Design and rationale of re-energize fontan: Randomized exercise intervention designed to maximize fitness in fontan patients.

In this manuscript, we describe the design and rationale of a randomized controlled trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic+resistance) intervention will improve cardiac and physical capacity; muscle mass, strength, and function; and endothelial function. Survival of children with single ventricles beyond the neonatal period has increased dramatically with the staged Fontan palliation. Yet, long-term morbidity remains high. By age 40, 50% of Fontan patients will have died or undergone heart transplantation. Factors that contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However, it is established that Fontan patients have poor exercise capacity which is associated with a greater risk of morbidity and mortality. Furthermore, decreased muscle mass, abnormal muscle function, and endothelial dysfunction in this patient population is known to contribute to disease progression. In adult patients with 2 ventricles and heart failure, reduced exercise capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction. Despite these known benefits of exercise, pediatric Fontan patients do not exercise routinely due to their chronic condition, perceived restrictions to exercise, and parental overprotection. Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few Fontan patients. Critically, adherence is a major limitation in pediatric exercise interventions delivered on-site, with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or workdays. To overcome these challenges, we utilize live-video conferencing to deliver the supervised exercise sessions. Our multidisciplinary team of experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to maximize adherence, and improve key and novel measures of health in pediatric Fontan patients associated with poor long-term outcomes. Our ultimate goal is the translation of this model to clinical application as an "exercise prescription" to intervene early in pediatric Fontan patients and decrease long-term morbidity and mortality.

Maternal Diabetes and Cardiovascular Health in the Offspring.

Pulse wave velocity (PWV) has been explored to predict cardiovascular health in adults. Less is known about neonatal PWV. We evaluated the association between arterial stiffness of neonates of mothers (NoM) with diabetes and childhood health. Neonatal brachial-femoral PWV (bfPWV) was measured after birth and neonates followed for a median of 5.2 years [1 month-6.6 years]. 36 pregnant women with pregestational diabetes mellitus PGDM (n = 12), gestational diabetes mellitus (GDM) (n = 13), and controls (n = 11) were enrolled. Neonates were similar in weight, gestational age, and delivery mode. 26 neonates had follow-up data including weight, height and blood pressure. More mothers with PGDM had poor glycemic control compared to mothers with GDM (83% vs. 8%; p = 0.0002). PWV was higher in NoM with PGDM than controls (3.4 ± 0.5 vs. 2.6 ± 0.8 m/s; p = 0.04). At follow-up, children of mothers with diabetes (n = 16) had higher weight percentile (78.5 ± 27.9 vs 49.5 ± 34.6%; p = 0.02) and diastolic blood pressure (DBP) (68 ± 13.6 vs 57.3 ± 4.3 mmHg; p = 0.01) than controls (n = 10). No correlation emerged between neonatal PWV and childhood body mass index (BMI) or maternal HbA1c. Results suggest maternal diabetes affect neonatal arterial stiffness and childhood blood pressure; however, the mechanism is unclear. The long-term implications of these findings warrant further investigation.

Physicians' Self-reported Exercise Testing and Physical Activity Recommendations in Kawasaki Patients.

Recommendations for management of patients with Kawasaki disease (KD) and coronary artery aneurysms (CAA) include physical activity (PA) promotion. This study aimed to characterize self-reported practices of KD providers to evaluate practice variation in use of cardiopulmonary exercise testing (CPET) and PA recommendations. We developed a REDCap survey with different clinical scenarios of KD patients. It was completed by members of the International Kawasaki Disease Registry (IKDR) and community pediatric cardiologists. Twenty-eight physicians responded; 63% practiced in the US, 63% practiced in an academic setting, 48% were general pediatric cardiologists, and 55% were IKDR members. Most respondents (69%) followed < 50 KD patients. The great majority (93%) agreed that patients with no CAA do not require CPET and could be cleared for all PA. For patients with small CAA, 43% of respondents recommended CPET and 75% cleared for all PA if CAAs regressed completely, but only 32% cleared if CAA persisted. For patients with medium CAA, 66% respondents cleared for PA if CAA regressed, and only 7% if CAA persisted; with 66% and 75% recommending CPET, respectively. For patients with large/giant CAA, 81% of respondents recommended CPET. No respondents felt comfortable clearing their patients with persistent large/giant CAA for PA and 19% would restrict from the entire physical education program. There is practice variation in use of CPET in KD patients with CAAs. Providers are hesitant to promote PA in KD patients with CAA despite known benefits and current guidelines.

Intraoperative epicardial echocardiography or transoesophageal echocardiography in CHD: how much does it matter?

BACKGROUND: Intraoperative imaging determines the integrity of surgical repairs. Transoesophageal echocardiography represents standard care for intraoperative imaging in CHD. However, some conditions preclude its use, and epicardial echocardiography is used alternatively. Minimal literature exists on the impact of epicardial echocardiography versus transoesophageal echocardiography. We aimed to evaluate accuracy between the two modalities and hypothesised higher imaging error rates for epicardial echocardiography. METHODS: We retrospectively reviewed all epicardial echocardiograms performed over 16 years and compared them to an age- and procedure-matched, randomly selected transoesophageal echocardiography cohort. We detected un- or misidentified cardiac lesions during the intraoperative imaging and evaluated patient outcomes. Data are presented as a median with a range, or a number with percentages, with comparisons by Wilcoxon two-sample test and Fisher's exact test. RESULTS: Totally, 413 patients comprised the epicardial echocardiography group with 295 transoesophageal echocardiography matches. Rates of imaging discrepancies, re-operation, and incision infection were similar. About 13% of epicardial echocardiography patients had imaging discrepancies versus 16% for transoesophageal (p = 0.2352), the former also had smaller body sizes (p < 0.0001) and more genetic abnormalities (33% versus 19%, p < 0.0001). Death/mechanical support occurred more frequently in epicardial echocardiography patients (16% versus 6%, p < 0.0001), while hospitalisations were longer (25 versus 19 days, p = 0.0003). CONCLUSIONS: Diagnostic accuracy was similar between patients undergoing epicardial echocardiography and transoesophageal echocardiography, while rates of death and mechanical support were increased in this inherently higher risk patient population. Epicardial echocardiography provides a reasonable alternative when transoesophageal echocardiography is not feasible.

Molecular characterization and investigation of the role of genetic variation in phenotypic variability and response to treatment in a large pediatric Marfan syndrome cohort.

PURPOSE: In a large cohort of 373 pediatric patients with Marfan syndrome (MFS) with a severe cardiovascular phenotype, we explored the proportion of patients with MFS with a pathogenic FBN1 variant and analyzed whether the type/location of FBN1 variants was associated with specific clinical characteristics and response to treatment. Patients were recruited on the basis of the following criteria: aortic root z-score > 3, age 6 months to 25 years, no prior or planned surgery, and aortic root diameter < 5 cm. METHODS: Targeted resequencing and deletion/duplication testing of FBN1 and related genes were performed. RESULTS: We identified (likely) pathogenic FBN1 variants in 91% of patients. Ectopia lentis was more frequent in patients with dominant-negative (DN) variants (61%) than in those with haploinsufficient variants (27%). For DN FBN1 variants, the prevalence of ectopia lentis was highest in the N-terminal region (84%) and lowest in the C-terminal region (17%). The association with a more severe cardiovascular phenotype was not restricted to DN variants in the neonatal FBN1 region (exon 25-33) but was also seen in the variants in exons 26 to 49. No difference in the therapeutic response was detected between genotypes. CONCLUSION: Important novel genotype-phenotype associations involving both cardiovascular and extra-cardiovascular manifestations were identified, and existing ones were confirmed. These findings have implications for prognostic counseling of families with MFS.

Variation in Pharmacologic Management of Patients with Kawasaki Disease with Coronary Artery Aneurysms.

OBJECTIVE: To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). STUDY DESIGN: Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. RESULTS: We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in <10% of their patients, and 3 centers used it in >20% of patients. Nonsteroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their patients with large/giant CAAs. CONCLUSIONS: In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

Paediatrician's guide to post-operative care for functionally univentricular CHD: a review.

IMPORTANCE: Single ventricle CHD affects about 5 out of 100,000 newborns, resulting in complex anatomy often requiring multiple, staged palliative surgeries. Paediatricians are an essential part of the team that cares for children with single ventricle CHD. These patients often encounter their paediatrician first when a complication arises, so it is critical to ensure the paediatrician is knowledgeable of these issues to provide optimal care. OBSERVATIONS: We reviewed the subtypes of single ventricle heart disease and the various palliative surgeries these patients undergo. We then searched the literature to detail the general paediatrician's approach to single ventricle patients at different stages of surgical palliation. CONCLUSIONS AND RELEVANCE: Single ventricle patients undergo staged palliation that drastically changes physiology after each intervention. Coordinated care between their paediatrician and cardiologist is requisite to provide excellent care. This review highlights what to expect when these patients are seen by their paediatrician for either well child visits or additional visits for parental or patient concern.

Paediatrician's guide to post-operative care for biventricular CHD: a review.

IMPORTANCE: Paediatricians play an integral role in the lifelong care of children with CHD, many of whom will undergo cardiac surgery. There is a paucity of literature for the paediatrician regarding the post-operative care of such patients. OBSERVATIONS: The aim of this manuscript is to summarise essential principles and pertinent lesion-specific context for the care of patients who have undergone surgery or intervention resulting in a biventricular circulation. CONCLUSIONS AND RELEVANCE: Familiarity with common issues following cardiac surgery or intervention, as well as key details regarding specific lesions and surgeries, will aid the paediatrician in providing optimal care for these patients.

Tele-Clinic Visits in Pediatric Patients with Marfan Syndrome Using Parentally Acquired Echocardiography.

OBJECTIVE: To test feasibility of tele-clinic visits using parentally acquired vital signs and focused echocardiographic images in patients with Marfan syndrome. STUDY DESIGN: We included patients with Marfan syndrome aged 5-19 years followed in our clinic. We excluded patients with Marfan syndrome and history of previous aortic root (AoR) surgery, cardiomyopathy, arrhythmia, or AoR ≥4.5 cm. We trained parents in-person to acquire focused echocardiographic images on their children using a hand-held device as well as how to use a stadiometer, scale, blood pressure (BP) machine, and a digital stethoscope. Before tele-clinic visits, parents obtained the echocardiographic images and vital signs. We compared tele-clinic and on-site clinic visit data. Parental and clinic echocardiograms were independently analyzed. RESULTS: Fifteen patient/parent pairs completed tele-clinic visits, conducted at a median of 7.0 (IQR 3.0-9.9) months from the in-person training session. Parents took a median of 70 (IQR 60-150) minutes to obtain the height, weight, heart rate, BP, cardiac sounds, and echocardiographic images before tele-clinic visits. Systolic BP was greater on-site than at home (median +13 mm Hg, P = .014). Height, weight, diastolic BP, heart rate, and AoR measurements were similar. CONCLUSIONS: This study provides information for implementing tele-clinic visits using parentally acquired vital signs and echocardiographic images in patients with Marfan syndrome. The results show that tele-clinic visits are feasible and that parents were able to obtain focused echocardiographic images on their children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03581682.

The benefit of exercise in children with congenital heart disease.

PURPOSE OF REVIEW: Children and adolescents with congenital heart disease (CHD) often have decreased exercise capacity and muscle mass. Exercise has numerous health benefits and can improve exercise capacity and muscle mass. As such, guidelines recommend 60 min of daily physical activity in the majority of pediatric CHD patients. Despite these known benefits and guidelines, children and adolescents with CHD often do not exercise regularly. The purpose of this review is to summarize the current literature on exercise in this population. RECENT FINDINGS: With recent advancements in the field, clinical focus in pediatric cardiology has expanded from improving mortality to improving long-term outcomes and quality of life. As part of this paradigm shift, there is ongoing research on safety, impact, and effective delivery of exercise to this population with the overarching goal of promoting an active lifestyle. SUMMARY: Exercise interventions are generally safe, feasible, and beneficial in children and adolescents with CHD. There is growing evidence demonstrating the benefits and utility of exercise as a prescription rather than restriction in pediatric CHD patients. Novel approaches are needed for effective delivery of exercise in this population. Further studies are warranted for assessment of long-term benefits of exercise in pediatric CHD patients.

Comparison of Initial Pediatric Outpatient Echocardiogram Indications between Community and Academic Practice.

OBJECTIVE: To compare the appropriateness and diagnostic yield of initial outpatient transthoracic echocardiography (TTE) between a community pediatric cardiology practice and an academic children's hospital. STUDY DESIGN: Initial outpatient pediatric TTE ordered by pediatric cardiologists between January and March 2014 at a community practice (Packard Children's Health Alliance [PCHA]; n = 238) and an academic tertiary center (Lucile Packard Children's Hospital [LPCH]; n = 76) were evaluated based on appropriate use criteria (AUC) released in December 2014. Multivariate logistic regression was used to identify predictors of "rarely appropriate" indications and abnormal TTE findings. RESULTS: Of 314 TTEs, 165 (52.5%) were classified as "appropriate," 40 (12.7%) were classified as "may be appropriate," 100 (31.9%) were classified as "rarely appropriate," and 9 (2.9%) were unclassifiable. The proportion of abnormal findings did not differ between the 2 practice settings (5.3% for LPCH vs 7.6% for PCHA; P = .61). TTEs performed at PCHA were significantly more likely to be "rarely appropriate" (OR, 2.57; 95% CI, 1.28-5.15; P = .008). Children aged <1 year (OR, 1.90; 95% CI, 1.03-3.50; P = .04) and ordering providers with <10 years since the completion of their fellowship (OR, 2.15; 95% CI, 1.20-3.87; P = .01) were associated with "rarely appropriate" indications. "Appropriate" TTEs were associated with abnormal findings (OR, 8.69; 95% CI, 1.77-42.68; P = .008). CONCLUSION: The community practice was independently associated with greater inappropriate ordering of initial outpatient pediatric TTEs compared with the academic practice. The assessment of practice patterns following AUC release should account for physician and practice-related factors that could influence differences in TTE ordering patterns.

Vascular Health of Children Conceived via In Vitro Fertilization.

OBJECTIVE: To evaluate whether in vitro fertilization (IVF) has an effect on the cardiovascular health of offspring. STUDY DESIGN: This was a cross-sectional pilot study. We performed vascular health assessment for 17 children aged 10-14 years who were conceived via IVF with autologous oocytes at Stanford University. Carotid artery ultrasound evaluated intima-media thickness and stiffness, carotid-femoral pulse wave velocity determined segmental arterial stiffness, and endothelial pulse amplitude testing assessed endothelial function. We compared IVF offspring with control adolescents assessed in the same laboratory, with all comparisons adjusted for age, sex, and race/ethnicity. RESULTS: All participants had normal body mass index and blood pressure. Compared with controls, IVF children had thicker common carotid artery intima-media thickness (0.44 ± 0.03 mm vs 0.38 ± 0.03 mm; P < .01), higher elastic modulus (395.29 ± 185.33 mm Hg vs 242.79 ± 37.69 mm Hg; P = .01), higher ßstiffness (2.65 ± 0.38 vs 2.28 ± 0.23; P < .01), and higher peak velocity (142.29 ± 31.62 cm/s vs 117.71 ± 32.69 cm/s; P = .04). The mean endothelial pulse amplitude testing reactive hyperemia index was not significantly different between IVF and controls. The mean pulse wave velocity was 4.69 ± 0.51 m/s compared with the controls 4.60 ± 0.57 m/s (P = .11), with 8 (47%) having abnormal values. CONCLUSION: In an assessment of endothelial function and arterial properties of children conceived via IVF, we found that children conceived via IVF seem to have evidence of abnormal vascular health. Further studies with larger sample size and long-term follow-up are warranted.

Healthy hearts in pediatric heart transplant patients with an exercise and diet intervention via live video conferencing-Design and rationale.

BACKGROUND: Pediatric heart transplant (PedHtx) patients have increased cardiovascular risk profiles that affect their long-term outcomes and quality of life. We designed a 12- to 16-week diet and exercise intervention delivered via live video conferencing to improve cardiovascular health. Our methodology and baseline assessment of the first 13 enrolled patients are reported. METHODS: Inclusion criteria are as follows: (a) 8-19 years old; (b) heart transplant >12 months; (c) ability to fast overnight; (d) cardiac clearance by cardiologist; and (e) presence of an adult at home during exercise sessions for patients <14 years old. Exclusion criteria are as follows: (a) acute illness; (b) latex allergy; (c) transplant rejection <3 months ago; and (d) multi-organ transplantation. The intervention consists of one diet and three exercise sessions weekly via live video conferencing. Study visits are conducted at baseline, intervention completion, and end of maintenance period. RESULTS: A total of 13 participants (15.2 [2.3] years) have been enrolled. Median percent-predicted VO2 max was 56.8 [20.7]% (10 patients <70%). Ten patients had abnormal endothelial function (reactive hyperemia index <1.9; 1.4 [0.325]) and 11 patients had stiff arteries (pulse wave velocity ≧5.5 m/s for 15-19 years, ≧4.5 m/s for 8-14 years; 5.6 [0.7] m/s). Patients had suboptimal diets (saturated fat: 22.7 [23.8] g/d, sodium: 2771 [1557] mg/d) and were sedentary at a median of 67.5 [13.8]% of their time. CONCLUSIONS: Baseline assessment confirms that PedHtx patients have abnormal cardiac, vascular, and functional health indices, poor dietary habits, and are sedentary. These results support the rationale to test the feasibility and impact of a non-pharmacologic lifestyle intervention in this patient population.

"Echo pause" for postoperative transthoracic echocardiographic surveillance.

BACKGROUND: No guidelines exist for inpatient postoperative transthoracic echocardiographic (TTE) surveillance in congenital heart disease. We prospectively evaluated indications for postoperative TTEs in patients with congenital heart disease to identify areas to improve upon (Phase 1) and then assessed the impact of a simple pilot intervention (Phase 2). METHODS: We included patients with RACHS-1 (Risk Adjustment for Congenital Heart Surgery) scores of 2 and 3 to keep the cohort homogenous. During Phase 1, we collected data prospectively to identify postoperative TTEs for which there were no new findings and no associated clinical management decisions ("potentially redundant" TTEs). During Phase 2, prior to placement of a TTE order, an "Echo Pause" was performed during rounds to prompt review of prior TTE results and indication for the current order. The number of "potentially redundant" TTEs during Phase 1 vs. Phase 2 was compared. RESULTS: During Phase 1, 98 postoperative TTEs were performed on 51 patients. Potentially "redundant" TTEs were identified in two main areas: (a) TTEs ordered to evaluate pericardial effusion and (b) TTEs ordered with the indication of "postoperative," "follow-up," or "discharge" in the setting of a prior complete postoperative TTE and no apparent change in clinical status. During Phase 2, 101 TTEs were performed on 63 patients. The number of "potentially redundant" TTEs decreased from 14/98 (14%) to 5/101 (5%) (P = .026). CONCLUSION: Our results suggest that the number of "potentially redundant" TTEs during inpatient postoperative surveillance of patients with congenital heart disease can be decreased by a simple intervention during rounds such as an "Echo Pause."

Practice Patterns in Postoperative Echocardiographic Surveillance after Congenital Heart Surgery in Children: A Single Center Experience.

OBJECTIVES: To review current institutional practice and describe factors contributing to variation in inpatient postoperative imaging surveillance after congenital heart surgery. STUDY DESIGN: We reviewed records of all children who underwent congenital heart surgery from June to December 2014. Number and primary indications for postoperative transthoracic echocardiograms (TTEs), providers involved, cardiovascular intensive care unit (CVICU) and total hospital length of stay, and Risk-Adjustment for Congenital Heart Surgery-1 scores were recorded. RESULTS: A total of 253 children (age at surgery: 8 months [2 days-19 years]) received 556 postoperative TTEs (median 1 TTE/patient [1-14]), and 23% had ≥3 TTEs. Fifteen of 556 TTEs (2.7%) revealed a new abnormal finding. The majority of TTEs (59%) were performed in the CVICU (1.5 ± 1.1 TTEs/week/patient), with evaluation of function as the most common indication (44%). Attending physician practice >10 years was not associated with fewer TTEs (P = .12). Patients with ≥3 TTEs had higher Risk-Adjustment for Congenital Heart Surgery-1 scores (P = .001), longer CVICU lengths of stay (22 vs 3 days; P < .0001), longer overall hospitalizations (28 vs 7 days; P < .0001), and a higher incidence of mechanical circulatory support (10% vs 0%; P < .0001) than those with <3 TTEs. Eight patients with ≥3 TTEs did not survive, compared with 3 with <3 TTEs (P = .0004). CONCLUSIONS: There was wide intra-institutional variation in echocardiographic use among similar complexity surgeries. Frequency of postoperative echocardiographic surveillance was associated with degree of surgical complexity and severity of postoperative clinical condition. Few studies revealed new abnormal findings. These results may help establish evidence-based guidelines for inpatient echocardiographic surveillance after congenital heart surgery.

Peripheral Endothelial Function After Arterial Switch Operation for D-looped Transposition of the Great Arteries.

Coronary artery re-implantation during arterial switch operation in patients with D-looped transposition of the great arteries (D-TGA) can alter coronary arterial flow and increase shear stress, leading to local endothelial dysfunction, although prior studies have conflicting results. Endothelial pulse amplitude testing can predict coronary endothelial dysfunction by peripheral arterial testing. This study tested if, compared to healthy controls, patients with D-TGA after arterial switch operation had peripheral endothelial dysfunction. Patient inclusion criteria were (1) D-TGA after neonatal arterial switch operation; (2) age 9-29 years; (3) absence of known cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, vascular disease, recurrent vasovagal syncope, and coronary artery disease; and (4) ability to comply with overnight fasting. Exclusion criteria included (1) body mass index ≥85th percentile, (2) use of medications affecting vascular tone, or (3) acute illness. We assessed endothelial function by endothelial pulse amplitude testing and compared the results to our previously published data in healthy controls (n = 57). We tested 20 D-TGA patients (16.4 ± 4.8 years old) who have undergone arterial switch operation at a median age of 5 days (0-61 days). Endothelial pulse amplitude testing indices were similar between patients with D-TGA and controls (1.78 ± 0.61 vs. 1.73 ± 0.54, p = 0.73).In our study population of children and young adults, there was no evidence of peripheral endothelial dysfunction in patients with D-TGA who have undergone arterial switch operation. Our results support the theory that coronary arterial wall thickening and abnormal vasodilation reported in these patients is a localized phenomenon and not reflective of overall atherosclerotic burden.

Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy.

BACKGROUND: The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. METHODS AND RESULTS: Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area-adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. CONCLUSIONS: Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome.

Expanding the phenotype of cardiovascular malformations in Adams-Oliver syndrome.

We describe a newborn with a phenotype consistent with Adams-Oliver syndrome and truncus arteriosus. Although cardiovascular malformations associated with this syndrome have been previously published in the literature, this is the first description of truncus arteriosus in a patient with Adams-Oliver syndrome. We review other reports of Adams-Oliver syndrome previously described with cardiovascular malformations, consider possible genetic and embryologic mechanisms, and emphasize the need for cardiology consultation when a diagnosis of Adams-Oliver syndrome is suspected in the differential diagnosis.

Tricuspid atresia with progressive ductal restriction in a fetus.

We report a unique case of tricuspid and pulmonary atresia with idiopathic progressive ductus arteriosus restriction in utero. Diligent predelivery planning and a controlled delivery environment led to a favorable outcome.

Minute Stroke Distance Is a More Reproducible Measurement Than Cardiac Output in the Assessment of Fetal Ventricular Systolic Function.

BACKGROUND: Echocardiographic quantification of fetal cardiac output (CO) aids clinical decision-making in the management of various cardiac and extracardiac diseases. Small variability in measuring semilunar valve dimension significantly reduces the reproducibility of the calculated CO. The authors propose minute stroke distance or velocity-time integral (VTI) as a more reproducible measure reflecting fetal ventricular systolic function. The aim of this study was to test the hypothesis that right and left ventricular minute VTI increase predictably with estimated fetal weight and are more reproducible than CO. METHODS: Five hundred seventy-one singleton fetuses without cardiovascular pathology between 16 and 36 weeks' gestation were reviewed retrospectively. Twenty-two fetuses with pathology resulting in low- or high-CO states were also assessed for comparison. VTI was measured in both ventricular outflow tracts at the level of the semilunar valve, excluding a Doppler insonation angle of >30°. Heart rate, semilunar valve dimension, and VTI determined minute VTI and CO. Inter- and intrarater variability were evaluated in a random 10% subset. RESULTS: Minute VTI and CO measurements were feasible in 67% to 89% of fetuses in this retrospective study. Minute VTI and CO increased with estimated fetal weight nonlinearly (R = 0.61-0.94). The mean inter- and intrarater variability for VTI, 6% and 5.7%, were significantly less than for CO, 25% and 23.7% (P < .001 for all). CONCLUSIONS: Minute VTI is an easily measured, highly reproducible method of quantifying fetal ventricular systolic function. Variability in calculated CO from valve measurement differences is minimized by solely using VTI. Nomograms of minute VTI provide an efficient and precise assessment of fetal systolic function and may be used to track fetuses in disease states with low or high CO.