Relationship of Left Ventricular Mass to Lean Body Mass in the Obese Pediatric Population.

Our primary aim was to investigate the relationship between LVM and anthropometric measures including lean body mass (LBM) in obese pediatric subjects compared to normal weight controls. A retrospective chart review identified subjects 2-18 years old who were normotensive and had normal echocardiograms between 1995 and 2020 at Boston Children's Hospital. LVM was calculated with the 5/6 area length rule from 2D echocardiograms. LBM was calculated with equations derived from dual-energy X-ray absorptiometry. Of the 2217 subjects who met inclusion criteria, 203 were obese and 2014 had normal weight. The median age was 11.9 (2.0-18.9); 46% were female. The median LVM was 94.5 g (59.3-134.3) in obese subjects vs. 78.0 g (51.5-107.7) in controls. The median LBM was 37.2 kg (18.9-50.6) in obese subjects vs. 30.5 kg (17.6-40.8) in controls. In control and obese subjects, LBM had the strongest correlation to LVM (R2 0.86, P < 0.001) and (R2 0.87, P < 0.001), respectively. There was at most a modest correlation between tissue Doppler velocity z-scores and LV mass, and the largest was Septal E' z-score in obese subjects (r = - 0.31, P = 0.006). In this cohort, LBM was found to have the strongest relationship to LVM in obese subjects. The largest correlation between tissue Doppler velocity z-scores and LV mass was Septal E' z-score. Future studies will evaluate which measurements are more closely aligned with clinical outcomes in obese children.

Myocardial fibrosis in patients with a history of Kawasaki disease.

OBJECTIVES: Cardiac magnetic resonance (CMR) measurements of myocardial extracellular volume fraction (ECV) and late gadolinium enhancement (LGE) in patients with a history of Kawasaki disease (KD) were analyzed to determine whether fibrosis was increased compared to controls. METHODS: In this single center retrospective study, patients with KD who had a CMR with ECV measurement and LGE assessment were included. The ECV was calculated in the mid-left ventricle by measuring T1 values for blood pool and myocardium before and after gadolinium administration with a Look-Locker technique. CMR findings were compared to 20 control subjects. RESULTS: KD patients (n = 13) had a median age at CMR of 14.9 years (range, 7.5-36.0). Control subjects (n = 20) had a median age at CMR of 16 years (range, 11.0-36.0). Twelve KD patients had coronary aneurysms. The KD patients had a significantly lower indexed LV mass (p = 0.03) and LV mass/volume ratio (p = 0.01). ECV was not significantly different in KD patients and controls (0.26 (range, 0.20-0.30) vs. 0.25 (range, 0.18-0.28), p = 0.28). One KD patient (8%) had an increased (>0.28) ECV. LGE indicating focal fibrosis was found in 5 of 13 (38%) of KD patients. Patients with LGE tended to have a higher maximum coronary dimension z-score (p = 0.09). CONCLUSIONS: In this study of KD patients, most of whom had aneurysms, ECV did not differ significantly from that in normal controls. Focal fibrosis based on LGE was common. Future larger studies should compare ECV in KD patients with and without aneurysms to define the risk of myocardial fibrosis after KD.

Myocardial ECV Fraction Assessed by CMR Is Associated With Type of Hemodynamic Load and Arrhythmia in Repaired Tetralogy of Fallot.

OBJECTIVES: The aim of this study was to investigate the extent of diffuse myocardial fibrosis by measuring left (LV) and right ventricular (RV) extracellular volume fraction (ECV) in patients with repaired tetralogy of Fallot (rTOF) and to explore its association with ventricular remodeling, hemodynamic load, and clinical parameters. BACKGROUND: Focal myocardial fibrosis is prevalent in patients with rTOF. However, little is known about the extent of diffuse myocardial fibrosis and its clinical implications in this population. METHODS: We measured ECV by pre- and post-gadolinium T1 measurements using a 1.5-T scanner in 84 patients with rTOF (median age 23.3 years). LV ECV was determined by averaging values from 6 short-axis mid-ventricular segments, and RV ECV was calculated by averaging values from the anterior-inferior and the diaphragmatic RV wall segments. RESULTS: LV ECV above the upper limit of normal (>28%) was observed in 11 patients and for RV ECV (>41%) in 9 patients. LV ECV correlated positively with RV ECV (r = 0.54; p < 0.001). Greater RV ECV was associated with female gender, lower RV mass-to-volume ratio, lower RV outflow tract pressure gradient, and having volume overload as the predominant hemodynamic burden (all p < 0.001). Similar associations were observed with LV ECV. In multivariable analysis, increased LV ECV was independently associated with arrhythmia, adjusting for age and RV mass index (odds ratio: 5.69; p = 0.031). CONCLUSIONS: In this cohort, LV and RV ECV values were positively correlated, indicating an adverse ventricular-ventricular interaction at the tissue level. Increased ECV was associated with RV volume overload and arrhythmia. These findings may lead to future studies exploring the role of ECV in improving risk stratification and guiding therapeutic interventions.

Left Ventricular Strain and Myocardial Fibrosis in Congenital Aortic Stenosis.

The aim of this study was to evaluate whether left ventricular (LV) systolic strain in children and young adults with congenital aortic stenosis (AS) and preserved ejection fraction was different from normal subjects and to determine whether any alterations in strain were related to myocardial fibrosis. In this retrospective study, 29 patients with congenital AS with a median age of 15.3 years (range 1.7 to 23.7), highest lifetime AS peak Doppler gradient of 73 mm Hg (22 to 110), most recent AS peak Doppler gradient of 49 mm Hg (0 to 90), and ejection fraction of 65 (55 to 79) were included. Strain was measured using 2-dimensional speckle-tracking echocardiography. Cardiac magnetic resonance was used to identify focal fibrosis by late gadolinium enhancement (LGE) and diffuse fibrosis by calculating the extracellular volume fraction (ECV) from T1 measurements. Compared to age-matched controls (n = 29), patients with AS had reduced LV longitudinal (17.0 ± 3.0% vs 20.6 ± 2.2%, p <0.001) and radial strain (28.8 ± 8.6% vs 34.9 ± 8.5%, p = 0.01), and similar circumferential strain (26.2 ± 5.9% vs 26.4 ± 3.9%, p = 0.79). Median ECV in patients with AS was 0.27 (0.22 to 0.38) and was not significantly correlated with systolic strain. Patients with LGE (n = 7) had lower longitudinal strain than those without LGE (n = 21; 15.0 ± 2.2 vs 17.7 ± 3.1, p = 0.036). In conclusion, in this cohort of children and young adults with congenital AS and preserved ejection fraction, longitudinal and radial strain were reduced, and decreased longitudinal strain was associated with LGE but not ECV.

Myocardial extracellular remodeling is associated with ventricular diastolic dysfunction in children and young adults with congenital aortic stenosis.

OBJECTIVES: This study sought to analyze cardiac magnetic resonance (CMR) measurements of myocardial extracellular volume fraction (ECV) and late gadolinium enhancement (LGE) in children and young adults with congenital aortic stenosis (AS) to determine the extent of fibrosis and examine their association with aortic valve and ventricular function. BACKGROUND: Patients with congenital AS frequently have impaired diastolic ventricular function and exercise capacity that may be related to myocardial fibrosis. METHODS: A total of 35 patients with congenital AS (median age 16 years) and 27 normal control subjects (median age 16 years) were evaluated by CMR. ECV was calculated from pre- and post-gadolinium contrast T1 measurements of blood and myocardium, and the hematocrit. RESULTS: ECV was significantly higher in AS patients than in normal subjects (median 0.27 [range 0.22 to 0.42] vs. 0.25 [range 0.18 to 0.27], p = 0.001). LGE was present in 8 (24%) of the AS patients. A higher ECV was correlated with echocardiographic indexes of diastolic dysfunction including a higher mitral E-wave z-score (r = 0.58, p = 0.002), E/septal E' z-score (r = 0.56, p = 0.003), E/mean E' z-score (r = 0.55, p = 0.003), and indexed left atrial volume (r = 0.56, p = 0.001). Other factors associated with an elevated ECV (>0.28) included a greater number of aortic valve interventions (p = 0.004) and a greater number of aortic valve balloon valvuloplasties (p = 0.003). ECV was not significantly associated with AS gradient, left ventricular mass, mass/volume ratio, or ejection fraction. CONCLUSIONS: In young patients with AS, myocardial ECV is significantly elevated compared with control subjects and is associated with echocardiographic indexes of diastolic dysfunction. ECV measured by CMR may be a useful method for risk stratification and monitoring therapies targeting fibrosis.

Outcome predictors and implications for management of scimitar syndrome.

BACKGROUND: Scimitar syndrome is a rare congenital anomaly. We evaluated risk factors for postoperative pulmonary vein stenosis or death and predictive factors for survival without scimitar vein surgery in patients with scimitar syndrome. METHODS: The records of patients with scimitar syndrome evaluated at our medical center between 1964 and 2011 were reviewed. RESULTS: Scimitar syndrome was identified in 80 patients, with a median follow-up of 4.5 years. Patients presenting less than 1 year of age had a higher incidence of symptoms, aortopulmonary collaterals, coexisting congenital heart disease (CHD), extracardiac anomalies, and pulmonary hypertension. Of 36 patients having scimitar vein surgery, 18 had postoperative pulmonary vein obstruction that occurred with similar frequency after baffle or reimplantation procedures, early or late in the study period, and tended to be more common in infants (P = .10). Overall, 19 (24%) of 80 died. Multivariate risk factors for death included systolic pulmonary pressure >0.5 systemic level (P = .007) and left pulmonary vein stenosis (P = .009). Pulmonary artery systolic pressure <0.5 systemic level (P = .01) and absence of CHD excluding atrial septal defect (P = .01) were predictive factors in 28 patients who survived and did not have scimitar vein surgery; these patients had no or mild right ventricular dilation and a ratio of pulmonary-to-systemic flow <1.6 either at baseline, after coiling aortopulmonary collaterals or nonscimitar vein intervention. CONCLUSIONS: Postoperative pulmonary vein obstruction is common after scimitar vein surgery regardless of redirection technique. Pulmonary hypertension and left pulmonary vein stenosis are risk factors for death, whereas patients without significant pulmonary hypertension or associated CHD did well without scimitar vein surgery. These observations may guide management decisions in patients with scimitar syndrome.

Neurotrophin and GDNF family ligands promote survival and alter excitotoxic vulnerability of neurons derived from murine embryonic stem cells.

Embryonic stem (ES) cells are genetically manipulable pluripotential cells that can be differentiated in vitro into neurons, oligodendrocytes, and astrocytes. Given their potential utility as a source of replacement cells for the injured nervous system and the likelihood that transplantation interventions might include co-application of growth factors, we examined the effects of neurotrophin and GDNF family ligands on the survival and excitotoxic vulnerability of ES cell-derived neurons (ES neurons) grown in vitro. ES cells were differentiated down a neural lineage in vitro using the 4-/4+ protocol (Bain et al., Dev Biol 168:342-57, 1995). RT-PCR demonstrated expression of receptors for neurotrophins and GDNF family ligands in ES neural lineage cells. Neuronal expression of GFRalpha1, GFRalpha2, and ret was confirmed by immunocytochemistry. Exposure to 30-100 ng/ml GDNF or neurturin (NRTN) resulted in activation of ret. Addition of NT-3 and GDNF did not increase cell division but did increase the number of neurons in the cultures 7 days after plating. Pretreatment with NT-3 enhanced the vulnerability of ES neurons to NMDA-induced death (100 microM NMDA for 10 min) and enhanced the NMDA-induced increase in neuronal [Ca2+]i, but did not alter expression of NMDA receptor subunits NR2A or NR2B. In contrast, pretreatment with GDNF reduced the vulnerability of ES neurons to NMDA-induced death while modestly enhancing the NMDA-induced increase in neuronal [Ca2+]i. These findings demonstrate that the response of ES-derived neurons to neurotrophins and GDNF family ligands is largely similar to that of other cultured central neurons.