William Ravekes

Right ventricular function in infants, children and adolescents: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 640 healthy patients and calculation of z score values.

BACKGROUND Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic measurement to assess right ventricular systolic function in adults. The aim of this study was to determine growth-related changes in TAPSE to establish references values. METHODS A prospective study was conducted in a group of 640 healthy pediatric patients (age range, 1 day to 18 years; body surface area range, 0.12-2.25 m(2)). The effects of age and body surface area on TAPSE were determined. RESULTS TAPSE ranged from a mean of 0.91 cm (z score +/- 3, 0.56-1.26 cm) in neonates to 2.47 cm (z score +/- 3, 1.84-3.10 cm) in 18-year-olds. TAPSE values showed positive correlations with age and body surface area. There was no significant difference in TAPSE values between female or male children. CONCLUSION In this study, z scores of TAPSE values were calculated and percentile charts were established to serve as reference data for ready application in patients with congenital heart disease in the future.

Systolic Right Ventricular Function in Preterm and Term Neonates: Reference Values of the Tricuspid Annular Plane Systolic Excursion (TAPSE) in 258 Patients and Calculation of Z-Score Values

Background: The tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic measurement to assess right ventricular systolic function in adults and children. Objective: We determined growth- and birth weight-related changes of TAPSE to establish reference values in preterm and term neonates. Methods: A prospective study was conducted in a group of 258 preterm and term neonates (age: 25+0 to 40+6 weeks of gestation, birth weight: 530–4,200 g). Results: The TAPSE ranged from a mean of 0.44 cm (Z-score ±2: 0.30–0.59 cm) in preterm neonates in the 26th week of gestation to 1.03 cm (Z-score ±2: 0.85–1.21 cm) in term neonates in the 41st week of gestation. The TAPSE values increased in a linear way from the 26th to 41st week of gestation. TAPSE, week of gestation and weight are strongly correlated: Pearson’s correlation coefficient was 0.93 for week of gestation – TAPSE (p < 0.001), 0.93 for week of gestation – birth weight (p < 0.001), and 0.89 for birth weight – TAPSE (p < 0.001). There was no statistically significant difference of normal TAPSE values between female and male patients (p = 0.987). Conclusion: Z-scores of TAPSE values were calculated and percentile charts were established to serve as reference data for ready application in preterm and term neonates with structurally normal hearts and with congenital heart disease in the future.

Risk Factors for Neo-Aortic Root Enlargement and Aortic Regurgitation Following Arterial Switch Operation

The objectives of this study were to evaluate changes in dimension of the neo-aortic annulus, aortic root, and aortic anastomosis following arterial switch operation (ASO) and to identify risk factors for developing abnormal neo-aortic root enlargement and aortic regurgitation (AR). Prior studies report development of neo-aortic root dilatation and AR in a small subset of patients after ASO. Predisposing factors for neo-aortic root dilatation and development of moderate/severe AR are poorly understood. We performed a retrospective review of all patients with d-transposition of the great arteries (d-TGA) or double-outlet right ventricle with subpulmonary ventricular septal defect (VSD) who underwent ASO from May 1986 to January 2001. Serial echocardiograms were reviewed to measure neo-aortic annulus, root, and anastomosis diameter (z scores) and to determine progression of AR. Potential risk factors were assessed for developing neo-aortic root enlargement and AR. There were 119 patients (44 female and 75 male): 73 patients had simple d-TGA, 36 had d-TGA with ventricular septal defect, and 10 had a Taussig–Bing heart. The median duration of follow-up was 65 months (range, 12–180). The median neo-aortic root (z = 0.55 ± 2.2; p < 0.01) and aortic annulus dimensions (z = 1.57 ± 1.75; p < 0.01) were significantly increased over the study period. Aortic anastomosis diameter correlated with growth of the ascending aorta (z = 0.55 ± 1.24). Development of severe neo-aortic root enlargement was associated with prior pulmonary artery (PA) banding (p < 0.01), the presence of a VSD (p = 0.03), and Taussig–Bing anatomy (p < 0.01) but was independent of coronary arterial anatomy, coronary arterial transfer technique, or associated lesions (p > 0.05). At latest follow-up, there was no or trivial AR in 88 patients, mild AR in 29 patients, and moderate to severe AR in 3 patients. Risk factors for developing mild or worse AR included severe or rapid neo-aortic root dilatation (p < 0.01). Only 3 patients required surgical intervention for AR. Despite the significant prevalence of neo-aortic root enlargement at intermediate follow-up after ASO, there is a low incidence of significant AR. Prior PA banding, the presence of VSD, and Taussig–Bing anatomy are risk factors for severe root enlargement. Surgical intervention for AR was rare (2%), however, serial surveillance of such patients is vital to monitor for neo-aortic root enlargement and potential aortic valve dysfunction.

Reference values of tricuspid annular peak systolic velocity in healthy pediatric patients, calculation of z score, and comparison to tricuspid annular plane systolic excursion.

The tricuspid annular peak systolic velocity (TAPSV) is an echocardiographic measurement assessing right ventricular systolic function in children and adults. We determined the growth-related changes of the TAPSV to establish the references values for the entire pediatric age group. A prospective study was conducted of a group of 860 healthy pediatric patients (age 1 day to 18 years; body surface area [BSA] 0.14 to 2.30 m(2)). We determined the effects of age, gender, and BSA on the TAPSV values. Stepwise linear multiple regression analysis was used to estimate the TAPSV from the age, BSA, and gender. A correlation of normal TAPSV with normal tricuspid annular plane systolic excursion values was performed. The TAPSV ranged from a mean of 7.2 cm/s (z score ± 2: 4.8 to 9.5 cm/s) in the newborn to 14.3 cm/s (z score ± 2: 10.6 to 18.6 cm/s) in the 18-year-old adolescent. The TAPSV values showed a positive correlation with age and BSA, with a nonlinear course. No significant difference was found in the TAPSV values according to gender. A significant correlation was found between the TAPSV and tricuspid annular plane systolic excursion values in our pediatric population. In conclusion, the z scores of the TAPSV values were calculated, and percentile charts were established to serve as reference data for patients with congenital heart disease.

Systolic Right Ventricular Function in Children and Young Adults with Pulmonary Artery Hypertension Secondary to Congenital Heart Disease and Tetralogy of Fallot: Tricuspid Annular Plane Systolic Excursion (TAPSE) and Magnetic Resonance Imaging Data

OBJECTIVE   The tricuspid annular plane systolic excursion (TAPSE), as echocardiographic index to assess right ventricular (RV) systolic function, has not been investigated thoroughly in children and young adults with tetralogy of Fallot (TOF) and pulmonary artery hypertension secondary to congenital heart disease (PAH-CHD). PATIENTS   TAPSE values of 49 patients with PAH-CHD and 156 patients with TOF were compared with age-matched normal subjects. TAPSE values were also compared with RV ejection fraction (RVEF) and RV indexed end-diastolic volume (RVEDVi) determined by magnetic resonance imaging in PAH-CHD and TOF patients. RESULTS   Patients with a PAH-CHD showed a positive correlation between TAPSE with RVEF (r= 0.81; P < 0.001) and a negative correlation between TAPSE with RVEDVi (r=-0.67; P < 0.001). Similarly, in our TOF patients, a positive correlation between TAPSE with RVEF (r= 0.65; P < 0.001) and a negative correlation between TAPSE with RVEDVi (r=-0.42; P < 0.001) was seen. CONCLUSIONS   Significant pressure overload in PAH-CHD patients and volume overload in TOF patients lead to a decreased systolic RV function, determined by TAPSE and magnetic resonance imaging and to increased RVEDVi values, determined by MRI, with time.

Systolic right ventricular function in pediatric and adolescent patients with tetralogy of Fallot: echocardiography versus magnetic resonance imaging.

OBJECTIVE The tricuspid annular plane systolic excursion (TAPSE) as an echocardiographic index to assess right ventricular (RV) systolic function has not been investigated thoroughly in pediatric patients and adolescents with tetralogy of Fallot (TOF) after surgical repair. METHODS TAPSE was determined in 131 patients with TOF and 252 age-matched normal subjects. TAPSE values were compared with RV ejection fraction (EF) and indexed RV end-diastolic volume (EDVi) determined by magnetic resonance imaging in a cross-sectional study design. TAPSE values were also correlated to QRS duration (QRSd) determined by electrocardiogram. RESULTS The TAPSE values showed a positive correlation with age in normal subjects. The TAPSE was not decreased in infants and young children with TOF compared with normal subjects. A significant reduction of TAPSE values with increasing time after surgical repair was observed. After a mean of 7 years after surgical repair, the TAPSE values become significantly reduced compared with age-matched controls, being below the lower bound of -2 standard deviations. A positive correlation between TAPSE with RVEF and a negative correlation between TAPSE with RVEDVi were observed. A significant positive correlation was found between QRSd and RVEDVi, and a significant negative correlation was found between QRSd and RVEF. CONCLUSION Although TAPSE was initially preserved, impaired TAPSE was observed with increasing time after surgical repair in pediatric patients with TOF.

The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC): results from phase I and scientific opportunities in phase II.

BACKGROUND Genetically triggered thoracic aortic conditions (GenTACs) represent an important problem for patients and their families. Accordingly, the National Heart, Lung, and Blood Institute established the first phase of its national GenTAC Registry in 2006. ENROLLMENT AND DIAGNOSES Between 2007 and 2010, 6 enrolling centers established the GenTAC I Registry consisting of 2,046 patients (Marfan syndrome 576 [28.2%], bicuspid aortic valve disease 504 [24.6%], aneurysm or dissection age <50 years 369 [18%], and others). Biologic samples for DNA analyses (white blood cells or saliva) are available in 97%, and stored plasma is available in 60% of enrollees. RESULTS Initial scientific inquiry using the GenTAC Registry has included validation studies of genetic causes for aortic syndromes, potential usefulness of transforming growth factor beta (TGFB) blood levels in Marfan subjects, and current surgical approaches to ascending aortic conditions. FUTURE OPPORTUNITY The second phase of GenTAC will allow biannual follow-up of GenTAC I enrollees for up to 9 years, enrollment of an additional 1,500 subjects, further integration of imaging findings with clinical and genetic data through utilization of an imaging core laboratory, important validation of phenotype-genotype correlations through a phenotyping core laboratory, and integration of a scientific advisory committee to help define the full range and depth of the Registrys scientific capabilities. The registry resources are available to the external scientific community through an application process accessible at https://gentac.rti.org.

Long-term implications of emergency versus elective proximal aortic surgery in patients with Marfan syndrome in the Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions Consortium Registry.

OBJECTIVE Patients with Marfan syndrome with aortic root aneurysms undergo elective aortic root replacement to avoid the life-threatening outcomes of aortic dissection and emergency repair. The long-term implications of failed aortic surveillance leading to acute dissection and emergency repair are poorly defined. We compared the long-term clinical courses of patients with Marfan syndrome who survive emergency versus elective proximal aortic surgery. METHODS The Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions Registry is a National Institutes of Health-funded multicenter database and biorepository that enrolls patients with genetically triggered thoracic aortic aneurysms. Of the 635 patients with Marfan syndrome enrolled as of March 2011, 194 had undergone proximal aortic replacement. Patients were grouped according to emergency (n = 47) or elective (n = 147) status at the time of surgery. RESULTS Patients in the emergency group were more likely to have incomplete proximal aortic resection; 83% of emergency procedures included aortic root replacement, compared with 95% of elective procedures. At long-term follow-up (mean, >6 years), the emergency group had a higher incidence of chronic dissection of the distal aorta and significantly larger diameters in distal aortic segments than elective patients. Patients in the emergency group had undergone more operations (1.31 vs 1.11 procedures/patient; P = .01) and had lower activity scores on a health-related quality of life survey. CONCLUSIONS For patients with Marfan syndrome, failed aortic surveillance and consequent emergency dissection repair have important long-term implications with regard to the status of the distal aorta, need for multiple procedures, and quality of life. These findings emphasize the importance of aortic surveillance and timely elective aortic root aneurysm repair for patients with Marfan syndrome.

The Need for Standardized Methods for Measuring the Aorta Multimodality Core Lab Experience from the GenTAC Registry

OBJECTIVES This study sought to evaluate variability in aortic measurements with multiple imaging modalities in clinical centers by comparing with a standardized measuring protocol implemented in a core laboratory. BACKGROUND In patients with aortic disease, imaging of thoracic aorta plays a major role in risk stratifying individuals for life-threatening complications and in determining timing of surgical intervention. However, standardization of the procedures for performance of aortic measurements is lacking. METHODS To characterize the diversity of methods used in clinical practice, we compared aortic measurements performed by echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI) at the 6 GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) clinical centers to those performed at the imaging core laboratory in 965 studies. Each center acquired and analyzed their images according to local protocols. The same images were subsequently analyzed blindly by the core laboratory, on the basis of a standardized protocol for all imaging modalities. Paired measurements from clinical centers and core laboratory were compared by mean of differences and intraclass correlation coefficient (ICC). RESULTS For all segments of the ascending aorta, echocardiography showed a higher ICC (0.84 to 0.93) than CT (0.84) and MRI (0.82 to 0.90), with smaller mean of differences. MRI showed higher ICC for the arch and descending aorta (0.91 and 0.93). In a mixed adjusted model, the different imaging modalities and clinical centers were identified as sources of variability between clinical and core laboratory measurements, whereas age groups or diagnosis at enrollment were not. CONCLUSIONS By comparing core laboratory with measurements from clinical centers, our study identified important sources of variability in aortic measurements. Furthermore, our findings with regard to CT and MRI suggest a need for imaging societies to work toward the development of unifying acquisition protocols and common measuring methods.

Aortic Complications Associated With Pregnancy in Marfan Syndrome: The NHLBI National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)

Background The risk of aortic complications associated with pregnancy in women with Marfan syndrome (MFS) is not fully understood. Methods and Results MFS women participating in the large National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) were evaluated. Among 184 women with MFS in whom pregnancy information was available, 94 (51%) had a total of 227 pregnancies. Among the women with pregnancies, 10 (10.6%) experienced a pregnancy‐related aortic complication (4 type A and 3 type B dissections, 1 coronary artery dissection, and 2 with significant [≥3 mm] aortic growth). Five of 7 aortic dissections, including all 3 type B, and the coronary dissection (75% of all dissections) occurred in the postpartum period. Only 5 of 8 women with pregnancy‐associated dissection were aware of their MFS diagnosis. The rate of aortic dissection was higher during the pregnancy and postpartum period (5.4 per 100 person‐years vs 0.6 per 100 person‐years of nonpregnancy; rate ratio, 8.4 [95% CI=3.9, 18.4]; P<0.0001). Conclusions Pregnancy in MFS is associated with an increased risk of aortic dissection, both types A and B, particularly in the immediate postpartum period. Lack of knowledge of underlying MFS diagnosis before aortic dissection is a major contributing factor. These findings underscore the need for early diagnosis, prepregnancy risk counseling, and multidisciplinary peripartum management.