Safety and feasibility of adjunct autologous cord blood stem cell therapy during the Norwood heart operation.

BACKGROUND: We conducted this phase I, open-label safety and feasibility trial of autologous cord blood (CB) stem cell (CBSC) therapy via a novel blood cardioplegia-based intracoronary infusion technique during the Norwood procedure in neonates with an antenatal diagnosis of hypoplastic left heart syndrome (HLHS). CBSC therapy may support early cardiac remodeling with enhancement of right ventricle (RV) function during the critical interstage period. METHODS: Clinical grade CB mononucleated cells (CBMNCs) were processed to NetCord-FACT International Standards. To maximize yield, CBSCs were not isolated from CBMNCs. CBMNCs were stored at 4 °C (no cryopreservation) for use within 3 days and delivered after each cardioplegia dose (4 × 15 mL). RESULTS: Of 16 patients with antenatal diagnosis, 13 were recruited; of these 13 patients, 3 were not treated due to placental abruption (n = 1) or conditions delaying the Norwood for >4 days (n = 2) and 10 received 644.9 ± 134 × 106 CBMNCs, representing 1.5 ± 1.1 × 106 (CD34+) CBSCs. Interstage mortality was 30% (n = 3; on days 7, 25, and 62). None of the 36 serious adverse events (53% linked to 3 deaths) were related to CBMNC therapy. Cardiac magnetic resonance imaging before stage 2 (n = 5) found an RV mass index comparable to that in an exact-matched historical cohort (n = 22), with a mean RV ejection fraction of 66.2 ± 4.5% and mean indexed stroke volume of 47.4 ± 6.2 mL/m2 versus 53.5 ± 11.6% and 37.2 ± 10.3 mL/m2, respectively. All 7 survivors completed stage 2 and are alive with normal RV function (6 with ≤mild and 1 with moderate tricuspid regurgitation). CONCLUSIONS: This trial demonstrated that autologous CBMNCs delivered in large numbers without prior cryopreservation via a novel intracoronary infusion technique at cardioplegic arrest during Norwood palliation on days 2 to 3 of life is feasible and safe.

Acute rheumatic fever and rheumatic heart disease in children and adolescents in Victoria, Australia.

AIM: To describe the epidemiology and clinical profile of children and adolescents with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in Victoria, Australia. METHODS: A retrospective audit was undertaken of children and adolescents with ARF and RHD attending the Royal Children's and Monash Children's Hospitals in Victoria, Australia between 2010 and 2019. Potential cases were identified by searching multiple sources for relevant ICD-10-AM codes and keywords, then reviewed manually. For confirmed cases, we collected data on patient demographics, clinical features, comorbidities and management. RESULTS: Of 179 participants included, there were 108 Victorian residents and 71 non-Victorian residents. 126 had at least one episode of ARF during the study period and 128 were diagnosed with RHD. In the Victorian resident group, the overall incidence of ARF was 0.8 per 100 000 5-14 year olds. This incidence was higher in Victorian Aboriginal and/or Torres Strait Islander (3.8 per 100 000) and Pacific Islander (32.1 per 100 000) sub-populations. Of 83 Victorian residents who had an ARF episode, 11 (13%) had a recurrence. Most Victorian residents with RHD had mixed aortic and mitral valve pathology (69.4%) and moderate to severe disease (61.9%). Most non-Victorian residents were Aboriginal and/or Torres Strait Islander people (80.3%) and were commonly transferred for tertiary or surgical management of RHD (83.1%). CONCLUSIONS: ARF and RHD continue to affect the health of significant numbers of children and adolescents living in Victoria, including severe and recurrent disease. Specialised services and a register-based control program may help to prevent complications and premature death.

In utero fetal left ventricular rupture and pseudoaneurysm formation: a case report.

BACKGROUND: Cardiac ventricular aneurysms affect 1 in 200,000 live births. To the best of our knowledge, no reported cases of a left ventricular pseudoaneurym and in utero rupture exist to guide optimal management. CASE PRESENTATION: We present a case of fetal left ventricular rupture with a large pericardial effusion, cardiac tamponade and subsequent pseudoaneurysm formation with concerns for a poor prognosis. Interventional drainage of the pericardial effusion led to resolution of tamponade and significant improvement in fetal condition. A multidisciplinary team was utilised to plan birth to minimise risk of pseudoaneurysmal rupture and a catastrophic bleed at birth. CONCLUSION: For similar cases we recommend consideration of birth by caesarean section, delayed cord clamping and a prostaglandin E1 infusion, to reduce the systemic pressures on the left ventricle during transition from fetal to neonatal circulations, until definitive surgical repair. In this case, this resulted in a successful outcome.

Berlin Heart EXCOR Support in the First Year of Life: A Single Centre Experience.

BACKGROUND: Berlin Heart EXCOR Pediatric Ventricular Assist Device (BHE) (Berlin Heart AG, Berlin, Germany, BHE) is used worldwide for mechanical circulatory support as a bridge to transplantation or recovery for children with end-stage heart failure. The study aim was to evaluate morbidity and mortality of children less than one year old supported with BHE to identify predictors of adverse outcomes. METHODS: Data of all children aged less than one year supported with BHE between 2005 and 2018 at the Royal Children's Hospital, Melbourne were reviewed. Adverse events were defined using PediMACS criteria. RESULTS: Fourteen (14) children under 1 year of age were implanted with BHE at a median age and weight of 0.37 years (IQR 0.09-0.7) and 5.7 kg (IQR 3.5-7.95) respectively. Four (4) patients were neonates, and 10 were older infants. Twelve (12) patients had cardiomyopathy and two, myocarditis. Preoperative extracorporeal membrane oxygenation (ECMO) support was required in six patients for a mean of 9 days (IQR 6-13). Sepsis occurred in five patients (36%) and thromboembolic stroke in two patients (14%). Survival to bridge to transplantation (11) and recovery (1) was achieved in 12 patients (86%). Mortality was 14%. The median duration of BHE support was 110 days (IQR 40-161). Both patients who died were neonates with myocarditis and required surgical re-intervention during BHE support. CONCLUSIONS: BHE provides excellent support as a bridge to transplantation or recovery in infants, with a low incidence of neurological dysfunction. Neonates with myocarditis may be at greater risk for death after BHE implantation.

Improving transport time for babies with antenatally diagnosed transposition of the great arteries reduces the need for ECMO.

OBJECTIVE: To assess the effect of reducing retrieval team response time on the outcomes of babies born outside a cardiac centre (outborn) with antenatally diagnosed transposition of the great arteries. STUDY DESIGN: Retrospective cohort study of all outborn babies with antenatally diagnosed TGA anticipated to require transfer for urgent balloon atrial septostomy over a 6-year period (15 babies pre intervention and 27 post intervention). The intervention involved a collaborative multicomponent practice change aiming to reduce retrieval team response time. RESULT: The mean (SD) time from birth to cardiac ICU arrival was 159 (12) min pre intervention and 103 (6) min post intervention (mean difference -57 min [95% CI, -81 to -32]). There was a significant decrease in need for extracorporeal membrane oxygenation (33% versus 4%), RR 0.11 [95% CI, 0.02-0.65]), with a number needed to treat of 3.4 to prevent one ECMO episode. CONCLUSION: Reducing retrieval time is achievable with collaborative systems, and significantly improves clinical outcomes.

Does fluid bolus therapy increase blood pressure in children with sepsis?

OBJECTIVE: To describe the effect of fluid bolus therapy (FBT) on blood pressure in children with sepsis. Secondary outcomes included the effect of FBT on systemic vascular resistance, shock index and shock phenotype (warm or cold). METHODS: This was a prospective observational study in the ED of The Royal Children's Hospital, Melbourne, Australia. Participants were children meeting international consensus criteria for sepsis who received FBT for tachycardia or hypotension. FBT was defined as 10-20 mL/kg of 0.9% saline. Mean blood pressure (MBP) was recorded at baseline, 5 and 60 min after FBT. Total systemic vascular resistance index (TSVRi), shock index, and shock phenotype were derived for each time point. Hypotension was defined as MBP <55 + 1.5 × age (years). Warm shock was defined as TSVRi <800 dyne s/cm5 /m2 . RESULTS: Fifty fluid boluses were recorded in 41 children. Median MBP was 78 mmHg (interquartile range [IQR] 63-86) at baseline, 72 mmHg (IQR 60-82) at 5 min, and 75 mmHg (IQR 66-84) at 60 min. Hypotension was observed in 16% at baseline, 26% at 5 min and 17% at 60 min. Median TSVRi was 1580 dyne s/cm5 /m2 (IQR 1242-2206) at baseline, 1254 dyne s/cm5 /m2 (IQR 1027-1787) at 5 min, and 1850 dyne s/cm5 /m2 (IQR 1265-2140) at 60 min. Median shock index was 1.60 (IQR 1.34-1.90) at baseline, 1.49 (IQR 1.25-1.76) at 5 min and 1.37 (IQR 1.22-1.61) at 60 min. Two percent of cases had warm shock at baseline, 12% at 5 min and 2% at 60 min. CONCLUSIONS: MBP initially decreased following FBT for paediatric sepsis, returning towards baseline over the subsequent 60 min. The utility of FBT for increasing MBP and its effect on patient-centred outcomes in children with sepsis warrants further exploration.

Bleeding and thrombotic events occur early in children on durable ventricular assist devices.

INTRODUCTION: Durable Ventricular Assist Devices (VADs) are increasingly used in children with end-stage heart failure. Major complications are bleeding and thromboembolism (TE). Our objective was to determine the timing, incidence and risk factors for bleeding and TE in children implanted with VADs. METHODS: This was a retrospective cohort of 8 years experience for children implanted with HeartWare HVAD and Berlin Heart EXCOR VADs at the Royal Children's Hospital, Melbourne. RESULTS: 44 patients were implanted with Berlin Heart EXCOR or HeartWare HVAD devices. Major bleeding occurred in 17 patients (39%), 7 (16%) experienced thromboembolic strokes, 13 (30%) required device exchange for TE, and 4 (9%) experienced arterial thromboembolism. Twenty-seven patients (61%) were transplanted, three (7%) recovered, and six (14%) remain on device when censored. Eight patients (18%) died on VAD, with leading causes being thromboembolic stroke and intracranial bleeding. The majority of bleeding events and thromboembolic events occurred while patients were on unfractionated heparin (bleeding 66%, TE 40.5%) or transitioning between heparin and warfarin (bleeding 22%, TE 38%). Majority of patients were on more than one antiplatelet agent at the time of a major bleeding (87%) or thromboembolic (89%) event. CONCLUSIONS: The majority of bleeding and TE events occurring in children supported with durable VADs occur when they are on unfractionated heparin or transitioning to warfarin. Modifications to anticoagulation and monitoring in the early post-operative periods should be a research focus.

Cardiac Index Changes With Fluid Bolus Therapy in Children With Sepsis-An Observational Study.

OBJECTIVES: Fluid bolus therapy is the initial recommended treatment for acute circulatory failure in sepsis, yet it is unknown whether this has the intended effect of increasing cardiac index. We aimed to describe the effect of fluid bolus therapy on cardiac index in children with sepsis. DESIGN: A prospective observational cohort study. SETTING: The Emergency Department of The Royal Children's Hospital, Melbourne, VIC, Australia. PATIENTS: A convenience sample of children meeting international consensus criteria for sepsis with acute circulatory failure. INTERVENTION: Treating clinician decision to administer fluid bolus therapy. MEASUREMENTS AND MAIN RESULTS: Transthoracic echocardiography was recorded immediately before, 5 minutes after, and 60 minutes after fluid bolus therapy. Cardiac index was calculated by a pediatric cardiologist blinded to the timing of the echocardiogram. Cardiac index was calculated for 49 fluid boluses in 41 children. The median change in cardiac index 5 minutes after a fluid bolus therapy was +18.0% (interquartile range, 8.6-28.1%) and after 60 minutes was -6.0% (interquartile range, -15.2% to 3.0%) relative to baseline. Thirty-one of 49 fluid boluses (63%) resulted in an increase in cardiac index of greater than 10% at 5 minutes, and these participants were considered fluid responsive. This was sustained in four of 31 (14%) at 60 minutes. No association between change in cardiac index at 5 or 60 minutes and age, baseline mean arterial blood pressure, fluid bolus volume, and prior volume of fluid bolus therapy was found on linear regression. CONCLUSIONS: Fluid bolus therapy for pediatric sepsis is associated with a transient increase in cardiac index. Fluid responsiveness is variable and, when present, not sustained. The efficacy of fluid bolus therapy for achieving a sustained increase in cardiac index in children with sepsis is limited.

Does respiratory variation of inferior vena cava diameter predict fluid responsiveness in spontaneously ventilating children with sepsis.

OBJECTIVE: The intent of fluid bolus therapy (FBT) is to increase cardiac output and tissue perfusion, yet only 50% of septic children are fluid responsive. We evaluated respiratory variation of inferior vena cava (IVC) diameter as a predictor of fluid responsiveness. METHODS: A prospective observational study in the ED of The Royal Children's Hospital, Melbourne, Australia. Patients were spontaneously ventilating children treated with FBT for sepsis-induced acute circulatory failure. IVC ultrasound was performed prior to FBT. Trans-thoracic echocardiography was performed prior to, 5 and 60 min after FBT. IVC collapsibility index and stroke distance were calculated by a blinded Paediatric Emergency Physician and blinded Paediatric Cardiologist, respectively. RESULTS: Thirty-nine fluid boluses were recorded in 33 children, 28/39 (72%) of which met criteria for fluid responsiveness at 5 min, which was sustained in 2/28 (7%) of initial fluid responders at 60 min. Sensitivity and specificity (95% confidence interval) of IVC collapsibility index were 0.44 (0.25-0.65) and 0.33 (0.10-0.65) with an area under the receiver operator characteristics curve (95% confidence interval) of 0.38 (0.23-0.55) at 5 min. Test characteristics 60 min after fluid bolus administration were not meaningful because of the infrequency of sustained fluid responsiveness in this patient group. There was no significant correlation between IVC collapsibility and fluid responsiveness at 5 or 60 min. CONCLUSIONS: IVC collapsibility has poor test characteristics for predicting fluid responsiveness in spontaneously ventilating children with sepsis.

Surgical Management of Extensive Perinatal Myocardial Infarction.

Extensive perinatal myocardial infarction caused by coronary artery thrombosis is extremely rare and has a dismal prognosis. We report a 3.5-kg neonate who presented at birth with an extensive myocardial infarction caused by aortic root and left main coronary artery thrombus after an emergency cesarean section. We performed emergency surgical thrombectomy and insertion of extracorporeal membrane oxygenation support. After subsequent conversion to long-term left ventricular assist device with an EXCOR device (Berlin Heart, Berlin, Germany), the patient had no ventricular recovery after 163 days of support. He was successfully bridged to transplantation.

Transcatheter closure of the patent ductus arteriosus: an intention to treat analysis.

BACKGROUND: In patients with patent ductus arteriosus (PDA), transcatheter closure is the current procedure of choice. There are multiple devices available with limited current comparative data and varied recommendations for device selection. OBJECTIVE: To assess the efficacy and safety of the Flipper coil (FC) and the Amplatzer Duct Occluder (ADO). METHODS: An intention to treat analysis of all children admitted to the catheter laboratory at a single institution for occlusion of PDA from 2003 to 2011 was performed. Patient and device selection were determined by the treating physician. Standard techniques for FC and ADO implantation were used. RESULTS: Two hundred and twenty eight children with median weight of 14.2 kg (range; 5.5-68 kg) underwent cardiac catheterisation, with successful occlusion in 96.2% of patients when attempted. In 16 patients, median angiographic PDA diameter of 0.8 mm (range; 0.4-1.2 mm), was considered too small to warrant closure. Eight patients with large PDA's underwent surgical ligation. FC was successfully used in 70 (34.3%) and ADO in 134 (66.7%) patients. ADO patients were smaller (P=0.004) with larger PDA's (P<0.0001) than the FC group. Median fluoroscopy time was longer for ADO patients (10.1 min vs 8.0 min; P<0.0001). ADO had a lower embolisation rate (0% vs 6.6%; P=0.005) and a higher complete occlusion rate at follow-up (100% vs 73.4%; P<0.0001). Length of hospital admission decreased with time in both groups. CONCLUSION: Transcatheter closure of the PDA has a high degree of safety and efficacy. This study suggests that the ADO may be the device of first choice in the current era.

Isolated innominate artery as a cause of subclavian steal and cerebral hemisphere atrophy.

A rare case of isolated innominate artery arising from a left persistent arterial duct with a right aortic arch is presented. Of interest in this case is the retrograde flow in the left carotid system, the history of developmental delay, and the magnetic resonance image (MRI) brain findings suggestive of asymmetric volume loss affecting the left cerebral hemisphere. The authors postulate a possible mechanism of subclavian steal.

Reconfiguration of the Amplatzer Vascular Plug II 5 months after occlusion of venovenous collateral in a bidirectional cavopulmonary circulation.

Venovenous anomalous vessels are a common complication seen in the bidirectional cavopulmonary circulation. In this report, we describe the use of the Amplatzer Vascular Plug II and subsequent demonstration of nitinol device memory with significant device reconfiguration at 5 months follow-up.