An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Survival-to-Hospital Discharge in Neonates With Congenital Heart Disease Supported With Prolonged Extracorporeal Membrane Oxygenation.

Factors that determine early outcomes in neonates with congenital heart disease (CHD) supported with prolonged venoarterial extracorporeal membrane oxygenation (ECMO) are not known and contemporary multicenter data are limited. This Extracorporeal Life Support Organization registry-based retrospective cohort study included all neonates (age ≤28 days) with CHD supported with venoarterial ECMO >7 days at 111 centers in the United States from January 2011 to December 2020. The primary outcome was survival-to-hospital discharge, and the secondary outcome was ECMO survival (successful decannulation before hospital discharge or death). Of the 2,155 total ECMO runs, 948 neonates received prolonged ECMO (gestational age [mean ± SD] 37.9 ± 1.8 weeks; birth weight 3.1 ± 0.6 kg; ECMO duration 13.6 ± 11.2 days). The ECMO survival rate was 51.6% (489 of 948), and the survival-to-hospital discharge rate was 23.9% (226 of 948). Body weight at ECMO (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.44 to 0.78/kg), gestational age (OR 0.89, 95% CI 0.79 to 1.00 per week), risk-adjusted congenital heart surgery-1 score (OR 1.22, 95% CI 1.04 to 1.45), and pump flow at 24 hours (OR 1.11, 95% CI 1.04 to 1.18 per 10 ml/kg/min) were significantly associated with survival-to-hospital discharge. Pre-ECMO mechanical ventilation duration, time to extubation after ECMO decannulation, and length of stay were inversely associated with hospital survival. Patient-specific (higher body weight and gestational age) and CHD-related (lower risk-adjusted congenital heart surgery-1 score) attributes are associated with better outcomes in neonates who receive prolonged venoarterial ECMO. Further elucidation of the factors associated with reduced survival to discharge in ECMO survivors is needed.

T1 mapping and conditional survival in paediatric dilated cardiomyopathy with advanced heart failure.

Myocardial fibrosis is associated with adverse events in idiopathic dilated cardiomyopathy. Cardiac MRI with late gadolinium enhancement can detect myocardial fibrosis. We evaluated the conditional survival of children and adolescents based on native T1 mapping (combined proton signal from myocytes and interstitium prior to contrast administration by the measurement of myocardial and blood relaxation time) as a means to assess myocardial fibrosis. This retrospective case-cohort over a 3-year period included all consecutive patients (aged ≤ 21 years) with advanced heart failure from dilated cardiomyopathy (echocardiographic left ventricular ejection fraction ≤ 45% and NYHA class ≥ 2) who underwent cardiac MRI.Conditional survival (follow-up ≥ 6 months after cardiac MRI) was assessed to include NYHA functional class and time to event (death or heart transplantation). A total of 57 patients (mean age 11.7 ± 6.1 years; 58% male) had a median NYHA Class III (31/57) and median left ventricular ejection fraction 25% (20-38%). Survival data were available in 82% patients (46/57) and the crude mortality rate was 24% (11/46) and one patient (2%) underwent heart transplantation. The median native T1 was elevated at 1351 ms (95% CI 1332, 1394) and it showed no difference between the groups who survived to those who died. Performing a multilevel regression analysis on prognosis failed to predict 6-month conditional survival.

Early primary graft failure after a pediatric heart transplant and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab.

Early primary graft failure after pediatric orthotopic heart transplantation (OHT) has a high mortality rate and can occur due to several causes including but not limited to prolonged graft ischemia time, suboptimal preimplant myocardial preservation, hyperacute rejection, and maladaptation of the graft to the host's hemodynamic status. Mechanical circulatory support with either extracorporeal membrane oxygenation (ECMO) or ventricular assist device has been used for the rescue of primary graft failure in pediatric patients after heart transplant. Cardiac arrest before ECMO initiation in these patients is associated with adverse neurologic outcome although those surviving to hospital discharge generally have excellent long-term outcome. We report a case of early primary graft failure after OHT who required ECMO support and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab.

Intermediate-Term Results After Extracardiac Conduit Fontan Palliation in Children and Young Adults with Single Ventricle Physiology-A Single-center Experience.

The Fontan operation and its modifications are currently the standard palliation in patients with single ventricle physiology. The advantages of extracardiac conduit Fontan operation (ECF) have previously been described. We evaluated the outcome of patients who underwent ECF operation at our center since the year 2000 to assess morbidity, mortality and New York Heart Association (NYHA) functional class in the current era. Medical records of 97 patients who underwent ECF operation from November 2000 till October 2013 were reviewed to determine the diagnosis, age at surgery, surgical technique, postoperative complications, NYHA class at last follow-up, echocardiographic parameters, and most recent Holter monitor results. The median age at surgery was 3.4 years with 4 total deaths until last follow-up (hospital mortality was 1 %, and mortality after hospital discharge was 3 %). Seventy-eight of the 97 patients (80 %) underwent fenestrated Fontan surgery. Median duration of follow-up was 3.9 years (IQR 0.2-12.2 years). At the latest follow-up, 62 patients (67 %) were determined to be in NYHA class I, 25 patients (27 %) in NYHA class II, and 6 (6 %) patients in NYHA class III, and the median oxygen saturation was 92 % (IQR 86-96). There were 15 patients with history of preoperative arrhythmias and 6 of them required pacemaker placement at the time of surgery. One patient developed ectopic atrial tachycardia, and 1 patient had clinical thromboembolism on follow-up. Systolic function of the single ventricle by transthoracic echocardiogram at the latest follow-up was described as normal in 77 patients (83 %), fair in 15 patients (16 %), and poor in 1 patient (1 %). The results of our study show that patients who undergo extracardiac conduit Fontan operation in the modern era may have significantly less morbidity and mortality when compared to earlier years.

Anthracycline-induced cardiotoxicity: a review of pathophysiology, diagnosis, and treatment.

OPINION STATEMENT: Anthracyclines have been widely used in children and adults to treat hematologic malignancies, soft-tissue sarcomas, and solid tumors. However, anthracyclines come with both short- and long-term cardiotoxic effects, ranging from occult changes in myocardial structure and function to severe cardiomyopathy and heart failure that may result in cardiac transplantation or death. Here, we review the progress made over the past two decades in understanding the molecular and genetic basis of anthracycline-induced cardiotoxicity; detecting and monitoring myocardial dysfunction; using adjunct cardioprotectant therapies, such as dexrazoxane; and improving cardioprotection with agents such as liposomal and pegylated doxorubicin. Despite this increased understanding, preventing drug-induced cardiotoxicity while maintaining oncologic efficacy to achieve the highest quality of life over a lifespan remain cornerstones of successful anthracycline chemotherapy during childhood.

Myocardial dysfunction in pediatric septic shock.

OBJECTIVE: To evaluate the prevalence and significance of myocardial dysfunction in children with septic shock. STUDY DESIGN: Thirty patients with septic shock were evaluated by transthoracic echocardiography within 24 hours of admission to a pediatric critical care unit. Transthoracic echocardiography evaluation included left ventricular (LV) size and function, mitral valve inflow velocities in early and late diastole, mitral valve annular velocities in systole and early and late diastole, and LV myocardial performance index. LV systolic dysfunction was defined as an ejection fraction or shortening fraction z-score <-2, and LV diastolic dysfunction was defined as a mitral valve inflow velocity/annular velocity in early diastole ratio z-score >2. Secondary outcomes included troponin I concentration, acute kidney injury, and 28-day mechanical ventilation-free duration. RESULTS: Mortality for the 30 patients (mean age, 9.5 ± 7 years) was 7%. The prevalence of LV systolic and/or diastolic dysfunction was 53% (16 of 30). Eleven patients (37%) had systolic dysfunction, 10 (33%) had diastolic dysfunction, and 5 (17%) had both. Systolic and/or diastolic dysfunction was significantly associated with troponin I level (P = .007) and acute kidney injury (P = .02), but not with ventilation-free duration (P = .12). Kaplan-Meier analyses for pediatric critical care unit and hospital length of stay identified no differences between patients with and those without myocardial dysfunction. CONCLUSION: Myocardial dysfunction occurs frequently in children with septic shock but might not affect hospital length of stay.

Posterior reversible encephalopathy syndrome: incidence and associated factors in a pediatric critical care population.

BACKGROUND: Posterior reversible encephalopathy syndrome may occur frequently and be underrecognized in children and young adults admitted to a pediatric critical care unit. METHODS: Patients <21 years of age with the diagnosis of posterior reversible encephalopathy syndrome were reviewed in this retrospective cohort study conducted over a 30-month period. RESULTS: There were 2588 admissions to pediatric critical care unit, 226 neurology service consultations, and 10 patients diagnosed with posterior reversible encephalopathy syndrome (incidence of 1 in 259 pediatric critical care unit admissions, 0.4%). The majority of posterior reversible encephalopathy syndrome patients (9/10) presented with generalized tonic and or clonic seizures. Apart from hypertension and cytotoxic medication use, anemia, a previously unreported risk factor, was found in all 10 (100%) patients with posterior reversible encephalopathy syndrome. One-year follow up available in eight patients showed no residual neurological deficits attributable to posterior reversible encephalopathy syndrome with significant resolution of white matter signal abnormalities on neuroimaging. CONCLUSION: Our case cohort includes an estimation of incidence of posterior reversible encephalopathy syndrome in children and young adults with 1-year follow-up and anemia as a potential previously unreported risk factor.

Mouse allergen skin sensitization in asthmatic children of suburban, rural, and inner-city populations.

Mouse allergen (MA) exposure is a well-known risk factor for allergic sensitization and is implicated in the pathogenesis of pediatric asthma. Although previous studies report high prevalence of MA sensitization in inner-city asthmatic children, no data exist on its comparison with either suburban or rural children with asthma. We did a retrospective cohort study by chart review of all children (≤18 years of age) who underwent allergy testing during a 6-month period in a tertiary care referral center. Patients were divided geographically into suburban, rural, and inner-city groups based on their zip codes. MA was tested using the standard allergy test panel by skin prick/puncture. Positive skin test reactivity was defined as wheal diameter ≥3 mm and erythema ≥5 mm. A total of 989 patients underwent allergy testing and 349 children were tested for MA with the overall positivity rate of 18.6% (65/349). In children with asthma (mean age, 12.8 years; SD ± 3.19) who had MA testing (n = 166), the rate of positive skin test reactivity was 18% (n = 30). Inner-city asthmatic children had significantly greater MA sensitization compared with either suburban or rural children. MA sensitization is highly prevalent among children with asthma, especially in inner-city populations but also among suburban and rural children. Although most allergists do not routinely test for MA sensitization during the initial evaluation, it may be useful to include it in the allergy testing for children with asthma.

Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES).

Children with sickle cell disease have a very high risk of lifelong neurologic morbidity and mortality. Cerebrovascular accidents are a known complication in children with sickle cell disease. Posterior reversible encephalopathy syndrome is a constellation of acute neurologic findings increasingly recognized in pediatric critical care population with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial cell dysfunction. This report, for the first time, describes a young adult with sickle cell disease who developed posterior reversible encephalopathy syndrome following blood transfusion.

Exercise testing is useful to screen for residual coarctation in children.

Twenty-seven children (ages 8 to 18 years) who had a history of successful coarctation repair (mean transisthmic Doppler gradient [TI-D] <20 mmHg at rest) and had not received antihypertensive medications underwent echocardiogram at rest and immediately following peak exercise with a standard treadmill test. All were normotensive or had isolated systolic hypertension at rest. Right arm-ankle (RA-A) systolic blood pressure (SBP) difference and TI-D were measured. Eleven children (41%) demonstrated exercise-induced hypertension (peak exercise SBP >98th percentile per body surface area) and 17 (63%) had a mean TI-D > or =40 mmHg. Eight underwent MRI or angiography; a residual coarctation (RCoA) was confirmed in three and excluded in five. RCoA was excluded in three other children who were normotensive at rest and had normal postoperative echocardiographic findings. No individual test (SBP, RA-A SBP, TI-D) at rest or with exercise testing was statistically useful to identify RCoA. However, the requirement for a RA-A SBP difference > or =20 mmHg and a TI-D > or =40 mmHg during exercise testing was a useful screen: RCoA was present in three of five children who fit these criteria but was absent in six of six who did not.

Natriuretic peptides in cardiovascular diseases of fetus, infants and children.

The natriuretic peptides (NP) appear to be functional by midgestation, respond to volume stimuli, and regulate blood pressure and salt and water balance in the developing embryo. In addition, the NP may help regulate the blood supply to the fetus, acting as vasodilators in the placental vasculature. Peaks of ANP and BNP expression during gestation coincide with significant events in cardiac organogenesis, suggesting a role for NP in the formation of the heart. Levels of atrial natriuretic peptide (ANP) are higher in the fetal circulation than in adults, and fetal ventricles express higher levels of ANP and B-type natriuretic peptide (BNP) than adult ventricles. In this comprehensive review we have discussed the role NP during development of the fetal heart and circulation and in various cardiovascular diseases of neonatal and pediatric age group.

A prospective study of iron status in exclusively breastfed term infants up to 6 months of age.

BACKGROUND: Can exclusive breastfeeding until six months of age maintain optimum iron status in term babies? We evaluated iron status of exclusively breastfed term infants in relation to breast milk iron and lactoferrin. METHODS: In this prospective study in Delhi, India, during the period 2003-2004 normally delivered babies of non-anemic [(Hemoglobin (Hb) = 11 g/dl, n = 68] and anemic (Hb 7 - 10.9 g/dl, n = 61) mothers were followed until 6 months of age. Iron parameters were measured in the cord blood at 14 weeks and 6 months. Breast milk iron and lactoferrin were measured at the same intervals. RESULTS: Iron parameters in babies of both groups were within normal limits at birth, 14 weeks and 6 months. Mean breast milk iron and lactoferrin in non-anemic (day 1: 0.89, 6 months: 0.26 mg/l; day 1: 12.02, 6 months: 5.85 mg/ml) and anemic mothers (day 1: 0.86, 6 months: 0.27 mg/l; day 1: 12.91, 6 months: 6.37 mg/ml) were not different on day one or at other times. No relationship was found between breast milk iron, lactoferrin and iron status of the babies. CONCLUSION: Exclusively breastfed infants of non-anemic and anemic mothers did not develop iron deficiency or iron deficiency anemia by six months of age.