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

Clin Biochem. 2013 Feb;46(3):230-4. doi: 10.1016/j.clinbiochem.2012.11.002. Epub 2012 Nov 13.

Abstract

Objectives: 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).

Design and methods: 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 1 week, 3, 6, and 12 months after CRT device implantation. Cardiac function was assessed echocardiographically.

Results: CRT 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).

Conclusions: Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiac Resynchronization Therapy / methods*
  • Cardiac Resynchronization Therapy Devices
  • Case-Control Studies
  • Chronic Disease / therapy
  • Echocardiography
  • Extracellular Matrix / pathology
  • Female
  • Heart Failure / pathology
  • Heart Failure / therapy*
  • Humans
  • Inflammation / therapy
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Male
  • Matrix Metalloproteinase 2 / blood
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-2 / blood
  • Treatment Outcome
  • Ventricular Remodeling*

Substances

  • IL1B protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Peptide Fragments
  • TIMP2 protein, human
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP2 protein, human
  • Matrix Metalloproteinase 2