Controversies, uncertainties and future research on the treatment of chronic thromboembolic pulmonary hypertension

A number of controversies exist regarding the pathophysiology, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Although CTEPH is regarded by many to be a complication of pulmonary embolism (PE) arising subsequent to venous thromboembolism (VTE)-the embolic hypothesis-it has been suggested that PE is rarely the sole cause of CTEPH and that primary arteriopathy with secondary in situ thrombosis may be relevant in the pathogenesis and progression of the disease-the thrombotic hypothesis. A number of lines of evidence support this. Only about half of patients referred with suspected CTEPH have a history of VTE. In addition, data suggest that acute PE is often diagnosed, and possibly misdiagnosed, in patients with preexisting pulmonary artery pathology. There has been much research and debate on the importance of distal arteriopathy in both the initiation and progression of CTEPH. Histopathologic studies have indicated distinct overlap in the microvascular pathology of CTEPH and idiopathic pulmonary arterial hypertension (IPAH), and it has been queried whether class IV CTEPH (increased pulmonary vascular resistance due to distal arteriopathy in the absence of central organized thrombi) and IPAH represent extremes of a disease continuum. Together, these issues may impact on effective diagnosis, preoperative screening criteria for pulmonary endarterectomy surgery, and the likelihood of persistent pulmonary hypertension or even mortality after surgery. They are particularly relevant when considering the possible future use of medical therapies in long-term disease management.     

Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism

Background

Early identification and treatment of chronic thromboembolic pulmonary hypertension (CTEPH) are critical to prevent disease progression. We determined the incidence and risk factors for CTEPH in patients with a first episode of acute pulmonary embolism (PE).

Methods

In this study, consecutive patients with first-episode acute PE were followed for ≤5 years. Pulmonary hypertension (PH) was screened for by echocardiography. Suspected cases were evaluated by right heart catheterization (RHC) and pulmonary angiography (PA). If invasive procedures were not permitted, PH was diagnosed by systolic pulmonary artery pressure (SPAP) >50 mmHg. Diagnosis of CTEPH was confirmed by PA, ventilation/perfusion (V/Q) lung scan, or computed tomography (CT) PA (CTPA).

Results

Overall, 614 patients with acute PE were included (median follow-up, 3.3 years). Ten patients were diagnosed with CTEPH: cumulative incidence 0.8% [95% confidence interval (CI), 0.0-1.6%] at 1 year, 1.3% (95% CI, 0.3-2.3%) at 2 years, and 1.7% (95% CI, 0.7-2.7%) at 3 years. No cases of CTEPH developed after 3 years. History of lower-limb varicose veins [hazard ratio (HR), 4.3; 95% CI, 1.2-15.4; P=0.024], SPAP >50 mmHg at initial PE episode (HR, 23.5; 95% CI, 2.7-207.6; P=0.005), intermediate-risk PE (HR, 1.2; 95% CI, 1.0-1.4; P=0.030), and CT obstruction index over 30% at 3 months after acute PE (HR, 42.5; 95% CI, 4.4-409.8; P=0.001) were associated with increased risk of CTEPH.

Conclusions

CTEPH was not rare after acute PE in this Chinese population, especially within 3 years of diagnosis. Lower-limb varicose veins, intermediate-risk PE with elevated SPAP in the acute phase, and residual emboli during follow-up might increase the risk of CTEPH.     

Incidence and prevalence of chronic thromboembolic pulmonary hypertension: from acute to chronic pulmonary embolism

The incidence and prevalence of chronic thromboembolic pulmonary hypertension (CTEPH) are yet to be accurately determined and may be significantly underestimated. Historically, the occurrence of CTEPH in patients diagnosed with acute pulmonary embolism (PE) has been considered rare. Data from autopsy studies estimated the incidence of CTEPH at 1-3% overall and at 0.1-0.5% in patients surviving acute PE. Data indicate that each year in the United States, approximately 600,000 individuals suffer an acute pulmonary embolic event and that the annual number of new CTEPH cases in the United States is between 500 and 2,500. This may underestimate the true frequency of CTEPH because the disease is often misdiagnosed due to nonspecific symptoms and variable disease course. A monocenter, prospective, longitudinal study assessing symptomatic CTEPH in patients with acute PE but without prior venous thromboembolism recently estimated the cumulative incidence of CTEPH to be 1.0% 6 mo after PE, 3.1% after 1 yr, and 3.8% after 2 yr; overall post-PE incidence was approximately 3%. Further studies are needed to better define the true rate of CTEPH. Acute embolic events can occur without symptoms, and symptomatic PE is often overlooked or misdiagnosed in practice. CTEPH is often identified during diagnostic work-up in patients with unexplained pulmonary hypertension, many of whom lack medical history suggesting previous PE. In a recent study in 142 consecutive patients with CTEPH, 90 (63%) had no previous history of symptomatic venous thromboembolism. Further prospective epidemiologic studies are needed to better define the incidence and prevalence of CTEPH.     

Update on chronic thromboembolic pulmonary hypertension

Chronic, unresolved thromboemboli are an important cause of pulmonary hypertension (PH) with specific treatment strategies differing from other types of PH. Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 PH by the World Health Organization. It is a rare, but underdiagnosed, complication of acute pulmonary embolism that does not resolve and results in occlusion of large pulmonary arteries with a fibro-thrombotic material. The etiology of CTEPH remains uncertain, and it is unknown why certain patients with acute pulmonary embolism develop this disorder. The evaluation for CTEPH is an important part of the evaluation for PH in general, and it is crucial not to overlook this diagnosis, as it is the only form of PH that is potentially curable. Patients diagnosed with CTEPH should be referred to an expert center for consideration of pulmonary endarterectomy, and surgical removal of the chronic thromboembolic material. Not all patients with CTEPH are surgical candidates, however, and there are emerging treatments—medical therapy and balloon pulmonary angioplasty—that have shown benefit in this patient population. Without treatment, CTEPH can lead to progressive pulmonary vascular obstruction, right heart failure, and death. Thus, it is important for clinicians to recognize this subtype of PH. In this review, we provide an overview of current understanding of the pathogenesis of CTEPH and highlight recommendations and recent advances in the evaluation and treatment of CTEPH.     

Update on the roles of imaging in the management of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH), classified as group 4 pulmonary hypertension (PH), is caused by stenosis and obstruction of the pulmonary arteries by organized thrombi that are incompletely resolved after acute pulmonary embolism. The prognosis of patients with CTEPH is poor if untreated; however, in expert centers with multidisciplinary teams, a treatment strategy for CTEPH has been established, dramatically improving its prognosis. CTEPH is currently not a fatal disease and is the only curable form of PH. Despite these advances and the establishment of treatment approaches, early diagnosis is still challenging, especially for non-experts, for several reasons. One of the reasons for this is insufficient knowledge of the various diagnostic imaging modalities, which are essential in the clinical practice of CTEPH. Imaging modalities should detect the following pathological findings: lung perfusion defects, thromboembolic lesions in pulmonary arteries, and right ventricular remodeling and dysfunction. Perfusion lung scintigraphy and catheter angiography have long been considered gold standards for the detection of perfusion defects and assessment of vascular lesions, respectively. However, advances in imaging technology of computed tomography and magnetic resonance imaging have enabled the non-invasive detection of these abnormal findings in a single examination. Cardiac magnetic resonance (CMR) is the gold standard for evaluating the morphology and function of the right heart; however, state-of-the-art techniques in CMR allow the assessment of cardiac tissue characterization and hemodynamics in the pulmonary arteries. Comprehensive knowledge of the role of imaging in CTEPH enables appropriate use of imaging modalities and accurate image interpretation, resulting in early diagnosis, determination of treatment strategies, and appropriate evaluation of treatment efficacy. This review summarizes the current roles of imaging in the clinical practice for CTEPH, demonstrating the characteristic findings observed in each modality.     

From acute pulmonary embolism to chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH), a disease associated with considerable morbidity and mortality, is the consequence of unresolved thromboembolic occlusion in pulmonary vasculature. CTEPH was considered a rare disease occurring in 0.1-0.5% of patients with pulmonary emboli who survive. Recently, a much higher incidence was reported and some risk factors such as a previous pulmonary embolism (PE), an idiopathic form of PE and the severity of perfusion defect at the time of diagnosis have been identified. Exertional dyspnea is the main symptom at the beginning of the disease while later on patients may suffer from syncope related to low cardiac output or hemoptysis as a consequence of high pulmonary artery pressure. In suspected patients, a confirmation of pulmonary arterial hypertension should be ascertained at transthoracic echocardiography. Then the obstructive nature of the disease may be revealed by ventilation-perfusion lung scan but is better described at pulmonary angiography. Computed tomography scan may be useful to rule out confounding disorders. To prevent recurrences, long-term oral anticoagulants to maintain an INR between 2.5 and 3.5 (target 3.0) are indicated. Treatment of severe CTEPH is essentially surgical (thromboendarterectomy). This procedure may be difficult when distal branches of pulmonary vascular tree are involved. In selected cases, alternative therapies may be the arterial pulmonary vessel angioplasty and lung transplantation.     

The post-PE syndrome: a new concept for chronic complications of pulmonary embolism

Long-term follow-up studies have consistently demonstrated that after an episode of acute pulmonary embolism (PE), half of patients report functional limitations and/or decreased quality of life up to many years after the acute event. Incomplete thrombus resolution occurs in one-fourth to one-third of patients. Further, pulmonary artery pressure and right ventricular function remain abnormal despite adequate anticoagulant treatment in 10–30% of patients, and 0.5–4% is diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) which represents the most severe long term complication of acute PE. From these numbers, it seems that CTEPH itself is the extreme manifestation of a much more common phenomenon of permanent changes in pulmonary artery flow, pulmonary gas exchange and/or cardiac function caused by the acute PE and associated with dyspnea and decreased exercise capacity, which in analogy to post-thrombotic syndrome after deep vein thrombosis could be referred to as the post-pulmonary embolism syndrome. The acknowledgement of this syndrome would both be relevant for daily clinical practice and also provide a concept that aids in further understanding of the pathophysiology of CTEPH. In this clinically oriented review, we discuss the established associations and hypotheses between the process of thrombus resolution or persistence, lasting hemodynamic changes following acute PE as well as the consequences of a PE diagnosis on long-term physical performance and quality of life.     

Chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially life-threatening condition characterized by obstruction of pulmonary arterial vasculature by acute or recurrent thromboemboli with subsequent organization, leading to progressive pulmonary hypertension and right heart failure. Until relatively recently, CTEPH was a diagnosis made primarily at autopsy, but advances made in diagnostic modalities and surgical pulmonary endarterectomy techniques have made this disease treatable and even potentially curable. Although published guidelines are available, in the absence of randomized controlled trials regarding CTEPH there is a lack of standardization, and treatment options have to be individualized.     

Identification of chronic thromboembolic pulmonary hypertension on CTPAs performed for diagnosing acute pulmonary embolism depending on level of expertise

BackgroundExpert reading often reveals radiological signs of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic PE on computed tomography pulmonary angiography (CTPA) performed at the time of acute pulmonary embolism (PE) presentation preceding CTEPH. Little is known about the accuracy and reproducibility of CTPA reading by radiologists in training in this setting.ObjectivesTo evaluate 1) whether signs of CTEPH or chronic PE are routinely reported on CTPA for suspected PE; and 2) whether CTEPH-non-expert readers achieve comparable predictive accuracy to CTEPH-expert radiologists after dedicated instruction.MethodsOriginal reports of CTPAs demonstrating acute PE in 50 patients whom ultimately developed CTEPH, and those of 50 PE who did not, were screened for documented signs of CTEPH. All scans were re-assessed by three CTEPH-expert readers and two CTEPH-non-expert readers (blinded and independently) for predefined signs and overall presence of CTEPH.ResultsSigns of chronic PE were mentioned in the original reports of 14/50 cases (28%), while CTEPH-expert radiologists had recognized 44/50 (88%). Using a standardized definition (≥3 predefined radiological signs), moderate-to-good agreement was reached between CTEPH-non-expert readers and the experts’ consensus (k-statistics 0.46; 0.61) at slightly lower sensitivities. The CTEPH-non-expert readers had moderate agreement on the presence of CTEPH (κ-statistic 0.38), but both correctly identified most cases (80% and 88%, respectively).ConclusionsConcomitant signs of CTEPH were poorly documented in daily practice, while most CTEPH patients were identified by CTEPH-non-expert readers after dedicated instruction. These findings underline the feasibility of achieving earlier CTEPH diagnosis by assessing CTPAs more attentively.     

Should Transesophageal Echocardiography Become a Routine Test in Patients with Suspected Pulmonary Thromboembolism?

Pulmonary thromboembolism presents in two clinical subsets: acute pulmonary embolism (PE) with or without right heart thrombi or paradoxical embolism and chronic thromboembolic pulmonary hypertension (CTEPH). Both PE and CTEPH have been underdiagnosed and carry high mortality rates. Acute massive PE is a hemodynamic entity leading to right ventricular overload readily identified with the use of transthoracic echocardiography. Transesophageal echocardiography (TEE) is a noninvasive bedside technique that has high diagnostic accuracy for the detection of central pulmonary thromboembolism. Due to the high prevalence of central pulmonary thromboembolism in acute PE, TEE is a useful method to provide the necessary proof for the institution of thrombolytic therapy. In the subset of patients with acute PE combined with right heart thrombi or paradoxical embolism, TEE is the technique of choice to guide surgery. CTEPH presents as primary pulmonary hypertension, but it has become a surgically curable disease. TEE is a fast, fairly sensitive, and highly specific diagnostic bedside modality to select surgical candidates with CTEPH. TEE should become a routine test in patients with suspected massive acute PE, suspected right heart thrombi, or paradoxical embolism associated with acute pulmonary embolism and in patients with primary pulmonary hypertension to select those having CTEPH who are suitable for surgery.     

Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by proximal pulmonary vascular obstruction by thrombo-fibrotic material, the origin of which has not been elucidated. Enhanced inflammation could contribute to persistent obstruction by impairing pulmonary vascular cell function in CTEPH. We investigated C-reactive protein (CRP) effects on pulmonary vascular cell function in vitro. Primary cultures of proximal pulmonary endothelial cells (ECs) and smooth muscle cells (SMCs) from CTEPH and nonthromboembolic pulmonary hypertension (PH) patients were established. Recombinant CRP effects on mitogenic activity, adhesion capacity, endothelin-1 and von Willebrand factor (vWF) secretion and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1 expression were investigated in ECs and/or SMCs. Expression of the CRP receptor, lectin-like oxidised low-density lipoprotein receptor (LOX)-1, was evaluated in proximal pulmonary arterial tissue and cells by Western blotting and immunofluorescence. CRP increased CTEPH-SMC proliferation by 250%. CRP increased adhesion capacity, endothelin-1 and vWF secretion by CTEPH-ECs by 37%, 129% and 694%, respectively. CRP-induced adhesion of CTEPH-ECs to monocytes was mediated by ICAM-1. CRP had no effect on cells from nonthromboembolic PH patients, probably because of overexpression of LOX-1 in CTEPH. Local expression of CRP was detected in ECs and SMCs within pulmonary arterial tissue. CRP may contribute to persistent obstruction of proximal pulmonary arteries in CTEPH by promoting vascular remodelling, endothelial dysfunction and in situ thrombosis.     

慢性血栓栓塞性肺动脉高压诊疗的研究进展

慢性血栓栓塞性肺动脉高压(CTEPH)是急性肺栓塞最严重的并发症,由于缺乏特异性的临床表现,常常会漏诊,造成患者死亡。近年来,虽然多种影像技术已应用于CTEPH 患者,但在CTEPH 的诊断、预后及治疗的选择决策上仍有不确定性,熟练掌握各类影像技术特点,可提升利用率。目前肺动脉内膜剥脱术是治疗CTEPH 的首选方式,对于无法手术治疗的患者,经皮肺动脉成形术可作为一种新的治疗选择。本文主要综述了影像学检查在CTEPH 的诊断、治疗及预后评估中的研究进展。     

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.     

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.     

Pilot study comparing SPECT perfusion scintigraphy with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension

Background and objective: The management of chronic thromboembolic pulmonary hypertension (CTEPH) is dependent on the extent of pulmonary artery obstruction, which is usually evaluated by planar perfusion scanning and CT pulmonary angiography (CTPA). We previously reported that SPECT perfusion scanning is more sensitive than planar scanning for detecting vascular obstruction in CTEPH. The purpose of this study is to compare SPECT with CTPA for detecting segmental pulmonary artery obstruction in CTEPH. Methods: SPECT and CTPA were carried out before pulmonary endarterectomy in 12 CTEPH patients. Field experts documented the anatomical distribution of perfusion defects disclosed by SPECT, the anatomical distribution of pulmonary arterial filling defects disclosed by CTPA and the segmental anatomy of the vascular obstructions based on a review of clinical and pathology records, without knowledge of scan results. Results: Clinical/pathological evaluation disclosed 140 obstructed (15.5 ± 2.5 per patient) and 40 unobstructed lung segments. SPECT scanning identified 87/140 (62%) of the obstructed and 29/40 (72%) of the unobstructed segments. By comparison, CTPA identified 67/140 (47.8%) of the obstructed and 32/40 (80%) of the unobstructed segments. Sensitivity for detecting obstructed segments was significantly higher for SPECT compared with CTPA (62 ± 4.1% vs 47.8 ± 2.9%, respectively; P = 0.03). Conclusions: SPECT is more sensitive than CTPA for identifying obstructed segments in this small sample of CTEPH patients. However, even SPECT under‐represents the extent of vascular obstruction from this disease.     

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.     

Thrombembolien und pulmonale Hypertonie

Chronic thrombembolic pulmonary hypertension (CTEPH) represents a common type of pulmonary hypertension and is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction. Unresolved thrombemboli and possible in situ thrombosis lead to obstruction of pulmonary arteries resulting in elevated pressures in those areas of the vasculature that were spared from thromboembolic occlusion. This can resemble pathomechanisms in patients with pulmonary arterial hypertension. However the understanding of pulmonary vascular remodeling in patients with CTEPH is incomplete. Pulmonary endarterectomy of the obstructing thromboembolic material should be performed in patients who are accessible to surgery. In patients who are judged inoperable or with persistent pulmonary hypertension treatment with pulmonary arterial hypertension medications can be considered. This could contribute to improved clinical outcome and survival, whereas further controlled studies are required addressing this question.     

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.     

Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment.

Chronic, major vessel thromboembolic pulmonary hypertension (CTEPH), is an uncommon condition which, in the past, was an autopsy curiosity. Advances in diagnostic approaches, surgical techniques and postoperative management have transformed this disorder into a potentially curable form of pulmonary hypertension. The predominant symptom is unexplained dyspnoea on exertion. In patients with this complaint, CTEPH should be considered. Numerous pitfalls exist along the diagnostic path. Perfusion lung scans point toward the diagnosis, but often underestimate the extent of central arterial obstruction. Pulmonary angiography is the key diagnostic procedure, but the many patterns of thrombus organization-recanalization require a base of experience for proper interpretation. Criteria for selection of patients for surgery are evolving, but assurance of thrombus accessibility to surgery is critical. Surgical thromboendarterectomy bears no resemblance to acute pulmonary embolectomy. Recognition of thrombus (versus normal intima), meticulous dissection and a bloodless surgical field are essential for adequate restoration of pulmonary vascular patency. Multiple complications may arise postoperatively, and detailed attention to these is required for patient survival. With a co-ordinated, multi-specialty team effort, however, haemodynamic and clinical outcomes have been rewarding and persist long-term. Surgical mortality should steadily decline with such a co-ordinated effort, as well as earlier diagnosis and advances in surgical and postoperative management techniques.     

Prostacyclin therapy before pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension

OBJECTIVES: The continuous IV administration of prostacyclin improves pulmonary hemodynamics and prognosis in patients with primary pulmonary hypertension. We investigated whether the administration of prostacyclin therapy to patients before they undergo pulmonary thromboendarterectomy ameliorates pulmonary hypertension in patients with the most severe form of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Of the 33 patients with CTEPH who were candidates for pulmonary thromboendarterectomy, 12 patients with severe pulmonary hypertension (pulmonary vascular resistance, > 1,200 dyne. s. cm(-5)) received IV prostacyclin prior to undergoing pulmonary thromboendarterectomy. Right heart catheterization and plasma brain natriuretic peptide (BNP) measurements were repeated at baseline, immediately before surgery, and 1 month after surgery. RESULTS: During a mean (+/- SEM) follow-up period of 46 +/- 12 days, the IV administration of prostacyclin resulted in a 28% decrease in pulmonary vascular resistance (1,510 +/- 53 to 1,088 +/- 58 dyne. s. cm(-5); p < 0.001) before surgery. Prostacyclin therapy markedly decreased plasma BNP level (547 +/- 112 to 188 +/- 30 pg/mL; p < 0.01), suggesting improvement in right heart failure. Pulmonary thromboendarterectomy caused a further reduction of pulmonary vascular resistance (302 +/- 47 dyne. s. cm(-5)) and plasma BNP levels (60 +/- 11 pg/mL) compared to each preoperative value (p < 0.05). Operative mortality rates were relatively low (8.3%) in patients with the most severe form of CTEPH. CONCLUSION: The IV administration of prostacyclin caused beneficial hemodynamic effects in patients with severe CTEPH and may serve as pretreatment for patients undergoing pulmonary thromboendarterectomy.