Evaluation and Management of Chronic Heart Failure in Children and Adolescents With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

With continued medical and surgical advancements, most children and adolescents with congenital heart disease are expected to survive to adulthood. Chronic heart failure is increasingly being recognized as a major contributor to ongoing morbidity and mortality in this population as it ages, and treatment strategies to prevent and treat heart failure in the pediatric population are needed. In addition to primary myocardial dysfunction, anatomical and pathophysiological abnormalities specific to various congenital heart disease lesions contribute to the development of heart failure and affect potential strategies commonly used to treat adult patients with heart failure. This scientific statement highlights the significant knowledge gaps in understanding the epidemiology, pathophysiology, staging, and outcomes of chronic heart failure in children and adolescents with congenital heart disease not amenable to catheter-based or surgical interventions. Efforts to harmonize the definitions, staging, follow-up, and approach to heart failure in children with congenital heart disease are critical to enable the conduct of rigorous scientific studies to advance our understanding of the actual burden of heart failure in this population and to allow the development of evidence-based heart failure therapies that can improve outcomes for this high-risk cohort.

Impact of the Pediatric ABO Policy Change on Listings, Transplants, and Outcomes for Children Younger Than 2 Years Listed for Heart Transplantation in the United States.

BACKGROUND: We assessed the impact of the liberalized ABO pediatric policy change on candidate characteristics and outcomes for children undergoing heart transplant (HT). METHODS AND RESULTS: Children <2 years undergoing HT with ABO strategy reported at listing and HT from December 2011 to November 2020 to the Scientific Registry of Transplant Recipients database were included. Characteristics at listing, HT, and outcomes during the waitlist and post-transplant were compared before the policy change (December 16, 2011 to July 6, 2016), and after the policy change (July 7, 2016 to November 30, 2020). The percentage of ABO-incompatible (ABOi) listings did not increase immediately after the policy change (P = .93); however, ABOi transplants increased by 18% (P < .0001). At listing, both before and after the policy change, ABOi candidates had higher urgency status, renal dysfunction, lower albumin, and required more cardiac support (intravenous inotropes, mechanical ventilation) than those listed ABO compatible (ABOc). On multivariable analysis, there were no differences in waitlist mortality between children listed as ABOi and ABOc before the policy change (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.61-1.05, P = .10) or after the policy change (aHR 1.2, 95% CI 0.85-1.6, P = .33). Post-transplant graft survival was worse for ABOi transplanted children before the policy change (aHR 1.8, 95% CI 1.1-2.8, P = .014), but not significantly different after the policy change (aHR 0.94, 95% CI 0.61-1.4, P = .76). After the policy change, ABOi listed children had significantly shorter waitlist times (P < .05). CONCLUSIONS: The recent pediatric ABO policy change has significantly increased the percentage of ABOi transplantations and decreased waitlist times for children listed ABOi. This change in policy has resulted in broader applicability and actual performance of ABOi transplantation with equal access to ABOi or ABOc organs, and thus eliminated the potential disadvantage of only secondary allocation to ABOi recipients.

Research Gaps in Pediatric Heart Failure: Defining the Gaps and Then Closing Them Over the Next Decade.

Given the numerous opportunities and the wide knowledge gaps in pediatric heart failure, an international group of pediatric heart failure experts with diverse backgrounds were invited and tasked with identifying research gaps in each pediatric heart failure domain that scientists and funding agencies need to focus on over the next decade.

Review on clinician bias and its impact on racial and socioeconomic disparities in pediatric heart transplantation.

This expert review seeks to highlight implicit bias in health care, transplant medicine, and pediatric heart transplantation to focus attention on the role these biases may play in the racial/ethnic and socioeconomic disparities noted in pediatric heart transplantation. This review breaks down the transplant decision making process to highlight points at which implicit bias may affect outcomes and discuss how the science of human decision making may help understand these complex processes.

Three decades of collaboration through the Pediatric Heart Transplant Society Registry: A journey through registry data with a highlight on children with single ventricle anatomy.

BACKGROUND: The Pediatric Heart Transplant Society (PHTS) Registry was founded 30 years ago as a collaborative effort among like-minded providers of this novel life-saving technique for children with end-stage heart failure. In the intervening decades, the data from the Registry have provided invaluable knowledge to the field of pediatric heart transplantation. This report of the PHTS Registry provides a comprehensive look at the data, highlighting both the longevity of the registry and one unique aspect of the PHTS registry, allowing for exploration into children with single ventricle anatomy. METHODS: The PHTS database was queried from January 1, 1993 to December 31, 2019 to include pediatric (age < 18 years) patients listed for HT. For our analysis, we primarily analyzed patients by era. The early era was defined as children listed for HT from January 1, 1993 to December 31, 2004; middle era January 1, 2005 to December 31, 2009; and recent era January 1, 2010 to December 31, 2019. Outcomes after listing and transplant, including mortality and morbidities, are presented as unadjusted for risk, but compared across eras. RESULTS: Since 1993, 11 995 children were listed for heart transplant and entered into the PHTS Registry with 9755 listed during the study period. The majority of listings occurred within the most recent era. Waitlist survival improved over the decades as did posttransplant survival. Other notable changes over time include fewer patients experiencing allograft rejection or infection after transplant. Waitlist and posttransplant survival have changed dramatically in patients with single ventricle physiology and significantly differ by stage of single ventricle palliation. SUMMARY: Key points from this PHTS Registry summary and focus on patients with single ventricle congenital heart disease in particular, include the changing landscape of candidates and recipients awaiting heart transplant. There is clear improvement in waitlist and transplant outcomes for children with both cardiomyopathy and congenital heart disease alike.

Mental Health Care for Children with Heart Disease and Their Families: Practical Approaches and Considerations for the Pediatric and Pediatric Cardiology Clinician.

Mental health conditions are a common comorbidity among children living with heart disease. Children with congenital heart disease are more likely to have a mental health condition than their unaffected peers or peers with other chronic illnesses, and mental health risk persists across their lifetime. While poorer mental health in adults with congenital heart disease is associated with worse overall health outcomes, the association between mental health and cardiac outcomes for children with heart disease remains unknown. Despite this, it is suspected that mental health conditions go undiagnosed in children with heart disease and that many affected children and adolescents do not receive optimal mental health care. In this article, we review mental health in congenital heart disease across the lifespan, across domains of care, and across diagnoses. Further directions to support mental health care for children and adolescents with heart disease include practical screening and access to timely referral and mental health resources.

Is the mRNA COVID-19 Vaccine Safe in Patients With a Prior History of Myocarditis?

BACKGROUND: Numerous studies have reported myocarditis resulting from messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination. However, to date, there have been no reports highlighting the safety of mRNA COVID-19 vaccines in children and adults with a prior history of myocarditis, which was the intent of this study. METHODS AND RESULTS: Children and adults cared for at the Cleveland Clinic were identified through the electronic health records, who had a history of myocarditis before the COVID-19 pandemic and had subsequently received at least 2 doses of the mRNA COVID-19 vaccines (n = 34). Only 1 patient in this series had recurrence of myocarditis confirmed by cardiac magnetic resonance imaging after receiving the second dose. He was a White man who had his first episode of myocarditis at age 20 and was 27 years of age at the time of recurrence. He was hospitalized for 2 days with no need for cardiac support or reported arrhythmias and was stable at outpatient follow-up. CONCLUSIONS: In patients with an old history of non-COVID-19 myocarditis, the risk of recurrent myocarditis after receipt of mRNA COVID-19 vaccination is low, and when it occurs it seems to be self-limiting. Our study will be valuable to clinicians while discussing the risk-benefit ratio of vaccinations in patients with a prior history of myocarditis.

Pediatric Pericarditis: Update.

PURPOSE OF REVIEW: While there have now been a variety of large reviews on adult pericarditis, this detailed review specifically focuses on the epidemiology, clinical presentation, diagnosis, and management of pediatric pericarditis. We have tried to highlight most pediatric studies conducted on this topic, with special inclusion of important adult studies that have shaped our understanding of and management for acute and recurrent pericarditis. RECENT FINDINGS: We find that the etiology of pediatric pericarditis differs from adult patients with pericarditis and has evolved over the years. Also, with the current COVID-19 pandemic, it is important for pediatric clinicians to be aware of pericardial involvement both due to the infection and from vaccination. Oftentimes, pericarditis maybe the only cardiac involvement in children with COVID-19, and so caregivers should maintain a high index of suspicion when they encounter children with pericarditis.  Large-scale contemporary epidemiological data regarding incidence and prevalence of both acute and recurrent pericarditis is lacking in pediatrics, and future studies should focus on highlighting this important research gap. Most of the current management strategies for pediatric pericarditis are from experiences gathered from adult data. Pediatric multicenter trials are warranted to understand the best management strategy for those with acute and recurrent pericarditis. CASE VIGNETTE: A 6-year-old child with a past history of pericarditis almost 2 months ago comes in with a 2-day history of chest pain and fever. Per mother, he stopped his steroids about 2 weeks ago, and for the last 2 days has had a temperature of 102F and has been complaining of sharp mid-sternal chest pain that gets worse when he lies down and is relieved when he sits up and leans forward. On examination, he is tachycardic (heart rate 160 bpm), with normal blood pressure for age. He appears to be in pain (5/10), and on auscultation has a pericardial friction rub. His lab studies are notable for elevated white blood cell count and inflammatory markers (CRP and ESR). His electrocardiogram reveals sinus tachycardia and diffuse ST-elevation in all precordial leads. His echocardiogram demonstrates normal biventricular function and a trace pericardial effusion. His cardiac MRI confirms recurrent pericarditis. He is started on indomethacin and colchicine. He has complete resolution of his symptoms by day 3 of admission and is discharged with close follow-up.

Contemporary Provider Management Practices and Attitudes Toward Referral for Advanced Heart Failure Therapies in Fontan Patients Across North America.

BACKGROUND: To date, no reports have described clinicians' management practices for patients with Fontan circulatory failure or their understanding of risk factors for mortality and transplant outcomes in these patients. METHODS AND RESULTS: A cross-sectional survey of caregivers across North America was conducted from February to September 2020. Responses were compared by primary specialty (heart failure/transplant vs non-heart failure/transplant), years of experience (early, mid, and late career), and Fontan center volume (low, medium, and high). Of 400 responses, the majority were from general cardiologists (111, 28%) followed by heart failure/transplant specialists (93, 23%). Although most agreed that patients with Fontan physiology will have signs/symptoms of heart failure (369 [93%]) and eventuate in heart transplant (286 [72%]), many disagreed (180 [45%]) that routine evaluation by a transplant cardiologist is needed without symptoms. Transplant providers were more likely than non-transplant providers to suggest referral for manifestations of Fontan circulatory failure such as protein-losing enteropathy, plastic bronchitis, liver fibrosis/cirrhosis, and worsening valve regurgitation. Non-transplant providers were more likely to suggest that protein-losing enteropathy, plastic bronchitis, and Fontan-associated liver disease lead to inferior outcomes after transplantation. Early career and transplant providers more favorably viewed ventricular assist device use for Fontan patients failing traditional heart failure therapy (P < .05 for all). CONCLUSIONS: There is significant variation in the management of Fontan patients, including heterogeneous timing of referral of such patients to the heart failure/transplant team, which may have implications for future outcomes.

Waitlist Outcomes for Children With Congenital Heart Disease: Lessons Learned From Over 5000 Heart Transplant Listings in the United States.

BACKGROUND: We evaluated the impact of pediatric heart-allocation policy changes over time and the approval of the Berlin ventricular assist device (VAD) on waitlist (WL) outcomes for children with congenital heart disease (CHD). METHODS: The Scientific Registry of Transplant Recipients database was evaluated to include all children (age < 18) with CHD and cardiomyopathy (CMP) on the WL between 1999 and 2019, divided into 4 eras: Era 1 (1999-2008); Era 2 (2009-2011); Era 3 (2012-2016); and Era 4 (2016-2019). WL characteristics and survival outcomes were evaluated for patients with CHD over time and were compared to those with CMP listed currently (Era 4). RESULTS: We included 5185 children with CHD on the WL during the study period; 1999 (39%) were listed in Era 1; 693 (13%) in Era 2; 1196 (23%) in Era 3; and 1297 (25%) in Era 4. Compared to the CHD WL in eras 1 and 2, those in Era 4 were less likely to be infants (48% vs 49% vs 43%), on mechanical ventilation (30% vs 26% vs 19%), on extracorporeal membrane oxygenation (15% vs 9.7% vs 6.2%), and were more likely to be on a VAD (2.4% vs 2.2% vs 6.0%) (P < .05 for all). WL survival improved in children with CHD from Era 1 to Era 4 (P < .001). However, in Era 4, children with CHD had lower WL survival than those with CMP (P < .001). CONCLUSION: Children with CHD are increasingly being listed with less advanced heart failure, and they have had improved WL survival over time; however, WL outcomes remain inferior to those with CMP. Advances in pediatric medical and VAD therapy may improve future WL outcomes.

Learning from each other: The hidden benefit of practice variation.

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.

Obesity and dyslipidemia predict cardiac allograft vasculopathy and graft loss in children and adolescents post-heart transplant: A PHTS multi-institutional analysis.

BACKGROUND: Obesity and dyslipidemia afflict children of all ages. We explored the prevalence of obesity and dyslipidemia in pediatric heart transplant (HT) recipients and its effects on cardiac allograft vasculopathy (CAV) and survival. METHODS: This study included primary HT recipients (≤18 years) transplanted between 01/1996 and 12/2018 included in the Pediatric Heart Transplant Society database. Obesity was categorized according to WHO/CDC guidelines and dyslipidemia according to the National Cholesterol Education Program. Kaplan-Meier analyses for CAV and graft loss stratified for BMI and lipid panels were generated and risk factors identified using multivariate analyses. RESULTS: Among 6291 HT patients (median age [range] at HT = 4.3 [0.6-12.8] years; 45% Female; 68% White), 56% had a normal BMI at HT. Obese patients at HT had an increased risk for graft loss (HR 1.19, 95% CI 1.01-1.4, p = .04). Poor total cholesterol (TC), LDL-C, and TG were associated with the risk of both CAV (HR 1.79, p < .0001; HR 1.65, p = .0015; HR 1.53, p < .0001, respectively) and graft loss (HR 1.58, p = .0008; HR 1.22, p = .04; HR 1.43, p = .0007, respectively). CONCLUSIONS: Pediatric patients who are obese at the time of HT and dyslipidemic at 1 year post-HT are at an increased risk for CAV and graft loss. Preventative interventions may reduce morbidity and mortality among this cohort.

Clinical approach to vasoplegia in the transplant patient from the Pediatric Heart Transplant Society.

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.

Clinical approach to antibody-mediated rejection from the pediatric heart transplant society.

OBJECTIVE: This document is designed to outline the definition, pathogenesis, diagnostic modalities and therapeutic measures to treat antibody-mediated rejection in children postheart transplant METHODS: Literature review was conducted by a Pediatric Heart Transplant Society (PHTS) working group to identify existing pediatric and adult studies on antibody-mediated rejection (AMR). In addition, the centers participating in PHTS were asked to submit their approach to diagnosis and management of pediatric AMR. This document synthesizes information gathered from both these sources to highlight a practical approach to diagnosing and managing a child with AMR postheart transplant. This document may not represent the practice at all centers in the PHTS and serves as a starting point to understand an approach to this clinical scenario.

Waitlist and Post-Heart Transplant Outcomes for Children with Kawasaki Disease in the United States.

We evaluated waitlist and post-heart transplant outcomes for children with Kawasaki disease and found that over 3 decades the number of patients requiring heart transplantation in the US is low. Also, patients with Kawasaki disease have similar waitlist and post-transplant outcomes compared with patients with dilated cardiomyopathy.

Racial and Ethnic Disparities Persist in the Current Era of Pediatric Heart Transplantation.

BACKGROUND: Previous studies have demonstrated that children in the United States who were of racial and ethnic minorities have inferior waitlist and post-heart transplant (HT) outcomes. Whether these disparities still exist in the contemporary era of increased ventricular assist device use remains unknown. METHODS: All children (age <18 years) in the Scientific Registry of Transplant Recipients database listed for HT from December 2011 to February 2019 were included and were separated into 5 races/ethnicities: Caucasian, African American, Hispanic, Asian, and Other. Differences in clinical characteristics and survival among children of different racial/ethnic groups were compared at listing and at HT. RESULTS: The waitlist cohort consisted of 2134 (52.2%) Caucasian, 840 (20.5%) African American, 808 (19.8%) Hispanic, 161 (3.9%) Asian, and 146 children of Other races (3.6%). At listing, Asian children mostly had cardiomyopathy (70.8%), whereas Caucasian children had congenital heart disease (58.7%). African American children were most likely to be listed as Status 1A and to have renal dysfunction and hypoalbuminemia at listing. African American and Hispanic children were most likely to be on Medicaid. After multivariable analysis, it was found that only African American children were at increased risk for waitlist mortality as compared to Caucasian children (adjusted hazard ratio = 1.25; P = 0.029). Post-HT, there were no disparities in early and midterm graft survival among groups, but African American children had increased numbers of rejection episodes compared to Caucasian and Hispanic children. CONCLUSION: African American children continue to experience increased waitlist mortality and have increased rejection episodes post-HT. Studies exploring barriers to health care access and implicit bias as reasons for these disparities need to be conducted.

Review of interactions between high-risk pediatric heart transplant recipients and marginal donors including utilization of risk score models.

BACKGROUND: Donor organ acceptance practices vary among pediatric heart transplant professionals. We sought to understand what is known about the interactions between the "high-risk" recipient and the "marginal donor," and how donor risk scores can impact this discussion. METHODS: A systematic review of published literature on pediatric HTx was undertaken with the assistance of a medical librarian. Two authors independently assessed search results, and papers were reviewed for inclusion. RESULTS: We found that there are a large number of individual factors, and clusters of factors, that have been used to label individual recipients "high-risk" and individual donors "marginal." The terms "high-risk recipient" and "marginal donor" have been used broadly in the literature making it virtually impossible to make comparisons between publications. In general, the data support that patients who could be easily agreed to be "sicker recipients" are at more risk compared to those who are clearly "healthier," albeit still "sick enough" to need transplantation. Given this variability in the literature, we were unable to define how being a "high-risk" recipient interplays with accepting a "marginal donor." Existing risk scores are described, but none were felt to adequately predict outcomes from factors available at the time of offer acceptance. CONCLUSIONS: We could not determine what makes a donor "marginal," a recipient "high-risk," or how these factors interplay within the specific recipient-donor pair to determine outcomes. Until there are better risk scores predicting outcomes at the time of organ acceptance, programs should continue to evaluate each organ and recipient individually.

Outcome of pediatric heart transplantation in blood culture positive donors in the United States.

Active donor infection at the time of organ procurement poses a potential infection risk and may increase post-transplant morbidity and mortality in recipients. Our hypothesis was that pediatric heart transplant recipients from blood culture positive donors (BCPD) would have increased morbidity and mortality compared to non-blood culture positive donors (NBCPD). A retrospective analysis of pediatric heart transplant recipients using the organ procurement and transplant network (OPTN) between 1987 and 2015 was conducted. Recipient as well as donor data were analyzed. Propensity score matching with 1:2 ratios was performed for recipient variables. Post-transplant morbidity and mortality were compared for recipients of BCPD and NBCPD. Among 9618 heart transplant recipients, 450 (4.7%) were from culture positive donors. Recipients of BCPD had longer duration of listing as Status 1; diagnosis of congenital heart disease or restrictive cardiomyopathy and required support (IV inotropes, Inhaled NO and LVAD) prior to transplant. Post-transplant survival between the 2 groups was not different. Propensity-matched recipients had similar length of stay; stroke rate; need for dialysis; pacemaker implantation and treated rejection episodes in the first year post-transplant. Careful acceptance of BCPD may have the potential to increase availability of donor hearts in the pediatric population.

Cardiovascular disease in survivors of childhood cancer.

PURPOSE OF REVIEW: We review the cardiotoxic chemotherapeutic agents, the clinical and subclinical presentations and progression of their cardiotoxicity, and the management of the subsequent cardiovascular disease in survivors of childhood cancer. We discuss various preventive measures, especially the cardioprotectant, dexrazoxane, whose use with anthracycline chemotherapy, including doxorubicin, is based on strong evidence. Most treatment recommendations for this unique population are based on expert opinion, not on empirical evidence. RECENT FINDINGS: As patients with childhood cancers live longer, morbidity from the cardiac side effects of chemotherapy is increasing. Treatment-related cardiac damage is irreversible and often progressive. It is imperative that such damage be prevented with strategies such as limiting the cumulative anthracycline dose, the use of anthracycline structural analogues and the use of cardioprotective agents. SUMMARY: A deeper understanding of the mechanisms of their cardiotoxicity reveals that there is no 'safe' dose of anthracyclines. However, certain risk factors, such as higher lifetime anthracycline cumulative doses, higher anthracycline dose rates, female sex, longer follow-up, younger age at anthracycline treatment and cardiac irradiation, are associated with more severe cardiotoxicity. We advocate the use of dexrazoxane to limit the cardiotoxic effects of anthracycline chemotherapy.