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).

Utility of cardiac CT for evaluating delayed contrast enhancement in dilated cardiomyopathy.

BACKGROUND: The presence of myocardial fibrosis is associated with adverse outcome in dilated cardiomyopathy (DCM). Delayed contrast-enhanced cardiac magnetic resonance (DE-CMR) currently represents the gold standard in noninvasive evaluation of myocardial scarring. However, a significant number of patients are unable to undergo DE-CMR study for various reasons. We sought to determine the diagnostic accuracy of cardiac CT (CCT) compared with CMR in the investigation of the presence of delayed contrast enhancement (DCE) in subjects with DCM. METHODS: We prospectively enrolled 17 consecutive patients with DCM, who were initially referred to our institution because of recently manifested heart failure due to unexplained left ventricular systolic dysfunction. In all subjects, CCT and DE-CMR were performed within 1 week. RESULTS: CCT and DE-CMR showed satisfactory agreement in detecting DCE (agreement in 82% cases, κ = 0.56) with 50% sensitivity, 100% specificity, and a positive predictive value of 100%. CONCLUSION: CCT may be a valuable method for detecting DCE in patients with DCM. CCT thus might be considered as an alternative method to DE-CMR in the assessment of the presence and extent of myocardial fibrosis in subjects who are not suitable for DE-CMR examination.

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.

[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.

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.

[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.

[Pulmonary endarterectomy--the surgical treatment of chronic thromboembolic pulmonary hypertension]. / Endarterektomie plicních tepen--chirurgická lécba chronické tromboembolické plicní hypertenze.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) in indicated cases can be successfully treated by the endarterectomy of pulmonary arteries (PEA). Symptomatically not treated CTEPH has highly unfavourable prognosis. Five years survival of patients with mean pulmonary pressure over 50 mmHg is only 10%. PEA was not available in the Czech Republic till 2004, when PEA program was initiated it the Cardiocenter of the General teaching hospital in Prague in collaboration with leading clinics in that field (Prof. Mayer, University of Mainz, BRD). METHODS AND RESULTS: Up-to-date surgical technique, which in various modifications has been used at majority of clinics, was elaborated by Jamieson and Daily at University of California in San Diego. It is based on reverse endarterectomy performed during complete circulatory arrest with brain protection by deep hypothermia. Till September 2005 twelve patients were operated with zero mortality. In one patient a suture of atrial septum defect was necessary to perform along. Average time of the circulatory arrest was 45 minutes; duration of the extracorporal circulation was 334 minutes. Average duration of the operation was 450 minutes. Duration of the mechanical ventilation was in average 45.5 hours. After one month already haemodynamic parameters (mPA, CI, PVR) significantly improved or normalized and the average length in the test of six minutes walking increased by 132 meters. CONCLUSION: PEA represents a treatment method for patients with CTEPH and surgically accessible pulmonary artery obstruction. Centralized care of those patients is a rational necessity enabling to get maximum experience with complicated diagnostics and treatment of those patients. Multidisciplinary collaboration is the essential condition for the success of the program.