BACKGROUND: Pulmonary arterial hypertension (PAH) is a common complication among patients with congenital heart disease (CHD). Despite advances in PAH treatment, evidence for the benefits of PAH therapies in CHD-PAH is limited. OBJECTIVES: This analysis aimed to evaluate outcomes in patients with repaired PAH-CHD receiving an approved PAH drug. METHODS: This was a pooled analysis including CHD-PAH patients whose CHD was repaired ≥1 year prior from 3 randomized, placebo-controlled, event-driven studies: GRIPHON (NCT01106014), SERAPHIN (NCT00660179), and COMPASS-2 (NCT00303459). The primary endpoint was time to first confirmed morbidity/mortality (M/M) event. HRs with 95% CIs were determined with random effects models. RESULTS: The analysis included 1,982 patients with PAH, 177 (8.9%) with CHD-PAH. In the overall PAH cohort, the mean age was 48 and 49 years in treatment and placebo groups; 80% and 77% were female. In the CHD-PAH cohort, the mean age was 41 and 39 years; 70% and 66% were female. Overall, ≥98% in each group were World Health Organization functional class II and III at baseline. There was a significant reduction in risk of M/M events vs placebo in the overall PAH and CHD-PAH cohorts: 37% reduction in the overall PAH cohort (HR: 0.63; 95% CI: 0.52-0.77) and 50% reduction in the CHD-PAH population (HR: 0.50; 95% CI: 0.26-0.94). CONCLUSIONS: Treatment with approved PAH drugs provided a similar reduction in M/M risk in patients with repaired CHD-PAH when compared with the overall PAH population. This pooled analysis provides important evidence to guide medical management in this patient population.
- Publikační typ
- časopisecké články 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
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.
AIMS: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short-term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH). METHODS AND RESULTS: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta-analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post-IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta-analysis Global Group in Chronic Heart Failure score-predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD-treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan-Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload-corrected exercise pulmonary capillary wedge pressure at the 6 months post-IASD study were associated with HFH. CONCLUSIONS: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large-scale ongoing randomized studies are required to confirm the potential benefit of this therapy.
- MeSH
- časové faktory MeSH
- funkce levé komory srdeční fyziologie MeSH
- hospitalizace trendy MeSH
- lidé MeSH
- míra přežití trendy MeSH
- následné studie MeSH
- prospektivní studie MeSH
- protézy a implantáty * MeSH
- senioři MeSH
- síňový tlak fyziologie MeSH
- srdeční katetrizace metody MeSH
- srdeční selhání mortalita patofyziologie chirurgie MeSH
- srdeční síně patofyziologie chirurgie MeSH
- tepový objem fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Austrálie MeSH
- Evropa MeSH
- Nový Zéland MeSH
BACKGROUND: Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. METHODS: We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. RESULTS: In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. CONCLUSIONS: Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed. TRIAL REGISTRATION: ClinicalTrials.org NCT01784562 . Registered February 4, 2013.
- MeSH
- antihypertenziva aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- chronická nemoc MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní hypertenze farmakoterapie patofyziologie MeSH
- pyrazoly aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- pyrimidiny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- synkopa chemicky indukované MeSH
- tromboembolie komplikace 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
- klinické zkoušky, fáze III 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: Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90-95), 91% (95% CI, 87-93), and 89% (95% CI, 86-92) in operated patients (n=404), and only 88% (95% CI, 83-91), 79% (95% CI, 74-83), and 70% (95% CI, 64-76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension-targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49-11.62; P=0.0065 and HR, 4.76; 95% CI, 1.76-12.88; P=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95-1.90; P=0.0992 and HR, 1.50; 95% CI, 1.20-1.88; P=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36-6.69; P=0.0065 and HR, 2.15; 95% CI, 1.18-3.94; P=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension-targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients. CONCLUSIONS: The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients.
- MeSH
- časové faktory MeSH
- chronická nemoc MeSH
- dospělí MeSH
- internacionalita * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- plicní embolie diagnóza epidemiologie terapie MeSH
- plicní hypertenze diagnóza epidemiologie terapie MeSH
- prospektivní studie MeSH
- registrace * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem 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 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.
