Semi-automatic quantification of mosaic perfusion of lung parenchyma and its correlation with haemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension.

AIM: To investigate the feasibility of semiautomatic quantification of mosaic perfusion and the associations between mosaic perfusion on computed tomography (CT; the ratio of hypoperfused parenchyma to the whole lung volume) and haemodynamic parameters through linear regression analysis. MATERIALS AND METHODS: Fifty-eight consecutive patients (mean age 66 years, 28 females) diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) in General University Hospital, Prague, in 2021 were evaluated retrospectively and underwent both right heart catheterisation and CT pulmonary angiography. The parameters derived from the CT examinations were correlated with the recorded haemodynamic parameters. RESULTS: A method was developed for semiautomatic detection of hypoperfused tissue from CT using widely available software and a statistically significant correlation was found between the proportion of hypoperfused parenchyma and the mean pulmonary artery pressure (mPAP; R2 0.22; p<0.01) and pulmonary vascular resistance (PVR; R2 0.09; p<0.05). CONCLUSIONS: The developed method facilitates the quantification of mosaic perfusion, which is associated with important haemodynamic parameters (mPAP and PVR) in patients with CTEPH.

The impact of atrial fibrillation and atrial tachycardias on the hemodynamic status of patients with pulmonary hypertension.

The impact of atrial fibrillation and atrial tachycardias (AF/AT), and their optimal treatment strategy in PH patients is still being discussed. The goal of this study was to evaluate the effect of AF/AT termination on the hemodynamic parameters in PH patients. We compared patients with pre-capillary pulmonary hypertension (PH group), left ventricular heart failure (LV-HF group), and a Control group. A repeated right heart catheterization was performed during the catheter ablation (CA) procedure. The first measurement was done in arrhythmia, the second after the sinus rhythm (SR) was restored. High frequency atrial stimulation was used to simulate AT in patients without arrhythmia presence at the time of the CA. The variation of pressure parameters in PH patients did not differ significantly from the Controls. There was a significant increase in the right ventricle pressure after the SR restoration in the LV-HF group compared to the Controls and PH group (+4 vs. -2 vs. -3 mmHg, p<0.05). The cardiac index (CI) variation was not significant when compared between the study groups. An increase of the CI after the SR restoration was found in those patients with AF (+0.31 l/min/m2 [IQR 0.18; 0.58]) in contrast to those patients with organized AT/high frequency atrial stimulation ( 0.09 l/min/m2, [IQR - 0.45; 0.19]). This difference was statistically significant (p<0.05). The acute hemodynamic response to arrhythmia termination was not significantly different in the PH patients when compared to the Controls. In contrast to AT/high frequency stimulation, the restoration of SR in AF patients leads to an increased CI, irrespective of the presence or absence of PH.

The Role of Pulmonary Artery Wedge Pressure on the Incidence of Atrial Fibrillation and Atrial Tachycardias in Patients With Isolated Pre-capillary Pulmonary Hypertension.

Atrial fibrillation and atrial tachycardias (AF/AT) have been reported as a common condition in patients with pulmonary hypertension (PH). As yet, limited data exists about the significance of the borderline post-capillary pressure component on the occurrence of AF / AT in patients with isolated pre-capillary PH. We retrospectively studied the prevalence of AF / AT in 333 patients (mean age 61 ± 15 years, 44% males) with pre-capillary idiopathic / familiar pulmonary arterial hypertension, and inoperable chronic thromboembolic pulmonary hypertension. The prevalence of AF / AT was analyzed in different categories of pulmonary artery wedge pressure (PAWP). In the study population overall, the mean PAWP was 10.5 ± 3 mmHg, median of 11 mmHg, range 2-15 mmHg. AF / AT was diagnosed in 79 patients (24%). The proportion of AF / AT among patients with PAWP below the median (?11 mmHg) was lower than in subjects with PAWP between 12 and 15 mmHg, 30 (16%) vs. 46 (35%), p = 0.0001. Compared to the patients with PAWP?11 mmHg, subjects with PAWP between 12 and 15 mmHg were older (65 ± 13 years vs. 58 ± 16), with more prevalent arterial hyperte\nsion [100 (70%) vs. 106 (55%)] and diabetes mellitus [50 (35%) vs. 48 (25%)], showed larger size of the left atrium (42 ± 7 vs. 40 ± 6 mm), and higher values of right atrium pressure (12 ± 5 vs. 8 ± 5 mm Hg), p < 0.05 in all comparisons. The prevalence of AF / AT in the group studied increased with the growing post-capillary component.

Long-term experience with implantable treprostinil pumps in pulmonary arterial hypertension.

OBJECTIVES: To compare clinical parameters and quality of life in patients with pulmonary arterial hypertension (PAH) at the time of diagnosis, at the time of LenusPro pump implantation and during intravenous treptostinil treatment. METHODS: Seven patients with severe PAH treated with intravenous treptostinil via implantable LenusPro pumps were evaluated, including NYHA classification, six­minute walking test, BNP and quality of life assessment using the EQ-5D-5L questionnaire before and after pump implantation. RESULTS: No significant changes were observed in NYHA class and six­minute walking distance test. There was however a significant improvement in the quality of life and a decrease in BNP levels. The mean EQ-5D-5L index assessed during subcutaneous treptostinil treatment was significantly worse when compared to that assessed during its intravenous application (0.39 ± 0.24 vs 0.78 ± 0.28, p ˂ 0.05); the same is true about the pain/discomfort dimension. Complications occurred, namely one nonfatal pneumothorax, one nonfatal hemothorax, and one event of nonfatal treptostinil intoxication after refilling. CONCLUSIONS: In patients who do not tolerate subcutaneous treptostinil treatment, the use of the LenusPro implantable pump results in a significant improvement in quality of life with an acceptable safety profile (Tab. 2, Fig. 2, Ref. 19).

Predictors of survival in patients with pulmonary hypertension and acute right heart failure.

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).

Effect of warfarin anticoagulation on thrombin generation in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Oral anticoagulant therapy is recommended for patients with pulmonary arterial hypertension (PAH). The rationale for the use of anticoagulant treatment is based on thrombophylic predisposition in PAH and improvement of survival in patients treated with anticoagulation. However, the target INR value has not been evaluated. The aim of this study was to analyze thrombin generation in patients with PAH treated with warfarin anticoagulation. METHODS: The study was performed in 58 patients with idiopathic PAH treated with warfarin at stable doses. Thrombin generation assay was performed in all subjects and three parameters were derived from the thrombin generation curves: lag time, maximal concentration of formed thrombin (peak thrombin) and area under the curve (AUC). Thrombin generation parameters were correlated with INR and compared between the patient groups with different intensity of anticoagulant therapy. RESULTS: Significant correlation between the lag time and INR was observed (r = 0.495, p < 0.001). Significant negative correlation between the maximal concentration of formed thrombin and INR and between the area under the curve of thrombin generation and INR was observed (r = -0.709, p < 0.001 and r = -0.784, p < 0.001, respectively). Thrombin generation was significantly reduced in patients with INR between 1.5 and 2.5. CONCLUSIONS: Low-intensity warfarin anticoagulation with target INR between 1.5 and 2.5 could be effective and sufficient to suppress thrombin generation in patients with idiopathic PAH (Fig. 3, Tab. 4, Ref. 12). Full Text in free PDF www.bmj.sk.

Pulmonary arterial hypertension--contemporary management strategy.

Pulmonary arterial hypertension (PAH) is a severe chronic disorder of pulmonary arteries with progressive precapillary pulmonary hypertension, characterized by poor life quality and very poor prognosis. Unless treated, it causes death within 2-3 years from diagnosis. PAH affects mainly younger women. The treatment of PAH should not only be symptomatic, but also directed towards the improvement in patient's survival and quality of life. Many novel drugs putting together so called specific PAH therapy (endothelin receptor antagonists, prostanoids, phosphodiesterase--5 inhibitors) were tested in randomized trials. PAH management requires a highly individualized approach, state of the art knowledge and adequate experience. Patients therefore should be referred to specialized PAH centers providing both complete diagnosis and therapy. In our region a close co-operation between Czech and Slovak PAH centers has also proved to be profitable. Data sources. Literature retrieval was accessed through MEDLINE using the terms pulmonary hypertension, PAH, diagnosis, treatment. Reference citations from publications identified were reviewed (Ref. 47). Full Text (Free, PDF) www.bmj.sk.

[Contemporary methods in the treatment of chronic pulmonary hypertension]. / Aktuální moznosti lécby chronické plicní hypertenze.

Pulmonary hypertension is involved in the development of various diseases and therefore it can be caused by several mechanisms from a simple pressure elevation in the pulmonary artery to the serious impairments of pulmonary vessels. The recently increased interest in the problems of pulmonary hypertension results namely from the new therapeutic means for the treatment of pulmonary arterial hypertension and chronic thrombembolic pulmonary hypertension. The algorism of pharmacotherapy results from the test of acute pulmonary vasodilation. Only the patients with positive test are indicated to the treatment with high doses of calcium channel blockers. Patients with negative test receive beside the chronic anticoagulation therapy also a specific pharmacotherapy (prostanoids, antagonists of endotheline receptors, phosphodiesterase 5 inhibitors) with not only vasodilatory but also with antiproliferative and antiaggregatory effects. When all possibilities of pharmacotherapy are exhausted, balloon atrial septostomy or lung transplantation should be considered. It has been shown recently that similar pharmacotheraeutic approaches as they are used in patients with pulmonary arterial hypertension are effective in some cases of other forms of chronic pulmonary hypertension. Method of choice in the treatment of chronic thromboembolic pulmonary hypertension is the pulmonary endarterectomy in patients with surgically curable thrombotic obstruction. In patients who are not suitable for surgical treatment it is necessary to try pharmacotherapy (prostacycline, bosentan, sildenafil) or lung transplantation. Complicated diagnosis and therapy of pulmonary hypertension requires concentrating the treatment into specialized centres with multidisciplinary background and sufficient experience. In the Czech Republic, the care of patients with pulmonary hypertension is concentrated into the Cardio Center of the 2nd Medical Department of the 1st Faculty of Medicine and General Teaching Hospital in Prague and into the Cardio Center of the Institute of Clinical and Experimental Medicine in Prague. Complex care to patients with chronic thromboembolic pulmonary hypertension is given at the Cardio Center of the General Teaching Hospital in Prague, where since September 2004, 99 patients were surgically treated with results comparable to the best similar departments abroad.

Thrombophilia and pulmonary endarterectomy.

UNLABELLED: In the present study, we compared groups of patients with and without thrombophilia, who underwent pulmonary endarterectomy (PEA), definitive treatment for chronic pulmonary hypertension resulting from thromboembolic disease. METHODS AND PATIENTS: Between September 2004 and June 2007, we operated 54 patients with CTEPH. We divided our patients into three groups. Group I patients, had one or more signs of serious thrombophilia (15 patients), Group II patients, had no signs of thrombophilia (23 patients without thrombophilia and without Methylenetetrahydrofolate Reductase (MTHFR)), and Group III patients with MTHFR (16 patients with MTHFR only, without any serious thrombophilia). RESULTS: After the surgery, there was a statistically considerable improvement of hemodynamic parameters (mPA, CI, PVR) in all groups, without a statistical difference between the groups. Comparison of all these groups showed more complications in-group I (thrombophilia), in particular reperfusion oedema, pericardial effusion, and renal insufficiency. Within one month, there was a considerable improvement or normalisation of haemodynamic parameters, an increase in walking distance at the six-minute walking test, and NYHA classification with no significant difference between the three groups. CONCLUSIONS: Early hemodynamic results of patients with thrombophilia after PEA, were comparable to the results of patients without thrombophilia, when we looked at both clinical and hemodynamic improvements. We did not find any differences when we looked at the results between Group II and Group III (MTHF), when we considered the number and type of complications. Patients with thrombophilia in Group I had statistically higher morbidity, especially when it came to a higher number of reperfusion oedema, pericardial effusion, and renal insufficiency.

Hemodynamic instability after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension correlates with cytokine network hyperstimulation.

BACKGROUND: Pulmonary endarterectomy (PEA) is an effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The present study tested the hypothesis that inflammation, as determined by circulating cytokine levels, may contribute to the difficulty in controlling arterial blood pressure after PEA. MATERIALS AND METHODS: Thirty-six patients with CTEPH (22 males and 14 females) underwent PEA using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest. Plasma concentrations of tumor necrosis factor alpha, interleukin (IL)-1beta, IL-6 and IL-8 were measured repeatedly in arterial blood samples. RESULTS: A significant correlation between norepinephrine support and IL-6 plasma concentrations was shown at the separation from CPB (k = 0.742) and 12 h after it (k = 0.801) as well as between norepinephrine support and IL-8 concentrations 12 h after the separation from CPB. Furthermore, a significant correlation was found between the cardiac index (CI) and both IL-6 and IL-8 at the separation from CPB. CONCLUSIONS: Hemodynamic instability after PEA has been associated with higher postoperative plasma concentrations of IL-6 and IL-8. The positive relation between inflammatory cytokines and CI, or cytokines and vasopressor support, is in accordance with the hypothesis that cytokine activation may be among the neurohumoral factors responsible for cardiodepression and systemic vasoplegia in CTEPH patients undergoing PEA.

Risk factors for chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by nonresolving pulmonary thromboemboli that can be treated by surgical pulmonary endarterectomy (PEA). The authors of the present study sought to confirm known and to identify novel CTEPH risk factors in a controlled retrospective cohort study of prevalent CTEPH cases collected in three European centres offering PEA. Data from CTEPH patients were compared with nonthromboembolic pre-capillary pulmonary arterial hypertension cohorts at the participating institutions. The study population comprised 687 patients assessed at the time of diagnosis between 1996 and 2007. Ventriculo-atrial shunts and infected pacemakers (odds ratio (OR) 76.40, 95% confidence interval (CI) 7.67-10,351), splenectomy (OR 17.87, 95% CI 1.56-2,438), previous venous thromboembolism (VTE; OR 4.52, 95% CI 2.35-9.12), recurrent VTE (OR 14.49, 95% CI 5.40-43.08), blood groups other than 0 (2.09, 95% CI 1.12-3.94), and lupus anticoagulant/antiphospholipid antibodies (OR 4.20, 95% CI 1.56-12.21) were more often associated with CTEPH. Thyroid replacement therapy (OR 6.10, 95% CI 2.73-15.05) and a history of malignancy (OR 3.76, 95% CI 1.47-10.43) emerged as novel CTEPH risk factors. In conclusion, the European database study confirmed previous knowledge of chronic thromboembolic pulmonary hypertension risk factors, and identified thyroid replacement therapy and a history of malignancy as new medical conditions associated with chronic thromboembolic pulmonary hypertension.

[The isolated form of cardiac amyloidosis in the form of beginning infiltrative cardiomyopathy without restrictive physiology]. / Izolovaná forma srdecní amyloidózy v podobe pocínající infiltrativní kardiomyopatie bez restriktivní fyziologie.

The authors describe an interesting case of isolated cardiac manifestation of AL-amyloidosis manifesting as an incipient infiltrative cardiomyopathy with heart failure symptoms due to moderate left ventricular diastolic dysfunction. Restrictive cardiomyopathy with severe diastolic dysfunction is considered as the characteristic manifestation of fully developed cardiac amyloidosis. However, the organ deposition of amyloid is progressive and left ventricular filling worsens continuously, starting with less advanced forms of diastolic dysfunction; the restrictive physiology is characteristic only for advanced phases of the disease. Therefore, the possibility of the incipient infiltrative cardiomyopathy due to the amyloidosis should be considered in patients with heart failure symptoms and echocardiographic findings of unexplained left ventricular hypertrophy with only mild or moderate diastolic dysfunction.

Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial.

BACKGROUND: Treatments for pulmonary arterial hypertension have been mainly studied in patients with advanced disease (WHO functional class [FC] III and IV). This study was designed to assess the effect of the dual endothelin receptor antagonist bosentan in patients with WHO FC II pulmonary arterial hypertension. METHODS: Patients with WHO FC II pulmonary arterial hypertension aged 12 years or over with 6-min walk distance of less than 80% of the normal predicted value or less than 500 m associated with a Borg dyspnoea index of 2 or greater were enrolled in this double-blind, placebo-controlled, multicentre trial. 185 patients were randomly assigned to receive bosentan (n=93) or placebo (n=92) for the 6-month double-blind treatment period via a centralised integrated voice recognition system. Primary endpoints were pulmonary vascular resistance at month 6 expressed as percentage of baseline and change from baseline to month 6 in 6-min walk distance. Analyses of the primary endpoints were done with all randomised patients who had a valid baseline assessment and an assessment or an imputed value for month 6. This trial was registered with ClinicalTrials.gov, number NCT00091715. FINDINGS: Analyses were done with 168 patients (80 in the bosentan group, 88 in the placebo group) for pulmonary vascular resistance and with 177 (86 and 91) for 6-min walking distance. At month 6, geometric mean pulmonary vascular resistance was 83.2% (95% CI 73.8-93.7) of the baseline value in the bosentan group and 107.5% (97.6-118.4) of the baseline value in the placebo group (treatment effect -22.6%, 95% CI -33.5 to -10.0; p<0.0001). Mean 6-min walk distance increased from baseline in the bosentan group (11.2 m, 95% CI -4.6 to 27.0) and decreased in the placebo group (-7.9 m, -24.3 to 8.5), with a mean treatment effect of 19.1 m (95% CI 3.6-41.8; p=0.0758). 12 (13%) patients in the bosentan group and eight (9%) in the placebo group reported serious adverse events, the most common of which were syncope in the bosentan group and right ventricular failure in the placebo group. INTERPRETATION: Bosentan treatment could be beneficial for patients with WHO FC II pulmonary arterial hypertension.

[Long-term experience with trerpostinil infusion treatment in patients with pulmonary arterial hypertension in the Czech Republic]. / Dlouhodobé zkusenosti s infuzní lécbou treprostinilem u nemocných s plicní arteriální hypertenzí v Ceské republice.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious primary illness of the pulmonary arterioles, characterised by progressive precapillary pulmonary hypertension. The conventional therapy for this condition is so-called specific pharmacotherapy, which addresses the key mechanisms in the pathophysiology of the illness, making use of drugs from the prostanoid group, endothelin receptor antagonists and phosphodiesterase inhibitors. Treprostinil is a stable analogue of prostacyclin, which can be administered subcutaneously, intravenously or by inhalation. PATIENT SAMPLE AND METHOD: In the centre for pulmonary hypertension in the Second Internal Clinic of Cardiology and Angiology of 1st Faculty of Medicine, Charles University, and the General Teaching Hospital in Prague, 22 patients with PAH (idiopathic PAH, familial PAH, PAH associated with congenital heart disease and PAH associated with systemic connective tissue disease) were treated with trerpostinil, 18 patients with a continuous subcutaneous infusion and 4 patients with a continuous intravenous infusion. The indicators followed were the distance reached in a 6-minute walking test, functional capacity assessed by NYHA classification and mortality. RESULTS: The patients for whom treprostinil treatment was indicated had an average pressure in the right atrium of 11.9 +/- 4.2 mm Hg, average pressure in the pulmonary artery of 56.8 +/- 10.7 mm Hg, a cardiac index of 1.78 +/- 0.25 l/min/m2 and a total pulmonary resistance of 16.26 +/- 4.48 WU. 15 patients were functionally NYHA III and 7 patients were NYHA IV. The average distance achieved in a 6-minute walk test before the start of treatment was 326 +/- 83 m. When treated with gradually increasing doses of treprostinil the distance achieved in the 6-minute walk test improved. After 6 months, the group that received subcutaneous treatment had extended their distance to 359 m, after 12 months it was 393 m, after 24 months 447 m and after 36 months 494 m. After 6 months, the group that received intravenous treatment had extended their distance to 473 m, which increased to 451 m after 12 months and 489 m after 24 months. Functional capacity also improved. In total 5 patients were unable to tolerate the subcutaneous infusion, of whom 3 were placed on intravenous treprostinil and 2 on oral bosentan. 7 of the patients died in the period examined (31.8%). CONCLUSION: Treprostinil improves symptoms and hemodynamics for PAH patients and reduces mortality.

[Pulmonary hypertension in Takayasu arteritis]. / Plicní hypertenze u Takayasuovy arteritidy.

Takayasu arteritis (TA) is a rare chronic vasculitis primarily involving the aorta and its main branches. The disease affects women much more frequently than men, the ratio being 8:1. The onset occurs in the teenage years, always before age of 40. Aortic regurgitation is rare. The pulmonary artery stenosis may also rarely occur. We report the case of a 49-year old female patient with Takayasu arteritis who presented with severe left pulmonary trunk stenosis resulting in pulmonary hypertension, severe aortic regurgitation due to the dilatation of the ascending aorta, mitral insufficiency, critical left renal artery stenosis, and probably with left main coronary artery stenosis. No severe stenosis or occlusion in the mid portion of mid subclavian artery lesion were present. Because the patient presented with serious congestive heart failure, she underwent mitral valvuloplasty and aortic valve replacement. However, the patient died in early postoperative period due to pulmonary hypertension which failed to respond to pharmacotherapy.

Implementation of a new programme for the surgical treatment of CTEPH in the Czech Republic--Pulmonary endarterectomy.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) in indicated cases can be successfully cured by endartectomy of pulmonary arteries (PEA). Symptomatic nontreated CTEPH has a very poor prognosis; the five-year survival rate in patients with a medium pressure of over 50 mmHg in the main pulmonary artery is as low as 10 %. This kind of operation was previously not available in the Czech Republic. In 2004, a PEA programme was launched at the Cardiocentre of the General Teaching Hospital in Prague in co-operation with the institution of a well known specialist in this field (Prof. Mayer, Johannes Gutenberg University in Mainz, Germany). PATIENTS: Between September 2004 and January 2006, 21 patients (14 males and 7 females; average age 48 years) with CTEPH were operated on, after a complex investigation. The mean pressure in the main pulmonary artery in these patients was 54.8 mmHg; 7 patients suffered from coagulopathy. METHOD: The new surgical technique, modifications of which are used at most facilities, was developed by Jamieson and Daily at the University of California in San Diego: an arrest of circulation in deep hypothermia to protect the brain is vital for the visualisation of distal branches of the pulmonary artery. RESULTS: 21 patients were operated on with a mortality of 4.76 % (1 patient died). Other surgeries performed were suture of a defect of the atrial septum (three times), aortocoronary bypass (three times), and cryoablation of the right atrium for flutter (once). The average circulatory arrest time was 42 minutes, the average total pumping time was 331 minutes, and the average total duration of an operation was 450 minutes; the average duration of mechanical ventilation was 58 hours. Within one month there was a considerable improvement or normalisation of haemodynamic parameters and an increase in the average walking distance on the six-minute walking test by 132 metres. CONCLUSIONS: PEA is a curative method for patients with CTEPH with a surgically accessible obstruction of the pulmonary artery. Centralisation of the care of these patients is a rational necessity, as this enables the centre to gain a maximum of experience with this complicated diagnosis and treatment. Multidisciplinary co-operation is a sine qua non for success in these programmes.

Initial experiences with novel therapy for pulmonary hypertension in Slovakia.

Pulmonary hypertension (PH) is the most serious and potentially devastating chronic disorder of the pulmonary circulation with diverse etiologies and pathogenesis characterized by abnormal increased vasoconstriction and vascular remodelling. Current specific therapy of PH is based on an understanding of its pathogenesis and is acting through pathogenic pathways and therefore changes therapeutic strategy, effectively improves clinical course and prolongs life. The authors discuss the actual classification, pathogenesis in short and particularly actual treatment modalities and the impact on the natural history of this disorder. In chronic thromboembolic pulmonary hypertension is pulmonary endarterectomy if correct indicated the curable method, warranted substantial improvement of life quality and survival. These novel therapies of PH were absent in Slovakia until recently. The authors present initial experiences, results of PH management up to date on the basis of cooperation with PH centres in Austria and Czech Republic (Tab. 1, Fig. 6, Ref. 32).

[New trends in diagnosis and treatment of systemic sclerosis]. / Nové trendy v diagnostice a lécbe systémové sklerodermie.

Systemic sclerosis (SSc) is a generalised connective tissue disease of unknown origin, which clinically shows by skin thickening and sclerosis of different extent (scleroderma) and by typical involvement of visceral organs. At the same time fibrotic and sclerotic changes occur in the blood vesel walls. SSc usually involves females at young and middle age. Myalgias, arthralgias and arthritis are nonspecific, tendon friction rubs in fingers are more typical for this diagnosis. Gastrointestinal involvement starts early in the oropharyngeal part, esophagus and proceeds into the distal parts. Fibrotic changes lead to slow transit dysmotility and pseudoobstruction and/or dilation of the bowels. The main symptoms are dysphagia, pyrosis, malabsorption and constipation. SSc produces two major patterns of abnormality within the lungs a fibrosing alveolitis or a primary pulmonary vascular disease. More frequently an insterstitial process develops which can be followed by pulmonary arterial hypertension. Cardiac involvement can also have different forms. Myocardial fibrosis usually appears at first in the conduction system by arrhythmias and various conduction blocks while pericarditis is mostly asymptomatic. Renal manifestation of SSc is observed in 8-10% patients. The most severe form--scleroderma renal crisis is characterised by the new onset of accelerated hypertension and rapidly progressive oliguric renal failure. No therapies have been proven to modify the course of SSc. Some of the drugs can affect only the skin changes. Majority of the currently applied agents have only a symptomatic effect.

[Contemporary prospects for the diagnostics and treatment of the chronic pulmonary hypertension]. / Soucasné moznosti diagnostiky a lécby chronické plicní hypertenze.

Pulmonary hypertension is defined as the rise of mean pressure in the pulmonary artery over 25 mmHg at rest or over 30 mmHg during activity with accompanying increase of pulmonary vascular resistance over 3 WU (Wood's unit). According to the recent WHO classification from 2003 pulmonary hypertension can be categorized as pulmonary arterial hypertension, pulmonary venous hypertension, hypoxic pulmonary hypertension, chronic thromboembolic pulmonary hypertension and pulmonary hypertension from other causes. Because symptoms of the pulmonary hypertension are non-specific, the diagnosis is frequently late. Patients with higher risk of pulmonary hypertension require frequent echocardiographic examination. Treatment of the pulmonary hypertension is rather complex and economically demanding. It should be therefore centralized in specialized units. Decision on the pharmacotherapy is based on the acute pulmonary vasodilatation test. Only patients with the positive test (10% of patients) are indicated to the treatment with calcium channel blockers. In case of negative test, the treatment of choice in NYHA III stadium is bosentam per orally, in the NYHA IV stadium it is epoprostenol intravenously. In patients with chronic thromboembolic pulmonary hypertension, organized thrombotic material should be surgically removed together with the layer of the pulmonary artery (pulmonary endarterectomy) after preceding anticoagulation treatment lasting at least three months. Pulmonary hypertension center of the Cardiocenter of the General teaching hospital is the only unit in the Czech Republic which beside the complex therapy of the pulmonary arterial hypertension can employ also the surgical treatment of the chronic thromboembolic pulmonary hypertension.