Kardiyak Resenkronizasyon Tedavisinin Kalp Yetersizliğine Etkisinin Moleküler Biyolojik Temellerinin Araştırılması.

Abstract

Heart failure is a complex clinical syndrome characterized by impaired myocardial performance and neuroendocrine system activation. Heart failure, appears to result not only from cardiac overload or injury but also from a complex interplay among genetic, neurohormonal, inflammatory, and biochemical changes acting on cardiac myocytes, the cardiac interstitium, or both. There are several biochemical changes in dyssynchronous heart failure rather than simple electrical stimulation problem. Pathogenetic pathways can be divided in six groups (inflammation, oxidative stress, extracellular-matrix remodeling, neurohormones, myocyte injury and myocyte stress) that involved several biomarkers. In the present study, six groups of biomarkers investigated in same patients before implantation and twelve months after. These biomarkers were interleukin-6, high sensitive C-reactive protein, myeloperoxidase, uric acid, matrix metalloproteinases-2 and 9, plasma procollagen type III, endothelin-1, troponin T, creatine kinase MB fraction, brain natriuretic peptide. Following CRT implantation, patients were monitorized for 12 months with echocardiographic evaluations defining responders by a 15% reduction in end-systolic volume. Levels of MPO, MMP-2, Troponin T, and BNP were significantly decreased in responder group [21,9 ng/ml (75,7-84,4) vs. 11,8 ng/ml (0,9-18,4), p=0,001; 128,1 ng/ml (84,1-218,0) vs. 64,3 ng/ml (5,6-172,9), p=0,001; 0,035 ng/ml (0,003-0,459) vs. 0,015 ng/ml (0,003-0,042), p=0,004; 164,5 pg/ml (13,0-1990,0) vs. 106 pg/ml (10-983), p=0,007, respectively]. Levels of MPO, MMP-2 were significantly decreased and level of uric acid was significantly increased in non-responder group [33,0 ng/ml (0,9-99,1) vs. 10,1 ng/ml (2,4-16,9), p=0,040; 151,9 ng/ml (85,8-243,7) vs. 101,6 ng/ml (54,2-181,3), p=0,003; 5,82±1,93 mg/dl vs. 7,25±2,25 mg/dl, p=0,030, respectively]. The greatest improvement was found in extracellular matrix remodeling (effect size=0,700, p=0,001) in CRT-responder patients. Significant reduction was also found in the level of oxidative stress (effect size=0,489; p=0,001 and myocyte stress (effect size=0,210; p=0,007). However, significant changes in inflammation, myocyte injury and neurohormones cannot be detected in CRT-responder patients.