Relationship between levels of sex hormones and response to cardiac resynchronisation therapy in men

Abstract

Aim. To study the relationship between levels of sex hormones and effectiveness of cardiac resynchronisation therapy (CRT) in men with chronic heart failure (CHF). Materials and methods: The best response to CRT (mean time, 38 [19,0;53,7] months) was identified by a maximum decrease in left ventricular end-systolic volume (LVESV) in 58 men (mean age, 54.8±9.6) with CHF (61% IHD). Based on testosterone (TES) level, patients were divided into group 1 (n=28; 48%) – TES median value. Exercise tolerance (ET), echocardiography (EchoCG) parameters, plasma levels of NT-proBNP, interleukin (IL) – 1β, IL-6, IL-10, tumor necrosis factor α (TNF-α), С-reactive peptide (CRP), galectin-3 (Gal-3), matrix metalloprotease-9 (ММР-9), tissue inhibitors of metalloproteinases TIMP-1, TIMP-4, and the indexes MMP-9/TIMP-1 and MMP-9/TIMP-4 were evaluated in dynamics. Levels of TES, progesterone (PGN), dehydroepiandrosterone sulphate (DHEAS), and es-tradiol (Е2) were measured at baseline. Based on LVESV changes, non-responders (LVESV decrease by <15%), responders (LVESV decrease by >15% but <30%), and super-responders (LVESV decrease by >30%) were identified. Results: In group 2, atrial fibril-lation (р=0.064) and radiofrequency ablation of atrioventricular connection (р=0.014) were observed more frequently; incidence of diabetes mellitus was lower (р=0.017); QRS was smaller (р=0.001); ET was higher both at baseline (р=0.022) and in dynamics (р=0.018); numbers of responders and super-responders were greater (р=0.007); levels of PGN (р=0.028), Il-1β (р=0.020), IL-10 (р=0.013), TNF-α (р=0.006) were higher; and Е2/TES was lower (р=0.004). While EchoCG parameters did not differ at baseline, group 2 showed a tendency towards greater changes in LVESV (р=0.069) and LV end systolic dimension (р=0.087), and a greater increase in LV ejection fraction (р=0.007). In dynamics: In group 1, a decrease in NT-proBNP was observed (р=0.015); in group 2, decreases in IL-1β (р=0.001), IL-6 (р=0.015), IL-10 (р=0.001), TNF-α (р=0.001), TIMP-1 (р=0.046), and Gal-3 (р=0.051) were observed. Levels of sex hormones were correlated with EchoCG parameters, biomarkers of immune inflammation, fibrosis, and NT-proBNP. The ROC analysis showed that a TES level not lower than 13.8 nmol/l was a predictor for a positive response to CRT with a sensitivity of 63.4% and specificity of 76.5% (AUC=0.687; р=0.026). Conclusions: High levels of TES and PGN were associated with better effectivity of CRT, higher ET, greater proportions of responders and super-responders, and reduced immune inflammation activity and fibrosis. A level of TES not lower than 13.8 nmol/l was a predictor for a positive response to CRT.