Effects and Problems of Continuous Infusion of Epoprostenol for Patients with Primary Pulmonary Hypertension.

Demachi²,

Nawata³

et al. 2009

Self Cite

Circ J 2009; 73: 523 -529 hronic epoprostenol infusion ameliorates the hemodynamics and prognosis of pulmonary artery hypertension (PAH), 1-5 which progresses early with an elevation in pulmonary artery pressure (PAP) and then shows a reduction in cardiac output (CO). 6 The sequence of the hemodynamic improvement after epoprostenol infusion therapy, however, has not been elucidated in detail.Some patients with PAH improve sufficiently to cease requiring further increases in the epoprostenol dosage (good responders), whereas others (poor responders) still require increasing doses. It is unclear what causes the difference in response to epoprostenol between good and poor responders. Moreover, the hemodynamic changes after ceasing incremental epoprostenol therapy are unclear.The primary purpose of the present study was to examine the differences in the hemodynamic response to epoprostenol therapy of good and poor responders treated with epoprostenol for 1 or more years. The secondary purpose was to investigate the hemodynamic course in good responders after cessation of incremental epoprostenol treatment. The third purpose was to clarify whether an increase in CO precedes lowering of the PAP, which reverses the progress in PAH. (Received December 16, 2007; revised manuscript received August 27, 2008; accepted October 26, 2008; released online January 29, 2009 Long-Term Epoprostenol Therapy in Pulmonary Artery Hypertension Sequence of Changes in Hemodynamic EffectsMasahito Sakuma, MD; Jun Demachi, MD*; Jun Nawata, MD**; Jun Suzuki, MD † ; Tohru Takahashi, MD † † ; Kunio Shirato, MD ‡ Background: Sequential changes in the hemodynamic effect of chronic epoprostenol therapy raise the following questions. Does an increase in cardiac output (CO) precede lowering of the pulmonary artery pressure (PAP) over the time course of improvement? What are the characteristics of good responders to chronic epoprostenol treatment? Methods and Results: Hemodynamics were evaluated by catheter examination. Most patients still alive after >1 year showed an increase in CO either with no change in mean PAP or accompanied by a decrease in mean PAP during increased dosing of epoprostenol. Immediately before cessation of the increase in epoprostenol dose in good responders, the ratio of total pulmonary resistance to total systemic resistance was low, and the pulmonary artery wedge pressure minus right atrial pressure was high compared with the newest data in poor responders. One year after fixing at the best dose of epoprostenol, the mean PAP further decreased. Conclusions:In good responders, pulmonary selectivity to epoprostenol is high, and the blood returning to the left-sided heart through the pulmonary circulation increases. Hemodynamics further improve, even after fixing at the best dose of epoprostenol. The present data did not show that an increase in CO precedes lowering of the PAP over the course of improvement. (Circ J 2009; 73: 523 -529)

Section: Hemodynamics At 1 Year After Stopping Increasing the Dose Ofmentioning

confidence: 99%

Long-Term Epoprostenol Therapy in Pulmonary Artery Hypertension

Demachi²,

Nawata³

et al. 2009

Self Cite

“…3 The 5-year survival rate of IPAH was equal to that in the West, approximately 60%. 38,39 Recently, epoprostenol, beraprost, bosentan and sildenafil have been used in the treatment for pulmonary arterial hypertension in Japan, [40][41][42] and have improved the prognosis. In the present study, the 5-year survival rate with PPHTN was approximately 80%, which is good compared with the previous reports, 3,43 and one reason may be the use of these medicines.…”

Section: Management and Prognosismentioning

confidence: 99%

Portopulmonary Hypertension

Souma

Kitamukai

et al. 2005

Self Cite

ortopulmonary hypertension (PPHTN) was previously known as idiopathic pulmonary arterial hypertension (IPAH) with liver injury, but is now established as a clinical entity that is defined as pre-capillary pulmonary hypertension accompanied by hepatic dysfunction and/or portal hypertension. 1 The appearance of PPHTN does not correlate with the severity of the liver dysfunction, 2 and although the cardiac index is relatively preserved, 1,3 there are no reports on the cardiac configuration, pulmonary vascular changes assessed by pulmonary angiography, and plasma levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP), which are indices of loading to the heart. We hypothesized that the changes described would be less prominent in patients with PPHTN, compared with those in IPAH. MethodsOur subjects were 10 patients with PPHTN (2 males, 8 females; mean age 38.5 years, range 22-57) ( Table 1) and 18 patients with IPAH (3 males, 15 females, p=1.00; mean age 38.9 years, range 19-76, p=0.87). The severity of liver failure was classified as A, B or C by Child-Pugh's score. 4 In all subjects, we measured the pulmonary arterial wedge pressure, pulmonary artery pressure, right atrial pressure, aortic pressure, oxygen content in the aorta and pulmonary artery, and cardiac output by routine catheter examination. Fractional pulse pressure was computed as the pulse pressure by the mean pulmonary artery pressure. 5 Additionally, in 8 PPHTN patients and 14 IPAH patients, pulmonary angiography was carried out to examine the configuration of the pulmonary artery tree. Within 1 week after cardiac catheter examination, enhanced electron beam tomography (EBT) (Imatron C-150) was carried out to assess both the ventricular volume and myocardial mass in 5 PPHNT patients and 12 IPAH patients. Electrocardiographic electrodes were attached to each patient's thorax to provide both continuous monitoring of the heart and a trigger signal to the scanner. Patients were placed in a supine position with a 17°axial (feet down) tilt and a 13°slew (to the patient's right) to approximate the short-axis view of the heart. 6-8 A total of 50-60 ml of iopamidol 370 contrast medium was injected into an antecubital vein at a rate of 0.8-1.2 ml/s. The gathering of data was started 40 s after the onset of injection. Ventricular and myocardial volumes were calculated using Simpson's rule from 1-cm slice images (7 mm width and 3 mm gap) in the cine mode (Fig 1). End-diastole was defined according to the timing of the R wave on electrocardiography, and end-systole at the smallest ventricular size. Ventricular volumes were calculated at both end-diastole and end-systole. The left ventricular myocardial volume, including that of the interventricular Background The goal of the present study was to examine the cardiac configuration and pulmonary vascular changes in patients with portopulmonary hypertension (PPHTN) and compare them with those of idiopathic pulmonary arterial hypertension (IPAH). Methods and ResultsThe subjects were 10 patients w...

“…[1][2][3] Although chronic use of epoprostenol has been used to improve the patients' quality of life, New York Heart Association (NYHA) functional class and the prognosis of PPH patients, deem such treatment as still insufficient. 4 The validity of combination therapy for pulmonary hypertension has been demonstrated in some animal models. [5][6][7] However, it is difficult to prove the clinical efficacy of such therapy in human.…”

mentioning

confidence: 99%

Efficacy of Acute Inhalation of Nitric Oxide in Patients With Primary Pulmonary Hypertension Using Chronic Use of Continuous Epoprostenol Infusion

Suzuki

et al. 2005

Self Cite

rimary pulmonary hypertension (PPH), considered to be a disease with a very poor prognosis, is characterized by advanced pulmonary hypertension of unexplained etiology and right heart failure. Recently, mutations in the bone morphogenetic protein receptor 2 gene have been identified in cases of familial and sporadic PPH. [1][2][3] Although chronic use of epoprostenol has been used to improve the patients' quality of life, New York Heart Association (NYHA) functional class and the prognosis of PPH patients, deem such treatment as still insufficient. 4 The validity of combination therapy for pulmonary hypertension has been demonstrated in some animal models. [5][6][7] However, it is difficult to prove the clinical efficacy of such therapy in human.In the current study, we investigated the clinical possibility of combination therapy by evaluating the acute additional effect of nitric oxide (NO) inhalation on the pulmonary blood vessels in PPH patients under chronic treatment with epoprostenol. Circulation Journal Vol.69, March 2005 MethodsFifteen patients with PPH (4 men and 11 women; 34.5±12.1 years old, ranging from 18 to 53) participated in the present study. Patients with secondary pulmonary hypertension, including pulmonary embolism, collagen pulmonary hypertension, portopulmonary hypertension, Eisenmenger syndrome and post-capillary pulmonary hypertension were carefully excluded using imaging techniques, cardiac catheterization, echocardiography, lung scintigraphy, abdominal ultrasound, computer tomography and laboratory tests. Cardiac catheterization was carried out before administering epoprosterol and during the chronic epoprostenol use (20.1±16.5 months). Measured hemodynamic indices were the following: pulmonary capillary wedge pressure, pulmonary arterial pressure, right ventricular pressure, right atrial pressure, aortic pressure and cardiac output. The mean dose of epoprostenol in the chronic phase was 32.1±13.8 ng·kg -1 ·min -1 (range: 8.5-52.4 ng·kg -1 ·min -1 ). The same hemodynamic indices were measured after 10 min inhalation of NO (40 ppm) at the time of right heart catheterization in the chronic phase. In 6 of these patients (6 women; 38.7±10.1 years old), the difference in the effect of acute NO loading before and after the epoprostenol therapy was evaluated. Fractional pulse pressure was calculated as pulmonary pulse pressure divided by mean pulmonary artery pressure. 8 In 5 patients, wedged pulmonary angiography was carried out both before and after administering epoprostenol without NO Background There have only been a few reports published on combination therapy for patients with primary pulmonary hypertension (PPH). Methods and ResultsFifteen patients with PPH (4 men and 11 women, 34.5±12.1 years old) had received chronic administration of epoprostenol and the additive effects of inhaled nitric oxide (NO) and the hemodynamic changes were evaluated. In addition, the difference in the effect of acute NO loading before and after the epoprostenol therapy was compared in 6 of these patients. U...