Correlation of potential noninvasive biomarkers of extracellular matrix remodeling with postoperative heart failure - a preliminary study

Background: Postoperative heart failure (PHF) is a major factor that prolongs hospital stay and contributes to increased cost and morbidity after surgery. Clinical predictors of PHF have been identified but lack specificity and predictive accuracy; therefore, identifying the candidates at risk for PHF remains difficult, thus, necessitating further investigation. Since cardiac fibrosis in the elderly contributes to abnormal cardiac contractility, elevated markers of extracellular matrix turnover can be used to identify those at risk for PHF. Purpose: To identify biomarkers in those at risk for PHF. Methods: Serum biomarkers of collagen synthesis (C-terminal propeptide type 1 of procollagen [PICP] and N-terminal propeptide of type III procollagen [PIIINP]), collagen degradation (C-terminal telopeptide of collagen type 1 [CITP]), and extracellular matrix remodeling (matrix metalloprotease-1 [MMP-1] and tissue inhibitor of metalloproteases-1 [TIMP-1]) were determined by ELISA in preoperative blood samples collected from patients with no prior history of heart failure who were undergoing cardiac surgery and correlated to PHF. Results: Of 45 patients enrolled (mean age 69 ± 11 years, 77% male), 11 (24%, mean age 66 ± 10 years) developed PHF requiring additional inotropic support (dobutamine) and management for heart failure. Overall, there were no significant differences in baseline demographics and comorbidities between those who did or did not develop PHF. Ventricular function was preserved, with no significant differences in left ventricular ejection fraction (60 ± 11% vs. 50 ± 16%; P=0.11) or atrial and ventricular dimensions and function between the two groups. Mean PICP levels showed elevated trend in PHF (661 ± 375 ng/ ml vs. 609 ± 410 ng/ml in the non-PHF group; P=0.07); however, PIIINP levels were not significantly different between the two groups (134 ± 72 in PHF vs. 157 ± 73; P=0.47). However, levels of CITP were significantly lower in PHF patients (6 ± 3 ng/ml vs. 9 ± 7 ng/ml; P=0.03). The overall ratio of PICP/CITP was higher in patients with PHF (119 vs. 108; P=0.7). The MMP-1, MMP-2 and TIMP-1 levels were not significantly different between the two groups. Conclusion: The preliminary data obtained from 45 patients demonstrated a trend toward higher PICP levels indicative of collagen synthesis in those at risk for PHF but was not statistically significant. This is likely due to the small sample size and the heterogeneity of the patients, indicating a larger number of heterogeneous patients are needed to demonstrate the prognostic significance of serum biomarkers of extracellular matrix remodeling