vestarВестник аритмологииJournal of Arrhythmology1561-86412658-7327НАО «Инкарт»10.35336/VA-1215vestar-1319Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLESАссоциация уровня тестостерона и активности оксидативного стресса с 10-летней выживаемостью мужчин с сердечной ресинхронизирующей терапиейAssotiation of testosterone levels and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapyhttps://orcid.org/0000-0002-7443-2952ЕнинаТ. Н.EninaT. N.

Енина Татьяна Николаевна

Томск, пер. Кооперативный, д.5

Tatiana N. Enina

Tomsk, 5 Kooperativnyi lane

enina@infarkta.nethttps://orcid.org/0000-0001-6251-4179ПетелинаТ. И.PetelinaT. I.

Томск, пер. Кооперативный, д.5

Tomsk, 5 Kooperativnyi lane

https://orcid.org/0000-0002-4325-2633ШироковН. Е.ShirokovN. E.

Томск, пер. Кооперативный, д.5

Tomsk, 5 Kooperativnyi lane

https://orcid.org/0000-0003-3675-1503ГорбатенкоЕ. А.GorbatenkoE. A.

Томск, пер. Кооперативный, д.5

Tomsk, 5 Kooperativnyi lane

РодионоваА. Е.RodionovaA. E.

Томск, пер. Кооперативный, д.5

Tomsk, 5 Kooperativnyi lane

https://orcid.org/0000-0002-3620-0659ГапонЛ. И.GaponL. I.

Томск, пер. Кооперативный, д.5

Tomsk, 5 Kooperativnyi lane

Тюменский кардиологический научный центр - филиал ФГБУ «Томский национальный исследовательский медицинский центр Российской академии наук»РоссияTyumen Cardiology Research Center the branch of the Federal State Budgetary Institution «Tomsk National Research Medical Center of the Russian Academy of Science»Russian Federation2024220120243111427Copyright © Енина Т.Н., Петелина Т.И., Широков Н.Е., Горбатенко Е.А., Родионова А.Е., Гапон Л.И., 20242024Енина Т.Н., Петелина Т.И., Широков Н.Е., Горбатенко Е.А., Родионова А.Е., Гапон Л.И.Enina T.N., Petelina T.I., Shirokov N.E., Gorbatenko E.A., Rodionova A.E., Gapon L.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestar.elpub.ru/jour/article/view/1319Цель

Цель. Изучить ассоциацию уровня тестостерона (TES) и активности оксидативного стресса, верифицированного уровнем миелопероксидазы (МПО), с 10-летней выживаемостью мужчин с сердечной ресинхронизирующей терапией (СРТ).

Материал и методы исследования. 86 мужчин с СРТ (59,0±9,8 года; 66,3% с ишемической болезнью сердца) разделены на 4 группы: 1 (n=19) - TES<медианы (16,4 нмоль/л) + МПО<медианы (32,5 нг/мл); 2 (n=18) - TES<медианы + МПО>медианы; 3 (n=23) - TES>медианы + МПО<медианы; 4 (n=26) - TES>медианы + МПО>медианы. Изучена динамика показателей эхокардиографии (ЭхоКГ), частота желудочковой экстрасистолии, TES в плазме, эстрадиол, прогестерон, дегидроэпиандростерона сульфат, норадреналин, МПО, NT-proBNP, матриксная металлопротеиназа, тканевой ингибитор металлопротеиназ. Прогностический уровень NT-proBNP оценен с помощью ROC-анализа, 10-летняя выживаемость методом Каплана-Майера, ассоциированные с ней факторы регрессией Кокса.

Результаты

Результаты. В 3 группе преобладали пациенты II ФК, в 4 - III (р3-4=0,010). Исходно: между группами не выявлено различий параметров ЭхоКГ, NT-proBNP, МПО, стероидов, матриксной металлопротеиназы; во 2 и 4 группах тканевой ингибитор металлопротеиназ-1 был выше; в 4 группе отмечен наибольший норадреналин. В динамике: обратное ремоделирование сердца отмечено в 3, 4 группах, большее в 3, ассоциированное со снижением NT-proBNP; в 1, 3 группах уровень МПО снизился, в 4 группе был наибольшим; в 1 группе увеличился эстрадиол; во 2 - отсутствовала динамика гормонов; в 3 - повысился TES, дегидроэпиандростерона сульфата, снизился прогестерон; в 4 - повысился TES, снизился прогестерон; в группах повысился норадреналин; в 4 группе увеличилось количество желудочковых экстрасистол. Прогностический уровень NT-proBNP составил 756,0 пг/мл (AUC=0,685; р=0,003; чувствительность 64%, специфичность 68%). 10-летняя выживаемость в группах составила: 15,4%; 33,5%; 76,3%; 24,4% соответственно (Log Rank test 1-2=0,378; 1-3<0,001; 1-4=0,070; 2-3=0,009; 2-4=0,772; 3-4=0,010). В 1 и 2 группах с выживаемостью ассоциированы срок лучшего ответа на СРТ (p=0,004), NT-proBNР > 756,0 пг/мл (р=0,001); в 3 и 4 группах - срок лучшего ответа на СРТ (р=0,001), фракция выброса левого желудочка в конце (р=0,046), МПО> медианы (р=0,041), прием амиодарона (0,008).

Выводы

Выводы. СРТ модулирует стероидогенез. Увеличение TES и дегидроэпиандростерона сульфата при низкой активности оксидативного стресса ассоциировано с большим обратным ремоделированием сердца, лучшей 10-летней выживаемостью. При высоком уровне TES факт превышения МПО более 32,5 пг/мл сопряжен с меньшим обратным ремоделированием сердца, увеличением желудочковых аритмий и худшей 10-летней выживаемостью, увеличением относительного риска смерти в 4,2 раза, прием амиодарона - в 5,2 раза. Связь 10-летней выживаемости со сроком лучшего ответа на СРТ свидетельствует о менее физиологичном характере интенсивных модулирующих эффектов СРТ.

Aim

Aim. To investigate the association of testosterone levels (TES) and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy (CRT).

Methods

Methods. 86 men with CRT (59.0±9.8 years; 66.3% ischemic cardiomyopathy) were divided into 4 groups: Gr.1 (n=19) TES<median level (16.4nmol/l) + myeloperoxidase (MPO) < median level (32.5 ng/mL); Gr.2 (n=18) TES<median level + MPO>median level; Gr.3 (n=23) TES> medians + MPO < median level; Gr.4 (n=26) TES > median level + MPO > median level. Echocardiography parameters, incidence of ventricular extrasystole, TES in plasma, estradiol, progesterone, dehydroepiandrosterone sulfate, norepinephrine, MPO, NT-proBNP, matrix metalloproteinase, tissue inhibitor of metalloproteinase were assessed. Prognostic level of NT-proBNP was assessed by ROC analysis; 10-year survival was measured by Kaplan-Meier method, factors associated with it were evaluated using Cox regression.

Results

Results. The majority of patients were NYHA II and NYHA III for Gr. 3 and Gr.4 respectively (р3-4=0,010). At baseline: there was no difference in echocardiography parameters, levels of NT-proBNP, MPO, steroids, matrix metalloproteinase between groups; tissue inhibitor of metalloproteinase was higher in Gr.2 and Gr.4; the highest norepinephrine levels was in Gr.4. Follow-up: reverse cardiac remodeling was associated with NT-proBNP decreasing and was registered in Gr.4 and Gr. 3. The level of MPO was decreased in Gr.3, Gr.4., and was the highest in Gr.4. The level of estradiol was increased in Gr.1; There were no difference in hormone levels in Gr.2. TES, dehydroepiandrosterone sulfate was increased, but progesterone was decreased in Gr.3 and in Gr.4. The norepinephrine`s levels were increased in all groups. The number of ventricular extrastimuli was increased in Gr.4. Predictive level of NT-proBNP was 756.0 pg/ml (AUC=0.685; p=0.003; sensitivity: 64%, specificity: 68%). The 10-year survival rate was 15.4%; 33.5%; 76.3%; 24.4% for Gr. 1-4 respectively (Log Rank test: Gr.1-2=0.378; Gr.1-3<0.001; Gr.1-4=0.070; Gr.2-3=0.009; Gr.2-4=0.772; Gr.3-4=0.010). The survivance was higher in patients with the best CRT response time (p=0.004), the level of NT-proBNP>756.0 pg/ml (p=0.001) in Gr.1, Gr.2; the best CRT response time (p=0.001), left ventricular ejection fraction (p=0.046), MPO>median (p=0.041), amiodarone administration (0.008) in Gr. 3, Gr. 4.

Conclusion

Conclusion. CRT modulates steroidogenesis. Increase of TES and dehydroepiandrosterone sulfate with lower oxidative stress activity is associated with greater reverse cardiac remodeling and better 10-year survival rate. The higher level of TES and simultaneously MPO more than 32.5 pg/ml were related to less reverse cardiac remodeling, higher rate of amiodarone administration by 5.2 times, increasment of ventricular arrhythmias rate and higher relative risk of death by 4.2 times. Relationship between 10-year survival rate and period of best CRT response indicates less physiological nature of forceful modulating effects of CRT.

сердечная ресинхронизирующая терапияполовые гормонытестостеронстероидогенезсердечная недостаточностьоксидативный стрессNT-proBNPвыживаемостьcardiac resynchronization therapysex hormonestestosteronesteroidogenesisheart failureoxidative stressNT-proBNPsurvivalReferencesDi Lodovico E, Facondo P, Delbarba A, et al. Testosterone, Hypogonadism, and Heart Failure. Circulation. Heart Failure. 2022;15(7): e008755. https://doi.org/10.1161/CIRCHEARTFAILURE.121.008755.Di Lodovico E, Facondo P, Delbarba A, et al. Testosterone, Hypogonadism, and Heart Failure. Circulation. Heart Failure. 2022;15(7): e008755. https://doi.org/10.1161/CIRCHEARTFAILURE.121.008755.Marra AM, D’Assante R, Salzano A, et al. Testosterone deficiency independently predicts mortality in women with HFrEF: insights from the T.O.S.CA. registry. ESC heart failure. 2023;10(1): 159-166. https://doi.org/10.1002/ehf2.14117.Marra AM, D’Assante R, Salzano A, et al. 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The authors declare that there are no conflicts of interest present.