk for major adverse cardiovascular events (MACE), namely fatal and non-fatal stroke and fatal and non-fatal myocardial infarction, and cardiorenal syndrome.  Material and methods This cohort prospective observational unicentric study had two arms (left ventricular ejection fraction (LVEF)> 40% and ≤ 40%). A total of 128 participants were included, with 64 per group. Gal-3, ST2, and GDF-15 will be assessed in vitroin serum and plasma, and iron kinetics will be evaluated in plasma. Kaplan-Meier survival estimates will be calculated for each endpoint. A univariate Cox propor-tional hazards model will be performed to achieve hazard ratios and 95% confidence intervals for each variable. Results We expect to establish a relation between high values of fibrosis biomarkers, absolute and functional iron deficiency, and impaired short-term outcome in patients admitted due to ADHF. Conclusions This study may yield knowledge regarding the role of myocardial fibrosis and bioenergetic dysfunction in HF short-term prognosis.