Humoral markers of fibrosis and vascular dysfunction are associated with cardiac remodeling and functional limitation in chronic heart failure
L Sahakyan, R Mayrapetyan, L U S Sahakyan, H SisakyanAbstract
Background
Neurohormonal activation contributes to myocardial remodeling, fibrosis, and disease progression in chronic heart failure. Dysregulation of humoral mediators involved in fibrotic signaling and vascular tone has been described; however, their relevance to cardiac structure, systolic function, and functional capacity in clinically stable patients remains insufficiently characterized.
Purpose
To evaluate the association of selected humoral biomarkers with echocardiographic parameters and exercise capacity in patients with compensated chronic heart failure.
Methods
We studied 83 patients with compensated chronic heart failure (mean age 67 ± 10 years, 35% women, New York Heart Association class II–III, left ventricular ejection fraction <45%). Serum levels of procollagen type I N-terminal propeptide, endothelin-1, and nitric oxide were measured. Associations with left ventricular structure, systolic function, and 6-minute walk test distance were analyzed using age- and sex-adjusted linear regression models. Model robustness was assessed using variance inflation factors.
Results
Procollagen type I N-terminal propeptide showed the most consistent associations with cardiac structure and function. Higher levels were independently associated with lower left ventricular ejection fraction (standardized β = −0.215, p = 0.048) and shorter 6-minute walk distance (β = −0.242, p = 0.020). Endothelin-1 was independently associated with smaller left ventricular end-diastolic diameter (β = −0.235, p = 0.022). Nitric oxide levels were independently associated with reduced exercise capacity (β = −0.208, p = 0.043). Age and sex were significant covariates across all models. No relevant multicollinearity was observed.
Conclusion
In patients with compensated chronic heart failure, procollagen type I N-terminal propeptide is independently associated with impaired systolic function and reduced exercise capacity, supporting its potential utility as a clinically relevant marker of myocardial fibrosis and early functional deterioration. The outcome-specific associations observed for endothelin-1 and nitric oxide suggest that humoral profiling may provide complementary information beyond conventional clinical assessment. These findings support further evaluation of multi-biomarker strategies for improved patient phenotyping, risk stratification, and monitoring in chronic heart failure.