Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by nonresolving major-vessel pulmonary thrombi, believed to result from single or recurrent pulmonary thromboemboli. Because CTEPH is associated with high morbidity and mortality the recognition of patients who are at risk has become an important goal. While current data suggest that CTEPH does not result from traditional known thrombophilia or defective plasma fibrinolysis, it has been suggested that levels of Factor VIII and antiphospholipid antibodies (alongside increased lupus anticoagulant), two thrombophilic factors associated with recurrent thrombosis, are elevated in association with CTEPH. Additional risk factors have been evaluated in CTEPH patients including blood groups and lipoprotein (a). Certain medical conditions (splenectomy, ventriculo-atrial shunt/(infected) intravenous lines, acute PE and chronic inflammatory states) have been established as independent risk factors for CTEPH. In particular, the link between splenectomy and CTEPH has gained considerable attention, with speculation that abnormal post-splenectomy erythrocyte activities or abnormal platelet activation may be involved. Although some patients may be genetically susceptible to pulmonary arterial hypertension, genetic variants linked with CTEPH have yet to be determined. Improved understanding of risk factors for CTEPH is an important goal, allowing better targeting of at-risk groups, facilitation of appropriate intervention and potential limitation of disease progression.

Chronická tromboembolická pľúcna hypertenzia (CTEPH) je charakterizovaná nerozpustenými trombami vo veľkých pľúcnych artériách, ktoré sú dôsledkom jednej alebo opakujúcich sa aták pľúcneho thromboembolizmu. Pretože CTEPH je spojená s vysokou chorobnosťou a úmrtnosťou, rozpoznanie rizikových pacientov je veľmi dôležitou úlohou. Zatiaľ čo súčasné vedomosti poukazujú na to, že CTEPH nevzniká v dôsledku už tradične známej trombofílie alebo porušenej fibrinolýzy, sú hladiny faktora VIII a antifosfolipidových protilátok (spolu so zvýšeným lupus antikoagulans), dvoch trombofilných faktorov asociovaných s rekurentnou trombózou, pri CTEPH zvýšené. Za ďalšie rizikové faktory CTEPH sa považujú krvné skupiny a lipoproteín (a). Niektoré chorobné stavy (splenektómia, ventrikulo-atriálny shunt, (infikované) intravenózne prístupy, akútna pľúcna embólia a chronické zápalové stavy) sa hodnotia ako nezávislé rizikové faktory pre CTEPH. Najmä súvisu splenektómie a CTEPH sa venuje značná pozornosť v predstave, že abnormálna aktivita erytrocytov po splenektómii alebo abnormálna aktivácia krvných doštičiek môžu hrať úlohu. I keď sa zvažuje, že niektorí pacienti by mohli byť geneticky predisponovaní k pľúcnej artériovej hypertenzii, doposiaľ sa genetická spojitosť s CTEPH nezistila. Lepšie poznanie rizikových faktorov CTEPH je dôležitým cieľom, ktorý umožní lepšie a cielené vyhľadávanie rizikových skupín, uľahčí adekvátnu intervenciu a potenciálne obmedzí progresiu ochorenia.

Každodenní trénink pro lepší tělesný pocit: prevence a pomoc při obtížích v každém věku. Posilování pánevního dna jen tak mimochodem: Jednoduché zařazení základních principů pohybu do všedního dne: při sezení, stání, chůzi nebo práci. Ideální začátek: Jak „zapnout“ a znovu uvolnit pánevní dno: jednoduchý cvičební program na začátek. Zdraví a dobrý tělesný pocit: Jak si díky cvikům na pánevní dno zlepšit držení těla i celkový zdravotní stav – třeba při bolestech v zádech nebo pro větší potěšení při sexu.

• MeSH
• pánev fyziologie   MeSH
• techniky cvičení a pohybu metody   MeSH
• zdraví žen MeSH
• Publikační typ
• příručky MeSH

• Konspekt
• Sport. Hry. Tělesná cvičení
• NLK Obory
• tělovýchovné lékařství
• gynekologie a porodnictví

• MeSH
• anorektika škodlivé účinky   MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• nemoci srdečních chlopní epidemiologie   etiologie   patofyziologie   MeSH
• plicní hypertenze škodlivé účinky   MeSH
• Check Tag
• lidé MeSH

The aim of the open label extension (OLE) of CTREPH study was to characterize multimodal treatment in patients with severe inoperable CTEPH, to describe long-term subcutaneous (SC) treprostinil safety and tolerability, and to evaluate change in functional class and exercise capacity over 24 months since completion of the blinded phase of CTREPH. The target population in the OLE consisted of patients who completed 24 weeks of blinded treatment with either high-dose treprostinil of around 30 ng/kg/min (former high-dose group), or low-dose treprostinil of around 3 ng/kg/min (former low-dose group) in the CTREPH study. From the start of OLE, treprostinil dose and any additional therapy were chosen according to the standard of care and physician's discretion. Out of 47 enrolled patients, 20 patients received other PH drugs during OLE and 17 patients underwent at least 1 BPA session. Number of treprostinil-related AEs was substantially higher in the former low-dose group in comparison to the former high-dose group. Related AEs were also more frequent during the first 6 months of the preceding blinded trial than over 24 months of OLE, especially infusion site pain and all local infusion site reactions. No new safety signal was detected. Evaluated clinical outcomes show sustained benefit from long-term treprostinil treatment. Long-term SC treprostinil is a safe and effective component of multimodal treatment for patients with severe CTEPH. Patients who tolerate treprostinil after initiation are likely to continue tolerating it over time, with the clinical benefit maintained over 24 months.

• Publikační typ
• časopisecké články MeSH

Since the last World Symposium on Pulmonary Hypertension in 2008, we have witnessed numerous and exciting developments in chronic thromboembolic pulmonary hypertension (CTEPH). Emerging clinical data and advances in technology have led to reinforcing and updated guidance on diagnostic approaches to pulmonary hypertension, guidelines that we hope will lead to better recognition and more timely diagnosis of CTEPH. We have new data on treatment practices across international boundaries as well as long-term outcomes for CTEPH patients treated with or without pulmonary endarterectomy. Furthermore, we have expanded data on alternative treatment options for select CTEPH patients, including data from multiple clinical trials of medical therapy, including 1 recent pivotal trial, and compelling case series of percutaneous pulmonary angioplasty. Lastly, we have garnered more experience, and on a larger international scale, with pulmonary endarterectomy, which is the treatment of choice for operable CTEPH. This report overviews and highlights these important interval developments as deliberated among our task force of CTEPH experts and presented at the 2013 World Symposium on Pulmonary Hypertension in Nice, France.

• MeSH
• chronická nemoc MeSH
• lidé MeSH
• plicní embolie diagnóza   epidemiologie   terapie   MeSH
• plicní hypertenze diagnóza   epidemiologie   terapie   MeSH
• srdeční katetrizace metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long-term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double-blind clinical trial comparing high-dose and low-dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high-dose arm vs. 8.6 in low-dose arm), but mean RRS change from baseline to Week 24 was greater in the high-dose treprostinil group than in the low-dose treprostinil group (-0.88 vs. -0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of -0.70 (95% confidence interval: -1.36 to -0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N-terminal pro-brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is a common, globally recognised, form of heart failure for which no treatment has yet been shown to improve symptoms or prognosis. The pathophysiology of HFPEF is complex but characterised by increased left atrial pressure, especially during exertion, which might be a key therapeutic target. The rationale for the present study was that a mechanical approach to reducing left atrial pressure might be effective in HFPEF. METHODS: The REDUCe Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF) study was an open-label, single-arm, phase 1 study designed to assess the performance and safety of a transcatheter interatrial shunt device (IASD, Corvia Medical, Tewkesbury, MA, USA) in patients older than 40 years of age with symptoms of HFPEF despite pharmacological therapy, left ventricular ejection fraction higher than 40%, and a raised pulmonary capillary wedge pressure at rest (>15 mm Hg) or during exercise (>25 mm Hg). The study was done at 21 centres (all departments of cardiology in the UK, Netherlands, Belgium, France, Germany, Austria, Denmark, Australia, and New Zealand). The co-primary endpoints were the safety and performance of the IASD at 6 months, together with measures of clinical efficacy, including functional capacity and clinical status, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01913613. FINDINGS: Between Feb 8, 2014, and June 10, 2015, 68 eligible patients were entered into the study. IASD placement was successful in 64 patients and seemed to be safe and well tolerated; no patient had a peri-procedural or major adverse cardiac or cerebrovascular event or need for cardiac surgical intervention for device-related complications during 6 months of follow-up. At 6 months, 31 (52%) of 60 patients had a reduction in pulmonary capillary wedge pressure at rest, 34 (58%) of 59 had a lower pulmonary capillary wedge pressure during exertion, and 23 (39%) of 59 fulfilled both these criteria. Mean exercise pulmonary capillary wedge pressure was lower at 6 months than at baseline, both at 20 watts workload (mean 32 mm Hg [SD 8] at baseline vs 29 mm Hg [9] at 6 months, p=0·0124) and at peak exercise (34 mm Hg [8] vs 32 [8], p=0·0255), despite increased mean exercise duration (baseline vs 6 months: 7·3 min [SD 3·1] vs 8·2 min [3·4], p=0·03). Sustained device patency at 6 months was confirmed by left-to-right shunting (pulmonary/systemic flow ratio: 1·06 [SD 0·32] at baseline vs 1·27 [0·20] at 6 months, p=0·0004). INTERPRETATION: Implantation of an interatrial shunt device is feasible, seems to be safe, reduces left atrial pressure during exercise, and could be a new strategy for the management of HFPEF. The effectiveness of IASD compared with existing treatment for patients with HFPEF requires validation in a randomised controlled trial. FUNDING: Corvia Medical Inc.

• MeSH
• implantace protézy MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• srdeční katetrizace MeSH
• srdeční selhání patofyziologie   chirurgie   MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: Age affects disease severity and patient outcomes in pulmonary arterial hypertension. This post-hoc analysis identified prognostic age groups and associated macitentan/selexipag treatment effects. METHODS: Randomized trials evaluated macitentan (SERAPHIN; NCT00660179) and selexipag (GRIPHON; NCT01106014) versus placebo (primary endpoint: time to morbidity/mortality [M/M]). This analysis defined age thresholds differentiating M/M risk in patients randomized to placebo (Cox regression determining treatment effect by age). RESULTS: Three age groups (< 35, 35-64, ≥ 65 years) showed good M/M risk discrimination (c-statistic 0.69, SERAPHIN; 0.66, GRIPHON). M/M risk was higher in placebo patients < 35 versus 35-64 years (SERAPHIN: hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10-2.72, p = 0.02; GRIPHON: HR 1.81, 95% CI 1.28-2.56, p < 0.001). M/M risk trended higher in patients ≥ 65 versus 35-64 years (SERAPHIN: HR 1.55, 95% CI 0.89-2.69, p = 0.12; GRIPHON (HR 1.08, 95% CI 0.75-1.55, p = 0.69). M/M risk was lower with macitentan/selexipag versus placebo: macitentan < 35 (HR 0.44, 95% CI 0.25-0.78; p = 0.005), 35-64 (HR 0.50, 95% CI 0.33-0.76; p < 0.001), ≥ 65 years (HR 0.69, 95% CI 0.30-1.58; p = 0.38); selexipag < 35 (HR 0.50, 95% CI 0.32-0.78; p = 0.002), 35-64 (HR 0.72, 95% CI 0.54-0.96; p = 0.03), ≥ 65 years (HR 0.55, 95% CI 0.33-0.91; p = 0.02). Adverse-event discontinuations were similar. CONCLUSIONS: The benefit (vs placebo) of macitentan/selexipag on reducing risk of M/M events was consistent across all ages, including the younger group where significant treatment effects were observed.

• Publikační typ
• časopisecké články MeSH