Vol 25, No 1 (2018)
Original articles — Clinical cardiology
Published online: 2017-09-28

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

Hamza Sunman, Adem Özkan, Hikmet Yorgun, Uğur Canpolat, Erdem Karabulut, Tülin Bayrak, Ergün Barış Kaya, Lale Tokgözoğlu, Necla Özer, Asuman Özkara, Kudret Aytemir, Ali Oto
Pubmed: 28980281
Cardiol J 2018;25(1):42-51.


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]-a, 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. (Cardiol J 2018; 25, 1: 42–51)

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