Management of systemic to pulmonary shunts and elevated pulmonary vascular resistance.

Background: Repair of systemic to pulmonary shunts is timed to prevent the development of irreversible pulmonary vascular disease, including in patients with other factors contributing to pulmonary hypertension. This study assessed outcomes of an individualised strategy for managing patients with mild-moderately elevated pulmonary vascular resistance (PVR) deemed borderline eligible for repair. Methods: A retrospective chart review was conducted of patients with systemic to pulmonary shunts and baseline indexed PVR (PVRi) ≥3 WU·m2 treated at a single centre from 1 January 2005 to 30 September 2019. Data included demographics, World Health Organization functional class (WHO FC), medications and haemodynamic data at baseline and serial follow-up. Results: 30 patients (18 females) met criteria for inclusion. Median age at diagnosis of pulmonary arterial hypertension was 1.3 years (range 0.03-54 years) and at surgery was 4.1 years (range 0.73-56 years). Median follow-up time was 5.8 years (range 0.2-14.6 years) after repair. Most patients received at least one targeted pulmonary arterial therapy prior to repair and the majority (80%) underwent fenestrated shunt closure. There was a significant decrease in mean pulmonary arterial pressure (mPAP) (p<0.01), PVRi (p=0.0001) and PVR/systemic vascular resistance (p<0.01) between baseline and preoperative catheterisation and a decrease in PVRi (p<0.005), mPAP (p=0.0001) and pulmonary to systemic flow ratio (p<0.03) from baseline to most recent catheterisation. WHO FC improved from FC II-III at baseline to FC I post repair in most patients (p<0.003). Conclusions: In carefully selected patients with systemic to pulmonary shunts and elevated PVR considered borderline for operability, the use of preoperative targeted therapy in conjunction with fenestrated or partial closure of intracardiac shunts is associated with improvement in WHO FC and clinical outcomes.

Gender Disparities in Presentation, Management, and Outcomes of Acute Pulmonary Embolism.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death; however, gender disparities in PE remain understudied. All PE cases at a single institution between January 2013 and June 2019 were retrospectively reviewed. The clinical presentation, treatment modalities, and outcomes were compared between men and women using univariate and multivariate analyses adjusting for differences in baseline characteristics. A total of 1,345 patients were diagnosed with acute PE, of whom 56.3% were women (n = 757). Women had a significantly higher mean body mass index (29.4 vs 28.4) and a higher frequency of hypertension (53% vs 46%) and hormone use (6.6% vs 0%; all p <0.02). Men had a higher frequency of smoking (45% vs 33%, p <0.0001). Women had significantly lower PE severity index classifications (p = 0.0009). The rates of intensive care unit admission, vasopressor requirements, extracorporeal membrane oxygenation cannulation, and mechanical ventilation were similar between the genders. There was no significant difference in the treatment modality used between the genders. Although the risk factors and PE severity index class differed between the genders, there was no significant difference in resource utilization or treatment modality. Gender was also not a significant predictor of in-hospital mortality, moderate or severe bleeding, increased length of stay, or readmission in the study population.

Iron deficiency in pulmonary vascular disease: pathophysiological and clinical implications.

AIMS: Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear. METHODS AND RESULTS: Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores. The relationships between iron deficiency and cardiac and pulmonary vascular function and structure and outcomes were assessed. The heart failure definition of iron deficiency endorsed by pulmonary hypertension guidelines did not identify patients with reduced peakVO2, 6-min walk test, and SF-36 (P > 0.208 for all), but defining iron deficiency as transferrin saturation (TSAT) <21% did. Compared to those with TSAT ≥21%, patients with TSAT <21% demonstrated lower peakVO2 [absolute difference: -1.89 (-2.73 to -1.04) mL/kg/min], 6-min walk test distance [absolute difference: -34 (-51 to -17) m], and SF-36 physical component score [absolute difference: -2.5 (-1.3 to -3.8)] after adjusting for age, sex, and hemoglobin (all P < 0.001). Patients with a TSAT <21% had more right ventricular remodeling on cardiac magnetic resonance but similar pulmonary vascular resistance on catheterization. Transferrin saturation <21% was also associated with increased mortality risk (hazard ratio 1.63, 95% confidence interval 1.13-2.34; P = 0.009) after adjusting for sex, age, hemoglobin, and N-terminal pro-B-type natriuretic peptide. CONCLUSION: The definition of iron deficiency in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines does not identify patients with lower exercise capacity or functional status, while a definition of TSAT <21% identifies patients with lower exercise capacity, worse functional status, right heart remodeling, and adverse clinical outcomes.

A 52-Year-Old Man With Chest Pain and Dyspnea.

CASE PRESENTATION: A 52-year-old man came to the cardiac surgery clinic for pulmonary thromboendarterectomy (PTE) evaluation. He had initially appeared at an outside hospital 1 year earlier, with chest pain and shortness of breath. He had no known chronic conditions. A CT pulmonary angiogram (CTPA) at that time showed a filling defect at the bifurcation of the main pulmonary artery. A transthoracic echocardiogram revealed mild mitral valve regurgitation, but otherwise the results were normal. As he was hemodynamically stable and not hypoxemic, he was treated solely by anticoagulation. Despite adhering to prescribed apixaban, he developed progressive dyspnea and reduced exercise tolerance over the subsequent year. A repeat CTPA performed 12 months after the initial presentation showed a persistent filling defect at the level of the pulmonary artery bifurcation, with a new extension now completely occluding the right main pulmonary artery. A pulmonary angiogram confirmed this complete occlusion, and right heart catheterization revealed precapillary pulmonary hypertension, with a mean pulmonary artery pressure of 50 mm Hg. His anticoagulation was transitioned to enoxaparin for presumed apixaban treatment failure, and an investigation for hypercoagulable conditions was initiated. His lupus anticoagulant test result was positive, but he did not meet the criteria for antiphospholipid syndrome because he was negative for anticardiolipin and ß2-glycoprotein antibodies. Assays for antithrombin III, protein C, prothrombin gene, and factor V Leiden mutations produced normal results.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Acute Kidney Injury After Pulmonary Thromboendarterectomy: Associated Factors and Impact.

BACKGROUND: Acute kidney injury (AKI) is a common complication after pulmonary thromboendarterectomy (PTE) that has been shown to be associated with worse outcomes. Our study assesses factors associated with the development of postoperative AKI after PTE and its impact on clinical outcomes. METHODS: We retrospectively analyzed 247 patients who underwent PTE at our institution between June 2009 and December 2020. Baseline characteristics, risk factors, and outcomes were compared between patients with and without postoperative AKI. The primary endpoint was development of postoperative AKI using the Kidney Disease Improving Global Outcomes definition, and secondary endpoints were length of hospital stay, hospital mortality, and 5-year mortality. RESULTS: The overall incidence of postoperative AKI in our study population was 49%. One hundred twenty-three patients (50.8%) did not develop AKI postoperatively, 87 patients (35.9%) developed stage 1 AKI postoperatively, 21 patients (8.7%) developed stage 2 AKI postoperatively, and 11 (4.5%) developed stage 3 AKI postoperatively. Patients who developed AKI postoperatively had longer hospital stays, higher in-hospital mortality rates, and higher 5-year mortality rates than patients who did not develop postoperative AKI. Higher body mass index, older age, low preoperative hemoglobin, low ejection fraction, and low creatinine were shown to be associated with postoperative AKI development. CONCLUSIONS: Patients who developed AKI after PTE had worse mortality and morbidity. Clinicians should have a lower threshold for suspecting AKI and consider implementing Kidney Disease Improving Global Outcomes-based AKI prevention bundles for patients with factors associated with development of AKI.

Impact of sex, race and socioeconomic status on survival after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

OBJECTIVES: Pulmonary thromboendarterectomy (PTE) is a definitive treatment for chronic thromboembolic pulmonary hypertension. Demographic-based disparities in PTE outcomes have not been well-studied. METHODS: We reviewed all patients who underwent PTE for chronic thromboembolic pulmonary hypertension between 2009 and 2019 at our institution, tracking demographic information including self-identified race, preoperative characteristics and 2-year survival. Socioeconomic status was assessed using the zip code-linked Distressed Communities Index, a validated holistic measure of community well-being. Survival was estimated using Kaplan-Meier method and factors associated with mortality were estimated using Cox regression. RESULTS: Of 235 PTE patients, 101 (42.9%) were white and 87 (37.0%) were black. White patients had a higher median age at surgery (57 vs 51 years, P = 0.035) and a lower degree of economic distress (33.6 vs 61.2 percentile, P < 0.001). Regarding sex, 106 (45.1%) patients were male and 129 (53.6%) were female. Male patients had a higher median age (59 vs 50 years, P = 0.004), greater rates of dyslipidaemia (34% vs 20.2%, P = 0.025), a lower ejection fraction (55% vs 57%, P = 0.046) and longer cross-clamp (77 vs 67.50 min, P = 0.004) and circulatory arrest times (42 vs 37.50 min, P = 0.007). No difference was observed in unadjusted 2-year survival after PTE between patients stratified by race and sex (P = 0.35). After adjustment for clinically relevant variables, neither socioeconomic status, sex nor race were associated with mortality in Cox proportional hazard analysis. CONCLUSIONS: Sex, socioeconomic status and race were not associated with adverse outcomes after PTE in our single-centre experience.

Characteristics and prognostic significance of right heart remodeling and tricuspid regurgitation after pulmonary endarterectomy.

OBJECTIVE: Right heart remodeling and tricuspid regurgitation (TR) are common in patients with chronic thromboembolic pulmonary hypertension. This study aimed to investigate the significance of right heart remodeling and TR after pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension. METHODS: Patients who underwent PEA with preoperative and postoperative transthoracic echocardiograms at our center between June 2010 and July 2019 were retrospectively reviewed. The composite end point was defined as death or hospitalization due to worsening heart failure, bleeding, or recurrent pulmonary embolism. RESULTS: In total, 158 patients were included for analysis. Right ventricular basal (48 [45-52] vs 43 [39-47] mm, P < .001), midcavitary (46 [42-50] vs 38 [34-42] mm, P < .001), and longitudinal dimensions (87 [83-93] vs 80 [75-84] mm, P < .001), along with the right atrial volume index (37 [25-51] vs 24 [18-34] mL/m2, P < .001), significantly decreased, whereas left ventricular and atrial sizes and left ventricular ejection fraction increased after PEA. Overall, 78 patients (49%) showed significant TR on preoperative transthoracic echocardiograms, and 33 (21%) had significant residual TR after PEA. Fourteen patients died, and 24 patients met the composite end point. Residual TR after PEA was independently associated with mortality (P = .005) and the composite end point (P = .003). Patients with residual TR had significantly worse survival (log-rank P < .001) and greater event rates (log-rank P = .003) than those without residual TR. CONCLUSIONS: Significant improvements in right heart remodeling were seen following PEA. However, residual TR was a poor prognostic marker.

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.

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

ST2 Is a Biomarker of Pediatric Pulmonary Arterial Hypertension Severity and Clinical Worsening.

BACKGROUND: Pediatric pulmonary hypertension is a severe disease defined by sustained elevation of pulmonary artery pressures and pulmonary vascular resistance (PVR). Noninvasive diagnostic and prognostic markers that are more pulmonary vascular specific have been elusive because of disease heterogeneity and patient growth. RESEARCH QUESTION: Is soluble suppressor of tumorigenicity (ST2) associated with pulmonary hemodynamic and functional changes in pediatric pulmonary hypertension? Does ST2 improve mortality risk models in pediatric pulmonary hypertension? STUDY DESIGN AND METHODS: Two pediatric cohorts (age < 21 years) were assayed for ST2 and N-terminal prohormone B-natriuretic peptide: a cross-sectional cohort from the National Heart Lung and Blood Institute-funded National Biological Sample and Data Repository for PAH (PAHB) (N = 182), and a second longitudinal cohort from Children's Hospital of Colorado (N = 61). Adjusted linear regression was used for association with clinical variables. Clinical mortality models (the Registry to Evaluate Early and Long-Term PAH Disease Management [REVEAL] score) with and without ST2 were used to predict worsening outcomes and compared. Pulmonary artery endothelial and smooth muscle cell ST2 expression and secretion were assayed in vitro. RESULTS: In an adjusted (age and sex) analysis in the PAHB, ST2 was significantly associated with shorter 6-min walk distance (P = .03) and increased PVR index (P = .02). In adjusted longitudinal regression in the Children's Hospital of Colorado cohort, ST2 was significantly associated with higher PVR index (P < .001), shorter 6-min walk distance (P = .01), and higher mean pulmonary artery pressure (P < .001). Although the REVEAL Risk Score Calculator 2.0 was predictive of clinical worsening in the PAHB (hazard ratio, 1.88), addition of ST2 significantly improved the model (hazard ratio, 2.05). In cell culture, ST2 was produced and secreted predominately by endothelial cells as opposed to smooth muscle cells (P < .0001). INTERPRETATION: In two pediatric PAH cohorts, elevated ST2 was associated with unfavorable pulmonary hemodynamics and functional measures, clinical worsening, and significantly improved prediction of clinical worsening. Pulmonary artery endothelial cellular expression of ST2 suggests that ST2 is a more pulmonary vascular-specific marker for pulmonary hypertension.

A novel unidirectional-valved shunt approach for end-stage pulmonary arterial hypertension: Early experience in adolescents and adults.

OBJECTIVES: Despite advances in treatment of idiopathic pulmonary arterial hypertension (IPAH), there remains no medical cure, and patients can experience disease progression leading to right heart failure, progressive exercise intolerance, and death. The reversed Potts shunt (left pulmonary artery to descending aorta) was reintroduced for treatment of end-stage IPAH to permit decompression of the suprasystemic right ventricle by right to left shunting, with preservation of upper body oxygenation. The shunt has the potential to delay the need for lung transplantation and offer a treatment for those who are transplant ineligible. To optimize shunt design and avoid the potential complications of bidirectional shunting, we developed a novel approach using a unidirectional-valved shunt (UVS) in patients with IPAH with suprasystemic pulmonary arterial pressure and poor right ventricular function. METHODS: A single-center retrospective review was performed of UVS cases done at Columbia University Medical Center-New York Presbyterian between November 1, 2016, and May 1, 2019. RESULTS: Five patients (4 female; ages 12-22 years) underwent UVS. All had suprasystemic pulmonary arterial pressure, poor right ventricular function, and World Health Organization functional class IV symptoms at baseline. All patients are alive and transplant-free at latest follow-up (range 3-33 months; median 6 ± 11 months). CONCLUSIONS: The UVS may offer an alternative solution to lung transplantation in adolescents and young adults with IPAH. Longer-term follow-up is needed to determine the ultimate impact of unidirectional unloading of the right ventricle in these patients and to determine whether the UVS will enable a broader approach to the treatment of patients with IPAH.

Targeted Therapy for Pulmonary Hypertension in Premature Infants.

Pulmonary hypertension (PH) is common in premature infants with bronchopulmonary dysplasia (BPD) and is associated with significant mortality. Despite expert consensus suggesting the use of targeted therapies such as phosphodiesterase inhibitors, endothelin receptor antagonists, and prostanoids, there is little data on safety and outcomes in infants with BPD-associated PH (BPD-PH) treated with these medications. We sought to describe the pharmacologic management of BPD-PH and to report outcomes at our institution. Premature infants with BPD-PH born between 2005 and 2016 were included. Follow-up data were obtained through January 2020. A total of 101 patients (61 male, 40 female) were included. Of these, 99 (98.0%) patients were treated with sildenafil, 13 (12.9%) with bosentan, 35 (34.7%) with inhaled iloprost, 12 (11.9%) with intravenous epoprostenol, and nine (8.9%) with subcutaneous treprostinil. A total of 33 (32.7%) patients died during the study period and 10 (9.9%) were secondary to severe to pulmonary hypertension. Of the surviving patients, 57 (83.8%) had follow-up data at a median of 5.1 (range 0.38-12.65) years and 44 (77.2%) were weaned off PH medications at a median 2.0 (range 0-8) years. Mortality for BPD-PH remains high mostly due to co-morbid conditions. However, for those patients that survive to discharge, PH therapies can frequently be discontinued in the first few years of life.

Elevated Interleukin-6 Levels Predict Clinical Worsening in Pediatric Pulmonary Arterial Hypertension.

OBJECTIVE: To assess whether circulating interleukin-6 (IL-6) is associated with measures of disease severity and clinical worsening in pediatric pulmonary arterial hypertension (PAH). STUDY DESIGN: IL-6 was measured by enzyme-linked immunosorbent assay in serum samples from a cross-sectional cohort from the National Heart, Lung, and Blood Institute Pulmonary Arterial Hypertension Biobank (n = 175) and a longitudinal cohort from Children's Hospital Colorado (CHC) (n = 61). Associations between IL-6, disease severity, and outcomes were studied with regression and Kaplan-Meier analysis. RESULTS: In analyses adjusted for age and sex, each log-unit greater IL-6 was significantly associated in the Pulmonary Arterial Hypertension Biobank cohort with greater pulmonary vascular resistance indices, lower odds of having idiopathic PAH or treatment with prostacyclin, and greater odds of having PAH associated with a repaired congenital shunt. In the CHC cohort, each log-unit greater IL-6 was significantly associated with greater mean pulmonary arterial pressure over time. Kaplan-Meier analysis in the CHC cohort revealed that IL-6 was significantly associated with clinical worsening (a composite score of mortality, transplant, or palliative surgery) (P = .037). CONCLUSIONS: IL-6 was significantly associated with worse hemodynamics at baseline and over time and may be associated with clinical worsening. IL-6 may provide a less-invasive method for disease monitoring and prognosis in pediatric PAH as well as a potential therapeutic target.

A rare childhood case of Behcet's disease and chronic thromboembolic pulmonary hypertension.

BACKGROUND: Pulmonary embolism and chronic thromboembolic pulmonary hypertension (CTEPH) are rare complications of Behcet's disease, especially in pediatric patients. AIMS/METHODS/RESULTS/CONCLUSIONS: This case report highlights a presentation of CTEPH in an adolescent with Behcet's disease. A multidisciplinary approach was required for managing this patient's CTEPH, which successfully reversed the patient's pulmonary hypertension.

Extracorporeal life support bridge for pulmonary hypertension: A high-volume single-center experience.

BACKGROUND: Application of extracorporeal life support (ECLS) for advanced pulmonary hypertension (PH) is evolving and may be deployed as a bridge to transplantation (BTT) or in one of several non-BTT uses, such as bridge to recovery (BTR) to the chronic PH clinical state in the setting of an acute PH trigger, bridge through non-transplant surgery (BTNTS), or bridge post-transplantation (BPT). METHODS: We conducted a retrospective analysis of all adult patients with World Symposium on Pulmonary Hypertension Group 1, 3, 4, or 5 PH who received ECLS at Columbia University Medical Center/New York Presbyterian Hospital between January 1, 2010 and August 18, 2018. We describe patient characteristics, outcomes, and our approach to medical and surgical management of these patients. RESULTS: There were 98 patients with significant PH in the cohort (54 female; median age, 48 years [interquartile range, 32-58]). Of these, 44 (45%) patients with PH received ECLS as non-BTT with intent to recover back to their baseline functional state, optimize therapy, or support through a definitive surgery, including 19 BTR, 17 BTNTS, and 8 BPT, and 54 (55%) patients received ECLS as BTT. In the overall cohort, 67 (68.4%) patients received venoarterial ECLS and 31 (31.6%) received venovenous (VV) ECLS. Out of 83 patients, 52 (63%) were liberated from invasive mechanical ventilation, and 85.2% of BTT patients with PH ambulated while on ECLS. Management of PH medications was individualized, often requiring titration with use of inhaled pulmonary vasodilators increased after cannulation in non-BTT. Overall 30-day survival was 73.5%, survival to ECLS decannulation was 66.3%, and survival to hospital discharge was 54.1%. All 8 BPT patients (100%) survived to hospital discharge, 64.7% of BTNTS patients survived to hospital discharge, and 32 (59.3%) BTT patients survived to lung transplantation. Early-era use of VV-ECLS for BTT had worse survival to discharge than those initially configured with venoarterial ECLS, impacting the overall survival and leading to limited use of VV-ECLS in the current era for BPT, BTNTS, and select BTR cases. CONCLUSIONS: ECLS instituted by a specialized, multidisciplinary team has a role in the management of advanced PH as BTT or as non-BTT (including BTR, BTNTS, and BPT). Careful selection of ECLS cannulation configurations, patient-specific optimization of PH medical therapies, and avoidance of endotracheal intubation may be effective strategies in managing these complex patients.

Racial and Ethnic Differences in Pediatric Pulmonary Hypertension: An Analysis of the Pediatric Pulmonary Hypertension Network Registry.

OBJECTIVE: To investigate racial and ethnic differences in pulmonary hypertension subtypes and survival differences in a pediatric population. STUDY DESIGN: This was a retrospective analysis of a cohort of patients with pulmonary hypertension (aged ≤18 years) enrolled in the Pediatric Pulmonary Hypertension Network registry between 2014 and 2018, comprising patients at eight Pediatric Centers throughout North America (n = 1417). RESULTS: Among children diagnosed after the neonatal period, pulmonary arterial hypertension was more prevalent among Asians (OR, 1.83; 95% CI, 1.21-2.79; P = .0045), lung disease-associated pulmonary hypertension among blacks (OR, 2.09; 95% CI, 1.48-2.95; P < .0001), idiopathic pulmonary arterial hypertension among whites (OR, 1.58; 95% CI, 1.06-2.41; P = .0289), and pulmonary veno-occlusive disease among Hispanics (OR, 6.11; 95% CI, 1.34-31.3; P = .0184). Among neonates, persistent pulmonary hypertension of the newborn (OR, 4.07; 95% CI, 1.54-10.0; P = .0029) and bronchopulmonary dysplasia (OR, 8.11; 95% CI, 3.28-19.8; P < .0001) were more prevalent among blacks, and congenital diaphragmatic hernia was more prevalent among whites (OR, 2.29; 95% CI, 1.25-4.18; P = .0070). An increased mortality risk was observed among blacks (HR, 1.99; 95% CI, 1.03-3.84; P = .0396), driven primarily by the heightened mortality risk among those with lung disease-associated pulmonary hypertension (HR, 2.84; 95% CI, 1.15-7.04; P = .0241). CONCLUSIONS: We found significant racial variability in the prevalence of pulmonary hypertension subtypes and survival outcomes among children with pulmonary hypertension. Given the substantial burden of this disease, further studies to validate phenotypic differences and to understand the underlying causes of survival disparities between racial and ethnic groups are warranted.

Sildenafil Use in Children with Pulmonary Hypertension.

OBJECTIVE: To assess the demographics, treatment algorithm, and outcomes in a large cohort of children treated with sildenafil. STUDY DESIGN: A retrospective cohort study of children with pulmonary hypertension (PH) treated with sildenafil at a single institution between 2004 and 2015. Baseline and follow-up data collected by chart review. RESULTS: There were 269 children included in this study: 47 with idiopathic pulmonary arterial hypertension, 53 with congenital heart disease, 135 with bronchopulmonary dysplasia, 24 with congenital diaphragmatic hernia, and 7 with other causes. Sildenafil was initial monotherapy in 84.8% and add-on therapy in 15.2%. Median follow-up time was 3.1 years (2 weeks-12.4 years). On follow-up, 99 (37%) remained on sildenafil or transitioned to tadalafil, 93 (35%) stopped sildenafil for improvement in PH, 54 (20%) died, and 20 (7%) were lost to follow-up. PH was most likely to improve in those with bronchopulmonary dysplasia, allowing for the discontinuation of sildenafil in 45%. Eighteen deaths were related to PH and 36 from other systemic causes. Two patients stopped sildenafil owing to airway spasm with desaturation. Overall survival was significantly lower in World Health Organization group 3 PH (bronchopulmonary dysplasia and congenital diaphragmatic hernia) vs group 1 (idiopathic pulmonary arterial hypertension and congenital heart disease), P = .02. CONCLUSIONS: In this retrospective experience in children with mainly World Health Organization groups 1 and 3 PH, low-dose sildenafil was well-tolerated, safe, and had an acceptable side effect profile. Although patients with group 3 PH have high mortality, survivors have a high likelihood of PH improving.