Abstract Background Left ventricular noncompaction (LVNC) is a distinct form of cardiomyopathy characterized by hypertrabeculation of the left ventricle. The LVNC phenotype may occur in isolation or ...with other cardiomyopathy phenotypes. Prognosis is incompletely characterized in children. Methods and Results According to diagnoses from the National Heart, Lung, and Blood Institute–funded Pediatric Cardiomyopathy Registry from 1990 to 2008, 155 of 3,219 children (4.8%) had LVNC. Each LVNC patient was also classified as having an associated echocardiographically diagnosed cardiomyopathy phenotype: dilated (DCM), hypertrophic (HCM), restrictive (RCM), isolated, or indeterminate. The time to death or transplantation differed among the phenotypic groups ( P = .035). Time to listing for cardiac transplantation significantly differed by phenotype ( P < .001), as did time to transplantation ( P = .015). The hazard ratio for death/transplantation (with isolated LVNC as the reference group) was 4.26 (95% confidence interval CI 0.78–23.3) for HCM, 6.35 (95% CI 1.52–26.6) for DCM, and 5.66 (95% CI 1.04–30.9) for the indeterminate phenotype. Most events occurred in the 1st year after diagnosis. Conclusions LVNC is present in at least 5% of children with cardiomyopathy. The specific LVNC-associated cardiomyopathy phenotype predicts the risk of death or transplantation and should inform clinical management.
Background Although the safety of the beach-chair position (BCP) is widely accepted, rare devastating neurologic complications have been reported and attributed to cerebral hypoperfusion. Cerebral ...oxygenation (regional oxygen saturation rSO2 ) can be monitored noninvasively using near-infrared spectroscopy. The purpose of this study was to determine the effect of BCP angle on cerebral oxygenation in patients undergoing shoulder surgery in the BCP. Methods Fifty patients undergoing shoulder arthroscopy were prospectively enrolled to participate. Following induction of general anesthesia, each patient's rSO2 was recorded at 0° of elevation and again at 30°, 45°, 60°, and 80° of elevation. Mean rSO2 values and mean differences in rSO2 were reported. Results An average total decrease of 5% in rSO2 was seen when comparing 0° with 80° ( P < .001). There were statistically significant differences in rSO2 values at beach-chair angles of 0° versus 30° ( P < .001), 30° versus 45° ( P = .007), and 45° versus 60° ( P < .001) but not between 60° and 80° ( P = .12). The decrease in rSO2 was similar between each progressive increase in the beach-chair angle, leading to a linear decline in rSO2 as the BCP increased (regression slope of −0.060%/°, P < .001). No patient's cerebral oxygenation dropped greater than 20% from baseline. Neither body mass index nor American Society of Anesthesiologists score had a significant impact on the relation of rSO2 to BCP angle. Conclusions The average drop in rSO2 is significantly less than the threshold of 20% used as an identifier for a cerebral deoxygenation event. This study illustrates the direct effect the BCP angle has on cerebral oxygenation.
Objectives The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)–negative ...children. Background ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals. Methods Using a prospective multisite cohort study design, echocardiograms taken between birth and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART−). Results Mean left ventricular (LV) mass z -scores were consistently lower in ART+ girls than in ART− girls: differences in mean z -scores were −0.46 at birth (p = 0.005), −1.02 at 6 months (p < 0.001), −0.74 at 12 months (p < 0.001), and −0.79 at 24 months (p < 0.001). Corresponding differences in z -scores for boys were smaller: 0.13 at 1 month (p = 0.42), −0.44 at 6 months (p = 0.01), −0.15 at 12 months (p = 0.37), and −0.21 at 24 months (p = 0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV fractional shortening was higher than in ART− infants; girls showed a greater difference. Conclusions Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness z -scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function.
Cardiomyopathy is a serious disorder of the heart muscle and, although rare, is a common cause of heart failure in children and the most common cause for heart transplantation in children older than ...1 year of age. Funded by the National Heart Lung and Blood Institute since 1994, the Pediatric Cardiomyopathy Registry (PCMR) has followed more than 3500 North American children with cardiomyopathy. Early analyses determined estimates for the incidence of pediatric cardiomyopathy (1.13 cases per 100,000 children per year), risk factors for cardiomyopathy (age <1 year, male sex, black race, and living in New England as opposed to the central southwestern states), the prevalence of heart failure at diagnosis (6%-84% depending on cause), and 10-year survival (29%-94% depending on cause). More recent analyses explored cause-specific functional status, survival and transplant outcomes, and risk factors in greater detail. For many topics these analyses are based on the largest and best-documented samples of children with disease such as the muscular dystrophies, mitochondrial disorders, and Noonan syndrome. Data from the PCMR continue to provide valuable information that guides clinical management and the use of life-saving therapies, such as cardiac transplantation and approaches to treating heart failure, and prepares children, their families, and their caregivers to deal with this serious condition.
The survival benefit of heart transplantation in adult heart failure is greatest for the sickest patients and negligible for patients not requiring inotropic or mechanical support. We hypothesized a ...similar survival benefit of heart transplantation for childhood cardiomyopathies with heart failure.
A merged data set of children registered in both the Pediatric Cardiomyopathy Registry and the Pediatric Heart Transplant Study was used to assess differences in mortality before and after transplant in patients with different levels of heart failure severity. Severity was scored 2 if mechanical ventilatory or circulatory support was required, 1 if intravenous inotropes were required, or 0 if no support was required.
For 332 eligible children, 12-month mortality after listing was 9% for those with a severity score of 0 (n = 105), 16% with a score of 1 (n = 118), and 26% with a score of 2 (n = 109; p = 0.002) with a 3%, 8%, and 20% mortality with severity scores at listing of 0, 1, and 2, respectively, occurring before transplant. Patients listed with a score of 0 frequently deteriorated: 50% received an allograft or died before transplant with severity scores of 1 or 2. The risk of deterioration increased with previous surgery (relative risk, 3.84; p = 0.03) in the short-term and with lower left ventricular mass z-score at time of presentation (relative risk, 1.74; p = 0.003) in the longer-term.
Pediatric cardiomyopathy patients who require high levels of support receive a survival benefit from heart transplantation that is not shared by patients not requiring intravenous inotropic or mechanical support.
Objectives The purpose of this study was to establish the incidence of and risk factors for sudden cardiac death (SCD) in pediatric dilated cardiomyopathy (DCM). Background The incidence of SCD in ...children with DCM is unknown. The ability to predict patients at high risk of SCD will help to define who may benefit most from implantable cardioverter-defibrillators. Methods The cohort was 1,803 children in the PCMR (Pediatric Cardiomyopathy Registry) with a diagnosis of DCM from 1990 to 2009. Cumulative incidence competing-risks event rates were estimated. We achieved risk stratification using Classification and Regression Tree methodology. Results The 5-year incidence rates were 29% for heart transplantation, 12.1% non-SCD, 4.0% death from unknown cause, and 2.4% for SCD. Of 280 deaths, 35 were SCD, and the cause was unknown for 56. The 5-year incidence rate for SCD incorporating a subset of the unknown deaths is 3%. Patients receiving antiarrhythmic medication were at higher risk of SCD (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.3, p = 0.025). A risk stratification model based on most recent echocardiographic values had 86% sensitivity and 57% specificity. Thirty of 35 SCDs occurred in patients who met all these criteria: left ventricular (LV) end-systolic dimension z- score >2.6, age at diagnosis younger than 14.3 years, and the LV posterior wall thickness to end-diastolic dimension ratio <0.14. Sex, ethnicity, cause of DCM, and family history were not associated with SCD. Conclusions The 5-year incidence rate of SCD in children with DCM is 3%. A risk stratification rule (86% sensitivity) included age at diagnosis younger than 14.3 years, LV dilation, and LV posterior wall thinning. Patients who consistently meet these criteria should be considered for implantable cardioverter-defibrillator placement. (Pediatric Cardiomyopathy Registry; NCT00005391 )
Summary The immune reconstitution inflammatory syndrome (IRIS) has emerged as an important early complication of antiretroviral therapy (ART) in resource-limited settings, especially in patients with ...tuberculosis. However, there are no consensus case definitions for IRIS or tuberculosis-associated IRIS. Moreover, previously proposed case definitions are not readily applicable in settings where laboratory resources are limited. As a result, existing studies on tuberculosis-associated IRIS have used a variety of non-standardised general case definitions. To rectify this problem, around 100 researchers, including microbiologists, immunologists, clinicians, epidemiologists, clinical trialists, and public-health specialists from 16 countries met in Kampala, Uganda, in November, 2006. At this meeting, consensus case definitions for paradoxical tuberculosis-associated IRIS, ART-associated tuberculosis, and unmasking tuberculosis-associated IRIS were derived, which can be used in high-income and resource-limited settings. It is envisaged that these definitions could be used by clinicians and researchers in a variety of settings to promote standardisation and comparability of data.
Background Although anaphylaxis is recognized as an important life-threatening condition, data are limited regarding its prevalence and characteristics in the general population. Objective We sought ...to estimate the lifetime prevalence and overall characteristics of anaphylaxis. Methods Two nationwide, cross-sectional random-digit-dial surveys were conducted. The public survey included unselected adults, whereas the patient survey captured information from household members reporting a prior reaction to medications, foods, insect stings, or latex and idiopathic reactions in the previous 10 years. In both surveys standardized questionnaires queried anaphylaxis symptoms, treatments, knowledge, and behaviors. Results The public survey included 1,000 adults, of whom 7.7% (95% CI, 5.7% to 9.7%) reported a prior anaphylactic reaction. Using increasingly stringent criteria, we estimate that 5.1% (95% CI, 3.4% to 6.8%) and 1.6% (95% CI, 0.8% to 2.4%) had probable and very likely anaphylaxis, respectively. The patient survey included 1,059 respondents, of whom 344 reported a history of anaphylaxis. The most common triggers reported were medications (34%), foods (31%), and insect stings (20%). Forty-two percent sought treatment within 15 minutes of onset, 34% went to the hospital, 27% self-treated with antihistamines, 10% called 911, 11% self-administered epinephrine, and 6.4% received no treatment. Although most respondents with anaphylaxis reported 2 or more prior episodes (19% reporting ≥5 episodes), 52% had never received a self-injectable epinephrine prescription, and 60% did not currently have epinephrine available. Conclusions The prevalence of anaphylaxis in the general population is at least 1.6% and probably higher. Patients do not appear adequately equipped to deal with future episodes, indicating the need for public health initiatives to improve anaphylaxis recognition and treatment.
Objectives This study sought to determine the incidence and predictors of recovery of normal echocardiographic function among children with idiopathic dilated cardiomyopathy (DCM). Background Most ...children with idiopathic DCM have poor outcomes; however, some improve. Methods We studied children <18 years of age from the Pediatric Cardiomyopathy Registry who had both depressed left ventricular (LV) function (fractional shortening or ejection fraction z- score <–2) and LV dilation (end-diastolic dimension LVEDD z- score >2) at diagnosis and who had at least 1 follow-up echocardiogram 30 days to 2 years from the initial echocardiogram. We estimated the cumulative incidence and predictors of normalization. Results Among 868 children who met the inclusion criteria, 741 (85%) had both echocardiograms. At 2 years, 22% had recovered normal LV function and size; 51% had died or undergone heart transplantation (median, 3.2 months), and 27% had persistently abnormal echocardiograms. Younger age (hazard ratio HR: 0.92; 95% confidence interval CI: 0.88 to 0.97) and lower LVEDD z- score (HR: 0.78; 95% CI: 0.70 to 0.87) independently predicted normalization. Nine children (9%) with normal LV function and size within 2 years of diagnosis later underwent heart transplantation or died. Conclusions Despite marked LV dilation and depressed function initially, children with idiopathic DCM can recover normal LV size and function, particularly those younger and with less LV dilation at diagnosis. Investigations related to predictors of recovery, such as genetic associations, serum markers, and the impact of medical therapy or ventricular unloading with assist devices are important next steps. Longer follow-up after normalization is warranted as cardiac failure can recur. (Pediatric Cardiomyopathy Registry; NCT00005391 )
Background A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. Objective We aimed for assessment of ...the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. Methods Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis–free, and overall survivals. Results GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB ( P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis–free, and overall survivals were 35%, 49%, and 54%, respectively. Limitations Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. Conclusions In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients.
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