Early identification of SOX17 deficiency in infants to guide management of heritable pulmonary arterial hypertension using PDA stent to create reverse Potts shunt physiology.

Heritable pulmonary arterial hypertension (HPAH) is a rare progressive condition that includes patients with an identified genetic cause of pulmonary arterial hypertension (PAH). HPAH and idiopathic PAH (IPAH) have an estimated combined incidence of 0.5-0.9 cases per million children-years. Several pathogenic variants have been associated with HPAH in children and adults, including genes BMPR2, TBX4, and ACVRL1, and more rarely with variants in genes such as SOX17. HPAH is often difficult to manage and has poor prognosis despite advances in medical therapy with many patients progressing to lung transplantation, right heart failure and death. Surgical and transcatheter Potts shunt creation can reduce systolic burden and has shown reduction in morbidity and mortality in children. Early genetic testing can provide both diagnostic and prognostic value in managing and counseling children with severe PAH and it can guide transcatheter or surgical management in refractory cases despite maximal medical therapies. We describe a patient with HPAH (SOX17 mutation) who underwent percutaneous patent ductus arteriosus stent for right ventricle decompression at 2 months of age with clinical management guidance by genetic testing results.

Stage 1 and 2 Palliation: Comparing Ductal Stenting and Aorto-Pulmonary Shunts in Single Ventricles with Duct-Dependent Pulmonary Blood Flow.

Patent ductus arteriosus stenting (PDAS) for ductal-dependent pulmonary blood flow (DDPBF) provides a new paradigm for managing neonates with single ventricles (SV). Currently, sparse data exist regarding outcomes for subsequent palliation. We describe our experience with inter-stage care and stage 2 (S2P) conversion with PDAS in comparison to a prior era of patients who received surgical aorto-pulmonary shunts (APS). Retrospective review of 18 consecutive DDPBF SV patients treated with PDAS between 2016 and 2021 was done and compared with 9 who underwent APS from 2010 to 2016. Patient outcomes and pulmonary artery (PA) growth were analyzed. S2P was completed in all 18 with PDAS with no cardiac arrests and one post-S2P mortality. In the 9 APS patients, there was one cardiac arrest requiring ECMO and one mortality inter-stage. Off cardiopulmonary bypass strategy was utilized in 10/18 in the PDAS and 1/9 in the APS group (p = 0.005) at S2P. Shorter ventilation time, earlier PO feeding, and shorter hospital stay were noted in the PDAS group (p = 0.01, p = 0.006, p = 0.03) (S2P). Median Nakata index increase inter-stage was not significant between the PDAS and APS at 94.1 mm2/m2 versus 71.7 mm2/m2 (p = 0.94). Median change in pulmonary artery symmetry (PAS) was - 0.02 and - 0.24, respectively, which was statistically significant (p = 0.008). Neurodevelopmental outcomes were better in the PDAS group compared to the APS group (p = 0.02). PDAS provides excellent PA growth, inter-stage survival, progression along multistage single-ventricle palliation, and potentially improved neurodevelopmental outcomes. Most patients can be transitioned through 2 stages of palliation without CPB.

Combination of PGE1 and Pulmonary Vasodilator Therapy in Managing a Challenging Case of Severe PAH Secondary to CDH.

Congenital diaphragmatic hernia (CDH) is a rare disease, which affects 1 in 2,500 newborns. Congenital diaphragmatic hernia can interfere with the normal development of the pulmonary parenchyma and vascular bed, and in severe cases, it can lead to the development of severe pulmonary arterial hypertension (PAH) and right ventricular failure. We present a neonate with CDH who developed severe PAH and right ventricular dysfunction and was managed with a unique strategy combining venoarterial extracorporeal membrane oxygenation, prostaglandin E1, and a variety of PAH therapies.

Urgent listing exceptions and outcomes in pediatric heart transplantation: Comparison to standard criteria patients.

BACKGROUND: United Network for Organ Sharing (UNOS) policy enables listing exceptions to avoid penalizing patients with waitlist mortality not captured by standard criteria. Outcomes among patients listed by exception have not been analyzed. METHODS: We performed a retrospective analysis of pediatric (≤17 years of age, n = 4,706) listings (2006 to 2015) for primary, isolated heart transplantation within the UNOS data set, assessing Status 1A exception (n = 211, 4.5%) use across regions and patient characteristics and evaluating waitlist outcomes compared with candidates listed using standard criteria. RESULTS: Death or removal for reason other than transplant did not differ between exception and standard criteria patients at 1 month (11.7% vs 16.2%, p = not statistically significant [NS]), 2 months (18.2% vs 29.0%, p = 0.11) or overall (16.1% vs 22.0%, p = NS) on the waitlist. Rates were higher than among Status 1B patients (1 month: 2.8%; 2 months: 5.6%; overall: 14.9%; p < 0.0001). The cumulative incidence of competing risks (transplantation, death/removal for reasons other than transplant and removal) did not differ when comparing Status 1A exception patients with Status 1A standard criteria patients. Use of 1A exceptions varied across UNOS regions (1.9% to 22.3%, p < 0.0001). Risk-adjusted modeling identified patients more (hypertrophic cardiomyopathy: odds ratio [OR] = 2.8, 95% confidence interval [CI] 1.5 to 5.0; restrictive cardiomyopathy: OR = 2.7, 95% CI 1.7 to 4.3) and less (low socioeconomic status: OR = 0.7, 95% CI 0.5 to 1.0) likely to use an exception. Use of exceptions was uncorrelated with regional outcomes. CONCLUSIONS: Waitlist mortality among Status 1A exception patients is similar to that among those listed by standard criteria. However, variation in exception use across geography and demography may contribute to inequities in access to transplantation, particularly for those with low socioeconomic status. Standardization of practices may decrease regional variation and minimize inequities.

Low body mass index is associated with increased waitlist mortality among children listed for heart transplant.

BACKGROUND: In adults, low body mass index (BMI) and high BMI have been associated with increased mortality after heart transplantation. Studies of BMI in children with heart failure have had inconsistent results. METHODS: The United Network for Organ Sharing database has 4,035 listings for primary, isolated heart transplant in patients 3 to 18 years old (1995-2012). BMI percentile-for-age (BMI%) was calculated, and patients were stratified based on BMI% into 4 groups: underweight (BMI% <5, n = 701 [17.4%]), normal weight (BMI% 5-84, n = 2,321 [57.5%]), overweight (BMI% 85-94, n = 440 [10.9%]), or obese (BMI% ≥95, n = 573 [14.2%]). Outcomes of patients on the waitlist and after transplantation were assessed. RESULTS: Unadjusted early waitlist mortality was highest in underweight patients (16.7%) compared with normal-weight (11.4%), overweight (10.9%), and obese (12.9%) patients (p = 0.04). In multivariable analysis, underweight patients had elevated risk-adjusted waitlist mortality (odds ratio = 1.4, 95% confidence interval = 1.0-2.2). Unadjusted post-transplant mortality did not differ across BMI% groups (underweight, 5.7%; normal weight, 5.4%; overweight, 5.5%; obese, 5.8%), but obese patients had borderline higher risk-adjusted post-transplant mortality (odds ratio = 1.7, 95% confidence interval = 1.0-3.0). Change in BMI% while waiting did not affect post-transplant mortality. CONCLUSIONS: Children listed for heart transplant are commonly either underweight or obese. Underweight patients have high risk-adjusted mortality before transplantation, whereas obese patients have borderline higher adjusted post-transplant mortality.

Creation of a quantitative score to predict the need for mechanical support in children awaiting heart transplant.

BACKGROUND: Due to the availability of new devices, the use of ventricular assist devices (VADs) in children has been increasing; however, patient selection and optimal timing of device implantation in this population remains uncertain. METHODS: A retrospective review of the United Network for Organ Sharing dataset identified 5,200 listings without mechanical circulatory support (MCS) for isolated pediatric heart transplant, 1995 to 2012. Patients were randomly divided into a derivation and validation cohort. A multivariable logistic regression model predicting the likelihood of death or need for MCS within 60 days was built using the derivation cohort and tested in the validation cohort. A simplified score (PedsMCS score) was developed and evaluated for accuracy. RESULTS: The predictive model consisted of variables present at listing (age, albumin level, creatinine clearance, serum bilirubin, mechanical ventilation, and inotropic support). It had good predictive ability (C statistic 0.7304) within the validation cohort. The simplified PedsMCS score was also predictive (C statistic 0.7217) and there was a strong correlation between predicted and expected outcomes (r=0.91, p<0.0001). Patients with PedsMCS score 16 or greater had a significantly higher risk of death or MCS within 2 months (36.6%) than those with low scores (<6) (1.5%, p<0.0001). A single point increase in PedsMCS score was associated with a 16.7% increase in the risk of death or MCS with 2 months (p<0.0001). CONCLUSIONS: We have developed and validated a simplified score to predict the need for MCS based on risk factors present at listing. This will provide more accurate prognostication in children awaiting heart transplant, and may improve patient selection.

Ventricular assist devices as a bridge-to-transplant improve early post-transplant outcomes in children.

BACKGROUND: The use of ventricular assist devices (VADs) to bridge pediatric patients to transplant or recovery has been expanding. There are few current pediatric data assessing the impact of VAD support on post-transplant survival. METHODS: We performed a retrospective review of all pediatric (≤18 years old, n = 4,028) transplants performed between 1995 and 2011 and contained within the United Network for Organ Sharing data set. Transplants were divided into three eras: early (1995 to 2002, n = 1,450); intermediate (2003 to 2007, n = 1,138); and recent (2008 to 2011, n = 1,440). VADs were present at transplant in 398 patients (9.8%). Outcomes among patients with and without VADs were assessed and compared across eras. RESULTS: The use of VADs for bridge to transplant has increased (early 1.1%, intermediate 10.5%, recent 17.9%; p < 0.0001). Mean weight among VAD-supported patients (early 63.5 kg, intermediate 42.3 kg, recent 28.8 kg; p < 0.0001) has decreased during this period. VAD patients <10 kg had an increased risk of stroke (odds ratio [OR] = 4.9, 95% confidence interval [CI] 2.1 to 10.8) compared with non-mechanical support patients. In multivariable analyses, extracorporeal VADs were the only type of VAD associated with higher post-transplant mortality (OR = 3.0, 95% CI 0.8 to 10.6). Other types of VAD had lower mortality (OR = 0.5, 95% CI 0.2 to 1.0). Long-term survival was unaffected by the use of a VAD pre-transplant. CONCLUSIONS: Pediatric patients bridged to transplantation with VADs are increasingly younger and smaller. Complication rates remain high among patients <10 kg. Early post-transplant survival among intracorporeal and paracorporeal VAD patients is excellent and better when compared with unsupported patients. The use of short-term support devices is associated with higher post-transplant mortality. Long-term survival is unaffected by VAD use.