Abstract 3078: Myocardial Collagen Metabolism In Failing Hearts Before And During Cardiac Resynchronization Therapy
Objective Cardiac resynchronization therapy (CRT) has proven efficacy in improving left ventricular ejection fraction (LVEF), LV diastolic function, NYHA functional class and outcome in patients with congestive heart failure (CHF), although a substantial number of patients respond poorly to CRT. We investigated whether myocardial collagen metabolism of patients with CHF is implicated in good or poor response to CRT.
Methods We analyzed collagen synthesis and degradation by measuring the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP, resp.) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with CHF before and 6 months after start of CRT. Patients had NYHA class III–IV, LVEF ≤35%, and QRS duration >120 ms.
Results In 46 patients, CRT resulted in >10% reduction of LV end-systolic volume (LVESV), referred to as responders, whereas in 18 patients LVESV did not change upon CRT or even increased, referred to as non-responders. Responders demonstrated an increase of serum PINP and PIIINP upon CRT, from 32.9±2.2 to 46.7±4.0 μg/L (p<0.001) and from 4.59±0.24 to 5.13±0.36 μg/L (p<0.05), respectively, whereas serum PINP and PIIINP of non-responders did not change upon CRT (from 41.8±4.3 to 43.8±6.2 μg/L and from 4.03±0.45 to 4.28±0.31 μg/L, resp.). Responders had higher serum levels of ICTP at baseline and at 6 months follow-up (from 3.38±0.54 to 3.12±0.48 μg/L) than non-responders at both time points (from 1.96±0.37 to 1.92±0.38 μg/L), although these differences were not statistically significant.
Conclusion Compared to future non-responders to CRT, future responders demonstrate relatively low levels of markers of collagen synthesis and relatively high levels of markers of collagen degradation at baseline. Unlike non-responders, responders show an increase in collagen synthesis in the first 6 months of CRT.