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

• Published in: Clinical biochemistry Vol. 46; no. 3; pp. 230 - 234
• Main Authors: Stanciu, Adina Elena, Vatasescu, Radu Gabriel, Stanciu, Marcel Marian, Iorgulescu, Corneliu, Vasile, Alexandra Ioana, Dorobantu, Maria
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2013
• Subjects: Aged; Cardiac resynchronization therapy; Cardiac Resynchronization Therapy - methods; Cardiac Resynchronization Therapy Devices; Case-Control Studies; Chronic Disease - therapy; Chronic heart failure; Echocardiography; Extracellular Matrix - pathology; Extracellular matrix remodeling; Female; Heart Failure - pathology; Heart Failure - therapy; Humans; Inflammation; Inflammation - therapy; Interleukin-1beta - blood; Interleukin-6 - blood; Male; Matrix Metalloproteinase 2 - blood; Middle Aged; Natriuretic Peptide, Brain - blood; NT-proBNP; Peptide Fragments - blood; Time Factors; Tissue Inhibitor of Metalloproteinase-2 - blood; Treatment Outcome; Ventricular Remodeling; CHF; TIMP-2; IL; CRT; Extracellular matrix remodeling; LVEF; NYHA class; LVESV; LV; Inflammation; IQR; Chronic heart failure; Cardiac resynchronization therapy; CS; SD; RAA; NT-proBNP; MLHFQ; MMP-2; LBBB; LVEDV; LVD; 6-MWT
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2012.11.002

Proinflammatory 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). We 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. CRT 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). Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling. [Display omitted] ► 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.