Case Report: Sustained ventricular arrhythmia in a child supported by a Berlin heart EXCOR ventricular assist device.

Mechanical circulatory support is an established therapy to support failing hearts as a bridge to transplantation. Although tolerated overall, arrhythmias may occur after ventricular assist device implantation and can complicate patient management. We report on an infant with dilated cardiomyopathy who developed ventricular tachycardia followed by recalcitrant ventricular fibrillation, refractory to comprehensive medical therapy post Berlin Heart EXCOR® (BHE) implant.

After the storm: Extracorporeal membrane oxygenation after hemicraniectomy in a child.

Ventricular arrhythmias following neurological injury have been attributed to sympathetic surge in subarachnoid hemorrhage and traumatic brain injury. Despite associated risks of bleeding and thrombosis, veno-arterial extracorporeal membrane oxygenation (ECMO) in critically ill, clinically unstable postoperative neurosurgical patients can be lifesaving. In the context of neurological injury and the neurosurgical population, the literature available regarding ECMO utilization is limited, especially in children. We report a case of successful ECMO utilization in a child with malignant ventricular tachycardia after decompressive craniectomy for refractory intracranial hypertension following evacuation of extensive subdural empyema.

Palliative Care Across the Life Span for Children With Heart Disease: A Scientific Statement From the American Heart Association.

AIM: This summary from the American Heart Association provides guidance for the provision of primary and subspecialty palliative care in pediatric congenital and acquired heart disease. METHODS: A comprehensive literature search was conducted from January 2010 to December 2021. Seminal articles published before January 2010 were also included in the review. Human subject studies and systematic reviews published in English in PubMed, ClinicalTrials.gov, and the Cochrane Collaboration were included. Structure: Although survival for pediatric congenital and acquired heart disease has tremendously improved in recent decades, morbidity and mortality risks remain for a subset of young people with heart disease, necessitating a role for palliative care. This scientific statement provides an evidence-based approach to the provision of primary and specialty palliative care for children with heart disease. Primary and specialty palliative care specific to pediatric heart disease is defined, and triggers for palliative care are outlined. Palliative care training in pediatric cardiology; diversity, equity, and inclusion considerations; and future research directions are discussed.

Patient and parent-reported outcomes in paediatric ventricular assist device support: a multi-center ACTION learning network feasibility and pilot experience.

BACKGROUND: Patient- and proxy-reported outcomes (PROs) are an important indicator of healthcare quality and can be used to inform treatment. Despite the widescale use of PROs in adult cardiology, they are underutilised in paediatric cardiac care. This study describes a six-center feasibility and pilot experience implementing PROs in the paediatric and young adult ventricular assist device population. METHODS: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative learning network comprised of 55 centres focused on improving clinical outcomes and the patient/family experience for children with heart failure and those supported by ventricular assist devices. The development of ACTION's PRO programme via engagement with patient and parent stakeholders is described. Pilot feasibility, patient/parent and clinician feedback, and initial PRO findings of patients and families receiving paediatric ventricular assist support across six centres are detailed. RESULTS: Thirty of the thirty-five eligible patients (85.7%) were enrolled in the PRO programme during the pilot study period. Clinicians and participating patients/parents reported positive experiences with the PRO pilot programme. The most common symptoms reported by patients/parents in the first month post-implant period included limitations in activities, dressing change distress, and post-operative pain. Poor sleep, dressing change distress, sadness, and fatigue were the most common symptoms endorsed >30 days post-implant. Parental sadness and worry were notable throughout the entirety of the post-implant experience. CONCLUSIONS: This multi-center ACTION learning network-based PRO programme demonstrated initial success in this six-center pilot study experience and yields important next steps for larger-scale PRO collection, research, and clinical intervention.

A Randomized Trial of an Exclusive Human Milk Diet in Neonates with Single Ventricle Physiology.

OBJECTIVE: To determine whether weight gain velocity (g/kg/day) 30 days after the initiation of feeds after cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet. STUDY DESIGN: In this multicenter, randomized, single blinded, controlled trial, term neonates 7 days of age or younger with single ventricle physiology and anticipated cardiac surgical palliation within 30 days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30 days after feeds were started postoperatively, infants in the intervention group received human milk fortified once enteral intake reached 60 mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100 mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed. RESULTS: We enrolled 107 neonates (exclusive human milk = 55, control = 52). Baseline demographics and characteristics were similar between the groups. The median weight gain velocity at study completion was higher in exclusive human milk vs control group (12 g/day [IQR, 5-18 g/day] vs 8 g/day [IQR, 0.4-14 g/day], respectively; P = .03). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively; P = .04). The incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between the groups. CONCLUSIONS: Neonates with single ventricle physiology have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet after stage 1 surgical palliation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (www. CLINICALTRIALS: gov, Trial ID: NCT02860702).

Finishing Well: Compassionate Extracorporeal Membrane Oxygenation Discontinuation.

Extracorporeal Membrane Oxygenation (ECMO) is associated with significant mortality. Provision of high-quality end-of-life (EOL) care for patients supported on ECMO entails specific physiological, pharmacological, and technical considerations. Limited guidance exists for clinicians on delivery of optimal EOL care on ECMO. In this article, we review the unique aspects of EOL care as they apply to ECMO support and propose a pragmatic, interdisciplinary framework for compassionate ECMO discontinuation in children and adults. The goal of compassionate ECMO discontinuation (CED) is to allow natural death from the underlying disease process while delivering high-quality EOL care to ensure a good death experience for patients and their families. The CED approach includes: 1) a family meeting to define goal-concordant EOL care and prepare families and patients for the dying process; 2) clinical preparation, including symptom management and discontinuation of other life-sustaining therapies; 3) technical aspects which necessarily vary according to patient factors and the circuit and cannulation strategy; and 4) bereavement support. The proposed CED considerations and checklist may serve as tools aiding provision of comprehensive, quality, individualized patient- and family-centered care for children and adults dying despite ECMO support. A structured CED may enhance EOL experiences for patients, family, and staff by providing a respectful and dignified death experience. Future research is required to determine feasibility and effectiveness of the framework, which must be adapted to the patient and institutional setting.

Pulsatile ventricular assist device as a bridge to transplant for the early high-risk single-ventricle physiology.

BACKGROUND: The use of ventricular assist devices (VADs) as a bridge-to-transplant in patients with single-ventricle physiology post-stage one palliation has been associated with poor outcomes. We describe our center's successful experience in the use of paracorporeal pulsatile VADs in the palliation of high-risk single ventricle physiology before or after the first stage of palliation with an impetus on pre-palliation implant. METHODS: This is a single-center retrospective review of univentricular patients implanted with the Berlin Heart EXCOR VAD. Our center's approach includes early implantation of the Berlin Heart EXCOR with common atrial cannulation, a cardiac index between 3.5 and 5 L/min/m2, and a bivalirudin-based anticoagulation regimen. Patient-related data were collected postimplant at week 1 and months 1, 2, and 3. Post-transplant data, including neurological outcomes, were collected. RESULTS: Nine patients were supported. Survival to discharge post-transplant was 83% (5/6) in patients bridged-to-transplant and 33% (1/3) in patients bridged-to-decision. Six patients had no previous palliation. Median hospital stay before implantation was 111 days for nonsurvivors versus 20 days for survivors. The need for extracorporeal membrane oxygenation and cardiopulmonary resuscitation in nonsurvivors versus survivors was 1 in 3 versus 1 in 6 and 2 in 3 versus 1 in 6, respectively. There were no major central nervous system complications except for 1 significant hemorrhagic event. The pediatric overall performance category score on follow-up was normal to mild disability in 83% of survivors. Limitations include hemolysis and intermittent periods of infection and/or inflammation. CONCLUSIONS: The use of pulsatile paracorporeal VADs is a feasible option as a bridge-to-transplant in the peri-stage one high-risk single ventricle.

Berlin Heart EXCOR and ACTION post-approval surveillance study report.

BACKGROUND: The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS: ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS: Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group. CONCLUSIONS: The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

Bivalirudin May Reduce the Need for Red Blood Cell Transfusion in Pediatric Cardiac Patients on Extracorporeal Membrane Oxygenation.

We retrospectively compared anticoagulation with heparin and bivalirudin for 32 consecutive children under 18 years old during extracorporeal membrane oxygenation (ECMO) in our pediatric cardiac intensive care unit (PCICU). Between September 2015 and January 2018, 14 patients received heparin, 13 venoarterial (VA), and 1 venovenous (VV). From February 2018 to September 2019, 18 received bivalirudin (all VA). The mean (standard deviation [SD]) percentage of time with therapeutic activated partial thromboplastin time and activated clotting time was bivalirudin 54 (14%) and heparin 57 (11%), p = 0.4647, and percentage of time supratherapeutic was bivalirudin 18 (10%) and heparin 27 (12%), p = 0.0238. Phlebotomy-associated blood loss per hour of ECMO was double in the heparin compared with bivalirudin group 1.08 ml/h (0.20 ml/h), compared with 0.51 ml/h (0.07 ml/h), p = 0.0003, as well as interventions to control bleeding. Packed red blood cell (PRBC) transfusions significantly correlated with higher blood loss in the heparin group (Pearson correlation coefficient = 0.49, p = 0.0047). Overall amount of blood product utilization was not different between the groups. Survival to ECMO decannulation was 89% for bivalirudin and 57% for heparin, p = 0.0396, although 6 month survival was not significantly different (67% versus 57%, p = 0.5809). Heparin may increase the need for PRBC transfusions and strategies to attenuate bleeding when compared with bivalirudin for children receiving ECMO in PCICU.

Bivalirudin and Alteplase for Pulmonary Embolism Requiring Veno-Arterial Extracorporeal Membrane Oxygenation in an Adolescent.

Saddle pulmonary embolism (PE) remains a challenge to diagnose and manage in pediatric patients. Current literature encourages early consideration of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in high-risk PE patients with impending right ventricular failure. We present a 17-year-old patient who was admitted to a pediatric cardiac intensive care unit with saddle PE requiring emergent VA-ECMO support because of cardiovascular collapse. Despite anticoagulation with bivalirudin and receiving systemic thrombolysis with alteplase, the clot burden was persistent with minimal improvement in right ventricular function. We proceeded to catheter thrombolysis while on VA-ECMO. This ultimately led to a successful resolution of the PE and allowed for weaning off VA-ECMO. PE is rare in children compared with adults, and pediatricians may be unaware of therapies becoming increasingly used in adults such as the use of VA-ECMO, with systemic and local thrombolysis. The concurrent use of a direct thrombin inhibitor for ECMO anticoagulation alongside the thrombolysis is a novel combination in this condition and age-group.

Utilization and Outcomes of Children Treated with Direct Thrombin Inhibitors on Paracorporeal Ventricular Assist Device Support.

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged <19 years) treated with a DTI (bivalirudin or argatroban) on paracorporeal VAD support, examining bleeding and thrombotic adverse events. From May 2012 to 2018, 43 children (21 females) at 10 centers in North America, median age 9.5 months (0.1-215 months) weighing 8.6 kg (2.8-150 kg), were implanted with paracorporeal VADs and treated with a DTI. Diagnoses included cardiomyopathy 40% (n = 17), congenital heart disease 37% (n = 16; single ventricle n = 5), graft vasculopathy 9% (n = 4), and other 14% (n = 6). First device implanted included Berlin Heart EXCOR 49% (n = 21), paracorporeal continuous flow device 44% (n = 19), and combination of devices in 7% (n = 3). Adverse events on DTI therapy included; major bleeding in 16% (n = 7) (2.6 events per 1,000 patient days of support on DTI), and stroke 12% (n = 5) (1.7 events per 1,000 patient days of support on DTI). Overall survival to transplantation (n = 30) or explantation (n = 8) was 88%. This is the largest multicenter experience of DTI use for anticoagulation therapy in pediatric VAD support. Outcomes are encouraging with lower major bleeding and stroke event rate than that reported in literature using other anticoagulation agents in pediatric VAD support.

Sub-acute neonatal hemochromatosis in an infant with hypoplastic left heart syndrome on ventricular assist device awaiting transplantation.

Single-ventricle pediatric patients, amongst other children waiting for OHT, are a vulnerable population, especially if candidacy is established before any palliation. NH is a rare disease with poor prognosis in the post-natal period. We present a case of sub-acute NH diagnosed in an infant with HLHS who was listed for OHT while bridged with a pulsatile paracorporeal VAD, with an emphasis on the evolution of the condition throughout the patient's clinical course and the ultimate decision for compassionate deactivation of VAD.

Outcomes of children supported with an intracorporeal continuous-flow left ventricular assist system.

BACKGROUND: Since 2012, there has been growing use of the HeartWare (Medtronic, Mounds View, MN) intracorporeal continuous flow (CF) ventricular assist device (VAD) in children, despite it not being labeled for use in pediatric patients. We sought to describe the use and outcomes of children with HeartWare VADs. METHODS: We identified all patients aged < 19 years and young adults aged 19 to 30 years supported with HeartWare who were entered into the pediatric portion (Pedimacs) of the Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) and the Intermacs registries, respectively, between September 2012 and June 2017. Adverse events and outcomes were analyzed and compared. RESULTS: We identified 192 children and 247 young adult HeartWare patients. Baseline characteristics of children differed from young adults, with lower median weight of 51.5 kg (range, 13.1-162) vs 75.8 kg (range, 29.8-191; p ≤ 0.0001) and body surface area of 1.5 m2 (range, 0.6-2.9 m2) vs 1.9 m2 (range, 1.1-3.2 m2; p ≤ 0.0001) . At the time of implant, 12 children weighed < 20 kg, and 58.3% of these children had congenital heart disease compared with 11.7% in children who weighed ≥ 20 kg and 6.1% in young adults (p ≤ 0.0001). Median duration of support was 2.8 months (IQR, 1.3-6.0 months) in children and 9.7 months (IQR 4.0-19.2 months) in young adults (p ≤ 0.0001). Serious adverse events in children and young adults included infection in 27% and 44% of patients, respectively (p=0.0002), major bleeding in 23% and 23%, respectively (p = 0.9), device malfunction/pump thrombosis in 11% and 19.0%, respectively (p = 0.04), and stroke in 10% and 12%, respectively (p = 0.5). Of the children who weighed < 20 kg at time of implant, 0% had major bleeding, 16.7% had infections, and 8.3% had stroke. Overall survival was not statistically different between children and young adults, and there was no increased mortality in children who weighed < 20 kg. Rate of discharge on HeartWare was 80% in young adults vs 48% in children who weighed ≥ 20 kg and only 33% in children who weighed < 20 kg. CONCLUSIONS: Survival in children supported with HeartWare is encouraging and comparable to young adults; however, adverse events are not uncommon in children. Ongoing evaluation of the HeartWare use in children is necessary to further decrease the rate of adverse events and understand obstacles to discharge.

Exogenous hydrogen sulfide (H2S) protects alveolar growth in experimental O2-induced neonatal lung injury.

BACKGROUND: Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT). Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S), carbon monoxide and nitric oxide (NO), belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD. METHODS: We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) to study its lung protective potential in vitro and in vivo. RESULTS: In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation. CONCLUSIONS: H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.

Effect of additives on the compressive strength and setting time of a Portland cement.

Improvements in strength and setting time of Portland cements (PC) are needed to enhance their performance as endodontic and load bearing materials. This study sought to enhance the compressive strength and setting time of a PC by adding one of the following additives: 20% and 30% poly-methylmethacrylate (PMMA), 20% and 30% irregular and spherical amalgam alloys, and 10% CaCl(2). The control consisted of unreinforced PC specimens. Setting time was determined using a Gillmore apparatus according to standardized methods while compressive strength was measured using a universal testing machine after 21 hours or 60 days of water storage. Data were analyzed by ANOVA, Tukey and Games-Howell tests (alpha = 5%). All additives significantly decreased both initial and final setting times as compared with the PC-control (p < .05). 30% PMMA and 30% irregular alloy had the lowest values of initial setting time. 30% irregular alloy also produced the lowest values of final setting time while 30% spherical alloy yielded the highest (p < .05). No differences were detected between the compressive strength values of 21 hours and 60 days. While 10% CaCl(2), 20% and 30% PMMA produced values significantly lower than the PC-control, 30% spherical alloy significantly improved the compressive strength of the reinforced PC (p < .05). In summary, all additives significantly reduced the setting time and 30% spherical amalgam alloy yielded a significant increase in compressive strength for the tested PC, which might represent an improved composition for PCs to expand their use as endodontic and potentially load bearing materials.

Effect of additives on the compressive strength and setting time of a Portland cement

Improvements in strength and setting time of Portland cements (PC) are needed to enhance their performance as endodontic and load bearing materials. This study sought to enhance the compressive strength and setting time of a PC by adding one of the following additives: 20 percent and 30 percent poly-methylmethacrylate (PMMA), 20 percent and 30 percent irregular and spherical amalgam alloys, and 10 percent CaCl2. The control consisted of unreinforced PC specimens. Setting time was determined using a Gillmore apparatus according to standardized methods while compressive strength was measured using a universal testing machine after 21 hours or 60 days of water storage. Data were analyzed by ANOVA, Tukey and Games-Howell tests (á = 5 percent). All additives significantly decreased both initial and final setting times as compared with the PC-control (p < .05). 30 percent PMMA and 30 percent irregular alloy had the lowest values of initial setting time. 30 percent irregular alloy also produced the lowest values of final setting time while 30 percent spherical alloy yielded the highest (p < .05). No differences were detected between the compressive strength values of 21 hours and 60 days. While 10 percent CaCl2, 20 percent and 30 percent PMMA produced values significantly lower than the PC-control, 30 percent spherical alloy significantly improved the compressive strength of the reinforced PC (p < .05). In summary, all additives significantly reduced the setting time and 30 percent spherical amalgam alloy yielded a significant increase in compressive strength for the tested PC, which might represent an improved composition for PCs to expand their use as endodontic and potentially load bearing materials.

Cuidados em UTI com o potencial doador de múltiplos órgãos / Care in intensive care units with the potential tissue donors

O maior contingente de órgãos para transplantes provém de doadores cadavéricos, definidos por critérios de morte encefálica (ME). Os autores fazem uma revisão bibliográfica sobre as alterações fisiológicas que ocorrem em pacientes em ME, bem como o manejo clínico e cuidados gerais necessários para obter o maior número, com a melhor qualidade, de enxertos