Effect of cardiac resynchronization therapy on broad neurohormone biomarkers in heart failure

Neurohormonal dysregulation contributes to heart failure (HF) progression. We sought to determine the effect of cardiac resynchronization therapy (CRT) on nerve growth factor (NGF), a biomarker that promotes the maturation and survival of sympathetic nerve endings, and amino-terminal propeptide of type III procollagen (PIIINP), a marker of type III collagen synthesis. This prospective study consisted of 45 consecutive patients who received cardiac resynchronization therapy defibrillator for advanced HF and 20 healthy age-matched controls. New York Heart Association class, distance of 6-min walk, echocardiography and plasma concentrations of NGF, PIIINP, b-type natriuretic peptide (BNP), norepinephrine, and epinephrine were measured before and 6 months after CRT. Response to CRT was defined as 15% or greater reduction in left ventricular end-systolic volume index at 6-month follow-up. The baseline BNP (2.61 +/- 0.51 vs. 1.53 +/- 0.44 ug/L, P < 0.01) and PIIINP (0.88 +/- 0.21 vs. 0.71 +/- 0.14 mu g/L, P = 0.01), but not other biomarkers, were elevated in HF compared to controls. Twenty-two of 45 patients (49%) responded to CRT. The responder group demonstrated significant decrease only in BNP level from 2.61 +/- 0.51 to 2.31 +/- 0.41 mu g/L (P = 0.04) at 6-month follow-up, paralleling the clinical improvements. The baseline PIIINP, rather than the other biomarkers, was lower in CRT responders than non-responders (0.80 +/- 0.20 vs. 0.96 +/- 0.19 mu g/L, P = 0.03). Univariate and multivariate analysis showed that less elevated plasma PIIINP level in HF might be an independent biomarker predicting better response to CRT (odds ratio = 0.20, 95% CI = 0.03-1.17, P = 0.07). The less elevated PIIINP level in HF, which is suggestive of a lesser amount of cardiac fibrosis, has a trend in association with a favorable response to CRT. Contrary to previous reports, NGF levels are not reduced during HF with optimal medical therapy, and there is no NGF rebound in CRT responders.