Pulmonary Endarterectomy Surgery Research Articles

The role of pharmacotherapy in the treatment of chronic thromboembolic pulmonary hypertension (RCD code: II-1A.5)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease caused by chronic obstruction of major pulmonary arteries. The median age of patients at diagnosis of CTEPH is 63 years and both genders are equally affected. The symptoms are usually nonspecific, particularly in the early stages of the disease, which significantly delays the diagnosis. All patients with pulmonary hypertension (PH) of the unknown aetiology should be diagnosed for CTEPH, even without the information on pulmonary embolism in the medical history. Ventilation-perfusion scintigraphy of the lungs has the highest sensitivity in the diagnosis of CTEPH. A positive result of scintigraphy suggestive of CTEPH is not enough to diagnose the disease. Right heart catheterization and angiography of the pulmonary arteries definitively confirm the diagnosis. All patients with CTEPH should receive chronic oral anticoagulation using generally vitamin K antagonists (warfarin, acenocumarol). Pulmonary endarterectomy (PEA) is the only effective treatment for eliminating the cause of the disease. However, not all patients can be referred for pulmonary endarterectomy surgery. According to data from the European CTEPH Registry of the years 2007-2009, over 40% of patients is not subjected to the operation mainly due to the distal location of thromboembolic changes. Currently, riociguat is the only approved therapeutic agent for the pharmacological treatment of inoperable/persistent CTEPH. In some cases, Off-lebel use of drugs approved for PAH may be considered in symptomatic patients with inoperable CTEPH/persistent PH after PEA. Recent advances in balloon pulmonary angioplasty make it a promising therapeutic alternative for selected patients with non-operable CTEPH. JRCD 2015; 2 (2): 4–8

S37 Vascular Endothelial Cell Growth Factor-a (vegf-a) Signalling And Neovascularisation Of Pulmonary Endarterectomy Material In Chronic Thromboembolic Pulmonary Hypertension (cteph)

Background Despite recent advances in the medical treatment of patients with CTEPH, relatively little is understood surrounding the underlying pathological mechanisms. Many patients have a historical documented venous thromboembolic event (VTE) and consequently, failed resolution of an acute VTE has been proposed as a key initiating factor in the subsequent development of CTEPH. Here we investigated VEGF-A levels, a key regulator of angiogenesis, in CTEPH patients prior to and following pulmonary endarterectomy (PEA) surgery to remove the thromboembolic material. We also examined the surgically excised PEA material and measured neovessel density in distal regions of the specimens. Methods and results Serum VEGF-A levels were measured by Luminex array in paired serum samples from n = 44 patients at baseline (before PEA surgery) and following PEA surgery. Following PEA surgery, serum VEGF-A levels were significantly reduced compared to baseline measurements (159.5 ± 174.8 vs. 194.4 ± 198.2, p = 0.0182). Distal regions of excised PEA material were cross sectioned and processed for histopathological examination. Neovessel density was calculated by counting the absolute number of vascular channels present within a cross-sectional area and normalised to tissue area using Image J. We also measured the time between documented VTE and subsequent PEA surgery (VTE-PEA time) in patients with a documented VTE (n = 40/44 [90%] patients), and identified an inverse correlation between neovessel density and VTE–PEA time. Conclusions Extensive angiogenesis was evident in distal PEA material from patients with CTEPH. VEGF-A is known to be a key regulator of angiogenesis and serum levels were significantly reduced following PEA surgery. Interestingly, a significant inverse correlation between neovessel density and VTE-PEA time was observed indicating that in the early stages following VTE, extensive angiogenesis is evident within the thromboembolus. Taken together these data provide further evidence that angiogenesis is an important mechanism in the attempted resolution of a VTE.

Pulmonary endarterectomy: Part II. Operation, anesthetic management, and postoperative care.

Chronic thromboembolic pulmonary hypertension (CTEPH) results from recurrent or incomplete resolution of pulmonary embolism. CTEPH is much more common than generally appreciated. Although pulmonary embolism (PE) affects a large number of Americans, chronic pulmonary thromboembolic hypertension remains underdiagnosed. It is imperative that all patients with pulmonary hypertension (PH) be screened for the presence of CTEPH since this form of PH is potentially curable with pulmonary endarterectomy (PEA) surgery. The success of this procedure depends greatly on the collaboration of a multidisciplinary team approach that includes pulmonary medicine, cardiothoracic surgery, and cardiac anesthesiology. This review, based on the experience of more than 3000 pulmonary endarterectomy surgeries, is divided into 2 parts. Part I focuses on the clinical history and pathophysiology, diagnostic workup, and intraoperative echocardiography. Part II focuses on the surgical approach, anesthetic management, postoperative care, and complications.

What Costs Can a U.S. Health Plan Expect if an Enrollee Has Chronic Thromboembolic Pulmonary Hypertension? A Guideline-Based Estimate of Healthcare Resource Use and Cost

SESSION TITLE: DVT/PE Posters

Right ventricular reverse remodeling after pulmonary endarterectomy: magnetic resonance imaging and clinical and right heart catheterization assessment.

The objective of this study was to assess the effect of pulmonary endarterectomy (PEA) on right ventricular (RV) reverse remodeling using magnetic resonance imaging (MRI) and to correlate MRI findings with clinical and hemodynamic outcomes postsurgery. We performed a retrospective analysis in 72 patients undergoing PEA surgery in whom MRI and right heart catheterization (RHC) were performed preoperation and 3 months postoperation. RV volumes and mass were assessed by MRI. Continuous variables were expressed as means, changes were compared with a paired t test, and associations between the variables were explored using Pearson correlation coefficients. The mean age was 57 years, and 51% were male. Both RV end-diastolic volume (EDV; 176-117 mL; P < 0.001) and RV end-systolic volume (ESV; 129-64 mL; P < 0.001) reduced significantly following PEA. Preoperative pulmonary artery pressure (PAP) correlated moderately with ESV (r = 0.46, P < 0.001). Postoperatively, PAP correlated with EDV (r = 0.45, P < 0.001) and ESV (r = 0.44, P < 0.001). Moderate correlation was present between hemodynamic parameters: PAP, pulmonary vascular resistance, and right atrial pressure with pre- and postoperation end-systolic and end-diastolic RV mass (P < 0.001). RHC and MRI measurements of cardiac output and RV volumes were significantly different (P < 0.001). In conclusion, RV reverse remodeling, as measured by improvement in RV volumes and mass by MRI, was observed for 3 months in patients who underwent PEA surgery. This is the largest series of patients with pre- and post-PEA MRI assessment so far reported. MRI detects changes in parameters reflecting cardiac remodeling and pulmonary clearance, but measurements are significantly different from those of RHC.

Successful treatment of pulmonary angiosarcoma along with pulmonary endarterectomy and pulmonary valve replacement

Pulmonary endarterectomy (PEA) is an effective treatment of choise for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Symptoms of pulmonary angiosarcoma (PS) can mimic CTEPH, showing similar radiological findings. In this article, we report on a 69-year-old male case with progressive dyspnea and angina. Clinical and radiographic examination revealed pulmonary hypertension with a mass extending to the pulmonary valve, indicating potential PS in the differential diagnosis. A pulmonary valve replacement was performed concurrently with PEA surgery. Histological examination confirmed the diagnosis of PS. The patient was referred into a local oncology service for adjuvant chemotherapy.

An Australian Tertiary Referral Center Experience of the Management of Chronic Thromboembolic Pulmonary Hypertension

The objective of this study was to report the outcome of pulmonary endarterectomy (PEA) surgery performed for chronic thromboembolic pulmonary hypertension (CTEPH) at a single tertiary center. The prospective study consisted of 35 patients with surgically amenable CTEPH undergoing PEA between September 2004 and September 2010. The main outcome measures were Functional (New York Heart Association [NYHA] class, 6-Minute Walk Distance), hemodynamic (echocardiography, right heart catheterization, and cardiac MRI), and outcome data (morbidity and mortality). Following PEA, there were significant improvements in NYHA class (pre 2.9±0.7 vs. post 1.3±0.5, P < 0.0001), right ventricular systolic pressure (pre 77.4±24.8 mmHg vs. post 45.1±24.9 mmHg, P = 0.0005), 6-Minute Walk Distance (pre 419.6±109.4 m vs. post 521.6±83.5 m, P = 0.0017), mean pulmonary artery pressure (pre 41.8±15.3 mmHg vs. post 24.7±8.8 mmHg, P = 0.0006), and cardiac MRI indices (end diastolic volume pre 213.8±49.2 mL vs. post 148.1±34.5 mL, P < 0.0001; ejection fraction pre 40.7±9.8 mL vs. post 48.1±8.9 mL, P = 0.0069). The mean cardiopulmonary bypass time was 258.77±26.16 min, with a mean circulatory arrest time of 43.83±28.78 min, a mean ventilation time of 4.7±7.93 days (range 0.2-32.7), and a mean intensive care unit stay of 7.22±8.71 days (range 1.1-33.8). Complications included reperfusion lung injury (20%), persistent pulmonary hypertension (17.1%), slow respiratory wean (25.7%), pericardial effusion (11.4%), and cardiac tamponade (5.7%). 1-year mortality post-procedure was 11.4%. Pulmonary endarterectomy can be performed safely with relatively low mortality.

Pulmonary endarterectomy: outcomes in patients aged &gt;70

Advanced age is not a barrier to cardiac surgery, with reports demonstrating excellent outcomes, but the effect of age on more complex surgery has not been studied. We assessed the outcomes of pulmonary endarterectomy (PEA) surgery in patients aged >70. A retrospective review of consecutive patients who underwent PEA between January 2006 and March 2011 at a national referral centre. The total cohort was dichotomized according to age on the day of surgery, either below or above 70 years. Outcomes were in-hospital mortality, overall survival and the length of ICU and hospital stays. Four hundred and eleven patients underwent PEA during the 5-year period. The mean age was 56.9 years (range, 17-84 years). The in-hospital mortality was 14 of 308 (4.6%) for patients <70 years compared with 8 of 103 (7.8%) for patients ≥70 years (P = 0.21). The overall survival at 1, 2 and 3 years was 91.4, 89.9 and 87.7% in the <70-year old group and 85.9, 84.1 and 84.1% in the >70-year old group (log-rank test, P = 0.07), respectively. The length of ICU and in-hospital stays was longer in the >70-year old group, by 1 and 2 days, respectively (P = 0.005 and 0.001). PEA surgery in patients ≥70 years is safe and carries a comparable risk of early mortality in younger patients, but there is an increase in resource use due to longer ICU and hospital stays. Advanced age should be taken into consideration when assessing suitability for PEA, but age per se should not be a contraindication to surgery.

Evaluation of Patients with Chronic Thromboembolic Pulmonary Hypertension for Pulmonary Endarterectomy

Pulmonary hypertension as a result of chronic thromboembolic disease (CTEPH) is potentially curable with pulmonary endarterectomy surgery. Consequently, correctly diagnosing patients with this type of pulmonary hypertension and evaluating these patients with the goal of establishing their candidacy for surgical intervention is of utmost importance. And as advancements in surgical techniques have allowed successful resection of segmental-level chronic thromboembolic disease, the number of CTEPH patients that are deemed suitable surgical candidates has expanded, making it even more important that the evaluation be conducted with greater precision. This article will review a diagnostic approach to patients with suspected chronic thromboembolic disease with an emphasis on the criteria considered in selecting patients for pulmonary endarterectomy surgery.

State-of-the-art chronic thromboembolic pulmonary hypertension diagnosis and management

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease caused by chronic obstruction of pulmonary artery branches following episodes of pulmonary embolism and incomplete thrombus resolution. The prognosis of patients with CTEPH is poor unless an early diagnosis is made and treatment is initiated. Chest radiography and echocardiography are used in the initial assessment of suspected pulmonary hypertension. A diagnosis of CTEPH may be confirmed by the presence of a mismatched wedge-shaped perfusion deficit during ventilation/perfusion scintigraphy or characteristic findings during multi-slice computed tomography (CT) angiography, including a mosaic perfusion pattern, dilatation of proximal pulmonary arteries and right heart chambers, and the presence of vascular stenosis or obstruction. Prior to possible surgery, pulmonary angiography remains the definitive diagnostic technique, indicating the site and accessibility of the obstruction. However, many centres utilise CT and magnetic resonance imaging following recent advances in these noninvasive techniques. Haemodynamic evaluation via right heart catheterisation is also mandatory, as pulmonary vascular resistance is the most important determinant of both prognosis and the risk associated with pulmonary endarterectomy surgery. Accurate CTEPH diagnosis and characterisation of its extent and distribution are imperative to allow the prompt initiation of treatment, particularly surgical pulmonary endarterectomy in eligible patients.

Risk factors for chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by obstruction and vascular remodelling of pulmonary arteries following pulmonary embolism. Risk factors that predispose patients to CTEPH include the size of the initial thrombus and numerous associated host or medical conditions. Haemostatic risk factors include elevated levels of factor VIII and phospholipid antibodies or intrinsic abnormalities in fibrinogen. Medical conditions that are associated with an increased risk of CTEPH include a history of splenectomy, cancer, ventriculoatrial shunt, chronic inflammatory disease, antiphospholipid antibodies and hypothyroidism. Although CTEPH is potentially curable by pulmonary endarterectomy (PEA), up to 40% of patients evaluated for PEA may be denied surgery depending on the level of surgical experience and disease accessibility after pre-operative assessment. Furthermore, an estimated 10-15% of patients are at risk for residual pulmonary hypertension following PEA surgery, due to significant concomitant small-vessel disease. However, pre-operative identification of small-vessel involvement remains a challenge. The current medications effective in the treatment of pulmonary arterial hypertension have not demonstrated efficacy in CTEPH. Accordingly, identification of CTEPH, followed by early referral for evaluation and treatment by an experienced PEA centre, is recommended.

Circulatory arrest versus cerebral perfusion during pulmonary endarterectomy surgery (PEACOG): a randomised controlled trial

For some surgical procedures to be done, a patient's blood circulation needs to be stopped. In such situations, the maintenance of blood flow to the brain is perceived beneficial even in the presence of deep hypothermia. We aimed to assess the benefits of the maintenance of antegrade cerebral perfusion (ACP) compared with deep hypothermic circulatory arrest (DHCA). Patients aged 18-80 years undergoing pulmonary endarterectomy surgery in a UK centre (Papworth Hospital, Cambridge) were randomly assigned with a computer generated sequence to receive either DHCA for periods of up to 20 min at 20°C or ACP (1:1 ratio). The primary endpoint was change in cognitive function at 12 weeks after surgery, as assessed by the trail-making A and B tests, the Rey auditory verbal learning test, and the grooved pegboard test. Patients and assessors were masked to treatment allocation. Primary analysis was by intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN84972261. We enrolled 74 of 196 screened patients (35 to receive DHCA and 39 to receive ACP). Nine patients crossed over from ACP to DHCA to allow complete endarterectomy. At 12 weeks, the mean difference between the two groups in Z scores (the change in cognitive function score from baseline divided by the baseline SD) for the three main cognitive tests was 0·14 (95% CI -0·14 to 0·42; p=0·33) for the trail-making A and B tests, -0·06 (-0·38 to 0·25; p=0·69) for the Rey auditory verbal learning test, and 0·01 (-0·26 to 0·29; p=0·92) for the grooved pegboard test. All patients showed improvement in cognitive function at 12 weeks. We recorded no significant difference in adverse events between the two groups. At 12 weeks, two patients had died (one in each group) [corrected]. Cognitive function is not impaired by either ACP or DHCA. We recommend circulatory arrest as the optimum modality for patients undergoing pulmonary endarterectomy surgery. J P Moulton Charitable Foundation.

Isolated Large Vessel Pulmonary Vasculitis as a Cause of Chronic Obstruction of the Pulmonary Arteries

Isolated pulmonary artery involvement by large vessel vasculitis is rare. This case report describes two patients with large vessel pulmonary vasculitis initially thought to have chronic thromboembolic pulmonary hypertension who had their diagnosis revised following pulmonary endarterectomy surgery. Advances in imaging techniques such as positron emission tomography and magnetic resonance imaging have permitted complementary radiological methods of diagnosis and follow up of large vessel disease and these are discussed in conjunction with the immunosuppressive and operative management of these patients.

P258 Is Chronic Thromboembolic Pulmonary Hypertension (CTEPH) under diagnosed in the UK?

IntroductionChronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare but treatable condition. In selected cases Pulmonary Endarterectomy (PEA) surgery is potentially curative, with 80–85 procedures performed annually at a single national...

P32 Delivering pulmonary hypertension services—5 year experience from a Satellite centre

IntroductionThere are currently no National Commissioning Group (NCG) designated Pulmonary Hypertension (PH) centres in the South West. As a result patients can travel up to 300 miles to access specialist...

Safety and Efficacy of Aprotinin and Tranexamic Acid in Pulmonary Endarterectomy Surgery With Hypothermia: Review of 200 Patients

The effectiveness and safety of aprotinin in cardiac surgery has been questioned. The study aim was to compare both the blood-sparing effect and side effects of aprotinin and tranexamic acid in patients undergoing pulmonary endarterectomy. Data were analyzed retrospectively for 200 consecutive patients who underwent pulmonary endarterectomy between October 2006 and September 2009. Pulmonary endarterectomy was performed with deep hypothermia (20°C) in all patients. Antifibrinolytic therapy changed from aprotinin to tranexamic acid in June 2008 after the withdrawal of aprotinin in the United Kingdom. Mean age was 55.9 years, and 58% of subjects were male. One hundred patients were studied in each group. Postoperatively, a higher incidence of seizures in the first 48 hours was seen with tranexamic acid compared with aprotinin (11% versus 4%, p = 0.06). This difference became statistically significant when excluding patients with structural brain lesions from both groups (7 versus 0, p = 0.02). Tranexamic acid patients had significantly higher median blood loss (700 mL versus 525 mL, p = 0.01). There was no significant difference between the groups in reexploration for bleeding, renal failure requiring hemofiltration, intensive care unit stay, median total stay in hospital, or in-hospital mortality. In our experience of patients undergoing pulmonary endarterectomy, the tranexamic acid group had a higher median blood loss and more seizures. The trend to increased seizure frequency in the tranexamic acid group may be a direct consequence of this treatment, consistent with other recently published reports.

Diagnostic Evaluation and Management of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Practice Guideline

Pulmonary embolism is a common condition. Some patients subsequently develop chronic thromboembolic pulmonary hypertension (CTEPH). Many care gaps exist in the diagnosis and management of CTEPH patients including lack of awareness, incomplete diagnostic assessment, and inconsistent use of surgical and medical therapies. A representative interdisciplinary panel of medical experts undertook a formal clinical practice guideline development process. A total of 20 key clinical issues were defined according to the patient population, intervention, comparator, outcome (PICO) approach. The panel performed an evidence-based, systematic, literature review, assessed and graded the relevant evidence, and made 26 recommendations. Asymptomatic patients postpulmonary embolism should not be screened for CTEPH. In patients with pulmonary hypertension, the possibility of CTEPH should be routinely evaluated with initial ventilation/perfusion lung scanning, not computed tomography angiography. Pulmonary endarterectomy surgery is the treatment of choice in patients with surgically accessible CTEPH, and may also be effective in CTEPH patients with disease in more 'distal' pulmonary arteries. The anatomical extent of CTEPH for surgical pulmonary endarterectomy is best assessed by contrast pulmonary angiography, although positive computed tomography angiography may be acceptable. Novel medications indicated for the treatment of pulmonary hypertension may be effective for selected CTEPH patients. The present guideline requires formal dissemination to relevant target user groups, the development of tools for implementation into routine clinical practice and formal evaluation of the impact of the guideline on the quality of care of CTEPH patients. Moreover, the guideline will be updated periodically to reflect new evidence or clinical approaches.

Outcome after Combined Pulmonary Endarterectomy and Mitral Valve Replacement

Concomitant pulmonary endarterectomy and cardiac surgery has rarely been described in the literature. We report a 30-year-old patient who underwent pulmonary endarterectomy and concomitant mitral valve replacement associated with closure of a patent foramen ovale.

Current differences in referral patterns for pulmonary endarterectomy in the UK

Pulmonary endarterectomy (PEA) surgery is the treatment of choice in surgically accessible chronic thromboembolic pulmonary hypertension and is potentially curative. The UK is served by seven specialist pulmonary hypertension centres and, consequently, there are regions which do not have a specialist unit. Since 2000, Papworth Hospital (Papworth Everard, UK) has been the sole PEA provider for the UK, offering the opportunity to study the national incidence of operable disease and give potential insight into factors that might affect geographical distribution within the UK. All 262 UK residents who underwent PEA surgery between April 2000 and May 2006 were included in the present study. The age-adjusted cumulative referral rates were compared between regions to test for uniformity. Overall, observed rates differed significantly from expected, with evidence of significant nonuniformity across the UK. The highest rates were observed in proximity to the nationally designated specialist centres and in particular in East Anglia and the West Midlands, nearest Papworth. These two regions differed by >2 x SD from the national mean rate. The present study demonstrates wide geographical variation in the number of patients referred for pulmonary endarterectomy surgery. This suggests that there may be patients who are not presently being offered this potentially curative option.

Improved Outcomes in Medically and Surgically Treated Chronic Thromboembolic Pulmonary Hypertension

The management of chronic thromboembolic pulmonary hypertension (CTEPH) has changed over recent years with the growth of pulmonary endarterectomy surgery and the availability of disease-modifying therapies. To investigate the prognosis of CTEPH in a national setting during recent years. All incident cases diagnosed in one of the five pulmonary hypertension centers in the United Kingdom between January 2001 and June 2006 were identified prospectively. Information regarding baseline characteristics, treatment, and follow-up was subsequently collected from hospital records. A total of 469 patients received a diagnosis, of whom 148 (32%) had distal, nonsurgical disease. One- and three-year survival from diagnosis was 82 and 70% for patients with nonsurgical disease and 88 and 76% for those treated surgically (P = 0.023). Initial functional improvement in patients with nonsurgical disease was noted but did not persist at 2 years. Significant functional and hemodynamic improvements were seen in surgically treated patients with an increase in six-minute-walk distance of 105 m (P < 0.001) at 3 months. Five-year survival from surgery in the 35% of patients who survived to 3 months but had persistent pulmonary hypertension was 94%. The prognosis in nonsurgical disease has improved. We have confirmed the previously described good outcome in surgically treated disease. However, we have also demonstrated that the long-term prognosis for patients who have persistent pulmonary hypertension at 3 months after surgery is good. The observed improvements in outcome during the modern treatment era reinforce the importance of identifying patients with this increasingly treatable condition.