Instituting Sexual Orientation and Gender Identity Training and Documentation to Increase Inclusivity at a Pediatric Health System.

In this mixed-methods quality improvement project, we implemented and evaluated sexual orientation and gender identity (SOGI) form rollout in the electronic medical record. Families in our gender diversity program completed a baseline survey in 2017 (55/328 responded) and follow-up in 2020 (180/721 responded) to evaluate the frequency of affirmed name and pronoun use in the hospital. Survey feedback informed system-wide inclusivity efforts and training. SOGI was implemented in 2020 after 1,662 providers completed an online training and 11,090 team members completed gender and sexual orientation inclusivity training. We recommend similar trainings for health systems utilizing SOGI.

Sildenafil Increases Systemic Saturation and Reduces Pulmonary Artery Pressure in Patients with Failing Fontan Physiology.

OBJECTIVE: The purpose of this study was to investigate the effect of sildenafil in patients with failing Fontan physiology. DESIGN: A retrospective chart review was performed to compare history and available data in patients with Fontan circulations before and after starting sildenafil. The paired and unpaired Student's t-tests were used for statistical analyses. PATIENTS: Six patients at our institution with Fontan physiology, persistent symptoms of cyanosis or effusion, and poor hemodynamics as measured in the catheterization laboratory were placed on sildenafil. One patient was not included in the analysis because of insufficient length of treatment. All patients had symptoms of failing Fontan hemodynamics with either persistent cyanosis or effusions. In this group, the mean pulmonary artery pressure was greater than 15 mm Hg (17.4 ± 1.5 mm Hg) with mean estimated pulmonary vascular resistance of 3.5 ± 1.0 Wood units × m(2) prior to starting sildenafil. RESULTS: Sildenafil significantly increased the systemic arterial oxyhemoglobin saturation in this group (82.8 ± 7.3% pre-treatment vs. 91.0 ± 5.5% post-treatment, P = .017). In the four out of five patients who have had follow-up catheterizations, there was a significant decrease in pulmonary artery pressure (17.4 ± 1.5 mm Hg pre-treatment vs. 13.8 ± 2.1 mm Hg post-treatment, P = .018) and in estimated pulmonary vascular resistance pre- and post-sildenafil treatment (3.5 ± 1.0 Wood units × m(2) pre-treatment vs. 2.0 ± 0.4 Wood units × m(2) post-treatment, P = .031). CONCLUSIONS: Sildenafil may be a useful adjunct to therapy in patients with failing Fontan physiology likely through its function as a pulmonary vasodilator.

Short- and long-term effects of inhaled iloprost therapy in children with pulmonary arterial hypertension.

OBJECTIVES: This study investigated the short- and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost. BACKGROUND: Inhaled iloprost has been approved for the treatment of adults with PAH, but little is known about the effects in children with PAH. METHODS: We evaluated the acute effects of inhaled iloprost on hemodynamic status and lung function and the response to long-term therapy in 22 children (range 4.5 to 17.7 years) with PAH (idiopathic, n = 12; congenital heart disease, n = 10). Cardiac catheterization, standard lung function testing before and after iloprost inhalation, 6-min walk test, World Health Organization functional class, and hemodynamic parameters were monitored. RESULTS: Acute administration of inhaled iloprost lowered mean pulmonary artery pressure equivalent to the response to inhaled nitric oxide with oxygen. Acute iloprost inhalation reduced forced expiratory volume in 1 s and mid-volume forced expiratory flow by 5% and 10%, respectively, consistent with acute bronchoconstriction. At 6 months, functional class improved in 35%, decreased in 15%, and remained unchanged in 50% of children. Sixty-four percent of patients continued receiving long-term iloprost therapy, 36% stopped iloprost, due to lower airway reactivity, clinical deterioration, or death. In 9 patients on chronic intravenous prostanoids, 8 transitioned from intravenous prostanoids to inhaled iloprost, which continued during follow-up. CONCLUSIONS: Inhaled iloprost caused sustained functional improvement in some children with PAH, although inhaled iloprost occasionally induced bronchoconstriction. Most patients tolerated the transition from intravenous to inhaled prostanoid therapy. Clinical deterioration, side effects, and poor compliance, owing to the frequency of treatments, could limit chronic treatment in children.

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

BACKGROUND: Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. METHODS: Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. RESULTS: Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). CONCLUSIONS: Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared with PVR alone.

Application of a microstructural constitutive model of the pulmonary artery to patient-specific studies: validation and effect of orthotropy.

We applied a statistical mechanics based microstructural model of pulmonary artery mechanics, developed from our previous studies of rats with pulmonary arterial hypertension (PAH), to patient-specific clinical studies of children with PAH. Our previous animal studies provoked the hypothesis that increased cross-linking density of the molecular chains may be one biological remodeling mechanism by which the PA stiffens in PAH. This study appears to further confirm this hypothesis since varying molecular cross-linking density in the model allows us to simulate the changes in the P-D loops between normotensive and hypertensive conditions reasonably well. The model was combined with patient-specific three-dimensional vascular anatomy to obtain detailed information on the topography of stresses and strains within the proximal branches of the pulmonary vasculature. The effect of orthotropy on stressstrain within the main and branch PAs obtained from a patient was explored. This initial study also puts forward important questions that need to be considered before combining the microstructural model with complex patient-specific vascular geometries.

Transition of stable pediatric patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil.

Intravenous epoprostenol was the first agent approved by the United States Food and Drug Administration for the management of pulmonary arterial hypertension (PAH). However, epoprostenol therapy carries the risks of a short half-life (<6 minutes) and side effects, including jaw pain, flushing, and headache. Recently, intravenous treprostinil has been studied, primarily in adults with PAH, and found to provide effective therapy. The effects of continuous intravenous treprostinil were retrospectively evaluated in 13 children with stable PAH who had been treated with epoprostenol for >1 year. Children were transitioned in the hospital over 24 hours using a rapid or slow strategy. The children were a mean age of 11 years (range 3 to 17) and were transitioned to treprostinil from August 2004 to August 2005. The baseline 6-minute walking distance was on average 516 +/- 115 m (n = 9) and did not change after transition. Patients were treated with treprostinil for 1.1 +/- 0.5 years. There were 2 deaths, and 2 patients transitioned to other therapy. Seven patients experienced > or =1 central-line infection. Despite a higher dose of treprostinil, the side effects were subjectively diminished. In conclusion, treprostinil provides an alternative therapy in children with PAH, with fewer side effects. However, evaluation regarding rates of infection requires further exploration.

Effects of long-term bosentan in children with pulmonary arterial hypertension.

OBJECTIVES: This study investigated the long-term outcome of children with pulmonary arterial hypertension (PAH) treated with bosentan therapy, with or without concomitant prostanoid therapy. BACKGROUND: Bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, improves hemodynamics and exercise capacity in adults with PAH; however, limited data are available on its long-term effects in children. METHODS: In this retrospective study, 86 children with PAH (idiopathic, associated with congenital heart or connective tissue disease) started bosentan with or without concomitant intravenous epoprostenol or subcutaneous treprostinil therapy. Hemodynamics, World Health Organization (WHO) functional class, and safety data were collected. RESULTS: At the cutoff date, 68 patients (79%) were still treated with bosentan, 13 (15%) were discontinued, and 5 (6%) had died. Median exposure to bosentan was 14 months. In 90% of the patients (n = 78), WHO functional class improved (46%) or was unchanged (44%) with bosentan treatment. Mean pulmonary artery pressure and pulmonary vascular resistance decreased (64 +/- 3 mm Hg to 57 +/- 3 mm Hg, p = 0.005 and 20 +/- 2 U x m2 to 15 +/- 2 U x m2, p = 0.01, respectively; n = 49). Kaplan-Meier survival estimates at one and two years were 98% and 91%, respectively. The risk for worsening PAH was lower in patients in WHO functional class I/II at bosentan initiation than in patients in WHO class III/IV at bosentan initiation. CONCLUSIONS: These data suggest that bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, with or without concomitant prostanoid therapy, is safe and efficacious for the treatment of PAH in children.

Portopulmonary hypertension in pediatric patients.

OBJECTIVES: To investigate the clinical presentation, manifestations, and response to therapy of portopulmonary hypertension (PPHTN) in pediatric patients. STUDY DESIGN: This study was a retrospective chart review describing the evaluation and course of 7 patients with PPHTN. RESULTS: Causes of portal hypertension (HTN) included biliary atresia (3 cases), cavernous transformation of the portal vein (2 cases), and primary sclerosing cholangitis and cryptogenic cirrhosis (1 case each). The median interval from the diagnosis of portal HTN to PPHTN was 12.1 years. Four patients presented with a new heart murmur, 4 presented with syncope, and 3 presented with dyspnea. Although electrocardiograms (ECGs) and chest x-rays were normal in 3 and 2 patients, respectively, echocardiograms diagnosed pulmonary HTN in all 7 patients. Five patients had cardiac catheterizations; the average mean pulmonary artery pressure was 65 +/- 20 mm Hg. Response to therapy was variable, and 4 patients died. Postmortem lung tissue examination revealed plexiform lesions and pulmonary arteriopathy. CONCLUSIONS: Because symptoms are subtle and may be overlooked, pediatric patients with portal HTN who develop a new heart murmur, dyspnea, syncope, or who are being evaluated for liver transplantation require evaluation for PPHTN. ECG and chest x-ray are insensitive screens for PPHTN. An echocardiogram and cardiology evaluation is essential for the diagnosis.

Weaning and discontinuation of epoprostenol in children with idiopathic pulmonary arterial hypertension receiving concomitant bosentan.

In 7 of 8 children with idiopathic pulmonary arterial hypertension treated with intravenous epoprostenol for >1 year, concomitant use of bosentan allowed a reduction of epoprostenol and decreased its associated side effects without deterioration of clinical and hemodynamic parameters. In 3 children with normal or near-normal pulmonary artery pressure on epoprostenol, the addition of bosentan allowed discontinuation of epoprostenol and stabilization of hemodynamics for up to 1 year.