Evaluating the effects of cardiac resynchronization therapy on pathophysiological pathways of heart failure using surrogate biomarkers

Abstract

Background: Several studies have investigated the effects of cardiac resynchronization therapy (CRT) on heart failure (HF), but none have evaluated the pathophysiological pathways involved in a single group of patients. Therefore, this study aims to assess the long-term effects of CRT on six different pathophysiological pathways involved in the process of HF by the use of surrogate biomarkers.

Methods: In a group 44 patients with HF, six groups of biomarkers were measured, both at baseline and 1 year after CRT implantation: inflammation (interleukin [IL]-4, IL-6, tumor necrosis factor [TNF]-alpha, high sensitive C-reactive protein [hsCRP]); oxidative stress (myeloperoxidase [MPO], oxidized low-density lipoprotein [oxLDL], uric acid); extracellular matrix (ECM) remodeling (matrix metalloproteinase [MMP]-2 and -9, galectin-3, procollagen III N-terminal propeptide [prokol-3NT]); neurohormonal pathways (endothelin-1, chromogranin-A); myocyte injury (troponin T, creatine kinase MB fraction [CK-MB]), myocyte stress (B-type natriuretic peptide [BNP]). CRT responders were defined as patients with >= 15% reduction in left ventricular end-systolic volume at 12 months post-CRT.

Results: At 1-year follow-up, 72.7% (n = 32) of the patients were categorized as CRT responders. In these patients, the levels of IL-6, MPO, oxLDL, MMP-2, galectin-3, troponin T, and BNP were significantly reduced as compared to baseline values. While the biomarkers for myocyte stress (effect size = 0.357; p = 0.001), ECM remodeling (effect size = 0.343; p = 0.015) and oxidative stress (effect size = 0.247; p = 0.039) showed a significant change in the CRT responders during follow-up, the biomarkers for other pathophysiological pathways did not show a significant alteration.

Conclusions: In the present study, a significant reduction was only observed in the biomarkers of myocardial stress, ECM remodeling, and oxidative stress among all the CRT responder subjects.