Cardiac MRI evaluation of aortic biophysical properties in paediatric Turner syndrome.

BACKGROUND: Aortopathy in Turner syndrome is associated with aortic dilation, and the risk of dissection is increased when the aortic size index is ≥ 2-2.5 cm/m2. We evaluated the aortic biophysical properties in paediatric Turner syndrome using cardiac MRI to determine their relationship to aortic size index. METHODS: Turner syndrome patients underwent cardiac MRI to evaluate ventricular function, aortic dimensions, and biophysical properties (aortic stiffness index, compliance, distensibility, pulse wave velocity, and aortic and left ventricular elastance). Spearman correlation examined correlations between these properties and aortic size index. Data was compared to 10 controls. RESULTS: Of 25 Turner syndrome patients, median age 14.7 years (interquartile range: 11.0-16.8), height z score -2.7 (interquartile range: -2.92 - -1.54), 24% had a bicuspid aortic valve. Turner syndrome had increased diastolic blood pressure (p < 0.001) and decreased left ventricular end-diastolic (p < 0.001) and end-systolic (p = 0.002) volumes compared to controls. Median aortic size index was 1.81 cm/m2 (interquartile range: 1.45-2.1) and 7 had an aortic size index > 2 cm/m2. Aortic and left ventricular elastance were greater in Turner syndrome compared to controls (both p < 0.001). Increased aortic size index correlated with increased aortic elastance (r = 0.5, p = 0.01) and left ventricular elastance (r = 0.59, p = 0.002) but not aortic compliance. Higher ascending aortic areas were associated with increased aortic compliance (r = 0.44, p = 0.03) and left ventricular elastance (r = 0.49, p = 0.01). CONCLUSION: Paediatric Turner syndrome with similar aortic size index to controls showed MRI evidence of abnormal aortic biophysical properties. These findings point to an underlying aortopathy and provide additional parameters that may aid in determining risk factors for aortic dissection.

T1 mapping of the myocardium and liver in the single ventricle population.

BACKGROUND: Fontan associated liver disease (FALD) is an increasingly recognized complication of the single ventricle circulation characterized by hepatic venous congestion leading to hepatic fibrosis. Within the Fontan myocardium, fibrotic myocardial remodeling may occur and lead to ventricular dysfunction. Magnetic resonance imaging (MRI) T1 mapping can characterize both myocardial and liver properties. OBJECTIVE: The aim of this study was to compare myocardial and liver T1 between single ventricle patients with and without a Fontan and biventricular controls. MATERIALS AND METHODS: A retrospective study of 3 groups of patients: 16 single ventricle patients before Fontan (SVpre 2 newborns, 9 pre-Glenn, 5 pre-Fontan, 31% single right ventricle [SRV]), 16 Fontans (56% SRV) and 10 repaired d-transposition of the great arteries (TGA). Native modified Look-Locker inversion T1 times were measured in the myocardium and liver. Cardiac MRI parameters, myocardial and liver T1 values were compared in the three groups. Correlations were assessed between liver T1 and cardiac parameters. RESULTS: Myocardial T1 was higher in SVpre (1,056 ± 48 ms) and Fontans (1,047 ± 41 ms) compared to TGA (1,012 ± 48 ms, P < 0.05). Increased liver T1 was found in both SVpre (683 ± 82 ms) and Fontan (727 ± 49 ms) patients compared to TGA patients (587 ± 58 ms, P < 0.001). There was no difference between single left ventricle (SLV) versus SRV myocardial or liver T1. Liver T1 showed moderate correlations with myocardial T1 (r = 0.48, confidence interval [CI] 0.26-0.72) and ejection fraction (r = -0.36, CI -0.66-0.95) but not with other volumetric parameters. CONCLUSION: Increased liver T1 at both pre- and post-Fontan stages suggests there are intrinsic liver abnormalities early in the course of single ventricle palliation. Increased myocardial T1 and its relationship to liver T1 suggest a combination of edema from passive venous congestion and/or myocardial fibrosis occurring in this population. Liver T1 may provide an earlier marker of liver disease warranting further study.

Cardiac MRI-Derived Myocardial Deformation Parameters Correlate with Pulmonary Valve Replacement Indications in Repaired Tetralogy of Fallot.

Right ventricular (RV) volumetric cardiac magnetic resonance (CMR) criteria serve as indicators for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF). Myocardial deformation and tricuspid valve displacement parameters may be more sensitive measures of RV dysfunction. This study's aim was to describe rTOF RV deformation and tricuspid displacement patterns using novel CMR semi-automated software and determine associations with standard CMR measures. Retrospective study of 78 pediatric rTOF patients was compared to 44 normal controls. Global RV longitudinal and circumferential strain and strain rate (SR) and tricuspid valve (TV) displacement were measured. Correlation analysis between strain, SR, TV displacement, and volumes was performed between and within subgroups. The sensitivity and specificity of strain parameters in predicting CMR criteria for PVR was determined. Deformation variables were reduced in rTOF compared to controls. Decreased RV strain and TV shortening were associated with increased RV volumes and decreased RVEF. Longitudinal and circumferential parameters were predictive of RVESVi (> 80 ml/m2) and RVEF (< 47%), with circumferential strain (> - 15.88%) and SR (> - 0.62) being most sensitive. Longitudinal strain was unchanged between rTOF subgroups, while circumferential strain trended abnormal in those meeting PVR criteria compared to controls. RV deformation and TV displacement are abnormal in rTOF, and RV circumferential strain variation may reflect an adaptive response to chronic volume or pressure load. This coupled with associations of ventricular deformation with traditional PVR indications suggest importance of this analysis in the evolution of rTOF RV assessment.

Right Ventricular Remodeling in Hypoplastic Left Heart Syndrome is Minimally Impacted by Cardiopulmonary Bypass: A Comparison of Norwood vs. Hybrid.

Right ventricular (RV) remodeling in hypoplastic left heart syndrome (HLHS) begins prenatally and continues through staged palliations. However, it is unclear if the most marked observed remodeling post-Norwood is secondary to cardiopulmonary bypass (CPB) exposure or if it is an adaptation intrinsic to the systemic RV. This study aims to determine the impact of CPB on RV remodeling in HLHS. Echocardiograms of HLHS survivors undergoing stage 1 Norwood (n = 26) or Hybrid (n = 20) were analyzed at pre- and post-stage 1, pre- and post-bidirectional cavo-pulmonary anastomosis (BCPA), and pre-Fontan. RV fractional area change (FAC), vector velocity imaging for longitudinal & derived circumferential deformation (global radial shortening (GRS) = peak radial displacement/end-diastolic diameter), and deformation ratio (longitudinal/ circumferential) were assessed. Both groups had similar age, clinical status and functional parameters pre-stage 1. No difference in RV size and sphericity at any stage between groups. RVFAC was normal (> 35%) throughout for both groups. Both Norwood and Hybrid patients had increased GRS (p = 0.0001) post-stage 1 and corresponding unchanged longitudinal strain, resulting in decreased deformation ratio (greater relative RV circumferential contraction), p = 0.0001. Deformation ratio remained decreased in both groups in subsequent stages. Irrespective of timing of the first CPB exposure, both Norwood and Hybrid patients underwent similar RV remodeling, with relative increase in circumferential to longitudinal contraction soon after stage 1 palliation. The observed RV remodeling in HLHS survivors were minimally impacted by CPB.

Tilt-table Echocardiography Unmasks Early Diastolic Dysfunction in Patients With Hemoglobinopathies.

Individuals with hemoglobinopathy (sickle cell anemia and thalassemia major) are at risk for cardiac complications such as heart failure and cardiomyopathy. Diastolic dysfunction is known to precede systolic dysfunction in many cardiac diseases. This study sought to determine whether changes in left atrial (LA) function during manipulation of cardiac preload by tilt-table echocardiography can unmask subclinical diastolic dysfunction in pediatric patients with hemoglobinopathies. Eleven sickle cell anemia, 9 transfusion-dependent thalassemia major, and 10 control subjects underwent tilt-table echocardiogram in the supine (loading) and 30-degree upright (unloading) positions and cardiac magnetic resonance imaging (MRI). Echocardiography assessed LA and left ventricular (LV) strain, strain rate, mitral inflow, and annular velocities. MRI assessed LV function, myocardial T1 and T2* for iron deposition. Both thalassemia major and sickle cell anemia patients had normal LV function and no evidence of cardiac iron deposition on MRI T2* measurements. During cardiac loading, controls appropriately increased LA conduit (P=0.002) and reservoir strain (P=0.002), mitral e' velocity (P<0.0001) and medial e' velocity (P=0.002), while the hemoglobinopathy patients showed no change in these parameters. In pediatric sickle cell anemia and thalassemia, tilt-table echocardiography unmasked a failure to augment LA function in response to loading, suggesting altered myocardial relaxation is present, before evidence of iron overload or systolic dysfunction.

Cardiac Magnetic Resonance Imaging in Pediatric Turner Syndrome.

OBJECTIVE: To compare the detection of cardiac lesions with the use of cardiac magnetic resonance imaging (CMR) and conventional echocardiography in children with Turner syndrome. STUDY DESIGN: Twenty-four girls with Turner syndrome, 8-18 years of age, were recruited through the Pediatric Endocrinology Program. Participants underwent CMR and echocardiography within a 2-year period, and discrepancies between the results of each modality were identified. RESULTS: Fifteen of 24 (63%) girls had a cardiac lesion identified on CMR or echocardiography. Both modalities identified the same lesion in 10 of 15 (67%); however, 6 of 15 (40%) participants had a lesion identified on CMR but not echocardiography. Participants with a missed lesion had a trend towards greater body mass index. Aortic dilation and bicuspid aortic valve were the most commonly missed lesions by echocardiography. CONCLUSIONS: CMR identifies significant cardiac lesions missed by echocardiography in pediatric patients with Turner syndrome, particularly along the aorta. These findings support the current guidelines that recommend screening CMR in addition to echocardiogram. Early identification of cardiac abnormalities in patients with Turner syndrome will allow for a greater understanding of the natural history in these patients and potentially identify candidates for earlier intervention.

Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy.

BACKGROUND: Childhood cancer survivors show evidence of diffuse myocardial fibrosis that is related to exercise capacity. The mechanism of reduced exercise tolerance in anthracycline cardiotoxicity remains unclear. We explored the determinants of exercise intolerance by evaluating left ventricular (LV) distensibility and functional reserve. METHODS: Patients (n = 22) and healthy controls (n = 10) underwent two-dimensional echocardiography while supine, upright, and during cycle exercise. LV distensibility was measured as the change in end-diastolic cavity area (EDCA) from supine to the upright position. LV functional reserve was assessed during peak exercise, and measured as the exercise-induced change in systolic circumferential strain rate (SR) and early-diastolic SR (EDSR). The peak rate of oxygen consumption was measured by indirect calorimetry. RESULTS: Median age of patients was 16 years (range 8-19) and controls 14 years (range 8-19). Median time since anthracycline therapy was 6 years (range 2-16). Peak oxygen consumption was significantly lower in patients compared to controls (35 ml/kg/min [28-60] vs. 45 ml/kg/min [44-53], P = 0.005). Transitioning from the supine position to the upright position caused a similar reduction in LV EDCA, suggesting similar LV distensibility between patients (-22% [-46 to -4]) and controls (-20% [-46 to -3], P = 0.3). However, during exercise, both systolic SR and EDSR reserve were significantly impaired in patients (∆SR: 93% [14-308], ∆EDSR: -4.5% [-88 to 121]) compared to controls (∆SR: 128% [54-230], P = 0.046; ∆EDSR: 74% [22-234], P = 0.02). CONCLUSIONS: Our findings suggest that impaired LV contractility and functional reserve play a role in the reduced exercise capacity in anthracycline cardiotoxicity rather than LV distensibility.

Adherence to clinical practice guidelines for pulmonary valve intervention after tetralogy of Fallot repair: A nationwide cohort study.

Objectives: To determine guideline adherence pertaining to pulmonary valve replacement (PVR) referral after tetralogy of Fallot (TOF) repair. Methods: Children and adults with cardiovascular magnetic resonance imaging scans and at least moderate pulmonary regurgitation were prospectively enrolled in the Comprehensive Outcomes Registry Late After TOF Repair (CORRELATE). Individuals with previous PVR were excluded. Patients were classified according to presence (+) versus absence (-) of PVR and presence (+) versus absence (-) of contemporaneous guideline satisfaction. A validated score (specific activity scale [SAS]) classified adult symptom status. Results: In total, 498 participants (57% male, mean age 32 ± 14 years) were enrolled from 14 Canadian centers (2013-2020). Mean follow-up was 3.8 ± 1.8 years. Guideline criteria for PVR were satisfied for the majority (n = 422/498, 85%), although referral for PVR occurred only in a minority (n = 167/498, 34%). At PVR referral, most were asymptomatic (75% in SAS class 1). One participant (0.6%) received PVR without meeting criteria (PVR+/indication-). The remainder (n = 75/498, 15%) did not meet criteria for and did not receive PVR (PVR-/indication-). Abnormal cardiovascular imaging was the most commonly cited indication for PVR (n = 61/123, 50%). The SAS class and ratio of right to left end-diastolic volumes were independent predictors of PVR in a multivariable analysis (hazard ratio, 3.33; 95% confidence interval, 1.92-5.8, P < .0001; hazard ratio, 2.78; 95% confidence interval, 2.18-3.55, P < .0001). Conclusions: Although a majority of patients met guideline criteria for PVR, only a minority were referred for intervention. Abnormal cardiovascular imaging was the most common indication for referral. Further research will be necessary to establish the longer-term clinical impact of varying PVR referral strategies.

Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling.

BACKGROUND: The late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors. METHODS: Thirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO(2)). CMR measured ventricular function, mass, T(1) and T(2) values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography. RESULTS: Patients had normal LVEF (59 ± 7%) but peak VO(2) was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = -0.49). Increased ECV correlated with decreased mass/volume ratio (r = -0.64), decreased LV wall thickness/height ratio (r = -0.72), lower peak VO(2)(r = -0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO(2) or cumulative dose. CONCLUSIONS: Myocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.

Regional Elevation of Liver T1 in Fontan Patients.

Background: Fontan-associated liver disease (FALD) is characterized by hepatic congestion and progressive hepatic fibrosis in patients with the Fontan operation. This condition is generally clinically silent until late, necessitating techniques for early detection. Liver T1 mapping has been used to screen for FALD, but without consideration of regional variations in T1 values. Methods: Liver T1 measured with a liver-specific T1 mapping sequence (PROFIT1) in Fontan patients was compared with cohorts of patients with biventricular congenital heart disease (BiV-CHD) and controls with normal cardiac function and anatomy. Results: Liver T1 was significantly elevated in the Fontan cohort (n = 20) compared with patients with BiV-CHD (n = 12) and controls (n = 9) (781, 678, and 675 milliseconds, respectively; P < 0.001), with a consistent pattern of significantly elevated T1 values in the peripheral compared with central liver regions (ΔT1 = 54, 2, and 11 milliseconds; P < 0.001). PROFIT1 also yielded simultaneous T2∗ maps and fat fraction values that were similar in all groups. Fontan liver T1 values were also significantly elevated as compared with BiV-CHD and controls as measured with the cardiac (modified Look-Locker inversion) acquisitions (728, 583, and 583 milliseconds, respectively; P < 0.001) and values correlated with PROFIT1 liver T1 (R = 0.87, P < 0.001). Conclusions: Fontan patients have globally increased liver T1 values and consistent spatial variations, with higher values in the peripheral liver regions as compared with spatially uniform values in BiV-CHD and controls. The spatial patterns may provide insight into the progression of FALD. Liver T1 mapping studies should include uniform spatial coverage to avoid bias based on slice locations in this population.

Contexte: L'hépatopathie associée à une intervention de Fontan (FALD, pour Fontan-associated liver disease) se caractérise par une congestion hépatique et une fibrose hépatique évolutive chez les patients qui ont subi une intervention de Fontan. Il s'agit d'un état pathologique silencieux en début de progression, pour lequel des techniques de détection précoce sont requises. La cartographie T1 du foie est utilisée pour le dépistage de la FALD, mais sans que les variations locales des valeurs obtenues soient prises en compte. Méthodologie: Des valeurs T1 hépatiques ont été mesurées avec une séquence cartographique conçue pour le foie (PROFIT1) chez des patients qui ont subi une intervention de Fontan. Ces valeurs ont été comparées à celles d'une cohorte de patients atteints de cardiopathie congénitale biventriculaire (CC-BiV) et à celles de témoins dont l'anatomie et la fonction cardiaques étaient normales. Résultats: Les valeurs T1 hépatiques étaient significativement plus élevées chez les patients ayant subi une intervention de Fontan (n = 20) que chez les patients atteints de CC-BiV (n = 12) et chez les témoins (n = 9) (781 ms, 678 ms, 675 ms, p < 0,001), et ces valeurs tendaient à être plus élevées dans les régions périphériques que dans les régions centrales du foie (ΔT1 = 54 ms, 2 ms, 11 ms, p < 0,001). La séquence PROFIT1 a aussi permis l'obtention des valeurs de cartographie T2∗ et de teneur en matières grasses dans le foie, et ces valeurs étaient comparables pour tous les groupes. L'utilisation d'une séquence cardiaque (MOLLI, pour modified Lock-Locker inversion) a également engendré des valeurs T1 hépatiques significativement plus élevées chez les patients ayant subi l'intervention de Fontan que chez les patients atteints de CC-BiV et les témoins (728 ms, 583 ms, 583 ms, p < 0,001). Ces valeurs étaient par ailleurs corrélées avec les valeurs T1 hépatiques obtenues par la séquence PROFIT1 (R = 0,87, p < 0,001). Conclusions: Dans l'ensemble, les patients ayant subi l'intervention de Fontan présentaient des valeurs T1 hépatiques élevées accompagnées de variations spatiales. Les valeurs périphériques étaient systématiquement plus élevées, tandis que celles obtenues chez les patients atteints de CC-BiV et chez les témoins étaient uniformes. Les tendances qui sous-tendent ces variations spatiales pourraient fournir des pistes pour mieux comprendre la progression de la FALD. Enfin, les études de cartographie T1 hépatiques dans cette population devraient couvrir uniformément le foie pour éviter les biais liés à la coupe.

Implementation of Virtual Fontan Heart Camps During a Pandemic.

BACKGROUND: Children with a Fontan operation represent a unique form of congenital heart disease (CHD) that requires multiple cardiac surgeries and procedures with an uncertain long-term outcome. Given the rarity of the types of CHD that require this procedure, many children with a Fontan do not know any others like them. METHODS: With the cancelation of medically supervised heart camps due to the COVID-19 pandemic, we have organized several physician-led virtual day camps for children with a Fontan operation to connect with others in their province and across Canada. The aim of this study was to describe the implementation and evaluation of these camps via the use of an anonymous online survey immediately after the event and reminders on days 2 and 4 postevent. RESULTS: Fifty-one children have participated in at least 1 of our camps. Registration data showed that 70% of participants did not know anyone else with a Fontan. Postcamp evaluations showed that 86% to 94% learned something new about their heart and 95% to 100% felt more connected to other children like them. CONCLUSION: We have demonstrated the implementation of a virtual heart camp to expand the support network for children with a Fontan. These experiences may help to promote healthy psychosocial adjustments through inclusion and relatedness.

Patient-Reported Outcomes After Tetralogy of Fallot Repair.

BACKGROUND: Comprehensive assessment of tetralogy of Fallot (TOF) outcomes extends beyond morbidity and mortality to incorporate patient-reported outcomes (PROs), including quality of life (QOL) and health status (HS). OBJECTIVES: This study explored PROs in adolescents and adults with TOF and delineated variables associated with PROs. METHODS: This was a cross-sectional observational study within a larger prospective registry of adolescents and adults with repaired TOF and moderate or greater pulmonary regurgitation from North America, Europe, and Asia. Participants completed PROs, including a QOL linear analogue scale (QOL-LAS) and an HS visual analogue scale (HS-VAS). Scores were classified according to age cohorts: <18, 18 to 25, 26 to 40, and >40 years. RESULTS: The study included 607 patients (46.3% female; median age 28.5 years). Median QOL-LAS scores (0-100) were similar across age cohorts (85, 80, 80, 80; P = 0.056). Median HS-VAS scores (0-100) were lowest for the oldest cohort (77) compared with the 3 younger cohorts (85, 80, 80) (P = 0.004). With advancing age, there were increased reports of poor mobility (P < 0.001) and pain or discomfort (P = 0.004); problems in these dimensions were reported by 19.1% and 37.2% of patients aged >40 years, respectively. Of factors associated with superior PROs on multivariable regression modeling (ie, being White, being nonsyndromic, having employment, and having better left ventricular function; P < 0.05), asymptomatic status (functional class I) was the variable associated with the greatest number of QOL and HS measures (P < 0.001). CONCLUSIONS: Strategies to improve TOF outcomes should consider PROs alongside conventional clinical variables. Factors associated with poorer PROs represent opportunities to intervene to improve the lives of patients with TOF.

Optimization of myocardial nulling in pediatric cardiac MRI.

BACKGROUND: Current protocols to determine optimal nulling time in late enhancement imaging using adult techniques may not apply to children. OBJECTIVE: To determine the optimal nulling time in anesthetised children, with the hypothesis that this occurs earlier than in adults. MATERIALS AND METHODS: Sedated cardiac MRI was performed in 12 children (median age: 12 months, range: 1-60 months). After gadolinium administration, scout images at 2, 3, 4 and 10 min and phase sensitive inversion recovery (PSIR) images from 5 to 10 min were obtained. Signal-to-noise ratio (SNR) and inversion time (TI) were determined. Quality of nulling was assessed according to a grading score by three observers. Data was analysed using linear regression, Kruskal-Wallis and quadratic-weighted kappa statistics. RESULTS: One child with a cardiomyopathy had late enhancement. Good agreement in nulling occurred for scout images at 2 (κ = 0.69) and 3 (κ = 0.66) min and moderate agreement at 4 min (κ = 0.57). Agreement of PSIR images was moderate at 7 min (κ = 0.44) and poor-fair at other times. There were significant correlations between TI and scout time (r = 0.61, P < 0.0001), and SNR and kappa (r = 0.22, P = 0.017). CONCLUSION: Scout images at 2-4 min can be used to determine the TI with little variability. Image quality for PSIR images was highest at 7 min and SNR optimal at 7-9 min. TI increases with time and should be adjusted frequently during imaging. Thus, nulling times in children differ from nulling times in adults when using standard adult techniques.

Outcome of fetuses and infants with double inlet single left ventricle.

Double-inlet left ventricle (DILV) includes a diverse range of anatomic variables that affect the surgical strategy. The aim of this study was to determine the impact of anatomic subtype, associated anomalies, and fetal diagnosis on the management and outcomes of fetuses and infants with DILV. The outcomes of fetuses and infants with DILV diagnosed from 1990 to 2004 at 3 major referral centers were reviewed. Sixty-five cases of DILV were detected prenatally. Twenty-one of these pregnancies were terminated, including 17 of 37 (46%) in which the diagnoses were made at < or =24 weeks of gestation. An additional 106 patients were diagnosed with DILV within the first 3 months of life. The percentage of patients diagnosed prenatally increased significantly over the study period. Transplantation-free survival was 88%, 82%, 79%, and 76% at 1 month, 1 year, 5 years, and 10 years, respectively. Factors associated with improved survival in univariate analysis included year of birth after 1994, no neonatal Norwood or Damus procedure, and no neonatal surgery at all. In multivariate analysis, any neonatal surgery was the only factor associated with worse survival. Associated anomalies and prenatal diagnosis were not associated with postnatal outcome. In conclusion, although the frequency of prenatal diagnosis of DILV has increased significantly over the past 15 years, prenatal diagnosis is not associated with better postnatal survival. During this same period, postnatal survival has improved substantially. Neonatal surgery of any type was the only independent risk factor for worse survival.

Reduced Right Ventricular Fractional Area Change, Strain, and Strain Rate before Bidirectional Cavopulmonary Anastomosis is Associated with Medium-Term Mortality for Children with Hypoplastic Left Heart Syndrome.

BACKGROUND: Ventricular dysfunction is associated with increased morbidity and mortality in children with hypoplastic left heart syndrome. The aim of this study was to assess the diagnostic performance of conventional and speckle-tracking echocardiographic measures of right ventricular (RV) function before bidirectional cavopulmonary anastomosis palliation in predicting death or need for heart transplantation (HTx). METHODS: RV fractional area change (RVFAC) and longitudinal and circumferential strain and strain rate (SR) were measured in 64 prospectively recruited patients with hypoplastic left heart syndrome from echocardiograms obtained before bidirectional cavopulmonary anastomosis surgery. The composite end point of death or HTx was examined. Receiver operating characteristic analysis was performed, and cutoff values optimizing sensitivity and specificity were derived. RESULTS: At a median follow-up of 5.0 years (interquartile range, 2.8-6.4 years), 13 patients meeting the composite end point had lower longitudinal strain and SR, circumferential SR, and RVFAC compared with survivors (n = 51). The conventional cutoff of RVFAC < 35% was specific for death or HTx (86%) but had poor sensitivity (46%), with an area under the curve of 0.73. Speckle-tracking echocardiographic variables showed similar areas under the curve (range, 0.69-0.79), with negative predictive values >90%. Addition of speckle-tracking echocardiographic variables to RVFAC < 35% showed no added benefit. However, in a subpopulation of patients with RVFAC ≥ 35% (n = 44), those meeting the composite end point (n = 7) had lower longitudinal SR (median, -1.0 1/sec [interquartile range, -0.8 to -1.1 1/sec] vs -1.21/sec [interquartile range, -1.0 to -1.3 1/sec], P = .03). Interobserver reproducibility was superior for longitudinal strain and SR (intraclass correlation coefficient > 0.92) compared with RVFAC (intraclass correlation coefficient = 0.75). CONCLUSIONS: Children with hypoplastic left heart syndrome with normal RVFAC and ventricular deformation before bidirectional cavopulmonary anastomosis have a low likelihood of death or HTx in the medium term. In the presence of reduced RVFAC, speckle-tracking echocardiography does not provide additional prognostic value. However, in patients with "normal" RVFAC, it may have a role in improving outcome prediction and warrants further investigation.

Outcome after prenatal diagnosis of tricuspid atresia: a multicenter experience.

BACKGROUND: The outcome of prenatally diagnosed tricuspid atresia (TA) is undefined. We sought to characterize clinical and echocardiographic features of fetal TA and to determine factors associated with mortality. METHODS AND RESULTS: All fetuses with TA (n = 88) seen at 3 tertiary care institutions from 1990 to 2005 were reviewed. There were 58 liveborn infants (median gestational age 38 weeks, range 24-40 weeks), 4 in utero demises, 25 terminations of pregnancy, and 1 mother lost to follow-up. Obstruction was present at the pulmonary valve in 27 (45%), aortic valve in 6 (10%), and aortic arch in 15 (25%). Three neonates received compassionate care, 1 died with multiple extracardiac anomalies, 2 were lost to follow-up, and 52 liveborns were actively managed with Blalock-Taussig shunt (23), Norwood palliation (14), pulmonary artery band (10), bidirectional cavopulmonary connection (3), atrial septostomy (1), and right outflow stent (1). Of those actively managed, there were 7 (14%) of 52 who died. Kaplan-Meier estimates of survival were 91% at 1 month, 87% at 6 months, and 83% at 1 year with no subsequent deaths for 13 years. By multivariate analysis, 2 independent factors were associated with an increase in time-related mortality in the actively managed group: presence of chromosomal anomaly or syndrome (P = .005) and use of extracorporeal membrane oxygenation (P = .002). CONCLUSIONS: This is the largest study describing TA in fetus. Compared with published observations of TA diagnosed postnatally, antenatal diagnosis of TA appears to have similar short-term survival in pregnancies surviving to birth.

Stress perfusion magnetic resonance imaging to detect coronary artery lesions in children.

BACKGROUND: Stress perfusion cardiovascular magnetic resonance (CMR) is used widely in adult ischemic heart disease, but data in children is limited. We sought to evaluate feasibility, accuracy and prognostic value of stress CMR in children with suspected coronary artery disease (CAD). METHODS: Stress CMR was reviewed from two pediatric centers over 5 years using a standard pharmacologic protocol. Wall motion abnormalities, perfusion deficits and late enhancement were correlated with coronary angiogram (CAG) when available, and clinical status at 1 year follow-up for major adverse cardiovascular events (MACE; coronary revascularization, non-fatal myocardial infarction and death due to CAD) was recorded. RESULTS: Sixty-four stress perfusion CMR studies in 48 children (10.9 ± 4.8 years) using adenosine; 59 (92%) and dipyridamole; 5 (8%), were reviewed. Indications were Kawasaki disease (39%), post arterial switch operation (12.5%), post heart transplantation (12.5%), post anomalous coronary artery repair (11%), chest pain (11%), suspected myocarditis or CAD (3%), post coronary revascularization (3%), and others (8%). Twenty-six studies were performed under sedation. Of all studies performed, 66% showed no evidence of ischemia or infarction, 28% had perfusion deficits and 6% had late gadolinium enhancement (LGE) without perfusion deficit. Compared to CAG, the positive predictive value (PPV) of stress CMR was 80% with negative predictive value (NPV) of 88%. At 1 year clinical follow-up, the PPV and NPV of stress CMR to predict MACE were 78 and 98%. CONCLUSION: Stress-perfusion CMR, in combination with LGE and wall motion-analysis is a feasible and an accurate method of diagnosing CAD in children. In difficult cases, it also helps guide clinical intervention by complementing conventional CAG with functional information.

Impaired Single Right Ventricular Function Compared to Single Left Ventricles during the Early Stages of Palliation: A Longitudinal Study.

BACKGROUND: Single right ventricles (SRV) are postulated to be disadvantaged compared with single left ventricles (SLV). We compared the evolution of SRV versus SLV function during infancy using conventional measures and speckle-tracking echocardiography (STE). We hypothesized that the SRV is mechanically disadvantaged during early infancy. METHODS: SRVs (n = 32) were compared with SLVs (n = 16) at the neonatal (presurgery) and pre-bidirectional cavopulmonary anastomosis (pre-BCPA) stages. Functional measures (fractional area change, indexed ventricular annular plane systolic excursion [iVAPSE], isovolumic acceleration [IVA], myocardial performance index, E and A velocities, tissue Doppler imaging annular velocities and STE-measured global longitudinal and circumferential strain, strain rate [SR], and early diastolic SR [EDSR]) were compared between SRV and SLV at each stage and between presurgery and pre-BCPA. RESULTS: Compared with SLV, presurgery SRV had lower circumferential strain (-10.6% vs -16.5%; P = .0002) and EDSR (1.41%/sec vs 2.13%/sec; P = .001). Pre-BCPA SRV had decreased IVA (1.2 vs 2.1 m/sec2; P = .006): longitudinal strain (-15.3% vs -19.1%; P = .001), SR (-0.97%/sec vs -1.53%/sec; P = .0001), EDSR (1.5%/sec vs 2.1%/sec; P = .001); circumferential strain (-10.6% vs -14.9%; P = .002), SR (-0.8%/sec vs -1.21%/sec; P = .0001), and EDSR (1.3%/sec vs 1.8%/sec; P = .009). SRV showed reduction of iVAPSE, IVA, s', e', a' velocities, longitudinal strain, SR, EDSR, and circumferential SR (P < .05) from presurgery to pre-BCPA, while circumferential strain was unchanged. SLV showed no significant change in these parameters during this interval. CONCLUSIONS: The progressive reduction in SRV longitudinal and circumferential function suggests that SRV may have a mechanical disadvantage from birth and progressive impairment with age.

Strain Rate in Children and Young Piglets Mirrors Changes in Contractility and Demonstrates a Force-Frequency Relationship.

BACKGROUND: In adult humans and pig models, strain rate (SR) correlates strongly with invasive measures of contractility but does not demonstrate a force-frequency relationship, which is a fundamental behavior of myocardial contraction. Given the considerable maturational changes of the myocardium from fetal stages to adulthood, extrapolation of adult findings to the young heart may not be appropriate. We sought to evaluate the SR response of the immature heart to increased heart rate (HR) and inotropic stimulation. METHODS: The study consisted of two parts. In part 1, children without obvious structural or functional cardiac abnormalities were evaluated following successful radiofrequency ablation. Echocardiography was performed at baseline HR and then with atrial pacing and isoprenaline infusion titrated to achieve 130% of baseline HR. Left ventricular (LV) speckle tracking-derived SR and tissue Doppler isovolumic acceleration (IVA, a load-independent marker of contractility) were measured. In part 2, young piglets were submitted to atrial pacing at 200, 230, and 260 bpm. Invasive LV dP/dt was assessed, and speckle tracking-derived SR was measured at all stages. Repeated measures analysis of variance was used for comparison with baseline values. RESULTS: In part 1, the LV SR and IVA (septal and lateral) in 23 children (ages 7.8-17.5 years) increased significantly with pacing and isoprenaline infusion (P < .001). In part 2, SR and invasive dP/dt increased significantly with increasing HR in young piglets (1-17 days; P < .01 and P < .001, respectively). Both LV SR and dP/dt plateaued at highest HRs concurrent with the decrease in LV end-diastolic dimension from baseline (73.0% ± 9.9% of the baseline value at 260 bpm; P < .001). CONCLUSIONS: SR in children is augmented with chronotropic and inotropic stimulation and in young infant piglets with chronotropic stimulation; in both children and piglets it has a force-frequency relationship, a behavior that is consistent with a measure of contractility.

Experience of percutaneous coronary intervention in the management of pediatric cardiac allograft vasculopathy.

In a retrospective study, we examined the procedural success rate and the short-, intermediate-, and long-term outcomes of coronary interventional procedures in children with cardiac allograft vasculopathy. Seven patients underwent 13 interventional procedures: balloon angioplasty alone (n = 3), angioplasty with stenting (n = 9), or angioplasty with brachytherapy (n = 1), with procedural success in all. Two major complications (cardiac arrest) and a single death occurred in the immediate postprocedural period. Five (83%) of the remaining 6 patients developed moderate to severe restenosis, diffuse disease, or progressive vasculopathy; 3 have been retransplanted, 1 died from progressive cardiac allograft vasculopathy, and 1 is awaiting retransplantation, 40 months after the procedure.