Background The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome ...randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. Methods and results Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area–adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. Conclusions Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome.
The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to ...receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement.
Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area-adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmaxZ score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process.
Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R(2) = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmaxZ scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmaxZ scores < 4.5.
The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility.
Two strategies for surgical management are used for infants with hypoplastic left heart syndrome (HLHS), primary heart transplantation and the Norwood procedure. We sought to determine how these 2 ...surgical approaches influence neurodevelopmental outcomes at school age.
A multicenter, cross-sectional study of neurodevelopmental outcomes among school-aged children (>8 years of age) with HLHS was undertaken between July 2003 and September 2004. Four centers enrolled 48 subjects, of whom 47 completed neuropsychologic testing. Twenty-six subjects (55%) had undergone the Norwood procedure and 21 (45%) had undergone transplantation, with an intention-to-treat analysis. The mean age at testing was 12.4 +/- 2.5 years. Evaluations included the Wechsler Abbreviated Scale of Intelligence, Clinical Evaluation of Language Fundamentals, Wechsler Individual Achievement Test, and Beery-Buktenica Developmental Test of Visual-Motor Integration.
The mean neurocognitive test results were significantly below population normative values. The mean full-scale IQ for the entire cohort was 86 +/- 14. In a multivariate model, there was no association of surgical strategy with any measure of developmental outcome. A longer hospital stay, however, was associated significantly with lower verbal, performance, and full-scale IQ scores. Aortic valve atresia was associated with lower math achievement test scores.
Neurodevelopmental deficits are prevalent among school-aged children with HLHS, regardless of surgical approach. Complications that result in prolonged hospitalization at the time of the initial operation are associated with neurodevelopmental status at school age.
The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. In this report ...we present treatment effects on aortic stiffness and determine whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. Echocardiograms at 0, 6, 12, 24, and 36 months from 608 subjects (6 months to 25 years) who met original Ghent criteria and had a maximum aortic-root z-score (ARz) >3 were centrally reviewed. Stiffness index (SI) and elastic modulus (EM) were calculated for aortic root and ascending aorta. Data were analyzed using multivariable mixed effects modeling and Cox regression. Heart rate–corrected aortic-root SI over 3 years decreased with atenolol but did not change with losartan (−0.298 ± 0.139 vs 0.141 ± 0.139/year, p = 0.01). In the entire cohort, above-median aortic-root SI (>9.1) and EM (>618 mm Hg) predicted a smaller annual decrease in ARz (p ≤0.001). Upper-quartile aortic-root EM (>914 mm Hg) predicted the composite outcome of aortic-root surgery, dissection, or death (hazard ratio 2.17, 95% confidence interval 1.02 to 4.63, p = 0.04). Crude 3-year event rates were 10.4% versus 3.2% for higher versus lower EM groups. In conclusion, atenolol was associated with a decrease in aortic-root SI, whereas losartan was not. Higher baseline aortic-root SI and EM were associated with a smaller decrease in ARz and increased risk for clinical outcomes. These data suggest that noninvasive aortic stiffness measures may identify patients at higher risk of progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy.
Tetralogy of Fallot Sharkey, Angela M.; Sharma, Anshuman
Seminars in cardiothoracic and vascular anesthesia,
06/2012, Volume:
16, Issue:
2
Journal Article
Peer reviewed
Tetralogy of Fallot is the most common form of cyanotic congenital heart disease. In this condition, episodic worsening of hypoxemia results from dynamic shifts in physiology, so-called “Tet spells.” ...The relative frequency of this lesion and the risks of exacerbating “Tet spells” make anesthetic management of this patient population challenging. The conduct of palliative and reparative cardiac surgery is determined in large part by the anatomic variations within the spectrum of this disorder, most notably the severity of right ventricular outflow tract obstruction. This review will address the impact that the anatomic substrate has on the perioperative management of this interesting patient population.
Clinical assessment of orofacial muscle tone is of interest for differential diagnosis of the dysarthrias, but standardized procedures and normative data are lacking. In this study, perceptual ...ratings of tone were compared with instrumental measures of tissue stiffness for facial, lingual, and masticatory muscles in 70 individuals with dysarthria. Perceptual and instrumental tone data were discordant and failed to discriminate between five dysarthria types. These results raised concerns about the validity of Myoton-3 stiffness measures in the orofacial muscles. Therefore, a second study evaluated contracted and relaxed orofacial muscles in 10 neurotypical adults. Results for the cheek, masseter, and lateral tongue surface followed predictions, with significantly higher tissue stiffness during contraction. In contradiction, stiffness measures from the superior surface of the tongue were lower during contraction. Superior-to-inferior tongue thickness was notably increased during contraction. A third study revealed that tissue thickness up to ~10 mm significantly affected Myoton-3 measures. Altered tissue thickness due to neuromuscular conditions like spasticity and atrophy may have undermined the detection of group differences in the original sample of dysarthric speakers. These experiments underscore the challenges of assessing orofacial muscle tone and identify considerations for quantification of tone-related differences across dysarthria groups in future studies.
In this work, we report a novel targetable ultrasonic contrast agent with the potential to noninvasively define and localize myriad pathological tissues for diagnosis or therapy. The agent is a ...biotinylated, lipid-coated, perfluorocarbon emulsion that has low inherent echogenicity unless bound to a surface or itself.
In study 1, emulsions with and without biotin were suspended in buffered saline and imaged with a 7.5-MHz linear-array transducer. Neither emulsion manifested significant ultrasonic backscatter until avidin was added. Avidin-induced aggregation produced a marked enhancement in backscatter from the biotinylated but not from the control emulsion. In study 2, porcine fibrin clots in vitro were pretargeted with biotinylated antifibrin monoclonal antibodies and then exposed to avidin and then to biotinylated or control perfluorocarbon emulsions. The basal acoustic reflectivity of clots imaged with a 7.5-MHz linear-array transducer was uniformly low and was increased substantially by exposure to the targeted biotinylated emulsion. In study 3, partially occlusive arterial thrombi were created in dogs and then exposed to antifibrin antibodies and avidin in situ. Biotinylated or control emulsion was administered either in situ or systemically. At baseline, all thrombi were undetectable with a 7.5-MHz linear-array transducer. Thrombi exposed to antifibrin-targeted contrast exhibited increased echogenicity (P < .05); control thrombi remained acoustically undetectable.
These data provide the first in vivo demonstration of a site-specific ultrasonic contrast agent and have potential for improved sensitivity and specificity for noninvasive diagnosis of thrombi and other pathological diseases.
Objective Children born with hypoplastic left heart syndrome (HLHS) may experience cardiac dysfunction after staged surgery or transplantation, which may worsen with age. We examined the hypothesis ...that exercise testing can address cardiovascular capacity and suggest interventions to improve quality of life. Study design Children with HLHS ≥8 years old performed treadmill or bicycle ergometric testing at 4 centers. Results were compared with norms for age and sex. Results Of the 42 participants, the mean age was 12.9 years (range, 8.5-17.0 years), 64% were boys, 20 had staged surgery, and 34 completed metabolic assessment. The percent of predicted maximal oxygen uptake (mVO2) was higher in younger children. Children aged 8 to 12 years achieved 70% of predicted mVO2; children aged 13 to 17 years achieved 60% of predicted mVO2 ( P = .02). The percent of predicted peak heart rate trended higher in younger patients (83% versus 75%, P = .07). Electrocardiographic changes were more common in older children. In treadmill testing, patients who had a transplant had better exercise performance than patients who underwent staged surgery in percent of predicted exercise time (82% versus 54%, P < .0001) and peak rate-pressure product (241 × 103 versus 195 × 103 , P = .02). The percent of predicted mVO2 did not differ between patients who had a transplant (66%) and patients who underwent staged surgery (61%, P = .25). Conclusion Children with HLHS showed considerable age-related decline in exercise performance, regardless of surgical strategy.
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