Publikácia sa zameriava na rôzne podoby translačnej mitochondriálnej medicíny. Určené odbornej verejnosti.

• MeSH
• mitochondriální nemoci terapie   MeSH
• mitochondriální proteiny MeSH
• mitochondrie MeSH
• translační biomedicínská věda MeSH
• translační modifikace proteinu MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• vnitřní lékařství
• molekulární biologie, molekulární medicína
• biochemie
• NLK Publikační typ
• kolektivní monografie

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

OBJECTIVES: To determine the long-term and transplantation-free survival of all patients after atrial correction of transposition of the great arteries (TGA) in the Czech and Slovak republics, including its preoperative and perioperative determinants. METHODS: Retrospective analysis of all 454 consecutive patients after atrial correction of TGA was performed. Of these, 126 (27.8%) were female, median age at operation was 7.4 months (Q1 5.3; Q3 13.3) and 164 (36.1%) underwent the Mustard procedure. The relationships between age, weight, the complexity of TGA, operative technique, additional surgical procedures, immediate postoperative presence of tricuspid regurgitation and revision procedures during follow-up to major composite outcome, as such defined as long-term and transplantation-free survival, were tested. RESULTS: Early 30-day mortality did not differ between the Mustard (9.76%) and Senning (8.97%) cohorts (p=0.866). The long-term and transplantation-free survival, which differed between the Mustard and Senning cohorts in favour of the Senning procedure (HR 0.43; 95% CI 0.21 to 0.87), was shorter in complex TGA (HR 2.4; 95% CI 1.59 to 3.78) and in complex surgical interventions (HR 3.51; 95% CI 2.31 to 5.56). The immediate presence of at least moderate tricuspid regurgitation after correction was associated with a shorter long-term and transplantation-free survival in the univariate but not in the multivariable model. CONCLUSIONS: The lower long-term survival of patients after an atrial switch operation of TGA in the Czech and Slovak republics is associated with greater complexity of TGA, complex surgical interventions and application of the the Mustard operative procedure.

• MeSH
• arterie MeSH
• kojenec MeSH
• korekce transpozice velkých arterií * škodlivé účinky   MeSH
• lidé MeSH
• následné studie MeSH
• retrospektivní studie MeSH
• transpozice velkých cév * MeSH
• trikuspidální insuficience * chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Background and Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic progressive disease, resulting from persistent arterial obstruction combined with small-vessel remodeling. Central and peripheral CTEPH are distinguished, according to the dominant lesion's location. This is important for surgical or percutaneous interventional assessment or for medical treatment. Material and Methods: Eighty-one patients (51 male/30 female) with confirmed CTEPH were analyzed, while the CENTRAL type included 51 patients (63%) and the PERIPHERAL type 30 patients (37%). Results: A significant difference in CENTRAL type vs. PERIPHERAL type was determined in gender (male 72.5% vs. 46.7%; p = 0.0198). No difference was found in age, functional status, or echocardiographic parameters. Invasive hemodynamic parameters showed a significant difference in mean pulmonary arterial pressure (46 vs. 58 mmHg; p = 0.0002), transpulmonary gradient (34 vs. 47 mmHg; p = 0.0005), and cardiac index (2.04 vs. 2.5 L.min.m2; p = 0.02) but not in pulmonary vascular resistance. Risk factors showed a significant difference only in acute pulmonary embolism (93.8% vs. 60%; p = 0.0002) and malignancy (2% vs. 13.3%; p = 0.0426). Conclusions: Our study showed hemodynamic differences between CENTRAL type vs. PERIPHERAL type CTEPH with a worse hemodynamic picture in CENTRAL form. This may indicate a different pathophysiological response and/or possible additional influences contributing especially to the peripheral pulmonary bed affection.

• MeSH
• cévní rezistence MeSH
• chronická nemoc MeSH
• hemodynamika MeSH
• lidé MeSH
• plíce MeSH
• plicní embolie * komplikace   MeSH
• plicní hypertenze * komplikace   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: To examine the current status of care and needs of adult congenital heart disease (ACHD) services in the Central and South Eastern European (CESEE) region. METHODS AND RESULTS: We obtained data regarding the national ACHD status for 19 CESEE countries from their ACHD representative based on an extensive survey for 2017 and/or 2018. Thirteen countries reported at least one tertiary ACHD centre with a median year of centre establishment in 2007 (interquartile range 2002-2013). ACHD centres reported a median of 2114 patients under active follow-up with an annual cardiac catheter and surgical intervention volume of 49 and 40, respectively. The majority (90%) of catheter or surgical interventions were funded by government reimbursement schemes. However, all 19 countries had financial caps on a hospital level, leading to patient waiting lists and restrictions in the number of procedures that can be performed. The median number of ACHD specialists per country was 3. The majority of centres (75%) did not have ACHD specialist nurses. The six countries with no dedicated ACHD centres had lower Gross Domestic Product per capita compared to the remainder (P = 0.005). CONCLUSION: The majority of countries in CESEE now have established ACHD services with adequate infrastructure and a patient workload comparable to the rest of Europe, but important gaps still exist. ACHD care is challenged or compromised by limited financial resources, insufficient staffing levels, and reimbursement caps on essential procedures compared to Western Europe. Active advocacy and increased resources are required to address the inequalities of care across the continent.

• MeSH
• dospělí MeSH
• kardiologie * MeSH
• konsensus MeSH
• lidé MeSH
• srdeční selhání * MeSH
• vrozené srdeční vady * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

OBJECTIVE: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. METHODS: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. RESULTS: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). CONCLUSION: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified.

• MeSH
• analýza dat * MeSH
• bezpečnost MeSH
• časové faktory MeSH
• chronická nemoc MeSH
• lidé středního věku MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• plicní embolie komplikace   farmakoterapie   MeSH
• plicní hypertenze farmakoterapie   etiologie   MeSH
• prospektivní studie MeSH
• pyrazoly škodlivé účinky   terapeutické užití   MeSH
• pyrimidiny škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• recidiva MeSH
• registrace * MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The aim of this study was to analyse survival of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) hospitalized due to an acute right heart failure (ARHF) with emphasis on risk factors and effectiveness of treatment following current guidelines. METHODS: We retrospectively analysed 117 hospitalizations of 70 patients (59 PAH patients; 11 CTEPH patients, mean age 53.1 ± 16.77 years, 54 % females) between 2004 and 2013. RESULTS: 96 cases were hospitalized at cardiology wards (CW) while 21 at intensive care unit (ICU). The overall hospital mortality was 12.8 %, CW mortality was 4 %, and ICU mortality was 52.4 %. Higher risk of in-hospital mortality was associated with younger age, lower sodium levels, severe forms of PAH (heritable PAH, CTD-PAH) and need of PAH combination treatment. The one-year survival from the first ARHF hospitalization was 67.6 % (95 % CI 57.1–80 %), the two-year survival was 41.9 % (95 % CI 30.8–56.9 %). The presence of ascites was a predictor of long-term mortality. CONCLUSIONS: Mortality in patients with PH and ARHF remains very high. Identification of its risk factors could be used as basis of risk-adapted therapy (Tab. 5, Fig. 2, Ref. 14).

• MeSH
• analýza přežití * MeSH
• antihypertenziva terapeutické užití   MeSH
• dysfunkce pravé srdeční komory MeSH
• hospitalizace MeSH
• interpretace statistických dat MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita v nemocnicích MeSH
• plicní arteriální hypertenze diagnóza   terapie   MeSH
• plicní hypertenze * diagnóza   terapie   MeSH
• randomizované kontrolované studie jako téma MeSH
• retrospektivní studie MeSH
• senioři MeSH
• srdeční selhání etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH

AIMS: Long-term persistence of perfusion defect after pulmonaryembolism (PE) may lead to the development of chronic thromboembolic pulmonary hypertension. Identification of patients at risk of such a complication using a scoring system would be beneficial in clinical practice. Here, we aimed to derive a score for predicting persistence of perfusion defects after PE. METHODS: 83 patients after PE were re-examined 6, 12 and 24 months after the PE episode. Data collected at the time of PE and perfusion status during follow-ups were used for modelling perfusion defects persistence using the Cox proportional hazards model and validated using bootstrap method. RESULTS: A simple scoring system utilizing two variables (hemoglobin levels and age at the time of PE) was developed. Patients with hemoglobin levels over 140 g/L who were older than 65 years were at the highest risk of perfusion defects; in patients with the same hemoglobin levels and age <65 years, the risk was reduced by 79%, and by 89% in patients with hemoglobin <140 g/L. CONCLUSION: The proposed scoring system may be useful in clinical practice for identifying patients with high risk of persisting perfusion defects, flagging them for closer follow up, thus improving the effectiveness of long-term treatment of patients after PE.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• dospělí MeSH
• echokardiografie MeSH
• hemoglobiny analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní embolie komplikace   farmakoterapie   MeSH
• plicní hypertenze farmakoterapie   etiologie   MeSH
• pravidla klinického rozhodování * MeSH
• proporcionální rizikové modely MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND: Treprostinil, a prostacyclin analogue, is effective for the treatment of pulmonary arterial hypertension. However, information is scarce regarding treprostinil for treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to examine the efficacy and safety of subcutaneous treprostinil in this setting. METHODS: In this 24-week, randomised, double-blind controlled trial, we enrolled patients with CTEPH, classified as non-operable, or with persistent or recurrent pulmonary hypertension after pulmonary endarterectomy, in six European expert centres in Austria, Czech Republic, Germany, and Poland. Patients in WHO functional class III or IV with a 6-min walk distance of 150-400 m were randomly assigned at a 1:1 allocation ratio to continuous high-dose subcutaneous treprostinil (target dose around 30 ng/kg per min at week 12) or low-dose subcutaneous treprostinil (target dose around 3 ng/kg per min at week 12). The primary endpoint was the change from baseline in 6-min walk distance at week 24. All patients who received at least one dose of the study drug were included in the intention-to-treat efficacy and safety analyses based on assessment of adverse events. The trial was registered at ClinicalTrialsRegister.eu EudraCT number 2008-006441-10 and ClinicalTrials.gov, number NCT01416636. FINDINGS: From March 9, 2009, to June 9, 2016, 105 patients were enrolled with 53 (50%) patients randomly assigned to high-dose and 52 (50%) patients to low-dose subcutaneous treprostinil. At week 24, marginal mean 6-min walk distance improved by 44·98 m (95% CI 27·52 to 62·45) in the high-dose group, and by 4·29 m (95% CI -13·34 to 21·92) in the low-dose group (treatment effect 40·69 m, 95% CI 15·86 to 65·53, p=0·0016). 12 serious adverse events were reported in ten (19%) of 52 patients from the low-dose group and 16 serious adverse events were reported in nine (17%) of 53 patients from the high-dose group. The most common treatment-related adverse events in both groups were infusion site pain and other infusion site reactions. INTERPRETATION: Treatment with subcutaneous treprostinil was safe, and improved exercise capacity in patients with severe CTEPH. Subcutaneous treprostinil provides a parenteral treatment option for patients of WHO functional class III or IV and those who do not tolerate other therapies or need combination treatment. FUNDING: SciPharm Sàrl.

• MeSH
• antihypertenziva aplikace a dávkování   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• epoprostenol aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• injekce subkutánní MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• plicní embolie komplikace   MeSH
• plicní hypertenze * diagnóza   farmakoterapie   etiologie   patofyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• test chůzí metody   MeSH
• tolerance zátěže účinky léků   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH