Tatiana N. Enina
1*, Vadim A. Kuznetsov
2, Anna M. Soldatova
1, Tatiana I. Petelina
1, Dmitriy V. Krinochkin
1, Alexander Yu. Rychkov
1, Olga Yu. Nochrina
11 Scientific researcher in Instrumental Laboratory of Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia
2 Director of Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia
Abstract
Introduction: Gender differences in cardiac resynchronisation therapy (CRT) response are not clear enough. This study aimed to assess gender influence on systemic inflammation, neurohormonal activation, fibrosis in patients with congestive heart failure (CHF) and CRT.
Methods: We compared group I (61 men) and group II (16 women) of patients undergoing CRT. Plasma levels of Nt-proBNP, interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), C-reactive protein, galectin-3 (Gal-3), metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase 1 and 4 (TIMP-1, TIMP-4), ratio MMP-9/TIMP-1, MMP-9/TIMP-4 were measured. According to dynamics of left ventricular end-systolic volume patients were classified into non-responders, responders, super-responders.
Results: Women more likely had left bundle branch block (81.3 vs 47.5%, P = 0.016), were more super-responders (66.7 vs 30.5%). Both groups showed decrease of IL-6 (P < 0.05), TNF-α (P < 0.001; P < 0.05), NT-proBNP (P = 0.001; P < 0.05), Gal-3 (P < 0.05). In women there was decrease of IL-6 by 44.4 vs 23.5% in men (P = 0.029), TNF-α by 41.4 vs 30.9%, NT-proBNP by 73.3 vs 46% (P = 0.002), Gal-3 by 82.3 vs 64.9% (P < 0.05). Group I also showed decrease of IL-10 by 34.2% (P < 0.05). Group dynamics of TIMP-1 was opposite: men showed tendency to reduction of TIMP-1 (P = 0.054), women showed increase of TIMP-1 (P < 0.05). Besides, men showed decrease of MMP-9 (P < 0.05) and ratio MMP-9/TIMP-4 (P < 0.05).
Conclusion: The best response to CRT is associated with female gender explained by greater decrease of neurohormonal activation, systemic inflammation and fibrosis. The revealed opposite dynamics of TIMP-1 in the groups can demonstrate the existence of gender features of matrix metalloproteinase system activity and their tissue inhibitors.