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. Summary 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.

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans. METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell–derived cardiomyocytes were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR (clustered regularly interspaced short palindromic repeats)-mediated knock-in mouse model hosting the Prdm16 ^Q187X allele was generated and subjected to ECG, histological, and transcriptional analysis. RESULTS: We report 2 probands with loss-of-function PRDM16 variants and pediatric left ventricular noncompaction cardiomyopathy. One proband hosts a PRDM16-Q187X variant with left ventricular noncompaction cardiomyopathy and demonstrated infant-onset heart failure, which was selected for further study. Induced pluripotent stem cell-derived cardiomyocytes prepared from the PRDM16-Q187X proband demonstrated a statistically significant impairment in myocyte proliferation and increased apoptosis associated with transcriptional dysregulation of genes implicated in cardiac maturation, including TGF-β–associated transcripts. Homozygous Prdm16 ^Q187X/Q187X mice demonstrated an underdeveloped compact myocardium and were embryonically lethal. Heterozygous Prdm16 ^Q187X/WT mice demonstrated significantly smaller ventricular dimensions, heightened fibrosis, and age-dependent loss of TGF-β expression. Mechanistic studies were undertaken in H9c2 cardiomyoblasts to show that PRDM16 binds TGFB3 promoter and represses its transcription. CONCLUSIONS: Novel loss-of-function PRDM16 variant impairs myocardial development resulting in noncompaction cardiomyopathy in humans and mice associated with altered TGF-β signaling.

We reviewed our single institutional experience with pediatric ventricular assist device (VAD) support over the last 2 decades, with an aim to improve our current management and gain an insight into the future direction. A retrospective review was conducted on all patients that had undergone VAD support between 1996 and 2017. Outcomes were analyzed based on the type of VADs, whether temporary or durable devices. Primary end points were positive outcomes, including bridge-to-transplantation, bridge-to-recovery, alive on device, and bridge-to-bridge to another VAD, or negative outcomes, including death during VAD support or in-hospital death after bridge-to-recovery. The Pediatric Interagency Registry for Mechanical Circulatory Support definition was used to classify adverse events. Overall, 201 VADs were implanted in 159 patients, with 82 (41%) and 119 (59%) being temporary and durable support, respectively. There has been a trend toward an increasing annual implant volume both with temporary and durable VADs. Positive outcomes were achieved in 80% (66 of 82) of those with temporary support, with bridge-to-recovery (53% [35 of 66]) and bridge-to-bridge to another VAD (38% [25 of 66]) being the predominant outcomes. Of those on durable support, 84% (100 of 119) achieved positive outcomes, with bridge-to-transplant (66% [78 of 119]) being the leading destination. The most notable change during the study period was the introduction of implantable continuous-flow VADs, resulting in outpatient management becoming a routine practice. No patients were discharged on VAD support before 2004, but 85% were discharged on VADs with discharge capability after 2013. The present study has demonstrated the evolutional changes of pediatric VAD support and their effect on clinical outcomes over the last 2 decades.

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.

Data are limited regarding body mass index (BMI) in pediatric patients supported by ventricular assist devices (VAD) and associated clinical outcomes and complications. We performed a retrospective single-center cohort study including patients aged ≤21 years on durable continuous-flow VAD support for ≥30 days from 2009 to 2020. Patients were classified based on BMI percentile at implant using the US Centers for Disease Control and Prevention criteria: underweight (<5th percentile), healthy weight (5th–<85th percentile, reference group), overweight (85th–<95th percentile), and obese (≥95th percentile). Primary outcomes were hospital mortality and length of stay (LOS) after implant. Secondary outcomes included infectious complications and pump thrombosis. Seventy-two patients (58 HeartWare, 13 HeartMateII, 1 HeartMate3) were included. At implant, the study cohort comprised 13% underweight, 53% healthy weight, 18% overweight, and 17% obese. BMI increased across all categories during support, with 29% gaining BMI categories. No patients with obesity reduced their BMI category. At explant, the study cohort comprised 1% underweight, 54% healthy weight, 22% overweight, and 22% obese. There was no significant difference in hospital mortality, postoperative LOS, or pump thrombosis. Patients who were overweight had more frequent non-VAD infections. Patients with obesity required longer duration on VAD support and were less likely to be transplanted. We concluded that pediatric patients on VAD support who are overweight or have obesity do not improve their BMI and instead have significant increase. Larger studies are needed to assess the impact of abnormal BMI on VAD complications in pediatric patients.