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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.

ImportanceThe prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.ObservationsWe describe the protocol for the Pediatric Observational Cohort Study of the NIH’sREsearchingCOVID toEnhanceRecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) ade novoRECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). Thede novocohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.Conclusions and RelevanceRECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.Clinical Trials.gov IdentifierClinical Trial Registration:http://www.clinicaltrials.gov. Unique identifier:NCT05172011

RATIONALE: There is currently no data supporting specific dosing and weaning strategies for parental prostanoid therapy in children with pulmonary arterial hypertension (PAH).OBJECTIVES: To describe the clinical practice of intravenous (IV) or subcutaneous (SC) prostanoid therapy in pediatric PAH and identify dosing strategies associated with favorable outcome.METHODS: From an international multicenter cohort of 275 children with PAH, 98 patients that received IV/SC prostanoid therapy were retrospectively analyzed.RESULTS: IV/SC prostanoids were given as monotherapy (20%), or combined with other PAH-targeted drugs as dual (46%) or triple therapy (34%). The median time-averaged dose was 37 ng/kg/min, ranging 2-136 ng/kg/min. During follow up, IV/SC prostanoids were discontinued and transitioned to oral or inhaled PAH-targeted therapies in 29 patients. Time-dependent ROC analyses showed specific hemodynamic criteria at discontinuation of IV/SC prostanoids (mean pulmonary arterial pressure (mPAP)25 ng/kg/min), early start after diagnosis and combination with other PAH-targeted drugs were associated with better transplant-free survival.CONCLUSIONS: Early initiation of IV/SC prostanoids, higher doses of IV/SC prostanoids and combination with additional PAH-targeted therapy were associated with favorable outcome. Transition from IV/SC prostanoid therapy to oral or inhaled therapies is safe on the long-term in selected children, identified by reaching hemodynamic criteria for durable IV/SC prostanoid discontinuation while on IV/SC prostanoid therapy.

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 Conclusions Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

Aims There is a wide spectrum of diseases associated with pulmonary hypertension, pulmonary vascular remodelling, and right ventricular dysfunction. The NIH-sponsored PVDOMICS network seeks to perform comprehensive clinical phenotyping and endophenotyping across these disorders to further evaluate and define pulmonary vascular disease. Methods and results Echocardiography represents the primary non-invasive method to phenotype cardiac anatomy, function, and haemodynamics in these complex patients. However, comprehensive right heart evaluation requires the use of multiple echocardiographic parameters and optimized techniques to ensure optimal image acquisition. The PVDOMICS echo protocol outlines the best practice approach to echo phenotypic assessment of the right heart/pulmonary artery unit. Conclusion Novel workflow processes, methods for quality control, data for feasibility of measurements, and reproducibility of right heart parameters derived from this study provide a benchmark frame of reference. Lessons learned from this protocol will serve as a best practice guide for echocardiographic image acquisition and analysis across the spectrum of right heart/pulmonary vascular disease.

BACKGROUND: PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification. OBJECTIVES: The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort. METHODS: Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1–5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death. RESULTS: A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1–3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1–4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21–24 mm Hg. Transplant-free survival was poorest in group 3 PH. CONCLUSIONS: PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1–3 and 1–4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887)

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 CONCLUSIONS Sex, socioeconomic status and race were not associated with adverse outcomes after PTE in our single-centre experience.

RATIONALE: Hemodynamic assessments direct care among children with pulmonary hypertension, yet the use of cardiac catheterization is highly variable, which could impact patient care and research. OBJECTIVES: We analyzed hemodynamic findings from right heart catheterization (RHC) and left heart catheterization and acute vasodilator testing (AVT) and the safety of catheterization in children with World Symposium on Pulmonary Hypertension (WSPH) group 1 and 3 subtypes in a large multicenter North American cohort. METHODS: Of 1,475 children enrolled in the Pediatric Pulmonary Hypertension Network Registry (2014–2020), there were 1,383 group 1 and 3 patients, of whom 671 (48.5%) underwent RHC at diagnosis and were included for analysis. RESULTS: Compared with those without diagnostic RHC, these children were older, less likely to be an infant or preterm, more often female, treated with targeted pulmonary hypertension medications at diagnosis, and had advanced World Health Organization functional class. Catheterization was performed without a difference in complication rates between WSPH groups. Pulmonary capillary wedge pressure was well correlated with left ventricular end-diastolic pressure and left atrial pressures. Results of AVT using three different methods were comparable; positive AVT results were observed in 8.0–11.8% of subjects, did not differ between WSPH groups 1 and 3, and were not associated with freedom from the composite endpoint of lung transplantation or death during follow-up. CONCLUSIONS: In a large pediatric pulmonary hypertension cohort, diagnostic RHC with or without left heart catheterization in WSPH group 1 and 3 patients was performed safely at experienced pediatric pulmonary hypertension centers. Hemodynamic differences were noted between group 1 and 3 subjects. Higher mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean systemic arterial pressure ratio were associated with a higher risk of death/transplantation. Findings suggest overall safety and potential value of RHC as a standard diagnostic approach to guide pulmonary hypertension management in children.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 ( n = 74) compared to the same period in 2019 ( n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

Patients with acute pulmonary embolism (PE) present on a spectrum of clinical severity with a subset at risk for significant morbidity and mortality. Individuals without contraindications should be treated with systemic anticoagulation therapy; however, advanced therapies including systemic fibrinolysis, catheter-based approaches, surgical embolectomy, and mechanical circulatory support may be considered in the setting of hemodynamic instability or deterioration. Catheter-based therapies, categorized into lytic and non-lytic based approaches, have recently broadened treatment options, and may be of benefit to patients who are in intermediate- or high-risk categories. These approaches may allow for rapid improvement of right ventricular function and have the potential to lower the risk of bleeding complications compared to systemic fibrinolytic therapy. Emerging strategies utilizing adjunctive mechanical circulatory support may improve outcomes in the highest risk patients, providing stabilization prior to definitive therapy and potentially obviating the need for invasive measures. To help navigate these rapidly evolving treatment paradigms, pulmonary embolism response teams (PERT) have been established. Further studies focusing on the safety and efficacy of novel therapies and impact of PERT will be crucial for advancement of the field. This review focuses on currently available therapies, recent advances, and future directions in the treatment of acute pulmonary embolism. Abbreviations: PE: pulmonary embolism; VTE; venous thromboembolism; CBT: catheter-based therapy; RV: right ventricle; AHA: American Heart Association; ACCP: American College of Chest Physicians; ESC: European Society of Cardiology; PESI: pulmonary embolism severity index; LV: left ventricle; DOAC: direct oral anticoagulant; FDA: Food and Drug Administration; tPA: tissue plasminogen activator; CTEPH: chronic thromboembolic pulmonary hypertension; USAT: ultrasound-assisted catheter-directed thrombolysis; VA-ECMO: veno-arterial extracorporeal membrane oxygenation; PERT: pulmonary embolism response team

Presently, with increasing survival of patients with congenital heart disease (CHD), pulmonary arterial hypertension (PAH) associated with CHD is commonly encountered in children and adults. This increased prevalence is seen despite significant advances in early diagnosis and surgical correction of patients with structural CHD. PAH is the cause of significant morbidity and mortality in these patients and comes in many forms. With the increased availability of targeted therapies for PAH, there is hope for improved hemodynamics, exercise capacity, quality of life, and possibly survival for these patients. There may also be opportunities for combined medical and interventional/surgical approaches for some.

Background: Hispanic and Latino patients are under-represented in existing healthcare disparities research in pulmonary embolism (PE). The goal of this study was to determine if differences in PE severity, treatment modality, or in-hospital outcomes exist for Hispanic or Latino patients with PE. Methods: All PE cases from 2013 to 2019 at a single institution were reviewed. Clinical characteristics, imaging findings, intervention types, and in-hospital and 30-day outcomes were collected. Two cohorts were created based on patients’ self-reported ethnicity. Outcomes were compared using univariate and multivariate analysis. Results: A total of 1265 patients were identified with confirmed PE; 474 (37%) identified as Hispanic or Latino. Hispanic or Latino patients presented with high-risk PE significantly less often (19% vs 25%, p = 0.03). On univariate analysis, Hispanic or Latino patients had lower rates of PE-specific intervention (15% vs 19%, p = 0.03) and similar rates of inpatient mortality (6.8% vs 7.5%, p = 0.64). On ordinal regression analysis, Hispanic or Latino ethnicity was associated with lower PE severity (OR 0.69, 95% CI 0.54–0.89, p = 0.003). In subgroup analyses of intermediate and high-risk PEs, ethnicity was not a significant predictor of receipt of PE-specific intervention or in-hospital mortality. Conclusions: At this institution, Hispanic or Latino patients were less likely to present with high-risk PE but had similar rates of inpatient mortality. Future research is needed to identify if disparities in in-hospital care are driving perceived differences in PE severity and what addressable systematic factors are driving higher-than-expected in-hospital mortality for Hispanic or Latino patients.

Pulmonary hypertension (PH) is a progressive disease that leads to cardiopulmonary dysfunction and right heart failure from pressure and volume overloading of the right ventricle (RV). Mechanical cardiopulmonary support has theoretical promise as a bridge to organ transplant or destination therapy for these patients. Solving the challenges of mechanical cardiopulmonary support for PH and RV failure requires its testing in a physiologically relevant animal model. Previous PH models in large animals have used pulmonary bead embolization, which elicits unpredictable inflammatory responses and has a high mortality rate. We describe a step-by-step guide for inducing pulmonary hypertension and right ventricular hypertrophy (PH-RVH) in sheep by left pulmonary artery (LPA) ligation combined with progressive main pulmonary artery (MPA) banding. This approach provides a controlled method to regulate RV afterload as tolerated by the animal in order to achieve PH-RVH, while reducing acute mortality. This animal model can facilitate evaluation of mechanical support devices for PH and RV failure.

Background Insulin-like growth factors (IGFs), and their binding proteins (IGFBPs), play a significant role in cardiovascular function and may influence the pathobiology of PAH. We determined the diagnostic and prognostic value of IGF1 and IGFBP2 in pediatric PAH. Methods Serum was analyzed by ELISA for IGF1 and IGFBP2 in pediatric PAH subjects from the NHLBI PAH Biobank (PAHB, n = 175) and a cohort of asthmatic subjects (n = 46, age 0-21 years) as a chronic pediatric pulmonary disease control. Biomarkers were analyzed with demographic and clinical variables for PAH severity. Results Serum IGF1 was significantly lower in PAH compared to controls, while IGFBP2 was elevated in PAH subjects compared to controls. In the PAHB, IGF1 was negatively associated with mPAP and PVR, while IGFBP2 was positively associated with PVR and negatively associated with cardiac output and 6-min walk distance. Higher IGFBP2 levels were associated with use of prostacyclin therapy. IGFBP2 was associated with death, transplant, or palliative shunt with a Cox proportional hazard ratio of 8.8 (p Conclusions Circulating IGFBP2 is a novel marker for pediatric PAH, which is associated with worse functional status, and survival. IGF axis dysregulation may be an important mechanistic target in pediatric pulmonary arterial hypertension. Impact Pediatric pulmonary hypertension is a severe disease, with poorly understood pathobiology.There are few studies looking at the pathobiology of pulmonary hypertension only in children.The IGF axis is dysregulated in pediatric pulmonary arterial hypertension.IGF axis dysregulation, with increased IGFBP2, is associated with worse clinical outcomes in pediatric pulmonary artery hypertension.IGF axis dysregulation gives new insight into the disease process and may be a mechanistic or therapeutic target.Fig. 1IGF1 AND IGFBP2 CONCENTRATION (NG/ML) IN PAH BIOBANK VERSUS CONTROLS.: a IGF1 concentration (ng/mL) in PAH Biobank versus asthmatic subjects. b IGFBP2 concentration (ng/mL) in PAH Biobank versus asthmatic subjects.Fig. 2ROC CURVE OF IGF1 AND IGFBP2 IN PAH BIOBANK VERSUS CONTROLS.: a ROC curve of IGF1 in PAH Biobank subjects versus controls. AUC 0.82. Cut point for IGF1 of 177 ng/mL gives a sensitivity of 73.9% and a specificity of 78.3%. b ROC curve of IGFBP2 in PAH Biobank subjects versus controls. AUC 0.80. Cut point for IGFBP2 of 185 ng/mL gives a sensitivity of 72.2% and a specificity of 80.4%.Fig. 3IGFBP2 CONCENTRATIONS IN PAH SUBJECTS BY MEDICATION COMBINATION.: a IGFBP2 concentration in PAH subjects on a PDE5 inhibitor, a PDE5 inhibitor and an ERA, a PDE5 inhibitor and IV/SQ PCA, or a combination of PDE5 inhibitor, ERA, and IV/SQ PCA. b IGFBP2 concentrations in PAH subjects on an IV/SQ PCA and any other therapy versus subject not on IV/SQ PCA and any other therapy.Fig. 4Kaplan-Meier curve showing time to death, transplant, or palliative shunt (Pott's shunt or atrial septostomy) dichotomized by the median IGFBP2 level.

BACKGROUND The age of patients with pulmonary arterial hypertension (PAH) has increased, with registries now reporting mean ages of 50 to 65 years old. Limited data exist on age-related differences in hemodynamic and functional assessments in PAH. METHODS Adults with PAH in the Pulmonary Hypertension Association Registry were divided into 3 groups (18–50, 51–65, and >65 years old). Analysis of variance and chi-square testing were used to assess for baseline differences. Linear regression was used to examine the association of age with continuous hemodynamic and functional variables. RESULTS A total of 769 patients with mean age of 56 ± 16 years were included. Older patients had more connective tissue disease–associated PAH and less drug-associated PAH. In linear regression models, each year of increased age was associated with shorter 6-minute walk distance (−3.37 meters; 95% CI, −3.97 to −2.76), lower mean pulmonary arterial pressure (−0.21 mm Hg; 95% CI, −0.27 to −0.15), and lower pulmonary vascular resistance (−0.06 Wood units; 95% CI, −0.09 to −0.04). Pulmonary arterial compliance, cardiac index, right ventricular stroke work index, and percent predicted 6-minute walk distance were unrelated to age; resistance-compliance time was negatively related to age (−3 milliseconds per year; 95% CI, −4 to −2). CONCLUSIONS Relative to their pulmonary vascular resistance, older patients have lower pulmonary artery compliance and worse right ventricular performance. Based on these findings, we suspect that age influences right ventricular loading conditions and the response of the right ventricle to increased afterload.

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.

Right ventricular failure (RVF) is a major cause of mortality in pulmonary hypertension (PH). Mechanical circulatory support holds promise for patients with medically refractory PH, but there are no clinical devices for long-term right ventricular (RV) support. Investigations into optimal device parameters and circuit configurations for PH-induced RVF (PH-RVF) are needed.Eleven sheep underwent previously published chronic PH model. We then evaluated a low-profile, ventricular assist device (VAD)-quality pump combined with a novel low-resistance membrane oxygenator (Pulmonary Assist Device, PAD) under one of four central cannulation strategies: right atrium-to-left atrium (RA-LA, N = 3), RA-to-pulmonary artery (RA-PA, N=3), pumpless pulmonary artery-to-left atrium (PA-LA, N = 2), and RA-to-ascending aorta (RA-Ao, N = 3). Acute-on-chronic RVF (AoC RVF) was induced, and mechanical support was provided for up to 6 hours at blood flow rates of 1 to 3 liter/min. Circuit parameters, physiologic, hemodynamic, and echocardiography data were collected.The RA-LA configuration achieved blood flow of 3 liter/min. Meanwhile, RA-PA and RA-Ao faced challenges maintaining 3 liter/min of flow due to higher circuit afterload. Pumpless PA-LA was flow-limited due to anatomical limitations inherent to this animal model. RA-LA and RA-Ao demonstrated serial RV unloading with increasing circuit flow, while RA-PA did not. RA-LA also improved left ventricular (LV) and septal geometry by echocardiographic assessment and had the lowest inotropic dependence.RA-LA and RA-Ao configurations unload the RV, while RA-LA also lowers pump speed and inotropic requirements, and improves LV mechanics. RA-PA provide inferior support for PH-RVF, while an alternate animal model is needed to evaluate PA-LA.

Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe life-threatening manifestation of SARS-CoV-2 infection. Acute cardiac dysfunction and resultant cardiogenic shock are common in children with MIS-C. While most children recover rapidly from acute illness, the long-term impact on the myocardium and cardiac function is unknown. Methods In this prospective study, cardiac MRI (CMR) was performed on patients 10 years old. Native T1 and T2 mapping values were compared with 20 children with normal CMR examinations. Results We performed CMRs on 13 subjects at a median age of 13.6 years (interquartile range [IQR] 11.9-16.0) and a median time from hospitalization of 8.2 months (IQR 6.8-9.6). Twelve subjects displayed normal ventricular function with a median left ventricle ejection fraction (LVEF) of 57.2% (IQR 56.1-58.4) and median right ventricular (RV) EF of 53.1% (IQR 52.0-55.7). One subject had low normal EF (52%). There was normal T2 and native T1 as compared to normal controls. There was qualitatively no evidence of edema by T2 weighted imaging. One subject had late gadolinium enhancement (LGE) at the inferior insertion point and mid-ventricular inferolateral region, with normal EF, no evidence of edema or perfusion defects, and normal T1 and T2 times. When stratifying by a history of abnormal LVEF (LVEF

Patients with pulmonary arterial hypertension (PAH) have quality of life (QoL) limitations, decreased exercise capacity, and poor prognosis if left untreated. Standard exercise testing is routinely performed for the evaluation of patients with PAH but may be limited in its ability to monitor activity levels in daily living. We evaluated the validity of the commercial Fitbit Charge HR as a tool to assess real time exercise capacity as compared to standard exercise testing in patients with PAH. Ambulatory pediatric and adult PAH patients were enrolled and given a Fitbit with instructions to continuously wear during waking hours. Subjects underwent a 6-minute walk test (6MWT), cardiopulmonary exercise test (CPET) and an SF-36 QoL survey on the day of enrollment and follow-up. Twenty-seven ambulatory subjects with PH were enrolled and 21 had sufficient data for analyses (median age 25, range 13-59, 14 F) were enrolled. Daily steps measured by the Fitbit had a positive correlation with 6MWT distance (r = 0.72, p = 0.03) and an inverse correlation with WHO functional class. On the QoL survey, 77% reported improvement in energy/fatigue (p = 0.055). At follow up there was a strong correlation between Fitbit steps and role limitations due to physical problems (r = 0.88, p = 0.020) and weaker correlations with less related QoL markers. These findings suggest activity monitors may have potential as a simple/novel method of assessing longitudinal exercise capacity and activity levels in PAH patients. Further study in larger cohorts of patients is warranted to determine the best accelerometric correlates with outcomes.

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.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.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/mSignificant improvements in right heart remodeling were seen following PEA. However, residual TR was a poor prognostic marker.

OBJECTIVE: To describe the safety and tolerability of treatment with ambrisentan and tadalafil in pediatric pulmonary hypertension (PH). STUDY DESIGN: This retrospective observational two center study included subjects(≤18 years of age)with PH receiving combination therapy with ambrisentan and tadalafil. Prior to initiating this therapy,many patients were on other therapies for PH. At baseline,patients either received no therapy or monotherapy with a phosphodiesterase 5 inhibitor(PDE5i) or endothelin receptor antagonist(ERA)(Group A),switched from a different PDE5i and ERA(Group B),or were on prostanoid therapy with or without a PDE5i and/or ERA(Group C and D). Demographics,symptoms, and adverse effects were collected. Pre and post values for exercise capacity,hemodynamics and biomarkers were compared. RESULTS: There were 43 subjects(26F, 17M) ages 4-17.5years (median 9.3) with World Symposium of PH group 1,3 and 5. Significant improvements were seen in change scores at follow-up in the entire sample and Group A for 6-minute walk distance: +37.0(6.5–71.0)[P=.022], mean pulmonary artery pressure:−6.0(−14.0 – −3.5)[P=.002], pulmonary vascular resistance: −1.7 (−6.2 – −1.0)[P=.003], NT-proBNP −32.9(−148.9– −6.7)[P=.025]. WHO functional class improved in 39.5% and was unchanged in 53.5%;PH risk scores improved in 16%; were unchanged in 56%; and declined in 14%. Three patients discontinued therapy (2 headaches,1 peripheral edema). Seven patients were hospitalized for worsening disease (2/7 had a Potts shunt placed,2/7 had an atrial septostomy). There were no deaths or lung transplantation. CONCLUSIONS: Combination therapy with ambrisentan and tadalafil was well-tolerated,with an acceptable safety profile in a select group of children. This therapy was associated with improved exercise capacity and hemodynamics in children who were treatment naïve or on monotherapy with a PH medication prior to the initiation of ambrisentan and tadalafil. Based on these early data,further study of combination therapy in pediatric PH is warranted.

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.

BACKGROUND In spring 2020, a novel hyperinflammatory process associated with severe acute respiratory syndrome coronavirus 2 multisystem inflammatory syndrome in children (MIS-C) was described. The long-term impact remains unknown. We report longitudinal outcomes from a New York interdisciplinary follow-up program. METHODS All children RESULTS In total, 45 children were admitted with MIS-C. The median time to last follow-up was 5.8 months (interquartile range 1.3–6.7). Of those admitted, 76% required intensive care and 64% required vasopressors and/or inotropes. On admission, patients exhibited significant nonspecific inflammation, generalized lymphopenia, and thrombocytopenia. Soluble interleukin (IL) IL-2R, IL-6, IL-10, IL-17, IL-18, and C-X-C Motif Chemokine Ligand 9 were elevated. A total of 80% (n = 36) had at least mild and 44% (n = 20) had moderate-severe echocardiographic abnormalities including coronary abnormalities (9% had a z score of 2–2.5; 7% had a z score > 2.5). Whereas most inflammatory markers normalized by 1 to 4 weeks, 32% (n = 11 of 34) exhibited persistent lymphocytosis, with increased double-negative T cells in 96% of assessed patients (n = 23 of 24). By 1 to 4 weeks, only 18% (n = 7 of 39) had mild echocardiographic findings; all had normal coronaries. At 1 to 4 months, the proportion of double-negative T cells remained elevated in 92% (median 9%). At 4 to 9 months, only 1 child had persistent mild dysfunction. One had mild mitral and/or tricuspid regurgitation. CONCLUSIONS Although the majority of children with MIS-C present critically ill, most inflammatory and cardiac manifestations in our cohort resolved rapidly.

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript discusses the latest development of the previously published ovine PH-RVF model that utilizes left pulmonary artery (PA) ligation and main PA occlusion. This model of PH-RVF is a versatile platform to control not only the disease severity, but also the RV’s phenotypic response. METHODS: Adult sheep (60–80 kg) underwent left PA (LPA) ligation, placement of main PA cuff, and insertion of RV pressure monitor. PA cuff and RV pressure monitor were connected to subcutaneous ports. Subjects underwent progressive PA banding twice per week for 9 weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO(2)). At the initiation and endpoint of this model, ventricular function and dimensions were assessed using echocardiography. RESULTS: In a representative group of 12 animal subjects, RV mean and systolic pressure increased from 28 ± 5 and 57 ± 7 mmHg at week 1, respectively, to 44 ± 7 and 93 ± 18 mmHg (mean ± standard deviation) by week 9. Echocardiography demonstrated characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The longitudinal trend of SvO(2) and PA cuff pressure demonstrate that the rate of PA banding can be titrated to elicit varying RV phenotypes. A faster PA banding strategy led to precipitous decline in SvO(2)