u-62840 and Heart-Defects--Congenital

Epoprostenol and the structurally related compounds treprostinil, iloprost, and beraprost are collectively referred to as prostanoids. The discovery of epoprostenol in 1976 and unequivocal demonstration of its efficacy in 1996 dramatically altered the approach to therapy for pulmonary arterial hypertension (PAH). Development of prostanoids available through multiple routes of administration and the discovery and development of other agents acting through alternative pathways continue to expand the array of therapeutic options. The use of prostanoids in combination with other PAH drugs and for treating pulmonary hypertensive disorders outside of the PAH classification are areas of ongoing research.

Topics: Antihypertensive Agents; Chronic Disease; Epoprostenol; Heart Defects, Congenital; Humans; Hypertension, Portal; Hypertension, Pulmonary; Iloprost; Prostaglandins; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome

The aim of this study is to evaluate the effects of treprostinil injection on the control of pulmonary blood pressure in children with congenital heart disease (CHD) complicated by severe pulmonary arterial hypertension (PAH).. Eighty children with CHD complicated by severe pulmonary arterial hypertension admitted to our hospital from January 2015 to June 2018 were selected and randomly divided into a control group (N.=40) and a treatment group (N.=40). Based on standard treatment, the treatment group was intravenously infused with 8-12 ng/kg·min treprostinil, while the control group received the same dose of normal saline. Hemodynamic parameters such as BP, AP, P and SpO2% were monitored before anesthesia induction (T0), before cardiopulmonary bypass (T1), 1 h after cardiopulmonary bypass (T2) and at the end of cardiopulmonary bypass (T3). Pulmonary arterial pressure parameters (PASP, PADP and PAMP) were measured at T1, T2 and T3 by transesophageal echocardiography.. For the treatment group, the HR values at T2 and T3 were lower than that at T0 (P<0.05). For the control group, HR at T3 was lower than that at T0 (P<0.05). HR at T3 of the treatment group was lower than that of the control group (P<0.05). SpO2 of the treatment group was higher than that of the control group at T3 (P<0.05). At T2 and T3, PASP, PADP and PAMP of both groups were lower than those before surgery (P<0.05), and the values of the treatment group were lower than those of the control group (P<0.05).. Treprostinil can improve cardiac function and reduce pulmonary circulation resistance in PAH children.

Topics: Antihypertensive Agents; Child; Epoprostenol; Familial Primary Pulmonary Hypertension; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) results from pulmonary vascular disease and may eventually lead to right heart failure and death. Vasodilator therapy has greatly improved PAH prognosis. Circulating microvesicles are considered as surrogate markers of endothelial and hematopoietic cell activation.. Thus, our purpose was to determine if MVs are upregulated in pediatric PAH such as reported in adult patients, and to analyze the impact of vasodilator therapies on MV count and function.. Population study consisted of 26 patients of median age 6.09 years, with Congenital Heart Disease (CHD) and elevated pulmonary vascular resistance (CHD-PAH) or idiopathic PAH (iPAH).. Compared to healthy controls, all circulating MV subpopulations were found higher in untreated PAH patients. No significant differences of annexin-V+ total MV, endothelial, or leukocyte derived-MV counts were found between untreated patients and those receiving oral vasodilator therapies. Conversely, platelet MVs were significantly lower in the group treated with SC-treprostinil compared with both untreated PAH and oral therapy groups (P = 0.01), and exhibited a significant decrease of phospholipid procoagulant activity. Control samples treated in vitro with treprostinil at therapeutic concentrations showed as expected a significant decrease of platelet aggregation but also a reduced spontaneous MV generation.. Our results suggest that treprostinil, besides vasodilation, might exert its beneficial effect through an inhibition of platelet activation, resulting in a decreased number and procoagulant activity of circulating MVs.

Topics: Adolescent; Adult; Antihypertensive Agents; Cell-Derived Microparticles; Child; Child, Preschool; Coagulants; Epoprostenol; Familial Primary Pulmonary Hypertension; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant; Lung; Male; Pulmonary Arterial Hypertension; Pulmonary Circulation; Vasodilator Agents; Young Adult

To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment.. Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study.. Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13). In the multivariate mixed model, mean increase in 6 min walk distance (6-MWD) from baseline to 12 months was 114 m (76; 152) (P<0.001). WHO FC improved significantly (P=0.001) and B-type brain natriuretic peptide decreased from 1259 (375; 2368) pg/mL to 380 (144; 1468) pg/mL (P=0.02). In those 14 patients who had haemodynamic data before and after initiation of treprostinil, pulmonary vascular resistance decreased significantly (from 18.4±11.1 to 12.6±7.9 Wood units, P=0.003). The most common adverse events were infusion-site erythema and pain. One patient stopped treatment because of intolerable infusion-site pain after 8 months of treatment. No other major treatment-related complications were observed. Five patients died during early follow-up, having experienced a decrease in their 6-MWD prior.. Subcutaneous treprostinil therapy is generally safe and effective for at least 12 months and may be used in CHD-related PAH class III and IV.

Topics: Adult; Antihypertensive Agents; Cohort Studies; Epoprostenol; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infusion Pumps; Infusions, Subcutaneous; Male; Natriuretic Peptide, Brain; Oxygen; Vascular Resistance; Walk Test

Pulmonary arterial hypertension (PAH) is a rare and progressive disorder. Current treatment in the pediatric population includes phosphodiesterase 5 inhibitors (PDE-5i), endothelin receptor antagonists (ERA), and both inhaled and intravenous prostacyclin pathway agonists. As of December 22, 2015 the first oral prostacyclin pathway agonist, selexipag (Uptravi

Topics: Acetamides; Adolescent; Antihypertensive Agents; Child; Epoprostenol; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Male; Pyrazines; Treatment Outcome; Walk Test; Young Adult

Pulmonary vasodilators in general and prostacyclin analogues in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cell (CEC) level could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that an efficient PAH-specific vasodilator therapy might decrease CEC level.. CECs were prospectively quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n = 30) or PAH secondary to congenital heart disease (PAH-CHD, n = 30): before, after treatment and during follow up. Controls were 23 children with reversible PAH. Oral treatment with endothelin receptor antagonists (ERA) and/or phosphodiesterase 5 inhibitors (PDE5) significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC) treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration.. CECs might be useful as a biomarker during follow-up of pediatric iPAH and PAH-CHD to assess response to treatment and to anticipate clinical worsening.

Topics: Administration, Oral; Adolescent; Adult; Antihypertensive Agents; Case-Control Studies; Child; Child, Preschool; Drug Resistance; Endothelial Cells; Endothelin Receptor Antagonists; Endothelium, Vascular; Epoprostenol; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Immunomagnetic Separation; Infant; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Prospective Studies; Severity of Illness Index; Vascular Resistance; Vasodilator Agents; Young Adult