Preparation of nano/micro-bimodal Ti/Al/(Mo, W, Cu) powders by simultaneous electrical explosion of dissimilar metal wires

Novel mixtures of micro- and nanoparticles have been obtained by simultaneous electrical explosion of three intertwisted wires (EEW). The possibility of obtaining of titanium‑aluminum micro- and nanoparticles alloyed with molybdenum, tungsten and copper by the electrical explosion of Ti/Al/(Mo, W, Cu – up to 6 at. %) wires has been shown. Spherical particle with sizes from 20 nm to 7 μm are formed under condition of introducing the electric energy at the level of 0.57–0.77 of the total sublimation energy. The mass content of particles with sizes less than 100 nm does not exceed 10%. The phase composition of powders includes double and triple intermetallic phases, titanium oxide (TiO) as well as phases of the initial metals. The study of the phase composition of bulk materials obtained by sintering powders Ti-Al-Mo, Ti-Al-W and Ti-Al-Cu for 2 h at 1000 °C showed the increase in the content of intermetallic phases, providing enhanced physical and mechanical properties of the titanium‑aluminum alloys. The results of the studies show that the obtained powders alloys can be used to produce feedstocks of TiAl alloys

КЛИНИЧЕСКИЕ И ПРОГНОСТИЧЕСКИЕ ОСОБЕННОСТИ ПАЦИЕНТОВ СТАРЧЕСКОГО ВОЗРАСТА С НЕСТАБИЛЬНОЙ СТЕНОКАРДИЕЙ ПРИ КОНСЕРВАТИВНОЙ ТАКТИКЕ ЛЕЧЕНИЯ В ЗАВИСИМОСТИ ОТ ФРАКЦИИ ВЫБРОСА ЛЕВОГО ЖЕЛУДОЧКА

Highlights High cardiovascular morbidity and mortality in the Russian Federation and in Kuzbass is mainly due to high number of elderly and senile patients; it simply reflects the current demographic situation in the country. Elderly and senile patients with acute coronary syndrome (ACS) account for 50% of hospitalized patients. In real clinical practice, a significant number of elderly patients with ACS receive conservative treatment, whereas the prognosis in this cohort is determined by the development of recurrent coronary events and the progression of heart failure. Due to small number of patients older than 75-80 years included in randomized clinical trials, there are certain gaps in the management of elderly patients with ACS and heart failure. Obviously, elderly patients require a special approach to patient management, taking into account the complexity of clinical and anamnestic factors affecting the prognosis. AbstractAim. To study clinical and prognostic features of elderly patients with unstable angina pectoris undergoing conservative treatment depending on left ventricular ejection fraction (LVEF).Methods. 130 elderly patients, with mean age of 82 (77; 89) years, hospitalized for unstable angina with a GRACE score of less than 140 to a vascular center in Kemerovo were included in the study. During hospitalization, standard laboratory and instrumental studies were performed, except coronary angiography. The quality of life was assessed using the EQ-5D 3L questionnaire. After 12 months, patient compliance with treatment recommendations, primary and secondary endpoints, and quality of life were analyzed.Results. All patients were diagnosed with heart failure, 50 (38.5%) patients presented with LV EF less than 40% (the group I), 80 (61.5%) patients presented with LV EF more than 40% (the group II). The groups were comparable in gender, age, presence of multifocal of atherosclerotic disease, prevalence of aortic stenosis, arrhythmias and comorbidities. Women predominated in both groups, and arterial hypertension was noted in all patients. In the group I, a history of myocardial infarction, coronary revascularization, and NYHA FC III were more common (p<0.05). The level of quality of life at discharge was low in both groups: 34.8 (29; 42) and 39.4 (34; 46) points, respectively (p>0.05). Almost all patients were on triple neurohumoral blockade (beta-blockers, renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists) for heart failure and dual antiplatelet therapy. One year later, 85.2% of patients in the group I and 90% of patients in the group II were taking all prescribed medication at low or medium therapeutic doses (without the need for drug titration). The overall mortality in the groups was 46% and 37.5%; cardiovascular deaths accounted for 32% and 30%, respectively (p>0.05). There were no differences in the frequency of endpoints (hospitalization, stroke, acute coronary syndrome, coronary revascularization) between the groups. The level of quality of life remained low in both groups.Conclusion. In patients over 75 years hospitalized for unstable angina, main clinical and anamnestic characteristics, annual prognosis and quality of life do not depend on LV EF, whereas the need for coronary revascularization during the 1 year remains high.Основные положенияРост сердечно-сосудистой заболеваемости и смертности в РФ, в том числе в Кузбассе, в основном вызван увеличением числа больных пожилого и старческого возраста, что отражает текущую демографическую ситуацию в стране. Пациенты пожилого и старческого возраста с острым коронарным синдромом (ОКС) составляют до 50% госпитализированных в стационар. В реальной клинической практике значительное количество больных старческого возраста с ОКС получают консервативное лечение, а прогноз в этой когорте обусловлен развитием повторных коронарных событий и прогрессированием сердечной недостаточности. В связи с небольшой долей лиц старше 75–80 лет, включенных в рандомизированные клинические исследования, в вопросах ведения пациентов старческого возраста с ОКС и сердечной недостаточностью остаются пробелы. Очевидно, что больные старческого возраста требуют особого подхода с учетом наличия комплекса клинических и анамнестических факторов, оказывающих влияние на прогноз. РезюмеЦель. Изучение клинических и прогностических особенностей когорты пациентов старческого возраста с нестабильной стенокардией при консервативной тактике стационарного лечения в зависимости от величины фракции выброса левого желудочка (ФВ ЛЖ).Материалы и методы. В исследование включены 130 больных старческого возраста, 82 (77; 89) лет, госпитализированных по поводу нестабильной стенокардии в первичный сосудистый центр г. Кемерово с баллом по шкале GRACE менее 140. В течение госпитализации больным проведены стандартные лабораторные и инструментальные исследования, за исключением коронароангиографии. Оценено качество жизни с помощью опросника EQ-5D 3L. Через 12 мес. проанализированы соблюдение рекомендаций по лечению, первичные и вторичные конечные точки, качество жизни.Результаты. У всех пациентов диагностирована сердечная недостаточность: у 50 (38,5%) – с ФВ ЛЖ менее 40% (группа I), у 80 (61,5%) – с ФВ ЛЖ более 40% (группа II). Сравниваемые группы не отличались по полу, возрасту, мультифокальности атеросклеротического поражения, частоте аортального стеноза, нарушениям ритма и сопутствующей патологии. В обеих группах преобладали женщины, у всех больных зарегистрирована артериальная гипертензия. В группе I в анамнезе чаще отмечены перенесенный инфаркт миокарда, реваскуляризация миокарда и III функциональный класс хронической сердечной недостаточности по классификации NYHA (р<0,05). Уровень качества жизни при выписке был низким в обеих группах: 34,8 (29; 42) и 39,4 (34; 46) балла соответственно (р>0,05). Практически все пациенты в соответствии с существовавшими на период проведения исследования рекомендациями получали тройную нейрогуморальную терапию сердечной недостаточности (блокаторы ренин-ангиотензин-альдостероновой системы, бета-блокаторы, антагонисты минералокортикоидных рецепторов) и двойную дезагрегантную терапию. Через год 85,2% больных группы I и 90% группы II принимали назначенные препараты в низких или среднетерапевтических дозах без титрации. Общая смертность в группах составила 46 и 37,5%; сердечно-сосудистая – 32 и 30% соответственно (р>0,05). Различий в частоте регистрации жестких конечных точек (госпитализация, инсульт, острый коронарный синдром, коронарная реваскуляризация) между группами не обнаружено. Уровень качества жизни оставался низким в обеих группах.Заключение. У пациентов старше 75 лет, госпитализированных по поводу нестабильной стенокардии, основные клинико-анамнестические характеристики, годовой прогноз и уровень качества жизни не зависят от величины ФВ ЛЖ, а потребность в реваскуляризации миокарда в течение года остается высокой.

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: 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 (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤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 (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF 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 pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk 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

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

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.)