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

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 identifed 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 (13.8 nmol/l) and group 2 (n=30; 52%) - TES > median value. Exercise tolerance (ET), echocardiography (EchoCG) parameters, plasma levels of NTproBNP, 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 estradiol (Е2) were measured at baseline. Based on LVESV changes, non-responders (LVESV decrease by 15% but 30%) were identifed.

Results: In group 2, atrial fibrillation (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 NTproBNP. 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 specifcity of 76.5% (AUC=0.687; р=0.026).

Conclusions: High levels of TES and PGN were associated with beter 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.