A case of severe pulmonary hypertension associated with COPD treated with epoprostenol

A rare case of chronic obstructive pulmonary disease (COPD) with severe pulmonary hypertension (PH) was found in a 68-year-old man. COPD was diagnosed in his 50s, from which time he received home oxygen therapy. In January 2007, he was admitted due to progression of dyspnea. On admission to our hospital, arterial blood gas analysis showed severe hypoxemia. Moreover, echocardiographic findings demonstrated severe deviation of the interventricular septum toward the left ventricle, with right ventricular dilatation. Cardiac catheterization data demonstrated pulmonary arterial hypertension with a low cardiac output. Because severe PH is uncommon in patients with COPD and there was no apparent etiology of PH other than COPD, we thought this case was predominantly a pulmonary vascular disease such as idiopathic pulmonary arterial hypertension. Though we first treated this patient with bosentan, it was not effective. Therefore, he was treated with continuous infusion of epoprostenol. Epoprostenol administration along with bosentan resulted in decrease of BNP and right ventricular function improvement. We report a case of severe PH due to severe COPD treated with continuous administration of epoprostenol.     

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.     

Sildenafil decreased pulmonary arterial pressure but may have exacerbated portal hypertension in a patient with cirrhosis and portopulmonary hypertension

Portopulmonary hypertension is a recognized but uncommon complication of cirrhosis. Liver transplantation may be contraindicated in patients with severe portopulmonary hypertension. In order to decrease the pulmonary arterial pressure, intravenous administration of epoprostenol has been shown to provide substantial beneficial results in these patients. Additionally, a recent case report demonstrated that long-term oral administration of sildenafil decreased pulmonary arterial pressure, but its effects on splanchnic hemodynamics were not measured. We report on a patient with cirrhosis and portopulmonary hypertension and the changes in the hemodynamic status after an oral administration of sildenafil. This case report clearly delineates that sildenafil decreases pulmonary arterial pressure but may exacerbate portal hypertension and hyperdynamic circulation in patients with cirrhosis and portopulmonary hypertension.     

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.     

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.     

Primary pulmonary hypertension treated with short-term epoprostenol infusion

We describe the use of short-term epoprostenol in a 61-year-old man with primary pulmonary hypertension. The patient was on a ventilator because of respiratory distress. Continuous infusion of epoprostenol was started and it initially reduced the pulmonary artery pressure by 32%. Epoprostenol was tapered, and even after discontinuation, the pulmonary artery pressure was controlled. The ventilator was removed, and the patient remained well on home oxygen therapy 3 months after discharge.     

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.     

Continuous intravenous epoprostenol therapy for pulmonary hypertension in Gaucher's disease.

Gaucher's disease is a rare disorder characterized by a deficiency of lysosomal beta-glucosidase. Pulmonary hypertension, the etiology of which is unclear, has been reported to occur in association with Gaucher's disease. We report the use of continuous intravenous epoprostenol (prostacyclin), which has been used to treat other forms of pulmonary hypertension, in a patient with pulmonary hypertension associated with Gaucher's disease. Although its mechanism of action remains unknown, epoprostenol may be an effective form of therapy for chronic pulmonary hypertension due to a variety of conditions, one of which is Gaucher's disease.     

Epoprostenol in chronic thromboembolic pulmonary hypertension with distal lesions.

BACKGROUND: Although patients with primary pulmonary hypertension and patients with chronic thromboembolic pulmonary hypertension with distal lesions may share similar pathophysiological characteristics, scarce information is available on the usefulness of epoprostenol in this form of secondary pulmonary hypertension. The aim of this study was to evaluate the feasibility, safety and efficacy of epoprostenol therapy in surgically untreatable patients with chronic thromboembolic pulmonary hypertension. METHODS: Continuous infusive therapy with epoprostenol was undertaken in 16 patients with primary pulmonary hypertension and in 11 surgically untreatable thromboembolic pulmonary hypertension patients. The median follow-up was 12.4 months (range 6-23 months). Patients underwent clinical, echocardiographic and hemodynamic evaluation at baseline and a 6-min walk test every 3 months after beginning epoprostenol; ultrasound evaluations were repeated in a subgroup of patients. RESULTS: Epoprostenol therapy improved the clinical status, exercise tolerance and NYHA functional class. A greater left ventricular end-diastolic volume was recorded at echocardiography in both groups. CONCLUSIONS: Epoprostenol therapy may be feasible, safe and clinically effective in patients with surgically untreatable chronic thromboembolic pulmonary hypertension.     

Weaning and discontinuation of epoprostenol in children with idiopathic pulmonary arterial hypertension receiving concomitant bosentan

In 7 of 8 children with idiopathic pulmonary arterial hypertension treated with intravenous epoprostenol for >1 year, concomitant use of bosentan allowed a reduction of epoprostenol and decreased its associated side effects without deterioration of clinical and hemodynamic parameters. In 3 children with normal or near-normal pulmonary artery pressure on epoprostenol, the addition of bosentan allowed discontinuation of epoprostenol and stabilization of hemodynamics for up to 1 year.     

Treatment with epoprostenol reverts nitric oxide non-responsiveness in patients with primary pulmonary hypertension

OBJECTIVE—To assess whether long term treatment with epoprostenol might restore primary non-responsiveness to nitric oxide (NO) in patients with primary pulmonary hypertension.
METHODS—Seven patients with primary pulmonary hypertension receiving intravenous epoprostenol continuously because of failure of NO to influence pulmonary haemodynamics during initial testing were followed over a period of 13-29 months. Afterwards, acute vascular reactivity towards NO was tested again during right heart catheterisation.
RESULTS—Administration of NO after continuous epoprostenol treatment for a mean period of 18 months improved arterial oxygen saturation (p < 0.01) and cardiac index (p < 0.05), and decreased mean pulmonary artery pressure (p < 0.01) and total pulmonary vascular resistance (p < 0.01) in patients previously unresponsive to NO.
CONCLUSIONS—Long term treatment with epoprostenol reverts initial refractoriness to NO in patients with primary pulmonary hypertension. Thus the addition of NO to epoprostenol treatment might cause further improvement in the course of the disease.


Keywords: primary pulmonary hypertension; epoprostenol; vascular reactivity     

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.     

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.     

Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension

Sildenafil and inhaled nitric oxide (iNO) relax smooth muscle by inhibiting the degradation and stimulating the production of cyclic guanosine monophosphate, respectively. We compared the acute pulmonary vasodilator effects of sildenafil, iNO, and epoprostenol and asked whether the combination of iNO with sildenafil had additive pulmonary vasodilator effects. We assessed the effects of extended use of sildenafil in a small cohort of patients. Twenty patients with pulmonary arterial hypertension underwent an acute vasodilator trial with sildenafil (all patients), iNO and iNO plus sildenafil (11), and epoprostenol (19). We also provided sildenafil to patients who were ineligible for, or had clinical deterioration on epoprostenol, treprostinil, or bosentan. Mean+/-se pulmonary artery pressure dropped by 13+/-3%, 19+/-4%, 14+/-3%, and 26+/-4% with epoprostenol, iNO, sildenafil, and iNO+sildenafil, respectively. Cardiac index increased with epoprostenol and sildenafil. A correlation was found between the effects of iNO and epoprostenol. Nine out of ten patients who were started on long-term sildenafil treatment alone or in combination with other vasodilators had symptomatic improvement. Three died of right heart failure. In conclusion, sildenafil is a potent acute pulmonary vasodilator, an effect that is potentiated by combination with iNO. Long-term therapy of pulmonary hypertension with sildenafil alone or in combination with other agents appears to be safe and well tolerated.     

Acute effects of nebulised epoprostenol in pulmonary hypertension due to systemic sclerosis.

Pulmonary hypertension often has a lethal outcome in systemic sclerosis and the treatment is challenging. Epoprostenol is a potent pulmonary vasodilator and its efficacy has been demonstrated when delivered by the intravenous and aerosolized routes. We report the haemodynamic and functional benefits of epoprostenol administered by inhalation to a spontaneously breathing patient with partially reversible pulmonary hypertension due to systemic sclerosis. Aerosolized epoprostenol, equivalent to the maximum tolerated intravenous dose (31.2 micrograms), produced a 58% fall in pulmonary vascular resistance, increased the cardiac output by 42% and improved functional performance by one MET (3.5 ml kg-1 min-1 of oxygen uptake) without any significant side-effects. Selective distribution of epoprostenol by the inhaled route may offer a new strategy for treatment of pulmonary hypertension.     

Acute effects of sildenafil in patients with primary pulmonary hypertension receiving epoprostenol

Epoprostenol therapy has improved survival in primary pulmonary hypertension; however, only two thirds of patients are alive 3 years after starting treatment. Combined therapy with sildenafil, a phosphodiesterase 5 inhibitor, may provide additional benefit. The authors prospectively evaluated the acute hemodynamic and biochemical effects of sildenafil and inhaled nitric oxide, alone and in combination, in 8 patients with primary pulmonary hypertension receiving chronic epoprostenol. Average duration of epoprostenol therapy was 2.9 +/- 1.6 years (mean +/- SD) and mean dose was 25.7 +/- 10.8 ng/kg/min. A single 50 mg dose of sildenafil decreased mean pulmonary arterial pressure 10% (P<.05), increased cardiac output 8%, and decreased pulmonary vascular resistance 24% (P<.005). Although nitric oxide led to a similar decrease in mean pulmonary arterial pressure of 10% (P<.05), cardiac output was unchanged, resulting in a decrease in pulmonary vascular resistance of only 13%, which was not statistically different from baseline. These results suggest that sildenafil has greater acute hemodynamic effects than nitric oxide and that it can further reduce pulmonary vascular resistance in patients already demonstrating a benefit from chronic epoprostenol.     

Acute circulatory failure caused by primary pulmonary hypertension or pulmonary embolism

Patients with acute massive pulmonary embolism or primary pulmonary hypertension may develop acute circulatory failure and are therefore admitted in the intensive care. The mortality rate of patients with pulmonary embolism and shock varies between 25 and 35% whereas the corresponding figure in patients with submassive embolism is less than 10%. Spiral computed tomography may be the most convenient test for diagnosing pulmonary embolism in the setting of acute circulatory failure. In the few patients who remain unstable despite adequate symptomatic treatment, transthoracic echocardiography combined with clinical judgement is appropriate. Inotropic support and thrombolytic therapy are clearly indicated for patients with massive embolism and shock. The role of the latter is more controversial in patients with right ventricular distension and normal blood pressure. The optimal duration of anticoagulant therapy for pulmonary embolism remains to be defined. Most patients are adequately treated with a six-month course of oral anticoagulants. A shorter duration may be sufficient when a transient risk factor is the cause of the initial event whereas patients with cancer or antithrombin deficiency may require a life long treatment. Primary pulmonary hypertension is a much more uncommon disease which can also lead to right ventricular failure. Symptomatic treatment combines oxygen, inotropic drugs, as well as the optimisation of right ventricular filling pressure. Specific treatment includes inhaled nitric oxide or intravenous epoprostenol followed by anticoagulants with either calcium channel blockers in patients responding acutely to vasodilators or a continuous infusion of epoprostenol in those who do not respond to acute challenge or who are not improving with calcium channel blockers. Although the long term survival has markedly improved as a result of epoprostenol treatment, some patients with refractory primary pulmonary hypertension remain candidates for lung transplantation.     

Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension

OBJECTIVE: To assess short-term and long-term responses to treatment with pulmonary vasodilators in patients with sarcoidosis-related pulmonary hypertension. METHODS: A prospective, observational study was performed on eight patients with moderate-to-severe sarcoidosis-related pulmonary hypertension. Patients underwent a short-term vasodilator trial, using inhaled nitric oxide (iNO), IV epoprostenol, and/or oral calcium-channel blockers. A favorable short-term response was considered a > or = 20% decrease in pulmonary vascular resistance (PVR). Five patients received long-term treatment with iNO (with one patient receiving epoprostenol in addition) and underwent follow-up hemodynamic and/or 6-min walk testing. Two patients received long-term treatment with calcium-channel blockers. RESULTS: Baseline (+/- SE) mean pulmonary artery pressure (mPAP) was 55 +/- 4 mm Hg and PVR was 896 +/- 200 dyne.s.cm(-5). A favorable short-term response was seen in seven of eight patients receiving iNO, four of six patients receiving epoprostenol, and two of five patients receiving calcium-channel blockers. With iNO, PVR decreased 31 +/- 5% (p = 0.006) and mPAP decreased 18 +/- 4% (p = 0.003); with epoprostenol, PVR decreased 25 +/- 6% (p = 0.016) and mPAP decreased 6 +/- 2% (p = not significant). Decreased systemic vascular resistance was the only significant response to treatment with calcium-channel blockers. Follow-up 6-min walk test results improved in all five patients receiving long-term treatment with iNO. Follow-up hemodynamic responses in three patients showed preserved vasoresponsiveness. These three patients subsequently died, as did the two patients receiving calcium-channel blockers. The two remaining patients continue to receive iNO. CONCLUSION: In the short term, pulmonary hypertension in patients with sarcoidosis is responsive to treatment with pulmonary vasodilators; these patients may benefit from long-term iNO therapy.