A comparison of nesiritide vs. epoprostenol in a patient with precapillary pulmonary hypertension due to scleroderma complicated by postcapillary pulmonary hypertension

To the best of our knowledge, acute decompensated left-sided heart failure with preserved left ventricular ejection fraction in a patient with scleroderma has not been previously reported. We describe a patient with severe pulmonary hypertension due to limited scleroderma in whom nesiritide led to marked reductions in pulmonary arterial and capillary wedge pressure as well as resolution of symptoms and pulmonary edema. Subsequent epoprostenol use was associated with an increase in pulmonary capillary wedge pressure and a recurrence of pulmonary edema. Thus, nesiritide may be the preferred agent in scleroderma patients with severe pulmonary hypertension and preserved left ventricular systolic function since epoprostenol may lead to adverse hemodynamic effects.     

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial

BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.     

Transition from intravenous to subcutaneous prostacyclin in pulmonary hypertension

Treatment of arterial pulmonary hypertension with epoprostenol (intravenous prostacyclin) improves survival and quality of life, but the need for an implanted central venous catheter is associated with frequent complications, that often (as in the case of infection or dislodgment) are serious and require catheter replacement. Treprostinil is a prostacyclin analogue suitable for continuous subcutaneous administration. We report the successful transition from intravenous epoprostenol to subcutaneuos treprostinil in four patients with severe pulmonary hypertension who suffered from serious complications associated with the epoprostenol infusion system.     

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension.

Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as "portopulmonary hypertension." Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (-34% +/- 18%), MPAP (-16% +/- 10%), and cardiac output (CO) (+21 +/- 18%), were statistically significant (P <.01). Long-term use of epoprostenol further lowered PVR (-47% +/- 12% from baseline and -31% +/- 22% from the acute change; P <.05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study.     

Outcome in 91 consecutive patients with pulmonary arterial hypertension receiving epoprostenol

Epoprostenol has markedly improved the treatment of pulmonary arterial hypertension, although predictors of outcome with epoprostenol are not well characterized. From June 1995 through August 2001, 91 patients with pulmonary arterial hypertension were treated with epoprostenol at our institution. We analyzed the effects of long-term epoprostenol treatment to determine features associated with outcome. Predictors of worse outcome included older age of disease onset (hazard ratio 3.2, 95% confidence interval 1.32-7.76 for patients above the median age of 44 years), World Health Organization functional Class IV, either at baseline or follow-up, (3.07, 1.42-6.62 compared with functional Class I, II, and III), and scleroderma spectrum of disease (2.32, 1.08-4.99). There were no baseline or follow-up hemodynamic factors predictive of outcome. Our results indicate that treatment with epoprostenol improves survival in patients with Primary Pulmonary Hypertension compared with that predicted by the National Institutes of Health Primary Pulmonary Hypertension Registry's survival equation and that their survival is significantly better than that of patients with scleroderma spectrum of disease (p = 0.001). Older patients treated with epoprostenol have significantly shorter survival, regardless of etiology.     

Pulmonary hypertension and beta-thalassemia major: report of a case, its treatment, and a review of the literature

Pulmonary hypertension is a common complication of beta-thalassemia major. We report a case of successful treatment of pulmonary hypertension in a patient with beta-thalassemia major and review the literature on pulmonary hypertension and beta-thalassemia major. A 28-year-old man with beta-thalassemia major, splenectomy, hepatitis C, and hemosiderosis who presented with increasing dyspnea on exertion was diagnosed with pulmonary hypertension. After receiving continuous epoprostenol infusion and desferoxamine, his functional capacity and hemodynamic status improved. To our knowledge, this is the first case of pulmonary hypertension associated with beta-thalassemia treated with continuous epoprostenol infusion and desferoxamine. Epoprostenol, beneficial in the treatment of other types of pulmonary hypertension, may ameliorate the morbidity and mortality of pulmonary hypertension associated with thalassemia.     

Epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension

Although HIV-associated pulmonary hypertension and primary pulmonary hypertension (PPH) are clinically and histologically similar, treatment options for the former are limited. Treatment with calcium channel blockers (CCB), proven to be beneficial in a subset of patients with PPH, has been disappointing in HIV-associated pulmonary hypertension and there are no data examining the effects of long-term epoprostenol in this entity. Six patients with severe HIV-associated pulmonary hypertension were treated with continuous intravenous epoprostenol infusions. Acute infusion of epoprostenol resulted in a significant (p < 0.05) decrease in mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) of 16. 4 and 32.7%, respectively, and a significant (p < 0.05) increase in mean cardiac output (CO) of 36.9%. At 1 yr, mean PAP and PVR had decreased by 21.7 and 54.9% (p < 0.05), respectively, and mean CO had increased by 51.4% (p < 0.05) when compared with baseline values. Repeat catheterizations of three patients at 2 yr and one patient at 40 mo demonstrated further improvement or maintenance of hemodynamics. In addition, NYHA functional class improved in all patients. We conclude that epoprostenol infusion is effective in improving hemodynamic and functional status in this cohort of six patients with HIV-associated pulmonary hypertension acutely and long-term.     

Imaging and clinical measurements

ABSTRACT:: Portopulmonary hypertension (POPH) is a not infrequent but serious complication of liver cirrhosis. Continuous intravenous epoprostenol infusion is a treatment option for this condition. Progressive splenomegaly with pancytopenia (hypersplenism) is associated with epoprostenol use in POPH. After recognizing a case of epoprostenol-induced hypersplenism that resolved upon stopping the drug, the authors retrospectively reviewed all patients treated with epoprostenol at the center for both POPH and pulmonary hypertension due to other causes. Five of 11 patients with POPH developed hypersplenism secondary to epoprostenol. In 1 patient, and possibly in a second, the hypersplenism resolved upon discontinuation of epoprostenol. None of 9 patients with pulmonary hypertension due to other causes developed splenomegaly. This report confirms hypersplenism as a complication of epoprostenol therapy for POPH. Furthermore, the authors demonstrate for the first time that hypersplenism may be reversed by stopping the medication and propose a mechanism for this phenomenon.     

Comparison of the haemodynamic effects of epoprostenol (prostacyclin) and tolazoline.

The haemodynamic effects of infusion of epoprostenol (prostacyclin) and bolus injection of tolazoline were compared in a crossover study in 11 children with pulmonary hypertension caused by pulmonary vascular disease. The children were studied during cardiac catheterisation, while they were anaesthetised, paralysed, and ventilated with 100% oxygen. The order of drug administration was not randomised because tolazoline has a half life of hours whereas epoprostenol has a half life of a few minutes. Both drugs caused pulmonary and systemic vasodilatation, and there were no significant differences between the two. The 95% confidence intervals suggest that tolazoline did not have a clinically important haemodynamic advantage over epoprostenol. Previous reports suggest that serious side effects are common when tolazoline is used in repeated doses; epoprostenol has only a few minor side effects that are rapidly reversible when the infusion is stopped. Epoprostenol is more expensive than tolazoline but this study suggests that epoprostenol is a more suitable pulmonary vasodilator if more than a single dose is required.     

Update on disease-modifying antirheumatic drugs in the treatment of systemic sclerosis

Treatment of systemic sclerosis has been somewhat haphazard and treatment has often been "borrowed" from the experience gained from treating other connective tissue diseases. There was a period of time that was focused mainly on organ-specific manifestations of systemic sclerosis and some advance in preventing vital organ damage (such as renal crisis) was achieved. The vast improvement in mortality from the use of ACE inhibitors raises one's hopes for other effective therapeutic interventions. At this juncture, the evidence is strong that the ACE inhibitors that are used in scleroderma renal crisis are disease-modifying, even without proving it by a randomized controlled trial. The evidence is strong that the use of epoprostenol for primary pulmonary hypertension is life-saving; however, whether epoprostenol is life-saving in the pulmonary hypertension in scleroderma remains to be proven. There are suggestions that bosentan (for the pulmonary hypertension of scleroderma), cyclophosphamide (for SSc alveolitis), stem cell transplant, interferon-gamma (for interstitial pulmonary fibrosis), and methotrexate (for the skin thickening of diffuse scleroderma) may improve organ function or functional activities, but whether they are truly disease-modifying remains to be proven. As we increase our understanding of the pathophysiology of systemic sclerosis and we learn how better to design trials for systemic sclerosis, we may be more successful in developing optimal disease-modifying therapy. Although the treatment of systemic sclerosis remains difficult, there are an increasing number of potentially effective regimens that are undergoing clinical investigations. A rational approach to therapy seems possible, based on a hypothesis of the pathogenesis of systemic sclerosis. Thus, there is accumulating evidence that supports the use of prostacyclin derivatives to treat systemic sclerosis, some evidence that antifibrotic regimens may be effective, and moderate evidence that immunosuppression also may be effective in certain stages of this disease.     

Comparison of the haemodynamic effects of epoprostenol (prostacyclin) and tolazoline

The haemodynamic effects of infusion of epoprostenol (prostacyclin) and bolus injection of tolazoline were compared in a crossover study in 11 children with pulmonary hypertension caused by pulmonary vascular disease. The children were studied during cardiac catheterisation, while they were anaesthetised, paralysed, and ventilated with 100% oxygen. The order of drug administration was not randomised because tolazoline has a half life of hours whereas epoprostenol has a half life of a few minutes. Both drugs caused pulmonary and systemic vasodilatation, and there were no significant differences between the two. The 95% confidence intervals suggest that tolazoline did not have a clinically important haemodynamic advantage over epoprostenol. Previous reports suggest that serious side effects are common when tolazoline is used in repeated doses; epoprostenol has only a few minor side effects that are rapidly reversible when the infusion is stopped. Epoprostenol is more expensive than tolazoline but this study suggests that epoprostenol is a more suitable pulmonary vasodilator if more than a single dose is required.     

Epoprostenol for treatment of pulmonary hypertension in patients with systemic lupus erythematosus

OBJECTIVE: Pulmonary hypertension with pathological changes similar to those observed in primary pulmonary hypertension occurs in patients with systemic lupus erythematosus (SLE). The efficacy of chronic epoprostenol therapy in SLE has not been well described. The objective of this paper is to describe our experience with long-term epoprostenol therapy in patients with pulmonary hypertension associated with SLE. DESIGN: Case series of six patients with SLE and associated pulmonary hypertension receiving chronic treatment with epoprostenol. RESULTS: All 6 patients had severe pulmonary hypertension. Mean pulmonary artery pressure (mPAP) was 57 +/- 9 mm Hg (mean +/- SD), and pulmonary vascular resistance was 14 +/- 7 units before beginning therapy with epoprostenol. In 4 patients who underwent repeat hemodynamic evaluation (9 to 16 months after starting epoprostenol), mean pulmonary artery pressure decreased by 38 +/- 21% and pulmonary vascular resistance by 58 +/- 12%. Clinically, all patients improved from New York Heart Association class III or IV to class I or II. Doses of epoprostenol ranged from 4 to 46 ng/kg/min, and the longest duration of therapy has been 2.5 years. Side effects from epoprostenol have not differed from those seen in patients with primary pulmonary hypertension, and except for one patient, there has been no exacerbation of SLE. CONCLUSION: Epoprostenol was effective for the treatment of pulmonary hypertension in this small group of patients with SLE. Further evaluation of epoprostenol therapy for patients with SLE and other diseases associated with pulmonary hypertension is warranted.     

Marked improvement with sildenafil in a patient with primary pulmonary hypertension unresponsive to epoprostenol

We report a 48-year-old woman with right heart failure due to primary pulmonary hypertension. Continuous infusion of epoprostenol (prostaglandin I2) for 1.5 years failed to control her condition, but she was later successfully treated with additional sildenafil for a few months. Her mean pulmonary artery pressure was originally 57 mmHg, increased to 62 mmHg with epoprostenol, and decreased to 45 mmHg with sildenafil. Additional sildenafil may be an effective and life-saving agent in patients with primary pulmonary hypertension who show a poor response to epoprostenol, which is considered to be very powerful medical treatment for the disease.     

Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study.

Continuous intravenous epoprostenol improves exercise capacity, haemodynamics, and survival in severe primary pulmonary hypertension. Pulmonary hypertension can also be life-threatening in patients with connective tissue diseases. In a prospective open monocentre uncontrolled study, the effects of epoprostenol were evaluated in patients with severe pulmonary hypertension secondary to connective tissue diseases who were unresponsive to oral vasodilators (including calcium channel blockers) and continued to be in the New York Heart Association (NYHA) functional class III or IV despite conventional medical therapy. Seventeen patients received epoprostenol administered by a portable infusion pump associated with conventional therapy (oral anticoagulants, diuretics, supplemental oxygen). During the first six weeks of therapy, two (12%) patients died, of pulmonary oedema (n = 1) and severe sepsis (n = 1). In the fifteen remaining subjects, clinical and haemodynamic parameters improved significantly at six weeks. These patients were subsequently monitored for 80+/-48 (range 14-154) weeks after initiation of epoprostenol. Five (33%) patients died, of right heart failure (n = 2), severe sepsis (n = 2) or syncope (n = 1) and two patients were successfully transplanted 24 and 52 weeks after initiation of epoprostenol. Seven of the remaining eight patients had a persistent clinical improvement. Short-term epoprostenol therapy is effective in some patients with connective tissue diseases as demonstrated by better clinical status and haemodynamics at six weeks. However, this study reports several cases of early and late major complications including severe sepsis and pulmonary oedema. Additional information is needed to evaluate the benefit: risk ratio of long-term epoprostenol therapy in pulmonary hypertension secondary to connective tissue diseases.     

Ten years' experience in continuous intravenous epoprostenol therapy in severe pulmonary arterial hypertension

INTRODUCTION: Primary pulmonary hypertension and its associated forms is a progressive and often fatal disease, the course of which has been favourably modified by prostacyclin therapy in the last decade. OBJECTIVE: The aim of this study is to analize retrospectively the efficacy of continuous intravenous epoprostenol (synthetic prostacyclin) therapy in pulmonary arterial hypertension, and to compare it with conventional therapy (anticoagulants, digoxin and diuretics). METHODS: Between 1990-2000, 31 patients with severe precapillary pulmonary hypertension in functional class III or IV went on continuous intravenous epoprostenol therapy, administered by a portable infusion pump through a Hickman catheter. We compared their survival with a group of 16 patients treated with conventional therapy alone. RESULTS: Time of follow-up was 33.25 months in the prostacyclin group and 20 months in the conventional group. The one- three- and five- year survival rates were 86%, 50% and 38% respectively for patients treated with epoprostenol compared with 40%, 40% and 8% survival rates at idetical periods for patients treated conventionally (p = 0,02). Functional class and the mean distance walked in the 6 minutes test were improved in patients treated with prostacyclin (p < 0,01). Serious complications attributable to the delivery system included 3 deaths, mainly due to infection. CONCLUSION: Continuous intravenous epoprostenol therapy improves survival and exercise capacity in patients with severe pulmonary arterial hypertension despite potentially serious complications attributable to the delivery system.     

Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension

RATIONALE: Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension. The prostacyclin analog treprostinil is also efficacious by subcutaneous infusion, is easier to administer, and has a longer half-life. With the demonstration of bioequivalence between subcutaneous and intravenous treprostinil, intravenous treprostinil may have an overall better risk-benefit profile than intravenous epoprostenol. OBJECTIVE: To evaluate the safety and efficacy of transitioning patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. METHODS: Patients enrolled in a 12-wk prospective open label study were switched from intravenous epoprostenol to intravenous treprostinil over 24 to 48 h. The intravenous treprostinil dose was adjusted to minimize symptoms/side effects. RESULTS: Thirty-one patients (mean age, 43 yr; 22 women) were enrolled. Twenty-seven patients completed the protocol; 4 patients transitioned back to epoprostenol. Six-minute walk distance (n = 27; baseline, 438 +/- 16 m; Week 12, 439 +/- 16 m), Naughton-Balke treadmill test time (n = 26; baseline, 582 +/- 50 s; Week 12, 622 +/- 48 s), functional class, and Borg score were maintained with intravenous treprostinil at Week 12 versus intravenous epoprostenol before transition. At Week 12, mean pulmonary artery pressure increased 4 +/- 1 mm Hg (n = 27, p < 0.01), cardiac index decreased 0.4 +/- 0.1 L/min/m2 (n = 27, p = 0.01), and pulmonary vascular resistance increased 3 +/- 1 Wood units x m2 (n = 26, p < 0.01). No serious adverse events were attributed to treprostinil. CONCLUSIONS: These data suggest that transition from intravenous epoprostenol to intravenous treprostinil is safe and effective; whether the hemodynamic differences associated with intravenous treprostinil are clinically important requires longer follow-up.     

Long term inhalation of iloprost in a child with primary pulmonary hypertension: an alternative to continuous infusion

Primary pulmonary hypertension is a rare disease in childhood associated with a poor prognosis. However, during the past 10 years, pulmonary vasodilator treatment has somewhat improved its prognosis. Long term continuous infusion of prostacyclin (epoprostenol) has been shown to improve physical capacity and to reduce mortality in primary and secondary pulmonary hypertension. It has been reported in adults that daily repetitive inhalation of iloprost, a prostacyclin analogue, seems also suitable for long term therapy of pulmonary hypertension. Repetitive inhalation of iloprost was administered to a 5 year old boy with severe primary pulmonary hypertension. He showed continuous clinical improvement without any side effects over the three years of treatment. This treatment may offer an alternative to continuous intravenous prostacyclin infusion and obviates the need for a permanent central venous catheter.


Keywords: iloprost; inhalation; prostacyclin; pulmonary hypertension     

Pregnancy and primary pulmonary hypertension : successful outcome with epoprostenol therapy

Primary pulmonary hypertension (PPH) associated with pregnancy carries a high maternal mortality rate. Short-term epoprostenol infusion has been demonstrated to improve the hemodynamic profile in patients with PPH. We report a successful maternal-fetal outcome with epoprostenol therapy during pregnancy, cesarean section, and postpartum in a patient with PPH. Epoprostenol therapy did not produce any physical or developmental abnormalities in the fetus. A favorable maternal-fetal outcome may occur with a multidisciplinary approach.     

Soluble thrombomodulin concentration is raised in scleroderma associated pulmonary hypertension

OBJECTIVE: To investigate the expression of thrombomodulin in scleroderma associated pulmonary hypertension. METHODS: Soluble thrombomodulin (sTM), was measured in plasma samples from 34 scleroderma patients shown to have pulmonary hypertension at echocardiogram, and comparison drawn against samples from 38 scleroderma control patients, and 20 healthy controls. Serial measurements of sTM were performed in the 34 patients with scleroderma associated pulmonary hypertension to investigate possible changes in sTM concentration with progression of the condition. RESULTS: Mean sTM was raised in scleroderma associated pulmonary hypertension when compared with scleroderma controls (mean sTM 65.4 ng/ml v 43.3 ng/ml, p<0.05), and when compared with healthy controls (mean sTM 38.1 ng/ml, p<0.05). There was no significant difference between mean sTM in scleroderma controls and healthy controls. Mean sTM concentration did not change with progression of pulmonary hypertension. CONCLUSION: Plasma sTM is raised in scleroderma associated pulmonary hypertension. The pathogenesis of scleroderma associated pulmonary hypertension may be distinct from the pathogenesis of other forms of pulmonary vascular disease.     

Continuous intravenous epoprostenol for chronic thromboembolic pulmonary hypertension.

Pathophysiological findings in chronic thromboembolic pulmonary hypertension (CTEPH) have suggested that a secondary small vessel arteriopathy may contribute to the haemodynamic impairment observed in these patients. It was hypothesised that this element of the elevated vascular resistance may be responsive to continuous intravenous epoprostenol therapy. Retrospectively, the clinical and haemodynamic responses to continuous intravenous epoprostenol were evaluated in nine CTEPH patients who subsequently underwent pulmonary thromboendarterectomy (PTE). Cardiopulmonary haemodynamics were determined prior to the initiation of epoprostenol, while on epoprostenol, prior to PTE, and after PTE. Six patients, treated for 2-26 months prior to PTE, experienced either clinical stability or improvement that was associated with a mean reduction in pulmonary vascular resistance (PVR) of 28% (median 33%, range 0-46%). Three patients, treated for 3-9 months, experienced clinical deterioration during epoprostenol administration, with a significant increase in PVR in two patients. Subsequent PTE resulted in a highly significant improvement of cardiac index, mean pulmonary artery pressure and total pulmonary resistance. To conclude, selected patients with chronic thromboembolic pulmonary hypertension may benefit clinically and haemodynamically from continuous intravenous epoprostenol treatment prior to pulmonary thromboendarterectomy. Factors predictive of a beneficial response, and whether this intervention influences either morbidity or mortality associated with pulmonary thromboendarterectomy, remain to be established.