Prediction of Left Ventricular Reverse Remodeling and Outcomes by Circulating Collagen-Derived Peptides

• Published in: JACC. Heart failure Vol. 11; no. 1; pp. 58 - 72
• Main Authors: Ravassa, Susana, Lupón, Josep, López, Begoña, Codina, Pau, Domingo, Mar, Revuelta-López, Elena, Moreno, María U., San José, Gorka, Santiago-Vacas, Evelyn, Cediel, Germán, Roncal, Carmen, Díez, Javier, Bayés-Genís, Antoni, González, Arantxa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023
• Subjects: Biomarkers; Cardiomyopathies; Collagen; Collagen Type I; Female; Fibrosis; Heart Failure; Humans; left ventricular ejection fraction; left ventricular reverse remodeling; outcomes; Peptide Fragments; Peptides; Procollagen; procollagen type-I C-terminal propeptide; Stroke Volume; Ventricular Function, Left; PICP; HHF; IRR; LVEF; LV; LAVI; left ventricular reverse remodeling; HFrEF; left ventricular ejection fraction; procollagen type-I C-terminal propeptide; NT-proBNP; outcomes; hs-TnT; IC; LVESD; SHR; CKD; NYHA; heart failure; AF; CITP/MMP; CMR; LVRR; sST2; LVEDD; HFmrEF; MRA; HF
• ISSN: 2213-1779; 2213-1787; 2213-1787
• DOI: 10.1016/j.jchf.2022.09.008

Myocardial fibrosis may increase vulnerability to poor prognosis in patients with heart failure (HF), even in those patients exhibiting left ventricular reverse remodeling (LVRR) after guideline-based therapies. This study sought to characterize fibrosis at baseline in patients with HF with left ventricular ejection fraction (LVEF) <50% by determining serum collagen type I–derived peptides (procollagen type I C-terminal propeptide [PICP] and ratio of collagen type I C-terminal telopeptide to matrix metalloproteinase-1) and to evaluate their association with LVRR and prognosis. Peptides were determined in 1,034 patients with HF at baseline. One-year echocardiography was available in 665 patients. Associations of peptides with 1-year changes in echocardiographic variables were analyzed by multivariable linear mixed models. LVEF was considered improved if it increased by ≥15% or to ≥50% or if it increased by ≥10% to >40% in patients with LVEF ≤40%. Cardiovascular death and HF-related outcomes were analyzed in all patients randomized to derivation (n = 648) and validation (n = 386) cohorts. Continuous associations with echocardiographic changes were observed only for PICP. Compared with high-PICP (≥108.1 ng/mL) patients, low-PICP (<108.1 ng/mL) patients exhibited enhanced LVRR and a lower risk of HF-related outcomes (P ≤ 0.018), with women and nonischemic patients with HF showing a stronger LVEF increase (interaction P ≤ 0.010). LVEF increase was associated with a better prognosis, particularly in low-PICP patients (interaction P ≤ 0.029). Only patients with both low PICP and improved LVEF exhibited a better clinical evolution than patients with nonimproved LVEF (P < 0.001). Phenotyping with PICP, a peptide associated with myocardial fibrosis, may be useful to differentiate patients with HF who are more likely to experience clinical myocardial recovery from those with partial myocardial improvement. [Display omitted]