The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft.

BACKGROUND: Much of our knowledge of organ rejection after transplantation is derived from rodent models. METHODS: We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data. RESULTS: Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells. CONCLUSIONS: Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure.

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.

Myocarditis in children 2024, new themes and continued questions.

PURPOSE OF REVIEW: While pediatric myocarditis incidence has increased since the coronavirus disease 2019 (COVID-19) pandemic, there remain questions regarding diagnosis, risk stratification, and optimal therapy. This review highlights recent publications and continued unanswered questions related to myocarditis in children. RECENT FINDINGS: Emergence from the COVID-19 era has allowed more accurate description of the incidence and prognosis of myocarditis adjacent to COVID-19 infection and vaccine administration as well that of multi-system inflammatory disease in children (MIS-C). As cardiac magnetic resonance technology has shown increased availability and evidence in pediatric myocarditis, it is important to understand conclusions from adult imaging studies and define the use of this imaging biomarker in children. Precision medicine has begun to allow real-time molecular evaluations to help diagnose and risk-stratify cardiovascular diseases, with emerging evidence of these modalities in myocarditis. SUMMARY: Recent information regarding COVID-19 associated myocarditis, cardiac magnetic resonance, and molecular biomarkers may help clinicians caring for children with myocarditis and identify needs for future investigations.

Arrhythmogenic cardiomyopathy is under-recognized in end-stage pediatric heart failure: A 36-year single-center experience.

BACKGROUND: Although ventricular failure is a late finding in adults with AC, we hypothesize that this is a presenting symptom in pediatric heart failure patients who undergo HT and that their ventricular arrhythmia burden could differentiate AC from other cardiomyopathies. METHODS: We performed a single-center retrospective cohort study reviewing 457 consecutive pediatric (≤18 years) HT recipients at our institution. Explanted hearts were examined to establish the primary diagnosis, based on pathologic findings. Demographic and clinical variables were compared between AC versus non-HCM cardiomyopathy cases. RESULTS: Forty-five percent (n = 205/457) had non-HCM cardiomyopathies as the underlying primary diagnosis. Ten cases (10/205 = 4.9%) were diagnosed with AC. All 10 had biventricular disease. In 8/10 patients (80%), AC diagnosis was unrecognized pre-HT. Compared with non-AC cardiomyopathies, the AC group was older at diagnosis (9.3 years vs. 4.3 years, p = .012) and transplant (11.1 years vs. 6.5 years, p = .010), had more ventricular arrhythmias (80.0% vs 32.8%, p = .003), and required more anti-arrhythmic use (80.0% vs 32.3%, p = .001). Genetic testing yielded causative pathogenic variants in all tested individuals (n = 5/5, 100%). CONCLUSION: AC is often an unrecognized cardiomyopathy pretransplant in children who undergo HT. Pediatric non-HCM phenotypes with heart failure who have a significant ventricular arrhythmia burden should be investigated for AC.

Decreased Heart Rate Variability in Children with Acute Decompensated Heart Failure is Associated with Poor Outcomes.

Heart rate variability (HRV) is a noninvasive indicator of the health of neurocardiac interactions of the autonomic nervous system. In adults, decreased HRV correlates with increased cardiovascular mortality. However, the relationship between HRV and outcomes in children with acute decompensated heart failure (ADHF) has not been described. Patients < 21 years old hospitalized with ADHF from 2013 to 2019 were included (N = 79). Primary outcome was defined as death, heart transplant, or mechanical circulatory support (MCS). The median standard deviation of the R-to-R interval in 5-min intervals (SDNN) was calculated from telemetry data obtained across the first 24 h of admission. Patients who met the primary outcome had significantly lower median SDNN (13.8 [7.8, 29.1]) compared to those who did not (24.6 [15.3, 84.4]; p = 0.004). A median SDNN of 20 ms resulted in a sensitivity of 68% and specificity of 69%. Median SDNN < 20 ms represented decreased freedom from primary outcome (p = 0.043) and a hazard ratio of 2.2 in multivariate analysis (p = 0.016). Pediatric patients with ADHF who died, underwent heart transplant, or required MCS had significantly decreased HRV at presentation compared to those that did not. This supports HRV as a noninvasive tool to improve prognostication in children in ADHF.

Epidemiology and long-term outcomes of cytomegalovirus DNAemia and disease in pediatric solid organ transplant recipients.

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6-12.9]) and intermediate-risk (4.36 [2.3-8.2]) CMV status and lung transplantation (4.63 [2.33-9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p < .01). DNAemia was not associated with an increase in graft failure, all-cause mortality, or other organ-specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.

LMOD2-related dilated cardiomyopathy presenting in late infancy.

Leiomodin-2 (LMOD2) is an important regulator of the thin filament length, known to promote elongation of actin through polymerization at pointed ends. Mice with Lmod2 deficiency die around 3 weeks of age due to severe dilated cardiomyopathy (DCM), resulting from decreased heart contractility due to shorter thin filaments. To date, there have been three infants from two families reported with biallelic variants in LMOD2, presenting with perinatal onset DCM. Here, we describe a third family with a child harboring a previously described homozygous frameshift variant, c.1243_1244delCT (p.L415Vfs*108) with DCM, presenting later in infancy at 9 months of age. Family history was relevant for a sibling who died suddenly at 1 year of age after being diagnosed with cardiomegaly. LMOD2-related cardiomyopathy is a rare form of inherited cardiomyopathy resulting from thin filament length dysregulation and should be considered in genetic evaluation of newborns and infants with suspected autosomal recessive inheritance or sporadic early onset cardiomyopathy.

Postoperative physiological parameters associated with severe acute kidney injury after pediatric heart transplant.

BACKGROUND: The primary objective was to evaluate associations between perioperative clinical variables and postoperative hemodynamic indices after HT with the development of severe AKI. The secondary objective was to evaluate associations between UOP or creatinine as AKI indicators and morbidity after HT. METHODS: Retrospective study of all patients who underwent HT 1/2016-11/2019 at a quaternary pediatric institution. Severe AKI was defined as KDIGO stage 2 or higher. RESULTS: Of 94 HT patients, 73 met inclusion criteria; 45% of patients developed severe AKI. In univariate analysis, non-Hispanic Black race, preoperative AKI, longer CPB duration, lower weight, and peak lactate within 12 h post-HT were associated with severe AKI. CVP ≤12 h post-HT had a quadratic relationship, rather than linear, with severe AKI. PPV >18% was significantly associated with severe AKI but equated to noncontiguous 10 min of high variation over a 12-h period, and thus was deemed not clinically significant. In multivariate analysis, Black race, longer CPB duration, and higher CVP remained associated with severe AKI (c: 0.84, 95% CI 0.73-0.92). Severe AKI per creatinine, but not UOP criteria, was associated with longer duration of ventilation (p = .012) and longer intensive care unit length of stay (p = .003). CONCLUSIONS: In pediatric HT patients, non-Hispanic Black race, longer CPB time, and higher postoperative CVP ≤12 h post-HT were associated with severe AKI. AKI based on creatinine, not UOP, was associated with postoperative HT morbidity.

Outcomes following use of pediatric and young adult donor hearts with bicuspid aortic valves: A single-center case series.

BACKGROUND: Valvular disease in pediatric and young adult donor hearts may be a relative contraindication to graft use. Outcomes following the use of donor hearts with bicuspid aortic valve (BAV) have not been previously reported in children. We describe 4 cases of pediatric heart transplantation (HTx) utilizing a donor heart with a BAV. CASE SERIES: Of the 469 HTx included in this study, 4 utilized a donor heart with a BAV. All recipients were female; median age was 11 years (range 0.3 to 19 years). In all cases, the BAV was not discovered until after HTx. All donors were less than 30 years old. The patients were followed for a median of 6 years (range 2 to 9 years) with all patients alive at last follow-up. Two patients have transitioned to adult care, and 2 patients continue to follow in our clinic. In follow-up, no patient has required an aortic valve intervention or had infective endocarditis. At last review, no patient had greater than mild aortic insufficiency or more than mild aortic stenosis. Three patients developed mild-to-moderate left ventricular hypertrophy in the first year post-transplant that improved over time. One patient experienced a peri-operative embolic stroke at time of transplant unrelated to the BAV. CONCLUSION: On short- and intermediate-term follow-up, pediatric and young adult donor hearts with BAV demonstrated acceptable graft longevity and valvular function. A functionally normal BAV in a pediatric heart transplant donor should not be a contraindication to organ acceptance.

Ventricular assist device support for children with chemotherapy-induced cardiomyopathy and advanced heart failure: Perspectives gained from a single-center experience.

BACKGROUND: Guidance and data on ventricular assist device (VAD) support for children with chemotherapy-induced cardiomyopathy, particularly within the first 2 years after chemotherapy, are limited. METHODS: We performed a single-center retrospective case series, reviewing medical records of children <18 years of age with chemotherapy-induced cardiomyopathy and advanced heart failure (HF) who received durable VAD support. RESULTS: Six patients met inclusion criteria-5 HeartWare™ HVAD, 1 Berlin Heart EXCOR® . Median age at cancer diagnosis was 6 years (IQR 4.5-10 years). Median dose of anthracycline received was 540 mg/m2 (IQR 450-630 mg/m2 ). All patients developed HF within 1 year after initiation of cancer treatment (median 8 months, IQR 6-11.5 months) and were initiated on durable VAD support at a median of 8 months after completion of cancer treatment (IQR 3.3-43.5 months). Four patients had significant right ventricular dysfunction needing oral pulmonary vasodilator therapy, one patient had a major bleeding complication, and two patients had thromboembolic strokes while on VAD support. Median duration of VAD support was 7.5 months (IQR 3-11.3 months). Two patients underwent VAD explant due to recovery of LV function, one died due to cancer progression, and three underwent heart transplantation. CONCLUSIONS: Durable VAD support should be considered as a therapeutic option for children who have advanced HF due to chemotherapy-induced cardiomyopathy, even within 2 years of completing cancer treatment. A multi-disciplinary approach is essential for appropriate patient selection prior to implant and to ensure comprehensive care throughout the duration of VAD support.

Clinical approach to acute cellular rejection from the pediatric heart transplant society.

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.

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.

Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study.

OBJECTIVES: Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited. DESIGN: Retrospective cohort study. SETTING: Single tertiary-quaternary referral center. PATIENTS: All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange. CONCLUSIONS: Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

Poor efficacy of oral iron replacement therapy in pediatric patients with heart failure.

INTRODUCTION: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure. METHODS: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test. RESULTS: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy. CONCLUSIONS: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

Immunosuppressant Drugs and Their Effects on Children Undergoing Solid Organ Transplant.

More than 112,000 men, women, and children are awaiting solid organ transplant (SOT) as of March 2020, and more than 39,000 transplants were performed in the United States in 2019. Approximately 2,000 children undergo SOT every year in the United States, and the number of children awaiting SOT continues to increase. Immunosuppression is the mainstay of prevention and treatment of solid organ rejection, a significant source of morbidity and mortality after SOT. There are several different classes of immunosuppressive drugs, and the phases of immunosuppression after SOT can be divided into early, maintenance, and rescue therapies. The specific class and dose of drug will be determined by the type of organ transplant, time since transplant, phase of therapy, and other patient-specific considerations. The goal of the transplant team is to find the optimal balance between too little immunosuppression and too much immunosuppression. Too little immunosuppression can result in organ rejection, but too much immunosuppression can result in increased infections, increased malignancy, and adverse drug events such as nephrotoxicity. Although the specific drug choice and dosage will be managed by specialized transplant physicians, these immunosuppressive drugs have many drug interactions with commonly prescribed medications and require dose titration. To provide the best care to children who have received a SOT, pediatricians should be aware of these interactions and be able to distinguish routine pediatric concerns from transplant immunosuppression-related infections or complications. Current vaccine recommendations for children receiving immunosuppression after SOT are also discussed.

Pediatric heart-liver transplant outcomes in the United States: A 25-year National Cohort Study.

BACKGROUND: Pediatric HLT remains uncommon in the United States and criteria for HLT are unclear. The objectives of this study were to review the indications, and outcomes of pediatric HLT. METHODS: Data from the Scientific Registry of Transplant Recipients heart and liver databases were used to identify 9245 pediatric isolated heart transplants (PHT), 14 134 pediatric isolated liver transplant (PLT), and 20 pediatric HLT (16 patients underwent sHLT [same organ donor] and four patients with a history of PHT followed by PLT [different organ donors]; age ≤21 years) between 1992 and 2017. Outcomes included patient survival, and 1-year rates of acute heart and liver rejection. RESULTS: The median age for pediatric HLT was 15.6 (IQR: 10.5, 17.9) years, and included 12 males (12/20 = 60%). In the HLT group, the most common indication for HT was CHD (12/20 = 60%), and the most common indication for liver transplant was cirrhosis (9/20 = 45%). The 1, 3, and 5 year actuarial survival rates in pediatric simultaneous HLT recipients (n = 16) were 93%, 93%, and 93%, respectively, and was similar to isolated PHT alone (88%, 81%, and 75.5%, respectively and isolated PLT alone (84%, 82%, and 80%), respectively. There was no heart or liver rejection reported in the HLT group versus 9.9% in heart and 10.6% in liver transplant-only groups, respectively. CONCLUSION: Pediatric HLT is an uncommon but acceptable option for recipients with combined end-organ failure, with intermediate survival outcomes comparable to those of single-organ recipients.

Hospital outcomes for pediatric heart transplant recipients undergoing tracheostomy: A multi-institutional analysis.

Tracheostomy is associated with increased mortality and resource utilization in children with CHD. However, the prevalence and hospital outcomes of tracheostomy in children with HTx are not known. We describe the prevalence and compare the post-HTx hospital outcomes of pediatric patients with Pre-TT and Post-TT to those without tracheostomy. A multi-institutional retrospective cohort study was performed using the Pediatric Health Information System database. Hospital mortality, mediastinitis, LOS, and costs were compared among patients with Pre-TT, Post-TT, and no tracheostomy. Pre-TT was identified in 29 (1.1%) and Post-TT was identified in 41 (1.6%) of 2603 index HTx hospitalizations. Patients with Pre-TT were younger and more likely to have CHD, a non-cardiac birth defect, or an airway anomaly compared to those without Pre-TT. Pre-TT was not independently associated with increased post-HTx in-hospital mortality. Age at HTx < 1 year, CHD, and Post-TT were associated with increased in-hospital mortality. Pre-TT that occurred during the HTx hospitalization and Post-TT were associated with increased resource utilization. Tracheostomy was not associated with mediastinitis.

Establishing Baseline Metrics of Heart Failure Medication Use in Children: A Collaborative Effort from the ACTION Network.

Heart failure metrics specific to the pediatric population are required to successfully implement quality improvement initiatives in children with heart failure. Medication use at the time of discharge following admission for decompensated heart failure has been identified as a potential quality metric in this population. This study aimed to report medication use at discharge in the current era for children admitted with acute decompensated heart failure. All patients < 21 years of age with an index admission (1/1/2011-12/31/2019) for acute heart failure and a coexisting diagnosis of cardiomyopathy were identified from the Pediatric Health Information System. Medication use patterns were described and compared across age groups and centers. A total of 2288 patients were identified for inclusion. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ACEi/ARB) was prescribed in 1479 (64.6%), beta blocker in 1132 (49.5%), and mineralocorticoid receptor antagonist (MRA) in 864 (37.8%) patients at discharge. The use of ACEi/ARB at discharge has decreased over time (64.6% vs. 69.6%, p = 0.001) and the use of beta blockers has increased (49.5% vs. 36.8%, p < 0.001) compared to a historical cohort (2001-2010). There is considerable variability in medication use across centers with an overall increase in beta blocker and decrease in ACEi/ARB use over time. Collaborative efforts are needed to standardize care and define quality metrics to identify best practices in the management of pediatric heart failure.

Iron Deficiency Is Associated with Adverse Outcomes in Pediatric Heart Failure.

OBJECTIVE: To evaluate the prevalence of iron deficiency and its association with outcomes in children with heart failure. STUDY DESIGN: A single-center retrospective cohort study of patients with heart failure aged 1-21 years from July 2012 to June 2017 with available serum iron studies was performed. Subjects were analyzed in 2 groups: biventricular systolic heart failure (BiV) and single-ventricle congenital heart disease with systolic heart failure (SV). Iron deficiency was defined as ≥2 of the following: serum iron <50 µg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, or transferrin saturation <15%. The primary outcome was a composite adverse event (CAE) of ventricular assist device implantation, heart transplantation, or death, at 3 and 6 months from time of iron studies. RESULTS: Of the 107 subjects (77 BiV, 30 SV) included in the study, 56% were iron deficient. Demographics, etiology of heart failure, and chronicity of heart failure symptoms were not associated with iron deficiency. On multivariable analysis, in group BiV, iron deficiency was associated with CAE at 3 months (79% iron deficiency in CAE group vs 37% iron deficiency in non-CAE, P = .001, OR 7, 95% CI 2-21) and 6 months (76% iron deficiency in CAE vs 35% iron deficiency in non-CAE, P = .002, OR 7, 95% CI 2-24). In group SV, iron deficiency was associated with CAE at 6 months (79% iron deficiency in CAE vs 29% iron deficiency in non-CAE, P = .014, OR 8, 95% CI 2-32). CONCLUSIONS: Iron deficiency was present in 56% of the pediatric patients with heart failure who were evaluated with iron studies. Iron deficiency was associated with greater risk of ventricular assist device implantation, heart transplantation, or death.

Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: A case report.

Pediatric recipients of SOT have a significantly increased risk of Clostridiodes (formerly Clostridium) difficile infection (CDI), which is associated with adverse outcomes after SOT. Alterations to the intestinal microbiota community structure increase the risk of CDI. FMT is a safe and effective treatment for recurrent CDI in immunocompetent children and adults. While there are increasing data that FMT in immunosuppressed patients is safe and effective without increased risk of infection, data regarding safety and efficacy of FMT in children after SOT are limited. To our knowledge, we report the youngest immunocompromised patient to undergo FMT and the third overall case of FMT in a child after HTx. Our patient presented with five episodes of rCDI in 6 months, and 16S rRNA genetic analysis revealed significant loss of overall microbiota community structure and diversity prior to FMT compared with a donor and a healthy, age-matched control. After FMT, marked and prolonged (at least 16 months) shifts in the recipient microbiota community structure and diversity were evident, approaching that of donor and healthy, age-matched control. FMT was well tolerated, restored microbial diversity without any graft or transplant complications, and prevented further rCDI episodes after more than 4 years of follow-up.