Prediction of Left Ventricular Reverse Remodeling and Outcomes by Circulating Collagen-Derived Peptides
Susana Ravassa1, Josep Lupón2, Begoña López1
1Program of Cardiovascular Diseases, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; Network Center for Biomedical Research into Cardiovascular Diseases (CIBERCV), Carlos III Institute of Health, Madrid, Spain.
Insights
Serum procollagen type I C-terminal propeptide (PICP) levels can identify heart failure patients with better prognosis and potential for myocardial recovery. Low PICP indicates enhanced left ventricular reverse remodeling and reduced risk of heart failure outcomes.
Area of Science:
- Cardiology
- Biomarkers
- Heart Failure Research
Background:
- Myocardial fibrosis is linked to poor prognosis in heart failure (HF), even with treatment.
- Left ventricular reverse remodeling (LVRR) may not fully mitigate fibrosis-related risks.
Purpose of the Study:
- To characterize baseline myocardial fibrosis in HF patients with reduced ejection fraction (<50%).
- To evaluate serum collagen type I-derived peptides (PICP) for association with LVRR and prognosis.
Main Methods:
- Measured serum PICP and other collagen peptides in 1,034 HF patients.
- Assessed 1-year echocardiographic changes in 665 patients using multivariable models.
- Analyzed associations with cardiovascular death and HF-related outcomes in derivation and validation cohorts.
Main Results:
- Serum PICP, but not other peptides, showed continuous association with echocardiographic changes.
- Low PICP (<108.1 ng/mL) patients demonstrated enhanced LVRR and lower HF outcome risk.
- Low PICP combined with improved LVEF predicted better clinical outcomes.
Conclusions:
- Serum PICP can phenotype heart failure patients based on myocardial fibrosis.
- PICP levels may differentiate patients likely to achieve significant myocardial recovery versus partial improvement.
Background:
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.
Objectives:
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.
Methods:
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.
Results:
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).
Conclusions:
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.
