Assotiation of testosterone levels and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy
Authors: Enina T. N. , Petelina T. I. , Shirokov N. E. , Gorbatenko E. A. , Rodionova A. E. , Gapon L. I. 
Published: January 2024

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. 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. 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. 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.