Plasma concentrations of tissue factor and its inhibitor in chronic thromboembolic pulmonary hypertension: a step closer to explanation of the disease aetiology?

BACKGROUND: The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not clearly understood. In some patients, the disease is preceded by acute pulmonary embolism (APE), and is characterised by intravascular thrombosis, vasoconstriction, inflammation and remodelling of pulmonary arteries. Ensuing pulmonary hypertension leads to potentially fatal chronic right ventricle failure. Both inborn and acquired risk factors were identified. Pathogenesis of haemostatic disorders is not completely explained, and extrinsic coagulation pathway disorders may play a role in CTEPH aetiology. AIM: To evaluate levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in CETPH, and to delineate their role in the disease pathogenesis. METHODS: Plasma concentrations of TF and TFPI were evaluated in 21 CTEPH patients, in 12 patients with pulmonary arterial hypertension (PAH), in 55 APE survivors without persistent pulmonary hypertension after at least 6 months from the acute episode, and in 53 healthy volunteers (control group C). Most patients were treated with vitamin K antagonists (VKA), and some with unfractionated or low molecular weight heparin. Exclusion criteria included malignancy, inflammation, and recent operation. RESULTS: Tissue factor concentration was lower in CTEPH and in post-APE patients, not stratified by anticoagulation modality, as compared to control group (p = 0.042; p = 0.011) and PAH group (p = 0.024, p = 0.014). Patients with CTEPH and post-APE on adequate VKA-anticoagulation had similar TF concentration to group C. TFPI concentration was similar in CETPH and post-APE patients irrespective of anticoagulation, and higher as compared to group C (respectively, p = 0.012; p = 0.024; p = 0.004). TFPI concentration was similar in patients with CETPH and in post-APE group, both on adequate VKA-anticoagulation when compared to group C. In the post-APE group, there was no significant difference in TFPI concentration between patients receiving adequate and subjects without anticoagulation. Group C was significantly (p = 0.000) younger than any other group, and showed correlation (r = 0.31) between age and TFPI concentration. CONCLUSIONS: In CTEPH there is a high consumption of TF, leading to reduction in plasma concentration of TF and increase in TFPI. Adequate VKA-anticoagulation normalises TF and TFPI plasma concentrations, as is the case of APE survivors.

Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry.

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.

[The role of spiral computer tomography in diagnostic algorithms in patients with suspected pulmonary embolism]. / Rola spiralnej tomografii komputerowej w algorytmach diagnostycznych u chorych z podejrzeniem zatorowosci plucnej.

The recognizing of the EP is still not satisfied because specifity and sensitivity of clinical symptoms is relatively low. SCT is an important examination in the diagnostic of pulmonary embolism and is the alternative to often nonconclusive scintigraphy and conclusive but invasive pulmonary angiography. The authors describe the role of SCT in the diagnostic algorithm of the suspected pulmonary embolism of the high and not high risk, discuss the interpretation of result of SCT due to the sort of SCT (SDCT or MDCT) and to clinical probability of PE and they discuss the problem of subsegmental PE.

[C-reactive protein in circulatory diseases]. / Bialko C reaktywne w chorobach ukladu krazenia.

C-reactive protein is the widely used marker in a clinical practice but also a mediator of the inflammatory process. In the introduction the authors describe the structure and function of the C-reactive protein in relation with inflammatory response to different morbidity stimulations. After this, there have been seen the oscillations of C-reactive protein plasma level of healthy people and in inflammatory, neoplastic and immunological diseases with an explanation of the clinical utilities. The current knowledge about presence of C-reactive protein in a different type of circulatory diseases, in heart failure and arrhythmia has been discussed. The importance of the role of C-reactive protein, especially high-sensivity C-reactive protein, in the prediction of circulatory diseases of the healthy members of the population and the prognostic value of C-reactive protein has been underlined.

[Pulmonary heart disease--cardiologist's point of view]. / Przewlekle serce plucne--punkt widzenia kardiologa.

This paper presents cardiologist's point of view on definition, diagnosis and treatment of pulmonary heart disease. Difficulties in interpretation of definition in clinical praxis and the role of medical history, physical examination, lung function tests, gasometry, chest X-ray and ECG in initial diagnosis of pulmonary heart disease are described. Author underlines the importance of echocardiographic study and pulmonary hemodynamics in confirmation of diagnosis and in differential diagnosis of "out of proportion" pulmonary hypertension. The current results of specific for pulmonary artery hypertension vasodilatory treatment in patients with pulmonary heart disease are discussed.

Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. METHODS AND RESULTS: The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%- 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. CONCLUSIONS: Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension-targeted treatments.

Clinical course of unoperated mild chronic thromboembolic pulmonary hypertension.

BACKGROUND: Pulmonary endarterectomy is the treatment of choice for a majority of patients with chronic thromboembolic pulmonary hypertension (CTEPH), however, haemodynamic criteria for the surgery have not been established. It is still unknown whether patients with mild CTEPH should be operated on and what is the clinical course of unoperated, anticoagulated mild CTEPH. AIM: To determine the clinical course in chronically anticoagulated, unoperated patients with mild CTEPH. METHODS: A single-centre, non-randomised, follow-up study involved 10 anticoagulated, unoperated patients (3 males and 7 females aged 46 to 77 years) with mild CTEPH (mean pulmonary artery pressure [MPAP] £ 30 mm Hg and pulmonary vascular resistance £ 300 dynes x s x cm(-5), ≥ 2 METs achieved during symptom limited treadmill exercise test) selected from 73 consecutive patients with CTEPH. The 3-year follow up included yearly echocardiographic evaluation of pulmonary artery systolic pressure (PASP), right ventricular end-diastolic diameter (RVEDD) and acceleration time (AcT) as well as NYHA functional class and symptom-limited treadmill exercise test. RESULTS: All the patients survived the 3-year follow-up. The PASP, RVEDD and AcT (mean ± SD) at baseline and at the end of follow-up were 43.9 ± 6.1 mm Hg and 25.6 ± 8.0 mm Hg, p = 0.0017, 25.4 ± 4.9 mm and 17.8 ± 3.82 mm, p = 0.00006, 68.3 ± 10.0 ms and 104.4 ± 16.48 ms, p = 0.0004, respectively. The NYHA functional class improved from 2.1 ± 0.32 to 1.3 ± 0.48, p = 0.002 and was accompanied by the trend to improve results of exercise test. CONCLUSIONS: The results of the study suggest that patients with mild CTEPH can be treated successfully by anticoagulation alone with excellent 3-year survival rate, improved functional status and with gradual decrease of pulmonary pressure and right ventricular overload.

[Chronic thromboembolic pulmonary embolism not preceded by clinical thromboembolic event - clinical, echocardiographic and haemodynamic course]. / Przebieg przewleklego zakrzepowo−zatorowego nadcisnienia plucnego niepoprzedzonego incydentem zatorowym ­ ocena kliniczna, echokardiograficzna i hemodynamiczna.

Chronic thromboembolic pulmonary embolism not preceded by clinical thromboembolic event(s) in a 50 year-old male with a history of three-year dyspnea on exertion was detected. Proximal chronic pulmonary embolism, mean pulmonary artery pressure 32 mm Hg, and pulmonary vascular resistance of 444 dyn x s(-1) x cm(-5) were found. We describe a 11-year clinical course of anticoagulated patient with monitoring of functional status and echocardiography and with control of pulmonary haemodynamics at the end of follow-up.

[Dysfunction of coagulation processes in patients after acute coronary syndrome--therapeutic implications]. / Zaburzenia procesów krzepniecia u chorych po ostrym zespole wiencowym--implikacje terapeutyczne.

In the guidelines for patients with acute coronary syndrome (ACS), reperfusion, antiplatelet treatment, completed with parenteral anticoagulant are the standard therapy. It is because ACS is the result of occlusion of related artery by thrombus compound mostly of platelets, with processes of aggregation and adhesion in its pathogenesis. However, many patients after ACS experience major adverse cardiovascular events (MACE) despite optimal long term antiplatelet therapy. The possible reasons seem to be not only the resistance to this drugs but also underestimated coagulation processes. This review describes the dysfunction of particular coagulation parameters in patients with coronary artery disease and their relationship with MACE after ACS.

[Non-invasive electrophysiologic study and radiofrequency current ablation of tachycardia responsible for numerous inappropriate ICD interventions in patient with post-infarction dilated cardiomyopathy]. / Nieinwazyjne badanie elektrofizjologiczne i ablacja czestoskurczu bedacego przyczyna bardzo licznych interwencji ICD-DDD u chorego z pozawalowa kardiomiopatia rozstrzeniowa.

We present a case of 75-year-old man with numerous inappropriate interventions of an implanted cardioverter-defibrillator (ICD). In this patient with ischaemic cardiomyopathy, ICD was implanted for primary prevention of sudden cardiac death following recurrent syncope. ICD interrogation and non-invasive electrophysiologic study (NIPS) confirmed a risk of reentry-mediated tachycardia and excluded the presence of a manifest or concealed accessory pathway. Invasive electrophysiologic study revealed a wide zone that triggered atrioventricular nodal reentrant tachycardia, and ablation of the slow pathway resulted in complete remission of the arrhythmia. NIPS performed using atrial and ventricular ICD leads and subsequent ICD interrogation confirmed long-term effectiveness of the procedure. At the same time, clinical improvement of heart failure was seen, leading to a suspicion of tachycardia-induced cardiomyopathy coexisting with ischaemic cardiomyopathy.

[Combined pulmonary fibrosis and emphysema - case report and literature review]. / Wspólistnienie wlóknienia i rozedmy pluc - opis przypadku i przeglad literatury.

We describe the case of a 61-year-old male patient, in which the search for the cause of chronic respiratory failure, severe pulmonary hypertension and secondary erythrocytosis resulted in a diagnosis of combined pulmonary fibrosis and emphysema (CPFE). This is a unique, recently characterised syndrome with upper-lobe emphysema and pulmonary fibrosis of the lower lungs. The cause is unknown, but one of the main risk factor remains smoking. The patient was a heavy smoker (over 40 pack-years). He complained of dyspnoea on exertion and cough. Physical examination revealed basal crackles and cyanosis. The patient had severe reduction in diffusing capacity, out of proportion to his lung volumes (DLCO 27% of predicted value, FEV1 2.95 l (100%), FVC 4.41 l (118%), FEV1/FVC (66%). The blood gas showed hypoxemia (pO2 37 mm Hg), hypocapnia and respiratory alkalosis. Diagnosis was based on chest computer tomography, which revealed upper lobe emphysema and lower lobe ground glass changes and honeycombing. Severe pulmonary hypertension (SPAP 80 mm Hg) was confirmed by echocardiography and right cardiac catherisation. The patient received long-term oxygen therapy, inhaled corticosteroid and Ca-blocker.