iloprost and Heart-Defects--Congenital

The Fontan circulation is the optimal treatment for patients with univentricular hearts. These patients are at high risk of circulatory failure. There is no consensus on the optimal drug treatment for the prevention of failure of the Fontan circulation. The aim of this systematic review was to provide an overview of evidence for drug therapy used in the prevention of Fontan circulatory failure.. We searched the Embase database for articles that reported drug therapy in Fontan patients. Studies published between 1997 and 2014 were included if efficacy or safety of medication was assessed, drug therapy aimed to prevent or treat failure of the Fontan circulation, and if the full text was available. Case reports were excluded.. A total of nine studies were included with a total of 267 Fontan patients; four studies evaluated the medication sildenafil, one iloprost, three bosentan, and one enalapril. Among all, two sildenafil studies reported improvement in exercise capacity, one in exercise haemodynamics, and one in ventricular performance. In the largest study of bosentan, an increase in exercise capacity was found. Enalapril did not result in improvements.. The studies analysed in this review suggest that bosentan, sildenafil, and iloprost may improve exercise capacity at the short term. Given the limitations of the studies, more, larger, placebo-controlled studies with longer follow-up periods are needed to better understand which drug therapies are effective in the prevention of failure of the Fontan circulation.

Topics: Bosentan; Endothelin Receptor Antagonists; Exercise Test; Exercise Tolerance; Fontan Procedure; Heart Defects, Congenital; Hemodynamics; Humans; Iloprost; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfonamides; Treatment Outcome; Vasodilator Agents

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

To investigate the effects of intravenous iloprost on pulmonary artery hypertension (PAH) in infants undergoing congenital heart surgery.. In this prospective, randomized study, the study group (n = 15) received a continuous infusion of iloprost (2.0 ng/kg/min) that was delivered immediately after weaning from cardiopulmonary bypass and continued for 72 h postoperatively. Patients in the control group (n = 12) were managed conventionally. The groups were compared in terms of postoperative data, including systolic and mean pulmonary artery (PA) pressures, PA/systemic pressure ratio, lactate level, PAH crisis, ventilation time, reintubation and lengths of intensive care unit (ICU) and hospital stay. Transthoracic echocardiography was used to assess PA pressures at 1 day, 7 days and 30 days after surgery.. No mortality occurred. PAH crisis occurred in 2 (16.6%) patients in the control group and 4 (26.7%) patients in the study group (P = 0.53). Postoperative PA pressures and PA/systemic pressure ratios were similar between the groups (P > 0.05). The durations of ICU (P = 0.40) and hospital (P = 0.98) stays were similar between the groups. Echocardiographic studies demonstrated a significant decrease in postoperative PA pressures in the control (P = 0.001) and study (P = 0.0001) groups. However, no significant change was observed between the groups (P > 0.05). The Tukey multiple comparison test showed a significant decrease in PA pressures at each follow-up in both groups (P < 0.05).. Intravenous iloprost demonstrated no additional benefit over the conventional management of infants with PAH after repair of intracardiac defects. Clinicians may prefer other alternative agents in infants with a high risk of PAH crisis.

Topics: Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Infant; Infusions, Intravenous; Male; Postoperative Care; Prospective Studies; Pulmonary Wedge Pressure; Treatment Outcome; Vasodilator Agents

Congenital heart disease (CHD) can cause pulmonary hypertension (PH) in children, and surgery to correct CHD may be complicated by postoperative pulmonary hypertensive crises (PHC). Clinical data regarding the use of inhaled iloprost to treat children with PH are scarce. Our aim was to determine the efficacy and safety of iloprost in children with PH following surgery to correct CHD. This was a randomized, placebo-controlled study of 22 children (median age 7 months) undergoing surgery to achieve biventricular repair. The combined clinical endpoint was a decrease of more than 20% in the ratio of systolic pulmonary arterial pressure to systolic arterial pressure or pulmonary resistance to systemic resistance, with no PHC or death. Patients were randomized to receive low-dose iloprost (30 ng/kg/min), high-dose iloprost (50 ng/kg/min), or placebo, for 10 min every 2 hr in the first 48 hr after surgery. PHC were experienced by two patients who received placebo and one patient treated with high-dose iloprost. The combined clinical endpoint was reached by six patients administered low-dose iloprost (P = 0.005) and four administered high-dose iloprost (P = 0.077), compared with none in the placebo group. Patients treated with iloprost showed a significant reduction from baseline in mean pulmonary vascular resistance index (-2.2 Wood units, P < 0.05), whereas patients who received placebo showed no significant change. This study supports the use of iloprost to treat children with PH following surgery to correct CHD.

Topics: Blood Pressure; Cardiac Surgical Procedures; Child; Child, Preschool; Double-Blind Method; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Infant; Infant, Newborn; Male; Treatment Outcome; Vasodilator Agents

To evaluate the therapy efficacy of iloprost combined with low dose tadalafil in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH).. Adult CHD patients with severe PAH were included and divided into the sequential combination therapy group [iloprost: 10 µg/inhalation, 6 times per day for 6 months, and then add oral tadalafil (5 mg/d) till 12 months, n = 32] and upfront combination therapy group [iloprost: 10 µg/inhalation, 6 times per day combined with oral tadalafil (5 mg) for 12 months, n = 36]. Data on 6 min walking test (6MWT), Borg dyspnea score, oxygen saturation measurement, WHO classification, and cardiac catheterization were obtained at baseline, 6 and 12 months.. Seventy-two patients were enrolled in the study and 68 patients completed the study. Pulmonary vascular resistance (PVR) was significantly reduced in the sequential combination therapy group[ (12.96 ± 6.48 ) Wood U vs. (16.94 ± 8.11) Wood U, P < 0.05] and in the upfront combination therapy group [(12.45 ± 7.32) Wood U vs. (16.73 ± 9.28) Wood U, P < 0.05] while pulmonary blood flow [(6.77 ± 3.17) L/min vs. (5.08 ± 2.36) L/min, P < 0.05; (6.95 ± 3.32) L/min vs. (5.03 ± 2.32) L/min, P < 0.05], the 6 MWD were significantly increased [(458 ± 59) m vs. (427 ± 65) m, P < 0.05; (494 ± 59) m vs. (436 ± 62) m, P < 0.01], the Borg dyspnea score (2.04 ± 0.72 vs. 2.52 ± 0.79, P < 0.05; 1.72 ± 0.73 vs. 2.51 ± 0.77, P < 0.01) was significantly improved in both groups at 6 months compared to baseline levels. In the upfront combination therapy group, venous oxygen saturation [(68.4 ± 9.3)% vs. (62.9 ± 9.5)%, P < 0.05] and systemic oxygen saturation during exercise[ (87.2 ± 9.7)% vs. (83.1 ± 15.6)%, P < 0.05]at 6 months were also significantly improved compared to baseline. At month 12, significantly lowered pulmonary artery pressure, PVR, Rp/Rs and increased pulmonary blood flow and cardiac index were evidenced in both groups compared to baseline.. Iloprost combined with low dose tadalafil regimen can effectively reduce PVR, increase 6MWD, and improve cardiopulmonary function in adults CHD patients with severe PAH. Compared with the sequential therapy regimen, the upfront combination therapy regimen can more rapidly improve the clinical symptoms of patients.

Topics: Adolescent; Adult; Carbolines; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Tadalafil; Treatment Outcome; Young Adult

Pulmonary arterial hypertension is of importance in congenital cardiac surgery as being a significant cause of morbidity and mortality. Although therapy options are limited, inhaled nitric oxide (NO) is used as a standard therapy. The present study aimed to compare inhaled NO and aerosolized iloprost in children with secondary pulmonary hypertension who underwent congenital cardiac surgery.. Sixteen children included in the study were randomized into either inhaled NO or aerosolized iloprost group. For both groups, the observation period terminated at 72 h after cardiopulmonary bypass.. There was no significant difference between the groups in terms of mean age, weight, cross clamp time, pump time, and extubation time. No significant change was observed in the arterial tension and central venous pressure of both groups before the operation, 30 min after the pump, 45 min after the pump, and after extubation, whereas an increase was observed in the heart rate and cardiac output, and a decrease was observed in the pulmonary artery pressure. The mean values at the above-mentioned time points showed no difference between the groups. No serious adverse event and mortality was detected.. Both inhaled NO and aerosolized iloprost were found to be effective and comparable in the management of pulmonary hypertension.

Topics: Administration, Inhalation; Aerosols; Antihypertensive Agents; Cardiac Surgical Procedures; Child; Child, Preschool; Familial Primary Pulmonary Hypertension; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Infant; Infant, Newborn; Nitric Oxide; Time Factors; Treatment Outcome; Turkey; Vasodilator Agents

Detection of pulmonary vasoreactivity is important for the evaluation of patient with pulmonary arterial hypertension (PAH). The present study aimed to investigate the acute hemodynamic responses to adenosine and iloprost in patients with congenital heart defects (CHDs) and severe PAH.. From Mar 2007 to Nov 2009, 75 patients with severe PAH secondary to left-to-right shunt CHDs underwent acute vasodilator test using aerosolized iloprost (n = 50) or intravenous adenosine (n = 25). The hemodynamics were detected and analyzed.. Decreased mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) were observed in 39 and 43 patients in the iloprost group, and in 16 and 19 patients in the adenosine group, respectively. However, the mean PAP was higher than 40 mm Hg in both groups. No significant difference was observed in the age and baseline hemodynamics between the patients with the decrease of PVR and mean pulmonary-to-aortic pressure (Pp/Ps) ratio greater than 10% and the remaining patients. Adenosine decreased both PAP and systemic arterial pressure significantly, while iloprost inhalation selectively reduced the PAP and increased the oxygen saturation of femoral arterial blood and the pulmonary-to-systemic flow (Qp/Qs) ratio. Compared with adenosine, iloprost caused a more profound decline in the Pp/Ps ratio, PVR and pulmonary-to-systemic vascular resistance ratio, and increase in the Qp/Qs ratio.. The acute haemodynamic responses to adenosine and iloprost varied among the patients with CHDs and severe PAH. Different to adenosine, inhaled iloprost exerted selective pulmonary vasodilative effects and was beneficial for pulmonary gas exchange.

Topics: Acute Disease; Adenosine; Administration, Inhalation; Adolescent; Adult; Child; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Severity of Illness Index; Young Adult

In congenital heart disease with increased pulmonary blood flow and pressure, progressive changes in the vascular structure can lead to irreversible pulmonary hypertension (PH). Pulmonary hemodynamic parameters are used to determine whether surgical correction is no longer indicated. In this study, aerosolized iloprost was used to assess pulmonary vasoreactivity in children with long-standing PH related to congenital heart disease.. Children with long-standing and severe PH secondary to congenital heart disease were included in this study. Various hemodynamic parameters were measured before and after iloprost inhalation (0.5 microg/kg), and vascular resistance was determined. Responders to the iloprost test were defined as those with a decrease in both pulmonary vascular resistance (PVR) and pulmonary-to-systemic vascular resistance ratio (R(p)/R(s)) of >10%.. Eighteen children aged between 7 months and 13 years with long-standing and severe PH secondary to congenital heart disease were studied. Thirteen children had a positive response, resulting in a mean (+/- SD) decrease of PVR from 9.3 +/- 4.6 to 4.6 +/- 2.7 Wood U x m(2) (P < 0.001), and a mean decrease of R(p)/R(s) from 0.54 +/- 0.37 to 0.24 +/- 0.14 (P = 0.005).. Iloprost-induced pulmonary vasodilator responses vary among children with PH related to congenital heart disease. The use of inhaled iloprost in the cardiac catheterization laboratory results in pulmonary vasoreactivity for some of these children particularly a reduction in PVR and the pulmonary-to-systemic vascular resistance ratio.

Topics: Administration, Inhalation; Adolescent; Aerosols; Blood Pressure; Cardiac Catheterization; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Infant; Male; Pulmonary Artery; Pulmonary Circulation; Severity of Illness Index; Vascular Resistance; Vasodilation; Vasodilator Agents

Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each.. A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P:<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation (P:<0.05).. In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Topics: Administration, Inhalation; Aerosols; Analysis of Variance; Child; Child, Preschool; Cyclic AMP; Cyclic GMP; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Infant; Lung; Nitric Oxide; Pulmonary Circulation; Vascular Resistance; Vasodilator Agents

Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular disease. However, these measurements and the interpretation thereof are challenging due to the heterogeneous aetiology of PH in childhood and potentially confounding factors in the catheterisation laboratory. Patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease who have a cardiovascular shunt need to undergo a completely different catheterisation approach than those with idiopathic PAH lacking an anatomical cardiovascular defect. Diagnostic cardiac catheterisation of children with suspected PH usually includes right and left heart catheterisation, particularly for the initial assessment (ie, at the time of diagnosis), and should be performed in experienced centres only. Here, we present graded consensus recommendations for the invasive evaluation of children with PH including those with pulmonary hypertensive vascular disease and/or ventricular dysfunction. Based on the limited published studies and our own experience we suggest a structured catheterisation protocol and two separate definitions of positive acute vasoreactivity testing (AVT): (1) AVT to assess prognosis and indication for specific PH therapy, and (2) AVT to assess operability of PAH associated with congenital heart disease. The protocol and the latter definitions may help in the systematic assessment of these patients and the interpretation of the obtained data. Beyond an accurate diagnosis in the individual patient, such a structured approach may allow systematic decision making for the initiation of a specific treatment and may assist in estimating disease progression and individual prognosis.

Topics: Administration, Inhalation; Adolescent; Anesthesia, General; Anesthesia, Local; Cardiac Catheterization; Child; Conscious Sedation; Consensus; Disease Management; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Nitric Oxide; Oxygen; Prognosis; Pulmonary Artery; Pulmonary Circulation; Respiration, Artificial; Vascular Resistance; Vasodilator Agents; Ventricular Function

Topics: Administration, Inhalation; Adult; Carbolines; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Male; Tadalafil; Young Adult

Inhaled nitric oxide (iNO) is considered standard therapy for pediatric postcardiac surgical pulmonary hypertension (PH). Limited data suggest that inhaled iloprost (inIlo), an aerosolized prostacyclin, may be a feasible and more affordable therapeutic alternative. The goal of this study was to determine if significant hemodynamic change or adverse events would occur in postoperative congenital heart surgery (CHS) patients with PH after their transition from iNO to inIlo. This retrospective review investigated CHS patients with postoperative PH (mean pulmonary artery pressure [mPAP] >25 mmHg) between January 1, 2010 and December 31, 2011 who transitioned from iNO to inIlo. By protocol, CHS patients receiving stable doses of iNO were gradually transitioned to inIlo. After full transition, the patients received inIlo every 2 h, with a final dosing range of 1.25-5 μg/dose. Both PAP and systemic arterial pressure (SAP) were invasively measured during the transition period. Seven patients ages 10 days to 1.5 years completed the protocol. Measurements of mPAP (p = 0.27) and systolic PAP (p = 0.25) did not differ between iNO and inIlo therapy alone. No serious adverse events or complications (bleeding or thrombocytopenia) occurred. The ratio of systolic PAP to SAP decreased in all patients receiving inIlo alone (p = 0.03). Pulmonary hypertension in postoperative CHS patients can be managed successfully with inIlo, and the measured hemodynamics with this agent are similar to those observed with iNO. For the management of postoperative PH, inIlo may be a reasonable alternative, thus reducing the need for costly iNO. Larger confirmatory studies would more robustly facilitate its integration into standard care.

Topics: Administration, Inhalation; Cardiac Surgical Procedures; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Infant; Infant, Newborn; Male; Nitric Oxide; Postoperative Complications; Retrospective Studies; Treatment Outcome; Vasodilator Agents

Topics: Administration, Inhalation; Child, Preschool; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Infant; Male; Retrospective Studies; Vasodilator Agents

Topics: Antihypertensive Agents; Cardiac Surgical Procedures; Familial Primary Pulmonary Hypertension; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Nitric Oxide; Vasodilator Agents

To compare the acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide (NO) in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH).. One hundred and eighty five adult CHDs with severe PAH were nonrandomized into two groups (iloprost, n=127; NO, n=58). Various hemodynamic parameters were measured before and after iloprost or NO inhalation.. Iloprost and NO inhalation resulted in significant reductions in pulmonary arterial pressure (from 110.6±21.8 mmHg to 105.5±22.3 mmHg, p<0.05; from 113.1±18.7 mmHg to 107.2±19.9 mmHg, p<0.05, respectively) and pulmonary vascular resistance (PVR) (from 13.4±8.3 Wood units to 9.6±6.4 Wood units, p<0.01; from 13.7±7.1 Wood units to 9.3±4.9 Wood units, p<0.01, respectively) and increases in pulmonary blood flow (from 6.7±3.3 L/min to 9.4±5.8 L/min, p<0.05; from 6.6±3.1 L/min to 9.6±5.9 L/min, p<0.01, respectively) and the Qp/Qs ratio (from 1.5±0.8 to 2.1±1.4, p<0.01; from 1.5±0.8 to 2.0±1.3, p<0.01, respectively). When the effects of inhaled iloprost and NO were compared, similar reductions in pulmonary arterial pressure and pulmonary vascular resistance were observed. Aerosolized iloprost and inhaled nitric oxide (iNO) were generally well tolerated and no patient experienced any side effects during inhalation.. Aerosolized iloprost can be effectively and safely used and might be an alternative to NO for testing pulmonary vascular reactivity and treating severe PAH in adult CHD patients.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Familial Primary Pulmonary Hypertension; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Nitric Oxide; Severity of Illness Index; Young Adult

To investigate the immediately effects of inhaled aerosolized iloprost in adult patients with severe pulmonary arterial hypertension (PAH) secondary to congenital heart diseases (CHD).. Adult patients with severe PAH secondary to CHD (n = 165) were included in this study. Right heart catheterization was performed, Pulmonary and systemic blood flow, the oxygen consumption VO(2) (ml/min) were calculated using Fick's principle. Pulmonary vascular resistances (PVR) were calculated with standard formulas and indexed to body surface area. Hemodynamic parameters were measured before and after iloprost inhalation (20 µg).. Post iloprost inhalation, heart rate, mean aortic pressure, pulmonary systolic pressure to aortic systolic pressure ratio all remained un changed (P > 0.05), while pulmonary artery pressure (PAP) were significantly reduced and Qp significantly increased from (7.2 ± 4.8) L/min to (9.9 ± 7.2) L/min (P < 0.01), PVR was also significantly reduced from (13.4 ± 8.7) Wood units to (9.5 ± 6.6) Wood units (P < 0.01), and left-to-right shunt volume increased from (3.2 ± 4.4) L/min to (5.5 ± 7.0) L/min (P < 0.01) and right-to-left shunt volume decreased from (1.0 ± 1.0) L/min to (0.7 ± 0.7) L/min (P < 0.01). Subgroup analysis showed that adult patients with patent ductus arteriosus and/or ventricular septal defects are more likely to develop severe pulmonary arterial hypertension or Eisenmenger syndrome than patients with atrial septal defects.. Inhaled Aerosolised iloprost use is effective and safe for adult patients with severe pulmonary arterial hypertension secondary to congenital heart diseases.

Topics: Administration, Inhalation; Adolescent; Adult; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Male; Vascular Resistance; Young Adult

Congenital heart disease (CHD) is responsible for pulmonary hypertension (PH) in children in about 50% of cases. This pre-operative dynamic pulmonary hypertension can be superimposed and aggravated by acute post-operative PH or persist as chronic PH, especially in children who are not operated on early enough. Inhaled iloprost, a stable prostacyclin analogue, is used for the post-operative management of PH in infants and children with CHD. In a prospective open-label proof-of-concept study, the efficacies of inhaled nitric oxide (iNO) and inhaled iloprost were directly compared. Primary endpoints were the occurrence of a major or minor pulmonary hypertensive crisis. No significant difference between the effects of iNO versus iloprost on peri-operative PH was observed. Neither substance on its own prevented pulmonary hypertensive crises in high-risk infants, so a combination of both substances should be tested in future trials. In China, there are more than 4 million untreated CHD patients. More than 50% of them are untreated adults. Acute pulmonary vasoreactivity tests were performed in CHD patients between 9 months and 43 years of age using inhaled iloprost, in order to find out whether a pre-operative response to inhaled iloprost is a good predictor for the post-operative performance of these patients. The results showed that patient selection criteria for surgery should include both a 20% reduction in pulmonary vascular resistance (PVR) index after iloprost inhalation and a resulting PVR index <11 Wood U/m(2). CHD children between 14 days and 11 years of age took part in a placebo-controlled pilot study that investigated the role of aerosolized iloprost in the treatment of PH after corrective surgery. They received either low- or high-dose iloprost or placebo. Inhaled iloprost significantly improved haemodynamics in a dose-dependent manner and prevented reactive PH and pulmonary hypertensive crises in most of these mechanically ventilated children after CHD repair.

Topics: Cardiac Surgical Procedures; Child; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Nitric Oxide; Perioperative Care; Postoperative Complications; Risk Factors; Vasodilator Agents

There are several animal models for studying human pulmonary hypertension (PH). An increased flow model in pigs was developed at the University Hospital in Heidelberg in order to simulate congenital heart disease. The high pulmonary blood flow is achieved by installation of a Blalock-Taussig anastomosis. In order to further improve this model by adding a pressure component, the left pulmonary artery is ligated. An acute model, which is used at the Innsbruck Medical University, addresses another disease entity. Human meconium is placed deeply into the trachea of the pigs in order to induce an acute respiratory distress syndrome-like response in the lungs. Animals were randomly assigned to four treatment groups. Inhaled iloprost, due to its pulmonary and intrapulmonary selectivity, was the only substance that significantly reduced intrapulmonary shunt volumes. In humans, PH encompasses multiple disease subtypes. Pulmonary arterial hypertension (PAH) accounts for only 6% of PH cases, however, all existing treatments are indicated only for PAH. This means that for 94% of patients with PH, no specific medication is available. Therefore, huge efforts have been made to better understand the pathophysiology of PH and to detect new signalling pathways that may allow new compounds to be developed that will ultimately improve the prognosis of PAH and non-PAH PH patients. Promising new substances include riociguat, a stimulator of the soluble guanylate cyclase (sGC), as well as cinaciguat, a sGC activator, and an elastase inhibitor. Riociguat (BAY 63-2521) is an oral agent that targets the intact/native form of sGC. It enhances the sensitivity of sGC to low levels of bioavailable nitric oxide (NO) and is also capable of stimulating native sGC independently of NO. Thus, unlike phosphodiesterase-5 inhibitors, the effect of riociguat is not limited by low NO levels. In a multicentre open-label phase II study, riociguat exerted strong and significant effects on pulmonary haemodynamics and exercise capacity in patients with PAH and in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Riociguat is currently being evaluated in phase III clinical trials both in PAH and in CTEPH patients. Clinical studies with riociguat in earlier development stages have addressed PH in lung diseases and systolic left ventricular failure. An elastase inhibitor is currently being investigated in phase I clinical trials in patients with PH owing to chronic obstructive pulmona

Topics: Animals; Disease Models, Animal; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Pyrazoles; Pyrimidines; Vasodilator Agents

To evaluate the efficacy of iloprost in acute vasodilatation test during cardiac catheterization and to explore a useful hemodynamic indication regarding operability in the patients with severe pulmonary hypertension (PH) related to congenital heart disease (CHD).. The clinical data of 46 patients [mean age (12 ± 9) years] with severe PH related to CHD from June 2006 to December 2008 was retrospectively analyzed. All patients underwent standard right and left cardiac catheterization and a trial of inhaled iloprost test during cardiac catheterization. The mean pulmonary arterial pressure was (80 ± 13) mm Hg (1 mm Hg = 0.133 kPa) and pulmonary vascular resistance index was (17 ± 10) wood.m². A positive response to inhaled iloprost was defined as a decrease of at least 20% in pulmonary vascular resistance index (PVRI) without changes on systemic artery pressure. Patients with positive response to iloprost underwent cardiac surgical repair. The pulmonary artery pressure and PVRI was monitored by Swan-Ganz catheter postoperatively.. Of the 46 patients, 29 (63.1%) showed a positive response after iloprost inhalation, defined by a significant reduction in PVRI from (15 ± 6) wood.m(2) at baseline to (9 ± 4) wood.m² in response to iloprost inhalation therapy (P < 0.05). The ratio of pulmonary to systemic resistance (Rp/Rs) decreased from 0.7 ± 0.2 to 0.4 ± 0.2 (P < 0.05). Seventeen patients (36.9%) didn't respond to iloprost displayed only little changes in PVRI [from (21 ± 10) wood.m(2) to (19 ± 9) wood.m²] and Rp/Rs (from 1.0 ± 0.5 to 0.9 ± 0.5). Out of 29 positive patients, 21 (72%) underwent successful cardiac surgical repair with a reduction of mean pulmonary arterial pressure (mPAP) to an average of (27 ± 10) mm Hg after the operation. Only 2 patients out of the 17 patients from the negative group were referred to surgery. Their mPAP was greater than 45 mm Hg.. A significant reduction in pulmonary artery pressure after cardiac surgery was observed in patients with positive response to inhaled iloprost. Inhaled iloprost may be a valuable tool in the preoperative evaluation of patients with severe PH related to CHD.

Topics: Administration, Inhalation; Adolescent; Child; Child, Preschool; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Infant; Lung; Male; Preoperative Care; Retrospective Studies; Vasodilator Agents; Young Adult

Pulmonary hypertensive crisis (PHC) is a significant contributor to the morbidity and mortality of surgery for congenital heart defect. Management of such a potentially fatal complication has been evolving for the past decades. Inhaled iloprost has been reported as an alternative treatment for this condition. We evaluated the use of aerosolized iloprost as a rescue therapy for PHC in children undergoing congenital heart surgery.. In this clinical study, 12 high risk children were monitored in order to identify postoperative PHC after congenital heart repair. Factors being monitored included pulmonary artery pressure, systemic blood pressure, left atrial pressure, transcutaneous oximetry and heart rate. PHC was defined as an acute rise in pulmonary pressure which causes cardiopulmonary compromise as reflected by desaturation and hypotension. Despite conventional medical treatment to prevent postoperative PHC, children with PHC were therefore administered with aerosolized iloprost (0.5 microg/kg).. Eight of the 12 children had one or more episodes of PHC, secondary to the pulmonary vasoreactivity. All responded to the aerosolized iloprost treatment, as demonstrated by a fall in their mean pulmonary pressure from 47.9 + or - 14.9 to 30.2 + or - 7.9 mmHg (p=0.012) and a rise in the arterial saturation from 82.2 + or - 16.7 to 93.4 + or - 11.5 % (p=0.012) while mean systemic blood pressure tended to increase from 59.4 + or - 12.1 to 64 + or - 10.3 mmHg (p=0.16).. In medical setting with limited access to the nitric oxide, inhaled iloprost is consider to be an effective alternative treatment for postoperative PHC in children undergoing congenital heart surgery.

Topics: Administration, Inhalation; Adolescent; Child; Child, Preschool; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Infant; Postoperative Complications; Prospective Studies

Pulmonary arterial hypertension (PAH) is a recognized complication of congenital heart disease. Despite differences in etiology and pathophysiology, successful therapy for idiopathic PAH may benefit in patients with congenital heart disease. We theorized that combination of oral and aerosolization prostacyclin will benefit this group of patients in long-term.. The study design was single group and open label study with intention to treat for patients with congenital heart disease with pulmonary artery (PA pressure) more than 50% of systemic pressure. All patients were given a combination of orally given beraprost sodium and inhalation of iloprost for 12 months. Data were collected prospectively consisting of functional class, O2 saturation, 6-minute walk test and right ventricular systolic pressure (RVSP).. There were 23 patients with an average right ventricular systolic pressure (+/- SD) of 94.8 +/- 14.5 mmHg and with average age of 27.8 +/- 14.9 years (2.5 to 50 years). The average oxygen saturation was 87.9 +/- 7 %. There were 12 patients with post surgical repair or cardiac catheterization interventional procedure and 11 with and Eisenmenger's syndrome. There were significant improvement of 6-minute-walk test from an average of 268 +/- 70 meters to 308 +/- 57 meters at the end of 12 months. The functional class of patients was also improving. However, there were no significant different in oxygen saturation.. Combination therapy of oral and inhalation of aerosolized vasodilators is a fascinating concept in the therapy of pulmonary hypertension. Treated patients showed an improvement in exercise capacity and right ventricular systolic pressure without a worsening in oxygen saturation.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Epoprostenol; Exercise Test; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Iloprost; Middle Aged; Oxygen; Vasodilator Agents; Ventricular Pressure

Topics: Administration, Inhalation; Blood Pressure; Cardiac Surgical Procedures; Child, Preschool; Female; Heart Defects, Congenital; Heart Rate; Heart Septal Defects; Humans; Hypertension, Pulmonary; Iloprost; Intraoperative Complications; Oxygen; Vasodilator Agents

Both aerosolized and intravenous infusion of iloprost caused a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance. Although intravenous infusion caused a large decrease in mean systemic arterial pressure, this was only slightly affected by aerosolized iloprost. Aerosolized iloprost caused a significant decrease in the pulmonary-to-systemic vascular resistance ratio; however, intravenous infusion did not cause a prominent decrease in this ratio.

Topics: Administration, Inhalation; Adolescent; Aerosols; Child; Child, Preschool; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Hypotension; Iloprost; Infant; Infusions, Intravenous; Pulmonary Wedge Pressure; Vascular Resistance; Vasodilator Agents