iloprost and Pulmonary-Arterial-Hypertension

Despite its low incidence, pulmonary hypertension in children places a substantial burden on families and society because survival can be shorter than 10 months and treatment options are limited and ineffective. Drugs to treat pulmonary hypertension include endothelin antagonists, phosphodiesterase type 5 inhibitors and prostacyclin, which is the most widely used to treat pediatric pulmonary hypertension. The main aim of this study was to provide a comprehensive overview of the advantages and disadvantages of prostacyclin and its analogs for treating pulmonary hypertension in children.. To retrieve a thorough collection of studies, we performed a search in PubMed using the following combination of keywords: (Prostacyclins) or (Epoprostenol) or (Iloprost) or (Treprostinil) or (Beraprost), (children) and (pulmonary arterial hypertension). The time limits used for the search were December 1983 to May 2021.. The search retrieved a total of 238 articles. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included.. Epoprostenol can be effective against severe pulmonary hypertension. Iloprost can treat severe persistent pulmonary hypertension in newborns and inhaled iloprost can be used in pulmonary vasoreactivity testing. Treprostinil is a long-acting prostacyclin analog, and it shows the highest antiproliferative activity among prostacyclins. Beraprost may be effective in premature infants, but available evidence comes from only one patient, so more clinical testing is needed.

Topics: Antihypertensive Agents; Child; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Iloprost; Infant, Newborn; Prostaglandins I; Pulmonary Arterial 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

Therapy with intravenous prostacyclin analogues in patients with pulmonary arterial hypertension (PAH) has been established for decades and is an integral component of the current guidelines for the treatment of pulmonary hypertension. Initially, these drugs were infused by external pump systems via tunnelled right atrial catheters with the need for cooling and frequent exchange of drug reservoirs. Associated complications included, among others, catheter-related infections. More recently, fully implantable pump systems have been developed with drug reservoirs that are filled transcutaneously, allowing intervals between refills of several weeks. This technique results in a low rate of infections. Epoprostenol, iloprost and treprostinil have all been used intravenously in PAH, but titration, dosing and dose escalation in long-term therapy are not standardized. Intravenous prostacyclin analogues are still under-used, despite available data suggesting that early and broad application of these therapies as part of risk-oriented, guideline-directed combination therapy for patients with PAH may lead to a survival benefit. This review provides a detailed overview of the drugs, infusion systems and dosing strategies used for intravenous therapy in patients with PAH.

Topics: Catheter-Related Infections; Drug Therapy, Combination; Epoprostenol; Female; Humans; Iloprost; Infusion Pumps; Infusion Pumps, Implantable; Infusions, Intravenous; Male; Practice Guidelines as Topic; Pulmonary Arterial Hypertension; Vascular Access Devices

Pulmonary arterial hypertension (PAH) is a rare condition, with an incidence of 15-50 cases per million annually. Available studies demonstrate that despite the longer survival of PAH patients, their quality of life (QoL) deteriorates as the condition progresses. Consequently, the goals of PAH therapy have expanded from increasing survival to improving health-related quality of life. The objective of this systematic review and meta-analysis was to summarize the available evidence about the level of QoL in patients with PAH.. A systematic search was performed using the Cochrane guidelines for conducting meta-analysis following the PRISMA statement. The meta-analysis includes findings from 11 studies evaluating the QoL of PAH patients at baseline and at follow-up (12 weeks) using the Short Form (36) Health Survey (SF-36), the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).. The mean physical component score (SF-36) for the group was 37.2 points (95% CI: 33.24-41.16) and the heterogeneity coefficient was I²=97.71% (p < 0.001). The mean mental component score (SF-36) was 46.38 (95% CI: 44.21-48.56) and the heterogeneity coefficient was I²=87.92% (p < 0.001). The result indicates improved QoL 12 weeks after the intervention, though three papers did not fully confirm this. The greatest improvement in QoL was found in patients treated with bosentan and iloprost and the smallest improvement in QoL was found in patients treated with epoprostenol sodium. The heterogeneity coefficient was I²=91.36%, p < 0.001 for CAMPHOR and I²=97.65%, p < 0.001 for MLHFQ.. PAH patients tend to have a poor QoL, mainly in the physical functioning domain, less so in the psychological functioning domain. QoL may be improved by therapeutic interventions, mainly pharmaceutical ones. Patients with PAH also tend to suffer from depression, anxiety, stress, or sleep disorders. All these factors are significantly correlated with poorer QoL.

Topics: Antihypertensive Agents; Bosentan; Humans; Iloprost; Pulmonary Arterial Hypertension; Quality of Life; Surveys and Questionnaires

Topics: Adult; Delivery of Health Care; Health Care Costs; Humans; Iloprost; Pulmonary Arterial Hypertension; Retrospective Studies; United States

A 25-year-old woman was admitted to our hospital with severe pulmonary arterial hypertension associated with systemic lupus erythematosus (SLE-PAH). Her mean pulmonary arterial pressure was 56 mmHg, and her SLE Disease Activity Index-2 K score was 14 on admission. In addition to a strong immunosuppressive regimen, which included steroid pulse therapy followed by high-dose oral prednisolone (1 mg/kg) and intravenous cyclophosphamide, an upfront combination of vasodilator therapy, including oral tadalafil, macitentan, and intravenous epoprostenol, was administered in the early phase. Two months later, her mean pulmonary arterial pressure was 29 mmHg, and her other haemodynamic markers showed significant improvement. She refused to start life-long intravenous epoprostenol therapy and so was switched to oral selexipag and inhaled iloprost. The transition was successful, and she has experienced no exacerbations of SLE-PAH during the 10 months since the onset of pulmonary arterial hypertension. To the best of our knowledge, this is the first report of intravenous epoprostenol being switched to alternative oral and inhaled therapy in a patient with SLE-PAH. In combination with adequate immunosuppressive therapy, it is probably easier to make this transition in patients with SLE-PAH than in those with pulmonary arterial hypertension of a different aetiology. Continuous infusion of epoprostenol can have potentially life-threatening complications and a detrimental effect on the quality of life. Our alternative treatment strategy was successful, and we hope that it will prove beneficial in other cases.

Topics: Acetamides; Adult; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Iloprost; Lupus Erythematosus, Systemic; Pulmonary Arterial Hypertension; Pyrazines; Quality of Life

Pulmonary arterial hypertension (PAH) is a severe, life-threatening disorder despite the availability of specific drug therapy. A lack of endogenous prostacyclin secondary to downregulation of prostacyclin synthase in PAH may contribute to vascular pathologies. Therefore, prostacyclin and its analogs including inhaled iloprost may decrease pulmonary arterial pressure and ventricular pressure.. Here, we studied that acute effects of iloprost used in pulmonary vasoreactivity testing on the intracardiac conduction system in patients with PAH. A total of 35 (15 idiopathic PAH, 20 congenital heart disease) patients with PAH were included in this prospective study. Patients were divided into two groups: 22 patients with negative pulmonary vasoreactivity in group 1 and 13 with positive pulmonary vasoreactivity in group 2. Electrophysiological parameters including basic cycle length, atrium-His (AH) interval, His-ventricle (HV) interval, PR interval, QT interval, QRS duration, Wenckebach period, and sinus node recovery time (SNRT) were evaluated before and after pulmonary vasoreactivity testing in both groups.. The AH interval (81 [74-93]; 80 [65.5-88], p = 0.019) and SNRT (907.7 ± 263.4; 854.0 ± 288.04, p = 0.027) was significantly decreased after pulmonary vasoreactivity testing. Mean right atrium pressure was found to be correlated with baseline AH (r = 0.371, p = 0.031) and SNRT (r = 0.353, p = 0.037).. Inhaled iloprost can improve cardiovascular performance in the presence of PAH, primarily through a reduction in right ventricular afterload and interventricular pressure. Decreased pressure on the interventricular septum and ventricles leads to conduction system normalization including of the AH interval and SNRT due to resolution of inflammation and edema.. HINTERGRUND: Die pulmonalarterielle Hypertonie (PAH) ist eine schwere, lebensbedrohliche Erkrankung trotz spezifischer medikamentöser Behandlung. Ein Mangel an endogenem Prostazyklin infolge einer Herabregulierung der Prostazyklinsynthase bei PAH kann zu Gefäßerkrankungen beitragen. Daher können Prostazyklin und seine Analoga einschließlich des inhalativen Iloprost den pulmonalarteriellen Druck und den Ventrikeldruck senken.. In der vorliegenden Studie wurden die akuten Wirkungen von dem zur Prüfung der pulmonalen Vasoreaktivität eingesetzten Iloprost auf das intrakardiale Erregungsleitungssystem bei Patienten mit PAH untersucht. In die prospektive Studie wurden 35 Patienten mit PAH (15 mit idiopathischer PAH, 20 mit kongenitaler Herzerkrankung) eingeschlossen. Die Patienten wurden in 2 Gruppen eingeteilt: 22 Patienten mit negativer pulmonaler Vasoreaktivität in Gruppe 1 und 13 mit positiver pulmonaler Vasoreaktivität in Gruppe 2. Vor und nach der Prüfung der pulmonalen Vasoreaktivität wurden elektrophysiologische Parameter einschließlich grundlegender Zyklusdauer, Atrium-His(AH)-Intervall, His-Ventrikel(HV)-Intervall, PR-Intervall, QT-Intervall, QRS-Dauer, Wenckebach-Periode und Sinusknotenerholungszeit (SKEZ) in beiden Gruppen gemessen.. Das AH-Intervall (81 [74–93]; 80 [65,5–88], p = 0,019) und die SKEZ (907,7 ± 263,4; 854,0 ± 288,04; p = 0,027) waren nach Prüfung der pulmonalen Vasoreaktivität signifikant erniedrigt. Der mittlere Druck im rechten Vorhof erwies sich als mit dem Ausgangs-AH-Intervall korreliert (r = 0,371; p = 0,031) und SKEZ (r = 0,353; p = 0,037).. Inhalatives Iloprost kann die kardiovaskuläre Leistung bei Vorliegen einer PAH verbessern, in erster Linie durch eine Reduktion der rechtsventrikulären Nachlast und des interventrikulären Drucks. Ein verminderter Druck auf das Interventrikularseptum und die Ventrikel führt zur Normalisierung des Erregungsleitungssystems einschließlich des AH-Intervalls und der SKEZ aufgrund der Rückbildung von entzündlichen Veränderungen und Ödemen.

Topics: Administration, Inhalation; Humans; Hypertension, Pulmonary; Iloprost; Prospective Studies; Pulmonary Arterial Hypertension; Vasodilator Agents

To evaluate clinical efficacy, safety and tolerability of long-term inhaled iloprost treatment in the daily practice for the management of pulmonary arterial hypertension (PAH).. A total of 115 patients with PAH on inhaled iloprost treatment were included. New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and 6-minute walk distance (6MWD) were recorded at baseline and at 3rd to 24th month visits. Safety and tolerability of iloprost treatment were also evaluated during follow-up, as were the survival, clinical worsening, and the related risk factors.. The treatment was associated with an increase in the percentage NYHA functional class II (from 0.0% at enrolment to 36.2% at 24th month visit) patients but no significant difference was noted in 6MWD values. Clinical worsening was observed in 63.5% patients, while survival rate was 69.6%. NT-proBNP levels were significantly higher in non-survivors than in survivors (p=0.042). Cox regression analysis revealed the association of female sex [odds ratio (OR)=0.318; 95% confidence interval (CI), 0.128-0.792; p=0.014] and scleroderma-related PAH (OR=0.347; 95% CI, 0.140-0.860; p=0.022) with significantly lower risk (3.14 fold and 2.88 fold, respectively) of mortality.. Our findings indicate favorable efficacy, safety, and tolerability of long-term iloprost treatment in the management of PAH, whereas improved NYHA functional class was not accompanied with a significant change in 6MWD values. Patient age was a risk factor for clinical worsening, while female sex, scleroderma subtype, and lower NT-proBNP levels were associated with significantly lower mortality risk.

Topics: Female; Humans; Hypertension, Pulmonary; Iloprost; Prospective Studies; Pulmonary Arterial Hypertension; Treatment Outcome

Pulmonary arterial hypertension restricts the ability of patients to perform routine physical activities. As part of pulmonary arterial hypertension treatment, inhaled iloprost can be administered via a nebulizer that tracks inhalation behavior. Pulmonary arterial hypertension treatment is guided by intermittent clinical measurements, such as 6-minute walk distance, assessed during regular physician visits. Continuous digital monitoring of physical activity may facilitate more complete assessment of the impact of pulmonary arterial hypertension on daily life. Physical activity tracking with a wearable has not yet been assessed with simultaneous tracking of pulmonary arterial hypertension medication intake.. We aimed to digitally track the physical parameters of patients with pulmonary arterial hypertension who were starting treatment with iloprost using a Breelib nebulizer. The primary objective was to investigate correlations between changes in digital physical activity measures and changes in traditional clinical measures and health-related quality of life over 3 months. Secondary objectives were to evaluate inhalation behavior, adverse events, and changes in heart rate and sleep quality.. We conducted a prospective, multicenter observational study of adults with pulmonary arterial hypertension in World Health Organization functional class III who were adding inhaled iloprost to existing pulmonary arterial hypertension therapy. Daily distance walked, step count, number of standing-up events, heart rate, and 6-minute walk distance were digitally captured using smartwatch (Apple Watch Series 2) and smartphone (iPhone 6S) apps during a 3-month observation period (which began when iloprost treatment began). Before and at the end of the observation period (within 2 weeks), we also evaluated 6-minute walk distance, Borg dyspnea, functional class, B-type natriuretic peptide (or N-terminal pro-B-type natriuretic peptide) levels, health-related quality of life (EQ-5D questionnaire), and sleep quality (Pittsburgh Sleep Quality Index).. Of 31 patients, 18 were included in the full analysis (observation period: median 91.5 days, IQR 88.0 to 92.0). Changes from baseline in traditional and digital 6-minute walk distance were moderately correlated (r=0.57). Physical activity (daily distance walked: median 0.4 km, IQR -0.2 to 1.9; daily step count: median 591, IQR -509 to 2413) and clinical measures (traditional 6-minute walk distance: median 26 m, IQR 0 to 40) changed concordantly from baseline to the end of the observation period. Health-related quality of life showed little change. Total sleep score and resting heart rate slightly decreased. Distance walked and step count showed short-term increases after each iloprost inhalation. No new safety signals were identified (safety analysis set: n=30).. Our results suggest that despite challenges, parallel monitoring of physical activity, heart rate, and iloprost inhalation is feasible in patients with pulmonary arterial hypertension and may complement traditional measures in guiding treatment; however, the sample size of this study limits generalizability.. ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407.. RR2-10.2196/12144.

Topics: Administration, Inhalation; Adult; Heart Rate; Humans; Hypertension, Pulmonary; Iloprost; Prospective Studies; Pulmonary Arterial Hypertension; Quality of Life; Treatment Outcome; Vasodilator Agents; Walking

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary vascular resistance that can lead to right ventricular failure and death. The use of medications that affect the prostacyclin pathway is an important treatment strategy in PAH. Inhaled iloprost is a prostacyclin analogue, and selexipag is an oral, non-prostanoid, prostacyclin IP receptor agonist. Data are limited on transitioning patients from inhaled iloprost to selexipag. In this case report, we describe the successful transition of a 57-year-old female with heritable PAH from inhaled iloprost to selexipag over 8 weeks in an out-patient setting. After initiation of selexipag, the patient's inhaled iloprost dose was gradually reduced and eventually discontinued. The patient tolerated the transition well with stable symptoms, 6-minute walk distance, and pulmonary hemodynamics. Additional studies are needed to better define the comparative efficacy and safety of inhaled iloprost and selexipag.

Topics: Acetamides; Antihypertensive Agents; Female; Humans; Hypertension, Pulmonary; Iloprost; Middle Aged; Pulmonary Arterial Hypertension; Pyrazines

Topics: Academies and Institutes; Administration, Inhalation; Angioplasty, Balloon; Antihypertensive Agents; Asian People; Bone Morphogenetic Protein Receptors, Type II; Bosentan; Calcium Channel Blockers; Cardiology; Cooperative Behavior; Endothelin Receptor Antagonists; Female; Growth Differentiation Factor 2; Guidelines as Topic; Humans; Iloprost; Mutation; Phenylpropionates; Pulmonary Arterial Hypertension; Pulmonary Embolism; Pulmonary Medicine; Pyridazines; Takayasu Arteritis; Vasodilator Agents

The presence of pulmonary hypertension (PH) significantly worsens outcomes in patients with advanced sarcoidosis, but its optimal management is unknown. We aimed to characterize a large sarcoidosis-associated pulmonary hypertension (SAPH) cohort to better understand patient characteristics, clinical outcomes, and management strategies including treatment with PH therapies. Patients at Duke University Medical Center with biopsy-proven sarcoidosis and SAPH confirmed by right heart catheterization (RHC) were identified from 1990-2010. Subjects were followed for up to 11 years and assessed for differences by treatment strategy for their SAPH, including those who were not treated with PH-specific therapies. Our primary outcomes of interest were change in 6-minute walk distance (6MWD) and change in N-terminal pro-brain natriuretic peptide (NT-proBNP) by after therapy. We included 95 patients (76% women, 86% African American) with SAPH. Overall, 70% of patients had stage IV pulmonary sarcoidosis, and 77% had functional class III/IV symptoms. Median NT-proBNP value was elevated (910 pg/mL), and right ventricular dysfunction was moderate/severe in 55% of patients. Median values for mean pulmonary artery pressure (49 mmHg) and pulmonary vascular resistance (8.5 Woods units) were consistent with severe pulmonary hypertension. The mortality rate over median 3-year follow-up was 32%. Those who experienced a clinical event and those who did not had similar overall echocardiographic findings, hemodynamics, 6MWD and NT-proBNP at baseline, and unadjusted analysis showed that only follow-up NT-proBNP was associated with all-cause hospitalization or mortality. A sign test to evaluate the difference between NT-Pro-BNP before and after PH therapy produced evidence that a significant difference existed between the median pre- and post-NT-Pro-BNP (-387.0 (IQR: -1373.0-109), p = 0.0495). Use of PH-specific therapy may be helpful in selected patients with SAPH and pre-capillary pulmonary vascular disease. Prospective trials are needed to characterize responses to PH-specific therapy in this subset of patients with SAPH.

Topics: Aged; Biomarkers; Cardiac Catheterization; Echocardiography; Epoprostenol; Female; Hemodynamics; Humans; Iloprost; Male; Middle Aged; Pulmonary Arterial Hypertension; Sarcoidosis, Pulmonary; Treatment Outcome; Vascular Resistance; Ventricular Dysfunction, Right