Faculty Bibliography

BACKGROUND:Heart transplantation (HT) is the gold standard for managing end-stage heart failure. Multiple quality metrics, including length of stay (LOS), have been used in solid organ transplantation. However, limited data are available regarding trends and factors influencing LOS after pediatric HT. We hypothesized that various donor, peri-transplant and recipient factors affect LOS after pediatric HT. METHODS:We analyzed patients <18years at time of HT from January 2005 to December 2018 in the Pediatric Heart Transplant Society database, and examined LOS trends, defined prolonged LOS (PLOS = LOS>30days after HT), identified factors associated with PLOS and assessed outcomes. RESULTS:Of 4827 patients undergoing HT, 4414 patients were discharged and included for analysis. Overall median LOS was 19days[13,34]. Median LOS was longer in patients with congenital heart disease(CHD = 25days[15,43] than with cardiomyopathy(CM = 17days[12,27] across all ages. Median LOS in age <1year was 26-days[16,45.5] and in age >10year was 16days[11,26]. PLOS was seen in 1313 patients(30%). Patients with PLOS were younger, smaller and had longer CPB times. There was no difference in utilization of VAD at HT between groups, however, ECMO use at listing(8.45% vs 2.93%,p < 0.05) and HT was higher in the PLOS group(9.22% vs 1.58%,p < 0.05). PLOS was more common in patients with previous surgery, CHD, single ventricle physiology, recipient history of cardiac arrest or CPR, end organ dysfunction, lower GFR, use of mechanical ventilation at HT and Status 1A at HT. CONCLUSION:We present novel findings of LOS distribution and define PLOS after pediatric HT, providing a quality metric for individual programs to utilize and study in their practice.

This review focuses on the maternal cardiovascular risk and outcomes of pregnancy in childhood, adolescent, and young adult cancer survivors who are achieving survival to their prime reproductive years. Childhood, adolescent, and young adult cancer survivors are a growing population and have increasing needs for reproductive care over decades of life. Female cancer survivors have an overall higher risk of maternal cardiovascular events compared to those without a history of cancer. In female cancer survivors with normal cardiac function before pregnancy, the incidence of new heart failure during pregnancy is low. In survivors with cardiotoxicity prior to pregnancy, the risk of heart failure during and immediately after pregnancy is much higher. We recommend cardiomyopathy surveillance with echocardiography before pregnancy for all female survivors treated with anthracyclines and chest radiation. Survivors with cardiotoxicity prior to pregnancy should be cared for by an expert multidisciplinary team, including obstetrics, cardiology, anesthesia, and specialized nursing, among others.

This manuscript outlines a clinical approach to vasoplegia incorporating the current state of knowledge regarding vasoplegia in pediatric patients immediately post-transplant and to identify modifiable factors both pre- and post-transplant that may reduce post-operative morbidity, end-organ dysfunction, and mortality. Centers participating in the Pediatric Heart Transplant Society (PHTS) were asked to provide their internal protocols and rationale for vasoplegia management, and applicable adult and pediatric data were reviewed. The authors synthesized the above protocols and literature into the following description of clinical approaches to vasoplegia highlighting areas of both broad consensus and of significant practice variation.

BACKGROUND:Early detection of cardiac allograft rejection is crucial for post-transplant graft survival. Despite the progress made in immunosuppression strategies, acute cellular rejection remains a serious complication during and after the first post-transplant year, and there is a continued lack of consensus regarding its treatment, especially in pediatric transplant patients. METHODS:An open request was placed via the listserv to the membership of the Pediatric Heart Transplant Society (PHTS). Along with a broad literature search, numerous institutional protocols were pooled, analyzed and consolidated. A clinical approach document was generated highlighting areas of consensus and practice variation. RESULTS:The clinical approach document divides cellular rejection by International Society for Heart and Lung Transplantation grades and provides management strategies for each, including persistent cellular rejection. CONCLUSIONS:Cellular rejection treatment can be tailored to the clinical status, graft function, and the grade of cellular rejection. A case of mild and asymptomatic rejection may not require treatment, whereas a higher-grade rejection or rejection with graft dysfunction or hemodynamic compromise may require aggressive intravenous therapies, changes to maintenance immunosuppression therapy and augmented surveillance.

It has long been recognized that there is significant variation in the way that centers approach clinical management and problems within pediatric transplantation. This has recently been highlighted in two publications by the PHTS showing practice variation in both surveillance for cardiac allograft vasculopathy and diagnosis of acute rejection. These differences in practice are important to recognize and serve as the foundation for collaborative learning, developing research questions, and implementing quality improvement initiatives. To further understand the practice variation within the society, and to begin the process of learning from each other, the society has developed a Clinical Approach Working Group, whose task is to tackle issues seen in transplant and integrate current literature with clinical protocols and experience from the individual sites. The early work of this group has results in the series of Clinical approach articles presented in this issue of Pediatric Transplantation.

BACKGROUND:Adult SOT recipients with COVID-19 have higher mortality rates when compared to general population. There is paucity of data on outcomes in pediatric SOT recipients. METHODS:This is a cross-sectional study investigating the prevalence of COVID-19 infection and outcomes in pediatric SOT (heart, liver, and kidney) recipients. We extracted demographic and clinical characteristics and COVID-19 testing (PCR or [Ab] test) results from medical records. Clinical characteristics were compared between patients who were positive for COVID-19 (PCR or Ab) and those who did not, using Mann-Whitney, Student's t test, or chi-square test. p value <.05 was statistically significant. RESULTS:A total of 108 SOT recipients with a median age of 13.1 (8.4, 17.8) years and median 4.2 (2.7, 7.9) years from transplant were checked for COVID-19 via a PCR or Ab test. A positive PCR was confirmed in 10 patients (9.3%), while 12 patients (11.1%) were positive for COVID-19 Ab. The patients who tested positive in our cohort were 9/50 (18%) heart, 6/68 (8.8%) kidney, and 7/50 (14%) liver transplant recipients. There were no differences in the clinical characteristics between patients with and without COVID-19 infection. All patients were either asymptomatic (50%) or had self-limiting symptoms. No changes were made to the immunosuppressive regimen. Only one patient was hospitalized and none had an oxygen requirement. CONCLUSIONS:In our cohort of pediatric SOT recipients, COVID-19 infection was asymptomatic or mild. This data may aid clinicians in counseling patients and families in this increased-risk population.

A patent foramen ovale (PFO) is a frequent incidental finding during echocardiography in otherwise healthy children. In most healthy children with a diagnosis of isolated incidental PFO, no further follow-up or intervention is necessary. In some children, PFO is associated with certain clinical syndromes such as cryptogenic stroke, decompression sickness, migraine, and platypnea-orthodeoxia syndrome. This review discusses PFO anatomy, diagnostic imaging, PFO-associated clinical situations, management options, and the role of PFO in certain congenital heart disease. This review also highlights the current deficiency of pediatric data guiding management of these uncommon but important PFO-associated conditions. Future multicenter randomized controlled studies are necessary to guide the management of these unique and challenging PFO-associated conditions.

INTRODUCTION/BACKGROUND:Over the past five decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result, an increasing number of children are long-term cancer survivors. With improved survival, however, has come an increased risk of treatment-related cardiovascular complications that can appear decades later. AREAS COVERED/METHODS:This review discusses the pathophysiology, epidemiology and effects of treatment-related cardiovascular complications from anthracyclines and radiotherapy in pediatric lymphoma survivors. There is a paucity of evidence-based recommendations for screening for and treatment of cancer therapy-induced cardiovascular complications. We discuss current preventive measures and strategies for their treatment. EXPERT OPINION/CONCLUSIONS:Significant cardiac adverse effects occur due to radiation and chemotherapy received by patients treated for lymphoma. Higher lifetime cumulative doses, female sex, longer follow-up, younger age, and preexisting cardiovascular disease are associated with a higher incidence of cardiotoxicity. With deeper understanding of the mechanisms of these adverse cardiac effects and identification of driver mutations causing these effects, personalized cancer therapy to limit cardiotoxic effects while ensuring an adequate anti-neoplastic effect would be ideal. In the meantime, expanding the use of cardioprotective agents with the best evidence such as dexrazoxane should be encouraged and further studied.