Jondavid Menteer

Ventricular assist device-associated anti-human leukocyte antigen antibody sensitization in pediatric patients bridged to heart transplantation

BACKGROUND Ventricular assist devices (VAD) are associated with the formation of antibodies to anti-human leukocyte antigens (HLA) or sensitization. The incidence and effects of VAD-associated anti-HLA sensitization have not been well studied in the pediatric population. METHODS A retrospective review of all patients undergoing VAD implant at our institution from 1998 to 2008 was performed. Panel reactive antibody (PRA) results before VAD implant, after VAD implant, and after orthotopic heart transplantation (OHT) were recorded. Patients who became sensitized (PRA for class I and/or II immunoglobulin G antibodies >or= 10%) on VAD support were compared with non-sensitized patients with regard to demographics, diagnosis, device type, and blood product exposure on VAD support. Outcomes after OHT were also compared between groups. RESULTS VAD support was initiated in 20 patients (median age, 14.4 years), with 75% survival to OHT or recovery. PRA data before and after VAD implant were available for 17 patients. VAD-associated sensitization developed in 35% of recipients. There were no differences between those sensitized in association with VAD support and non-sensitized patients with regard to age, gender, diagnosis, device type, extracorporeal membrane oxygenation use, or blood product exposure on VAD support. Black race predicted sensitization on VAD (p = 0.02). There were no differences in survival or rejection between groups. CONCLUSIONS VAD therapy was associated with the development of anti-HLA sensitization in 35% of recipients. Black race predicted sensitization, but there were no differences in overall survival or outcomes after OHT.

Vitamin D deficiency, cardiac iron and cardiac function in thalassaemia major

Vitamin D25‐OH and D1‐25OH levels were compared with cardiac R2* (1/T2*), left ventricular ejection fraction (LVEF), age, ferritin and liver iron in 24 thalassaemia major patients. Vitamin D25‐OH levels were reduced in 13/24 patients while vitamin D1‐25OH levels were often elevated. Vitamin D25‐OH levels decreased with age (r2 = 0·48) and with liver iron (r2 = 0·20). Cardiac R2* was inversely related with the ratio of D25‐OH to D1‐25OH levels (r2 = 0·42). LVEF was also proportional to the D25‐OH/D1‐25OH ratio (r2 = 0·49). Vitamin D deficiency may be associated with cardiac iron uptake and ventricular dysfunction in thalassaemia major patients.

Quantifying Regional Right Ventricular Function in Tetralogy of Fallot

Right ventricular (RV) function is notoriously difficult to quantify. Patients with tetralogy of Fallot (TOF) have decreased systolic performance. We measure regional RV performance using MRI with 1-dimensional myocardial tissue tagging. By tagging cine-MRI in two views, we measured regional shortening in 12 regions throughout the RV. We image 32 pediatric patients: 21 normal patients and 11 patients with repaired TOF. We establish a normal range for each RV region. TOF patients have decreased shortening on a region-by-region basis. We conclude that regional RV performance can be measured using this technique, and that decreased performance can be demonstrated in TOF patients.

Systemic endothelial dysfunction in children with idiopathic pulmonary arterial hypertension correlates with disease severity

BACKGROUND Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease manifested by progressive pulmonary vascular remodeling, compromised pulmonary blood flow and right heart failure. Most studies have explored how pulmonary endothelial function modulates disease pathogenesis. We hypothesize that IPAH is a progressive panvasculopathy, affecting both pulmonary and systemic vascular beds, and that systemic endothelial dysfunction correlates with disease severity. Recent studies have demonstrated systemic endothelial dysfunction in adults with pulmonary hypertension; however, adults often have additional comorbidities affecting endothelial function. Systemic endothelial function has not been explored in children with IPAH. METHODS In this single-center, prospective, cross-sectional study we examined brachial artery flow-mediated dilation (FMD), a nitric oxide-mediated, endothelial-dependent response, in children with IPAH and matched controls. FMD measurements were compared with clinical and echocardiographic measures of IPAH severity. RESULTS Thirteen patients and 13 controls were studied, ranging in age from 6 to 20 years. FMD was decreased in IPAH subjects compared with controls (5.1 ± 2.1% vs 9.7 ± 2.0%; p < 0.0001). In IPAH subjects, FMD correlated directly with cardiac index (R(2) = 0.34, p = 0.035), and inversely with tricuspid regurgitation velocity (R(2) = 0.57, p = 0.019) and right ventricular myocardial performance index (R(2) = 0.44, p = 0.028). CONCLUSIONS The presence of systemic endothelial dysfunction in children with IPAH and its strong association with IPAH severity demonstrate that IPAH is a global vasculopathy. Although morbidity in IPAH is typically associated with pulmonary vascular disease, systemic vascular changes may also relate to disease pathogenesis and progression. Further study into shared mechanisms of systemic and pulmonary endothelial dysfunction may contribute to future therapies for IPAH.

Exercise Recommendations for Childhood Cancer Survivors Exposed to Cardiotoxic Therapies: An Institutional Clinical Practice Initiative

Childhood cancer survivors who have received treatment with anthracyclines are at risk for developing cardiomyopathy in dose-dependent fashion. Historically, restrictions on certain types of physical activity that were intended to preserve cardiac function have been recommended, based on a mixture of evidence-based and consensus-based recommendations. In the LIFE Cancer Survivorship & Transition Program at Children’s Hospital Los Angeles, the authors reevaluated their recommendations for exercise in survivors who were exposed to anthracyclines, with or without irradiation in proximity to the myocardium. The primary goal was to develop consistent, specific, practical, safe, and (where possible) evidence-based recommendations for at-risk survivors in the program. To accomplish this, the authors referred to current exercise guidelines for childhood cancer survivors, consulted recent literature for relevant populations, and obtained input from the program’s pediatric cardiology consultant. The resulting risk-based exercise recommendations are designed to complement current published guidelines, maximize safe exercise, and help childhood cancer survivors return to a normal life that emphasizes overall wellness and physical activity. This article describes a single institution’s experience in modifying exercise recommendations for at-risk childhood survivors and includes the methods, findings, and current institutional practice recommendations along with sample education materials.

Pediatric rheumatic disease in the intensive care unit: lessons learned from 15 years of experience in a tertiary care pediatric hospital.

Objective: This study describes the 15-yr experience of a large urban tertiary care children’s hospital in treating critically ill patients with pediatric rheumatic diseases. Design: Retrospective case series. Setting: Children’s Hospital Los Angeles, a large urban tertiary care children’s hospital. Patients: All patients with pediatric rheumatic diseases admitted to the Children’s Hospital Los Angeles pediatric intensive care unit from January 1995 to July 2009. Interventions: None. Measurements and Main Results: An internal database and medical records were reviewed for demographics, diagnoses, treatments, organ dysfunction, interventions, infections, and outcomes. Standardized mortality ratio was calculated based on Pediatric Risk of Mortality III estimated mortality. Factors associated with mortality were identified by univariate analyses. Ninety patients with 122 total admissions were identified. The majority of patients were Hispanic (63%), female (73%), and had systemic lupus erythematosus (62%). Pediatric rheumatic disease-related complications (50%) were the most common reason for admission; 32% of admissions involved multiorgan dysfunction. Eighteen admissions (15%) resulted in mortality. Deaths were most commonly attributed to combined infection and active rheumatic disease (50%), infection only (22%), rheumatic disease only (11%), or other causes (17%). In 30 (25%) admissions, a new rheumatologic diagnosis was established. Standardized mortality ratio was 0.72 (95% confidence interval 0.38-1.25) for pediatric rheumatic disease patients compared to 0.87 (95% confidence interval 0.79-0.96) for all pediatric intensive care unit patients. Factors associated with mortality included use of mechanical ventilation, vasopressors, and renal replacement (continuous venovenous hemodialysis) (all p < .05). Conclusions: Pediatric rheumatic disease-related complications were the principal cause of pediatric intensive care unit admission. Deaths occurred most often from severe infections in patients with active rheumatic disease. Pediatric rheumatology patients admitted to the pediatric intensive care unit had outcomes similar to the global pediatric intensive care unit population when adjusted for severity of illness.

Relative vs. absolute values: using patient and population norms for echocardiography in pediatric cardiac transplant recipients.

Raczek KK, Dorey F, Wong PC, Szmuszkovicz JR, Menteer J. Relative vs. absolute values: Using patient and population norms for echocardiography in pediatric cardiac transplant recipients.
Pediatr Transplantation 2010: 14:182–187.

Symptoms of Dysautonomia, Sleep Disturbance, and Abnormal Cognition in Pediatric Heart Failure

Sleep disorders, autonomic dysfunction, and abnormal cognition are important comorbidities in adult patients with heart failure and are associated with disease progression, morbidity, and mortality. The clinical incidence of these conditions is unknown in children with heart failure. We sought to determine the incidence of symptoms that may be attributable to autonomic dysfunction among children with dilated cardiomyopathy and heart failure. We performed a retrospective chart review of patients with dilated cardiomyopathy seen at our institution between 1999 and 2005. We reviewed charts for symptoms of dysautonomia, sleep problems, or abnormal cognition. From the records of 204 pediatric patients, we identified 69 patients aged 7–18 years with severe dilated cardiomyopathy. Of these, 55 (80%) had symptoms attributable to dysautonomia, 20 (29%) had evidence of sleep disturbance, and 3 (4%) had abnormal cognition. Dysautonomia and sleep disturbances are prevalent in children with heart failure, congruent with studies of adult patients. Based on our data, it is not possible to draw conclusions about any cognitive deficits in this population. Because relatively few subjects’ charts explored symptoms of sleep disturbance, we speculate that sleep symptoms may be underappreciated.

Heart failure following the norwood procedure: An analysis of the single ventricle reconstruction trial

BACKGROUND Heart failure results in significant morbidity and mortality in young children with hypoplastic left heart syndrome (HLHS) after the Norwood procedure. METHODS We studied subjects enrolled in the prospective Single Ventricle Reconstruction (SVR) Trial who survived to hospital discharge after a Norwood operation and were followed up to age 6 years. The primary outcome was heart failure, defined as heart transplant listing after Norwood hospitalization, death attributable to heart failure, or symptomatic heart failure (New York Heart Association [NYHA] Class IV). Multivariate modeling was undertaken using Cox regression methodology to determine variables associated with heart failure. RESULTS Of the 461 subjects discharged home following a Norwood procedure, 66 (14.3%) met the criteria for heart failure. Among these, 15 died from heart failure, 39 were listed for transplant (22 had a transplant, 12 died after listing, and 5 were alive and not yet transplanted), and 12 had NYHA Class IV heart failure but were never listed. The median age at heart failure identification was 1.28 (interquartile range 0.30 to 4.69) years. Factors associated with early heart failure included post-Norwood lower fractional area change, need for extracorporeal membrane oxygenation, non-Hispanic ethnicity, Norwood perfusion type, and total support time (p < 0.05). CONCLUSIONS By 6 years of age, heart failure developed in nearly 15% of children after the Norwood procedure. Although transplant listing was common, many patients died from heart failure before receiving a transplant or without being listed. Shunt type did not impact the risk of developing heart failure.

Outcomes of Berlin Heart EXCOR® pediatric ventricular assist device support in patients with restrictive and hypertrophic cardiomyopathy

The outcomes of pediatric ventricular assist device support in patients with diastolic heart failure have not been well described. This study reviews the North American experience with Berlin Heart EXCOR® ventricular assist device implants in children with such physiology. The Berlin Heart clinical database was reviewed. Patients with primary diastolic dysfunction are included in this study. Twenty pediatric patients with restrictive cardiomyopathy (n = 13), hypertrophic cardiomyopathy (n = 3), or congenital heart disease with restrictive physiology (n = 4) who were supported with EXCOR® were identified. Of these, nine (45%) were successfully bridged to transplant, one (5%) weaned from support, and 10 (50%) died after support was withdrawn. Of patients under age 3 years (n = 13), 38.5% survived, whereas those aged 3 or older (n = 7) had 71.4% survival (P = .35). Biventricular assist device (BiVAD) patients experienced a 27.3% survival, vs 77.8% for patients with left ventricular assist device only (P = .07). Primary causes of death included stroke, infection, acidosis, multisystem organ failure, and bleeding. Pediatric patients with diastolic heart failure comprise a high‐risk population for mechanical circulatory support. However, half of patients with this physiology have been successfully supported to explant with EXCOR®. The trends toward higher mortality for younger patients and those receiving BiVAD support warrant consideration.