Patent Ductus Arteriosus and Lung MRI Phenotype in Moderate and Severe Bronchopulmonary Dysplasia-Pulmonary Hypertension.

RATIONALE: A hemodynamically significant patent ductus arteriosus (hsPDA) in premature infants has been associated with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). However, these associations remain incompletely understood. OBJECTIVES: The aim was to assess the association between hsPDA duration with clinical outcomes, PH, and phenotypic differences on lung MRI. METHODS: This retrospective cohort study identified all infants with BPD <32 weeks gestation who also underwent a research lung MRI <48 weeks postmenstrual age (PMA) from 2014-2022. Clinical echocardiograms were reviewed for hsPDA, and categorized into no hsPDA, hsPDA 1-60 days, and hsPDA >60 days. Outcome variables included BPD severity, PH at 36 weeks PMA, PH after 36 weeks PMA in the absence of shunt (PH-PVD), tracheostomy or death, and lung phenotype by MRI via modified Ochiai score, indexed total lung volume (TLVI), and whole lung hyperdensity (WLH). Logistic regression and ANOVA analysis were used. MEASUREMENTS AND MAIN RESULTS: In total, 133 infants born at 26.2 ± 1.9 weeks and 776 ± 276g were reviewed (47 no hsPDA, 44 hsPDA 1-60 days, 42 hsPDA >60 days). hsPDA duration >60 days was associated with BPD severity (p<0.01), PH at 36 weeks PMA (aOR 9.7 [95% CI: 3.3-28.4]), PH-PVD (aOR 6.5 [95% CI: 2.3-18.3]), and tracheostomy or death (aOR 3.0 [95% CI: 1.0-8.8]). Duration of hsPDA > 60 days was associated with higher Ochiai score (p=0.03) and TLVI (p=0.01), but not WLH (p=0.91). CONCLUSIONS: In infants with moderate or severe BPD, prolonged exposure to hsPDA is associated with BPD severity, PH-PVD, and increased parenchymal lung disease by MRI.

Wireless Pulmonary Artery Pressure Monitor Implantation in a Patient with Duchenne Muscular Dystrophy.

Assessing heart failure progression in patients with Duchenne Muscular Dystrophy (DMD) is challenging given the multi-system nature of disease. Herein we describe the first case use of an implantable pulmonary artery pressure monitor and describe the potential clinical utility of this approach in patients with DMD.

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.

Ventricular global function index is associated with clinical outcomes in pediatric pulmonary hypertension.

BACKGROUND: Multiple right ventricular (RV) metrics have prognostic value in pulmonary hypertension (PH). A cardiac magnetic resonance imaging (CMR) derived global ventricular function index (GFI) provided improved prediction of composite adverse outcome (CAO) in adults with atherosclerosis. GFI has not yet been explored in a PH population. We explored the feasibility of GFI as a predictor of CAO in a pediatric PH population. METHODS: Two center retrospective chart review identified pediatric PH patients undergoing CMR from Jan 2005-June 2021. GFI, defined as the ratio of the stroke volume to the sum of mean ventricular cavity and myocardial volume, was calculated for each patient. CAO was defined as death, lung transplant, Potts shunt, or parenteral prostacyclin initiation after CMR. Cox proportional hazards regression was used to estimate associations and assess model performance between CMR parameters and CAO. RESULTS: The cohort comprised 89 patients (54% female, 84% World Health Organization (WHO) Group 1; 70% WHO-FC ≤ 2; and 27% on parenteral prostacyclin). Median age at CMR was 12 years (IQR 8.1-17). Twenty-one (24%) patients experienced CAO during median follow up of 1.5 years. CAO cohort had higher indexed RV volumes (end systolic-145 vs 99 mL/m2, p = 0.003; end diastolic-89 vs 46 mL/m2, p = 0.004) and mass (37 vs 24 gm/m2, p = 0.003), but lower ejection fraction (EF) (42 vs 51%, p < 0.001) and GFI (40 vs 52%, p < 0.001). Higher indexed RV volumes (hazard ratios [HR] 1.01, CI 1.01-1.02), lower RV EF (HR 1.09, CI 1.05-1.12) and lower RV GFI (HR 1.09, CI 1.05-1.11) were associated with increased risk of CAO. In survival analysis, patients with RV GFI < 43% demonstrated decreased event-free survival and increased hazard of CAO compared to those with RV GFI ≥ 43%. In multivariable models, inclusion of GFI provided improved prediction of CAO compared to models incorporating ventricular volumes, mass or EF. CONCLUSIONS: RV GFI was associated with CAO in this cohort, and inclusion in multivariable models had increased predictive value compared to RVEF. GFI uses readily available CMR data without additional post-processing and may provide additional prognostic value in pediatric PH patients beyond traditional CMR markers.

Pulmonary artery compliance in different forms of pulmonary hypertension.

OBJECTIVE: Pulmonary artery compliance (PAC), estimated as stroke volume (SV) divided by pulmonary artery pulse pressure (PP), may be a predictor of survival in pulmonary arterial hypertension (PAH). Resistance-compliance (RC) time, the product of PAC and pulmonary vascular resistance, is reported to be a physiological constant. We investigated if differences in PAC and RC time exist between pulmonary hypertension (PH) subgroups and examined whether PAC is an independent predictor of transplant-free survival in PAH. METHODS: This was a retrospective analysis of adult PAH (n=532) and chronic thromboembolic PH (CTEPH, n=84) patients enrolled in the US Pulmonary Hypertension Association Registry from 2015 to 2019. PAC and RC time were compared between PH subgroups (connective tissue disease-PAH (CTD-PAH), idiopathic/heritable-PAH (i/h-PAH), drug/toxin-PAH (d/t-PAH)). Cox proportional hazards models were constructed for transplant-free survival, adjusting for REVEAL 2.0 risk score. RESULTS: There were no differences in estimated PAC between PAH subgroups, nor between PAH and CTEPH. RC time was shorter in CTEPH compared with PAH (median 0.55 (IQR 0.45-0.64) vs 0.62 (0.52-0.73) s, p<0.0001). RC time was shortest in CTD-PAH when compared with i/h-PAH and d/t-PAH ((0.59±0.18) vs (0.65±0.20) vs (0.73±0.25) s, p=0.0001). PAC was associated with transplant-free survival (HR 0.72, 95% CI 0.55 to 0.94, p=0.02) but was not an independent predictor of outcome after adjustment for REVEAL 2.0 score. CONCLUSION: PAC was similar between PH groups and was not an independent predictor of transplant-free survival in PAH. RC time was different between PH subgroups, challenging RC time constancy. TRIAL REGISTRATION NUMBER: NCT04071327.

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.

The impact of the COVID-19 pandemic on individuals with Fontan circulation: Focus on gaps in care.

Background: Gaps in subspecialty cardiology care could potentially delay identification and care for multi-organ complications common in patients with Fontan circulation. This study analyzed the frequency of gaps in care for individuals with Fontan circulation during the COVID-19 pandemic and associated demographic and clinical factors. Methods: This retrospective study evaluated individuals with Fontan circulation followed at our center since 2010. A gap in care was defined as an absence of any formal cardiology provider-patient contact (clinic visit or telehealth) for >15 months. Results: Over a third of 308 patients with Fontan circulation experienced at least one gap in care between 2010 and 2022, and 77 experienced a gap in care during the COVID-19 pandemic. Of this latter group, 27 (35%) had never experienced a prior gap in cardiology care until the pandemic. Those who experienced gaps in care during the pandemic were on average older (18.0 [IQR 9.6-25.6] vs. 14.2 [7.2-21.2] years, p = 0.01), more likely to be of Black/African American race (23.4% vs 7.4%, p = 0.001), and less likely to have a diagnosis of protein-losing enteropathy or plastic bronchitis (0% vs. 8.6%, p = 0.005). Those without a gap in care during the pandemic were more likely to have utilized telehealth visits (13% vs 3%, p = 0.02). Conclusion: Gaps in care are common and appear to have been exacerbated by the COVID-19 pandemic in those with a Fontan circulation. Such gaps are particularly common among African American and adult patients, and may potentially be mitigated by expanding telehealth access.

Lung Transplantation for Bronchopulmonary Dysplasia.

BACKGROUND: Patients with bronchopulmonary dysplasia (BPD) have poor respiratory trajectories and are at increased risk of lung function decline with age. Lung transplant (LTx) is a possible treatment option for this growing patient population, but little has been published on LTx in this patient group. RESEARCH QUESTION: What are the characteristics of patients with BPD who are listed for LTx? How do waitlist and post-LTx outcomes for BPD compare with LTx for other diagnoses? STUDY DESIGN AND METHODS: The United Network for Organ Sharing (UNOS) registry was queried for patients of all ages listed for or who underwent LTx (2000-2020). Descriptive analysis, waitlist outcomes, and post-LTx survival at 1, 5, and 10 years were assessed comparing patients with BPD vs LTx patients with other diagnoses. Post-LTx survival for patients with BPD born in the pre-surfactant era (pre-SE, before 1990) and those born in the post-surfactant era (post-SE) was compared. Propensity score matching was performed to control for the risk factors and match patients with BPD with other LTx patients on a 1:1 ratio. RESULTS: BPD was reported in 65 patients, of whom 32 (49.2%) underwent LTx. Patients with BPD at listing were younger than those with other diagnoses (median age, 21 [interquartile range, 5-31] years vs 57 [45-63] years; P < .001), and more were likely to receive mechanical ventilation at listing (23% vs 3.7%; P < .001). Patients with BPD had an FEV1 of 17% compared with 34% predicted in other patients (P = .002). Patients with BPD had an overall similar post-LTx survival compared with patients with other diagnoses (P = .106), even following propensity score matching (P = .41). INTERPRETATION: LTx for BPD has increased over the last 20 years. Patients with BPD have similar post-LTx outcomes compared with those of other patient populations in the modern era. Thus, LTx could be considered for patients with BPD experiencing progressive respiratory deterioration.

Occult Diastolic Dysfunction and Adverse Clinical Outcomes in Adolescents and Young Adults With Fontan Circulation.

Background In Fontan circulation, diastolic dysfunction portends a worse clinical outcome but may be concealed during routine assessment. Invasive evaluation with rapid volume expansion (RVE) can identify patients with occult diastolic dysfunction (ODD). We sought to evaluate the association between ODD and adverse clinical outcomes at medium-term follow-up. Methods and Results We conducted a single-center observational study of patients with Fontan circulation who underwent clinical catheterization with RVE from 2012 to 2017. ODD was defined as post-RVE end-diastolic pressure ≥15 mm Hg. A composite adverse clinical outcome included mortality, cardiac transplant, ventricular assist device, plastic bronchitis, protein-losing enteropathy, arrhythmia, stroke/thrombus, or cardiac-related hospital admission. Proportional hazards regression was used to compare the ODD-positive and ODD-negative groups for risk of the composite adverse clinical outcome. Eighty-nine patients with Fontan circulation (47% female patients) were included at a median age of 14 years. ODD was identified in 31%. Fontan duration was longer in the ODD group (P=0.001). The composite adverse clinical outcome occurred more frequently in the ODD group (52 versus 26%, P=0.03) during a median follow-up duration of 2.9 years after catheterization. ODD (hazard ratio [HR], 2.68 [95% CI, 1.28-5.66]; P=0.02) and Fontan duration (HR, 1.07 [95% CI, 1.02-1.12]; P=0.003) were associated with the composite adverse clinical outcome. When stratified by Fontan duration, ODD remained significantly associated with the hazard of adverse clinical outcomes in patients with a Fontan duration ≥10 years (HR, 2.57 [95% CI, 1.03-6.57]; P=0.04). Conclusions Cardiac catheterization with rapid volume expansion reveals a significant incidence of ODD, which relates to Fontan duration. ODD is associated with an increased hazard of adverse clinical outcomes during medium-term follow-up, especially in patients with longer Fontan duration. ODD may portend a worse prognosis in Fontan circulation.

Is the practice of using oversized organs for recipients with elevated pulmonary vascular resistance justified?

OBJECTIVE: The purpose of this study was to assess post-transplantation outcomes in recipients with increased pulmonary vascular resistance (PVR) in relation to donor size. METHODS: The United Network for Organ Sharing database was used to identify patients ages 0 to 18 years at time of listing who underwent transplantation from 2010 to 2019 and for whom cardiac catheterization and donor-recipient weight ratio data were available. Patients were divided according to listing PVR into <3, 3 to 6, and >6 Wood units. Donor-recipient weight ratio was categorized as undersized (≤0.80), midsize (0.81-1.2), and oversized (>1.2). Subgroup analysis was done with an additional supersized group (>2.0). RESULTS: Fourteen hundred ninety-one patients met study criteria. Median age was 10 (interquartile range, 3-15) years and 45% were female. Four percent of heart transplantation cases used undersized, 45% used midsize, and 51% used oversized organs. More patients with PVR >6 were received an oversized organ transplant compared with patients with PVR <3; 59% (148/252) versus 48% (430/894); P = .003. There was no difference in survival among organ size groups regardless of PVR; this includes patients with PVR >6 at listing who received an oversized organ transplant versus an undersized (P = .359) or midsized (P = .956) organ. In subgroup analysis, even in patients who received a supersized organ transplant, there was no survival difference noted regardless of PVR. CONCLUSIONS: Despite a persistent practice pattern to transplant oversized organs in high-PVR patients, there remains no difference in post-transplantation survival among these patients and those who received smaller organ transplants. Therefore, transplants in patients with high PVR should not be delayed by waiting for larger donors.

Surgical Repair of Complete Common Atrioventricular Canal in a Conjoined Twin Following Separation.

Congenital heart disease (CHD) is common in conjoined twins but reports of surgical repair in this population are rare. We present the case of a conjoined twin diagnosed prenatally with a complete common atrioventricular canal defect (CAVC). Due to wound complications from twin separation, definitive repair was deferred and pulmonary arterial banding was performed initially. At 6 months, a complete CAVC repair was performed. The present case adds to the literature on successful cardiac surgical repairs in conjoined twins.

Transplantation-Associated Thrombotic Microangiopathy Risk Stratification: Is There a Window of Opportunity to Improve Outcomes?

Transplantation-associated thrombotic microangiopathy (TA-TMA) can range from a self-limiting condition to a lethal transplantation complication. It is important to identify TA-TMA patients at risk for severe multiorgan endothelial injury to implement targeted therapies in a timely manner. Current therapeutic approaches with complement blockade have improved survival markedly in high-risk TA-TMA patients, yet one-third of these patients respond inadequately to eculizumab therapy. Poor response may indicate that substantial endothelial injury has already occurred and raises the possibility that earlier intervention may improve outcomes. The goal of this study was to identify additional TA-TMA patients who would benefit from early targeted intervention and update TA-TMA risk stratification methods to reflect these findings. We studied 130 HSCT recipients with a diagnosis of TA-TMA who were screened prospectively and stratified into 3 TA-TMA risk groups (high-risk, n = 64; moderate-risk, n = 48; 18 low-risk, n = 18). We specifically examined TA-TMA biomarkers and clinical outcomes in subjects who were not offered complement blocking therapy (moderate-risk and low-risk TA-TMA subjects) and compared them with those who received TA-TMA-targeted therapy (high-risk TA-TMA subjects). One-year post-HSCT survival for subjects with untreated moderate-risk TA-TMA was similar to those with high-risk TA-TMA receiving eculizumab therapy (71% versus 66%; P = .40), indicating that a subset of moderate-risk patients may benefit from therapy. A detailed analysis of moderate-risk subjects highlighted the importance of relative as well as absolute complement pathway activation in determining organ injury. We demonstrated that activated terminal complement (measured by elevated blood sC5b-9) alone is a valuable indicator of reduced survival. Moderate-risk TA-TMA subjects with elevated sC5b-9 levels had a nearly 3-fold higher risk of mortality that was statistically significant in multivariant analyses (P = .01). A "dose effect" also was observed, and higher sC5b-9 levels were associated with worse outcomes. Furthermore, all moderate-risk patients with sustained sC5b-9 elevation for >2 weeks ultimately developed multiorgan dysfunction syndrome (MODS). This indicates that scheduled sC5b-9 measurements could promptly identify patients at risk for poor outcomes and would facilitate early TA-TMA-directed therapy to prevent organ injury. Untreated low-risk TA-TMA patients had a 1-year post-HSCT survival of 94% and should be observed without targeted interventions. Routine TA-TMA screening and complement-blocking therapies have markedly improved the outcomes for high-risk TA-TMA patients, and our study suggests that additional patients may benefit from TA-TMA treatment. This study provides further support for prospective TA-TMA screening as an integral tool for identifying patients at greatest risk for organ injury and death from TA-TMA. An updated TA-TMA risk algorithm that incorporates relevant laboratory biomarkers, clinical findings, and comorbid conditions was generated using this study's findings, and we propose clinical implementation of this algorithm for the management of TA-TMA.

Building a dedicated pediatric pulmonary hypertension program: A consensus statement from the pediatric pulmonary hypertension network.

Pediatric pulmonary hypertension (PH) is a severe, life-threatening disease associated with diverse cardiac, pulmonary, and systemic disorders, which generally requires expertise from multiple disciplines for management. Unfortunately, expert centers are limited, often due to inadequate resources or unfamiliarity with needed components for success. The Pediatric Pulmonary Hypertension Network (PPHNet) includes expert centers in North America specifically dedicated to advancing the field of pediatric PH through research and excellent clinical care. PPHNet member sites were queried for valuable program components and these findings were discussed for consensus. Here we provide a collective overview of key elements of an optimal pediatric PH program: team composition, access to services, and commitment to education. It is our intention that this document will assist newer and/or smaller programs identify avenues and resources for growth and provide avenues for collaboration.

Endocarditis in Bovine Vein Grafts in the Pulmonary Position Placed Surgically & Percutaneously.

Background: Infective endocarditis (IE) is one of the major complications following pulmonary valve replacement (PVR). This analysis hopes to evaluate the incidence, outcomes and possible risk factors of IE associated with trans-catheter and surgical placement of a bovine jugular vein (BJV) graft in the pulmonary position. Methods: In this single-center retrospective study, all records of trans-catheter and surgical PVR from 3/2010 to 12/2019 were reviewed. IE was defined as positive blood cultures, with vegetations seen on echocardiography or sudden increase in peak gradient across the valve or vegetations confirmed at time of valve replacement. Poor dental hygiene:1.dental procedures without S.B.E prophylaxis AND/OR 2.one or more dental cavities, caries, dental abscess. Results: 165 patients had PVR with BJV:107 trans-catheter and 63 surgical. 7%(12/170) of PVRs developed IE(catheter:n = 10, surgery:n = 2) at a median time from valve placement of 38 months. The incidence of IE in the catheter group:3-per-100patient-years and in surgical group:1-per-100patient-years. Multivariate cox regression showed that poor dental hygiene was significantly associated with IE [HR(95% CI):16.9(4.35-66.2)](p value <.001). Kaplan-Meier curves showed a significant difference in freedom from IE between patients with poor and appropriate dental hygiene (p value<.001). Conclusions: There is a 7% incidence of IE with the use of BJV grafts in the pulmonary position at mid-term follow-up. Though the rate in catheter placed BJV seems 3x higher than surgically placed ones, their cohorts are quite different making this comparison flawed. Poor dental hygiene is a strong predictor for post-operative IE and offers a significant opportunity for lowering the rate of infective endocarditis.

Bronchopulmonary dysplasia from chest radiographs to magnetic resonance imaging and computed tomography: adding value.

Bronchopulmonary dysplasia (BPD) is a common long-term complication of preterm birth. The chest radiograph appearance and survivability have evolved since the first description of BPD in 1967 because of improved ventilation and clinical strategies and the introduction of surfactant in the early 1990s. Contemporary imaging care is evolving with the recognition that comorbidities of tracheobronchomalacia and pulmonary hypertension have a great influence on outcomes and can be noninvasively evaluated with CT and MRI techniques, which provide a detailed evaluation of the lungs, trachea and to a lesser degree the heart. However, echocardiography remains the primary modality to evaluate and screen for pulmonary hypertension. This review is intended to highlight the important findings that chest radiograph, CT and MRI can contribute to precision diagnosis, phenotyping and prognosis resulting in optimal management and therapeutics.

Transcatheter pulmonary valve-in-valve implantation within the expandable Inspiris Resilia® bioprosthetic valve.

Transcatheter pulmonary valve implantation (TPVI) is a common intervention for patients with repaired congenital heart disease. A key issue relates to the presence of an appropriately sized implantation zone for the transcatheter valve. We report the first case, to our knowledge, of TPVI within the newly engineered Inspiris Resilia® bioprosthetic valve, intentionally designed with a balloon-expandable valve ring (a.k.a. VFit zone) for prospective valve implantation.

Biomarkers of Pulmonary Hypertension Are Altered in Children with Down Syndrome and Pulmonary Hypertension.

OBJECTIVE: To evaluate the performance of pulmonary hypertension (PH) biomarkers in children with Down syndrome, an independent risk factor for PH, in whom biomarker performance may differ compared with other populations. STUDY DESIGN: Serum endostatin, interleukin (IL)-1 receptor 1 (ST2), galectin-3, N-terminal pro hormone B-natriuretic peptide (NT-proBNP), IL-6, and hepatoma-derived growth factor (HDGF) were measured in subjects with Down syndrome and PH (n = 29), subjects with Down syndrome and resolved PH (n = 13), subjects with Down syndrome without PH (n = 49), and subjects without Down syndrome with World Symposium on Pulmonary Hypertension group I pulmonary arterial hypertension (no Down syndrome PH group; n = 173). Each biomarker was assessed to discriminate PH in Down syndrome. A classification tree was created to distinguish PH from resolved PH and no PH in children with Down syndrome. RESULTS: Endostatin, galectin-3, HDGF, and ST2 were elevated in subjects with Down syndrome regardless of PH status. Not all markers differed between subjects with Down syndrome and PH and subjects with Down syndrome and resolved PH. NT-proBNP and IL-6 levels were similar in the Down syndrome with PH group and the no Down syndrome PH group. A classification tree identified NT-proBNP and galectin-3 as the best markers for sequentially distinguishing PH, resolved PH, and no PH in subjects with Down syndrome. CONCLUSIONS: Proteomic markers are used to improve the diagnosis and prognosis of PH but, as demonstrated here, can be altered in genetically unique populations such as individuals with Down syndrome. This further suggests that clinical biomarkers should be evaluated in unique groups with the development of population-specific nomograms.

Angiostatic Peptide, Endostatin, Predicts Severity in Pediatric Congenital Heart Disease-Associated Pulmonary Hypertension.

Background Endostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH. Methods and Results Serum endostatin was measured in cross-sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH-CHD, N=185). Outcomes, assessed by regression and Kaplan-Meier analysis, included hemodynamics, change in endostatin over time, and transplant-free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH-CHD. In APAH-CHD, endostatin was associated with a shorter 6-minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant-free survival. Addition of endostatin to an NT-proBNP (N-terminal pro-B-type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells. Conclusions Endostatin is associated with disease severity, disease improvement, and worse survival in APAH-CHD. Endostatin with NT-proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH-CHD.