Impact of ventricular assist device use on pediatric heart transplant waitlist mortality: Analysis of the scientific registry of transplant recipients database.

BACKGROUND: Children awaiting heart transplant (Tx) have a high risk of death due to donor organ scarcity. Historically, ventricular assist devices (VADs) reduced waitlist mortality, prompting increased VAD use. We sought to determine whether the VAD survival benefit persists in the current era. METHODS: Using the Scientific Registry of Transplant Recipients, we identified patients listed for Tx between 3/22/2016 and 9/1/2020. We compared characteristics of VAD and non-VAD groups at Tx listing. Cox proportional hazards models were used to identify risk factors for 1-year waitlist mortality. RESULTS: Among 5054 patients, 764 (15%) had a VAD at Tx listing. The VAD group was older with more mechanical ventilation and renal impairment. Unadjusted waitlist mortality was similar between groups; the curves crossed ~90 days after listing (p = .55). In multivariable analysis, infant age (HR 2.77, 95%CI 2.13-3.60), Black race (HR 1.57, 95%CI 1.31-1.88), congenital heart disease (HR 1.23, 95%CI 1.04-1.46), renal impairment (HR 2.67, 95%CI 2.19-3.26), inotropes (HR 1.28, 95%CI 1.09-1.52), and mechanical ventilation (HR 2.23, 95%CI 1.84-2.70) were associated with 1-year waitlist mortality. VADs were not associated with mortality in the first 90 waitlist days but were protective for those waiting ≥90 days (HR 0.43, 95%CI 0.26-0.71). CONCLUSIONS: In the current era, VADs reduce waitlist mortality, but only for those waitlisted ≥90 days. The differential effect by race, size, and VAD type is less clear. These findings suggest that Tx listing without VAD may be reasonable if a short waitlist time is anticipated, but VADs may benefit those expected to wait >90 days.

Factors Associated with Growth in a Cohort of Children with Complex Biventricular Congenital Heart Disease.

OBJECTIVES: To evaluate patterns and determinants of longitudinal growth among children requiring complex biventricular repair for congenital heart disease, as well as to assess for associations of growth with early feeding modality, comorbidities, postoperative complications, and socioeconomic characteristics. STUDY DESIGN: A single-institution retrospective cohort study was performed in children born February 1999 to March 2009 with complex congenital heart disease who underwent biventricular repair before age 4 years, defined by Risk Adjustment in Congenital Heart Surgery-1 category 3-5. Clinical characteristics, height, weight, and body mass index (BMI) from ages 2-12 years were collected by chart review. Neighborhood-level socioeconomic data were identified using a geographic information system approach. The adjusted association of covariates with growth outcomes was estimated using multivariable linear regression models using generalized estimating equations. RESULTS: Compared with population growth curves, the cohort (n = 150) trended toward early decrease in age-adjusted weight and height. Early tube feeding was significantly associated with decreased BMI before adolescence (-0.539; 95% CI -1.02, -0.054; P = .029). In addition, other clinical and perioperative characteristics had significant associations with growth, including low birth weight, preoperative tube feeds, need for multiple bypass runs, and diagnosis of feeding disorder. CONCLUSIONS: Early childhood growth in children with complex biventricular repair may be impaired. Early tube feeding was associated with decreased BMI over the course of early childhood, which may indicate a need for continued close nutrition follow-up and support even beyond the duration of tube feeds.

Seventh Annual Society of Thoracic Surgeons Pedimacs Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs). METHODS: From September 19, 2012, to December 31, 2022, 1463 devices in 1219 patients aged <19 years were reported to the registry from 40 North American hospitals. RESULTS: Cardiomyopathy remains the most common underlying etiology (59%), followed by congenital heart disease (26%) and myocarditis (8%). Implantable continuous devices were most common (39%) type, followed by paracorporeal pulsatile (28%) and paracorporeal continuous (27%) devices. At 6 months after VAD implantation, a favorable outcome (transplant, recovery, or alive on device) was achieved in 85% of patients, which was greatest among those on implantable continuous VADs (92%) and least for paracorporeal continuous VADs (68%), although the patient population supported on these devices is different. CONCLUSIONS: This Seventh Pedimacs Report demonstrates the continued importance of VADs in the treatment of children. With the complexity of cardiac physiologies and sizes of patients, multiple types of devices are used, including paracorporeal continuous, paracorporeal pulsatile, and implantable continuous devices. The preoperative risk factors and differences in patient populations may account for some of the differences in survival observed among these devices. This report, along with other collaborative work, continues to advance the care of this challenging and vulnerable population.

Continuous Prostanoid Initiation in Severe Pulmonary Hypertension in the Pediatric Cardiac Intensive Care Unit.

OBJECTIVE: Limited data exists regarding prostanoid (PGI2) use in critically ill patients with pulmonary hypertension. (PH) in the pediatric cardiac intensive care unit (CICU) setting. MATERIALS AND METHODS: Single center, retrospective study of patients with diagnosis of PH who received continuous PGI2 and were admitted to CICU from January/2015 to April/2022. Data collected included patient demographics and clinical characteristics including diagnosis, etiology of PH, vasoactive and ventilatory support, length of stay, and survival. Type, initial, maximum, and final dose of PGI2 as well as hemodynamic data was obtained. Data reported as mean ± standard deviation. Significance taken p value < 0.05. RESULTS: 24 patients received PGI2 therapy at a mean age of 3.1 years, range (0-16.6 years). PGI2 was in the form of IV epoprostenol in 12 patients, IV treprostinil in 6, and SQ treprostinil in 6 patients. Mean initial dose was 2.79 ng/kg/min, max dose 18.75 ng/kg/min, and mean duration of therapy was 38.5 days. At PGI2 initiation, 21 (87.5%) were on vasoactive infusions, 19 (79.2%) mechanically ventilated (MV), and 6 (25%) were on extracorporeal membrane oxygenation (ECMO). The in-hospital mortality rate was 37.5% (n = 9). Patients MV and on ECMO support had higher risk of death (p = 0.04, and < 0.01, respectively). CONCLUSION: PGI2 therapy was tolerated in approximately 50% of patients with the most common side effect being hypotension leading to discontinuation in 1/3rd of patients. Ongoing evaluation of the benefits of PGI2 for patients in the CICU setting will help better identify patient selection, type, and dosing of PGI2.

Expanding use of the HeartMate 3 ventricular assist device in pediatric and adult patients within the Advanced Cardiac Therapies Improving Outcomes Network (ACTION).

BACKGROUND: We report current outcomes in patients supported with the HeartMate 3 (HM3) ventricular assist device in a multicenter learning network. METHODS: The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HM3 implants between 12/2017 and 5/2022. Clinical characteristics, postimplant course, and adverse events were collected. Patients were stratified according to body surface area (BSA) (<1.4 m2, 1.4-1.8 m2, and >1.8 m2) at device implantation. RESULTS: During the study period, 170 patients were implanted with the HM3 at participating network centers, with median age 15.3years; 27.1% were female. Median BSA was 1.68 m2; the smallest patient was 0.73 m2 (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with BSA <1.4 m2 had a higher incidence of infection, renal dysfunction, and ischemic stroke. CONCLUSIONS: In this updated cohort of predominantly pediatric patients supported with the HM3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care.

Comparison of Multisystem Inflammatory Syndrome in Children-Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine-Related Myocarditis in Children.

Background Although rare, classic viral myocarditis in the pediatric population is a disease that carries significant morbidity and mortality. Since 2020, myocarditis has been a common component of multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection. In 2021, myocarditis related to mRNA COVID-19 vaccines was recognized as a rare adverse event. This study aims to compare classic, MIS-C, and COVID-19 vaccine-related myocarditis with regard to clinical presentation, course, and outcomes. Methods and Results In this retrospective cohort study, we compared patients aged <21 years hospitalized at our institution with classic viral myocarditis from 2015 to 2019, MIS-C myocarditis from March 2020 to February 2021, and vaccine-related myocarditis from May 2021 to June 2021. Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had vaccine-related myocarditis. At presentation, ejection fraction was lowest for those with classic myocarditis, with ejection fraction <55% present in 58% of patients. Nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with vaccine-related myocarditis (n=9, 100%) had normal left ventricular ejection fraction at the time of discharge compared with 70% (n=30) of the classic myocarditis group (P<0.001). At 3 months after discharge, of the 21 children discharged with depressed ejection fraction, none of the 10 children with MIS-C myocarditis had residual dysfunction compared with 3 of the 11 (27%) patients in the classic myocarditis group. Conclusions Compared with classic myocarditis, those with MIS-C myocarditis had better clinical outcomes, including rapid recovery of cardiac function. Patients with vaccine-related myocarditis had prompt resolution of symptoms and improvement of cardiac function.

Relationship of ventricular assist device support duration with pediatric heart transplant outcomes.

BACKGROUND: There is wide variability in the timing of heart transplant (HTx) after pediatric VAD implant. While some centers wait months before listing for HTx, others accept donor heart offers within days of VAD surgery. We sought to determine if HTx within 30 days versus ≥ 30 after VAD impacts post-HTx outcomes. METHODS: Children on VAD pre-HTx were extracted from the Pediatric Heart Transplant Study database. The primary endpoints were post-HTx length of hospital stay (LOS) and one-year survival. Confounding was addressed by propensity score weighting using inverse probability of treatment. Propensity scores were calculated based on age, blood type, primary cardiac diagnosis, decade, VAD type, and allosensitization status. RESULTS: A total of 1064 children underwent VAD prior to HTx between 2000 to 2018. Most underwent HTx ≥ 30 days post-VAD (70%). Infants made up 22% of both groups. Patients ≥ 12 years old were 42% of the < 30 days group and children 1 to 11 years comprised 47% of the ≥ 30 days group (p < 0.001). There was no difference in the prevalence of congenital heart disease vs. cardiomyopathy (p = 0.8) or high allosensitization status (p = 0.9) between groups. Post-HTx LOS was similar between groups (p = 0.11). One-year survival was lower in the < 30 days group (adjusted mortality HR 1.76, 95% CI 1.11-2.78, p = 0.016). CONCLUSIONS: A longer duration of VAD support prior to HTx is associated with a one-year survival benefit in children, although questions of patient complexity, post-VAD complications and the impact on causality remain. Additional studies using linked databases to understand these factors will be needed to fully assess the optimal timing for post-VAD HTx.

The impact of pre-implant illness severity on the outcomes of pediatric patients undergoing durable ventricular assist device.

BACKGROUND: Durable ventricular assist devices (VADs) are increasingly used to treat children with heart failure. Studies demonstrate worse outcomes for those in cardiogenic shock at the time of VAD, but limited data exist on less acutely ill children. We describe the association between illness severity and outcomes in this population. METHODS: Data were analyzed from 373 children (aged <19 years) receiving durable VADs from 46 centers in the Pediatric Interagency Registry for Mechanical Circulatory Support. Outcomes were compared by Interagency Registry for Mechanical Circulatory Support (INTERMACS) Patient Profile (PP) and pre-implant characteristics using competing risks methodology. RESULTS: Analyses identified 97 patients in cardiogenic shock (PP 1), 222 with progressive decline (PP 2), and 42 stable on inotropes (PP 3). There were 39 infants, 124 were aged 1 to 9 years and 210 were aged 10 to 19 years. A majority had cardiomyopathy and 66 had congenital heart disease (CHD). There were 224 (62%) continuous-flow VADs. Before implant, 40% received mechanical ventilation (MV). Within 6 months post-implant, 57% underwent transplant and 14% died. PP 1 mortality was highest (25% vs 10% for PP 2, hazard ratio [HR]: 2.5, 95% CI: 1.4-4.4, p = 0.02). In PP 1, CHD was an independent mortality risk factor (HR: 2.9, 95% CI: 1.1-7.8, p = 0.03). In PP 2, pulsatile VADs were associated with death (HR: 3.9, 95% CI: 1.6-9.5, p = 0.003). Patients on MV had high mortality (20%-30%) across PP 1 to PP 3 (HR: 3.0 vs no MV, p < 0.001). CONCLUSIONS: Children in shock at the time of VAD implant have poor outcomes. MV is associated with increased mortality even in lower acuity INTERMACS profiles. Further study is needed to identify modifiable risk factors in this population.

Longitudinal growth in patients with single ventricle cardiac disease receiving tube-assisted feeds.

OBJECTIVE: Children with single ventricle cardiac disease (SVCD) have poor growth in early life. Tube-assisted feeding (TF) is used to improve weight gain, but its impact on long-term growth remains unknown. We sought to compare the longitudinal growth of SVCD patients receiving TF after initial cardiac surgery with those fed entirely by mouth. DESIGN: We conducted a retrospective cohort study of SVCD patients who underwent initial surgical palliation between 1999 and 2009. We defined TF as the use of nasogastric, gastrostomy, or jejunostomy TF. We compared maximal attained growth z-scores for each year of life between TF and non-TF patients. A secondary analysis compared surgical and clinical factors between groups. RESULTS: A total of 134 patients were included; 64% were male and 68% underwent the Norwood operation. One third of patients (44) received TF. Adjusting for age, TF patients had an average of 0.56 lower weight-for-age z-score (WAZ) than non-TF patients (P = 0.007) through the age of 6 years. Longitudinal height was not affected by TF status (P = 0.15). In a subanalysis of Norwood patients, TF patients had lower WAZ at initial hospital discharge despite longer LOS. TF patients had diminished WAZ after adjusting for complications, interstage hospitalizations, and timing of subsequent operations. CONCLUSIONS: In this single-center study, patients with SVCD requiring TF at discharge from initial surgical palliation had diminished WAZ at discharge and on long-term follow-up, despite controlling for other identifiable risk factors. Further investigation is needed to understand the mechanisms underlying this phenomenon and to risk stratify infants who go home on TF.

Elevated Troponin in the First 72 h of Hospitalization for Pediatric Viral Myocarditis is Associated with ECMO: An Analysis of the PHIS+ Database.

Serum troponin (Tn) is often elevated in viral myocarditis; however, its prognostic significance is unknown. We tested the hypothesis that abnormal serum Tn is associated with mortality in children hospitalized with myocarditis. We retrospectively studied data from six large children's hospitals participating in the Pediatric Health Information System Plus (PHIS+) database. Analysis was performed on patients hospitalized with viral myocarditis between 2007 and 2013, in whom at least one Tn was recorded within 72 h of admission. Abnormal baseline Tn was defined as any value outside the upper limit of normal within the first 72 h. Primary outcome was mortality. Secondary outcomes included mechanical support, defined as use of extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD), cardiac transplantation, intravenous immunoglobulin (IVIg), mechanical ventilation, and inotrope use. A total of 149 patients with myocarditis (61% male, 48% adolescents) across all PHIS+ centers had TnI (n = 113) or TnT (n = 36) recorded. At least one abnormal Tn was present in 81% of cases. Overall mortality was 7.3% and was not associated with abnormal baseline Tn. Abnormal baseline Tn was associated with ECMO (7.1 vs. 25.6%, p = 0.03) and IVIg (46.4 vs. 83.5%, p < 0.001). Abnormal baseline Tn was not associated with transplantation, mechanical ventilation or inotrope use. Abnormal Tn in the first 72 h of hospitalization for myocarditis was associated with the use of ECMO and IVIg, but was not associated with mortality. This finding may help risk stratify this population if it can be prospectively validated.

The Parasternal Short-Axis View Improves Diagnostic Accuracy for Inferior Sinus Venosus Type of Atrial Septal Defects by Transthoracic Echocardiography.

BACKGROUND: Sinus venosus defects (SVD) of the inferior vena cava (IVC) type, or inferior SVDs, are an uncommon form of atrial communication located outside the confines of the fossa ovalis and involve override of the IVC. Despite numerous studies describing the anatomical and echocardiographic features of the inferior SVD, distinguishing this defect from a large secundum atrial septal defect (ASD) by echocardiography is often challenging. Accurate diagnosis of an inferior SVD and correct differentiation from a secundum ASD is essential for appropriate presurgical planning. Absence of the posterior rim in the parasternal short-axis views may serve as a useful clue in diagnosing inferior SVDs. We sought to determine the utility of using the presence or absence of a posterior atrial rim in the parasternal short-axis view to help distinguish an inferior SVD from a secundum ASD. This sign may help clinch the diagnosis when subcostal imaging is suboptimal. METHODS: We retrospectively reviewed transthoracic echocardiograms from 15 patients with a known surgical diagnosis of an inferior SVD between 2004 and 2015. The presence or absence of a posterior rim in the parasternal short-axis view was determined by two primary investigators. The posterior rim was also evaluated in 14 patients with a secundum ASD repair as controls. Echocardiograms were then reviewed blindly by attending-level echocardiographers and cardiology fellows in training. Diagnostic accuracy was assessed both with and without the use of the posterior rim criterion. Statistical analysis was used to determine the effect of using the rim criterion on inferior SVD diagnosis. We also reviewed all surgically diagnosed secundum ASDs that were incorrectly diagnosed as inferior SVD by preoperative imaging and determined whether use of the posterior rim criterion would have resulted in the correct diagnosis. RESULTS: The posterior rim was absent in all 15 patients with a surgical diagnosis of inferior SVD and present in all 14 patients with a secundum ASD. For all observers, there was a statistically significant increase in diagnostic accuracy of inferior SVDs with the use of the rim criterion (P < .0001). We noted that secundum ASDs with inferior extension also have persistent posterior rims. The rim criterion correctly classified all large secundum ASDs with inferior extension that were previously misdiagnosed by echocardiogram preoperatively. CONCLUSIONS: Absence of the posterior rim ("bald" posterior wall) is a consistent finding in patients with an inferior SVD and distinguishes an inferior SVD from a large secundum ASD with inferior extension. Parasternal short-axis evaluation of the posterior atrial rim is a helpful tool for all levels of physician training in improving diagnostic accuracy for detecting inferior SVDs and in distinguishing them from secundum ASDs.

Fulminant chemical ventriculomeningitis following intrathecal liposomal cytarabine administration.

Intrathecal liposomal cytarabine (ITLC) has shown prolonged time to neurological deterioration in some patients with leptomeningeal spread of breast cancer. We describe a patient with fulminant chemical ventriculomeningitis leading to cerebral edema and death following ITLC administration. A 56-year-old Caucasian female developed progressive headache, depressed level of consciousness and adventitious movements immediately following ITLC. Neurological examination was normal prior to injection. This progressed to loss of all brainstem function and a head CT scan demonstrated diffuse cerebral edema. Due to the absence of neurological function on examination, the family opted to withdraw care. To our knowledge we report the first patient with fulminant chemical ventriculomeningitis leading to cerebral edema and death following ITLC administration. Adjunctive glucocorticoids are recommended. Treatment options are limited and complicated by the liposomal formulation of intrathecal cytarabine.