Funding Acknowledgements Type of funding sources: None. Background Pulmonary arterial hypertension (PAH) is a disease characterised by an increase in pulmonary vascular resistance and pulmonary artery pressure. Phosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric PAH. There has more recently been a transition to once-daily tadalafil suspensions. Herein, we present a multicenter experience detailing safety, tolerability and haemodynamic data utilizing tadalafil suspension alone or in combination for the management of pediatric PAH. Methods and materials We performed a retrospective review of all infants and children at two North American paediatric PH centres between December 2013 and April 2022. We included all patients less than 9 years of age who were treated with a tadalafil suspension after an initial treatment with sildenafil. Demographic, clinical, imaging, and laboratory data were collected. Results Over the study period, 158 children were treated with tadalafil therapy: 41 (25.9%) had group 1 PAH, 81 (51.3%) had group 3 PH, and 33 (20.9%) had group 5 PH. The median initial dose of tadalafil was 1.0 mg/kg once daily with a median time to maximum dose of 1 day. The majority of patients required the suspension formulation due to an inability to take oral tablets or the need for nasogastric or nasojejunal feeding. We observed improvements in median echocardiographic parameters in the six months following initiation, namely, in RVFAC from 34.7% (Q1 = 31.0%, Q3 = 42.0%) to 37.0% (Q1 = 31.0%, Q3 = 44.0%) and in TAPSE from 1.0 (Q1 = 0.8, Q3 = 1.7) cm to 1.3 (Q1 = 1.0, Q3 = 1.7) cm. We observed median decreases in RVSp from 51.0 (Q1 = 35.0, Q3 = 69.0) mmHg to 37.0 (Q1 = 30.0, Q3 = 50.0) mmHg and in NT pro BNP levels from 439.0 (Q1 = 217.0, Q3 = 2051.0) ng/L to 313.0 (Q1 = 193.0, Q3 = 1110.0) ng/L. Tadalafil therapy was well tolerated over the six-month period: at baseline, only four patients (2.5%) reported gastrointestinal side effects, two (1.3%) reported adverse skin adverse effects (i.e., rash and flushing), and one (0.6%) reported adverse neurological effects. At six months, 150 patients (94.9%) reported no adverse effects. Conclusion Tadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile once patients are established on sildenafil therapy. Following 6 months of once daily tadalafil suspension, alone or in combination, showed a trend towards improvement in clinical parameters, echocardiographic measurements, and laboratory results for pediatric PAH. All patient adverse effects were managed with non pharmacological measures and there was good patient compliance.
IntroductionThe clinical deterioration commonly experienced by pediatric patients with pulmonary arterial hypertension (PAH) has motivated a shift in the treatment of pulmonary hypertension (PH) through innovations in surgical salvage interventions. The Occlutech fenestrated atrial septal defect (FASD) Occluder and the atrial flow regulator (AFR), which provides a protective, atrial-level shunt during hypertensive crises, have found an important role in treating pediatric patients with PAH. Other groups of pediatric patients with PH may also benefit from a similar protective physiology. The primary aim of this work is to present a single center's experience with AFR and FASD devices for managing a heterogeneous group of pediatric PH patients. A secondary goal is to identify hemodynamic changes and complications following device implantation.Materials and MethodsWe performed a retrospective review of all pediatric PH patients who, after being found suitable, either successfully or unsuccessfully received an FASD or AFR device between January 2015 and December 2021 at the Stollery Children's Hospital in Edmonton, Canada.ResultsFourteen patients (eight female) with a median age of 4.6 (range 0.3–17.9) years and a median body mass index of 15.1 (Q1 = 13.8, Q3 = 16.8) kg/m2 underwent device implantation: five received FASDs, eight received AFRs, and one was ultimately unable to receive an implant due to thrombosed iliac vessels and required surgical intervention. Of the fourteen patients, seven were in group 1 (PAH), one was in group 3 (lung disease), and six were in group 5 (primarily pulmonary hypertension vascular disease) under the World Symposium PH classification. All patients were on mono-, dual-, or triple-drug PH therapy. Device stabilization was not possible for two patients, who then required a repeat catheterization. Of the group 1 patients, three AFR and three FASD implants were successful, while one FASD implant was unsuccessful due to thrombosed vessels. At a six-month clinical assessment, all group 1 patients had patent devices and improved WHO FCs.ConclusionThis work presents a single center's experience with AFR and FASD implants in a heterogeneous group of fourteen pediatric patients with severe PH. This treatment strategy is novel in the pediatric population and so this work provides momentum for future studies of interventional cardiac catheterization procedures for pediatric patients with PH. Further collaborations are required to develop criteria to identify ideal pediatric candidates and optimally time interventions in order to maximize the benefits of this treatment.
Funding Acknowledgements Type of funding sources: None. Background The introduction of the oral prostanoid selexipag for treating severe adult pulmonary arterial hypertension (PH) has contributed to reduced rates of death and secondary complications in PAH. Pediatric physicians have extrapolated from the adult literature to utilize this medication to treat severe pediatric pulmonary hypertension. However, longitudinal, multicenter data on the therapeutic benefits of selexipag for pediatric patients is lacking. Materials and Methods We performed a retrospective review describing the clinical outcomes of pediatric PH patients receiving selexipag for pulmonary hypertension (PH) therapy in addition to standard pulmonary vasodilator therapy across three North American pediatric PH centers between January 2005 and June 2021. Results Across three Canadian centers, 24 patients (15 female) with a mean age at diagnosis of 5.4 (0.9) years were included. Of this cohort, 19 (79.2%) had group 1 PAH, 4 (16.7%) had group 3 PH, and 1 (4.2%) had group 4 PH. Genetic syndromes were noted in 7 (29.2%) patients. Dosing was targeted to achieve 20–30 mcg/kg/dose orally every 12 hours; the mean dosage after 12 months was 31.2 (10.3) mcg/kg/dose. Twelve months following selexipag initiation, a median increase of 71.5 m (p = 0.44) in six-minute walk test distance was observed together with median decreases of 0.2 cm (p = 0.17) in tricuspid annular plane systolic excursion, 3.5 mmHg (p = 0.95) in right ventricle systolic pressure, and 6.1 mmHg (p = 0.09) in mean pulmonary artery pressure. 2 patients (8.3%) died, 1 (4.2%) was referred for a heart transplant, and 1 (4.2%) received an atrial flow regulator. One patient (4.2%) required admission to a pediatric intensive care unit during their treatment course this was related to profound desaturation, six (25.0%) had gastrointestinal symptoms, and two (8.3%) had facial flushing. Conclusion Selexipag appears to be a beneficial adjunctive therapy for selected pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Further prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed.
IntroductionSelexipag, an oral nonprostanoid prostaglandin receptor agonist, has led to reduced morbidity and mortality in adults with pulmonary arterial hypertension (PAH). While the adult literature has been extrapolated to suggest selexipag as an oral treatment for severe pediatric pulmonary hypertension (PH), longitudinal, multicenter data on the benefits of selexipag in this population are lacking. The purpose of this study is to present a longitudinal, multicentre experience with selexipag in a relatively large cohort of pediatric PH patients and add to the existing selexipag literature.Materials and methodsWe performed a retrospective, multicenter review describing the clinical outcomes of pediatric PH patients receiving selexipag in addition to standard oral pulmonary vasodilator therapy across three Canadian centers between January 2005 and June 2021.ResultsTwenty-four pediatric patients (fifteen female) with a mean age of 9.7 (range 2.0–15.5) years were included. Of this cohort, eighteen (75.0%) were in group 1, one (4.2%) was in group 2, four (16.7%) were in group 3, and one (4.2%) was in group 4. Twenty-two (91.7%) patients were on dual PH therapy after six months. Dosing was targeted to achieve 20–30 mcg/kg/dose orally every twelve hours. Median dose after twelve months was 30 mcg/kg/dose. Twelve months following selexipag initiation, median decreases of 0.2 cm in tricuspid annular plane systolic excursion, 3.5 mmHg in right-ventricular systolic pressure, and 6.1 mmHg in mean pulmonary arterial pressure were observed; none of these changes were statistically significant. Three patients died, one clinically deteriorated and required admission to a pediatric intensive care unit, ten had gastrointestinal symptoms, and three had flushing.ConclusionSelexipag appears to be a safe and effective adjunctive therapy for pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Additional prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed. Future research should aim to identify subgroups that stand to benefit from the addition of selexipag as well as optimal timing and dosing for the pediatric population.
IntroductionPhosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH).Methods and materialsThis is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation.ResultsOver the study period, 154 children with a median age of 1.0 (range 0.0–6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients.ConclusionTadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means.
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