Left Juxtaposition of the Right Atrial Appendage: Pitfalls in Diagnosis.

Several congenital anomalies of the right atrial appendage (RAA) have been described including aneurysm, herniation (in association with a pericardial defect), and left juxtaposition. The left juxtaposition of the RAA (LJRAA), first described by Birmingham in 1893 and subsequently introduced by Dixon in 1954, is usually associated with complex cardiac malformations such as obstruction of the left ventricular outflow tract. In this case report, we will describe an unusual variant of LJRAA in the absence of any other cardiac defects, which was initially misinterpreted as an aortic dissection. The correct diagnosis was made after careful reinterpretation and the use of multiple imaging modalities as highlighted.

Nutritional markers accompanying acquired chylothorax in infants: a systematic review.

CONTEXT: Chylothorax is a well-established acquired complication of thoracic surgery in infants. Current data suggest acquired chylothorax may affect infant growth and nutrition because of a loss of essential nutrients via chylous effusion. OBJECTIVE: The 3 objectives for this study were: (1) identify nutritional markers affected by the development of acquired chylothorax in infants; (2) highlight the variability in methods used to assess nutritional status and growth in this patient population; and (3) highlight nutritional deficits that can serve as treatment targets during postoperative feeding protocols. DATA SOURCES: A systematic literature search was conducted between May 31, 2021, and June 21, 2022, using the PubMed, Embase, CINAHL, and Web of Science databases. Search terms included, but were not limited to, "chylothorax," "infants," and "nutrition." DATA EXTRACTION: Inclusion criteria required studies that measured quantitative markers of nutrition in ≥10 participants aged <1 year with acquired chylothorax. A total of 575 studies were screened and all but 4 were eliminated. Nutritional markers were categorized into 4 different groups: total serum protein level, triglyceride levels, growth velocity, and weight for length. DATA ANALYSIS: The variation in methods, time points, interventional groups, and nutritional markers did not facilitate a meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias in Nonrandomized Studies assessment tool. CONCLUSION: This review highlights the need for reliable quantitative markers of nutrition that will enable providers to assess the nutritional needs of infants with chylothorax. Future studies must focus on measuring markers of nutrition at regular intervals in larger study populations.

Impact of prenatal opioids on cardiac and autonomic development: systematic review and meta-analysis.

Prenatal opioid exposure has recently risen four-fold with limited data on the developmental effects on neonatal physiology. The objective of this systematic review is to develop an association between prenatal opioid exposure and fetal and neonatal cardiac and autonomic development and function. The review was conducted in accordance with PRISMA Guidelines, and searches were conducted using PubMed, Embase, CINAHL, and Web of Science between May 25 and October 27, 2020. Twenty studies fit inclusion criteria, in four categories: (1) fetal cardiac outcomes, (2) neonatal cardiac outcomes, (3) noninvasive autonomic outcomes, and (4) clinical and behavioral measures. For the meta-analysis, three studies (total of 210 subjects) were included. Effect sizes were measured as the mean difference in fetal heart rate between opioid-exposed and non-exposed groups. Mothers with prenatal opioid use had a significantly lower fetal heart rate as compared to mothers without prenatal opioid use, requiring further studies to determine clinical significance.

Obese and Type 2 Diabetic Youth Have Increased Forward and Backward Wave Reflections.

OBJECTIVE: Pulse wave analysis estimates arterial wave reflections relating to left ventricular dysfunction and cardiovascular event risk in adults. Forward and backward waves (Pf and Pb) may improve risk stratification for cardiovascular events. Data in youth are lacking. We hypothesized that a significant difference in wave reflections would be identified in young subjects with adverse cardiovascular risk factors. Approach and Results: Vital signs and labs were obtained in 551 patients aged 10 to 24 years who were lean (L=199), obese (O=173), or had type 2 diabetes (T=179). Wave separation was performed. Differences in cardiovascular risk factors and wave reflections were assessed using ANOVA. General linear models were constructed to elucidate independent predictors of wave reflections. O and T subjects had an adverse cardiovascular risk profile versus L. O and T subjects had higher Pf and Pb versus L (P≤0.05). When adjusted for adiposity and other cardiovascular risk factors, reflection magnitude increased from L to O to T with higher T versus L values (P≤0.05) and near-significant O versus L values (P=0.06). Adiposity and blood pressure were major determinants of wave reflections. Pb influenced log left ventricular mass index, log E/e', and log composite carotid intima-media thickness. CONCLUSIONS: Adolescents and young adults with obesity and type 2 diabetes have altered forward and backward wave reflections versus lean controls related to adiposity, BP, and insulin levels. These parameters may help risk stratify patients with adverse cardiovascular risk factors.

Markers of cholesterol synthesis are elevated in adolescents and young adults with type 2 diabetes.

BACKGROUND: Changes in cholesterol absorption and cholesterol synthesis may promote dyslipidemia and cardiovascular disease in individuals with type 2 diabetes mellitus (T2DM). OBJECTIVE: To assess cholesterol synthesis and absorption in lean individuals, obese individuals, and individuals with T2DM. METHODS: We measured lathosterol and lanosterol (markers of cholesterol synthesis) as well as campesterol and ß-sitosterol (markers of cholesterol absorption) in the serum of 15 to 26 years old individuals with T2DM (n = 95), as well as their lean (n = 98) and obese (n = 92) controls. RESULTS: Individuals with T2DM showed a 51% increase in lathosterol and a 65% increase in lanosterol compared to lean controls. Similarly, obese individuals showed a 31% increase in lathosterol compared to lean controls. Lathosterol and lanosterol were positively correlated with body mass index, fasting insulin and glucose, serum triglycerides, and C-reactive protein, and negatively correlated with HDL-cholesterol. In contrast, campesterol and ß-sitosterol were not altered in individuals with T2DM. Moreover, campesterol and ß-sitosterol were negatively correlated with body mass index, fasting insulin, and C-reactive protein and were positively correlated with HDL-cholesterol. CONCLUSIONS: Adolescents and young adults with T2DM show evidence of increased cholesterol synthesis compared to non-diabetic lean controls. These findings suggest that T2DM may promote cardiovascular disease by increasing cholesterol synthesis, and provide additional rationale for the use of cholesterol synthesis inhibitors in this group.

Accelerated Early Vascular Aging Among Adolescents With Obesity and/or Type 2 Diabetes Mellitus.

Background The normal rate of subclinical vascular aging from adolescence to young adulthood has not been well-characterized. We conducted a 5-year longitudinal study among adolescents with normal-weight, obesity, and/or type 2 diabetes mellitus to examine trajectories of early vascular aging. Methods and Results Adolescents (mean [SD] age 17.6 [3.5]; 35.3% male) had either normal weight (n=141), obesity (n=156), or type 2 diabetes mellitus (n=151) at baseline. Primary metrics used for early vascular aging included measures of vascular structure (carotid intima-media thickness [cIMT]; common, internal, and bulb) and arterial stiffness (carotid-femoral pulse wave velocity, and augmentation index). Longitudinal (5-year) outcomes were examined using generalized estimating equations adjusting for baseline value, sex, race, and age. Compared with participants with normal weight, those with obesity had greater positive change in common cIMT (0.05 mm [0.03, 0.06]; P<0.001), bulb cIMT (0.02 mm [0.00, 0.05]; P=0.033), internal cIMT (0.03 mm [0.01, 0.05]; P<0.001), and pulse wave velocity carotid-femoral (0.38 m/sec [0.14, 0.61]; P=0.001), and those with type 2 diabetes mellitus had greater positive change in common cIMT (0.05 mm [0.04, 0.07]; P<0.001), bulb cIMT (0.06 mm [0.04, 0.09]; P<0.001), internal cIMT (0.04 mm [0.02, 0.07]; P<0.001), augmentation index (4.67% [2.20, 7.13]; P<0.001), and pulse wave velocity carotid-femoral (0.74 m/sec [0.46, 1.02]; P<0.001). Higher baseline systolic blood pressure was associated with greater positive change in common cIMT (0.007 mm [0.003, 0.011]; P<0.001), bulb cIMT (0.009 mm [0.002, 0.016]; P=0.01), internal cIMT (0.008 mm [0.003, 0.013]; P=0.001), and pulse wave velocity carotid-femoral (0.066 m/sec [0.002, 0.130]; P=0.042). Conclusions These longitudinal data support the hypothesis that the presence of obesity, type 2 diabetes mellitus, and elevated baseline systolic blood pressure in early life accelerates the progression of risk factors key in the development of early vascular aging.

Type 1 diabetes is associated with an increase in cholesterol absorption markers but a decrease in cholesterol synthesis markers in a young adult population.

BACKGROUND: To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes. OBJECTIVE: The objective of the study was to compare plasma levels of campesterol and ß-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes. METHODS: Serum samples were obtained from adolescent subjects with type 1 diabetes (n = 175, mean age 15.2 years, mean duration of diabetes 8.2 years) and without diabetes (n = 74, mean age 15.4 years). Campesterol, ß-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, compared between groups, and correlated with the available cardiometabolic variables. RESULTS: Campesterol and ß-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure. CONCLUSION: Plasma markers suggest that cholesterol absorption is increased, whereas cholesterol synthesis is decreased in adolescent subjects with type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed.

Development of a System to Measure and Improve Outcomes in Congenital Heart Disease: Heart Institute Safety, Quality, and Value Program.

Achieving excellent outcomes for patients with congenital heart disease requires coordinated effort and resources, and a need has developed for a structure that facilitates improvement and measures cardiac centers' progress toward optimal patient care. METHODS: The Heart Institute (HI) at Cincinnati Children's Hospital developed a Safety, Quality and Value (SQV) program to formalize the use of quality improvement (QI) methods with the goal of optimizing patient outcomes, experience, and value. The SQV program adopted a conceptual framework that considers aspects of structure, process, outcome, and value in defining quality metrics, and the program used the Model for Improvement to guide design and implementation of QI interventions. RESULTS: In the first four years since its inception, the SQV program facilitated important improvements in clinical outcomes, cost reductions, and safety. In addition to achieving measurable improvements, the creation of a formal SQV program fostered a culture of transparency and accountability, providing a new structure for how the HI shares clinical data among clinicians, hospital leadership, and the public. CONCLUSION: The creation of an infrastructure to strategically design, implement, and support QI efforts in a clinically busy pediatric acquired and congenital heart institute was successful in meeting its initial aims and is a promising approach and model for other programs.

Comparison of Left Ventricular Mass Calculation Methods via Two-Dimensional Echocardiogram in Children, Adolescents, and Young Adults With Systemic Hypertension.

Left ventricular (LV) mass is a major determining tool for myocardial injury in hypertensive patients. Issues with LV mass calculations exist given that there are multiple methods to assess mass, including from the parasternal long axis (PLA), parasternal short axis (PSA), and 2-dimensional (2D) volumetric methods. The aim of this study was to compare the agreement of LV mass calculations using the PLA, PSA, and 2D volumetric methods. This study retrospectively reviewed 200 consecutive, initial echocardiograms for the indication of hypertension. A single reader calculated the LV mass in each patient via the PLA, PSA, and 2D volumetric methods. Percent differences for each study were calculated. LV mass threshold cutoffs of 51 g/m2.7 (cardiac organ injury) and 38.6 g/m2.7 (elevated LV mass) were used to compare categorical differences between the different measurement methods. Paired comparisons demonstrated an absolute mean percent difference of 8.46% to 9.41% among the different methods. LV mass calculated by the 2D volumetric method was less compared with PLA and PSA methods (31.64 vs 33.90 vs 35.51 g/m2.7; p < 0.0001). Fewer patients were classified as having cardiac target organ injury or elevated LV mass via 2D volumetric calculation, compared with PLA and PSA methods (p = 0.02 and p = 0.03, respectively). In conclusion, there is a small but important difference in LV mass calculations for patients with hypertension. These results emphasize the need for consistency within echocardiography laboratories as surveillance studies are common in this patient population.

Consensus recommendations for echocardiography in adults with congenital heart defects from the International Society of Adult Congenital Heart Disease (ISACHD).

The population of adults with congenital heart disease (ACHD) is increasing constantly due to medical, surgical and interventional successes and the input from advanced cardiovascular imaging. ACHD patients are at continuing risk of residua and sequelae related to their CHD contributing to significant morbidity and mortality. Consequently, lifelong expert surveillance is recommended for most patients. Healthcare providers are still working out how best to achieve this objective, how to train enough experts to provide high quality care, and how to organize the delivery of care. Echocardiography is crucial to clinical surveillance providing a comprehensive assessment of cardiac morphology, physiology, pathophysiology, and function. Thus it contributes significantly to the overall clinical management of ACHD patients. The International Society for Adult Congenital Heart Disease (ISACHD; www.isachd.org) is the leading organization of professionals worldwide dedicated to the pursuit of excellence in the care of ACHD patients. Recognizing the critical role of imaging in the diagnosis and management of ACHD, ISACHD established a task force to provide guidance on echocardiographic studies and reporting. The rationale is that standardization of echocardiographic imaging and reporting carries the potential to improve the overall quality of these exams around the world and facilitate collaborative multicenter research. The standardized ACHD protocols provided by the ISACHD task force (found in the appendices) include specific recommendations for data acquisition and reporting for each of the major adult congenital heart lesions. These protocols give a comprehensive and structured approach in the evaluation of ACHD patients and help to ensure excellent patient care.

Clinical Implications of the Revised AAP Pediatric Hypertension Guidelines.

BACKGROUND AND OBJECTIVES: New pediatric hypertension definitions were recently published in a clinical practice guideline (CPG). We evaluated the impact of the CPG, compared with the previous guideline ("Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents"), on the prevalence of hypertension and associations with target organ damage (TOD) in high-risk youth. METHODS: Participants (10-18 years old) undergoing an evaluation of the cardiovascular effects of obesity and type 2 diabetes mellitus in youth were studied. Blood pressure was categorized according to the 2 guidelines as normal, elevated, and hypertension (stages 1 and 2). Measures of TOD (carotid artery intima-media thickness, pulse wave velocity, left ventricular mass, and diastolic function) were obtained. Associations between blood pressure categories and TOD and the sensitivity of hypertension classification in identifying TOD were evaluated. RESULTS: Data were available for 364 participants (65% female sex; 15.1 ± 2.1 years of age). Hypertension was identified in 8% and 13% as defined in the Fourth Report and CPG, respectively (P = .007). The 2 guidelines revealed similar associations with TOD; however, the CPG demonstrated improved sensitivity of TOD detection in hypertensive participants. For example, the proportion of participants with an abnormal left ventricular mass categorized as hypertensive increased from 20% to 31% as defined in the Fourth Report and CPG, respectively (P < .001). CONCLUSIONS: Incorporation of the CPG increased the prevalence of pediatric hypertension in a population of high-risk youth and improved the sensitivity of TOD identification in hypertensive participants.

Arterial Thickness and Stiffness Are Independently Associated with Left Ventricular Strain.

BACKGROUND: The aim of this study was to examine the association between myocardial strain and arterial thickness and stiffness in young adults. Increased common carotid artery intima media thickness and peripheral arterial stiffness are known to precede coronary artery disease and cardiovascular (CV) events such as myocardial infarction and congestive heart failure. However, subclinical cardiac dysfunction can be detected in high-risk adults by myocardial strain echocardiography. The authors hypothesized that increased carotid artery intima media thickness would be associated with abnormal myocardial strain in young subjects who had obesity and type 2 diabetes mellitus. METHODS: CV risk factors were collected in 338 young adults participating in a prospective, cross-sectional study. The CV parameters collected included intima-media thickness, peripheral arterial stiffness by brachial distensibility, and myocardial strain and strain rate. General linear models were constructed to determine if vascular structure and function measures were independently associated with myocardial strain and strain rate. RESULTS: A linear relationship was found between global longitudinal strain obtained from the four-chamber view and global strain rate in systole and carotid intima-media thickness (four-chamber global longitudinal strain: ß = 3.0, CV risk factor-adjusted R2 = 0.34; global strain rate in systole: ß = 0.0053, R2 = 0.21; P ≤ .0001) and between four-chamber global longitudinal strain and lower brachial distensibility (ß = -0.42, R2 = 0.22; P < .001). CONCLUSIONS: Adverse changes in vascular structure and function are simultaneously present with reduced myocardial systolic function.

Association of Habitual Physical Activity With Cardiovascular Risk Factors and Target Organ Damage in Adolescents and Young Adults.

BACKGROUND: We aimed to (1) compare a subjective and objective measure of habitual physical activity (PA), (2) determine the association of PA and cardiovascular risk factors, and (3) test the hypothesis that PA is an independent determinant of target organ damage in youth. METHODS: Cross-sectional analysis of youth with and without type 2 diabetes [mean age = 22 (3.9) y]. PA was measured with International Physical Activity Questionnaire and Actical accelerometer. Target organ damage was assessed with echocardiography and peripheral arterial testing. Subjects were stratified into tertiles of total PA, and differences were tested by analysis of variance and χ2 tests. General linear models tested for independent associations. RESULTS: The correlation between International Physical Activity Questionnaire and accelerometry was weak (r = .23, P = .0003). Less active subjects had worse cardiovascular risk profiles and target organ damage, including stiffer arteries (P < .01). These outcome differences did not reach statistical significance when adjusted for covariates, such as lipid levels and glycemic control. CONCLUSION: Survey assessment of PA is complicated by inaccurate reporting. There is a strong association of habitual PA with cardiovascular risk factor clustering. PA may exert its beneficial effect on arterial stiffness in obese youth through improved glycemic control.

Lipoprotein particle number and size predict vascular structure and function better than traditional lipids in adolescents and young adults.

BACKGROUND: In adults, dyslipidemia is associated with higher carotid thickness and arterial stiffness, predictors of cardiovascular events. In young subjects, lipid concentrations have not been consistently associated with vascular measures. OBJECTIVE: The objective of the study was to compare nuclear magnetic resonance (NMR) measures of lipoprotein particle number (low-density lipoprotein [LDL] particle, low-density lipoprotein [HDL] particle, very low-density lipoprotein [VLDL] particle) and size (LDL size, HDL size, and VLDL size) to determine if they were associated with vascular measures more strongly than lipid concentrations (LDL cholesterol, HDL cholesterol, and triglyceride [TG]). METHODS: We evaluated 214 lean (L), 228 obese (O), and 214 diabetic (T2DM) subjects aged 10 to 24 years (33% male and 39% Caucasian). Cardiovascular risk factors, vascular structure, and arterial stiffness were measured. General linear models were constructed including demographics, risk factors, and traditional or NMR lipid parameters. A composite vascular function score was developed as the outcome in receiver operator characteristic scores for determining which lipid parameter was superior in predicting vascular damage. RESULTS: Risk factors worsened from L to O to T. However, LDL cholesterol was similar in O and T, whereas LDL size differentiated the 3 groups (T > O > L, P ≤ .0001). Models demonstrated the superiority of NMR values, which entered for all but 1 vascular outcome and explained more of the variance than traditional lipid concentrations. Receiver operator characteristic curves demonstrated that NMR values were superior in predicting vascular outcomes. Models stratified by race were similar but cutpoints predicting vascular outcomes differed by race for TG, TG/HDL, and VLDL. CONCLUSION: Lipoprotein particle number and size are more strongly related to vascular structure and function than traditional lipid values. NMR lipid measures may be a better indicator of risk for target organ damage than traditional lipid measures in adolescents and young adults.

Longitudinal Cardiovascular Outcomes of Sleep Disordered Breathing in Children: A Meta-Analysis and Systematic Review.

Objectives: The presence of sleep disordered breathing (SDB) is known to impact long-term cardiovascular morbidity in adults; however, the long-term effects in children are poorly understood. We aimed to systematically review and synthesize studies published to date on the long-term effects of SDB in children. Study Design: Meta-analysis and systematic review using PubMed, CINAHL, Embase, and Scopus (all indexed years). Methods: We searched for English-language articles containing original human data from prospective studies, with ≥7 participants, in children ≤18 years of age. Data regarding study design, demographics, clinical characteristics, outcomes, level of evidence, and risk of bias were obtained. Articles were independently reviewed by three investigators. Retrospective and cross-sectional studies were excluded. Results: Of 1701 identified abstracts, 25 articles (combined n = 1418) were ultimately included. All studies reported longitudinal outcomes following treatment of SDB, 21 studies exclusively reporting outcomes after adenotonsillectomy. Therefore, studies were combined to objectively assess the effect of SDB treatment on cardiovascular outcomes. Although all cardiovascular parameters were within the normal range at baseline, at follow-up there was a significant decrease in mean pulmonary artery pressure, right ventricular end diastolic diameter, heart rate, mitral Em/Am ratio, and C-reactive protein. There was no significant change in interventricular septum thickness, left ventricular parameters (shortening fraction, systolic and end diastolic diameters, ejection fraction, posterior wall thickness, isovolumetric relaxation time), left atrial diameter, and aortic and pulmonary valve peak velocities. Conclusions: Studies assessing the long-term cardiovascular effects of SDB in children are limited. The available literature indicates effects on autonomic function, right, and left heart function following treatment for SDB. However, well-designed, large-scale, prospective cohort studies (using standardized outcomes) are needed to better understand the relationship of cardiovascular morbidity in the context of pediatric SDB.

Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target. OBJECTIVE: We compared serum PCSK9 levels in young adults, with and without type 2 diabetes. SUBJECTS AND METHODS: Cross-sectional analysis was conducted in a cohort, aged 15 to 26 years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects. Correlative analyses were conducted to determine significant covariates of PCSK9 by group and sex, and multivariate linear regression models were used to study the independent determinants of PCSK9. RESULTS: In females, PCSK9 levels were significantly increased in the obese and type 2 diabetes subjects relative to the lean controls (P < .01). Moreover, PCSK9 was positively correlated with multiple metabolic parameters in females: body mass index, systolic blood pressure, fasting glucose, fasting insulin, and C-reactive protein levels (P ≤ .02). In males, PCSK9 levels were decreased overall compared with females (P = .03), and did not differ between the lean, obese, or type 2 diabetes groups. CONCLUSIONS: Obesity and type 2 diabetes were associated with significantly higher levels of PCSK9 in young women, but not in young men. These data suggest that sex could modify the effects of obesity and diabetes on PCSK9 in young adults.