Cardiac resynchronization therapy in patients with chronic heart failure is associated with anti-inflammatory and anti-remodeling effects

ObjectivesProinflammatory cytokines, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural remodeling. We aimed to investigate the effects of cardiac resynchronization therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic peptide (NT-proBNP), some interleukins (IL-1β, IL-6, IL-8), MMP-2 and TIMP-2 in patients with chronic heart failure (CHF).Design and methodsWe studied 27 patients (15 M/12 F) with CHF, III–IV NYHA class, implanted with a biventricular pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were collected at baseline and 1 week, 3, 6, and 12 months after CRT device implantation. Cardiac function was assessed echocardiographically.ResultsCRT induced significant improvement in the NYHA class (baseline 3.2 ± 0.5 vs. 1.0 at 12 months, P = 0.0002) and significant LV reverse remodeling, with a 41% (P = 0.001) reduction in LV end-systolic volume (LVESV). This was associated with a significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P = 0.003) from baseline value at 12 months and the correlation with LVESV reduction was 0.41 (P = 0.001).ConclusionsStructural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling.

Figure optionsDownload as PowerPoint slideHighlights
► Elevated levels of NT-proBNP, IL-6, IL-8, MMP-2 are associated with heart failure.
► Cardiac resynchronization therapy exerts an early and gradual decrease of NT-proBNP.
► Cardiac resynchronization therapy has anti-inflammatory and anti-remodeling effects.
► Decreased MMP-2/TIMP-2 leads to reverse ventricular remodeling in heart failure.