AIMS: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF. METHODS AND RESULTS: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12-1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF. CONCLUSIONS: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk-benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02661217.

• MeSH
• aminobutyráty terapeutické užití   MeSH
• bifenylové sloučeniny terapeutické užití   MeSH
• fixní kombinace léků MeSH
• lidé MeSH
• následná péče MeSH
• propuštění pacienta MeSH
• srdeční selhání * farmakoterapie   MeSH
• valsartan terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

AIMS: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). METHODS AND RESULTS: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46). CONCLUSIONS: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02661217.

• MeSH
• aminobutyráty aplikace a dávkování   MeSH
• antagonisté receptorů pro angiotenzin aplikace a dávkování   MeSH
• fixní kombinace léků MeSH
• hemodynamika účinky léků   fyziologie   MeSH
• lidé MeSH
• následné studie MeSH
• neprilysin MeSH
• propuštění pacienta trendy   MeSH
• senioři MeSH
• srdeční selhání farmakoterapie   patofyziologie   MeSH
• tetrazoly aplikace a dávkování   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

AIMS: Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity. METHODS: TRANSITION, a randomized, open-label study compared sacubitril/valsartan initiation pre-discharge vs. post-discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10-week and 26-week post-randomization. RESULTS: Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril/valsartan target dose (97/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre-discharge or post-discharge respectively [diabetes subgroup: 47% (n = 105/226) vs. 50% (n = 115/228); relative risk ratio (RRR), 0.923; P = 0.412; non-diabetes subgroup: 45% (n = 119/267) vs. 51% (n = 133/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49/51 mg or 97/103 mg bid [diabetes subgroup: 61.1% (n = 138/226) vs. 67.5% (n = 154/228); RRR, 0.909; P = 0.175; non-diabetes subgroup: 62.9% [n = 168/267] vs 69.3% [n = 181/261]; RRR, 0.906; P = 0.118] or any dose for ≥2 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192/226) vs. 88.2% (n = 201/228); RRR, 0.966; P = 0.356; non-diabetes subgroup: 86.9% (n = 232/267) vs. 90.8% (n = 237/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre-discharge or post-discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non-diabetes subgroups at 10 weeks, respectively: pre-discharge (7.5% vs. 7.1%) or post-discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT-proBNP (P < 0.005) and hs-TnT (P < 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non-diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non-diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks. CONCLUSIONS: Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up-titration and tolerability as in those without diabetes.

• MeSH
• aminobutyráty terapeutické užití   MeSH
• antagonisté receptorů pro angiotenzin terapeutické užití   MeSH
• bifenylové sloučeniny terapeutické užití   MeSH
• diabetes mellitus * MeSH
• lidé MeSH
• následná péče MeSH
• propuštění pacienta MeSH
• srdeční selhání * MeSH
• tepový objem fyziologie   MeSH
• tetrazoly terapeutické užití   MeSH
• valsartan terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

• Publikační typ
• komentáře MeSH
• souhrny MeSH

Akutní srdeční selhání (SS) je nejběžnějším důvodem pro hospitalizaci v zemích západního světa. Přitom platí, že 30 40 % pacientů je znovu hospitalizováno do 12 mě síců. V průběhu zranitelného období po propuštění (2 3 měsíce) může míra opakovaných hospitalizací dosáhnout 25 % v prvních 30 dnech. Mortalita v této době činí asi 10 %. Hospitalizace pacienta tak představuje důležitou dobu, kdy máme příležitost pro zahájení a úspěšnou titraci doporučených terapií.

• Klíčová slova
• sacubitril-valsartan, TRANSITION,
• MeSH
• fixní kombinace léků * MeSH
• kardiovaskulární látky aplikace a dávkování   MeSH
• lidé MeSH
• propuštění pacienta MeSH
• randomizované kontrolované studie jako téma MeSH
• srdeční selhání * farmakoterapie   MeSH
• statistika jako téma MeSH
• valsartan aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• sakubitril/valsartan, studie TRANSITION,
• MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• neprilysin * antagonisté a inhibitory   MeSH
• srdeční selhání * farmakoterapie   MeSH
• valsartan terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• rozhovory MeSH

• MeSH
• longitudinální studie MeSH
• populační dynamika MeSH
• zdravotní stav MeSH
• Geografické názvy
• Ukrajina MeSH

• Konspekt
• Sociologie
• NLK Obory
• sociologie
• demografie
• NLK Publikační typ
• studie

Our study demonstrates that nanoplasmonic sensing (NPS) can be utilized for the determination of the phase transition temperature (Tm) of phospholipids. During the phase transition, the lipid bilayer undergoes a conformational change. Therefore, it is presumed that the Tm of phospholipids can be determined by detecting conformational changes in liposomes. The studied lipids included 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Liposomes in gel phase are immobilized onto silicon dioxide sensors and the sensor cell temperature is increased until passing the Tm of the lipid. The results show that, when the system temperature approaches the Tm, a drop of the NPS signal is observed. The breakpoints in the temperatures are 22.5 °C, 41.0 °C, and 55.5 °C for DMPC, DPPC, and DSPC, respectively. These values are very close to the theoretical Tm values, i.e., 24 °C, 41.4 °C, and 55 °C for DMPC, DPPC, and DSPC, respectively. Our studies prove that the NPS methodology is a simple and valuable tool for the determination of the Tm of phospholipids.

• MeSH
• fosfolipidy chemie   MeSH
• liposomy chemie   MeSH
• povrchová plasmonová rezonance metody   MeSH
• tranzitní teplota * MeSH
• změna skupenství * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Projekt navazuje na dlouhodobé/již 6leté sledování vývoje kardiovaskulárního rizika u žen středního věku přecházejících do menopauzy. V souboru 400 žen prospektivně definovaných dle reprodukčního stavu budou stanoveny parametry vlastností tepenné stěny a jejich asociace s tradičními, nově zkoumanými (epigenetickými, hematologickými) parametry postižení cévní stěny, včetně protektivních faktorů (endoteliální progenitorové buňky). Z hlediska Resortního programu výzkumu III tento projekt spojuje několik priorit: zlepšení výzkumu v oblasti vlivu zevního prostředí na výskyt nejzávažnějších a nejčastějších onemocnění na vznik chorob srdce a cév s využitím dat z longitudinální populačně založené studie žen v různých stádiích přechodu do menopauzy.; The project is based on already ongoing 6 year study focused on detection of development of cardiovascular risk in middle-aged women in menopausal transition. In a group of 400 women prospectively defined according to their reproductive state the parameters of arterial wall properties and their association with traditional and newly surveyed (epigenetic, hematological) parameters of vascular impairment, including protective factors (endothelial progenitor cells) will be established. In terms of departmental research program, this project combines a number of priorities: improving research focused on the impact of environmental factors on the occurrence of the most serious and most common diseases using data from a longitudinal population-based study of women in various stages of transition to menopause.

• MeSH
• endoteliální progenitorové buňky MeSH
• kouření MeSH
• longitudinální studie MeSH
• menopauza MeSH
• rizikové faktory MeSH
• ženy MeSH

• Konspekt
• Hygiena. Lidské zdraví
• NLK Obory
• angiologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• MeSH
• etnicita MeSH
• longitudinální studie MeSH
• populační dynamika MeSH
• zdravotní stav MeSH

• Konspekt
• Společenské vědy
• NLK Obory
• sociologie
• demografie