Association of hydroxyurea adherence with transcranial Doppler screenings in children with sickle cell disease.

BACKGROUND: National sickle cell disease (SCD) guidelines recommend oral hydroxyurea (HU) starting at 9 months of age, and annual transcranial Doppler (TCD) screenings to identify stroke risk in children aged 2-16 years. We examined prevalence and proportion of TCD screenings in North Carolina Medicaid enrollees to identify associations with sociodemographic factors and HU adherence over 3 years. STUDY DESIGN: We conducted a longitudinal study with children ages 2-16 years with SCD enrolled in NC Medicaid from years 2016-2019. Prevalence of TCD screening claims was calculated for 3 years, and proportion was calculated for 12, 24, and 36 months of Medicaid enrollment. Enrollee HU adherence was categorized using HU proportion of days covered. Multivariable Poisson regression assessed for TCD screening rates by HU adherence, controlling for age, sex, and rurality. RESULTS: The prevalence of annual TCD screening was between 39.5% and 40.1%. Of those with 12-month enrollment, 77.8% had no TCD claims, compared to 22.2% who had one or higher TCD claims. Inversely, in children with 36 months of enrollment, 36.7% had no TCD claims compared to 63.3% who had one or higher TCD claims. The proportion of children with two or higher TCD claims increased with longer enrollment (10.5% at 12 months, 33.7% at 24 months, and 52.6% at 36 months). Children with good HU adherence were 2.48 (p < .0001) times more likely to have TCD claims than children with poor HU adherence. CONCLUSION: While overall TCD screening prevalence was low, children with better HU adherence and longer Medicaid enrollment had more TCD screenings. Multilevel interventions are needed to engage healthcare providers and families to improve both evidence-based care and annual TCD screenings in children with SCD.

Two-Dimensional Ultrasound Assessment of Long-Term Intra-Abdominal Organ Changes in Children with Sickle Cell Anemia during Steady State: A Comparative Study.

BACKGROUND: Sickle cell anemia (SCA) is a hereditary blood disorder with global prevalence, including in Nigeria. Despite advancements in SCA care management, understanding the long-term impact on organs during steady state has remained inconclusive. AIM: This study aimed to investigate the long-term changes in intra-abdominal organs of SCA children compared with non-SCA children during steady state using two-dimensional ultrasound assessment. MATERIALS AND METHODS: A total of 116 children (58 SCA and 58 controls) were enrolled between June 2021 and July 2022. Clinico-demographic data were collected through an interviewer-administered questionnaire. Two-dimensional ultrasound was used to measure the liver, spleen, kidneys, and inferior vena cava in all subjects. Age-matched controls had AA or AS genotypes. RESULTS: Of the 58 patients with SCA, 65.5% were males with an overall mean age of 8.1 ± 3.4 years, while among the non-SCA cohort (n = 58), 48.3% were males with an overall mean age of 8.7 ± 3.9 years. There was no statistically significant difference in the age and gender distribution between the SCA and non-SCA cohorts (P = 0.390 and P = 0.091, respectively). SCA subjects had a larger mean hepatic size than non-SCA subjects (12.09 cm ± 2.23 vs. 11.67 cm ± 1.96; P = 0.276) but smaller mean splenic size (8.01 cm ± 1.89 vs. 8.19 cm ± 1.61; P = 0.577) and inferior vena cava diameter (1.16 cm ± 0.29 vs. 1.25 cm ± 0.33; P = 0.100). Left kidney length and breadth were significantly greater in SCA patients (8.91 ± 1.16 vs. 8.27 ± 1.30; P = 0.006 and 4.15 ± 0.92 vs. 3.79 ± 0.48; P = 0.008, respectively). CONCLUSION: This study highlights the utility of two-dimensional ultrasound assessment in monitoring intra-abdominal organ changes in SCA children, suggesting its cost-effective benefits in monitoring health outcomes in SCA patients.

Positive rate and quality assessment of CT pulmonary angiography in sickle cell disease: a case‒control study.

BACKGROUND: Pulmonary complications are common in sickle cell disease (SCD) and can mimic pulmonary embolisms (PEs), leading to potential overuse of computed tomography pulmonary angiography (CTPA). Maximizing the quality of CTPA is essential for its diagnostic accuracy. However, little is known about the positive rate and quality of CTPA in SCD. METHODS: This retrospective case‒control study aimed to determine the positive rate and quality of CTPA studies performed to rule out PE in SCD (HbSS genotype) patients compared to a control group. Logistic regression analysis was used to identify independent factors associated with suboptimal CTPA studies, defined as a mean enhancement of < 210 HU in the pulmonary artery. RESULTS: The study included 480 patients, consisting of 240 SCD patients and 240 controls. The positive rate of PE was 4.0%, with a similar rate in both SCD patients and the control group (4.2% vs. 3.8%, p = 0.08). However, SCD patients had significantly lower contrast enhancement of the pulmonary artery than the control group (266.1 ± 90.5 HU vs. 342.2 ± 116.1 HU, p < 0.01). Notably, 25.4% of SCD patients had suboptimal scans. The logistic regression model demonstrated that SCD was significantly associated with suboptimal pulmonary arterial contrast enhancement compared to the control group (OR = 4.4; 95% CI: 2.4-8.3). CONCLUSIONS: This study revealed a relatively low positive rate of CTPA in both SCD patients and the control group. However, SCD was significantly associated with suboptimal image quality due to inadequate contrast enhancement of the pulmonary artery. Further research is needed to identify measures that can enhance the quality of CTPA studies in SCD patients and to establish a specific imaging protocol for this patient population.

Distribution of sickle cell disease and assessment of risk factors based on transcranial Doppler values in the Gulf region.

Background/Objective: Stroke is a potentially fatal complication of sickle cell disease (SCD). Transcranial Doppler (TCD) is useful at identifying increased risk of stroke in children with SCD and vasospasm after subarachnoid hemorrhage. The main aim of this study was to determine the proportion of patients with SCD in the Gulf region who are at a high risk of stroke, as determined by TCD.Methods: This multicenter (Oman, Qatar, and UAE), descriptive, cross-sectional study in patients (aged 2-16 years) with SCD included a baseline visit, 1 follow-up visit for patients with conditional TCD, and 3-year retrospective data analysis for all patients.Results: Of the 410 eligible patients (Oman, 86.5%; Qatar, 8.2%; UAE, 5.1%), most had a TCD finding (left side, 91.7%; right side, 92.0%) of normal velocity (<155 cm/s) at baseline. For 6 of 7 patients with conditional velocity (155-179 cm/s) and 1 patient with high velocity (≥180 cm/s), baseline TCD results were not confirmed at follow-up. As per bivariate linear regression, age, race, transfusion type, and transfusion frequency were significant predictors of the TCD velocities. Multivariate logistic regressions revealed that TCD velocities were significantly correlated with sex, race, and type of transfusion. No patients reported any adverse events at follow-up. No deaths occurred during the study.Discussion/Conclusions: The study results show that far fewer patients with SCD in the Gulf have abnormal TCD findings than the internationally reported. Larger studies are needed to identify the factors underlying this observation.

ASSESSMENT OF MACULAR VASCULATURE OF CHILDREN WITH SICKLE CELL DISEASE COMPARED TO THAT OF HEALTHY CONTROLS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: This study aims at describing the macular vascular features of the eyes of pediatric patients with the homozygous form of sickle cell disease (SCD) using optical coherence tomography angiography. METHODS: This is a retrospective case series of eyes of pediatric patients with SCD, race- and age-matched to those of healthy individuals. Using optical coherence tomography angiography images of superficial capillary plexus and deep capillary plexus, the nonflow area, vascular density, and foveal avascular zone were measured. The remodeled microvascular foveal architectures obtained on optical coherence tomography angiography and fluorescein angiography were compared. RESULTS: A total of 19 eyes of patients with SCD and 18 eyes of race-matched healthy controls were examined. The best-corrected visual acuity ranged from 75 to 85 letters in all cases. In the SCD series, 8 eyes displayed signs of retinopathy on funduscopy. The foveal avascular zone was significantly enlarged, the foveal vascular density was 8% lower, and there were more perifoveal vascular alterations in the eyes of patients with SCD compared to those of controls. CONCLUSION: The foveal vascular density was significantly reduced and area of the foveal avascular zone was significantly increased in the eyes of patients with SCD. Consistent architectural changes in the perifoveal capillaries were also observed in the pediatric patients with SCD.

A method for age-matched OCT angiography deviation mapping in the assessment of disease- related changes to the radial peripapillary capillaries.

PURPOSE: To present a method for age-matched deviation mapping in the assessment of disease-related changes to the radial peripapillary capillaries (RPCs). METHODS: We reviewed 4.5x4.5mm en face peripapillary OCT-A scans of 133 healthy control eyes (133 subjects, mean 41.5 yrs, range 11-82 yrs) and 4 eyes with distinct retinal pathologies, obtained using spectral-domain optical coherence tomography angiography. Statistical analysis was performed to evaluate the impact of age on RPC perfusion densities. RPC density group mean and standard deviation maps were generated for each decade of life. Deviation maps were created for the diseased eyes based on these maps. Large peripapillary vessel (LPV; noncapillary vessel) perfusion density was also studied for impact of age. RESULTS: Average healthy RPC density was 42.5±1.47%. ANOVA and pairwise Tukey-Kramer tests showed that RPC density in the ≥60yr group was significantly lower compared to RPC density in all younger decades of life (p<0.01). Average healthy LPV density was 21.5±3.07%. Linear regression models indicated that LPV density decreased with age, however ANOVA and pairwise Tukey-Kramer tests did not reach statistical significance. Deviation mapping enabled us to quantitatively and visually elucidate the significance of RPC density changes in disease. CONCLUSIONS: It is important to consider changes that occur with aging when analyzing RPC and LPV density changes in disease. RPC density, coupled with age-matched deviation mapping techniques, represents a potentially clinically useful method in detecting changes to peripapillary perfusion in disease.

Magnetic Resonance Imaging Assessment of Kidney Oxygenation and Perfusion During Sickle Cell Vaso-occlusive Crises.

BACKGROUND: Our understanding of the pathophysiologic processes underlying sickle cell nephropathy remains incomplete. We performed a pilot study to investigate the potential value of magnetic resonance imaging (MRI) for the assessment of kidney oxygenation and detection of potential changes to tissue perfusion and cellular integrity during a vaso-occlusive crisis. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: 10 homozygous patients with sickle cell disease (SCD), without kidney disease (based on estimated glomerular filtration rate and albuminuria), underwent renal MRI during a vaso-occlusive crisis episode. The imaging data obtained were compared with those for a second MRI performed at steady state (median, 56 [IQR, 37-72] days after the vaso-occlusive crisis MRI). The control group consisted of 10 apparently healthy individuals. MEASUREMENTS: Deoxyhemoglobin level assessed by R2* value was calculated using the blood oxygen level-dependent technique. The intravoxel incoherent motion diffusion-weighted imaging technique was used to calculate D, D*, and F parameters. RESULTS: Median medullary R2* values on steady-state MRI were significantly higher for patients with SCD than for controls (P=0.01) and did not change significantly during the vaso-occlusive crisis. No significant differences in median cortical R2* values were observed. Both cellular integrity (D) and local perfusion (D* and F) were significantly altered in medullary and cortical areas during vaso-occlusive crises in comparison to steady state in patients with SCD. These parameters did not differ significantly between patients with SCD assessed at steady state and the control group. LIMITATIONS: Small sample size, estimation of glomerular filtration rate according to CKD-EPI creatinine equation without adjustment for race. CONCLUSIONS: Deoxyhemoglobin levels in the medullary area are higher in patients with SCD, during vaso-occlusive crises and at steady state, than in controls. Alterations to the tissue perfusion and cellular integrity of renal parenchyma are a common finding during vaso-occlusive crises that provide additional evidence that a vaso-occlusive crisis may be associated with subclinical kidney injury detectable on MRI.

Transcranial Doppler Screening Among Children and Adolescents With Sickle Cell Anemia.

IMPORTANCE: With transcranial Doppler (TCD) screening, we can identify children and adolescents with sickle cell anemia who are at the highest risk of stroke. An accurate claims-based method for identifying children and adolescents with sickle cell anemia was recently developed and validated that establishes the necessary groundwork to enable large population-based assessments of health services utilization among children and adolescents with sickle cell anemia using administrative claims data. OBJECTIVE: To assess the feasibility of using administrative claims data to identify and describe the receipt of TCD screening among children and adolescents with sickle cell anemia and to characterize opportunities for intervention. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cross-sectional study using Medicaid claims data from 2005 to 2010. Medicaid claims data were obtained from the following states: Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Children and adolescents 2 to 16 years of age with sickle cell anemia were identified by the presence of 3 or more Medicaid claims with a diagnosis of sickle cell anemia within a calendar year (2005-2010). A total of 4775 children and adolescents contributed 10 787 person-years throughout the study period. Data were analyzed in 2015. A subset of children and adolescents enrolled for 2 or more consecutive years was identified to examine potential predictors of TCD screening, which included age, sex, previous receipt of TCD screening, state of residence, and health services utilization (well-child visits, outpatient visits, emergency department visits, and inpatient visits). MAIN OUTCOMES AND MEASURES: Receipt of TCD screening was assessed by year and state. Using logistic regression with generalized estimating equations, we included associated predictors in a multivariable model to estimate odds of TCD screening. RESULTS: For a total of 4775 children and adolescents 2 to 16 years of age, TCD screening rates increased over the 6-year study period from 22% to 44% (P < .001); rates varied substantially across states. A subset of 2388 children and adolescents with sickle cell anemia (50%) was enrolled for 2 or more consecutive years. Each year of increasing age was associated with 3% lower odds of TCD screening (odds ratio, 0.97 [95% CI, 0.95-0.98]; P = .002). Previous receipt of TCD screening (odds ratio, 2.44 [95% CI, 2.11-2.81]; P < .001) and well-child visits (odds ratio, 1.10 [95% CI, 1.03-1.18]; P = .007) were associated with higher odds of receiving a TCD screening. CONCLUSIONS AND RELEVANCE: Despite national recommendations, TCD screening rates remain low. Successful strategies to improve TCD screening rates may capitalize on the numerous health care interactions among children and adolescents with sickle cell anemia.

Tissue Doppler Imaging-derived Diastolic Function Assessment in Children With Sickle Cell Disease and Its Relation With Ferritin.

Diastolic dysfunction has been shown to occur earlier than systolic dysfunction in iron overload states in adult patients with sickle cell disease (SCD). Tissue Doppler imaging (TDI)-derived E/E' has emerged as a noninvasive marker of diastolic function. We sought to determine diastolic function in children with SCD and study its relation with iron overload. A retrospective review of medical records of 225 pediatric patients with SCD who received an echocardiogram between January 2008 and December 2012 was performed. Echocardiographic measures including M-mode, spectral Doppler, and TDI-derived E/E' were compared with previously published data in healthy children. The left ventricular end-diastolic and end-systolic dimensions were significantly higher in SCD (P<0.0001) and the shortening fraction was similar (P=0.66). E/E' ratio was significantly higher in SCD at the mitral annulus, septum, and tricuspid annulus. In 54% of subjects, the septal E/E' was >8, indicating elevated left ventricular filling pressure. However, there was no significant correlation between ferritin level and E/E' ratios. Pediatric patients with SCD have a high prevalence of elevated estimated left ventricular filling pressure, but this does not correlate with ferritin levels.

Doppler assessment of renal hemodynamic alterations in homozygous sickle cell disease and sickle Beta-thalassemia.

We evaluated the renal vascular indices in children and adolescents with sickle cell disease (SCD) using Doppler ultrasonography. We also assessed the renal hemodynamics alterations in patients with homozygous SCD and sickle beta-thalassemia (sickle ß-thalassemia). We studied 75 patients (age range = 3-20 years; M = 9.95 ± 4.15) with SCD: 42 patients suffering from homozygous SCD and 33 patients diagnosed with sickle ß-thalassemia. Thirty, age- and sex-matched, normal subjects were also included as a control group. Both patients and control groups had Doppler assessment of pulsatility (PI) and resistivity (RI) indices of main renal, segmental, interlobar, and arcuate arteries. Both PIs and RIs were significantly higher in SCD patients, compared with the control group. Among patients, PIs and RIs in the main renal, segmental, interlobar, and arcuate arteries were significantly higher in patients with homozygous SCD as compared with those with sickle ß-thalassemia (p values <0.01, <0.001, <0.001, and <0.001 for PIs and <0.001, <0.001, <0.001, and <0.01 for RIs, respectively). We concluded that renal vascular resistance is raised in children and adolescents with SCD. This is more pronounced in patients with homozygous SCD as compared with those with sickle ß-thalassemia.

Transcranial Doppler screening of Medicaid-insured children with sickle cell disease.

Transcranial Doppler screening reduces the risk of stroke in children with sickle cell disease. We tested the effect of informational letters sent to parents and doctors of Medicaid-insured children on improving screening efficiency. The letters did not improve the low baseline screening rates, suggesting the need for more aggressive outreach. Hematologist visits were correlated with increased screening rates.

Assessment of ventricular function in adults with sickle cell disease: role of two-dimensional speckle-tracking strain.

BACKGROUND: Sickle cell disease (SCD) is a hemoglobinopathy that is common worldwide. It usually presents with cardiac involvement, although data on systolic function are somewhat controversial. The aim of this study was to investigate the value of speckle-tracking strain, a deformation index, in detecting ventricular dysfunction in SCD. METHODS: Ninety adult patients with SCD were compared with 20 healthy controls. Doppler echocardiography with Doppler tissue imaging was performed in all, and the left and right ventricles were analyzed by the use of two-dimensional speckle-tracking strain. RESULTS: The mean age of the patients with SCD was 26 years, and 43% were men. Left ventricular (LV) dimensions and mass were higher in patients with SCD, whereas LV ejection fraction did not differ from the controls. E and A waves, as well as E/e' ratio, were also higher in patients with SCD. Two-dimensional speckle-tracking strain of both ventricles in the patients with SCD was not different from that of controls. The factors independently associated with LV longitudinal strain were age (P = .009), oximetry (P = .001), lactate dehydrogenase (P = .014), LV ejection fraction (P < .001), and right ventricular systolic annular velocity (P = .010). CONCLUSIONS: Ventricular enlargement with normal ventricular function was a frequent finding in SCD. Two-dimensional speckle-tracking strain of both ventricles was similar in patients and controls, suggesting normal myocardial contractility in patients with SCD. LV global longitudinal strain was associated with age, intensity of hemolysis, and ventricular function.

The clinical effectiveness and cost-effectiveness of primary stroke prevention in children with sickle cell disease: a systematic review and economic evaluation.

BACKGROUND: Sickle cell disease (SCD) is a recessive genetic blood disorder, caused by a mutation in the ß-globin gene. For children with SCD, the risk of stroke is estimated to be up to 250 times higher than in the general childhood population. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique which measures local blood velocity in the proximal portions of large intracranial arteries. Screening with TCD ultrasonography identifies individuals with high cerebral blood velocity; these children are at the highest risk of stroke. A number of primary stroke prevention strategies are currently used in clinical practice in the UK including blood transfusion, treatment with hydroxycarbamide and bone marrow transplantation (BMT). No reviews have yet assessed the clinical effectiveness and cost effectiveness of primary stroke prevention strategies in children with SCD identified to be at high risk of stroke using TCD ultrasonography. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of primary stroke prevention treatments for children with SCD who are identified (using TCD ultrasonography) to be at high risk of stroke. DATA SOURCES: Electronic databases were searched from inception up to May 2011, including the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), EMBASE, the Health Technology Assessment (HTA) database, ISI Web of Science Proceedings, ISI Web of Science Citation Index, the NHS Economic Evaluation Database (NHS EED) and MEDLINE. REVIEW METHODS: The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. A de novo Markov model was developed to determine the cost-effectiveness of TCD ultrasonography and blood transfusion, where clinically appropriate, in patients with SCD. RESULTS: Two randomised controlled trials met the inclusion criteria involving a study population of 209 participants. One compared blood transfusion with standard care for children who are identified as being at high risk of stroke using TCD ultrasonography. In this trial, one patient in the transfusion group had a stroke (1/63) compared with 11 children in the standard care group (11/67). The other trial assessed the impact of halting chronic transfusion in patients with SCD. Sixteen patients in the transfusion-halted group had an event (16/41) (two patients experienced stroke and 14 reverted to abnormal TCD velocity); there were no events in the continued-transfusion group (0/38). No meta-analyses of these trials were undertaken. No relevant economic evaluations were identified for inclusion in the review. The de novo modelling suggests that blood transfusions plus TCD scans (compared with just TCD scans) for patients with SCD at high risk of stroke, aged ≥ 2 years, may be good value for money. The intervention has an incremental cost-effectiveness ratio of £24,075 per quality-adjusted life-year gained, and helps avoid 68 strokes over the lifetime of a population of 1000 patients. The intervention costs an additional £13,751 per patient and generates 0.6 extra years of life in full health per patient. The data available for the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusion of the model is reliable but further research is required to validate these findings. LIMITATIONS: The main limitations relate to the availability of published clinical data; no completed randomised controlled trials were identified which evaluated the efficacy of either BMT or hydroxycarbamide for primary stroke prevention. Both the clinical and cost data available for use in the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusions of the model are reliable, but further research is required to validate these findings. CONCLUSIONS: The use of TCD ultrasonography to identify children at high risk of stroke, and treating these children with prophylactic blood transfusions, appears to be both clinically effective and cost-effective compared with TCD ultrasonography only. However, given the limitations in the data available, further research is required to verify this conclusion. Several research recommendations can be proposed from this review. Clinically, more research is needed to assess the effects and optimal duration of long-term blood transfusion and the potential role of hydroxycarbamide in primary stroke prevention. From an economics perspective, further research is required to generate more robust data on which to base estimates of cost-effectiveness or against which model outputs can be calibrated. More data are required to explain how utility weights vary with age, transfusions and strokes. Research is also needed around the cost of paediatric stroke in the UK. STUDY REGISTRATION: PROSPERO CRD42011001496. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Stenosis or hyperperfusion in sickle cell disease--ultrasound assessment of cerebral blood flow volume.

Increased blood flow velocity (BFV) in basal cerebral arteries measured by transcranial color-coded sonography (TCCS) is a stroke risk factor in sickle cell disease (SCD). Raised BFV may be caused by vessel narrowing or by hyperperfusion. In 44 SCD patients and 14 controls, intracranial arterial BFVs and global cerebral blood flow (CBF) were analyzed by TCCS and extracranial duplex ultrasound, respectively. Magnetic resonance imaging and magnetic resonance angiography were performed in all patients with pathologic intracranial BFV rise. Intracranial BFVs and CBF in SCD were significantly higher than in controls. CBF in SCD correlated with BFV in all intracranial arteries and correlated inversely with age and hemoglobin values. Magnetic resonance angiography failed to demonstrate any stenosis in our SCD patients, thus raised intracranial BFVs must be interpreted as an anemia-dependent cerebral hyperperfusion. These findings suggest that the pathomechanism of stenosis-derived arterio-arterial embolism might be less relevant in SCD-related ischemic stroke, and other factors like small vessel disease or sickle cell-induced microvascular blood clotting have to be considered.

Segmentation and quantification of pulmonary artery for noninvasive CT assessment of sickle cell secondary pulmonary hypertension.

PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive vascular disease that results in high mortality and morbidity in sickle cell disease (SCD) patients. PAH diagnosis is invasive via right heart catheterization, but manual measurements of the main pulmonary artery (PA) diameters from computed tomography (CT) have shown promise as noninvasive surrogate marker of PAH. The authors propose a semiautomated computer-assisted diagnostic (CAD) tool to quantify the main PA size from pulmonary CT angiography (CTA). METHODS: A follow-up retrospective study investigated the potential of CT and image analysis to quantify the presence of PAH secondary to SCD based on PA size. The authors segmented the main pulmonary arteries using a combination of fast marching level sets and geodesic active contours from smoothed pulmonary CTA images of 20 SCD patients with proven PAH by right heart catheterization and 20 matched negative controls. From the PA segmentation, a Euclidean distance map was calculated and an algorithm based on fast marching methods was used to compute subvoxel precise centerlines of the PA trunk (PT) and main left/right PA (PM). Maximum distentions of PT and PM were automatically quantified using the centerline and validated with manual measurements from two observers. RESULTS: The pulmonary trunk and main were significantly larger (p < 0.001) in PAH/SCD patients (33.73 +/- 3.92 mm for PT and 25.17 +/- 2.90 for PM) than controls (27.03 +/- 2.94 mm for PT and 20.62 +/- 3.06 for PM). The discrepancy was qualitatively improved when vessels' diameters were normalized by body surface area (p < 0.001). The validation of the method showed high correlation (mean R=0.9 for PT and R = 0.91 for PM) and Bland-Altman agreement (0.4 +/- 3.6 mm for PT and 0.5 +/- 2.9 mm for PM) between CAD and manual measurements. Quantification errors were comparable to intraobserver and interobserver variability. CAD measurements between two different users were robust and reproducible with correlations of R = 0.99 for both PT and PM and Bland-Altman agreements of -0.13 +/- 1.33 mm for PT and -0.08 +/- 0.84 mm for PM. CONCLUSION: Results suggest that the semiautomated quantification of pulmonary artery has sufficient accuracy and reproducibility for clinical use. CT with image processing and extraction of PA biomarkers show great potential as a surrogate indicator for diagnosis or quantification of PAH, and could be an important tool for drug discovery and noninvasive clinical surveillance.

Assessment of cardiac functions in sickle cell anemia with Doppler myocardial performance index.

BACKGROUND: The purpose of this study was to evaluate left and right ventricular functions by using the Doppler myocardial performance index (MPI), in children with sickle cell anemia (SCA). METHODS: We examined 32 patients with SCA and 30 age-matched healthy children. Echocardiography and Doppler examinations were completed for each of the subjects. MPI was calculated from the Doppler tracings. RESULTS: Compared with controls, left ventricle (LV) end-diastolic diameter, end-systolic diameter, early-diastolic mitral flow velocity and late-diastolic mitral flow velocity were significantly higher in the patients with SCA. Although, the LV ejection fractions were in the normal ranges in patients and controls, both LV and right ventricle (RV) MPI were significantly higher in patients than those in normal children. CONCLUSION: MPI may be a useful noninvasive and sensitive tool for assessing the sub-clinical cardiac LV and RV dysfunctions in patients with SCA.

Standard measures of right ventricular function assessment in adult patients with acute sickle cell crises.

Chronic sickle cell (SC) disease is known to cause pulmonary hypertension (PH) which eventually affects right as well as left ventricular function. However, the acute effects of SC crisis on right ventricular (RV) function in adults have not been well described. Our echocardiography database was queried for patients followed in the outpatient hematology clinic, who were admitted with SC crises, and had an inpatient echocardiogram. Comparisons of RV fractional area change (RVFAC) and tricuspid annular peak systolic excursion (TAPSE) were then made to a group of healthy patients and a group with mild PH. TAPSE was normal in patients with SC disease (3.05+/-0.56). However, the SC patients had significantly larger RV's compared to controls and mild PH patients (31.33+/-7.23 cm(2) vs. 19.07+/-4.49 cm(2) and 21.51+/-6.07 cm(2), respectively, P<0.0001). RVFAC was reduced in SC patients, and was comparable to patients with mild PH (46+/-9% vs. 49 +/-14%, P=0.4). We found no correlation between hemoglobin level (8.1+/-2.5 g) and RVFAC, TAPSE, or PH severity. We found that adult patients admitted with SC crises have frequent dilatation of the RV with an abnormal reduction in RVFAC, despite normal TAPSE values. Therefore, caution should be exercised in using TAPSE to estimate RV function in this patient population.

Transcranial Doppler scanning and the assessment of stroke risk in children with HbSC [corrected] disease.

OBJECTIVE: To assess the role of transcranial Doppler (TCD) scanning in assessing the risk of stroke in children with haemoglobin SC (HbSC) disease. TCD scanning has an established role in primary stroke prevention in sickle cell anaemia but its value in HbSC is unknown. DESIGN: A retrospective audit of routinely performed TCD scans and routinely collected clinical data. SETTING: A paediatric sickle cell clinic in a teaching hospital in south London, UK. PATIENTS: 46 children with HbSC disease who have undergone routinely performed TCD scans and steady-state blood tests. MAIN OUTCOME MEASURES: The time-averaged mean of the maximum velocity (TAMMV) in the middle cerebral artery circulation correlated with clinical and laboratory data. RESULTS: The mean TAMMV was 94 cm/s, with a 98(th) centile of 128 cm/s. This is significantly less than the published ranges for HbSS, with a mean reading of 129 cm/s. One child had a stroke at the age of 5 years, when her TAMMV was measured at 146 cm/s. CONCLUSIONS: Further studies are needed to assess stroke risk in HbSC disease, but we suggest that TCD measurements are potentially useful in this condition, and that readings greater than 128 cm/s are abnormally high and warrant further investigation.

Quantitative assessment of ventricular function in sickle cell disease: effect of long-term erythrocytapheresis.

BACKGROUND: Previous studies on cardiac function in patients with sickle cell disease (SCD) demonstrated abnormalities of systolic and diastolic function including elevated left ventricular myocardial performance index (LVMPI) on chronic transfusion protocols. LVMPI has been validated as a useful and easy non-invasive measure of overall cardiac function. Up to now, there are no reported studies on cardiac function in patients with SCD maintained on long-term erythrocytapheresis (LTE). PROCEDURES: We recorded LVMPI in 22 patients with SCD aged 3-20 years and we compared the results between non-transfused patients (NT-SCD) and patients on LTE (T-SCD). RESULTS: Males with SCD had higher mean LVMPI than females (P = 0.04). There were significant differences among T-SCD, severe NT-SCD, and mild NT-SCD patients with respect to hemoglobin (Hb) levels (P = .003) and TR velocity (P = .03). T-SCD patients showed elevated LVMPI compared to NT-SCD patients with severe and mild disease (P = 0.002). Pair-wise comparisons demonstrated that T-SCD patients had LVMPI that was significantly higher than NT-SCD (mild) patients (P = 0.01). CONCLUSIONS: Our study demonstrates that patients SCD on LTE have cardiac dysfunction based on elevated LVMPI. This may be a reflection of the global severity of disease. Our findings merit further investigation with serial monitoring of LVMPI on a larger number of patients with SCD.

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. METHODS: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. RESULTS: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.