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Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2 , respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.

Standard of care echocardiography can have limited diagnostic accuracy in certain cases of fetal congenital heart disease. Prenatal cardiovascular magnetic resonance (CMR) imaging has potential to provide additional anatomic imaging information, including excellent soft tissue images in multiple planes, improving prenatal diagnostics and in utero hemodynamic assessment. We conducted a literature review of fetal CMR, including its development and implementation into clinical practice, and compiled and analyzed the results. Our findings included the fact that technological and innovative approaches are required to overcome some of the challenges in fetal CMR, in part due to the dynamic nature of the fetal heart. A number of reconstruction algorithms and cardiac gating strategies have been developed over time to improve fetal CMR image quality, allowing unique investigations into fetal hemodynamics, oxygenation, and growth. Studies demonstrate that incorporating CMR in the prenatal arena influences postnatal clinical management. With further refinement and experience, fetal CMR in congenital heart disease continues to evolve and demonstrate ongoing potential as a complementary imaging modality to fetal echocardiography in the care of these patients.

As an essential component of the sarcomere, actin thin filament stems from the Z-disk extend toward the middle of the sarcomere and overlaps with myosin thick filaments. Elongation of the cardiac thin filament is essential for normal sarcomere maturation and heart function. This process is regulated by the actin-binding proteins Leiomodins (LMODs), among which LMOD2 has recently been identified as a key regulator of thin filament elongation to reach a mature length. Few reports have implicated homozygous loss of function variants of LMOD2 in neonatal dilated cardiomyopathy (DCM) associated with thin filament shortening. We present the fifth case of DCM due to biallelic variants in the LMOD2 gene and the second case with the c.1193G>A (p.W398*) nonsense variant identified by whole-exome sequencing. The proband is a 4-month male infant of Hispanic descent with advanced heart failure. Consistent with previous reports, a myocardial biopsy exhibited remarkably short thin filaments. However, compared to other cases of identical or similar biallelic variants, the patient presented here has an unusually late onset of cardiomyopathy during infancy. Herein, we present the phenotypic and histological features of this variant, confirm the pathogenic impact on protein expression and sarcomere structure, and discuss the current knowledge of LMOD2 -related cardiomyopathy.

Objective: Prenatal detection rates for tetralogy of Fallot (TOF) vary between 23 and 85.7%, in part because of the absence of significant structural abnormalities of the 4-chamber view (4CV), as well as the relative difficulty in detection of abnormalities during the screening examination of the outflow tracts. The purpose of this study was to evaluate whether the 4CV and ventricles in fetuses with TOF may be characterized by abnormalities of size and shape of these structures., Methods: This study retrospectively evaluated 44 fetuses with the postnatal diagnosis of TOF. Measurements were made from the 4CV (end-diastolic length, width, area, global sphericity index, and cardiac axis) and the right (RV) and left (LV) ventricles (area, length, 24-segment transverse widths, sphericity index, and RV/LV ratios). Logistic regression analysis was performed to identify variables that might separate fetuses with TOF from normal controls., Results: The mean gestational age at the time of the last examination prior to delivery was 28 weeks 5 days (SD 4 weeks, 4 days). The mean z-scores were significantly lower in fetuses with TOF for the 4CV and RV and LV measurements of size and shape. Logistic regression analysis identified simple linear measurements of the 4CV, RV, and LV that had a sensitivity of 90.9 and specificity of 98.5% that outperformed the 4CV cardiac axis (sensitivity of 22.7%) as a screening tool for TOF., Conclusions: Measurements of the 4CV, RV, and LV can be used as an adjunct to the outflow tract screening examination to identify fetuses with TOF., (© 2021 American Institute of Ultrasound in Medicine.)

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs)., Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease., Results: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics., Conclusions: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live-born patients died before hospital discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23-center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live-born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live-born patients, 7 received comfort care, 11 died <24 hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricular exclusion. At discharge, 56% of the cohort had a biventricular circulation (13% following intervention) and 19% were palliated. Lower tricuspid regurgitation jet velocity (odds ratio [OR], 2.3 [1.1-5.0], 95% CI, per m/s; P =0.025) and lack of antegrade flow across the pulmonary valve (OR, 4.5 [1.3-14.2]; P =0.015) were associated with neonatal mortality by multivariable logistic regression. These variables, along with smaller pulmonary valve dimension, were also associated with a palliated outcome. Conclusions Among neonates with Ebstein anomaly or tricuspid valve dysplasia diagnosed in utero, a variety of management strategies were used across centers, with poor outcomes overall. High-risk patients with low tricuspid regurgitation jet velocity and no antegrade pulmonary blood flow should be considered for right ventricular exclusion to optimize their chance of survival.

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs)., Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2020 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association's 2020 Impact Goals., Results: Each of the 26 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics., Conclusions: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Background: The left atrium (LA) modulates left ventricular filling pressure and is a strong prognosticator in heart failure. Although anthracycline exposure may lead to impaired left ventricular (LV) function, the effects on LA function are not well-described in the younger population. We aim to evaluate LA function in children exposed to anthracyclines., Methods: Children exposed to anthracyclines with pre- and post-treatment echocardiographic imaging were enrolled. Measures of LA function (LA ejection fraction [LA EF], global longitudinal strain [GLS], and peak GLS rate) were quantified using 2D speckle tracking echocardiography pre- and post-anthracycline therapy and were compared. Segments with poor tracking were excluded., Results: Fifty-five children (age 13 [SD 5] years) treated with anthracyclines were evaluated. LA EF, GLS, and peak GLS rate were lower after anthracycline exposure. Mean changes were as follows: LA EF (pre-73.5 [SD 7.7]% vs post-70.6 [SD 8.2]%, P = 0.06), GLS (-34.2 [SD 8.4]% vs -31.9 [SD 7.1]%, P = 0.09), peak GLS rate (2.2 [SD 0.8] s -1 vs 2.0 [SD 0.6] s -1 , P = 0.18). When stratified by pre- (≤12 years old) vs post-puberty (>12 years old), prepubescent patients (n = 21) had statistically significant changes in pre/post LA GLS (P = 0.01) and LA EF (P = 0.01). In models adjusted for radiation dose, age, gender, body surface area, or cumulative anthracycline dose, there were no significant relationships in the absolute difference between pre/post LA EF (P = 0.34) or LA GLS (P = 0.18)., Conclusions: In children exposed to anthracyclines, short-term effects on LA function were minimal in those with preserved LV EF. Age-dependent LA susceptibility to anthracycline requires further study., (© 2018 Wiley Periodicals, Inc.)

Competing Interests: The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

Objective: The objective of this study was to develop quality metrics (QMs) relating to the ambulatory care of children after complete repair of tetralogy of Fallot (TOF)., Design: A workgroup team (WT) of pediatric cardiologists with expertise in all aspects of ambulatory cardiac management was formed at the request of the American College of Cardiology (ACC) and the Adult Congenital and Pediatric Cardiology Council (ACPC), to review published guidelines and consensus data relating to the ambulatory care of repaired TOF patients under the age of 18 years. A set of quality metrics (QMs) was proposed by the WT. The metrics went through a two-step evaluation process. In the first step, the RAND-UCLA modified Delphi methodology was employed and the metrics were voted on feasibility and validity by an expert panel. In the second step, QMs were put through an "open comments" process where feedback was provided by the ACPC members. The final QMs were approved by the ACPC council., Results: The TOF WT formulated 9 QMs of which only 6 were submitted to the expert panel; 3 QMs passed the modified RAND-UCLA and went through the "open comments" process. Based on the feedback through the open comment process, only 1 metric was finally approved by the ACPC council., Conclusions: The ACPC Council was able to develop QM for ambulatory care of children with repaired TOF. These patients should have documented genetic testing for 22q11.2 deletion. However, lack of evidence in the literature made it a challenge to formulate other evidence-based QMs., (© 2017 Wiley Periodicals, Inc.)

Background: 4D Multiphase Steady State Imaging with Contrast (MUSIC) acquires high-resolution volumetric images of the beating heart during uninterrupted ventilation. We aim to evaluate the diagnostic performance and clinical impact of 4D MUSIC in a cohort of neonates and infants with congenital heart disease (CHD)., Methods: Forty consecutive neonates and infants with CHD (age range 2 days to 2 years, weight 1 to 13 kg) underwent 3.0 T CMR with ferumoxytol enhancement (FE) at a single institution. Independently, two readers graded the diagnostic image quality of intra-cardiac structures and related vascular segments on FE-MUSIC and breath held FE-CMRA images using a four-point scale. Correlation of the CMR findings with surgery and other imaging modalities was performed in all patients. Clinical impact was evaluated in consensus with referring surgeons and cardiologists. One point was given for each of five key outcome measures: 1) change in overall management, 2) change in surgical approach, 3) reduction in the need for diagnostic catheterization, 4) improved assessment of risk-to-benefit for planned intervention and discussion with parents, 5) accurate pre-procedural roadmap., Results: All FE-CMR studies were completed successfully, safely and without adverse events. On a four-point scale, the average FE-MUSIC image quality scores were >3.5 for intra-cardiac structures and >3.0 for coronary arteries. Intra-cardiac morphology and vascular anatomy were well visualized with good interobserver agreement (r = 0.46). Correspondence between the findings on MUSIC, surgery, correlative imaging and autopsy was excellent. The average clinical impact score was 4.2 ± 0.9. In five patients with discordant findings on echo/MUSIC (n = 5) and catheter angiography/MUSIC (n = 1), findings on FE-MUSIC were shown to be accurate at autopsy (n = 1) and surgery (n = 4). The decision to undertake biventricular vs univentricular repair was amended in 2 patients based on FE-MUSIC findings. Plans for surgical approaches which would have involved circulatory arrest were amended in two of 28 surgical cases. In all 28 cases requiring procedural intervention, FE-MUSIC provided accurate dynamic 3D roadmaps and more confident risk-to-benefit assessments for proposed interventions., Conclusions: FE-MUSIC CMR has high clinical impact by providing accurate, high quality, simple and safe dynamic 3D imaging of cardiac and vascular anatomy in neonates and infants with CHD. The findings influenced patient management in a positive manner.

Purpose: To summarize our single-center safety experience with the off-label use of ferumoxytol for magnetic resonance imaging (MRI) and to compare the effects of ferumoxytol on monitored physiologic indices in patients under anesthesia with those of gadofosveset trisodium., Materials and Methods: Consecutive patients who underwent ferumoxytol-enhanced (FE) MRI exams were included. Adverse events (AEs) were classified according to the Common Terminology Criteria for Adverse Events v4.0. In a subgroup of patients examined under general anesthesia, recording of blood pressure, heart rate, oxygen saturation, and end-tidal CO 2 was performed. A comparable group of 23 patients who underwent gadofosveset-enhanced (GE) MRI under anesthesia with similar monitoring was also analyzed., Results: In all, 217 unique patients, ages 3 days to 94 years, underwent FE-MRI. No ferumoxytol-related severe, life-threatening, or fatal AEs occurred acutely or at follow-up. Two patients developed ferumoxytol-related nausea. Between-group (FE- vs. GE-MRI) comparisons showed no statistical difference in heart rate (P = 0.69, 95% confidence interval [CI] 96-113 bpm), mean arterial blood pressure (MAP) (P = 0.74, 95% CI 44-52 mmHg), oxygen saturation (P = 0.76, 95% CI 94-98%), and end-tidal CO 2 (P = 0.73, 95% CI 31-37 mmHg). No significant change in MAP (P = 0.12, 95% CI 50-58 mmHg) or heart rate (P = 0.25, 95% CI 91-105 bpm) was noted between slow infusion of ferumoxytol (n = 113) vs. bolus injection (n = 104)., Conclusion: In our single-center experience, no serious AEs occurred with the diagnostic use of ferumoxytol across a wide spectrum of age, renal function, and indications. Because of the limited sample size, firm conclusions cannot be drawn about the generalizability of our results. Thus, vigilance and monitoring are recommended to mitigate potential rare adverse reactions., Level of Evidence: 2 J. Magn. Reson. Imaging 2017;45:804-812., (© 2016 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

In fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD), poor hemodynamic status is associated with worse neonatal outcome. It is not known whether EA/TVD fetuses with more favorable physiology earlier in gestation progress to more severe disease in the third trimester. We evaluated if echocardiographic indexes in EA/TVD fetuses presenting <24 weeks of gestation are reliable indicators of physiologic status later in pregnancy. This multicenter, retrospective study included 51 fetuses presenting at <24 weeks of gestation with EA/TVD and serial fetal echocardiograms ≥4 weeks apart. We designated the following as markers of poor outcome: absence of anterograde flow across the pulmonary valve, pulmonary valve regurgitation, cardiothoracic area ratio >0.48, left ventricular (LV) dysfunction, or tricuspid valve (TV) annulus Z-score >5.6. Median gestational age at diagnosis was 21 weeks (range, 18 to 24). Eighteen fetuses (35%) had no markers for poor hemodynamic status initially, whereas only 7 of these continued to have no markers of poor outcome in the third trimester. Nine of 27 fetuses (33%) with anterograde pulmonary blood flow on the first echocardiogram developed pulmonary atresia; 7 of 39 (18%) developed new pulmonary valve regurgitation. LV dysfunction was present in 2 (4%) patients at <24 weeks but in 14 (37%) later (p <0.001). The TV annulus Z-score and cardiothoracic area both increased from diagnosis to follow-up. In conclusion, progressive hemodynamic compromise was common in this cohort. Our study highlights that care must be taken in counseling before 24 weeks, as the absence of factors associated with poor outcome early in pregnancy may be falsely reassuring., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Ebstein anomaly and tricuspid valve dysplasia are rare congenital tricuspid valve malformations associated with high perinatal mortality. The literature consists of small, single-center case series spanning several decades. We performed a multicenter study to assess the outcomes and factors associated with mortality after fetal diagnosis in the current era., Methods and Results: Fetuses diagnosed with Ebstein anomaly and tricuspid valve dysplasia from 2005 to 2011 were included from 23 centers. The primary outcome was perinatal mortality, defined as fetal demise or death before neonatal discharge. Of 243 fetuses diagnosed at a mean gestational age of 27±6 weeks, there were 11 lost to follow-up (5%), 15 terminations (6%), and 41 demises (17%). In the live-born cohort of 176 live-born patients, 56 (32%) died before discharge, yielding an overall perinatal mortality of 45%. Independent predictors of mortality at the time of diagnosis were gestational age <32 weeks (odds ratio, 8.6; 95% confidence interval, 3.5-21.0; P<0.001), tricuspid valve annulus diameter z-score (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P<0.001), pulmonary regurgitation (odds ratio, 2.9; 95% confidence interval, 1.4-6.2; P<0.001), and a pericardial effusion (odds ratio, 2.5; 95% confidence interval, 1.1-6.0; P=0.04). Nonsurvivors were more likely to have pulmonary regurgitation at any gestational age (61% versus 34%; P<0.001), and lower gestational age and weight at birth (35 versus 37 weeks; 2.5 versus 3.0 kg; both P<0.001)., Conclusion: In this large, contemporary series of fetuses with Ebstein anomaly and tricuspid valve dysplasia, perinatal mortality remained high. Fetuses with pulmonary regurgitation, indicating circular shunt physiology, are a high-risk cohort and may benefit from more innovative therapeutic approaches to improve survival., (© 2015 American Heart Association, Inc.)

Imaging of complex congenital heart diseases (CHDs) in children is challenging. This article reviews the complementary role of high temporal and high spatial resolution magnetic resonance (MR) angiographic imaging techniques in evaluation of a patient with complex congenital cardiovascular disease and related postsurgical complications. A 4-year-old female patient with complex CHD and multiple previous palliative surgical procedures underwent MR angiography to evaluate the cause of refractory hypoxia. High-resolution MR angiography demonstrated the complex postsurgical cardiovascular anatomy and also assisted in the evaluation of cavopulmonary shunt patency and secondary venovenous shunt formation. Time-resolved MR angiography evaluated pulmonary perfusion and demonstrated a significant pulmonary arteriovenous malformation. This information guided physicians in planning further managements, which resulted in a satisfactory clinical outcome., (© 2011 Wiley Periodicals, Inc.)

Objective: The purpose of this study is to evaluate combined time-resolved and high-spatial resolution contrast-enhanced MR angiography (MRA) for assessment of cavopulmonary connections in adult patients with congenital heart disease., Materials and Methods: Twenty-eight adults with various surgical cavopulmonary connections (Glenn shunt and Fontan connection) underwent high-spatial-resolution contrast-enhanced MRA (voxel size, 1.95 mm(3); temporal resolution, 22 seconds) and time-resolved contrast-enhanced MRA (voxel size, 6.5-9.3 mm(3); temporal resolution, < 1.2 seconds). Ten patients had 2D phase contrast flow quantification measurements performed at the same setting. Two readers independently assessed anatomic dimensions of cavopulmonary connections (using high-spatial-resolution contrast-enhanced MRA) and pulmonary artery (PA) perfusion patterns (using time-resolved contrast-enhanced MRA)., Results: High-spatial-resolution contrast-enhanced MRA yielded diagnostic-quality images for morphologic assessment of cavopulmonary connections in 27 of 28 (96%) patients. The anatomic dimensions (cross-sectional area) of the PA and cavopulmonary connections showed a wide variation (right PA, 0.99-5.67 cm(2); left PA, 0.80-5.69 cm(2); Glenn shunt, 0.93-6.94 cm(2); and Fontan connection, 1.25-6.67 cm(2)). The anatomic dimensions could be assessed with excellent interobserver agreement on high-spatial-resolution contrast-enhanced MRA (r = 0.895). Time-resolved contrast-enhanced MRA yielded diagnostic-quality images in all patients and enabled characterization of PA perfusion via the superior vena cava as follows: preferential inflow to the right PA (n = 12), preferential inflow to the left PA (n = 5), and balanced inflow to the right and left PA (n = 11). In those patients who had technically successful flow quantification measurements, phase contrast data confirmed patency of the cavopulmonary connections., Conclusion: Combined time-resolved contrast-enhanced MRA and high-spatial-resolution contrast-enhanced MRA allowed detailed morphologic and dynamic evaluation of cavopulmonary connections in adult patients with congenital heart disease. A wide variation in anatomic dimensions and perfusion patterns was confidently identified in this patient population.

Background: Friedreich ataxia (FRDA) is commonly associated with hypertrophic cardiomyopathy, but little is known about its frequency, severity, or treatment. In this 6-month randomized, double-blind, controlled study, we sought to determine whether idebenone improves cardiac measures in FRDA., Methods: Seventy pediatric subjects were treated either with idebenone (450/900 mg/d or 1,350/2,250 mg/d) or with placebo. Electrocardiograms (ECGs) were assessed at each visit, and echocardiograms, at baseline and week 24., Results: We found ECG abnormalities in 90% of the subjects. On echocardiogram, 81.4% of the total cohort had left ventricular (LV) hypertrophy, as measured by increased LV mass index-Dubois, and the mean ejection fraction (EF) was 56.9%. In linear regression models, longer PR intervals at baseline were marginally associated with longer GAA repeat length (P = .011). Similarly, GAA repeat length did not clearly predict baseline EF (P = .086) and LV mass by M-mode (P = .045). Left ventricular mass index, posterior wall thickness, EF, and ECG parameters were not significantly improved by treatment with idebenone. Some changes in echocardiographic parameters during the treatment phase correlated with baseline status but not with treatment group., Conclusions: Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA. The present study does not provide evidence of benefit in this cohort over a 6-month treatment period., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: The grading of pulmonary regurgitation (PR) severity by two-dimensional (2D) and Doppler echocardiography is not standardized. Cardiovascular magnetic resonance imaging is the clinical gold standard for PR quantification. The purpose of this study was to determine the best 2D and Doppler echocardiographic predictors of severe PR., Methods: Thirty-six patients with tetralogy of Fallot or pulmonary valve stenosis with prior pulmonary valvuloplasty or transannular or subannular patch repair underwent 2D and Doppler echocardiography and cardiovascular magnetic resonance. Two-dimensional and Doppler echocardiographic measurements used to predict severe PR included diastolic flow reversal in the main or branch pulmonary arteries, PR jet width > or = 50% of the pulmonary annulus, PR pressure half-time < 100 ms, and PR index < 0.77., Results: With the exception of PR index, all indices were significant independent predictors of severe PR. The best univariate predictor of severe PR was branch pulmonary artery diastolic flow reversal., Conclusion: Two-dimensional and Doppler echocardiography reliably identified severe PR in this cohort., (Copyright 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Kawasaki disease (KD) is an acute inflammatory vasculitis of childhood which was initially described more than 4 decades ago, yet the specific etiology remains unknown. It has become the most common cause of acquired cardiovascular disease in children in the United States. Advances in clinical therapies have reduced, but not eliminated, the incidence of coronary artery abnormalities in affected children. Pathophysiology seems to include an intense elaboration of cytokines, endothelin, and other vasoactive mediators resulting in the development of vascular endothelial changes that may leave a permanent impact on vascular integrity. Treatment with intravenous immune globulin and aspirin remains the primary management strategy and steroid therapy remains contoversial. In severe circumstances, coronary reperfusion strategies are required, and coronary artery surgery in children with KD has been required, albeit infrequently. KD may be a harbinger for early onset coronary artery disease in adults. Recently developed AHA recommendations have amended diagnostic strategies and indicated a stratified approach to the long-term follow up of this enigmatic yet widespread disease.

Objective: Aortic regurgitation after balloon dilation of congenital aortic stenosis may be treated with valve repair as an alternative to replacement., Methods: Charts and echocardiograms of all patients undergoing aortic valve operations after balloon dilation of congenital aortic stenosis at our institution between January 1988 and December 1999 were reviewed., Results: Twenty-one patients underwent valvuloplasty for predominant aortic regurgitation 9 months to 15 years (mean, 6.1 years) after balloon dilation. The mean +/- SD age at the time of the operation was 11 +/- 7 years. Aortic regurgitation was caused by a combination of commissural avulsion (10), cusp dehiscence with retraction (9), cusp tear (5), central incompetence (2), perforated cusp (1), or cusp adhesion to the aortic wall (1). Repair techniques included commissural reconstruction with a pericardial patch (8), pericardial patch cusp augmentation (6), primary suture repair (6), raphae release and debridement (4), commissurotomy (4), commissural resuspension with sutures (3), and cusp release (1). There were no deaths. At a mean follow-up of 30.1 months (range, 9 months-8 years), all patients were asymptomatic, and the grade of aortic regurgitation had been significantly reduced (P <.001). Left ventricular end-diastolic dimension z scores and proximal regurgitant jet/aortic anulus diameter ratios were significantly reduced (P <.001) and remained so over time. Freedom from reoperation for late failure was 100%, and overall freedom from reintervention was 80% at 3 years., Conclusion: Aortic valve repair for balloon-induced aortic regurgitation is reproducible and durable at medium-term follow-up.

To determine the usefulness of heart size on chest radiograph (CXR) in predicting cardiac enlargement (CE) in children, we prospectively evaluated 95 consecutive outpatients, who had both a CXR and echocardiography performed. Their median age was 5.0 years (2 days to 19.9 years). All patients underwent CXR assessment by a pediatric radiologist, with classification of cardiac silhouette as normal, borderline, or enlarged. Echocardiographic assessment of CE was performed by a pediatric echocardiographer. Sensitivity, specificity, and predictive values of the pediatric radiologist's interpretation of heart size on CXR were estimated. The presence of CE by echocardiography was used as the gold standard. Seventy-nine patients (83.2%) had no CE on CXR, and 16 patients (16.8%) had CE. Sensitivity of the CXR to identify CE was 58.8%, 95% confidence interval (CI) [32.9, 81.6], with a positive predictive value of 62.5% [35.4, 84.8]. Specificity was 92.3% [84.0, 97.1], with a negative predictive value of 91.1% [82.6, 96.4]. These data suggest that the assessment of CE on CXR to predict CE by echocardiography has a relatively high specificity and negative predictive value, but a low sensitivity and positive predictive value. The limitations of CXR as a diagnostic test should be understood by clinicians using the test when screening children for cardiac disease.

There is strong evidence that the onset of atherosclerosis occurs in childhood. Identifying and treating children and adolescents at risk for hypercholesterolemia should lead to a decrease in adult atherosclerotic disease. Based on current information, and the National Cholesterol Education Program (NCEP) guidelines, screening in children and adolescents should be limited to those individuals with specific cardiac risk factors or those from families with a strong history of atherosclerotic disease. Treatment of identified patients should be initiated with dietary control. Subsequent use of cholesterol-lowering medication is best limited to those patients who fail at least 6 months of dietary control measures. Drug therapy includes the use of bile acid sequestrants, nicotinic acid and, more recently, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. There has been limited experience with HMG CoA reductase inhibitors in children and adolescents. However, preliminary data suggests that they are both more effective and have less side effects than either bile acid sequestrants or niacin. Long-term cohort studies will be needed to determine whether screening and treating children and adolescents with hypercholesterolemia is truly of long-term benefit and, if so, which treatment strategies will be preferred.

Coronary artery pathology is a major determinant of treatment strategy and outcome in patients with pulmonary atresia and intact ventricular septum (PA/IVS). For this reason, infants with PA/IVS routinely undergo preoperative cardiac catheterization. The goal of this study was to identify echocardiographic predictors of coronary artery pathology in infants with PA/IVS. The initial preoperative echocardiograms of 30 consecutive infants with PA/IVS (median age at diagnosis 1 day) were reviewed for indexes predicting the degree of coronary pathology. The tricuspid valve (TV) annulus diameter Z- score was determined and evidence of abnormal flow in the coronary arteries by Doppler was evaluated. Coronary pathology was defined by angiography and graded as: 0 = no fistulae; 1 = fistulae/no right ventricular (RV)-dependent coronary arteries; 2 = fistulae with 1 RV-dependent coronary; 3 = fistulae with >/=2- vessel RV-dependent coronary arteries. Outcome was classified as: 2 ventricles, "1.5" ventricles, and 1 ventricle. By angiography, 30% of the patients had grade 0 coronary pathology, 30% had grade 1, 20% had grade 2, and 20% had grade 3. There was 1 death in a patient with grade 3 coronary pathology. Among the survivors (median age at follow-up 28. 6 months), biventricular circulation existed in 12 patients (41%), 7 patients (24%) were 1.5, and 10 (34%) were 1 ventricle. All patients with TV Z-score -2.5. The sensitivity, specificity, positive, and negative predictive values of TV Z-score

While balloon dilation (BD) has become the initial treatment for congenital valvar aortic stenosis (CVAS) at many institutions, repeat BD for recurrent obstruction has been reported only in a few. Between January 1985 and December 1996, 298 patients (70 neonates) underwent BD, 34 of whom underwent a repeat BD without mortality. A greater proportion of neonates had a repeat BD (26% vs. 8%, P < 0.001). At repeat BD (1 day-7.5 years post initial BD), the mean peak-to-peak gradient was reduced from 67+/-24 to 36+/-16 mm Hg (P < 0.0001). Aortic regurgitation (AR) increased immediately in 26%, being moderate or more in 24%. During a mean follow-up of 5.2 years, there was one surgically related death. Of the 33 survivors, 6 had surgery for residual stenosis and/or AR. Among the remaining 27 patients, 96% were asymptomatic, the peak instantaneous aortic valve Doppler gradient was 50+/-15 mm Hg with AR absent in 8%, mild in 62%, and moderate or more in 31%. In conclusion, repeat BD is effective and without mortality. AR was at least moderate in 24% of patients immediately after a second BD. Repeat BD was more common in patients who underwent the initial BD as neonates.