Effects of thyroxine therapy on bone metabolism in postmenopausal women with hypothyroidism.

OBJECTIVE: To evaluate whether thyroid stimulating hormone-suppressive thyroxine replacement therapy increases bone loss in postmenopausal women. MATERIALS AND METHOD: The study had a cross-sectional design. Fifty-four postmenopausal women on long-term treatment with thyroxine for primary hypothyroidism, who showed suppressed thyroid stimulating hormone levels were enrolled in our study. In these patients and in a control group of 54 healthy postmenopausal women we evaluated bone mineral density at distal radius and the main biochemical parameters of bone turnover. Student's t test, Wilcoxon signed rank-test, Chi-square test and the univariate linear regression in the statistical analysis of the data were employed. RESULTS: Bone mineral density values, expressed as z-scores, in the treated group were significantly decreased in comparison with the control group (p < 0.01). We did not detect a significant relationship between different L-thyroxine doses administered and bone mineral density z-scores. On the contrary, an inverse correlation was detected between length of treatment and bone mineral density z-scores. Treated patients showed a significantly higher concentration of serum alkaline phosphatase, osteocalcin, urinary calcium/creatinine and hydroxyproline/creatinine in comparison with the controls. CONCLUSIONS: Our study suggests that thyroxine replacement therapy in patients with suppressed thyroid stimulating hormone levels increases postmenopausal bone loss

Effects of long-term different physical activity training on human LHCN-M2 myoblast differentiaiton

Introduction: Contracting skeletal muscle releases different myokines that exert both local and endocrine positive metabolic effects (1). Besides, physical exercise seems to modulate skeletal muscle plasticity. The aim of this study was to evaluate whether different-type, long-term training might modulate myogenic differentiation using in vitro system. Methods: Human LHCN-M2 myoblasts (2) were exposed for 4 days to culture medium supplemented with low concentration of serum from n. 5 aerobic (Swimmers) or n. 5 anaerobic (Body Builders) male subjects trained for long-term (mean 5 years). Myogenic differentiation was assessed by calculating the fusion index (FI) number and by evaluating expression levels of MyoD and Myogenin using phase contrast microscopy and western blotting, respectively. Results: LHCN-M2 myoblasts treatment with aerobic sera induced about 1.2-fold increase in myotube formation (FI mean 72% vs 59%) to respect to anaerobic sera as well as increased ratio of myogenin/MyoD expression resulting of about 2-fold greater in cells treated with Swimmers to respect to Body Builders sera. Conclusion: Long-term aerobic training seems to enhance skeletal muscle differentiation at greater extent to respect to anaerobic exercise. References: 1. Pedersen BK., 2011 Brain Behav. Immun.; 25:811; 2. Zhu CH. et al, 2007 Aging Cell. 6:515 Acknowledgements: we thanks Dr Mouly V. for the gift of LHCN-M2 cells (Institut de Myologie-CNRS UMR 7000 Faculte´ de Medecine, Paris 6, France). Grants for this research were purchased from IRCCS SDN, Naples-Italy

A Randomized Study of Cardiac Resynchronization Therapy Defibrillator Versus Dual-Chamber Implantable Cardioverter-Defibrillator in Ischemic Cardiomyopathy With Narrow QRS: The NARROW-CRT Study

Background-Current recommendations require a QRS duration of ≥120 ms as a condition for prescribing cardiac resynchronization therapy (CRT). This study was designed to test the hypothesis that patients with heart failure (HF) of ischemic origin, current indications for defibrillator implantation, and QRS <120 ms may benefit from CRT in the presence of marked mechanical dyssynchrony. Methods and Results-Patients with intraventricular dyssynchrony on echocardiography were randomly assigned to CRT or dual-chamber defibrillator implantation (CRT defibrillator and dual-chamber implantable cardioverter-defibrillator arm, respectively). The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The secondary end point was the cumulative survival from HF hospitalization and HF death. An additional secondary end point was the composite of HF hospitalization, HF death, and spontaneous ventricular fibrillation. Twenty-three of 56 patients with CRT defibrillator showed an improvement in their clinical composite response at 1 year, compared with 9 of 55 patients with dual-chamber implantable cardioverter-defibrillator (41% versus 16%; P=0.004). After a median follow-up of 16 months, the CRT defibrillator arm showed a nonsignificant higher survival from HF hospitalization and HF death (P=0.077), and a significantly higher survival from the combined end point of HF hospitalization, HF death, and spontaneous ventricular fibrillation (P=0.028). Conclusions-In this comparison of CRT defibrillator and dual-chamber implantable cardioverter-defibrillator, CRT improved clinical status in some patients with ischemic cardiomyopathy, mild-to-moderate symptoms, narrow QRS duration, and mechanical dyssynchrony on echocardiograph

Serum from differently exercised subjects induces myogenic differentiation in LHCN-M2 human myoblasts

Myogenesis is the formation of muscle tissue from muscle precursor cells. Physical exercise induces satellite cell activation in muscle. Currently, C2C12 murine myoblast cells are used to study myogenic differentiation. Herein, we evaluated whether human LHCN-M2 myoblasts can differentiate into mature myotubes and express early (myotube formation, creatine kinase activity and myogenin) and late (MyHC-β) muscle-specific markers when cultured in differentiation medium (DM) for 2, 4 and 7 days. We demonstrate that treatment of LHCN-M2 cells with DM supplemented with 0.5% serum from long-term (3 years) differently exercised subjects for 4 days induced myotube formation and significantly increased the early (creatine kinase activity and myogenin) and late (MyHC-β expression) differentiation markers versus cells treated with serum from untrained subjects. Interestingly, serum from aerobic exercised subjects (swimming) had a greater positive effect on late-differentiation marker (MyHC-β) expression than serum from anaerobic (body building) or from mixed exercised (soccer and volleyball) subjects. Moreover, p62and anti-apoptotic Bcl-2 protein expression was lower in LHCN-M2 cells cultured with human sera from differently exercised subjectst han in cells cultured with DM. In conclusion, LHCN-M2 human myoblasts represent a species-specific system with which to study human myogenic differentiation induced by serum from differently exercised subjects

Design and rationale of the Impact of MultiPoint pacing in CRT patients with reduced RV-to-LV delay (IMAGE-CRT) study

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration. A biventricular device is implanted to achieve faster activation and more synchronous contraction of the ventricles. Despite the convincing effect of CRT, 30-40% of patients do not respond. We decided to investigate the role of multipoint pacing (MPP) in a selected group of patients with right ventricle (RV)-to-left ventricle (LV) intervals less than 80 ms that do not respond to traditional CRT. METHODS: We will enrol 248 patients in this patient-blinded, observational, clinical study aiming to investigate if MPP could decrease LV end-systolic volume (ESV) in patients with RV-to-LV interval less than 80 ms. MPP will be activated ON at implant in patients with RV-to-LV delay less than 80 ms and OFF in RV-to-LV at least 80 ms. At follow-up the activation of MPP will be related to CRT response. The primary study endpoint will be the responder rate at 6 months, defined as a decrease in LV ejection fraction, LV end-diastolic volume, LV end-systolic volume (LVESV) at least 15% from baseline. Secondary outcomes include 12 months relative percentage reduction in LVESV and a combined clinical outcome measure of response to CRT defined as the patient being alive, no hospitalization due to heart failure, and experiencing an improvement in New York Heart Association functional class (Composite-Score). CONCLUSION: Reducing the nonresponder rate continues to be an important goal for CRT.If an increase in reverse remodelling can be achieved by MPP, this study supports the conduct of larger trials investigating the role of MPP on clinical outcomes in selected patients treated, right now, only with traditional CRT. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02713308. Registered on 18 March 2016

Fractional flow reserve in patients with reduced ejection fraction.

Fractional flow reserve (FFR) has never been investigated in patients with reduced ejection fraction and associated coronary artery disease (CAD). We evaluated the impact of FFR on the management strategies of these patients and related outcomes. From 2002 to 2010, all consecutive patients with left ventricular ejection fraction (LVEF) ≤50% undergoing coronary angiography with ≥1 intermediate coronary stenosis [diameter stenosis (DS)% 50-70%] treated based on angiography (Angiography-guided group) or according to FFR (FFR-guided group) were screened for inclusion. In the FFR-guided group, 433 patients were matched with 866 contemporary patients of the Angiography-guided group. For outcome comparison, 617 control patients with LVEF &gt;50% were included. After FFR, stenotic vessels per patient were significantly downgraded compared with the Angiography-guided group (1.43 ± 0.98 vs. 1.97 ± 0.84; P &lt; 0.001). This was associated with lower revascularization rate (52% vs. 62%; P &lt; 0.001) in the FFR-guided vs. the Angiography-guided group. All-cause death at 5 years of follow-up was significantly lower in the FFR-guided as compared with Angiography-guided group [22% vs. 31%. HR (95% CI) 0.64 (0.51-0.81); P &lt; 0.001]. Similarly, rate of major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, revascularization, and stroke) was significantly lower in the FFR-guided group [40% vs. 46% in the Angiography-guided group. HR (95% CI) 0.81 (0.67-0.97); P = 0.019]. Higher rates of death and MACCE were observed in patients with reduced LVEF compared with the control cohort. In patients with reduced LVEF and CAD, FFR-guided revascularization was associated with lower rates of death and MACCE at 5 years as compared with the Angiography-guided strategy. This beneficial impact was observed in parallel with less coronary artery bypass grafting and more patients deferred to percutaneous coronary intervention or medical therapy