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

Abstract

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 1week, 3, 6, and 12months 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 12months, 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 12months 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.