Alterations in diastolic function and cardiac geometry in children: a longitudinal study across the spectrum of dialysis and transplant.

BACKGROUND: Children with kidney failure have increased risk for cardiovascular morbidities before and after transplantation. Ejection fraction is often preserved, masking cardiac dysfunction until severe. Data on longitudinal changes in diastolic function and cardiac geometry are limited. METHODS: A prospective study was conducted to investigate longitudinal changes in diastolic function and structure pre- and post-kidney transplant compared with healthy peers. Transplant recipients (n = 41) had echocardiograms pre-transplant, 1, 18, 30, and 42 months post-transplant. The controls (n = 26) underwent one echocardiogram. Diastolic function and cardiac geometry were assessed by E/e' lateral, E/A, interventricular septal end diastole diameter, left ventricular internal end diastole diameter, left ventricular posterior wall end diastole diameter, and left atrial dimension. RESULTS: E/e' of patients remained worse than controls until 30 months post-transplant, and E/A was impaired at all time points compared to the controls. Left ventricular geometry was abnormal in 46% pre-transplant and remained altered in 44.7%, 32.3%, 30.7%, and 27.2% at 1, 18, 30, and 42 months post-transplant. Determinants of diastolic dysfunction included hemodialysis, uncontrolled hypertension, steroid exposure, and metabolic syndrome; abnormal geometry was associated with glomerular diagnosis, dialysis duration, obesity, steroids, and metabolic syndrome. Abnormal diastolic function and structure were associated with left ventricular hypertrophy. CONCLUSION: Diastolic dysfunction and geometry partially improve after transplant but remain abnormal in a subset of patients compared to healthy peers. Traditional indicators of systolic function are preserved. Modifiable risk factors include dialysis modality and duration, uncontrolled hypertension, corticosteroids, obesity, and metabolic syndrome. Attention to diastolic changes provides opportunity for early intervention. A higher resolution version of the Graphical abstract is available as Supplementary information.

Children with Heterozygous Familial Hypercholesterolemia in the United States: Data from the Cascade Screening for Awareness and Detection-FH Registry.

OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.

Effect of levocarnitine supplementation on myocardial strain in children with acute kidney injury receiving continuous kidney replacement therapy: a pilot study.

BACKGROUND: Carnitine plays a key role in energy production in the myocardium and is efficiently removed by continuous kidney replacement therapy (CKRT). Effects of levocarnitine supplementation on myocardial function in children receiving CKRT have not been investigated. METHODS: This controlled pilot cohort study of 48 children investigated effects of levocarnitine supplementation on myocardial strain in children receiving CKRT for acute kidney injury (AKI). Children (n = 9) with AKI had total (TC) and free plasma carnitine (FC) measurements and echocardiogram for longitudinal and circumferential strain at baseline (prior to CKRT) and follow-up (on CKRT for > 1 week with intravenous levocarnitine supplementation, 20 mg/kg/day). Intervention group was compared with three controls: (1) CKRT controls (n = 10) received CKRT > 1 week (+AKI, no levocarnitine), (2) ICU controls (n = 9) were parenteral nutrition-dependent for > 1 week (no AKI, no levocarnitine), and (3) healthy controls (n = 20). RESULTS: In the Intervention group, TC and FC increased from 36.0 and 18 µmol/L to 93.5 and 74.5 µmol/L after supplementation. TC and FC of unsupplemented CKRT controls declined from 27.2 and 18.6 µmol/L to 12.4 and 6.6 µmol/L, which was lower vs. ICU controls (TC 32.0, FC 26.0 µmol/L), p < 0.05. Longitudinal and circumferential strain of the Intervention group improved from - 18.5% and - 18.3% to - 21.1% and - 27.6% after levocarnitine supplementation; strain of CKRT controls (-14.4%, -20%) remained impaired and was lower vs. Intervention and Healthy Control groups at follow-up, p < 0.05. CONCLUSIONS: Levocarnitine supplementation is associated with repletion of plasma carnitine and improvement in myocardial strain and may benefit pediatric patients undergoing prolonged CKRT.

Prevalence of unsuspected abnormal echocardiograms in adolescents with down syndrome.

The purpose of this article is to describe the prevalence of cardiac disease previously undiagnosed in healthy asymptomatic children and adolescents with Down syndrome (DS). Subjects with DS ages 10-20 years were recruited from two sites, the Children's Hospital of Philadelphia (Philadelphia, PA) and Children's National Health System (Washington, DC) for a cross-sectional study of body composition and cardiometabolic risk. Echocardiographic and clinical data were collected from patients enrolled in the parent study of cardiometabolic risk. Nine (6%) new cardiac diagnoses were identified out of 149 eligible patients. All new findings resulted in outpatient referrals to pediatric cardiology. Current guidelines recommend screening all newborns with DS for congenital heart disease. Older patients with DS may benefit from rescreening.

Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome.

Median survival in Down syndrome (DS) is 60 years, but cardiovascular disease risk and its markers such as left ventricular mass (LVM) have received limited attention. In youth, LVM is typically scaled to height2.7 as a surrogate for lean body mass (LBM), the strongest predictor of LVM, but whether this algorithm applies to DS, a condition which features short stature, is unknown. To examine the relationships of LVM and function with height, LBM, and moderate-to-vigorous physical activity(MVPA) in DS, DS youth aged 10-20 years, and age-, sex-, BMI-, race-matched nonDS controls underwent echocardiography for LVM, ejection fraction (EF), and left ventricular diastolic function (measured as E/E'); dual-energy X-ray absorptiometry (DXA)-measured LBM; accelerometry for MVPA. (DS vs. nonDS median [min-max]): DS had lower height (cm) (144.5 [116.7-170.3] vs. 163.3 [134.8-186.7]; p < 0.0001); LBM (kg) (33.48 [14.5-62.3] vs 41.8 [18.07-72.46], p < 0.0001); and LVM (g) (68.3 [32.1-135] vs 94.0 [43.9-164.6], p < 0.0001); similar EF (%) (65 [54-77] vs 64 [53-77], p = 0.59); and higher E/E' (8.41 [5.54-21.4] vs 5.81 [3.44-9.56], p < 0.0001). In height2.7-adjusted models, LVM was lower in DS (ß = - 7.7, p = 0.02). With adjustment for LBM, LVM was even lower in DS (ß = - 15.1, p < 0.0001), a finding not explained by MVPA. E/E' remained higher in DS after adjustment for age, height, HR, SBP, and BMI (ß = 2.6, p < 0.0001). DS was associated with stiffer left ventricles and lower LVM, the latter magnified with LBM adjustment. Scaling to height2.7, the traditional approach for assessing LVM in youth, may underestimate LVM differences in DS. Whether lower LVM and diastolic function are intrinsic to DS, pathologic, or protective remains unknown.Clinical Trial Registration: NCT01821300.

Comparison of BMI, waist circumference, and waist-to-height ratio for identification of subclinical cardiovascular risk in pediatric kidney transplant recipients.

BACKGROUND: Kidney transplant recipients are at high risk for CV morbidity. However, the measure of obesity that best predicts CV risk has not been established. OBJECTIVE: A prospective, controlled study was conducted to compare the ability of BMI, WC, and WHr to identify CV risk in pediatric kidney transplant recipients. METHODS: Transplant recipients, aged 3-20 years, had echocardiogram, CIMT, BMI, WC, WHr, blood pressure, lipids, and leptin measured. Receiver operating characteristic analysis was used to compare the ability of BMI, WC, and WHr to detect a composite adverse CV outcome. Presence of the composite outcome was defined by ≥3 of the following five criteria: (a) LVH, (b) high CIMT, (c) impaired myocardial strain, (d) dyslipidemia, and/or (e) hypertension. Multivariate analysis was conducted by generalized estimating equation regression. RESULTS: We analyzed 108 visits of 42 transplant recipients. Prevalence of obesity by WHr (43.5%) was higher than BMI (24.1%) and WC (12.0%). Proportion of WHr-obese who met criteria for the adverse CV outcome was higher (62.2%) than BMI (34.6%) and WC-obese (33.3%). Leptin levels were higher in children with obesity. Area under the ROC curve for WHr-obese (0.77) was higher compared to BMI (0.47) and WC (0.48) to detect the CV outcome, P = 0.0006. WHr-obesity was associated with 5.72 increased odds of having the adverse CV outcome, P = 0.0001, while BMI and WC were not significant. CONCLUSION: WHr is more sensitive than BMI or WC to detect subclinical CV risk and should be included in screening of pediatric kidney transplant recipients.

Increased carotid intima-media thickness in African American pediatric kidney transplant recipients.

Early signs of subclinical CV dysfunction can be detected by ultrasound for CIMT. Although A-A are at high risk for CV disease, CIMT of A-A kidney transplant recipients has not been previously investigated. The aim of this prospective, controlled, longitudinal study was to investigate determinants of CIMT in a multiracial pediatric kidney transplant population, with a focus on A-A. Transplant recipients (n = 42) had BMI, waist-to-height ratio, fasting glucose, lipid panel, HbA1c%, and CIMT measured at 1, 18, and 30 months post-transplant. Twenty-four healthy children (14 A-A) served as controls. CIMT of A-A transplant (0.49, 0.49, and 0.48 mm) was higher than non-AA transplant (0.43, 0.44, and 0.44 mm) at 1, 18, and 30 months and higher than A-A controls (0.47 mm). Hyperparathyroidism prior to transplant predicted high CIMT-for-race. A-A race was associated with 10% higher CIMT vs non-A-A transplant. Metabolic syndrome was associated with 0.03 ± 0.01 mm increase in CIMT among A-A transplant recipients only. In conclusion, A-A kidney transplant recipients have increased CIMT. Metabolic syndrome disproportionately affects CIMT of A-A children post-transplant. Identification of subclinical CV damage, detected by CIMT, may provide an opportunity for early detection of CV risk in this vulnerable population.

Effects of obesity and metabolic syndrome on cardiovascular outcomes in pediatric kidney transplant recipients: a longitudinal study.

BACKGROUND: Obesity and metabolic syndrome (MS) are common after kidney transplantation, but their contribution to adverse cardiovascular (CV) outcomes in children are not well known. A prospective, controlled, longitudinal cohort study was conducted to investigate the effects of obesity and MS on left ventricular hypertrophy (LVH) and myocardial strain in pediatric kidney transplant recipients. METHODS: Transplant recipients (n = 42) had anthropometrics [body mass index (BMI), waist circumference, waist-to-height ratio], biochemical parameters (fasting glucose, lipid panel, HbA1c%), and echocardiogram with speckle tracking analysis for strain measured at 1, 18, and 30 months post-transplant. Additionally, 35 pre-transplant echocardiograms were analyzed retrospectively. Healthy children (n = 24) served as controls. RESULTS: Waist-to-height ratio detected abdominal obesity in 46% of transplant patients, whereas only 8.1% were identified as obese by waist circumference. Ejection fraction and fractional shortening of the transplant group were normal. Prevalence of LVH was 35.2%, 17.1%, and 35.5% at 1, 18, and 30 months respectively. The longitudinal strain of transplant group was worse than controls at all time points (p < 0.001). Hemodialysis was independently associated with 21% worse longitudinal strain during the pre-transplant period (p = 0.04). After transplantation, obesity, MS, and systolic hypertension predicted increased odds of LVH (p < 0.04). Worse longitudinal strain was independently associated with obesity, MS, hypertension, and the combination of MS with elevated low density lipoprotein (LDL) cholesterol (p < 0.04), whereas higher estimated glomerular filtration rate (eGFR) conferred a protective effect (p < 0.001). CONCLUSION: Obesity and MS adversely affect CV outcomes after transplantation. Further studies are needed to investigate speckle tracking echocardiography as a tool for early detection of subclinical myocardial dysfunction in this population.

Correction to: Effects of obesity and metabolic syndrome on cardiovascular outcomes in pediatric kidney transplant recipients: a longitudinal study.

As originally published, this article contained errors owing to oversights in typesetting. The article has now been amended accordingly.

The Impact of a Designated Cardiology Team Involving Telemedicine Home Monitoring on the Care of Children with Single-Ventricle Physiology After Norwood Palliation.

We evaluated the effect of an interdisciplinary single-ventricle task force (SVTF) that utilizes a family-driven, telemedicine home monitoring program on clinical outcomes of stage II admissions and its acceptance by parents and cardiologists. Study population was divided into two cohorts, one with Norwood surgery dates before the SVTF (pre-SVTF) and one interventional (post-SVTF). Post-SVTF data also included surveys of parents and cardiologists on the efficacy of the SVTF. Comparative and multivariate statistical testing was performed. Compared to the pre-SVTF group, the post-SVTF group had lower complications after stage II (18.4 vs. 34.1 %, p = 0.02), higher weight-for-age z scores at stage II (-1.5 ± 0.97 vs. -1.58 ± 1.34, p = 0.02) and were less likely to have a stage II weight-for-age z score below -2 (26.5 vs. 31.7 %, p = 0.03). A multivariate regression analysis showed providing a written red-flag action plan to parents at discharge was independently associated with higher weight at stage II (ß = 0.42, p = 0.04) and higher weight-for-age z score (ß = 0.48, p = 0.02). Parents' satisfaction with SVTF (α = 0.97) was 4.34 ± 0.62; (95 % CI 4.01-4.67) and cardiologists' acceptance (α = 0.93) was 4.1 ± 0.7 (95 % CI 3.79-4.42). Development of SVTF was associated with a reduction in complications post-stage II and improved weight status at stage II. A written red-flag action plan provided to parents at the time of Norwood discharge was associated with higher weight status at stage II. Parents and cardiologists expressed satisfaction with the utility of SVTF and encouraged expansion to cover all children with congenital heart disease.

Quality improvement through collaboration: the National Pediatric Quality improvement Collaborative initiative.

PURPOSE OF REVIEW: The National Pediatric Quality Improvement Collaborative (NPCQIC) was established to improve outcomes and quality of life in children with hypoplastic left heart syndrome and other single ventricle lesions requiring a Norwood operation. The NPCQIC consists of a network of providers and families collecting longitudinal data, conducting research, and using quality improvement science to decrease variations in care, develop and spread best practices, and decrease mortality. RECENT FINDINGS: Initial descriptive investigation of the collaborative data found interstage care process variations, different surgical strategies, diverse feeding practices, and variable ICU approaches between centers and within sites. Analysis and evaluation of these practice variations have allowed centers to learn from each other and implement change to improve processes. There has been an improvement in performance measures and most importantly, a 39.7% reduction in mortality. SUMMARY: The NPCQIC has shown, in a rare disease such as hypoplastic left heart syndrome that a network based on multicenter collaboration, patient (parent) engagement, and quality improvement science can facilitate change in practices and improvement in outcomes.

Utility of hand-held echocardiography in outpatient pediatric cardiology management.

Adult patient series have shown hand-held echocardiography (echo) units (HHE) to be accurate for rapid diagnosis and triage. This is the first study to evaluate the ability of HHE to inform decision making in outpatient pediatric cardiology. New pediatric cardiology patients in outpatient clinics staffed by six pediatric cardiologists (experience 1-17 years) were prospectively enrolled if an echocardiogram (echo) was ordered during their initial visit. After history and physical examination and before a standard echo, the cardiologists performed a bedside HHE examination (GE Vscan 1.7-3.8 MHz), documented findings, and made a clinical decision. Diagnoses and decisions based on HHE were compared with final management after the standard echo. The study enrolled 101 subjects (ages 9 days to 19 years). The cardiologists considered HHE imaging adequate for decision making for 80 of the 101 subjects. For 77 of the 80 subjects with acceptable HHE imaging (68/68 normal and 9/12 abnormal standard echoes), the HHE-based primary diagnoses and decisions agreed with the final management. The sensitivity of HHE was 75 % (95 % confidence interval [CI] 43-94 %) and the positive predictive value 100 % (95 % CI 66-100 %) for pediatric heart disease. The agreement between standard echocardiography and HHE imaging was substantial (κ = 0.82). Excluding one of the least experienced cardiologists, HHE provided the basis for correct cardiac diagnoses and management for all the subjects with acceptable HHE imaging (58/58 normal and 9/9 abnormal echoes). In outpatient pediatric cardiology, HHE has potential as a tool to complement physical examination. Further investigation is needed to evaluate how value improves with clinical experience.

Alarming rate of liver cirrhosis after the small conduit extracardiac Fontan: A comparative analysis with the lateral tunnel.

BACKGROUND: The association between the prevalence of cirrhosis and the types of Fontan operations remains unclear. METHODS: We conducted a retrospective chart review of 332 patients who underwent the Fontan procedure at our institution. Four patients who underwent the atriopulmonary connection Fontan were excluded from the analysis. Patients who had intracardiac-extracardiac conduit (126) between 1989 and 2021 were pooled with those having extracardiac conduit (ECC) (134). The 260 patients who underwent the ECC and the 68 patients who had the lateral tunnel (LT) Fontan constitute the core of the study. RESULTS: Median age at the Fontan procedure was 23.7 months (interquartile range [IQR], 20.8-32.6) in the LT group, compared with 28.8 months (IQR, 24.6-39.5) in the ECC group (P < .01). The median follow-up was 14.8 years (IQR, 12.5-16.5) in the LT group and 7 years (IQR, 2.8-10.4) in the extracardiac conduit group. During the follow-up period, 3 patients (4.4%) with LT and 17 patients (6.5%) with ECC (11 patients with 16 mm or less conduit size) were diagnosed with cirrhosis. The prevalence of cirrhosis at 1, 5, 10, and 15 years was 0%, 0%, 0%, and 4.4% in the LT group, respectively, and 0%, 0.9%, 7.7%, and 29.8% in the ECC group (P < .01) Rates of mortality, Fontan revision, Fontan takedown, transplant, and complications were comparable between the 2 groups. CONCLUSIONS: The extracardiac conduit Fontan seems to be associated with faster development of cirrhosis.

Association Between Remote Monitoring and Interstage Morbidity and Death in Patients With Single-Ventricle Heart Disease Across Socioeconomic Groups.

BACKGROUND: Despite improvements in survival over time, the mortality rate for infants with single-ventricle heart disease remains high. Infants of low socioeconomic status (SES) are particularly vulnerable. We sought to determine whether use of a novel remote monitoring program, the Cardiac High Acuity Monitoring Program, mitigates differences in outcomes by SES. METHODS AND RESULTS: Within the Cardiac High Acuity Monitoring Program, we identified 610 infants across 11 centers from 2014 to 2021. All enrolled families had access to a mobile application allowing for near-instantaneous transfer of patient information to the care team. Patients were divided into SES tertiles on the basis of 6 variables relating to SES. Hierarchical logistic regression, adjusted for potential confounding characteristics, was used to determine the association between SES and death or transplant listing during the interstage period. Of 610 infants, 39 (6.4%) died or were listed for transplant. In unadjusted analysis, the rate of reaching the primary outcome between SES tertiles was similar (P=0.24). Even after multivariable adjustment, the odds of death or transplant listing were no different for those in the middle (odds ratio, 1.7 [95% CI, 0.73-3.94) or highest (odds ratio, 0.997 [95% CI, 0.30, 3.36]) SES tertile compared with patients in the lowest (overall P value 0.4). CONCLUSIONS: In a large multicenter cohort of infants with single-ventricle heart disease enrolled in a digital remote monitoring program during the interstage period, we found no difference in outcomes based on SES. Our study suggests that this novel technology could help mitigate differences in outcomes for this fragile population of patients.

Phenotype and course of Hutchinson-Gilford progeria syndrome.

BACKGROUND: Hutchinson-Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke. The genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription. METHODS: We enrolled 15 children between 1 and 17 years of age, representing nearly half of the world's known patients with Hutchinson-Gilford progeria syndrome, in a comprehensive clinical protocol between February 2005 and May 2006. RESULTS: Clinical investigations confirmed sclerotic skin, joint contractures, bone abnormalities, alopecia, and growth impairment in all 15 patients; cardiovascular and central nervous system sequelae were also documented. Previously unrecognized findings included prolonged prothrombin times, elevated platelet counts and serum phosphorus levels, measured reductions in joint range of motion, low-frequency conductive hearing loss, and functional oral deficits. Growth impairment was not related to inadequate nutrition, insulin unresponsiveness, or growth hormone deficiency. Growth hormone treatment in a few patients increased height growth by 10% and weight growth by 50%. Cardiovascular studies revealed diminishing vascular function with age, including elevated blood pressure, reduced vascular compliance, decreased ankle-brachial indexes, and adventitial thickening. CONCLUSIONS: Establishing the detailed phenotype of Hutchinson-Gilford progeria syndrome is important because advances in understanding this syndrome may offer insight into normal aging. Abnormal lamin A (progerin) appears to accumulate with aging in normal cells. (ClinicalTrials.gov number, NCT00094393.)

Circulating de novo Donor Specific Antibodies and Carotid Intima-media Thickness in Pediatric Kidney Transplant Recipients, A Pilot Study.

Background: The presence of circulating de novo donor specific anti-HLA antibodies (dnDSA) has been implicated in an immune-mediated form of accelerated systemic arteriosclerosis in adult heart and kidney transplant recipients, however this has not been previously investigated in pediatric kidney transplant recipients. Carotid intima-media thickness (CIMT) is a reliable method for detection of arteriosclerosis. We hypothesized that children who develop dnDSA after kidney transplant would have increased CIMT compared with those who remain dnDSA negative. Methods: A prospective, controlled pilot cohort study of 38 transplant patients and 20 healthy controls was conducted to investigate the association between CIMT and development of dnDSA after kidney transplant. CIMT, anthropometrics, blood pressure and lipid panel were measured at 1, 18, and 30 months post-transplant. DSA was checked at 6, 12, 18, 24 and 30 months post-transplant. CIMT of DSA positive transplant recipients was compared to DSA negative and controls. Results: Of the 38 transplant recipients, 7 patients developed dnDSA by 18-30 months post-transplant. Among 5 dnDSA positive patients who did not receive treatment for DSA prior to CIMT measurement (n=6 observations), the median CIMT was 0.505 mm (95% CI 0.454-0.560 mm) at 18-30 months post-transplant, compared to 0.455 mm (95% CI 0.440-0.470) in DSA negative transplant recipients (n = 54 observations of 30 patients) and 0.450 mm (95% CI 0.436-0.460) in the healthy controls (20 observations of 20 patients). Presence of dnDSA was independently associated with a 7.8% increase in CIMT compared to those without dnDSA (p=0.006), after adjusting for race, hypertension, dyslipidemia, and abdominal obesity. Conclusions: Development of dnDSA was associated with increased CIMT, an indicator of arteriosclerosis, in a cohort of dnDSA positive pediatric kidney transplant recipients. The association between dnDSA and CIMT was independent of traditional CV risk factors, including hypertension, dyslipidemia, and abdominal obesity.

Update on Preventive Cardiology.

Although progress had been made in reducing cardiovascular disease (CVD) mortality, the positive trend has reversed in recent years, and CVD remains the most common cause of mortality in US women and men. Youth represent the future of CVD prevention; emerging evidence suggests exposure to risk factors in children contributes to atherosclerosis and results in vascular changes and increased CVD events. The contributors to CVD include those commonly seen in adults. This article reviews hypercholesterolemia, hypertension, obesity, diabetes, and smoking. It discusses the prevalence of each disease, diagnosis, treatment, and cardiovascular complications.

Effectiveness and Safety of Statin Therapy in Children: A Real-World Clinical Practice Experience.

BACKGROUND: Statin use for hypercholesterolemia in children is predominantly reported from short-term clinical trials. In this study, we assess the efficacy and safety of statin treatment in clinical pediatric practice. METHODS: Records of all patients who began statin treatment at age <18 years and remained on statins for >6 months from 5 pediatric lipid clinics were reviewed. Information at baseline and from all clinic evaluations after statin initiation was recorded, including lipid measurements, statin drug/dose, safety measures (anthropometry, hepatic enzymes, creatine kinase levels), and symptoms. Lipid changes on statin therapy were assessed from baseline to 6 ± 3 months and from 6 ± 3 months to last follow-up with a mixed-effects model, using piecewise linear splines to describe temporal changes, controlling for repeated measures, sex, and age. RESULTS: There were 289 patients with median low-density lipoprotein cholesterol (LDL-C) of 5.3 mmol/L (interquartile range [IQR]:4.5-6.5) and mean age of 12.4 ± 2.9 years at statin initiation. Median duration of therapy was 2.7 years (IQR: 1.6-4.5) with 95% on statins at last evaluation. There were significant decreases in total cholesterol, LDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to 6 ± 3 months (P < 0.001) and from 6 ±3 months to last follow-up (P < 0.001). Triglycerides and HDL-C were unchanged but the triglyceride to HDL-C ratio decreased significantly by late follow-up. At final evaluation, median LDL-C had decreased to 3.4 mmol/L (IQR:2.8-4.2). No patient had statins discontinued for safety measures or symptoms. CONCLUSIONS: In real-world clinical practice, intermediate-term statin treatment is effective and safe in children and adolescents with severe LDL-C elevation.

CONTEXTE: Les statines sont fréquemment employées pour traiter l'hypercholestérolémie chez les enfants dans le cadre d'essais cliniques de courte durée. Dans l'étude présentée ici, nous évaluons l'efficacité et l'innocuité de l'emploi de statines dans la pratique clinique en pédiatrie. MÉTHODOLOGIE: Nous avons passé en revue les dossiers de tous les patients de cinq cliniques pédiatriques des lipides qui ont commencé à prendre une statine avant l'âge de 18 ans et qui ont poursuivi le traitement pendant plus de six mois. Les valeurs mesurées au départ et à chacune des évaluations cliniques après l'instauration d'un traitement par une statine ont été consignées, notamment la lipidémie, le type et la dose de la statine prescrite, les paramètres d'évaluation de l'innocuité (anthropométrie, enzymes hépatiques, taux de créatine kinase) et les symptômes. La variation de la lipidémie chez les patients recevant une statine a été évaluée sur deux périodes, soit entre le début du traitement et l'évaluation effectuée à 6 ± 3 mois ainsi qu'entre l'évaluation effectuée à 6 ± 3 mois et la dernière évaluation de suivi, à l'aide d'un modèle à effets mixtes et de splines linéaires par morceaux pour décrire les changements temporels, en contrôlant pour les mesures répétées, le sexe et l'âge. RÉSULTATS: L'étude portait sur 289 patients ayant un taux de cholestérol des lipoprotéines de basse densité (C-LDL) médian de 5,3 mmol/l (intervalle interquartile [IIQ] : 4,5 à 6,5) et âgés de 12,4 ± 2,9 ans en moyenne au moment de l'instauration du traitement par une statine. La durée médiane du traitement était de 2,7 ans (IIQ : 1,6 à 4,5), 95 % des sujets étant toujours sous statine à la dernière évaluation. Les taux de cholestérol total, de C-LDL et de cholestérol des lipoprotéines non de haute densité (C-non-HDL) avaient diminué de manière significative entre le début du traitement et l'évaluation à 6 ± 3 mois (p < 0,001) et entre l'évaluation à 6 ± 3 mois et la dernière évaluation de suivi (p < 0,001). Les taux des triglycérides et du C-HDL n'avaient pas bougé, mais le rapport triglycérides/C-HDL avait diminué considérablement vers la fin du suivi. À l'évaluation finale, le taux de C-LDL avait diminué à 3,4 mmol/l (IIQ : 2,8 à 4,2). Aucun patient n'avait abandonné le traitement par une statine en raison de problèmes d'innocuité ou des symptômes. CONCLUSIONS: En situation réelle dans la pratique clinique, le traitement à moyen terme par une statine est efficace et sûr chez les enfants et les adolescents présentant une élévation grave du taux de C-LDL.

Ezetimibe treatment of pediatric patients with hypercholesterolemia.

OBJECTIVE: To review the efficacy of ezetimibe monotherapy for treatment of hypercholesterolemia in pediatric patients. STUDY DESIGN: This is a retrospective review of all pediatric patients who received ezetimibe monotherapy as treatment for hypercholesterolemia and for whom follow-up clinical and lipid results were available. Of 36 identified patients, 26 had lipoprotein profiles suggestive of familial hypercholesterolemia (FH), and 10 had profiles suggestive of familial combined hyperlipidemia (FCHL). RESULTS: After a mean 105 days of treatment with ezetimibe (range, 32-175 days), total cholesterol (TC) levels decreased from 7.3 +/- 1.0 mmol/L to 5.7 +/- 1.0 mmol/L (P < .0001), and low-density lipoprotein cholesterol (LDL-C) levels decreased from 5.3 +/- 0.9 mmol/L to 3.9 +/- 0.8 (P < .0001) in patients with FH. In patients with FCHL, TC levels decreased from 6.4 +/- 2.0 mmol/L to 5.6 +/- 0.4 mmol/L (P < or = .002), and LDL-C levels decreased from 4.7 +/- 1.0 mmol/L to 3.8 +/- 0.6 mmol/L (P < or = .005). For all patients, the mean decrease in individual LDL-C values was 1.5 +/- 0.9 mmol/L or 28%. There was no significant change in triglyceride or high-density lipoprotein cholesterol levels with ezetimibe. Patients were maintained on ezetimibe with no adverse effects attributable to the medication for as long as 3.5 years. At a mean of 13.6 months (range, 1-44 months) after the initiation of ezetimibe, LDL-C levels remained decreased at 4.0 +/- 0.6 mmol/L. CONCLUSIONS: In this small retrospective series of children and adolescents with hypercholesterolemia, ezetimibe was safe and effective in lowering LDL-C levels.

Community study to uncover the full spectrum of rheumatic heart disease in Uganda.

OBJECTIVE: Estimates of the prevalence of rheumatic heart disease (RHD) in many endemic countries are limited to samples of children attending schools, which generate an incomplete picture of disease burden in communities. The present study conducted household-based RHD screening in a representative community in Gulu district, Uganda. METHODS: Members of households identified through a two-stage cluster-sampling approach between the ages of 5 years and 50 years were invited to undergo limited cardiac testing with a handheld echocardiogram to assess for the presence of RHD. Suspicious cases underwent confirmatory echocardiogram with a fully functional machine. RESULTS: Of the 2453 community members screened, 2.45% (95% CI 1.87% to 3.14%) showed echocardiographic evidence of RHD with 1.26% (95% CI 0.860% to 1.79%) having definite RHD. The overall prevalence of RHD among participants <20 years was 2.52% (95% CI 1.78% to 3.45%), with a borderline prevalence of 1.97% (95% CI 1.33% to 2.82%) and a definite prevalence of 0.544% (95% CI 0.235% to 1.07%). Prevalence rates among youth increased with age and peaked in the age group of 16-20 years. The overall adult prevalence (>20 years) of RHD was 2.34% (95% CI 1.49% to 3.49%). The majority of definite cases were mild (81%) and marked by mitral regurgitation and associated morphological valve changes (71%). CONCLUSION: Our data reveal a high prevalence of undiagnosed RHD within an endemic community and fill a critical gap in RHD epidemiology in African adults.