iloprost and Familial-Primary-Pulmonary-Hypertension

Pediatric pulmonary hypertension (PAH) is a rare disease that carries a poor prognosis if left untreated. Although there are published guidelines for the treatment of children with pulmonary hypertension, due to the limited number of robust pediatric clinical trials, recommendations are often based on limited data or clinical experience. Furthermore, many practical aspects of care, particularly for the pediatric patient, are learned through experience and best navigated with a multidisciplinary team. While newer PAH therapies have been approved for adults, there is still limited but expanding experience in pediatrics. This new information will help improve the targets of goal-oriented therapy. Lastly, this review highlights practical aspects in the use of the different therapies available for the treatment of pediatric pulmonary hypertension.

Topics: Adolescent; Adult; Bosentan; Calcium Channel Blockers; Child; Child, Preschool; Epoprostenol; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Iloprost; Infant; Infant, Newborn; Phenotype; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Prognosis; Pulmonary Arterial Hypertension; Pyridazines; Pyrimidines; Receptors, Endothelin; Sildenafil Citrate; Sulfonamides; Tadalafil; Young Adult

Pulmonary hypertension is a medical condition characterized by elevated pulmonary arterial pressure and secondary right heart failure. Pulmonary arterial hypertension is a subset of pulmonary hypertension, which is characterized by an underlying disorder of the pulmonary arterial vasculature. Pulmonary hypertension can also occur secondarily to structural cardiac disease, autoimmune disorders, and toxic exposures. Although pregnancies affected by pulmonary hypertension and pulmonary arterial hypertension are rare, the pathophysiology exacerbated by pregnancy confers both high maternal and fetal mortality and morbidity. In light of new treatment modalities and the use of a multidisciplinary approach to care, maternal outcomes may be improving.

Topics: Anesthesia, Obstetrical; Bosentan; Carbolines; Directive Counseling; Epoprostenol; Extracorporeal Membrane Oxygenation; Familial Primary Pulmonary Hypertension; Female; Humans; Iloprost; Infant, Newborn; Piperazines; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, High-Risk; Prognosis; Pulmonary Circulation; Purines; Sildenafil Citrate; Sulfonamides; Tadalafil

Since continuous IV epoprostenol was approved in the U.S., parenteral prostanoid therapy has remained the gold standard for the treatment of patients with advanced pulmonary arterial hypertension (PAH). Prostanoid agents can be administered as continuous intravenous infusions, as continuous subcutaneous infusions and by intermittent nebulization therapy. This article presents data from clinical trials of available prostanoid agents, and their varied routes of administration. The varied routes of administration allow for the incremental use of this class of agents in advanced PAH, and if PAH progresses. Prostanoids will remain a major component of PAH therapy for the foreseeable future.

Topics: Administration, Inhalation; Antihypertensive Agents; Epoprostenol; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous

This paper provides an overview of the current state of pharmacotherapy in children with pulmonary arterial hypertension (PAH) and a brief introduction to the potentially novel pharmacologic targets for PAH. Currently, 3 classes of drugs including prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase-5 inhibitors are approved for the treatment of PAH in children, which has led to improved hemodynamics, increased exercise capacity and prolonged survival. Despite these improvements, there is still a need to carry out well-designed, randomized, controlled studies with larger samples. In addition, novel drugs targeting other molecular pathways should be developed.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Bosentan; Calcium Channel Blockers; Child; Epoprostenol; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Iloprost; Sulfonamides

Iloprost (Ventavis, Bayer Schering Pharma, Germany) is a synthetic prostacyclin that is used in its inhalative form for the therapy of pulmonary arterial hypertension. Long-term therapy can increase exercise capacity and quality of life. The use of modern nebulizers especially designed for the administration of iloprost guarantees the pulmonary deposition of the required doses and systematically minimizes side effects. Regarding existing data, inhalative iloprost acts in effective and safe combination with other classes of medication; indeed, such combination therapy is frequently necessary in pulmonary arterial hypertension.

Topics: Administration, Inhalation; Animals; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Evidence-Based Medicine; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Iloprost; Nebulizers and Vaporizers; Risk Assessment; Treatment Outcome; Vasodilation; Vasodilator Agents

The Rho-kinase pathway has been shown to be involved in the pathogenesis of PAH. As yet, however, the acute effects of the Rho-kinase inhibitor fasudil have not been compared with established pulmonary selective vasodilators in patients with PAH. We compared the acute effects of intravenous fasudil with inhaled iloprost in patients with pulmonary arterial hypertension (PAH).. Using a crossover design, 50 patients with PAH (idiopathic PAH, PAH associated with repaired left-to-right cardiac shunts, or connective tissue disease) were randomized to iloprost inhalation (5 μg) and intravenous fasudil (30 mg over 30 min). Hemodynamic data were collected at baseline and during acute drug exposure.. Comparable decreases were observed in mean pulmonary artery pressure (-4.6 ± 4.3 mmHg vs. -4.8 ± 4.2 mmHg) and pulmonary vascular resistance (-3.0 ± 3.0 Wood U vs. -2.2 ± 2.7 Wood U) with fasudil infusion and iloprost inhalation, respectively, during acute challenge. However, fasudil infusion resulted in a more pronounced increase in mean cardiac output and mixed venous oxygen saturation compared with iloprost inhalation (13.7 ± 17.1% vs. 6.9 ± 15.0%; p=0.044 and 4.5 ± 5.3% vs. 2.7 ± 8.2%; p=0.044, respectively). Whereas inhaled iloprost resulted in a non-significant increase in mean systemic arterial oxygen saturation (0.8 ± 3.6%), infused fasudil resulted in a non-significant reduction (-0.6 ± 1.1%).. Infused fasudil improved pulmonary hemodynamics in patients with PAH without significant toxicity.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Administration, Inhalation; Adolescent; Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Familial Primary Pulmonary Hypertension; Female; Hemodynamics; Humans; Iloprost; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Vasodilator Agents; Young Adult

Inhaled treprostinil is a prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) that may provide a more convenient treatment option for patients receiving inhaled iloprost while maintaining the clinical benefit of inhaled prostacyclin therapy.. In this open-label safety study, 73 PAH patients were enrolled with primarily World Health Organization Class II (56%) or III (42%) symptoms. At baseline, most patients (93%) were receiving 5 μg of iloprost per dose but 38% of patients reported a dosing frequency below the labeled rate of 6-9 times daily. Patients initiated inhaled treprostinil at 3 breaths four times daily (qid) at the immediate next scheduled iloprost dose. The primary objective was to assess the safety of rapid transition from iloprost to inhaled treprostinil; clinical status and quality of life were also assessed.. Most patients (84%) achieved the target treprostinil dose of 9 breaths qid and remained on study until transition to commercial therapy (89%). The most frequent adverse events (AEs) were cough (74%), headache (44%), and nausea (30%), and five patients prematurely discontinued study drug due to AE (n = 3), disease progression (n = 1), or death (n = 1). At week 12, the time spent on daily treatment activities was reduced compared to baseline, with a mean total savings of 1.4 h per day. Improvements were also observed at week 12 for 6-min walk distance (+16.0; P < 0.001), N-terminal pro-B-type natriuretic peptide (-74 pg/mL; P = 0.001), and the Cambridge Pulmonary Hypertension Outcome Review (all domains P < 0.001).. Pulmonary arterial hypertension patients can be safely transitioned from inhaled iloprost to inhaled treprostinil while maintaining clinical status.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Antihypertensive Agents; Arterial Pressure; Drug Administration Schedule; Drug Substitution; Epoprostenol; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Prospective Studies; Pulmonary Artery; Quality of Life; Time Factors; Treatment Outcome; United States; Vasodilation; Vasodilator Agents; 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

Systemic artery to pulmonary artery fistulas (SA-PAFs), are extremely rare in people without congenital heart disease. In this group of patients pulmonary arterial hypertension was reported in the single case. Then, we describe a case of multiple SA-PAFs, which were the cause of severe nonreversible arterial pulmonary hypertension in a patient who had a right-sided pneumothorax 35 years earlier.. 52-year-old male Caucasian patient with echocardiographically confirmed pulmonary hypertension (PH) was admitted to cardiology department due to exertional dyspnea and signs of right ventricle failure. Routine screening for causes of secondary PH was negative. Right heart catheterization (RHC) confirmed a high degree arterial PH [mean pulmonary artery pressure (mPAP); 50,6 mmHg, pulmonary wedge pressure (PWP); 11,3 mmHg, pulmonary vascular resistance (PVR); 11,9 Wood's units (WU)] irreversible in the test with inhaled nitric oxide. Oxygen saturation (SaO. Non-congenital SA-PAFs are extremely rare, however, they should be excluded in patients with pulmonary arterial hypertension and history of inflammatory or infectious disease of the lung and pleura, pneumothorax, cancer or Takayashu's disease and after chest trauma.

Topics: Arterio-Arterial Fistula; Cardiac Catheterization; Computed Tomography Angiography; Familial Primary Pulmonary Hypertension; Fatal Outcome; Heart Failure; Humans; Iloprost; Lung; Male; Middle Aged; Pneumothorax; Pulmonary Artery; Pulmonary Wedge Pressure; Sildenafil Citrate; Vascular Resistance

The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.. We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.. The rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).. The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.

Topics: Administration, Inhalation; Adult; Aged; Arterial Pressure; Atrial Natriuretic Factor; Calcium Channel Blockers; Endarterectomy; Familial Primary Pulmonary Hypertension; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Protein Precursors; Retrospective Studies; Software; Vasodilator Agents

This study aimed to identify the relationship between pulmonary vascular capacitance (PVC) and vasoreactivity in patients with idiopathic pulmonary arterial hypertension (IPAH), and the value of PVC in predicting long-term response to CCB treatment.. Pulmonary vasodilator testing with inhaling iloprost was performed in 308 newly diagnosed IPAH patients. Acute vasodilator-responsive patients accepted CCBs treatment. Patients who benefit from long-term CCB were defined as those being in World Health Organization (WHO) functional class II or I after at least 1 year on CCB monotherapy.. PVC had significant correlations with WHO function class, 6-min walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance (r = -0.363, p < 0.001; r = 0.333, p < 0.001; r = -0.514, p < 0.001; r = -0.739, p < 0.001). Thirty-five acute vasodilator-responsive IPAH patients (11.4 %) displayed less severe disease and a higher baseline PVC (1.5 ± 0.6 vs. 1.1 ± 0.7 ml/mmHg, p = 0.003). During acute vasodilator testing, PVC increased significantly by mean of 79 ± 48 % and reached to a higher absolute value of 2.6 ± 1.5 ml/mmHg compared with non-responsive patients (1.4 ± 1.5 ml/mmHg, p < 0.001). Furthermore, PVC increased more during acute vasodilator testing in the 24 patients who benefit from long-term CCB treatment (1.4 ± 1.3 vs. 0.5 ± 0.4 ml/mmHg, p = 0.004). The OR of increased PVC during vasodilator testing for predicting patients with long-term response to CCB was 1.24 (95 % CI 1.02-1.50, p = 0.031) as assessed by multivariable logistic regression analysis.. PVC was higher in acute vasodilator-responsive IPAH patients and may be a predictor of long-term response to CCBs therapy.

Topics: Adult; Arterial Pressure; Calcium Channel Blockers; Cardiac Output; Familial Primary Pulmonary Hypertension; Female; Humans; Iloprost; Male; Middle Aged; Predictive Value of Tests; Pulmonary Artery; Severity of Illness Index; Time Factors; Vascular Capacitance; Vascular Resistance; Vasodilation; Vasodilator Agents; Walk Test; Young Adult

The vasoreactivity test is usually performed to identify pulmonary arterial hypertension (PAH) patients who may benefit from long-term calcium channel blocker (CCB). The first and most commonly used agent is intravenous epoprostenol. A few other agents such as intravenous adenosine and inhaled nitric oxide are also used. In Thailand, epoprostenol is not available and the others are costly. Therefore, inhaled iloprost or oral sildenafil may be alternatives to test vasoreactivity.. To evaluate the hemodynamic effect and response rate of inhaled iloprost and oral sildenafil during acute vasoreactivity test in PAH patients.. In this retrospective descriptive study, the authors recruited patients with idiopathic PAH (IPAH) or PAHassociated with connective tissue disease (PAH-CNT) seen at the Medicine department Siriraj Hospital between January 2005 and December 2011 for whom acute vasoreactivity test was indicated. All patients used 20 microgram of inhaled iloprost via Delphinus® nebulizer for the test. Hemodynamic parameters were recorded before and after iloprost administration. Eight of those patients subsequently had a repeated test using 100 mg of oral sildenafil.. Fifteen patients had acute vasoreactivity testing. Eleven patients were IPAH and four were PAH-CNT Using ESC/ERS guidelines criteria for responsiveness to vasoreactivity test, the response rate was 13% (2 out of 15 patients) using inhaled iloprost. Hemodynamic change was seen as early as five minutes after the inhalation and the effect lasted up to 35 minutes. The response rate was 25% (2 out of 8 patients) using oral sildenafil. Hemodynamic change was seen as early as 30 minutes after sildenafil ingestion and lasted up to 480 minutes.. Inhaled iloprost can be used for acute vasoreactivity test in Thailand. The hemodynamic parameters should be recorded immediately after iloprost inhalation. Oral sildenafil, however, is not a suitable agent for acute vasoreactivity test due to its extended effect.

Topics: Administration, Inhalation; Administration, Oral; Adult; Blood Pressure; Calcium Channel Blockers; Familial Primary Pulmonary Hypertension; Female; Humans; Iloprost; Male; Middle Aged; Piperazines; Pulmonary Artery; Purines; Retrospective Studies; Severity of Illness Index; Sildenafil Citrate; Sulfonamides; Thailand; Vasodilator Agents

As an important method of hemodynamic assessment in idiopathic pulmonary arterial hypertension (IPAH), cardiac catheterization combined with pulmonary vasoreactivity testing remains with limited experience in children, and the acute pulmonary vasodilator agents as well as response criteria for vasoreactivity testing remain controversial. The aim of this study was to investigate the clinical importance, agent selection, and responder definition of cardiac catheterization combined with pulmonary vasoreactivity testing in pediatric IPAH.. The patients admitted to Department of Pediatric Cardiology of Beijing Anzhen Hospital between April 2009 and September 2013 with suspected IPAH, under 18 years of age, with WHO functional class II or III, were enrolled. All the patients were arranged to receive left and right heart catheterization and pulmonary vasoreactivity testing with inhalation of pure oxygen and iloprost (PGI2) respectively. Hemodynamic changes were analyzed, and two criteria, the European Society of Cardiology recommendation criteria (Sitbon criteria) and traditional application criteria (Barst criteria), were used to evaluate the test results.. Thirty-nine cases of children with suspected IPAH underwent cardiac catheterization. In 4 patients IPAH was excluded; 4 patients developed pulmonary hypertension crisis. The other 31 patients received standard cardiac catheterization and pulmonary vasoreactivity testing. Baseline mean pulmonary artery pressure (mPAP) was (66 ± 16) mmHg (1 mmHg = 0.133 kPa), and pulmonary vascular resistance index (PVRI) (17 ± 8) Wood U · m². After inhalation of pure oxygen, mPAP fell to (59 ± 16) mmHg, and PVRI to (14 ± 8) Wood U · m² (t = 4.88 and 4.56, both P < 0.001) . After inhalation of PGI2, mPAP fell to (49 ± 21) mmHg, and PVRI to (12 ± 9) Wood U · m² (t = 7.04 and 6.33, both P < 0.001). According to the Sitbon criteria, the proportion of pure oxygen responders was 6.5% (3/31) , while PGI2 responders was 35.5%, and the difference was significant (P = 0.004). According to the Barst criteria, the proportion of pure oxygen responders was 16.1% (5/31), while PGI2 responders was 51.6% (16/31), and the difference was significant (χ² = 0.09, P = 0.001).. For children with IPAH, cardiac catheterization combined with pulmonary vasoreactivity testing has important value in differential diagnosis, severity estimation, and treatment (including the emergency treatment) choices. Pulmonary hypertension crisis is an important complication of cardiac catheterization in pediatric IPAH. Younger age, general anesthesia, crisis history, and poor heart function are important risk factors for pulmonary hypertension crisis. PGI2 is a relatively ideal agent for vasoreactivity testing in children with IPAH, which has more responders than traditionally used pure oxygen.. of responders are not completely consistent using different criteria, and comprehensive evaluation should be done according to the goals of treatment in clinical practice.

Topics: Administration, Inhalation; Adolescent; Anesthesia, General; Cardiac Catheterization; Child; Child, Preschool; Familial Primary Pulmonary Hypertension; Female; Hemodynamics; Humans; Iloprost; Infant; Male; Pulmonary Artery; Pulmonary Circulation; Pulmonary Wedge Pressure; Severity of Illness Index; Vascular Resistance; Vasodilator Agents

There are limited data on the effect of iloprost therapy in patients with Eisenmenger syndrome (ES). The aim of our study was to evaluate the effect of inhaled iloprost therapy on exercise capacity, quality of life (QoL), cardiac function, and hemodynamics in patients with ES. Eighteen consecutive patients with ES and exertional dyspnea according to the World Health Organization functional class III or IV were prospectively recruited. Exercise capacity was assessed by a 6-minute walk test, and QoL was measured on a 12-Item Short-Form Health Survey. Echocardiographic measurements included peak systolic and mean pulmonary arterial pressures, pulmonary vascular resistance, and myocardial performance index of the right ventricle (RV). All patients underwent comprehensive evaluation at baseline and after 24 weeks of treatment. Of the 18 patients with ES, 13 were included for analysis. After 24 weeks of iloprost therapy, 6-minute walk test distance significantly increased (289.1 ± 76.9 to 369.5 ± 93.4 m, p = 0.032) in addition to concomitant improvements in the 12-Item Short-Form Health Survey physical and mental component summaries (20.6 ± 19.3 to 52.6 ± 28.0, p <0.05; 33.9 ± 19.7 to 54.9 ± 21.3, p <0.05, respectively). RV myocardial performance index improved significantly after treatment (0.80 ± 0.31 to 0.59 ± 0.12, p = 0.042). Pulmonary arterial pressure and pulmonary vascular resistance did not improve with iloprost therapy. This study showed that 24 weeks of inhaled iloprost therapy in patients with ES led to significant improvements in exercise capacity, QoL, and RV function. These results likely explain the symptomatic relief reported by patients with ES receiving iloprost therapy.

Topics: Administration, Inhalation; Adult; Cohort Studies; Echocardiography, Doppler; Eisenmenger Complex; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Prospective Studies; Quality of Life; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Ventricular Dysfunction, Right

Idiopathic pulmonary arterial hypertension (IPAH), formerly called primary pulmonary hypertension, is a rare disease (incidence and prevalence rates of approximately one and six cases per million inhabitants, respectively) with different clinical phenotypes. A group of diverse conditions manifest pulmonary arterial hypertension (PAH) and share similar pathological and/or clinical findings with IPAH. By definition, IPAH is diagnosed only after alternative diagnoses have been ruled out. Extensive investigation is needed to determine if PAH is associated with thyroid diseases, infectious diseases, autoimmune conditions, exposure to certain drugs (particularly anorexigens), certain genetic mutations, and so on. The presence of genetic abnormalities and risk factors (such as specific drug exposures) reinforces the "multiple hit" concept for the development of pulmonary hypertension. Fortunately, within the past two decades, therapeutic options have become available for IPAH, resulting in improved survival and clinical outcomes. At least seven different compounds have been registered for PAH treatment. However, even with aggressive PAH-specific therapy, mortality rates remain high (∼40% at 5 years). Given the high mortality rates, the use of combinations of agents that work by different pathways has been advocated (either as "add-on" therapy or initial "up front" therapy). Further, new therapeutic agents and treatment strategies are on the near horizon, aiming to further improve survival from the remarkable progress already seen.

Topics: Aminorex; Antihypertensive Agents; Appetite Depressants; Bosentan; Dasatinib; Epoprostenol; Familial Primary Pulmonary Hypertension; Fenfluramine; Genetic Predisposition to Disease; Humans; Hypertension, Pulmonary; Iloprost; Phenylpropionates; Piperazines; Protein Kinase Inhibitors; Purines; Pyrazoles; Pyridazines; Pyrimidines; Risk Factors; Sildenafil Citrate; Sulfonamides; Sulfones; Thiazoles; Vasodilator Agents

The objective of this study was to evaluate the incidence of the most severe vascular complications, such as pulmonary arterial hypertension, scleroderma renal crisis, and digital necrosis requiring amputation, in a monocentric group of systemic sclerosis (SSc) patients cyclically treated with intravenous iloprost. We reviewed the record-charts of 115 patients affected by SSc (18 men and 97 women, mean age 58.9.1 ± 14.2 years) regularly receiving iloprost for at least 3 years; the mean duration of the treatment was 98.8 ± 37.5 months (a total of 946.8 years of therapy). Demographic and clinical features were recorded. None of the patients died of SSc-associated vascular complications. After iloprost administration digital gangrene requiring amputation developed in 2 patients who had concomitant peripheral arterial disease (a total of 3 episodes; annual incidence of 0.31 for 100 years of iloprost therapy). Four patients were diagnosed with pulmonary arterial hypertension during iloprost treatment (annual incidence of 0.42 for 100 years of drug therapy); in none of the cases did the complication show a progressive course. No cases of scleroderma renal crisis were observed. With the limits of an observational study and in the absence of a control group, our experience suggests that prolonged cyclic iloprost therapy may limit the incidence/progression of severe digital and visceral SSc-vasculopathy.

Topics: Adult; Aged; Amputation, Surgical; Familial Primary Pulmonary Hypertension; Female; Finger Injuries; Gangrene; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Peripheral Arterial Disease; Scleroderma, Systemic; Severity of Illness Index; Toes; Vasodilator Agents

Systemic sclerosis (SSc) is a chronic disease of unknown etiology which affects the vascular system and connective tissue. A wide series of studies showed an increased prevalence of cancer in patients with SSc than the normal population. Prostacyclin (PGI2) is an endogenously produced element that is basically synthesized by arachiodonic acid through prostacyclin synthesis in vascular system endothelial cells. Iloprost is a stable analogue of PGI2 which is used in the treatment of pulmonary arterial hypertension (PAH). In a limited number of animal models, the anti-metastatic activity of PGI2 is observed. Herein, we report iloprost treatment of a 60-year-old-woman with SSc, who lately developed PAH as a complication of her disease and lung adenocarcinoma as a co-incidence simultaneously. These two mortal complications were both treated successfully with inhaled iloprost until her death due to gastrointestinal complications of SSc.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Administration, Inhalation; Antihypertensive Agents; Antineoplastic Agents; Biopsy; Disease Progression; Familial Primary Pulmonary Hypertension; Fatal Outcome; Female; Gastrointestinal Diseases; Humans; Hypertension, Pulmonary; Iloprost; Immunohistochemistry; Lung Neoplasms; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Scleroderma, Systemic; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents

We investigated the short-term and medium-term results in patients with pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) undergoing transcatheter closure. Fifteen patients with severe PAH associated with ASD who underwent successful occluder implantation from 2007 to 2010 were included. Clinical, echocardiographic, and hemodynamic data were reviewed. Severe PAH was defined as pulmonary arterial systolic pressure measured by catheterization was ≥60 mmHg and pulmonary vascular resistance (PVR) ≥6 Wood Units (WU). Compared with baseline, the 6-minwalking distance significantly increased by 29.7 ± 26.3 m (P < 0.001) at 3 months (short-term) and 65.4 ± 63.6 m (P < 0.001) at 23.4 ± 9.7 months (medium-term), World Health Organization function class considerably improved after postclosure short-term and medium-term. Repeat cardiac catheterization (n = 7) showed that mean pulmonary arterial pressure decreased from 51.6 ± 9.4 mmHg at baseline to 21.0 ± 3.8 mmHg (P < 0.001) at follow-up of 12 months. The PVR decreased by 5.6 ± 1.1 WU (P < 0.001). Through carefully selected patients with severe PAH associated with ASD, transcatheter closure can be safely performed with a promising short-term and medium-term outcome. Trial occlusion is an effective way for deciding the reversibility of severe PAH in ASD patients. The role of aerosolized iloprost for pulmonary vasoreactivity testing in patients with severe PAH secondary to ASD requires further investigation.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Arterial Pressure; Cardiac Catheterization; Catheterization, Swan-Ganz; Chi-Square Distribution; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Predictive Value of Tests; Pulmonary Artery; Recovery of Function; Retrospective Studies; Septal Occluder Device; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography; Vascular Resistance; Walking; Young Adult

We performed a retrospective analysis of patients with pulmonary arterial hypertension receiving inhaled iloprost in a single centre to evaluate long-term tolerability, safety, and efficacy of chronic inhaled iloprost therapy in children.. A total of 20 patients with either idiopathic or associated pulmonary arterial hypertension were treated with iloprost between April, 2003 and January, 2010. The median age and weight of the patients were 3.8 years--ranging from 4 months to 19 years--and 12.3 kilograms--ranging from 4 to 73 kilograms-- respectively. Pulmonary arterial hypertension was idiopathic or hereditary in eight patients (40%) and associated with congenital cardiac disease in 12 patients (60%).. Of the 20 patients, 15 had combined therapy--12 patients with two and three patients with three different classes of drugs. In all, six patients died during follow-up. The median follow-up time was 18 months, ranging from 6 to 74 months. The 6-minute walking test was performed in 7 out of 20 patients at baseline and on follow-up. The median 6-minute walking test increased from 420 to 490 metres after iloprost therapy (p = 0.028). After initiation of iloprost therapy, one patient complained of headache and another had a rash around his mouth, none necessitating discontinuation of therapy. Overall compliance with inhaled iloprost was good.. Pulmonary hypertension is associated with significant morbidity and mortality. Careful assessment of each patient and timely combination of specific vasodilator therapy is needed to improve clinical outcomes. This study suggests that inhaled iloprost, with or without concomitant endotelin receptor antagonist and/or phosphodiesterase inhibitor, is safe and efficacious for treatment of pulmonary arterial hypertension in children.

Topics: Administration, Inhalation; Adolescent; Child; Child, Preschool; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Iloprost; Infant; Longitudinal Studies; Male; Retrospective Studies; Treatment Outcome; Vasodilator Agents; Young Adult

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 summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis.. On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed.. After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea.. Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

Topics: Administration, Inhalation; Adult; Blood Pressure; Child; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Young Adult

In the past 5-10 years, drug treatment of idiopathic pulmonary arterial hypertension has evolved considerably. Experience and results from use of such updated treatment in Norway has not been reported.. 32 patients newly diagnosed with idiopathic pulmonary arterial hypertension, were consecutively assessed with respect to hemodynamics and physical capacity. The results after three months were compared with those after 12 months. Observed survival was compared with estimated survival from the time when only conventional treatment was available.. The patients (78% women) were 42 ± 14 years, had dyspnea in NYHA class 2.9 ± 0.4 and a maximal oxygen uptake of 12.0 ± 3.9 ml/kg/min (37 ± 13% of the expected). Updated treatment led to significantly improved hemodynamics and physical capacity, which persisted during follow-up. During 43 ± 31 months follow-up, seven patients died while two underwent bilateral lung transplantation. Observed transplantation-free survival was 81% after one, two and three years, while that for estimated transplantation-free survival was 70%, 58% and 49% respectively.. Treatment of idiopathic pulmonary arterial hypertension with updated treatment improves hemodynamics and thereby symptoms. Mortality remains high, but is probably lower than it was when only conventional treatment was available.

Topics: Adult; Airway Resistance; Antihypertensive Agents; Bosentan; Epoprostenol; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Iloprost; Lung Transplantation; Lung Volume Measurements; Male; Middle Aged; Oxygen Consumption; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyridazines; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Vasodilator Agents

Intravenous periodic Iloprost is proven effective in the treatment of Raynaud phenomenon (RP) related to connective tissue disorder (CTD). It's well known that synthetic prostaglandins are effective drugs for the treatment of pulmonary arterial hypertension (PAH), and that PAH is frequently associated with CTD.. The aim of the study is to evaluate in the chronic effect of cyclic intravenous Iloprost on pulmonary arterial pressure.. We studied 17 consecutive patients with CTD (14 systemic sclerosis, 3 mixed CTD) and RP, at the entry and after at least 6months of treatment of RP with cyclic Iloprost. On both occasions, in all patients we performed transthoracic Doppler echocardiography and we determined NT-proBNP plasma levels, NYHA functional class, 6 Minute-Walk Distance (6MWD).. At follow-up (8.2±1.9months; range 6-12) mean values of pulmonary arterial systolic pressure (PASP) significantly decreased (from 32.2±9.2 to 29.2±7.6mmHg, p<0.04) and mean values of 6MWD significantly increased (from 407.5±101.5 to 448.3±89.9m, p<0.01). Moreover, we observed a significant direct correlation between PASP and NT-proBNP values and a significant inverse correlation both between NT-proBNP and 6MWD values and between PASP and 6MWD values.. Our results suggest that cyclic intravenous Iloprost may protect against the development or worsening of PAH in patients with CTD and RP.

Topics: Adult; Aged; Cardiovascular Agents; Connective Tissue Diseases; Dose-Response Relationship, Drug; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Male; Middle Aged; Pulmonary Wedge Pressure; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Adult; Antihypertensive Agents; Bosentan; Combined Modality Therapy; Drug Therapy, Combination; Extracorporeal Membrane Oxygenation; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Iloprost; Lung Transplantation; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Vasodilator Agents

The majority of patients with idiopathic pulmonary arterial hypertension (IPAH) in functional classes II and III are currently being treated with non-parenteral therapies, including endothelin receptor antagonists (ERA), phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these substances. If these treatments fail, current guidelines recommend the addition of parenteral prostanoid therapy. There is, however, limited evidence for the efficacy of parenteral prostanoids when added to combinations of non-parenteral therapies.. In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival.. During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome.. In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs.

Topics: Administration, Oral; Adult; Drug Therapy, Combination; Endothelin Receptor Antagonists; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Iloprost; Injections, Intravenous; Male; Middle Aged; Phosphodiesterase Inhibitors; Retrospective Studies; Survival Analysis; Treatment Outcome; Vasodilator Agents