9 research outputs found
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Microstructural, Densitometric and Metabolic Variations in Bones from Rats with Normal or Altered Skeletal States
Background: High resolution ΌCT, and combined ΌPET/CT have emerged as non-invasive techniques to enhance or even replace dual energy X-ray absorptiometry (DXA) as the current preferred approach for fragility fracture risk assessment. The aim of this study was to assess the ability of ”PET/CT imaging to differentiate changes in rat bone tissue density and microstructure induced by metabolic bone diseases more accurately than current available methods. Methods: Thirty three rats were divided into three groups of control, ovariectomy and vitamin-D deficiency. At the conclusion of the study, animals were subjected to glucose (18FDG) and sodium fluoride (Na18F) PET/CT scanning. Then, specimens were subjected to ”CT imaging and tensile mechanical testing. Results: Compared to control, those allocated to ovariectomy and vitamin D deficiency groups showed 4% and 22% (significant) increase in 18FDG uptake values, respectively. DXA-based bone mineral density was higher in the vitamin D deficiency group when compared to the other groups (cortical bone), yet ΌCT-based apparent and mineral density results were not different between groups. DXA-based bone mineral density was lower in the ovariectomy group when compared to the other groups (cancellous bone); yet ΌCT-based mineral density results were not different between groups, and the ΌCT-based apparent density results were lower in the ovariectomy group compared to the other groups. Conclusion: PET and micro-CT provide an accurate three-dimensional measurement of the changes in bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity. As osteomalacia is characterized by impaired bone mineralization, the use of densitometric analyses may lead to misinterpretation of the condition as osteoporosis. In contrast, ”CT alone and in combination with the PET component certainly provides an accurate three-dimensional measurement of the changes in both bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
CT, PET <sup>18</sup>FDG and PET Na<sup>18</sup>F images from representative animals from CON, OVX and VIT-D groups.
<p>CT, PET <sup>18</sup>FDG and PET Na<sup>18</sup>F images from representative animals from CON, OVX and VIT-D groups.</p
Study time-line highlighting surgical procedure and measurements.
<p>Study time-line highlighting surgical procedure and measurements.</p
An illustration of the tensile testing mechanism used in the study.
<p>An illustration of the tensile testing mechanism used in the study.</p
DXA-based aBMD changes over the 4 months study period in CON, OVX and VIT-D groups in both trabecular and cortical bone tissues (* indicates significance between CON and OVX groups, ** denotes significance between CON and VIT-D groups, â indicates significance between the OVX and VIT-D groups).
<p>DXA-based aBMD changes over the 4 months study period in CON, OVX and VIT-D groups in both trabecular and cortical bone tissues (* indicates significance between CON and OVX groups, ** denotes significance between CON and VIT-D groups, â indicates significance between the OVX and VIT-D groups).</p
Body mass changes over the 4 months study period in CON, OVX and VIT-D groups (* indicates significance between CON and OVX groups, ** denotes significance between CON and VIT-D groups, â indicates significance between the OVX and VIT-D groups).
<p>Body mass changes over the 4 months study period in CON, OVX and VIT-D groups (* indicates significance between CON and OVX groups, ** denotes significance between CON and VIT-D groups, â indicates significance between the OVX and VIT-D groups).</p
Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure
BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)