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).

Rs6922269 marker at the MTHFD1L gene predict cardiovascular mortality in males after acute coronary syndrome.

Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the traditional risk factors for MI are responsible for approximately 50% of cases of MI cases. Attention therefore has recently focused on genetic variants that are not associated with conventional risk factors. One of them is the marker rs6922269, which has been suggested as a risk factor for development of MI in Western populations. We analyzed the relationship between rs6922269 variant on MTHFD1L gene and (i) risk of the acute coronary syndrome (ACS) in the Czech population and (ii) mortality in 7 years follow up. Rs6922269 (G>A) variant was analyzed (CR 99.3% for patients and 98.0% for controls) by PCR-RFLP in consecutively examined 1614 men and 503 women with ACS (age below 65 years) and in population-based controls--1191 men and 1368 women (aged up to 65 years). ANOVA and Chi square were used for statistical analysis. The genotype frequencies were almost identical (P=0.87) in the ACS patients and in controls and no differences were observed, if males (P=0.73) and females (P=0.93) were analysed separately. In addition, rs6922269 polymorphism was not associated with the classical risk factors (dyslipidemia, hypertension, obesity, smoking, diabetes) in control population. Cardiovascular mortality was significantly higher in males, carriers of the AA genotype (P<0.001, OR 2.52, 95% CI 1.40-4.55, for AA vs. +G). We conclude, that rs6922269 variant at MTHFD1L gene could be an important prognostic factor for cardiovascular mortality in patients after ACS.

Prediction of coronary vessel involvement on the basis of atherosclerosis risk factor analysis.

The prediction of coronary vessel involvement by means of noninvasive tests is one of the fundamental objectives of preventive cardiology. This review describes the current possibilities of coronary vessel involvement prediction by means of ultrasonographic examination of carotid arteries, analysis of polymorphisms in the genes encoding enzymes responsible for production of nitric oxide and carbon monoxide and assessment of levels of certain proinflammatory cytokines. In the presented work these noninvasive markers are correlated with the extent of coronary vessel involvement as assessed by coronary angiography, intravascular ultrasound and virtual histology (Fig. 5, Ref. 40).

Association between a marker on chromosome 9 and acute coronary syndrome. confirmatory study on Czech population.

Myocardial infarction (MI) is the leading cause of death in industrialized countries. All the classical risk factors for MI are responsible for approximately 50 % of MI cases. Attention has therefore recently been attracted to those genetic variants that are not associated with conventional risk factors. One of them is the marker rs10757274 in the "genefree" zone on chromosome 9, which has been repeatedly recognized as a risk factor for development of MI in Western populations. We analysed the relationship between the rs10757274 variant on chromosome 9 and risk of the acute coronary syndrome (ACS) in Czech population. The rs10757274 (A > G) variant was successfully analysed (CR = 99.4 % for patients and 98.4 % for controls) by PCR-RFLP in consecutively examined 1,046 men and 281 women with ACS (age below 65 years) and in population-based controls - 1,162 men and 1,355 women (aged up to 65 years). ANOVA and χ2 were used for statistical analysis. We confirmed that GG homozygotes are more frequent (codominant model of analysis) among patients with myocardial infarction than in the control group both in men (28.5 % vs. 22.0 %, P = 0.0001, OR 1.73, 95 % CI 1.36-2.19) and women (32.0 % vs. 24.6 %, P = 0.02, OR 1.62, 95 % CI 1.13-2.34). However, rs10757274 polymorphism was not associated with the classical risk factors either in control population or in ACS patients. We conclude that the rs10757274 variant at 9p23.1 is an important genetic risk factor for ACS development in the Czech population.

Intracoronary injection of autologous bone marrow-derived mononuclear cells in patients with large anterior acute myocardial infarction and left ventricular dysfunction: a 24- month follow up study.

OBJECTIVE AND BACKGROUND: Despite the use of reperfusion therapies, outcomes in patients with large myocardial infarction (MI), late reperfusion and left ventricular (LV) dysfunction are poor. We investigated long-term safety and efficacy of intracoronary injections of autologous bone marrow-derived mononuclear cells (BMNCs). METHODS: 27 patients with anterior MI (age 59±12 years, mean baseline LV ejection fraction (LVEF) 39±5 %), who underwent percutaneous coronary intervention 4-24 hours after the onset of symptoms, were randomly assigned either to intracoronary BMNCs injection (n=17, BMNCs group, out of which 14 underwent long-term follow-up), or to standard therapy (n=10, Control group). The LVEF, the LV end-diastolic and end-systolic volumes (LVEDV, LVESV) were assessed by echocardiography at discharge, Month 4 and 24. Myocardial perfusion was assessed using SPECT at baseline and Month 4. RESULTS: At 24-month, there was no difference in rates of serious clinical events (36 % vs 50 %, p=0.54). At Month 4 LVEF improved to similar extent in both groups (absolute change +5.8 % vs +7.6 %, p=0.75), with similar infarct size reductions (-10.9 % vs -12.2 %, p=0.47). However, at Month 24, LVEF further improved in BMNCs patients (+12 % vs +8.5 %, p=0.03). This effect resulted from a more pronounced reduction in LVESV (-2.6 ml vs -1.8 ml, p=0.26) and a smaller increase in LVEDV (+16.7 ml vs +17.9 ml, p=0.27) suggesting beneficial long-term effects on LV remodeling. CONCLUSIONS: BMNCs injections in patients with MI and LV dysfunction were associated with a significant improvement of global LVEF during long term follow-up compared to standard therapy (Tab. 3, Fig. 1, Ref. 50). Full Text in PDF www.elis.sk.

Genetic variants in haem oxygenase-1 and endothelial nitric oxide synthase influence the extent and evolution of coronary artery atherosclerosis.

The genetic basis for atherosclerosis development and progression is poorly characterized. We aimed to assess the relationship between endothelial nitric oxide synthase (ENOS) 894 G/T, haem oxygenase-1 (HO1) dinucleotide-length promoter polymorphisms and coronary artery atherosclerotic invol vement and its changes during statin therapy. Coronary angiography, intravascular ultrasound (IVUS), IVUS-derived virtual histology (VH) and genetic polymorphism analysis were performed at study entry. Patients were randomized 1:1 to standard or aggressive hypolipidaemic treatment, and a follow-up evaluation was performed after twelve months. Plaque magnitude was significantly higher in carriers of HO1 risk variants when compared with carriers of the protective variants (< 25 GT repeats). Similarly, the total coronary atherosclerotic burden was significantly greater in HO1 risk variant carriers than in HO1 protective variant carriers. Both parameters did not differ with respect to the ENOS genotype. A higher prevalence of thin-cap fibroatheroma (TCFA) in HO1 risk variant carriers was observed, compared with the HO1 protective variant carriers. The prevalence of TCFA was not influenced by the ENOS genotype. Baseline plaque composition did not differ significantly with respect to both polymorphisms. Significant interactions between plaque composition changes and ENOS and HO1 genotypes were observed during statin treatment. In conclusion, the protective HO1 promoter polymorphism correlates with a lower coronary artery plaque burden, whereas the protective ENOS 894 G/T polymorphism seems to favourably influence changes of coronary artery plaque composition during statin therapy, but has no significant correlation to the magnitude of coronary atherosclerosis.

Reduced thrombin generation and soluble P-selectin after intravenous enoxaparin during PCI.

PURPOSE: The objective of our study was to identify changes in the coagulation and serum concentration of soluble P-selectin (sP-sel) after i.v. bolus of 0.75 mg/kg enoxaparin in a group of 33 patients during PCI. METHODS AND RESULTS: As compared to baseline, i.v. enoxaparin increased anti -Xa activity and FIIa inhibition together with APTT and thrombin time tests within 20 min, that persisted for 60 min. At 6 h, the results of all tests had returned to baseline. In contrast, the level of prothrombin fragments (F1 + 2) decreased persistingly for a period of 6 h (baseline 1.19 ± 0.42 nmol/l, after 20 min 1.03 ± 0.46 nmol/l, after 60 min 1.06 ± 0.43 nmol/l, after 6 h 0.95 ± 0.40 nmol/l, p < 0.001 vs. baseline for all values). In addition, i.v. enoxaparin decreased serum sP-sel level (baseline 111.80 ± 37.05 ng/ml, after 20 min 87.80 ± 33.17 ng/ml, after 60 min 86.45 ± 29.15 ng/ml, after 6 h 92.24 ± 31.34 ng/ml, p < 0.001 vs. baseline value for all). sP-sel level mildly correlated with both F Xa inhibition (r = -0.275, p < 0.05) and F1 + 2 level (r = 0.274, p < 0.05). CONCLUSION: Intravenous enoxaparin induced target F Xa inhibition (>0.6 IU/ml) for 60 min in 82% of study patients. During the 6 h of monitoring, a decrease of thrombin generation (F1 + 2) and sP-selectin levels were observed.

Why we are not able to find the coronary heart disease gene - apoE as an example.

The apoprotein E gene ranks among the most discussed candidate genes for cardiovascular disease. We studied whether the association between apoprotein E gene polymorphism and manifestation of acute coronary syndrome is modulated by the presence/absence of traditional cardiovascular risk factors. The population under study were 1066 patients (men under 65 years) admitted between 2006- 2009 to five coronary care units in Prague (GENetic DEtermination of Myocardial Infarction in Prague) and the control population (1066 age-matched men selected from the Czech population sample). The frequency of disadvantage genotype E4+ was significantly higher (P < 0.01) in acute coronary syndrome patients (22.38 %) than in controls (16.76 %). When the acute coronary syndrome group was step by step limited to non-smokers, non-diabetics and normotensive individuals, the odds ratio displayed a gradual increase from 1.35 (for the entire group) through 1.48 (non-smokers), 1.53 (non-smokers+non-diabetics) to 1.71 (non-smokers+non-diabetics+normotensives). The effect of the apoprotein E gene on the individual risk of acute coronary syndrome is nonhomogenous within the patient groups. This association of apoprotein E gene with acute coronary syndrome is strongly modified by the presence/absence of traditional cardiovascular factors of atherosclerosis in a high-risk Czech population.

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.

[Atherosclerosis in childhood]. / Ateroskleróza v detském veku.

Atherosclerosis and its complications are at the first place in mortality of adult population not only in Czech Republic, but among all developed countries through the world. It is well known today that atherosclerotic changes are present even in childhood, especially in children with mothers with hypercholesterolemia. Primary prevention should be therefore focused on very early stages of atherosclerosis in childhood. In all children the active prevention must start as early as possible and include smoking, obesity, metabolic syndrome, blood lipids and blood pressure. The article contains summary of current knowledge about atherosclerosis in childhood as well as information on the active prevention of its development.

[Tako-tsubo cardiomyopathy]. / Tako-tsubo kardiomyopatie.

Tako-tsubo cardiomyopathy is new clinical syndrome which mimic acute myocardial infarction. The main characteristic is apical ballooning of the left ventricular wall during systole and normal findings on coronary arteries. Pathophysiology is not known, very important is definitively the role of catecholamines. The electrocardiography, echocardiography, left ventricular angiography and coronary angiography are methods used in diagnosis of this syndrome. The therapy is only symptomatic, in cases with severe complications mechanical support of circulation should be used.

[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.

Apolipoprotein E Arg136 --> Cys in individuals with premature myocardial infarction.

Coronary artery disease is a serious health problem worldwide caused by interactions between genetic and environmental risk factors. One of the candidate genes is the gene for apolipoprotein E. We present a case report of two young smoking and obese carriers (man 45 years and woman 32 years old) of the apolipoprotein E (p.Arg136Cys) mutation, but with no severe dyslipidaemias detected among 1,671 survivors (1,483 men, 188 women, aged 21-75 years) of acute coronary syndrome screened for genetic and traditional cardiovascular risk factors. Between acute coronary syndrome survivors, the mutation has not yet been described. Even though this mutation raises suspicion to be a risk factor for cardiovascular disease (based on previous publications), its frequency was very low and similar to the control population (12 detected carriers of the mutation within the 9,386 screened individuals). Therefore, whether this rare mutation is causal for the development of myocardial infarction needs to be further evaluated.

[Myocardial infarction, left ventricle remodeling and cellular therapy]. / Infarkt myokardu, remodelace levé komory a bunecná terapie.

The paper brings an overview of results of the most important and significant clinical studies dealing with the issues of bone marrow stem cell implantation in patients with acute myocardial infarction. On the world scale, research has been focused on this area for several years. Much hope is put primarily on the possibility to prevent the process of progressive remodelling of the left ventricle, the substitution of necrotic or fibrotic tissue and the resulting prevention of development and progression of heart failure. In the centre of attention are especially patients whose long-term prognosis is often very poor in spite of progress in contemporary medicine.

Intravascular ultrasound assessment of coronary artery involvement in Fabry disease.

AIM: We used intravascular ultrasound (IVUS) to characterize coronary artery involvement in patients with Fabry disease (FD). METHODS: Nine FD patients (5 women) were matched to 10 control patients (5 women) chosen from our IVUS database. Standard volumetric IVUS analyses were performed along with assessment of plaque echodensity. RESULTS: Plaques in FD patients were diffuse and hypoechogenic compared with more focal and more echogenic lesions in control patients. Echogenicity of plaques was significantly lower in FD patients (median 30.7 +/- 12.9 vs 55.9 +/- 15.7, p = 0.0052, mean 37.2 +/- 15.6 vs 66.2 +/- 13.3, p = 0.0014). Diffusiveness was assessed as differences between mean and median plaque burden versus the plaque burden in each of the analysed cross-sections. These differences were lower in FD vs controls (5.8 +/- 4.8 vs 8.7 +/- 6.6, p < 0.001 for mean, and 5.8 +/- 4.9 vs 8.8 +/- 7.3, p < 0.001 for median) indicating a more diffuse involvement. The occurrence of lipid cores was significantly higher in FD patients than in controls (2.4 +/- 1.5 vs 1.0 +/- 0.94, p = 0.02). CONCLUSION: IVUS showed diffuse hypoechogenic plaques in patients with FD. The explanation may be higher lipid content in plaques and accumulation of glycosphingolipid in smooth-muscle and endothelial cells.

Autologous intra-arterial infusion of bone marrow mononuclear cells in patients with critical leg ischemia.

AIM: The injection of bone marrow mononuclear cells (BMMC) into the gastrocnemius muscle has given promising results in patients with critical limb ischemia (CLI). In this article, we have assessed whether a less invasive procedure, i.e. intravascular BMMC infusion, could be effective in this population of patients. METHODS: A total of 28 limbs in 24 patients with CLI were treated. An amount of 276-700 mL of marrow blood was harvested from posterior iliac crests and BMMC were obtained by standard procedure used for bone marrow transplantation. After performance of digital subtraction angiography, BMMC were injected laterally through a 4 Fr sheet. Primary outcome was efficacy of the procedure measured as healing of defects, frequency of high amputations and change of ischemia grade; among secondary outcomes were safety of the procedure, angiographic changes and changes in quality of life. RESULTS: One year after treatment, all patients were alive and only 2 patients have undergone high amputation. Eleven of 14 defects have healed (78%) and Fontaine grade of ischemia has changed from median grade 3.5 to median grade 2 (P<0.0001). Collateral vessel development has improved by mean 1.13 and 1.3 points on a four-point semiquantitative scale in calf and foot, respectively (P<0.0001). There were no grade III-IV adverse events. According to the SF-36 quality of life questionnaire, 1 year after the procedure patients have reported significant improvement in all measured items. CONCLUSION: Intra-arterial infusion of BMMC can lead to significant and long-lasting subjective and objective improvements in patients with CLI. The results merit validation by randomized controlled studies in patients with less critical limb ischemia.

The impact of gender on outcomes of patients with ST elevation myocardial infarction transported for percutaneous coronary intervention: analysis of the PRAGUE-1 and 2 studies.

BACKGROUND: Data comparing survival outcomes for women versus men transported for pPCI were absent. OBJECTIVES: To assess the impact of gender on 30-day mortality of patients with STEMI transported for pPCI. METHODS: The data from the PRAGUE-1 and PRAGUE-2 trials were analysed. Studies compared thrombolysis in the community hospital and pPCI after transportation to cardiocentre. A group of 520 patients treated with thrombolysis, and 530 transported for pPCI, were analysed. RESULTS: Women were older, with a higher risk profile. They had longer ischaemia time. Mortality of patients treated with TL was significantly higher in women than in men (15% vs 9%, p = 0.043). There was no significant gender difference in mortality in the PCI group (8.2% of women vs 6.2% of men, p = 0.409). Mortality of women treated with on-site TL was nearly twice as high as mortality of women transported for pPCI (p = 0.043). After adjustment in a multivariate model the odds ratio for mortality in women was 0.74 (95% CI 0.26 to 2.05; p = 0.556). CONCLUSION: Long-distance transportation of women with STEMI from a community hospital to a tertiary PCI centre is a significantly more effective treatment strategy than on-site TL. Gender did not determine survival in patients transported for pPCI.

[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.

[Molecular genetics of myocardial infarction]. / Molekulární genetika infarktu myokardu.

The incidence of atherosclerosis is very high and the typical risk factors such as lipids, blood pressure, smoking, dietary habits and lifestyle in general have an 80% share in its development. Heredity also has a significant share and genome-related information has been given growing attention in recent years. A number of links between polymorphisms found at certain gene positions and the probability of acute myocardial infarction at a young age have been currently described. Cross-sectional studies have been focused on the identification of particular genotypes and alleles which can be responsible for early development of atherosclerosis and acute myocardial infarction. The article summarises some of the knowledge acquired so far in the field of genetic makeup of patients with acute myocardial infarction.