Diagnosis and Management of Cancer Treatment-Related Cardiac Dysfunction and Heart Failure in Children.

It is disheartening for parents to discover that their children have long-term cardiac dysfunction after being cured of life-threatening childhood cancers. As the number of childhood cancer survivors increases, early and late oncology-therapy-related cardiovascular complications continues to rise. It is essential to understand that cardiotoxicity in childhood cancer survivors is persistent and progressive. A child's cancer experience extends throughout his lifetime, and ongoing care for long-term survivors is recognized as an essential part of the cancer care continuum. Initially, there was a lack of recognition of late cardiotoxicities related to cancer therapy. About 38 years ago, in 1984, pioneers like Dr. Lipshultz and others published anecdotal case reports of late cardiotoxicities in children and adolescents exposed to chemotherapy, including some who ended up with heart transplantation. At that time, cardiac tests for cancer survivors were denied by insurance companies because they did not meet appropriate use criteria. Since then, cardio-oncology has been an emerging field of cardiology that focuses on the early detection of cancer therapy-related cardiac dysfunction occurring during and after oncological treatment. The passionate pursuit of many healthcare professionals to make life better for childhood cancer survivors led to more than 10,000 peer-reviewed publications in the last 40 years. We synthesized the existing evidence-based practice and described our experiences in this review to share our current method of surveillance and management of cardiac dysfunction related to cancer therapy. This review aims to discuss the pathological basis of cancer therapy-related cardiac dysfunction and heart failure, how to stratify patients prone to cardiotoxicity by identifying modifiable risk factors, early detection of cardiac dysfunction, and prevention and management of heart failure during and after cancer therapy in children. We emphasize serial longitudinal follow-ups of childhood cancer survivors and targeted intervention for high-risk patients. We describe our experience with the new paradigm of cardio-oncology care, and collaboration between cardiologist and oncologist is needed to maximize cancer survival while minimizing late cardiotoxicity.

Trends in Contemporary Use of Ventricular Assist Devices in Children Awaiting Heart Transplantation and Their Outcomes by Race/Ethnicity.

This retrospective study included children aged ≤18 years who had durable ventricular assist devices (VADs) as a bridge to transplantation from the United Network Organ Sharing (UNOS) database between 2011 and 2020. We evaluated 90 day waitlist mortality and 1 year posttransplant mortality after VAD implantation in children stratified by race/ethnicity: Black, White, and Others. The VAD was used in a higher proportion of Black children listed for heart transplantation (HT) (26%) versus Other (25%) versus White (22%); p < 0.01. Black children had Medicaid health insurance coverage (67%) predominantly at the time of listing for HT. There was no significant overall difference in waitlist survival among the three groups supported with VAD at the time of listing (log-rank p = 0.4). On the other hand, the 90 day waitlist mortality after the VAD implantation at listing and while listed was the lowest among Black (6%) compared with White (13%) and Other (14%) ( p < 0.01). The multivariate regression analysis showed that Other race (hazard ratio [HR], 2.29; p < 0.01), Black race (HR, 2.13; p < 0.01), use of mechanical ventilation (HR, 1.72; p = 0.01), and Medicaid insurance (HR, 1.54; p = 0.04) were independently associated with increased 1 year posttransplant mortality. In conclusion, Black children had more access to durable VAD support than White children. The 90 day waitlist mortality was significantly lower in Black children compared with White and Other after VAD implantation. However, Black and Other racial/ethnic children with VAD at transplant had higher 1 year posttransplant mortality than White children. Future studies to elucidate the reasons for these disparities are needed.

Racial and Ethnic Disparity in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 in Mississippi, USA.

We aimed to study the disparity in the clinical profile and outcomes of hospitalized Multisystem Inflammatory Syndrome in Children (MIS-C) patients at our center. The second goal was to examine the temporal association with preceding SARS-CoV-2 infection by race/ethnicity in our community in Mississippi. We found the racial disparity in the prevalence of MIS-C exceeded its temporal association with SARS-CoV-2 infections. We included 51 consecutive MIS-C patients hospitalized, whose median age was 9 (interquartile range [IQR] 5-12) years, 58% were male, 71% were black, 25% were white, and 4% belonged to other groups. We found a delay between onset of symptoms and hospitalization in black patients compared with white patients with a median of 2 (IQR 0-7) vs median of 0 (0-5) urgent care visits (P = .022), respectively. Black patients were hospitalized longer (median 8, IQR 2-39 days) than whites (median 5, IQR 3-14 days), P = .047. A total of 38.9% of blacks and 23.1% of whites were admitted to intensive care unit (P = .498); 36.1% of blacks had severe cardiac involvement vs 23.1% of white patients, P = .531. Future studies of MIS-C are required to improve health equity for children.

Impact of 2016 UNOS pediatric heart allocation policy changes on VAD utilization, waitlist, and post-transplant survival outcomes in children with CHD versus Non-CHD.

AIMS: We analyzed the impact of the revised pediatric heart allocation policy on types of ventricular assist device (VAD) utilization, and waitlist (WL) and post-heart transplant (HT) survival outcomes in congenital heart disease (CHD) versus non-CHD patients before (Era-1) and after (Era-2) pediatric heart allocation policy implementation. METHODS: We retrospectively reviewed the UNOS database from December 16, 2011, through March 31, 2021, for patients < 18 years old and listed for primary HT. We compared the differences observed between Era-1 and Era-2. RESULTS: 5551 patients were listed for HT, of whom 2447(44%) were in Era-1 and 3104(56%) were in Era-2. CHD patients were listed as status 1A unchanged, but the number of patients listed as status 1B decreased in Era-2, whereas the number of non-CHD patients listed as status 1A decreased, but status 1B increased. In Era-2 compared to Era-1, both temporary (1% to 4%, p < .001) and durable VAD (13.6% to 17.8%, p < .001) utilization increased, and the transplantation rate per 100-patient years increased in both groups. The median WL period for CHD patients increased marginally from 70 to 71 days (p = .06), whereas for non-CHD patients it decreased from 61 to 54 days (p < .001). Adjusted 90-day WL survival increased from 84% to 88%, p = .016 in CHD, but there was no significant change in non-CHD patients (p = .57). There was no significant difference in 1-year post-HT survival in CHD and non-CHD patients between Era-1 and Era-2. CONCLUSIONS: In summary, after the revised heart allocation policy implementation, temporary and durable VAD support increased, HT rate increased, waitlist duration marginally increased in the CHD cohort and decreased in the non-CHD cohort, and 90-day WL survival probability improved in children with CHD without significant change in 1-year post-HT outcomes. Future studies are needed to identify changes to the policy that may further improve the listing criteria to improve WL duration and post-HT survival.

Further Evidence of Autosomal Recessive Inheritance of RPL3L Pathogenic Variants with Rapidly Progressive Neonatal Dilated Cardiomyopathy.

Neonatal dilated cardiomyopathy (DCM) is rare with high etiologic heterogeneity. Recently, biallelic, autosomal recessive, pathogenic variants in RPL3L (ribosomal protein L3-like) have been reported in the literature with severe early-onset DCM. In the present brief report, we identified two pathogenic RPL3L variants, each harbored in unaffected heterozygous parents: mother (RPL3L c.1076_1080delCCGTG (p.Ala359Glyfs*4)) and father (RPL3L c.80G > A (p.Gly27Asp)). Pathogenic variants were segregated as autosomal recessive to two offspring born with compound heterozygous RPL3L variants and affected by neonatal DCM. This is the second report in the literature to the best of our knowledge and our findings support the pathogenicity of biallelic RPL3L pathologic variants associated with rapidly progressive neonatal DCM and heart failure with a poor prognosis.

Posterior reversible encephalopathy syndrome in a pediatric heart transplant recipient with coarctation of aorta.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome reported in children with hypertension due to renal diseases, immunosuppression after solid organ transplant, cytotoxic agents for chemotherapy, and many others rare instances. We described PRES in a 6-year-old child with hypertension secondary to an incidental postoperative coarctation of the aorta after heart transplantation (HT). Her blood pressure was well controlled with amlodipine during the outpatient visits and home monitoring of blood pressure, but she had hypertension when presented with neurological symptoms. This case's unique feature is that although PRES has been described after pediatric HT, this is the first case report due to a postoperative coarctation of the proximal descending aorta related to scarring from previous multiple sternotomies leading to inadvertent external compression of the aorta with scar tissue. We discussed the risk factors associated with hypertension before PRES and the correlation of brain magnetic resonance imaging findings with clinical outcomes.

Correlation among Hemolysis Biomarkers in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation.

Hemolysis is a common complication associated with mortality on extracorporeal membrane oxygenation (ECMO). Plasma-free hemoglobin (PFH) is the most commonly used biomarker reported for hemolysis on ECMO. This test is not readily available at all institutions, and other more readily available tests may indicate hemolysis nearly as well or as well as PFH. The purpose of this study was to study the correlation of other biomarkers of hemolysis to PFH on ECMO. All patients younger than 21 years placed on ECMO in a quaternary children's hospital between January 2013 and December 2016 were included in the study; biomarkers (urine hemoglobin [U-Hb], PFH, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], gross hemolysis, and red cell distribution width (RDW)) were collected from the medical record. Descriptive statistics and repeated bivariate analyses were determined using SPSS 22.0. The median age on day 0 of ECMO was 29 days (.08 years) (IQR: 2; 319 days (.005; .875 years)). The median weight was 3.9 kg (IQR: 2.8; 8.6), and the median total duration of the ECMO run was 10.48 days (IQR: 4.25; 14), with 82% of all the patients being on venoarterial ECMO. There was no correlation between hematuria on urinalysis and the level of PFH (p = .338). There was a statistically significant positive correlation between PFH and the following respective biomarkers: gross hemolysis on the routine chemistry studies (p < .01, Rho = .439), AST (p < .01, Rho = .439), RDW (p < .01, Rho = .190), LDH (p < .01, Rho = .584), and AST (when associated elevated alanine transaminase (ALT) levels were censored) (p < .01, Rho = .552). U-Hb correlated poorly with PFH. The serum biomarkers AST (in the absence of ALT elevation) and LDH can be useful surrogates for PFH to quantify hemolysis on ECMO in pediatric patients.

Antithymocyte globulin induction therapy and myocardial complement deposition in pediatric heart transplantation.

BACKGROUND: Antithymocyte globulin (ATG) consists of polyclonal antibodies directed primarily against human T lymphocytes but may contain antibodies with affinity for other tissues in the transplanted organ, resulting in complement (C4d) deposition. This phenomenon has been demonstrated in endomyocardial biopsies (EMBs) of adult cardiac transplants. We examined the relationship of induction immunosuppression with ATG and C4d deposition in EMB of pediatric cardiac transplants. METHODS: Results of C4d immunohistochemistry were available from all EMB of patients transplanted at our center between June 2012 and April 2018 (n = 48) who received induction immunosuppression with either ATG (n = 20) or basiliximab (n = 28) as the standard of care. RESULTS: C4d deposition in the first year post-heart transplant was more commonly seen among patients who received ATG induction (20% of EMBs in ATG group vs 1% of EMBs in basiliximab group; p < .0001). C4d deposition related to ATG was observed early post-transplant (50% ATG vs 0% basiliximab on first EMB; p < .0001 and 35% ATG vs 0% basiliximab on the second EMB; p = .0012). While this difference waned by the third EMB (5% ATG vs 0% basiliximab; p = .41), positive C4d staining persisted to the sixth EMB in the ATG group only (6%). CONCLUSION: C4d deposition is common on EMB up to 1 year post-pediatric cardiac transplant following ATG induction. This high rate of positive C4d staining in the absence of histologic AMR after ATG induction therapy must be accounted for in making clinical decisions regarding cardiac allograft rejection diagnosis and treatment.

Outcomes of Pediatric Patients Treated With Extracorporeal Membrane Oxygenation for Intractable Supraventricular Arrhythmias.

OBJECTIVES: Extracorporeal membrane oxygenation is used to support refractory cardiorespiratory failure. Outcomes and complications when extracorporeal membrane oxygenation is used to support cardiorespiratory failure secondary to arrhythmia in pediatric patients remain poorly defined. Our purpose is to describe pediatric patients requiring extracorporeal membrane oxygenation support for supraventricular arrhythmias in the context of normal cardiac anatomy and congenital heart disease and identify patient/peri-extracorporeal membrane oxygenation variables associated with extracorporeal membrane oxygenation-related complications and survival. DESIGN: Retrospective multicenter review from 1993 to 2016. SETTING: Extracorporeal Life Support Organization registry. SUBJECTS: Patients younger than 21 years old requiring extracorporeal membrane oxygenation support for supraventricular arrhythmias. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 342 patients were identified (weight, 3.8 kg [3.2-7.5 kg]; age at extracorporeal membrane oxygenation initiation, 24 d [6-222]; 61% male). Sixty-five percentage survived to hospital discharge. Complications were frequent (85%) and most commonly cardiac related (31%). In multivariable modeling, mortality was associated with congenital heart disease, time from intubation to extracorporeal membrane oxygenation initiation, use of bicarbonate prior to extracorporeal membrane oxygenation, extracorporeal membrane oxygenation duration, and the presence of a complication. The presence of any complication was associated with a three-fold increase in the odds of death. In subgroup analysis of isolated supraventricular arrhythmias patients, similar patient and extracorporeal membrane oxygenation characteristics were associated with outcome. A lower pre-extracorporeal membrane oxygenation pH and PCO2 and site of venous cannulation were associated with complications (p < 0.02). CONCLUSIONS: Extracorporeal membrane oxygenation use for medically refractory supraventricular arrhythmias was associated with a 65% survival to hospital discharge. However, there was a high rate of complications, the presence of which was associated with decreased survival. Complications appeared to be related to pre-extracorporeal membrane oxygenation clinical status and whether earlier extracorporeal membrane oxygenation cannulation prior to patient deterioration would improve outcomes needs additional evaluation.

Resource utilisation in paediatric patients with secundum atrial septal defects.

BACKGROUND: There is variation in care of secundum atrial septal defects. Defects <3 mm and patent foramen ovale are not clinically significant. Defects >3 mm are often followed clinically and may require closure. Variation in how these lesions are monitored may result in over-utilisation of routine studies and higher than necessary patient charges. PURPOSE: To determine utilisation patterns for patients with secundum atrial septal defects diagnosed within the first year of life and compare to locally developed optimal utilisation standard to assess charge savings. METHODS: This was a retrospective chart review of patients with secundum atrial septal defects diagnosed within the first year of life. Patients with co-existing cardiac lesions were excluded. Total number of clinic visits, electrocardiograms, and echocardiograms were recorded. Total charge was calculated based on our standard institutional charges. Patients were stratified based on lesion and provider type and then compared to "optimal utilisation" using analysis of variance statistical analysis. RESULTS: Ninety-seven patients were included, 40 had patent foramen ovale (or atrial septal defect <3 mm), 43 had atrial septal defects not requiring intervention and 14 had atrial septal defects requiring intervention. There was a statistically significant difference in mean charge above optimal for these lesions of $1033, $2885, and $5722 (p < 0.02), respectively. There was statistically significant variation of charge among types of provider as well. Average charge savings per patient would be $2530 with total charge savings of $242,472 if the optimal utilisation pathway was followed. CONCLUSION: Using optimal utilisation and decreasing variation could save the patient significant unnecessary charges.

Virtual dissection and endocast three-dimensional reconstructions: maximizing computed tomographic data for procedural planning of an obstructed pulmonary venous baffle.

We present a case of pulmonary venous baffle obstruction in a child with a history of congenitally corrected transposition status post double switch repair. We highlight two forms of volume rendering three-dimensional reconstructions from computed tomographic data which allowed for detailed pre-surgical planning. These reconstructions emphasise the concept of maximizing previously obtained two-dimensional data in a time-efficient and cost-effective manner. The benefits of these reconstructions are reviewed, highlighting the relatively novel virtual dissection reconstruction technique that appeared identical to what the surgeon encountered in the operating theatre. This technique allowed the surgeon to quickly advance a preconceived detailed surgical repair.

Ping-Pong Ball, Tumor or Thrombus in the Right Atrium? A Case Report.

Tumors and thrombi are the most common cardiac masses of the right atrium. The use of noninvasive imaging to differentiate between the two can be deceiving, and the clinical judgment of a cardiologist and the emergency of the situation should be partnered to decide on the next step of the management. We present the case of a 29-year-old lady who was receiving neoadjuvant treatment for her rhabdomyosarcoma and was incidentally found to have a very large, very mobile right atrial mass that was protruding in the right ventricle with each cardiac cycle along with findings of a small segmental right lower lobe pulmonary embolism. Along with noninvasive imaging, frozen section analysis procured the wrong diagnosis, and the mass was ultimately found to be a right atrial thrombus on definite pathology review. Exact management of right atrial masses continues to be not well delineated, and when in doubt, final diagnosis might need to be "a posteriori" and based on the treatment response.