Multimodality Noninvasive Imaging in the Monitoring of Pediatric Heart Transplantation.

Orthotopic heart transplantation is a well-established and effective therapeutic option for children with end-stage heart failure. Multiple modalities, including noninvasive cardiac imaging, cardiac catheterization, angiography, and endomyocardial biopsy, are helpful to monitor these patients for graft dysfunction, rejection, and vasculopathy. Because of morbidities associated with invasive monitoring, noninvasive imaging plays a key role in the surveillance and evaluation of symptoms in pediatric transplant recipients. Echocardiography with or without stress augmentation may provide serial data on systolic and diastolic function, ventricular deformation, and tissue characteristics in children after transplantation. Although not perfectly sensitive or specific, advanced two- and three-dimensional echocardiographic detection of functional changes in cardiac grafts may allow early recognition of allograft rejection. Magnetic resonance imaging has shown promise for characterization of edema and scar and myocardial perfusion reserve, as well as potential application for the detection of microvasculopathic changes in the transplanted heart. Cardiac computed tomography is particularly well suited for the demonstration of coronary artery dimensions and anatomic residual lesions. In combination, these noninvasive imaging techniques help the transplantation cardiologist screen for graft dysfunction, detect critical graft events, and identify situations that require invasive testing of the transplanted heart. Advanced multimodality imaging techniques are likely to increasingly shape the monitoring practices for children following heart transplantation.

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.

Left ventricular rotational mechanics in Tanzanian children with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a common inherited hemoglobinopathy. Adults with SCD manifest both systolic and diastolic cardiac dysfunction, though the age of onset of dysfunction has not been defined. Left ventricular (LV) rotational mechanics have not been studied in children with SCD. The aim of this study was to investigate whether cardiac rotational mechanics differed between children with SCD and age-matched controls. METHODS: Basal and apical LV short-axis images were acquired prospectively in 213 patients with SCD (mean age, 14.1 ± 2.6 years) and 49 controls (mean age, 13.3 ± 2.8 years) from the Muhimbili Sickle Cohort in Dar es Salaam, Tanzania. The magnitude of basal and apical rotation, net twist angle, torsion, and untwist rate were obtained by two-dimensional speckle-tracking. The timing of events was normalized to aortic valve closure. RESULTS: Mean basal rotation was significantly lower in patients with SCD compared with controls (P = .012), although no difference was observed in apical rotation (P = .37). No statistically significant differences in torsion or net twist angle were detected. Rotation rate at the apex (P = .001) and base (P = .0004) were significantly slower in subjects with SCD compared with controls. Mean peak untwisting rate was also significantly slower in patients with SCD (P = .006). No associations were found between hemoglobin concentration and apical rotation, basal rotation, net twist, and torsion. CONCLUSION: This study demonstrates alterations in LV rotational mechanics in children with SCD, including lower basal rotation, peak differential twist, and untwist rate. These abnormalities denote subclinical changes in LV systolic and diastolic performance in children with SCD. Future work may reveal an association between rotational metrics and long-term patient outcomes.

Ventricular septal defect.

BACKGROUND: Ventricular septal defects are the commonest congenital cardiac malformations. They can exist in isolation, but are also found as integral components of other cardiac anomalies, such as tetralogy of Fallot, double outlet right ventricle, or common arterial trunk. As yet, there is no agreement on how best to classify such defects, nor even on the curved surface that is taken to represent the defect. METHODS: Based on our previous pathological and clinical experiences, we have reviewed the history of classification of holes between the ventricles. We proposed that the defects are best defined as representing the area of deficient ventricular septation. This then permits the recognition of clinically significant variants according to the anatomic borders, and the way the curved surface representing the area of deficient septation opens into the morphologically right ventricle. RESULTS: Clinical manifestation depends on the size of the defect, and on the relationship between systemic and pulmonary vascular resistances. Symptoms include failure to thrive, along with the manifestations of the increase in flow of blood to the lungs. Diagnosis can be made by physical examination, but is confirmed by echocardiographic interrogation, which delineates the precise anatomy, and also provides the physiologic information required for optimal clinical decision-making. Cardiac catheterization offers additional information regarding hemodynamics, particularly if there is a concern regarding an increase in pulmonary vascular resistance. Hemodynamic assessment is rarely necessary to make decisions regarding management, although it can be helpful if assessing symptomatic adults with hemodynamically restrictive defects. In infants with defects producing large shunts, surgical closure is now recommended in most instances as soon as symptoms manifest. Only in rare cases is palliative banding of the pulmonary trunk now recommended. Closure with devices inserted on catheters is now the preferred approach for many patients with muscular defects, often using a hybrid procedure. Therapeutic closure should now be anticipated with virtually zero mortality, and with excellent anticipated long-term survival. CONCLUSION: Ventricular septal defects are best defined as representing the borders of the area of deficient ventricular septation. An approach on this basis permits recognition of the clinically significant phenotypic variants.

Coronary artery spasm during angiography in a pediatric heart transplant recipient: subsequent prevention by intracoronary nitroglycerin administration.

Coronary artery spasm can occur during coronary angiography in pediatric heart transplant recipients. The angiographic appearance can suggest allograft vasculopathy. We report coronary artery spasm in a pediatric heart transplant recipient in whom intracoronary nitroglycerin administration prevented a repetition of spasm upon subsequent diagnostic coronary angiography. Additional studies of dose response, particularly in cardiac transplant recipients, may help determine whether lower doses of intracoronary nitrates, such as that administered to our patient, can be effective in preventing coronary artery vasospasm in pediatric heart transplant recipients.

Serum amyloid A protein regulates the expression of porcine genes related to lipid metabolism.

Serum amyloid A protein (SAA) is an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of HDL. Porcine hepatic SAA mRNA is increased by dietary docosahexaenoic acid (DHA) treatment. The purpose of this study was to investigate the role of SAA protein in regulating gene expression related to lipid metabolism in pigs. First, we demonstrated that the 100-micromol/L DHA treatment increased SAA and apoA1 mRNA expression in porcine hepatic cell cultures (P < 0.05). Secondly, we produced porcine SAA recombinant protein and found that the addition of SAA to porcine preadipocytes in culture stimulated interleukin-6 (IL-6) mRNA expression (P < 0.05), indicating a similar biological function of porcine SAA and human SAA. We also found PPARalpha and PPARgamma mRNA were decreased (40 and 60%, respectively) in differentiated adipocytes after treatment with 2 mumol/L SAA. SAA treatment also increased inflammatory cytokine gene expression (IL-6 and tumor necrosis factor alpha) and glycerol release (P < 0.05), indicating increased lipolysis. Because the expression of perilipin, a lipid droplet-protective protein, was reduced by the SAA treatment, we hypothesized that SAA increased lipolysis by decreasing the expression of perilipin, which would then allow an increase in hormone sensitive lipase activity. In conclusion, we demonstrated that the DHA-induced SAA gene expression decreased PPAR expression and consequently downregulated the expression of several genes involved in lipid metabolism. Accordingly, SAA may play a critical role in mediating the function of dietary DHA on lipid metabolism and could be a factor in regulating obesity.