Prevalence of hepatic steatosis and fibrosis in Turner syndrome: A prospective case-control study.

BACKGROUND AND AIMS: Abnormal liver chemistries are common in Turner syndrome (TS). Guidelines suggest that TS patients undergo annual screening of liver enzymes, but the role of non-invasive screening for steatosis and fibrosis is not clearly defined. We compared the prevalence of hepatic steatosis and fibrosis among TS patients to healthy controls using ultrasound with shear-wave elastography (SWE) and assessed for risk factors associated with steatosis and fibrosis in TS. METHODS: Prospective case-control study of TS versus control patients from 2019 to 2021. All patients underwent abdominal ultrasound with doppler and SWE to assess hepatic fibrosis and steatosis. Risk factors were compared between TS and controls, as well as within the TS group. RESULTS: A total of 55 TS and 50 control patients were included. Mean age was 23.6 years vs. 24.6 years in the control group (p = .75). TS patients had significantly more steatosis (65% vs. 12%, stage 1 vs. 0, p < .0001) and fibrosis (39% vs. 2%, average Metavir F2 vs. F0, p < .00001) than controls. These findings remained significant after adjusting for body mass index (BMI) (p < .01). GGT is more sensitive than AST or ALT in identifying these changes. CONCLUSION: TS is associated with an increased prevalence of hepatic steatosis and fibrosis compared to healthy controls. Our findings suggest that serum GGT and ultrasound with SWE may help identify TS patients with liver disease. Early risk factor mitigation including timely oestrogen replacement, weight control, normalization of lipids and promoting multidisciplinary collaboration should be encouraged.

Machine Learning-Enabled Fully Automated Assessment of Left Ventricular Volume, Ejection Fraction and Strain: Experience in Pediatric and Young Adult Echocardiography.

BACKGROUND: Left ventricular (LV) volumes, ejection fraction (EF), and myocardial strain have been shown to be predictive of clinical and subclinical heart disease. Automation of LV functional assessment overcomes difficult technical challenges and complexities. We sought to assess whether a fully automated assessment of LV function could be reliably used in children and young adults. METHODS: Fifty normal volunteers (22/28, female/male) were prospectively recruited for research echocardiography. LV volumes, EF, and strain were measured both manually and automatically. An experienced sonographer performed all the manual analysis and recorded the analysis timing. The fully automated analyses were accomplished by 5 groups of observers with different knowledge and medical background. AutoLV and AutoSTRAIN (TomTec) were employed for the fully automated LV analysis. The LV volumes, EF, strain, and analysis time were compared between manual and automated methods, and among the 5 groups of observers. RESULTS: Software-determined endocardial border detection was achievable in all subjects. The analysis times of the experienced sonographer were significantly shorter for AutoLV and AutoSTRAIN than manual analyses (both p < 0.001). Strong correlations were seen between conventional EF and AutoLV (r = 0.8373), and between conventional three view global longitudinal strain (GLS) and AutoSTRAIN (r = 0.9766). The volumes from AutoLV and three view GLS from AutoSTRAIN had strong correlations among different observers regardless of level of expertise. EF from AutoLV analysis had moderately strong correlations among different observers. CONCLUSION: Automated pediatric LV analysis is feasible in normal hearts. Machine learning-enabled image analysis saves time and produces results that are comparable to traditional methods.

Progression of left ventricular diastolic function in the neonate and early childhood from transmitral color M-mode filling analysis.

BACKGROUND: We implemented sophisticated color M-mode analysis to assess age-dependent progression of left ventricular (LV) diastolic function. METHODS: Normal infants were prospectively enrolled for serial echocardiograms at 1 week, 1 month, 6 months, 1 year, and 2 years. From color M-mode scans, propagation velocity (VP), strength of filling (VS), and intraventricular pressure difference (IVPD) in 3 segments along apex-to-mitral valve scan line were measured. RESULTS: Age-wise comparisons of diastolic filling from 121 echocardiograms in 31 infants showed VP (cm/s), VS (cm2/s), and E-wave IVPD (mmHg) at 1 week to be 66.2 ± 11.9, 75.3 ± 19.9, and 1.5 ± 0.4, respectively, while VP, VS, and E-wave IVPD at 1 month were 80.3 ± 14.4, 101.2 ± 28.3, and 2.42 ± 1.1, respectively. There were significant differences in VP and segmental IVPD between first week and first month (p < 0.005) and IVPD between the age groups (p < 0.001). CONCLUSIONS: Comprehensive analysis of transmitral color M-mode data is feasible in infants, enabling calculation of pressure drop between the LV base and apex and strength of propagation from two distinct slopes. Profound changes very early followed by relatively constant filling mechanics in later infancy indicate significant LV maturation occurring during the first month of life. IMPACT: We implemented sophisticated analytic methods for color M-mode echocardiography in infants to assess age- and dimension-dependent changes in left ventricular diastolic function. Comprehensive characterization of transmitral color M-mode flow was feasible, enabling calculation of pressure drop between left ventricular base and apex and strength of propagation. Left ventricular diastolic filling function has predictable maturational progression, with significant differences in the intraventricular pressure between infants from birth to 2 years. This study forms the basis for future studies to examine alteration of early diastolic filling in congenital heart disease.

Age-Related Changes in Inferior Vena Cava Dimensions among Children and Adolescents with Syncope.

OBJECTIVE: To test the hypothesis that increased venous compliance manifested as inferior vena cava (IVC) dilation is an important substrate for syncope in children. STUDY DESIGN: IVC diameters were measured in 191 children and adolescents with syncope and in 95 controls. Subjects were divided based on age <12 years (younger group) and ≥12 years (older group). IVC measurements at the right atrial junction (IVC-RA), 10 mm below the IVC-RA junction (IVC-RA10), and at the point of maximal diameter (IVCmax) were made. The linear relation to body surface area (BSA) was confirmed, as were dimensions indexed to BSA (iIVC). Relationships between iIVC and the time of day were evaluated. RESULTS: In the syncope group, the mean age was 12.9 ± 3.6 years, mean weight was 54.7 ± 23 kg, and mean BSA was 1.5 ± 0.4 m2. Among controls, all IVC dimensions varied linearly with BSA (P < .001). In the older group (140 patients with syncope and 60 controls), all iIVC dimensions were larger in the syncope cohort: iIVC-RA, 9 vs 7.7 mm/m2 (P < .0001); iIVC-RA10, 9.4 vs 8.1 mm/m2 (P < .0001); iIVCmax, 11.7 vs 10.6 mm/m2 (P = .002). In the younger group (51 patients with syncope and 35 controls), there were no differences in iIVC measurements between the syncope cohort and controls: iIVC-RA, 10.2 vs 11.3 mm/m2; iIVC-RA10, 11.7 vs 12.0 mm/m2; iIVCmax, 14.2 vs 14.7 mm/m2 (P > .05 for all). CONCLUSIONS: The IVC is enlarged in teenagers with syncope compared with controls, suggesting that venous capacitance and resultant pooling play roles in the pathogenesis of syncope. In contrast, younger children with syncope do not demonstrate IVC dilation, suggesting that their syncope arises from a different mechanism.

Impaired myocardial deformation and ventricular vascular coupling in obese adolescents with dysglycemia.

BACKGROUND: It is unknown that dysglycemia in obese adolescents has effects on myocardial deformation that are more pronounced when compared to obesity alone. We hypothesized that obesity associated abnormal glucose tolerance (dysglycemia) would have adverse effects on two-dimensional speckle tracking echocardiography derived longitudinal, radial and circumferential strain (LS, RS, CS) compared to age and gender lean controls. We also examined if changes in deformation would be reflected in abnormal ventricular vascular coupling indices (VVI). METHODS: In a prospective cross-sectional design 39 obese adolescents (15.9 ± 1.7 years; 101.5 ± 39 kg; female - 58%) were compared to age and gender matched lean controls (15.7 ± 1.8 yrs, 60 ± 12.8 kg). Based on results from an oral glucose tolerance test (OGTT), obese adolescents were categorized as obese normoglycemic (ONG, n = 25) or obese dysglycemic (ODG, n = 14). Left ventricular (LV) global and average LS, CS, RS and strain rate were measured. LV ejection fraction and mass index were measured and VVI approximated as ratio of arterial elasticity (Ea) and end-systolic elastance (Ees). RESULTS: Adolescents with ODG had significantly (P = 0.005) impaired global LS (- 20.98% ± 2.8%) compared to controls (- 23.01% ± 2.3%). A similar (P = 0.0027) reduction was observed in average LS for adolescents with ODG (18.87% ± 2.5%) compared to controls (20.49% ± 2%). Global CS was also decreased (P = 0.03) in ODG (- 23.95%) compared to ONG (- 25.80). A similar trend was observed in average CS after multivariate regression for BMI and blood pressure. CS correlated with HbA1c in both groups (P = 0.05). VVI had a negative correlation with both LS (r = - 0.4, P = 0.025) and CS rate (r = - 0.36, P = 0.04). CONCLUSIONS: Myocardial strain and strain rate were significantly altered in obese adolescents. Unfavorable subclinical reductions in global and average CS were more pronounced in adolescents with dysglycemia compared to obese adolescents with normoglycemia and controls. These data indicate progressive worsening of subendocardial function across the spectrum of glucose tolerance. Strain rate was predictive of VVI in obese adolescents, suggesting strain rate may be a sensitive marker for cardiac remodeling in abnormal glucose homeostasis states.

Persistence of right ventricular dysfunction and altered morphometry in asymptomatic preterm Infants through one year of age: Cardiac phenotype of prematurity.

INTRODUCTION: Prematurity impacts myocardial development and may determine long-term outcomes. The objective of this study was to test the hypothesis that preterm neonates develop right ventricle dysfunction and adaptive remodelling by 32 weeks post-menstrual age that persists through 1 year corrected age. MATERIALS AND METHODS: A subset of 80 preterm infants (born <29 weeks) was selected retrospectively from a prospectively enrolled cohort and measures of right ventricle systolic function and morphology by two-dimensional echocardiography were assessed at 32 weeks post-menstrual age and at 1 year of corrected age. Comparisons were made to 50 term infants at 1 month and 1 year of age. Sub-analyses were performed in preterm-born infants with bronchopulmonary dysplasia and/or pulmonary hypertension. RESULT: In both term and preterm infants, right ventricle function and morphology increased over the first year (p < 0.01). The magnitudes of right ventricle function measures were lower in preterm-born infants at each time period (p < 0.01 for all) and right ventricle morphology indices were wider in all preterm infants by 1 year corrected age, irrespective of lung disease. Measures of a) right ventricle function were further decreased and b) morphology increased through 1 year in preterm infants with bronchopulmonary dysplasia and/or pulmonary hypertension (p < 0.01). CONCLUSION: Preterm infants exhibit abnormal right ventricle performance with remodelling at 32 weeks post-menstrual age that persists through 1 year corrected age, suggesting a less developed intrinsic myocardial function response following preterm birth. The development of bronchopulmonary dysplasia and pulmonary hypertension leave a further negative impact on right ventricle mechanics over the first year of age.

Local-Community Interests and South Carolinian Newspapers' Coverage of Smoke-Free Policies.

In this quantitative content analysis, we assess how smoke-free policies are presented in South Carolinian newspapers. In particular, this study examines the extent to which newspapers' coverage of smoke free-policies has represented the interests of their local communities. We compare newspapers in the communities whose economy relies heavily on the tourism and hospitality industry (The Post & Courier in Charleston and The Sun News in Myrtle Beach) and newspapers elsewhere (The State in Columbia and The Greenville News in Greenville), and see whether there are meaningful differences between the newspapers in the way they portray smoke-free policies, particularly in terms of their selective uses of news sources and key arguments. Our findings indicate that South Carolinian newspapers portrayed smoke-free policies largely as a political issue. Many political reasons to either support or oppose the policies were found in almost two out of three articles. We also found that The Post & Courier and The Sun News were more likely than The State and The Greenville News to make arguments against smoke-free policies, and this was particularly so when they were talking about economic impacts of the policies. Public health and media advocacy implications are discussed in detail.

Media coverage of smoke-free policies after their innovation.

Smoke-free policies are critical to global tobacco control, and prior research on media coverage of smoke-free policies primarily focused on the period when they were first innovated; however, the scientific basis for smoke-free policies has broadened, and how media coverage has changed, if at all, is unknown. The authors characterized the actors, arguments, and favorability of media coverage of smoke-free policies from 2006 to 2009, by content-analyzing 452 news stories in the 4 primary newspapers in South Carolina. Most media coverage was favorable (45%) or mixed (43%) toward smoke-free policies, and negative coverage decreased over time (B = -1.001, SE = 0.326; p = .008). The most prevalent argument concerned the harms of secondhand smoke (44%). A higher percentage of articles mentioned economic arguments against (26%) than for (17%) smoke-free policies (χ(2) = 10.89, p < .01, for the difference between 26% and 17%), and these percentages did not change over time. Advocates and media should improve communications to more effectively represent scientific evidence regarding the null or positive impact of smoke-free policies on businesses.

Semi-automated quantification of tricuspid valve dynamics and structure in tetralogy of Fallot and hypoplastic left heart syndrome using three-dimensional echocardiography.

Anomalies of the tricuspid valve (TV) are associated with worsened prognosis in congenital heart disease (CHD). Here, we present a descriptive study examining changes in TV morphology in two CHD conditions-repaired tetralogy of Fallot (rTOF) and hypoplastic left heart syndrome (HLSH), using three-dimensional echocardiography. Full volume acquisitions of the TV and right ventricle (RV) were performed from an RV-focused apical view using ECG gating over 2-5 consecutive cardiac cycles using 3D echocardiography, from which TV annulus and leaflet parameters were quantified. A total of 40 rTOF patients (age 14 ± 9.8 years), 40 HLHS patients (age1.0 ± 1.5 years) and 80 age and gender matched controls were included. Among leaflet parameters, antero-posterior and posterior-septal TV coaptation heights were smaller in rTOF (p < 0.001) vs. control. Conversely, only the short-axis TV height was different in HLHS vs. controls (HLHS 1.6 ± 0.4 cm vs. control 1.4 ± 0.3 cm). TV leaflet parameters tended to be larger in HLHS, while leaflet coaptation distances were similar between groups. We demonstrate that 3D echocardiography for assessment of the TV is feasible in rTOF and HLHS patients and identifies unique differences in TV morphology. Future studies should clarify the clinical significance of TV morphology in these patient populations.

Assessment of mitral valve function in children and young adults with hypertrophic cardiomyopathy using three-dimensional echocardiography.

OBJECTIVE: The objective of this study was to assess papillary muscle (PM) and mitral valve (MV) structure and function in children and young adults with mild and moderate hypertrophic cardiomyopathy (HCM) using real-time three-dimensional echocardiography (3DE) and to correlate them with HCM related adverse outcomes. METHODS: Transthoracic research 3DE was performed in HCM patients and controls matched for age and gender. Anterolateral and posteromedial PM mass, apical displacement of anterolateral PM, and left ventricular (LV) mass were measured and indexed to body surface area. The MV annulus and leaflet structure and function were analyzed. Individual PMs were manually planimetered by tracing the endocardial borders on each mid systole frame, taking care to distinguish PMs as distinct from the LV wall. Apical PM displacement was expressed as ratio of the distance between the apex and the base of the anterolateral PM to the entire length of the LV lateral wall (APL index). All 3DE measurements were correlated to adverse outcomes. RESULTS: Forty subjects were studied, including 20 HCM patients (age 18.1 ± 9.6 years, 16 male and 4 female), and 20 controls (18.2 ± 9.6 years, 16 male and 4 female). The indexed LV mass in HCM was 74.8 ± 25.8 g/m2 compared to 50.8 ± 12.4 g/m2 in controls (p = 0.001). The anterolateral, posteromedial and combined PM mass were 3.1 ± 2.2 g/m2, 1.7 ± 1.2 g/m2 and 4.9 ± 2.7 g/m2 in HCM, in contrast to respective measurements of 1.1 ± 0.6 g/m2, 1.2 ± 0.6 g/m2 and 2.3 ± 0.8 g/m2 in controls (p < 0.001, p = 0.062, and p < 0.001, respectively). The mitral valve annular parameters (annulus circumference, height and area) in HCM were not significantly different from controls. The APL index in HCM was less than in controls (0.44 ± 0.07 vs. 0.55 ± 0.04, p < 0.001). The LV lateral wall length and LV mass correlated with adverse HCM outcomes, while the APL index and PM total mass were not associated with adverse events. CONCLUSION: It is feasible to evaluate PM muscles and MV annulus geometry in children and young adults with HCM using 3DE. The morphologic and functional changes of anterolateral PM may occur in the absence of MV annulus changes. Prospective validation will be required to determine if LV lateral wall length and LV mass may be used as predictors of adverse events.

Characterization of left ventricular cavity flow, wall stress and energy loss by color doppler vector flow mapping in children and adolescents with cardiomyopathy.

BACKGROUND: Vector flow mapping is an emerging echocardiographic method allowing for investigation of intracardiac blood flow mechanics, wall shear stress (WSS), and energy loss (EL). We hypothesized that alterations in EL and WSS will differ among subjects with hypertrophic (HCM), dilated (DCM) cardiomyopathy, and normal controls. METHODS: Echocardiograms were prospectively performed with the ProSound F75CV (Hitachi HealthCare., Tokyo, Japan) on all subjects. 2D color Doppler cine loop images were obtained from apical 5 and the apical long axis views and stored digitally. Measurements were averaged over three cardiac cycles using VFM software to derive flow patterns, WSS, and EL. Standard left ventricular (LV) systolic and diastolic functional parameters were also obtained. RESULTS: A total of 85 subjects, 22 with HCM (age 18 ± 9 yrs.), 18 DCM (age 18 ± 9 yrs.), and 45 age and gender matched controls were included in the study. Diastolic wall shear stress was found significantly different in HCM (0.004 ± 0.185 N/m2) compared with DCM (0.397 ± 0.301 N/m2, P < 0.001), and controls (0.175 ± 0.255 N/m2, P = 0.027). Furthermore, indexed systolic EL was found to be significantly elevated in HCM (13.91 ± 13.17 mW/m2/m3) compared with DCM (8.17 ± 9.77 mW/m2/m3, P < 0.001), but not controls (6.45 ± 7.47 mW/m2/m3). CONCLUSION: Differences in abnormal ventricular mechanics observed in HCM and DCM are reflected in both EL and WSS, and are suggestive that changes in energetic parameters may represent novel indices of ventricular dysfunction.

Dynamic Systolic Changes in Tricuspid Regurgitation Vena Contracta Size and Proximal Isovelocity Surface Area in Hypoplastic Left Heart Syndrome: A Three-Dimensional Color Doppler Echocardiographic Study.

BACKGROUND: The aims of this study were to investigate the dynamic changes in the vena contracta (VC) and proximal isovelocity surface area (PISA) through systole in patients with hypoplastic left heart syndrome and tricuspid regurgitation and to identify the stage of systole (early, mid, or late) in which VC and PISA radius are optimal. METHODS: Twenty-eight patients with hypoplastic left heart syndrome were prospectively studied using continuous two-dimensional (2D) and three-dimensional (3D) echocardiography. Two-dimensional VC width, 3D VC area, and PISA radii (2D and 3D) were measured frame by frame throughout systole. The maximal 2D VC width, 3D VC area, and PISA radii in the first, middle, and last thirds of systole were compared, and correlations were explored with 3D tricuspid annular areas, right atrial volumes, and right ventricular volumes. RESULTS: In all, 35 data sets that met inclusion criteria were analyzed. On frame-by-frame analysis, maximal 2D VC width and 3D VC area were found in the first third of systole in 17% and 20% of studies, in the second third in 34% and 31%, and in the final third in 49% and 49%. Similarly, the maximal 2D and 3D PISA radii were found in the first third of systole in 26% and 17% of studies, in the second third in 28% and 34%, and in the final third in 46% and 49%. CONCLUSIONS: In hypoplastic left heart syndrome, detailed temporal analysis of tricuspid regurgitation-associated VC and PISA by 2D and 3D echocardiography reveals no reliable pattern predicting when in systole these parameters peak. Frame-by-frame measurement is necessary for identification of maximal VC and PISA radius on 2D and 3D color Doppler echocardiography because the severity of tricuspid regurgitation could be underestimated because of temporal variability in VC and PISA.

Altered Biatrial Phasic Function after Heart Transplantation in Children.

PURPOSE: We used two-dimensional echocardiographic speckle-tracking to investigate whether left and right atrial (LA and RA) phasic function in pediatric heart transplantation (HT) patients is altered and explored the relationship to HT-related clinical variables. METHODS: Eighty-six subjects (36 HT and 50 normal children) were prospectively enrolled in two centers. Clinical data included age at HT, bypass time, ischemia time, donor age, and incidence of rejection. Atrial deformation indices including strain and strain rates (SRs) were measured using two-dimensional echocardiographic speckle-tracking. Components of phasic atrial function-reservoir (εr, SRr), conduit (εcd, SRcd), and booster (εct, SRct) were calculated. Comparisons with controls were made using t test or Kruskal-Wallis test, and correlations to clinical variables were explored. RESULTS: The mean age and body surface area of HT subjects were 10.2 ± 6.2 years and 1.2 ± 0.6 m2, respectively. The mean heart rates were higher in HT (96 ± 18 vs 88 ± 21 in controls). There were reductions in RA and LA reservoir (εr, SRr), conduit (εcd, SRcd), and booster (εct, SRct) function in HT compared with controls. There was no relationship of LA and RA deformation indices with mean age at HT, bypass time, or ischemia time. The LA εcd correlated weakly with donor age (r = -0.49, P = .04) and RA SRr, and SRcd showed association with duration of HT (P < .05). Nineteen HT recipients had follow-up studies 0.24 ± 0.18 years after the first examination, and deformational indices were not significantly changed. CONCLUSIONS: Atrial strain determination is feasible in pediatric HT recipients and demonstrates disruption of reservoir, conduit, and booster function of both atria in this population; we speculate this may be a consequence of ventricular diastolic dysfunction.

Maturational patterns in right ventricular strain mechanics from the fetus to the young infant.

AIM: To test the hypothesis that right ventricular (RV) function has age-specific patterns of development, we tracked the evolution of RV strain mechanics by 2D-speckle tracking echocardiography (2DSTE) in healthy subjects from mid-gestation through one year of age. METHODS: We conducted a prospective longitudinal echocardiography study in 50 healthy subjects at five time periods across gestation (16-20 weeks, 21-25 weeks, 26-30 weeks, 31-35 weeks, and 36-40 weeks) and four time periods following delivery (1 week, 1 month, 6 months, and 1 year of age). We characterized RV function by measuring RV global and free wall longitudinal strain and systolic strain rate, and segmental longitudinal strain at the apical-, mid-, and basal- ventricular levels of the free wall. Possible associations of gestational age, postnatal age, estimated fetal weight, body surface area, gender, and heart rate on strain were investigated. RESULTS: The magnitudes of RV global and free wall longitudinal strain and global strain rate were decreased throughout gestation (p < 0.05 for all). Following birth, the magnitudes of all measures increased from one week through one year (p < 0.001 for all). RV segmental longitudinal strain maintained a base-to-apex gradient (highest-to-lowest) from mid-gestation through one year (p < 0.001). There was no significant difference in strain patterns based on gender or hear rate. CONCLUSION: The maturational patterns of RV strain are gestational- and postnatal age- specific. With accepted physiological maturation patterns in healthy subjects, these myocardial deformation parameters can provide a valid basis that allows comparison between health and disease.

Clinical Outcome of Patients With Inducible Capillary Blood Flow Abnormalities During Demand Stress in the Presence or Absence of Angiographic Coronary Disease.

BACKGROUND: Our aim was to determine the cardiovascular outcome of patients with capillary blood flow (CBF) abnormalities detected during demand stress in the absence of obstructive coronary artery disease. METHODS AND RESULTS: We identified 380 consecutive patients referred for coronary angiography (CA) after dobutamine or exercise stress echocardiography (SE) between 2008 and 2013 performed with real-time perfusion imaging to examine myocardial CBF with a continuous ultrasound contrast infusion. Patients with left ventricular ejection fraction <40% were excluded. There were 3 groups based on results: positive SE/negative CA, patients who had abnormal regional CBF but no significant angiographic disease; positive SE/positive CA, those with abnormal CBF and significant disease on subsequent CA; and negative SE/negative CA, patients with normal CBF and negative CA. Event-free survival examining death and nonfatal myocardial infarction was compared. Median follow-up was 4 years. There were 91 positive SE/negative CA, 189 positive SE/positive CA, and 100 negative SE/negative CA patients over the study period. The positive SE/negative CA patients were more frequently women and had a lower prevalence of hypertension and hyperlipidemia (all P<0.001). Analysis of event-free survival with Cox regression demonstrated that death/nonfatal myocardial infarction rates were higher in the positive SE/positive CA (hazard ratio, 2.10; CI, 1.02-4.29) and positive SE/negative CA (hazard ratio, 2.02; CI, 0.99-4.31) groups when compared with negative SE/negative CA groups. CONCLUSIONS: Patients with inducible CBF abnormalities in the absence of significant obstructive disease at CA still have similar death/nonfatal myocardial infarction rates as those with significant disease at CA.

Depressed left and right ventricular cardiac output in fetuses of diabetic mothers.

INTRODUCTION: We compared right and left ventricular cardiac output (RVCO and LVCO) in fetuses of diabetic mothers (FDM) to a large normal cohort. METHODS: We prospectively enrolled 264 normal fetuses and 30 FDM. Fetal CO parameters: semilunar valve velocity time integrals (AVVTI, PVVTI), ventricular outflow diameters (LVOTD, RVOTD), stroke volumes (AVSV, PVSV) were measured, and LVCO and RVCO calculated.  These were normalized using nonlinear regression to estimated fetal weight (EFW) to provide means and standard deviations. Among FDMs, mean Z-scores and 95% confidence limits (CL) were calculated, and compared to zero. RESULTS: LVCO, RVCO, and parameters they were calculated from, increased predictably and non-linearly with increasing EFW.  In FDM, LVCO was depressed (mean Z -1.679, 95% CL -2.404, -0.955, p<0.001), and AVVTI, LVOTD, AVSV significantly lower than normal.  Similarly, RVCO (mean Z = -1.119, CL -1.839, -0.400, p=0.003), RVOTD (mean -2.085, CL -3.077, -1.093, p<0.001), and PVSV (mean -1.184, CL -1.921, -0.446, p=0.003) were lower than normal, however, PVVTI was not different (mean Z 0.078, CL -0.552, +0.707, p=0.803). CONCLUSION: Normal biventricular stroke volumes and outputs follow a nonlinear regression with EFW. FDM have significantly lower right and left heart stroke volumes and outputs for weight than do normal fetuses.

Echocardiographic phenotype in osteogenesis imperfecta varies with disease severity.

BACKGROUND AND OBJECTIVES: Our purpose was to investigate cardiovascular abnormalities in children with osteogenesis imperfecta (OI). METHODS: Two hundred children (100 OI, 100 matched volunteers) were prospectively studied. Aortic and left ventricular (LV) measurements were performed using transthoracic echocardiography. Patients were typed according to modified phenotypical Sillence classification as published in the Nosology and Classification of Genetic Skeletal disorders: 2015 Revision. RESULTS: Patients (age 9.6±4.1 years, body surface area 1.08±0.47 m2) consisted of OI types: 1 (n=44), 3/4 (n=54), 4 (n=1) and 15 (n=1). The 95% CIs for Z-score of aortic annulus, sinus, sinotubular junction and ascending aorta for OI were 0.43 to 0.73, 0.56 to 0.94, 0.28 to 0.70 and 0.78 to 1.24, respectively. In type 1, sinus, sinotubular junction and ascending aorta diameters were 2.29 cm, 1.81 cm and 2.05 cm, respectively, which did not differ compared with controls. The LV dimensions were larger in type 1. In type 3/4, aortic dimensions were larger than controls at all levels: annulus (1.61 vs 1.50 cm, p<0.001), sinus (2.19 vs 2.05 cm, p=0.001), sinotubular junction (1.77 vs 1.64 cm, p<0.001) and ascending aorta (1.98 vs 1.82 cm, p<0.001), but LV dimensions were normal. CONCLUSIONS: Cardiovascular effects are identifiable in childhood even in mild forms of OI. Aortic dilation was the predominant finding, while valvular abnormalities were infrequent. Patients with more severe skeletal pathology (types 3/4) have more significant findings. Aortic and LV dilation in type 1 vs type 3/4 appears to differ based on the biochemical mechanism of disease.

Left Ventricular Rotational and Twist Mechanics in the Human Fetal Heart.

BACKGROUND: The authors investigated left ventricular (LV) rotational indices, twist, and torsion in a large cohort of fetuses using two-dimensional speckle-tracking echocardiography. METHODS: Pregnant women (N = 102) were prospectively recruited for fetal two-dimensional speckle-tracking echocardiography. Because of variable fetal position, ventricular orientation was established using the location of the liver and LV position in relation to the right ventricle. Twist measurements required correction to account for fetal position, reconciling directionality across all fetal orientations. Peak apical and basal rotations, global longitudinal strain, global circumferential strain (GCS), longitudinal strain rate, circumferential strain rate (CSR), twist, and torsion were reported and tested for associations with gestational age (GA) and estimated fetal weight (EFW). RESULTS: Measurement of rotational indices was feasible in 175 examinations (73%). The mean maternal age was 31 ± 6 years, the mean GA 24 ± 6 weeks, and the EFW 1.0 ± 1.0 kg. Mean peak apical rotation, basal rotation, twist, and torsion were 9.5 ± 2.0°, -4.4 ± 1.1°, 13.1 ± 2.3°, and 7.9 ± 3.4°/cm, respectively. Mean global longitudinal strain, GCS, longitudinal strain rate, and CSR were -22.3 ± 4.3%, -25.0 ± 6.1%, -1.4 ± 0.5 sec-1, and -1.6 ± 0.5 sec-1, respectively. Absolute GCS, CSR, apical rotation, and twist declined moderately with GA and EFW (P < .05). There were strong negative nonlinear correlations of torsion with GA and EFW: torsion = 1,104 × GA-1.591 (r2 = 0.760, P < .001); torsion = 115.88 × EFW-0.427 (r2 = 0.772, P < .001). CONCLUSIONS: Determination of fetal LV rotational mechanics is feasible and reproducible using two-dimensional speckle-tracking echocardiography. Basal rotation, longitudinal strain, and strain rate vary little with EFW and GA. Interpretation of LV apical rotation, twist, torsion, GCS, and CSR, however, must take GA or EFW into account. These data form the basis for comparison with findings in fetuses with abnormal cardiac anatomy and function.

Right Atrial Deformation in Predicting Outcomes in Pediatric Pulmonary Hypertension.

BACKGROUND: Elevated right atrial (RA) pressure is a risk factor for mortality, and RA size is prognostic of adverse outcomes in pulmonary hypertension (PH). There is limited data on phasic RA function (reservoir, conduit, and pump) in pediatric PH. We sought to evaluate (1) the RA function in pediatric PH patients compared with controls, (2) compare the RA deformation indices with Doppler indices of diastolic dysfunction, functional capacity, biomarkers, invasive hemodynamics, and right ventricular functional indices, and (3) evaluate the potential of RA deformation indices to predict clinical outcomes. METHODS AND RESULTS: Sixty-six PH patients (mean age 7.9±4.7 years) were compared with 36 controls (7.7±4.4 years). RA and right ventricular deformation indices were obtained using 2-dimensional speckle tracking (2DCPA; TomTec, Germany). RA strain, strain rates, emptying fraction, and right ventricular longitudinal strain were measured. RA function was impaired in PH patients versus controls (P<0.001). There were significant associations between RA function with invasive hemodynamics (P<0.01). RA reservoir, pump function, the rate of RA filling, and atrial minimum volume predicted adverse clinical outcomes (hazard ratio [HR], 0.15; confidence interval [CI], 0.03-0.73; P<0.01; HR, 0.05; CI, 0.003-0.43; P<0.004; HR, 0.04; CI, 0.006-0.56; P<0.01; and HR, 8.6; CI, 1.6-37.2; P<0.01, respectively). CONCLUSIONS: RA deformation properties are significantly altered in pediatric PH patients. Progressive worsening of RA reservoir and conduit functions is related to changes in right ventricular diastolic dysfunction. RA reservoir function, pump function, the rate of atrial filling, and atrial minimum volume emerged as outcome predictors in pediatric PH.