Abstract

To study the relationship between levels of sex hormones and effectiveness of cardiac resynchronisation therapy (CRT) in men with chronic heart failure (CHF). 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. 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). 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.

Highlights

  • Современным стандартом лечения больных ХСН со сни­женной ФВ ЛЖ, имеющих расширенный комплекс QRS, является сердечная ресинхронизирующая терапия (СРТ), эффективность которой составляет примерно 70 %

  • Исходно методом конкурентного твердофазного хемилюминесцентного иммуноферментного анализа были исследованы плазменные уровни TES, прогестерона (PGN), дегидроэпиандростерона-сульфата (DHЕАS), эстрадиола (E2)

  • Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP et al Correlation between Testosterone and the Inflammatory Marker Sol‐ uble Interleukin-6 Receptor in Older Men. The Journal of Clinical En‐ docrinology & Metabolism

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Summary

Summary

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. Цель работы – изучение у мужчин с ХСН взаимосвязи уровня половых гормонов с эффективностью СРТ. Были исследованы плазменные уровни N-концевого фрагмента мозгового натрийуретического пептида (NT-proBNP), интерлейкинов (ИЛ) – 1β, ИЛ-6, ИЛ-10, ФНО-α, галектина-3 (Гал-3), матриксной металлопротеиназы 9 (ММР-9), тканевых ингибиторов металлопротеиназ (TIMP-1 и TIMP-4) методом твердофазного хемилюминесцентного иммуноферментного анализа («сэндвич-метод») на анализаторе IMMULITE 1000 (Siemens Diagnostics, США). Исходно методом конкурентного твердофазного хемилюминесцентного иммуноферментного анализа были исследованы плазменные уровни TES, прогестерона (PGN), дегидроэпиандростерона-сульфата (DHЕАS), эстрадиола (E2). ФК – ФК по классификации NYHA; ПИКС – постинфарктный кардиосклероз; АКШ – аорто-коронарное шунтирование; ТБКА – транс‐ люминальная баллонная коронарная ангиопластика; ПБЛНПГ – полная блокада левой ножки пучка Гиса; ФП – фибрилляция предсер‐ дий; РЧА – радиочастотная аблация; нд – недостоверно (р>0,05); антиаритмики (кордарон, сотагексал); АМКР – антагонисты минера‐ локортикоидных рецепторов; иАПФ – ингибиторы ангиотензин-превращающего фермента

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