The effect of exercise training on endothelial function in postmenopausal women with breast cancer under aromatase inhibitor therapy.

BACKGROUND: Breast cancer is the leading non-cardiovascular cause of death in women. In endocrine receptor positive women, aromatase inhibitors (AI) are the therapy of choice despite the fact that a decrease in systemic estrogen levels may result in endothelial dysfunction and eventually in cardiovascular disease. In this study, we assessed whether exercise training (ET), which has repeatedly shown to lead to an improvement of endothelial dysfunction, will also exert this effect in postmenopausal women with AI treated breast cancer. METHODS: Thirty two postmenopausal women with AI treated breast cancer were randomized to an intervention group (ET; 6 months, supervised training plus 6 months without intervention) or control group of usual care (UC; 12 months without intervention plus initial exercise counseling). Endothelial function was assessed via Reactive Hyperemia Index (RHI) measured non-invasively with the EndoPAT-System at baseline, 6 and 12 months. RESULTS: After 6 months of supervised ET, changes in maximal exercise capacity were significantly greater in ET than in UC (∆W: 24.1 ± 11.5 vs. 1.1 ± 8.2 watts; p < 0.001). Even though 43.8% of all participants had endothelial dysfunction at baseline, there were no significant group differences in the changes of RHI between ET (∆RHI: -0.1 ± 1.04) and UC (0.02 ± 0.75; p = 0.323) after 6 months. CONCLUSION: Even though ET led to significantly greater improvement in exercise capacity in postmenopausal women with AI treated breast cancer than exercise counseling only, it did not exert any measurable effects on endothelial dysfunction.

Habitual Physical Activity in Older Adults Undergoing TAVR: Insights From the FRAILTY-AVR Study.

OBJECTIVES: The authors sought to assess the distribution and prognostic significance of habitual physical activity (HPA) in older adults undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Low HPA is associated with mortality and disability in community-dwelling older adults. In the setting of TAVR, it is unclear whether low HPA is a risk factor for downstream morbidity or a byproduct of severe aortic stenosis that improves following its correction. METHODS: Older adults undergoing TAVR in the prospective multicentre FRAILTY-AVR (Frailty in Aortic Valve Replacement) study were interviewed to quantify their HPA in kilocalories/week using a validated questionnaire at baseline and follow-up. The primary endpoint was all-cause mortality at 12 months. RESULTS: The cohort consisted of 755 patients with a median age of 84.0 years (interquartile range [IQR]: 80.0 to 87.0 years). At baseline, median HPA was 1,116 kcal/week (IQR: 227 to 2,715 kcal/week) with 73% of patients performing <150 min/week of moderate or vigorous HPA. Sedentary patients were more likely to be older, female, frail, cognitively impaired, depressed, and have multimorbidity, although they had similar left ventricular function and aortic stenosis severity. In the logistic regression model adjusting for these covariates, HPA was found to be associated with mortality at 12 months (odds ratio: 0.84/100 kcal; 95% confidence interval: 0.73 to 0.98). HPA was associated with longer length of stay, discharge to health care facilities, and disability. At 12 months, median HPA among survivors was 933 kcal/week (IQR: 0 to 2,334 kcal/week) with pre-existing frailty being independently predictive of worsening HPA following TAVR. CONCLUSIONS: Sedentary patients have a higher risk of mortality and functional decline following TAVR.

Does low serum TSH within the normal range have negative impact on physical exercise capacity and quality of life of healthy elderly people?

Objective Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit. Materials and methods Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise. Results From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention. Conclusions We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Modifications of skeletal muscle ryanodine receptor type 1 and exercise intolerance in heart failure.

BACKGROUND: In experimental heart failure animal models, remodeling of skeletal and cardiac muscle ryanodine receptors (RyR), including phosphorylation, S-nitrosylation and oxidation, have been reported to contribute to pathologic Ca2+ release, impaired muscle function and fatigue. However, it is not known whether similar remodeling of RyR1 in skeletal muscle occurs in patients with heart failure, and if this is associated with impairment of physical activity. METHODS: We studied 8 sedentary patients with New York Heart Association (NYHA) Class III heart failure and 7 age-matched, healthy, but sedentary controls. All heart failure patients had NYHA Class III and peak VO2, echocardiography and NT-proBNP data consistent with moderate to severe heart failure. The age-matched controls included were allowed hypertension but sub-clinical heart failure was to have been ruled out by normal peak VO2, echocardiography and NT-proBNP. RESULTS: Exercise capacity (VO2max) differed by almost 2-fold between heart failure patients and age-matched controls. Compared with controls, skeletal muscle RyR1 in heart failure patients was excessively phosphorylated, S-nitrosylated and oxidized. Furthermore, RyR1 from heart failure patients was depleted of its stabilizing protein FK 506-binding protein 12 (FKBP12, or calstabin1). CONCLUSIONS: For the first time we show that skeletal muscle RyR1 from human heart failure is post-translationally modified, which corroborates previous data from experimental animal studies. This indicates pathologic Ca2+ release as a potential mechanism behind skeletal muscle weakness and impaired exercise tolerance in patients with heart failure and suggests a potential target for pharmacologic intervention.