Occurrence of sleep-disordered breathing in children with pulmonary hypertension.

BACKGROUND: Obstructive sleep apnea (OSA) has been associated with pulmonary hypertension (PH) through a complex and bidirectional relationship. The prevalence of OSA and other forms of sleep-disordered breathing (SDB) among children with PH is not well understood. A better understanding could help elucidate contributing factors for PH, guide diagnostic testing, and inform therapies. We therefore determined the proportion of SDB codiagnosis and OSA risk factors among a cohort of children with PH. METHODS: Retrospective chart review was performed for children 0-21 years old with PH who underwent polysomnography (PSG) between 1 January 2010 and 31 August 2020. The primary outcome was OSA occurrence and risk based on demographics, diagnoses, and PH classification. The secondary outcome was occurrence and risk of other SDB diagnoses based on PH classification. RESULTS: Among 89 children identified, diagnoses included OSA (N = 79, 89%), central sleep apnea (N = 11, 12%), sleep-related hypoventilation (N = 6, 7%), and non-apneic hypoxemia (N = 28, 31%). Trisomy 21 diagnosis (N = 38, 43%) was associated with increased OSA risk (RR: 1.24, 95% CI: [1.09-1.42]) and age >12 months at PSG was associated with decreased OSA risk (N = 52, 58%, RR: 0.60, 95% CI: [0.45-0.81]). There was no difference in SDB risk based on Group 1 (N = 56, 63%) or Group 3 (N = 33, 37%) PH and no difference in OSA severity based on demographics and diagnoses. CONCLUSION: OSA was diagnosed among a majority of children with PH, and other SDB diagnoses were identified in a significant proportion of children. These findings support routine screening for SDB with PSG in children with PH.

Factors leading to supranormal cardiac index in pediatric pulmonary hypertension patients treated with parenteral prostanoid therapy.

Parenteral prostanoid therapy (PPT) can result in supranormal cardiac index (SCI; >4 L/min/m2) in pediatric pulmonary hypertension (PPH) patients. We evaluated the incidence, hemodynamic factors, and outcomes associated with SCI in PPH. This retrospective cohort study included 22 PPH patients on PPT from 2005 to 2020. Hemodynamic profiles were compared between the baseline and 3-6 month follow-up catheterization in the SCI and non-SCI cohorts. Cox regression analysis examined time to composite adverse outcome (CAO; Potts shunt, lung transplant, or death) controlling for initial disease severity. SCI developed in 17 (77%) patients, of whom 11 (65%) developed SCI within 6 months. The SCI cohort was characterized by significant augmentation of cardiac index (CI) and stroke volume (SV) as well as reductions in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR). Conversely, the non-SCI cohort had unchanged SV despite a modest rise in CI as well as persistent vasoconstriction. After median follow-up of 4.3 years (range 0.2-13 years), non-SCI patients were at significantly increased risk for the CAO (5/5: three deaths, two Potts shunts) compared with SCI patients (5/17: two deaths, three lung transplants; adjusted hazard ratio 14.0 [95% confidence interval: 2.1-91.3], p < 0.001). A majority of PPH patients developed SCI within 6-12 months of starting PPT and demonstrated lower risk of adverse outcomes compared with non-SCI patients. These data suggest that change in SVR and SV after 3-6 months of PPT may be early markers of therapeutic response and prognosis.

Long-term exercise and pulmonary function outcomes in a contemporary cohort of children with congenital diaphragmatic hernia.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) survivors are at risk for long-term exercise impairment and pulmonary morbidity, but the generalizability of prior reported cohorts are limited by reduced disease severity and older surgical eras. We assessed the mid-childhood exercise and pulmonary function outcomes in a contemporary cohort of CDH survivors. STUDY DESIGN: In this retrospective cohort study, we identified 36 consecutive pediatric CDH survivors who underwent cardiopulmonary exercise testing (CPET) and spirometry from 2014 to 2021. Inferential statistics compared survivors with age-, sex-, and size-matched healthy controls; univariate analyses identified factors associated with abnormal testing. RESULTS: Maximal effort CPET and resting spirometry were completed by 27/36 (75%) and 31/36 (86%) subjects, respectively (median age: 8.1 years [interquartile range: 7.5, 10]; 16 females [44%]). Abnormal CPET (percent predicted [pp] peak VO2 < 80%) was more common in the CDH cohort (12 vs. 1, p < 0.001) and associated with longer neonatal intensive care unit (NICU) stay (p = 0.02) and oxygen therapy at discharge (p = 0.03). Exercise impairment was mild (pp peak VO2 70%-80%), moderate (60%-70%), and severe (<60%) in 6, 4, and 2 survivors, respectively. Abnormal spirometry was more common in the CDH cohort (21 vs. 3, p < 0.001; obstructive [n = 15], restrictive [n = 6]) and associated with decreased gestational age (p = 0.046), longer mechanical ventilation in the NICU (p = 0.02), and orthopedic abnormalities (p = 0.03). CONCLUSION(S): Exercise capacity was normal or mildly impaired in most CDH survivors, however, approximately two-thirds demonstrated abnormal spirometry. Impaired exercise capacity and lung function were associated with severity of lung disease postnatally. These data support cardiopulmonary follow-up throughout childhood.

Prognostic Value of Change in Cardiac Index After Prostacyclin Initiation in Pediatric Pulmonary Hypertension.

Invasive hemodynamic assessment remains the gold standard for the diagnosis of pediatric pulmonary hypertension and for longitudinal assessment of response to therapy. This analysis sought to describe the changes in hemodynamic variables after initiation of prostacyclin therapy and determine which changes bear predictive power of adverse clinical outcomes. A retrospective chart review of established patients at Cincinnati Children's Hospital with pulmonary arterial hypertension (PAH) who required prostacyclin therapy between 2004 and 2018 was performed. The baseline hemodynamic parameters at diagnosis as well as change in those parameters between initial catheterization and post-prostacyclin initiation catheterization were independent variables. Cox proportional hazard regression and recursive partitioning analysis were used to characterize which hemodynamic factors predicted the composite adverse outcome (CAO) defined as death, lung transplantation, or reverse Pott's shunt surgery. During the study period, 29 patients met inclusion criteria in which there were 7 CAOs: 4 deaths, 3 lung transplants, and 2 reverse Pott's shunts. Median time between catheterizations was 86 days and between the initiation of prostacyclin therapy and the second catheterization was 54 days. Cox regression revealed that only baseline pulmonary artery pressure (> 51 mmHg) and a failure to increase cardiac index illustrated statistically significant hazard for occurrence of the CAO (p < 0.01). These criteria significantly dichotomized the population in a Kaplan-Meier analysis into likelihoods of experiencing the CAO. While controlling for other hemodynamic variables, the absence of augmentation of cardiac index after the initiation of prostacyclin therapy is a valuable prognostic indicator of adverse PAH outcomes in pediatrics.

Cost-Utility of Sildenafil for Persistent Pulmonary Hypertension of the Newborn.

OBJECTIVE: While advanced therapies for severe persistent pulmonary hypertension of the newborn (PPHN) such as inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) are standard treatments in high-income countries, these therapies are often unavailable in resource-limited settings such as middle-income countries. However, there are small clinical trials illustrating the efficacy of sildenafil at reducing mortality in PPHN. This analysis sought to determine the cost-utility of enteral sildenafil for the treatment of severe PPHN. STUDY DESIGN: A Markov-state transition model was constructed for the two clinical approaches to compare costs, clinical outcomes, and quality of life: (1) "conventional," (2) "sildenafil." The impact of sildenafil was modeled as a relative risk modifier of the conventional strategy's mortality risk. Transitional probabilities, costs, and utility metrics were extracted from the literature. Sensitivity analyses for each model input as well as 100-patient Monte Carlo simulations were used to test the durability of the model conclusion. RESULTS: The sildenafil strategy was cost-effective for upper but not lower middle-income countries with an incremental cost-effectiveness ratio of $2,339 per quality-adjusted life year. This conclusion was durable across a wide-range of model assumptions; the sildenafil strategy only failed to meet criteria for cost-effectiveness when sildenafil therapy had a mortality relative risk efficacy of >0.89, if life expectancy in that country is <40 years, or if the lifetime forecasted costs of a survivor's life was quite high. CONCLUSION: Enteral sildenafil is a cost-effective intervention for severe PPHN for upper middle-income countries where ECMO and iNO are not available. KEY POINTS: · PPHN is a common life-threatening condition in newborns.. · Sildenafil improves survival of PPHN.. · Sildenafil is cost-effective for upper-middle income countries..

Balloon atrial septostomy as initial therapy in pediatric pulmonary hypertension.

Balloon atrial septostomy is a palliative procedure currently used to bridge medically refractory pulmonary hypertension patients to lung transplantation. In the current report, we present balloon atrial septostomy as an initial therapy for high-risk pediatric pulmonary hypertension patients at our institution. Nineteen patients with median age of 4.3 years (range 0.1-14.3 years) underwent balloon atrial septostomy during initial admission for pulmonary hypertension. There were no procedural complications or deaths within 24 h of balloon atrial septostomy. Patients were followed for a median of 2.6 years (interquartile range 1.0-4.8 years). Three (16%) patients died, 3 (16%) underwent lung transplantation, and 1 (5%) underwent reverse Potts shunt. Transplant-free survival at 30 days, 1 year, and 3 years was 84%, 76%, and 67% respectively. This single-center experience suggests early-BAS in addition to pharmacotherapy is safe and warrants consideration in high-risk pediatric pulmonary hypertension patients.

Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients.

INTRODUCTION: We observed pulmonary hypertension (PH), pericardial effusions, and left ventricular systolic dysfunction (LVSD) in multiple critically ill hematopoietic stem cell transplant (HSCT) recipients. We implemented routine structured echocardiography screening for HSCT recipients admitted to the pediatric intensive care unit (PICU) using a standardized multidisciplinary process. METHODS: HSCT recipients admitted to the PICU with respiratory distress, hypoxia, shock, and complications related to transplant-associated thrombotic microangiopathy were screened on admission and every 1-2 weeks thereafter. Echocardiography findings requiring intervention and/or further screening included elevated right ventricular pressure, LVSD, and moderate to large pericardial effusions. All echocardiograms were compared to the patient's routine pretransplant echocardiogram. RESULTS: Seventy HSCT recipients required echocardiography screening over a 3-year period. Echo abnormalities requiring intervention and/or further screening were found in 35 (50%) patients. Twenty-four (34%) patients were noted to have elevated right ventricular pressure; 14 (20%) were at risk for PH, while 10 (14%) had PH. All patients with PH were treated with pulmonary vasodilators. LVSD was noted in 22 (31%) patients; 15/22 (68%) received inotropic support. Moderate to large pericardial effusions were present in nine (13%) patients, with six needing pericardial drain placement. DISCUSSION: Echocardiographic abnormalities are common in critically ill HSCT recipients. Utilization of echocardiogram screening may allow for early detection and timely intervention for cardiac complications in this high-risk cohort.

Changes in Ventricular Geometry Predict Severity of Right Ventricular Hypertension.

Changes in ventricular geometry are often seen in patients with right ventricular hypertension secondary to pulmonary hypertension (PH). Progressive systolic bowing of the inter-ventricular septum occurs with increasing right ventricular pressure (RVp) and can be quantified with the left ventricular end-systolic eccentricity index (LVEI). Only limited data exist in children to evaluate the relationship between the LVEI and invasive RVp. We sought to assess the correlation between the LVEI and an invasively measured peak systolic RVp to aortic pressure (pAo) ratio. Medical records of patients undergoing echocardiography within 30 days of right and left heart catheterization for evaluation of PH between February 2009 and March 2014 were retrospectively reviewed. Forty-six studies in 29 subjects (median age 3.8 years, 46 % female), with a median time from echocardiogram to catheterization of -1.0 days, were included for analysis. The mean LVEI was 1.6 ± 0.5, and mean RVp/pAo ratio was 0.68 ± 0.26. There was a significant positive correlation (r = 0.76, p < 0.001) between LVEI and RVp/pAo ratio. ROC analysis demonstrated an area under the curve = 0.91 for prediction of RVp/pAo >0.50 by the LVEI. An LVEI >1.48 had a sensitivity of 76 % and specificity of 100 % in predicting RVp/pAo >0.50, while an LVEI >1.24 had a sensitivity of 88 % and specificity of 83 %. Echocardiographically derived LVEI is strongly correlated with invasively determined RVp/pAo ratio. In combination with other noninvasive measures of RVp, LVEI may help minimize the need for invasive patient evaluation.

Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.

Abnormal echocardiography 7 days after stem cell transplantation may be an early indicator of thrombotic microangiopathy.

Cardiac complications after hematopoietic stem cell transplantation (HSCT) can lead to significant morbidity and mortality. Cardiac evaluation during the first 100 days after HSCT is usually performed only if clinically indicated, and no studies have examined whether routine screening is beneficial in this patient population at high risk for tissue injury. We conducted a single-center prospective clinical study to screen for cardiac complications in pediatric and young adult patients. One hundred consecutive HSCT patients underwent scheduled echocardiographic screening on day +7 after transplantation, independent of their clinical condition. At least 1 abnormality was identified in 30% of cases. Seventeen children had a pericardial effusion, 13 elevated right ventricular pressure, and 3 reduced left ventricular function. Survival was reduced in children with any echocardiographic abnormality at day 7 (67% versus 80% in those with and without, respectively, abnormality, P = .073). Moreover, raised right ventricular pressure at day +7 was significantly associated with transplant-associated thrombotic microangiopathy (TA-TMA; P = .004) and may indicate early vascular injury in the lungs. These data suggest that echocardiography 7 days after HSCT can detect early cardiac complications of HSCT and may identify early vascular injury associated with TA-TMA.