Architecture of fibrin network inside thrombotic material obtained from the right atrium and pulmonary arteries: flow and location matter

Pulmonary embolectomy is a treatment option in selected patients with high-risk pulmonary embolism (PE). Efficiency of thrombus degradation in PE largely depends on the architecture of its fibrin network, however little is known about its determinants. We present the case of a 56-year-old woman with high-risk PE and proximal deep-vein thrombosis, whose thrombotic material removed during embolectomy from the right atrium and pulmonary (lobar and segmental) arteries has been studied using scanning electron microscopy (SEM). SEM images showed that distally located thrombi are richer in densely-packed fibrin fibers and contain more white cells and less erythrocytes than the proximal ones and the atrial thrombus. Fibrin fibers alignment along the flow vector was observed in the thrombi removed from high-velocity flow pulmonary arteries, and not in the atrial thrombus. The content of denser fibrin network and platelet aggregates was increased in segmental thromboemboli. Our findings describe the relation between thrombus architecture and location, and might help to elucidate thrombus resistance to anticoagulant therapy in some PE patients.     

Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: How can patients be better selected?

Chronic thromboembolic pulmonary hypertension (CTEPH) comprises organizing thrombotic obstructions in the pulmonary arteries by nonresolving thromboemboli, formation of fibrosis and remodeling of pulmonary blood vessels. Surgical pulmonary endarterectomy (PEA) is the therapy of choice for patients with surgically accessible CTEPH, which leads to a profound improvement in hemodynamics, functional class and survival. Select- ing the candidates that will benefit from surgery is still a challenging task. Criteria for surgical suitability have been described but the decision-making for or against surgical intervention remains still subjective. The optimal characterization of the reciprocal contribution of large vessel and small vessel disease in the elevation of pulmonary vascular resistance is crucial for the indication and outcome of PEA. Recently, Toshner et al intended to validate the partition resistance into small and large vessels compartments (upstream resistance:Rup) by the occlusion technique in the preoperative assessment of PEA. We discuss the advantages and disadvantages of Rup and compare it with other hemodynamic predictor to evaluate operative risk in CTEPH patients.     

Chronic Thromboembolic Pulmonary Hypertension Medical Management

Chronic thromboembolic pulmonary hypertension (CTEPH) is a common long-term complication of pulmonary embolism characterized by thromboembolic obstruction of the pulmonary arteries, vascular arteriopathy, vascular remodeling, and ultimately pulmonary hypertension (PH). Although pulmonary endarterectomy (PEA) surgery is the standard of care, approximately 40% of patients in the international CTEPH registry were deemed inoperable. In addition to lifelong anticoagulation, the cornerstone of PH-specific medical management is riociguat, a soluble guanylate cyclase stimulator. Medical management should be started early in CTEPH patients and may be used as a bridge to PEA surgery or balloon pulmonary angiography. Medical management is indicated for inoperable CTEPH patients and patients who have recurrence of PH after PEA surgery.     

Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary hypertension.

BACKGROUND. Chronic thromboembolic pulmonary hypertension (CTEPH) is a disorder characterized by pulmonary arterial hypertension as a consequence of organized thrombotic material in the central pulmonary arteries. Incomplete resolution of acute pulmonary emboli is believed to be pathogenically important; however, the mechanism for poor thrombus dissolution remains to be explained. We undertook this study to assess the major determinants of plasma fibrinolysis in patients with CTEPH (n = 32). METHODS AND RESULTS. Immunological and functional levels of tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) were quantified in platelet-poor plasma (PPP) from patients with CTEPH as well as age-matched controls. Although basal PPP t-PA antigen levels (CTEPH mean, 29.5 ng/ml; control mean, 2.7 ng/ml) and PAI-1 antigen levels (CTEPH mean, 55.8 ng/ml; control mean, 21.0 ng/ml) were higher in the CTEPH group, no between-group differences were detected in the enzymatic activities of these two molecules. The CTEPH group demonstrated a greater rise in t-PA antigen (CTEPH mean rise, 53.0 ng/ml; control mean rise, 5.6 ng/ml) and PA activity (CTEPH mean rise, 10.5 IU/ml; control mean rise, 1.2 IU/ml) than controls in response to an experimentally induced venous occlusion. Immunoprecipitation and fibrin autography of PPP from two patients with markedly elevated basal t-PA antigen levels demonstrate that the t-PA antigen was present in PPP primarily in complex with PAI-1. CONCLUSIONS. Although abnormalities of the fibrinolytic system were detected, neither a high resting plasma PAI-1 activity nor a blunted response of t-PA to venous occlusion can be invoked as an etiology for CTEPH.     

Architecture of the thrombi removed from coronary artery bypass grafts in a patient with acute myocardial infarction

Using scanning electron microscopy we analyzed thrombotic material removed from coronary bypass grafts in a 57-year-old woman with multilevel atherosclerosis presenting with acute myocardial infarction (AMI). A white thrombotic material removed from the marginal branch bypass that contained large amounts of activated platelets displaying pseudopodia clearly visible at a higher magnification with a relatively low amount of fibrin. The other thrombus obtained from the right posterior descendent branch (RPD) bypass showed a highly organized fibrin structure composed of thicker fibers with low amounts of cellular components. Our findings indicate that the thrombus structure is different in AMI patients in whom the infarct-related vessel is vein anastomosis compared to those with a native coronary artery occluded. These findings help explain resistance of such thrombi to fibrinolysis and faster plaque growth related to fibrin accumulation.     

Pulmonary microvascular disease in chronic thromboembolic pulmonary hypertension

Distal, small-vessel vasculopathy is generally considered a major contributor to the progression of pulmonary hypertension (PH) as chronic thromboembolic pulmonary hypertension (CTEPH) develops over time and is a major determinant of postoperative outcome after pulmonary endarterectomy (PEA). The pathogenesis and natural history of microvascular disease in CTEPH remain uncharacterized. Mechanisms for significant distal disease may involve the following processes: (1) predominant obstructions of "small" subsegmental elastic pulmonary arteries, (2) classical pulmonary arteriopathy of small muscular arteries and arterioles distal to nonobstructed vessels, (3) pulmonary arteriopathy of small muscular arteries and arterioles distal to totally or partially obstructed vessels. Patients in whom obstructed vessels are mainly subsegmental are considered poor surgical candidates. Distal pulmonary vasculopathy in both the occluded and nonoccluded pulmonary vascular bed is characterized by lesions considered typical for idiopathic pulmonary arterial hypertension, including plexiform lesions. The pathogenesis and time course of these vascular lesions remain unclear, but may involve endothelial and/or platelet production and release of mediators and/or altered pulmonary blood flow. The reciprocal contribution of large-vessel (operable) and small-vessel lesions in CTEPH is crucial for the indication and results of PEA. A combination of investigations is used to identify the extent of small-vessel disease, including right-heart catheterization, perfusion lung scan, multidetector spiral computed tomography, pulmonary angiography, and pulmonary arterial occlusion wave-form analysis. Preliminary evidence suggests that medical therapy may provide hemodynamic and clinical benefits for patients in whom PEA cannot be applied, in those who have persistent postoperative PH, or in selected patients with advanced preoperative hemodynamic changes.     

The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study.

The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, many patients develop a severe progressive small vessel pulmonary arteriopathy that is inaccessible to surgical intervention and is associated with poor survival. The purpose of the present study was to evaluate the medium-term efficacy and safety of the dual endothelin receptor antagonist, bosentan, in inoperable CTEPH. Forty-seven patients with inoperable CTEPH (distal disease or persistent pulmonary hypertension following PEA) underwent evaluation after 1 yr of bosentan therapy. Outcomes included assessment of 6-min walk test (6MWT), haemodynamics and World Health Organization functional classification. Monitoring of serious adverse effects and changes in therapy was undertaken. Patients showed sustained improvements in 6MWT (49+/-8 m), functional classification, cardiac index (+0.2+/-0.07 L.min(-1).m(-2)) and total pulmonary resistance (-139+/-42 dyn.s.cm(-5)). Those patients with persisting pulmonary hypertension following PEA showed the greatest improvement. One-yr survival was 96%, and bosentan was well tolerated with only one patient developing deranged liver function. Although all patients with chronic thromboembolic pulmonary hypertension should be considered for pulmonary endarterectomy, bosentan provides an alternative medical therapy to improve function and delay the progression of this devastating disease in those in whom surgery is not suitable.     

Chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension is a severe disease that has been ignored for a long time. However, over the past 20 yrs chest physicians, cardiologists and thoracic surgeons have shown increasing interest in this disease because of the development of new therapies, that have improved both the outcome and quality of life of patients, including pulmonary transplantation and prostacyclin therapy. Chronic thromboembolic pulmonary arterial hypertension (CTEPH) can be cured surgically through a complex surgical procedure: the pulmonary thromboendarterectomy. Pulmonary thromboendarterectomy is performed under hypothermia and total circulatory arrest. Due to clinically evident acute-pulmonary embolism episodes being absent in > 50% of patients, the diagnosis of CTEPH can be difficult. Lung scintiscan showing segmental mismatched perfusion defects is the best diagnostic tool to detect CTEPH. Pulmonary angiography confirms the diagnosis and determines the feasibility of endarterectomy according to the location of the disease, proximal versus distal. The technique of angiography must be perfect with the whole arterial tree captured on the same picture for each lung. The lesions must start at the level of the pulmonary artery trunk, or at the level of the lobar arteries, in order to find a plan for the endarterectomy. When the haemodynamic gravity corresponds to the degree of obliteration, pulmonary thromboendarterectomy can be performed with minimal perioperative mortality, providing definitive, excellent functional results in almost all cases.     

Therapie der chronischen Thromboembolie (CTEPH)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a frequent cause of pulmonary hypertension, however, it still is underdiagnosed. Up to 4% of all individuals that survive pulmonary embolism develop CTEPH. Increasing insights into the pathophysiology of CTEPH indicate a distinct overlap with pulmonary arterial hypertension (PAH). Pulmonary endarterectomy (PEA), which lowers pulmonary resistance and can lead to normalization of hemodynamics, is the treatment of choice for eligible patients, however, only a proportion of patients fulfill the criteria for surgical intervention. Patients who are not eligible for PEA may benefit from specific medical therapy for pulmonary hypertension, as do patients before and after PEA with significant peripheral involvement of the pulmonary vasculature. Direct evidence from clinical trials in CTEPH is promising, but is to date limited. Further studies are necessary to define criteria for specific medical therapy for CTEPH.     

Chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease that results from obstruction of the major pulmonary arteries by incompletely resolved or organized pulmonary emboli that have become incorporated into the pulmonary artery wall, eventually causing an increase in pulmonary vascular resistance. From 0.1 to 4.0% of patients recovering from acute pulmonary embolism develop CTEPH. Without intervention, CTEPH is a progressive and lethal disease for which there is no effective medical therapy. Pulmonary endarterectomy (PEA) is the treatment of choice. Careful pre- and postoperative management is essential for a successful outcome after PEA. Lung transplantation is indicated only in few cases when PEA is not feasible. In 1994, we started a program (in Pavia, Italy) in which members of a multidisciplinary team work closely with the aim of increasing experience in the challenging problems these patients present in the evaluative, surgical, and postoperative phases of their care. To date, 134 PEAs have been performed. Preoperatively, New York Heart Association (NYHA) class distribution was three class II, 56 class III, and 75 class IV patients, respectively; mean pulmonary artery pressure and pulmonary vascular resistance values were 47 +/- 13 mm Hg and 1149 +/- 535 dyn/s/cm (-5), respectively. The overall operative mortality has been 9.7% (4.5% in 2004). Survival at 3-month, 1-year, and 3-year follow-up was 89.5 +/- 2.6%, 87.8 +/- 2.9%, and 83.3 +/- 3.5%, respectively; this last rate was unchanged up to 10 years. After PEA, mean pulmonary artery pressure and pulmonary vascular resistance values were 25 +/- 9 mm Hg and 322 +/- 229 dyn/s/cm (-5), respectively, and these results were stable over time. At the 3-year follow-up, 94% of patients were in NYHA class I or II and were being treated with oral anticoagulants only.     

Resolutive pulmonary endarterectomy in a non-compliant patient with systemic lupus erythematosus and antiphospholipid syndrome

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have poor prognosis, and pulmonary endarterectomy (PEA) is considered the treatment of choice for this condition. We report a case and review the literature of successful PEA for CTEPH due to antiphospholipid syndrome associated with systemic lupus erythematosus. The definitive and decisive approach needed to treat this high-risk patient with a history of comorbidity, long-term illness and poor compliance was found with a therapy of PEA.     

Advances in understanding the pathogenesis of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) comprises organizing thrombotic obstructions in the pulmonary arteries. While roughly 40% of CTEPH cases are not preceded by a venous thromboembolic event, 0·1–5·1% of acute pulmonary thromboemboli evolve into organized obstructions of the pulmonary artery. In patients with predominantly proximal disease, surgical pulmonary endarterectomy provides a potential cure of the disease. For years, the scientific debate of CTEPH was mainly focused around its thromboembolic nature because of striking dissimilarities to classical venous thromboembolism, for example, the lack of risk factors for venous thrombosis, the lack of clinically apparent pulmonary embolism in many patients, the difficulty to reproduce the disease in animal models of thrombosis, and the nature of the pulmonary vascular obstructions that are dissociated from the degree of hemodynamic compromise. Recent studies have confirmed an association between venous thromboembolism and the evolution of CTEPH, and have shed light on disease‐modifying conditions.     

Recent progress in the diagnosis and management of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by non-resolving thromboembolisms of the pulmonary arteries. In Japan, in contrast to Western countries, CTEPH is more prevalent in women. A Japanese multicenter study reported that a form of CTEPH unrelated to deep vein thrombosis is associated with HLA-B?5201, suggesting that this form of CTEPH may be associated with vasculopathy. CTEPH can be cured by pulmonary endarterectomy, provided that the thrombi are surgically accessible; thus, early diagnosis is important, and all patients with exertional dyspnea should be evaluated for pulmonary hypertension. Ventilation/perfusion scans provide an excellent non-invasive means to distinguish CTEPH from pulmonary arterial hypertension. Similarly, computed tomographic pulmonary angiograms allow for the detection of thrombi and evaluation of pulmonary hemodynamics in a minimally invasive manner. Importantly, the absence of subpleural perfusion on pulmonary angiograms can suggest the presence of small vessel disease. Small vessel disease might be involved in the pathogenesis of CTEPH, and its detection is essential in preventing operative death. Although no modern therapies for pulmonary arterial hypertension have been approved for treatment of CTEPH, a recent randomized control trial of riociguat in patients with CTEPH demonstrated that riociguat significantly improved 6-min walking distance. Further investigations into treatments that target endothelial dysfunction and hyperproliferative CTEPH cells are needed. Recently, balloon pulmonary angioplasty has emerged as a promising treatment modality in Japan. A specialized medical team, including at least one expert surgeon, should make decisions regarding patients' candidacy for pulmonary endarterectomy and/or balloon pulmonary angioplasty.     

Occlusion pressure analysis role in partitioning of pulmonary vascular resistance in CTEPH

Flow-directed pulmonary artery occlusion is posited to enable partitioning of vascular resistance into small and large vessels. As such it may have a role in assessment for pulmonary endarterectomy. To test if the occlusion technique distinguished small from large vessel disease we studied 59 subjects with chronic thromboembolic pulmonary hypertension (CTEPH), idiopathic pulmonary arterial hypertension (IPAH), and connective tissue disease (CTD)-associated PAH. At right heart catheterisation, occlusion pressures were recorded. With fitting of the pressure decay curve, pulmonary vascular resistance was partitioned into downstream (small vessels) and upstream (large vessels, Rup). 47 patients completed the study; 14 operable CTEPH, 15 inoperable CTEPH, 13 idiopathic or CTD-PAH and five post-operative CTEPH. There was a significant difference in mean Rup in the proximal operable CTEPH group 87.3 (95% CI 84.1-90.5); inoperable CTEPH mean 75.8 (95% CI 66.76-84.73), p=0.048; and IPAH/CTD, mean 77.1 (95% CI 71.86-82.33), p=0.003. Receiver operating characteristic curves to distinguish operable from inoperable CTEPH demonstrated an area under the curve of 0.75, p=0.0001. A cut-off of 79.3 gave 100% sensitivity (95% CI 73.5-100%) but 57.1% specificity (95% CI 28.9-82.3%). In a subgroup analysis of multiple lobar sampling there was demonstrable heterogeneity. Rup is significantly increased in operable proximal CTEPH compared with non-operable distal CTEPH and IPAH/CTD-PAH. Rup variability in patients with CTEPH and PAH is suggestive of pathophysiological heterogeneity.     

Thrombotic risk factors in pulmonary hypertension.

Thrombotic lesions are consistently observed in chronic thromboembolic pulmonary hypertension (CTEPH) and frequently found in primary pulmonary hypertension (PPH). It remains unknown, however, whether thrombosis is related to defects of the antithrombotic pathway or to previous vascular injury. This study therefore analysed the frequency of both hereditary and acquired thrombotic risk factors in CTEPH and PPH. One hundred and forty-seven consecutive patients with CTEPH investigated in the author's institution were compared to 99 consecutive patients with PPH. In 116 CTEPH patients and 83 PPH patients, phospholipid-dependent antibodies (antiphospholipid antibodies and lupus anticoagulant) were analysed by both immunological and clotting assays. In patients enrolled since 1994 (46 CTEPH and 64 PPH), hereditary thrombotic risk factors were also determined. Antithrombin, protein C and protein S activities were measured by functional assays. Mutations of factor V and factor II were identified by polymerase chain reaction. The prevalence of hereditary thrombotic risk factors was not increased in patients with either PPH or CTEPH. In contrast, a high frequency of phospholipid-dependent antibodies was observed in PPH (10%) and more notably in CTEPH (20%). Moreover, in PPH, antibodies were present only in low titre whereas in CTEPH, half of the patients with antiphospholipid antibodies had high titres. In addition, in CTEPH all but one of the patients with lupus anticoagulant also had antiphospholipid antibodies. The most striking finding of this study was the high prevalence of phospholipid-dependent antibodies but their clinical relevance appears to be different in primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension. In primary pulmonary hypertension, these antibodies in low titre probably reflect endothelial dysfunction. In contrast, in chronic thromboembolic pulmonary hypertension the presence of antibodies in high titre associated with lupus anticoagulant, underlines the role of thrombosis in the pathogenesis of this condition.     

Single photon emission computed tomography in chronic thromboembolic pulmonary hypertension

Background and objective: The management of chronic thromboembolic pulmonary hypertension (CTEPH) is largely dependent on the extent of obstruction in the pulmonary arteries. Planar perfusion scans are commonly used to quantify perfusion defects in CTEPH patients. However, planar scans typically under‐represent the extent of vascular obstruction in CTEPH. We conducted this study to test the hypothesis that SPECT lung perfusion scans are more accurate than planar scans for determining the location and extent of perfusion defects in patients with CTEPH. Methods: Planar ventilation scans, planar and SPECT perfusion scans were performed preoperatively in patients undergoing pulmonary thromboendarterectomy for treatment of CTEPH. Two clinical experts independently documented the segmental anatomy of the vascular obstructions by reviewing clinical records, pulmonary and CT angiograms, and surgical specimens. A nuclear medicine expert documented the segmental anatomy of the perfusion defects observed by planar and SPECT scans independently. Results: Clinical/pathological evaluation disclosed 241 obstructed and 99 unobstructed lung segments in 17 patients. Sensitivity for detecting obstructed segments was significantly higher for SPECT than for planar scanning (63.5 ± 3.1% vs 42.7 ± 3.2%, respectively; P < 0.01). Specificities of SPECT and planar scanning were not significantly different (62.6 ± 4.8% vs 76.8 ± 4.2%, respectively; P = 0.092). Conclusions: The SPECT is more sensitive than planar perfusion scanning for identifying obstructed segments in CTEPH. However, even SPECT under‐represents the true extent of the vascular occlusions in CTEPH.     

Collagen and elastin metabolism in hypertensive pulmonary arteries of rats

We evaluated the processes controlling the accumulation of collagen and elastin in main pulmonary arteries of rats during an episode of hypoxic pulmonary hypertension. Explant cultures of main pulmonary arteries were incubated with [3H]proline to measure collagen and protein synthesis and percent collagen synthesis. Elastin synthesis was measured by [14C]valine incorporation into insoluble elastin. Relative collagen synthesis increased twofold (from 1.1 +/- 0.2 x 10(3) to 2.0 +/- 1.0 x 10(3) disintegrations per minute [14C]hydroxyproline/vessel/hr/mg protein), relative collagen synthesis doubled (from 2% to 4-5% of total protein synthesis), and elastin synthesis increased ninefold (from 0.4 +/- 0.2 x 10(4) to 3.6 +/- 0.6 x 10(4) dpm [14C]valine/vessel/hr/mg protein) in early hypertension. The level of pro alpha l(I) collagen RNA paralleled the relative collagen synthetic rate during the study period. Within 7 days of recovery from hypoxia, collagen and elastin contents were normal. We conclude that collagen and elastin in main pulmonary arteries are synthesized rapidly during an episode of hypoxic pulmonary hypertension and that collagen and elastin are rapidly removed from the hypertensive vessel during normoxic recovery.     

Chronic thromboembolic pulmonary hypertension (CTEPH): updated Recommendations of the Cologne Consensus Conference 2011

In the 2009 European Guidelines on the diagnosis and treatment of pulmonary hypertension (PH), one section covers aspects of pathophysiology, diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The practical implementation of the guidelines for this disease is of crucial importance, because CTEPH is a subset of PH which can potentially be cured by pulmonary endarterectomy (PEA). Nowadays, CTEPH is commonly underdiagnosed and not properly managed. Any patient with unexplained PH should be evaluated for the presence of CTEPH, and a ventilation/perfusion (V/Q) lung scan is recommended as screening method of choice. If the V/Q scan or CT angiography reveals signs of CTEPH, the patient should be referred to a specialized center with expertise in the medical and surgical management of this disease. Every case has to be reviewed by an experienced PEA surgeon for the assessment of operability. In this updated recommendation, important contents of the European guidelines were commented, and more recent information regarding diagnosis and treatment was added.     

Medical therapies for chronic thromboembolic pulmonary hypertension: an evolving treatment paradigm

Pulmonary endarterectomy (PEA) is recommended as the treatment of choice for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, only a proportion of patients fulfill the criteria for surgical intervention. In addition, operated patients with CTEPH may experience a gradual hemodynamic and symptomatic decline related to a secondary hypertensive arteriopathy in the small precapillary pulmonary vessels. It has also been questioned what can be done to reduce risks from PEA surgery to improve outcome in "high risk" patients with CTEPH with substantial impairment of pulmonary hemodynamics before surgery. Such patients may benefit from preoperative reduction of pulmonary vascular resistance by means of medical therapy. Conventional medical treatments, such as anticoagulation, diuretics, digitalis, and chronic oxygen therapy, show low efficacy in the treatment of CTEPH as they do not affect underlying disease processes. Over the last decade, several novel therapies have been developed for pulmonary arterial hypertension (PAH), including prostacyclin analogs (epoprostenol, beraprost, iloprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase-5 inhibitors (sildenafil). Evidence of efficacy in PAH, coupled with studies showing histopathologic similarities between CTEPH and PAH, provides a rationale to extend the use of some of these medications to the treatment of CTEPH. However, direct evidence from clinical trials in CTEPH is limited to date. This article reviews evidence supporting, and issues surrounding, the possible use of novel PAH medications in CTEPH.     

Balloon pulmonary angioplasty vs. pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis

Heart Failure Reviews - Although balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) are effective in chronic thromboembolic pulmonary hypertension (CTEPH), the comparison of...