Extracardiac Manifestations Fail to Predict the Severity of Cardiac Phenotype in Children and Young Adults with Marfan Syndrome.

We performed a secondary analysis of the Pediatric Heart Network (PHN) Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and aortic phenotypes in study participants. Aortic aneurysm phenotype was defined as aortic root Z-score ≥4.5, aortic root growth rate ≥75th percentile, aortic dissection, and aortic surgery. Severe cardiac phenotype was defined as aortic dissection, aortic Z-score ≥4.5, aortic valve surgery, at least moderate mitral regurgitation, mitral valve surgery, left ventricular dysfunction, or death. Extracardiac manifestations were characterized by specific organ system involvement and by a novel aggregate extracardiac score (AES) that was created for this study based on the original Ghent nosology. Mixed effects logistic regression analysis compared AES and systems involvement to outcomes. Of 608 participants (60% male), the median age at enrollment was 10.8 years (interquartile range: 6, 15.4). Aortic aneurysm phenotype was observed in 71% of participants and 64% had severe cardiac phenotype. On univariable analysis, skeletal (OR: 1.95, 95% CI: 1.01, 3.72; p = 0.05), skin manifestation (OR: 1.62, 95% CI: 1.13, 2.34; p = 0.01) and AES (OR: 1.17, 95% CI: 1.02, 1.34; p = 0.02) were associated with aortic aneurysm phenotype but were not significant in multivariable analysis. There was no association between extracardiac manifestations and severe cardiac phenotype. Thus, the severity of cardiac manifestations in Marfan syndrome (MFS) was independent of extracardiac phenotype and AES. Severity of extracardiac involvement did not appear to be a useful clinical marker for cardiovascular risk-stratification in this cohort of children and young adults with MFS.

Extracardiac Manifestations Fail to Predict the Severity of Cardiac Phenotype in Children and Young Adults with Marfan Syndrome.

We performed a secondary analysis of the Pediatric Heart Network Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and aortic phenotypes in study participants. Aortic aneurysm phenotype was defined as aortic root Z-score ≥ 4.5, aortic root growth rate ≥ 75th percentile, aortic dissection, and aortic surgery. Severe cardiac phenotype was defined as aortic dissection, aortic Z-score ≥4.5, aortic valve surgery, at least moderate mitral regurgitation, mitral valve surgery, left ventricular dysfunction, or death. Extracardiac manifestations were characterized by specific organ system involvement and by a novel aggregate extracardiac score that was created for this study based on the original Ghent nosology. Logistic regression analysis compared aggregate extracardiac score and systems involvement to outcomes. Of 608 participants (60% male), the median age at enrollment was 10.8 years (interquartile range: 6, 15.4). Aortic aneurysm phenotype was observed in 71% of participants and 64% had severe cardiac phenotype. On univariate analysis, skeletal (OR: 1.95, 95% CI: 1.01, 3.72; p = 0.05), skin manifestation (OR: 1.62, 95% CI: 1.13, 2.34; p = 0.01) and aggregate extracardiac score (OR: 1.17, 95% CI: 1.02, 1.34; p = 0.02) were associated with aortic aneurysm phenotype but were not significant in multivariate analysis. There was no association between extracardiac manifestations and severe cardiac phenotype. Thus, the severity of cardiac manifestations in Marfan syndrome was independent of extracardiac phenotype and aggregate extracardiac score. Severity of extracardiac involvement did not appear to be a useful clinical marker for cardiovascular risk-stratification in this cohort of children and young adults with Marfan syndrome.

Guidelines for Performing a Comprehensive Pediatric Transthoracic Echocardiogram: Recommendations From the American Society of Echocardiography.

Echocardiography is a fundamental component of pediatric cardiology, and appropriate indications have been established for its use in the setting of suspected, congenital, or acquired heart disease in children. Since the publication of guidelines for pediatric transthoracic echocardiography in 2006 and 2010, advances in knowledge and technology have expanded the scope of practice beyond the use of traditional modalities such as two-dimensional, M-mode, and Doppler echocardiography to evaluate the cardiac segmental structures and their function. Adjunct modalities such as contrast, three-dimensional, and speckle-tracking echocardiography are now used routinely at many pediatric centers. Guidelines and recommendations for the use of traditional and newer adjunct modalities in children are described in detail in this document. In addition, suggested protocols related to standard operations, infection control, sedation, and quality assurance and improvement are included to provide an organizational structure for centers performing pediatric transthoracic echocardiograms.

Appropriateness of cardiovascular computed tomography and magnetic resonance imaging in patients with conotruncal defects.

BACKGROUND: To promote the rational use of cardiovascular imaging in patients with congenital heart disease, the American College of Cardiology developed Appropriate Use Criteria (AUC), but its clinical application and pre-release benchmarks have not been evaluated. We aimed to evaluate the appropriateness of indications for cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) in patients with conotruncal defects and to identify factors associated with maybe or rarely appropriate (M/R) indications. METHODS: Twelve centers each contributed a median of 147 studies performed prior to AUC publication (01/2020) on patients with conotruncal defects. To incorporate patient characteristics and center-level effects, a hierarchical generalized linear mixed model was used. RESULTS: Of the 1753 studies (80% CMR, and 20% CCT), 16% were rated M/R. Center M/R ranged from 4 to 39%. Infants accounted for 8.4% of studies. In multivariable analyses, patient- and study-level factors associated with M/R rating included: age <1 year (OR 1.90 [1.15-3.13]), truncus arteriosus (vs. tetralogy of Fallot, OR 2.55 [1.5-4.35]), and CCT (vs. CMR, OR 2.67 [1.87-3.83]). None of the provider- or center-level factors reached statistical significance in the multivariable model. CONCLUSIONS: Most CMRs and CCTs ordered for the follow-up care of patients with conotruncal defects were rated appropriate. However, there was significant center-level variation in appropriateness ratings. Younger age, CCT, and truncus arteriosus were independently associated with higher odds of M/R rating. These findings could inform future quality improvement initiatives and further exploration of factors resulting in center-level variation.

Utility of Screening Fetal Echocardiogram Following Normal Anatomy Ultrasound for In Vitro Fertilization Pregnancies.

In vitro fertilization (IVF) is associated with a higher incidence of congenital heart disease, resulting in universal screening fetal echocardiograms (F-echo) even when cardiac structures on obstetric scan (OB-scan) are normal. Recent studies suggest that when OB-scan is normal, F-echo may add little benefit and increases cost and anxiety. We aim to determine the utility of screening F-echo in IVF pregnancies with normal cardiac anatomy on prior OB-scan. We conducted a retrospective chart review of IVF pregnancies referred for F-echo at the Seattle Children's Hospital between 2014 and 2020. OB-scan results and subspecialty of interpreting physician (Obstetrics = OB; Maternal Fetal Medicine = MFM; Radiology = Rads), F-echoes, and postnatal outcomes were reviewed. Cardiac anatomy on OB-scans was classified as complete if 4-chamber and outflow-tract views were obtained. Supplemental views (three-vessel and sagittal aortic arch views) on OB-scan were also documented. Of 525 IVF referrals, OB-scan reports were available for review in 411. Normal anatomy was demonstrated in 304 (74%) interpreted by OB (128; 42%), MFM (80; 26%), and Rads (96; 32%). F-echo was normal in 278 (91%). Of the 26 abnormal F-echo, none required intervention (17 muscular and 5 perimembranous ventricular septal defects, and 4 minor valve abnormalities). There was no difference in OB-scan accuracy for identifying normal cardiac anatomy when comparing 4-chamber and outflow-tract views vs. addition of supplemental views (91% vs 92% normal F-echo; p > 0.1). Evaluation of OB-scan accuracy by interpreting physician subspecialty demonstrated normal F-echo in 95%, 85%, and 92% (p = 0.95) as read by OB, MFM, and Rads, respectively. A majority of IVF referrals with normal cardiac anatomy visualized on OB-scan using 4-chamber and outflow-tract views resulted in normal F-echo, regardless of interpreting physician subspecialty or addition of supplemental views. Of the minority with abnormal F-echo, none required intervention. Consideration should be given to the cost/benefit of screening F-echo for the indication of IVF if normal cardiac anatomy is demonstrated on OB-scan.

Pediatric Heart Network Echocardiographic Z Scores: Comparison with Other Published Models.

BACKGROUND: Different methods have resulted in variable Z scores for echocardiographic measurements. Using the measurements from 3,215 healthy North American children in the Pediatric Heart Network (PHN) echocardiographic Z score database, the authors compared the PHN model with previously published Z score models. METHODS: Z scores were derived for cardiovascular measurements using four models (PHN, Boston, Italy, and Detroit). Model comparisons were performed by evaluating (1) overlaid graphs of measurement versus body surface area with curves at Z = -2, 0, and +2; (2) scatterplots of PHN versus other Z scores with correlation coefficients; (3) Bland-Altman plots of PHN versus other Z scores; and (4) comparison of median Z scores for each model. RESULTS: For most measurements, PHN Z score curves were similar to Boston and Italian curves but diverged from Detroit curves at high body surface areas. Correlation coefficients were high when comparing the PHN model with the others, highest with Boston (mean, 0.99) and lowest with Detroit (mean, 0.90). Scatterplots suggested systematic differences despite high correlations. Bland-Altman plots also revealed poor agreement at both extremes of size and a systematic bias for most when comparing PHN against Italian and Detroit Z scores. There were statistically significant differences when comparing median Z scores between the PHN and other models. CONCLUSIONS: Z scores from the multicenter PHN model correlated well with previous single-center models, especially the Boston model, which also had a large sample size and similar methodology. The Detroit Z scores diverged from the PHN Z scores at high body surface area, possibly because there were more subjects in this category in the PHN database. Despite excellent correlation, significant differences in Z scores between the PHN model and others were seen for many measurements. This is important when comparing publications using different models and for clinical care, particularly when Z score thresholds are used to guide diagnosis and management.

Practice Variations in Pediatric Echocardiography Laboratories.

Quantification guidelines for pediatric echocardiograms were published in 2010 establishing consensus regarding standard measurements. However, a standard protocol for performance and analysis of pediatric echocardiograms was not defined. This study aims to identify practice variations among pediatric laboratories. A survey was sent to 85 North American pediatric laboratory directors. The survey included 29 questions assessing: demographics, methods of image acquisition, parameters routinely evaluated and reported, and methods used to assess chamber sizes, valves, and ventricular function. There were 47/85 (55%) responses; 83% were academic centers and 77% in an urban setting. Wide variations exist in acquisition method (clips versus sweeps) and color scale settings. The most commonly used methods for left ventricular (LV) function are M-mode shortening fraction, qualitative assessment, and Doppler Tissue Imaging. The most commonly used parameter for right ventricular function is qualitative. LV mass is routinely measured by the majority of centers with variations in methods of calculation. Conversely, while a minority measure left atrial volume, there is consensus regarding the preferred method. While multiple techniques exist for assessing valves, qualitative assessment is reported to be the preferred method. Despite quantification guidelines, there is a lack of uniformity in performance and analysis of pediatric echocardiograms. Further studies are needed to determine why variations exist and whether development of consensus guidelines might improve interpretation, consistency and quality of reports, patient care, and provide a standardized system allowing for comparative research among centers.

Cardiovascular Health in Turner Syndrome: A Scientific Statement From the American Heart Association.

Girls and women with Turner syndrome face a lifelong struggle with both congenital heart disease and acquired cardiovascular conditions. Bicuspid aortic valve is common, and many have left-sided heart obstructive disease of varying severity, from hypoplastic left-sided heart syndrome to minimal aortic stenosis or coarctation of the aorta. Significant enlargement of the thoracic aorta may progress to catastrophic aortic dissection and rupture. It is becoming increasingly apparent that a variety of other cardiovascular conditions, including early-onset hypertension, ischemic heart disease, and stroke, are the major factors reducing the life span of those with Turner syndrome. The presentations and management of cardiovascular conditions in Turner syndrome differ significantly from the general population. Therefore, an international working group reviewed the available evidence regarding the diagnosis and treatment of cardiovascular diseases in Turner syndrome. It is recognized that the suggestions for clinical practice stated here are only the beginning of a process that must also involve the establishment of quality indicators, structures and processes for implementation, and outcome studies.

Frequency of Ventricular Arrhythmias and Other Rhythm Abnormalities in Children and Young Adults With the Marfan Syndrome.

Patients with the Marfan syndrome (MFS) are at risk for sudden death. The contribution of arrhythmias is unclear. This study examines the prevalence of arrhythmias in children with the MFS and their relation to clinical and/or echocardiographic factors. Data from the Pediatric Heart Network randomized trial of atenolol versus losartan in MFS were analyzed (6 months to 25 years old, aortic root diameter z-score > 3.0, no previous aortic surgery and/or dissection). Baseline 24-hour ambulatory electrocardiographic monitoring was performed. Significant ventricular ectopy (VE) and supraventricular ectopy (SVE) were defined as ≥10 VE or SVE/hour, or the presence of high-grade ectopy. Three-year composite clinical outcome of death, aortic dissection, or aortic root replacement was analyzed. There were 274 analyzable monitors on unique patients from 11 centers. Twenty subjects (7%) had significant VE, 13 (5%) significant SVE; of these, 2 (1%) had both. None had sustained ventricular or supraventricular tachycardia. VE was independently associated with increasing number of major Ghent criteria (odds ratio [OR] = 2.13/each additional criterion, p = 0.03) and greater left ventricular end-diastolic dimension z-score (OR = 1.47/each 1 unit increase in z-score, p = 0.01). SVE was independently associated with greater aortic sinotubular junction diameter z-score (OR = 1.56/each 1 unit increase in z-score, p = 0.03). The composite clinical outcome (14 events) was not related to VE or SVE (p ≥ 0.3), but was independently related to heart rate variability (higher triangular index). In conclusion, in this cohort, VE and SVE were rare. VE was related to larger BSA-adjusted left ventricular size. Routine ambulatory electrocardiographic monitoring may be useful for risk stratification in select MFS patients.

Altered aortic 3D hemodynamics and geometry in pediatric Marfan syndrome patients.

BACKGROUND: Blood flow dynamics make it possible to better understand the development of aortopathy and cardiovascular events in patients with Marfan syndrome (MFS). Aortic 3D blood flow characteristics were investigated in relation to aortic geometry in children and adolescents with MFS. METHODS: Twenty-five MFS patients (age 15.6 ± 4.0 years; 11 females) and 21 healthy controls (age 16.0 ± 2.6 years; 12 females) underwent magnetic resonance angiography and 4D flow CMR for assessment of thoracic aortic size and 3D blood flow velocities. Data analysis included calculation of aortic diameter and BSA-indexed aortic dimensions (Z-score) along the thoracic aorta, 3D mean systolic wall shear stress (WSSmean) in ten aortic segments and assessment of aortic blood flow patterns. RESULTS: Aortic root (root), ascending (AAo) and descending (DAo) aortic size was significantly larger in MFS patients than healthy controls (Root Z-score: 3.56 ± 1.45 vs 0.49 ± 0.78, p < 0.001; AAo Z-score 0.21 ± 0.95 vs -0.54 ± 0.64, p = 0.004; proximal DAo Z-score 2.02 ± 1.60 vs 0.56 ± 0.66, p < 0.001). A regional variation in prevalence and severity of flow patterns (vortex and helix flow patterns) was observed, with the aortic root and the proximal DAo (pDAo) being more frequently affected in MFS. MFS patients had significantly reduced WSSmean in the proximal AAo (pAAo) outer segment (0.65 ± 0.12 vs. 0.73 ± 0.14 Pa, p = 0.029) and pDAo inner segment (0.74 ± 0.17 vs. 0.87 ± 0.21 Pa, p = 0.021), as well as higher WSSmean in the inner segment of the distal AAo (0.94 ± 0.14 vs. 0.84 ± 0.15 Pa, p = 0.036) compared to healthy subjects. An inverse relationship existed between pDAo WSSmean and both pDAo diameter (R = -0.53, p < 0.001) and % diameter change along the pDAo segment (R = -0.64, p < 0.001). CONCLUSIONS: MFS children and young adults have altered aortic flow patterns and differences in aortic WSS that were most pronounced in the pAAo and pDAo, segments where aortic dissection or rupture often originate. The presence of vortex flow patterns and abnormal WSS correlated with regional size of the pDAo and are potentially valuable additional markers of disease severity.

Hyponatremia Is a Feature of Kawasaki Disease Shock Syndrome: A Case-Control Study.

Kawasaki disease (KD) shock syndrome (KDSS) is hypotension with KD. We compared children with KDSS and matched control children with KD. Children with KDSS more often were female, had a lower platelet count and sodium concentration, had a condition refractory to immunoglobulin, and had abnormal echocardiography results. KDSS is a unique subset of KD.

The Effect of Image Review before Patient Discharge on Study Completeness and Sonographer Job Satisfaction in a Pediatric Echocardiographic Laboratory.

BACKGROUND: Incomplete echocardiographic assessment accounts for approximately 10% of preventable diagnostic errors and may place children at risk for adverse outcomes or increased testing. The aim of this study was to determine if physician review of images improves study completeness. METHODS: A prospective quality improvement (QI) study initiated physician review of first-time echocardiographic studies for completeness before patient discharge. Studies were incomplete if not all anatomic structures were diagnostically demonstrated. QI examinations were compared with controls obtained before study initiation. Demographic and clinical information and duration of scan were collected during the control and QI periods. An anonymous survey was administered to the sonographers to assess perceptions of the intervention. RESULTS: There were no differences between the QI (n = 63) and control (n = 63) groups in age, height, weight, and technical barriers. After study completion, 35% of control scans versus 5% of QI scans were incomplete (P < .001). In the QI group, the sonographer, physician, or both returned to scan in 12 (19%), nine (14%), and two (3%) studies, respectively. QI studies were longer than control studies (44 vs 36 min, P = .003) before review. Physician review added a median of 6 min (range, 1-28 min). The majority of sonographers believed that immediate review improved communication, and 50% believed that it improved their job satisfaction. CONCLUSIONS: Review of initial outpatient echocardiographic examinations before patient discharge significantly improves study completeness. Review adds a nominal amount of time to total study duration, improves sonographer-physician communication, and may prevent unnecessary testing, potentially reducing the cost of care.

Atenolol versus losartan in children and young adults with Marfan's syndrome.

BACKGROUND: Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS: We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS: From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS: Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).

Reproducibility of tricuspid regurgitant jet velocity measurements in children and young adults with sickle cell disease undergoing screening for pulmonary hypertension.

The reproducibility of tricuspid regurgitant jet velocity (TRJV) measurements by Doppler echocardiography has not been subjected to systematic evaluation among individuals with sickle cell disease (SCD) undergoing screening for pulmonary hypertension. We examined sources of disagreement associated with peak TRJV in children and young adults with SCD. Peak TRJV was independently measured and interpreted a week apart by separate sonographers and readers, respectively, in 30 subjects (mean age, 15.8 ± 3.3 years) who provided 120 observations. We assessed intra-/inter-reader, intra-/inter-sonographer, sonographer-reader, and within subject agreement using Intraclass Correlation Coefficient (ICC) and Cohen's kappa (κ). Agreement was examined graphically using Bland-Altman plots. Although sonographers could estimate and measure peak TRJV in all subjects, readers designated tricuspid regurgitation nonquantifiable in 10-17% of their final interpretations. Intra-reader agreement was highest (ICC = 0.93 [95% CI 0.86, 0.97], P = 0.0001) and within subject agreement lowest (ICC = 0.36 [95% CI 0.02, 0.64], P = 0.021) for single TRJV measurements. Similarly, intra-reader agreement was highest (κ = 0.74 [95% CI 0.53, 0.95], P = 0.0001) and within subject lowest (κ = 0.14 [95% CI -0.17, 0.46], P = 0.38) when sonographers and readers categorized TRJV measurements. On Bland-Altman plots, absolute differences in observations increased with higher mean TRJV readings for intra-/inter-reader agreement. Peak TRJV measurements in individual children and young adults with SCD are affected by several sources of disagreement, underscoring the need for methodological improvements that ensure reproducibility of this screening modality for making clinical decisions in this population.

Functional capacity in children and young adults with sickle cell disease undergoing evaluation for cardiopulmonary disease.

Although cardiopulmonary disease is associated with decreased functional capacity among adults with sickle cell disease (SCD), its impact on functional capacity in children with SCD is unknown. We evaluated 6-min walk (6MW) distance in 77 children and young adults with SCD undergoing screening for cardiopulmonary disease. Of 30 subjects who also underwent cardiopulmonary exercise testing, we found evidence for decreased exercise capacity in a significant proportion. Exercise capacity was related to baseline degree of anemia and was significantly lower in subjects with a history of recurrent acute chest syndrome. We found that 6MW distance adjusted for weight and body surface area was shorter in subjects with restrictive lung disease but that only 6MW adjusted for weight remained significantly shorter when we controlled for baseline hemoglobin. Exercise capacity was not significantly different in subjects with and without cardiopulmonary disease. We conclude that restrictive lung disease is associated with shorter 6MW distances in children and young adults with SCD, but that variables associated with decreased exercise capacity, other than anemia, remain unclear. Our study underscores the importance of further delineating the direct pathophysiologic processes that contribute to decreased exercise capacity observed among individuals with SCD and cardiopulmonary disease.

Tricuspid regurgitant jet velocity elevation and its relationship to lung function in pediatric sickle cell disease.

Concerns about the morbidity and mortality associated with tricuspid regurgitant jet velocity (TRJV) elevation, which may indicate pulmonary hypertension (PHT), in adults with sickle cell disease (SCD) have prompted growing interest in screening the pediatric sickle cell population. The goals of our study were to estimate the prevalence of TRJV elevation and determine its relationship to pulmonary function in children and young adults with SCD at baseline. Seventy-eight subjects (10-24 years old) with SCD underwent prospective screening by Doppler echocardiogram (ECHO), complete lung function evaluation, and laboratory testing as part of standard care at steady state. Tricuspid regurgitation was quantifiable in 68/78 (87%) subjects and peak TRJV was > or =2.5 m/sec in 26/78 (33.3%) evaluated. The frequency of obstruction, restriction, or abnormal gas exchange found on lung function evaluation was not significantly different in subjects with and without TRJV elevation. However, significant inverse correlations were observed between TRJV and both % predicted forced vital capacity (FVC) (r = -0.29, P = 0.022) and oxygen saturation (r = -0.26, P = 0.036). When compared to subjects without TRJV elevation, subjects with TRJV elevation had significantly lower % predicted forced expiratory volume in 1 sec (FEV(1)) (78.9 +/- 14.4 vs. 86.6 +/- 13.0%, P = 0.023), FVC (82.8 +/- 14.1 vs. 90.7 +/- 12.9%, P = 0.017), and oxygen saturation (95.8 +/- 3.2 vs. 97.5 +/- 2.4%, P = 0.016). We found that the combination of low hemoglobin and low % predicted FVC best predicted TRJV elevation (chi(2) = 17.05, P = 0.001) in our cohort, correctly identifying 70% of cases and resulting in positive and negative predictive values of 60 and 74%, respectively. We conclude that in this young population with SCD, TRJV elevation that is not significantly associated with abnormal lung function is common at baseline.

Prolonged QTc interval in children and young adults with sickle cell disease at steady state.

BACKGROUND: Prolongation of the QTc interval may be more common than previously believed among individuals with sickle cell disease (SCD). The clinical associations and natural history of QTc prolongation remain unclear in this population. Our objectives were to determine the prevalence of prolonged QTc and evaluate its relationship to clinical factors in children and young adults with SCD. PROCEDURES: We analyzed data from subjects 10 to 25 years old with SCD enrolled in our pulmonary hypertension screening protocol. Screening included echocardiography (ECHO), 12-lead electrocardiogram (ECG) and laboratory testing at steady state. QTc interval >440 msec was considered prolonged. RESULTS: ECG data from 76 subjects (57% male, mean age 14.2 +/- 3 years old, range 10-24) were analyzed. We observed prolonged QTc in 29/76 (38%) subjects. Despite evidence of left ventricular hypertrophy (LVH) in 50/76 (66%) subjects, the frequency of LVH was not significantly different in subjects with and without QTc prolongation. When compared to subjects with normal QTc, subjects with prolonged QTc had higher mean tricuspid regurgitant jet velocity (2.51 +/- 0.27 m/sec vs. 2.33 +/- 0.26 m/sec, P = 0.010) as well as higher mean lactate dehydrogenase (433 +/- 142 IU/L vs. 343 +/- 142 IU/L, P = 0.000) and aspartate aminotransferase (48 +/- 20 IU/L vs. 39 +/- 15 IU/L, P = 0.026). A larger proportion of subjects with prolonged QTc also had a history of recurrent acute chest syndrome (66% vs. 38%, P = 0.038). CONCLUSIONS: We conclude that QTc prolongation is a frequent finding in SCD not associated with LVH. Elevated pulmonary pressures, hemolysis and acute chest syndrome may represent risk factors for prolonged QTc in this population.

Tricuspid regurgitant jet velocity is associated with hemolysis in children and young adults with sickle cell disease evaluated for pulmonary hypertension.

Tricuspid regurgitant jet velocity (TRJV) >or= 2.5 m/sec. on echocardiography is a surrogate marker for pulmonary hypertension (PHT) in adults with sickle cell disease (SCD). We prospectively examined the relationship between TRJV and laboratory markers of hemolysis in 51 children and young adults with SCD at baseline. We found significant correlations between TRJV and lactate dehydrogenase (LDH), hemoglobin (Hb), reticulocyte count (retic) and aspartate aminotransferase (AST). LDH, retic and AST were significantly higher and Hb was lower in subjects with TRJV >or= 2.5 m/sec. We conclude that hemolysis significantly contributes to TRJV elevation in children and young adults with SCD.