Strengths, Limitations, and Geographical Discrepancies in the Eligibility Criteria for Sport Participation in Young Patients With Congenital Heart Disease.

OBJECTIVE: Benefits of physical activity has been shown in children with congenital heart disease (CHD). In several forms of CHD, the risk of sudden death remains a major concern both for parents and clinicians, who in turn will have to consider the risk-benefit ratio of sport participation versus restriction. DATA SOURCE: A literature search was performed within the National Library of Medicine using the keywords: Sport, CHD, and Eligibility. The search was further refined by adding the keywords: Children, Adult, and Criteria. MAIN RESULTS: Fifteen published studies evaluating sport eligibility criteria in CHD were included. Seven documents from various scientific societies have been published in the past decade but which of them should be adopted remains unclear. Our research highlighted accuracy and consistency of the latest documents; however, differences have emerged between the US and European recommendations. Eligibility criteria were consistent between countries for simple congenital heart defects, whereas there are discrepancies for borderline conditions including moderate valvular lesions and mild or moderate residual defects after CHD repair. Furthermore, some of the more severe defects were not evaluated. Multiple recommendations have been made for the same CHD, and cut-off values used to define disease severity have varied. Published eligibility criteria have mainly focused on competitive sports. Little attention was paid to recreational activities, and the psychosocial consequences of activity restriction were seldom evaluated. CONCLUSIONS: Comprehensive consensus recommendations for sport eligibility evaluating all CHD types and stages of repair are needed. These should include competitive and recreational activities, use standardized classifications to grade disease severity, and address the consequences of restriction.

Echocardiographic assessment of pediatric semilunar valve disease.

We reviewed echocardiography literature for the assessment and management of semilunar valve disease in children. A search was performed within the National Library of Medicine using the keywords aortic stenosis (AS), aortic regurgitation, pulmonary stenosis (PS), and pulmonary regurgitation in children. The search was further refined adding the keywords-pediatric, neonates, echocardiographic definition, classification, evaluation. Thirty-eight studies were included. For stenotic lesions, there were sufficient consistencies between Doppler and invasive gradients (especially for PS), while other quantitative parameters used in adults showed significant limitations when applied to children. Heterogeneities remain in the range of Doppler measurements utilized to define mild vs moderate vs severe AS/PS, and to guide management. There is sufficient consensus regarding indications for interventions. In regurgitant lesions, there is weak evidence supporting the use of quantitative or semiquantitative parameters after correction for body surface area; clear indications for intervention are lacking. Because adult echocardiographic recommendations cannot be simply translated to the pediatric age, more specific pediatric guidelines and standards for the assessment of semilunar valve disease are needed.

Strengths and Limitations of Current Adult Nomograms for the Aorta Obtained by Noninvasive Cardiovascular Imaging.

Normalized measurements for the evaluation of aortic disease severity are preferred to the adoption of generic cutoff values. The purpose of this review is to evaluate the strengths and limitations of currently available aortic nomograms by echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI). A literature search was conducted accessing the National Library of Medicine using the keywords normal values, aorta, echocardiography, CT, and MRI. Addition of these keywords further refined the results: reference values, nomograms, aortic arch, and adults. Thirty studies were included in the final analysis. Despite the strengths noted in the recent investigations, multiple methodological and numerical limitations emerged. The numerical limitations included sample size limitation in most of the studies (only few investigations consisted of >800 subjects and many had 70-300), lack of aortic arch measurements, and paucity of data for non-Caucasian subjects. Methodological limitations consisted of lack of standardization in measurements (systole vs. diastole, internal vs. external border, axial vs. orthogonal planes), heterogeneity and data normalization issues (various age intervals used, body size often not evaluated, data expressed as observed values rather than estimated values by z-score), and study design issues. The designs were mostly retrospective with poorly defined inclusion and exclusion criteria. The nomograms presented range of normality with significant differences, but also with some reproducible pattern. Despite recent advances, multiple methodological or numerical limitations exist in adult nomograms for the aorta. Comprehensive nomograms of aortic dimensions at multiple levels including the aortic arch for different imaging techniques, involving a wide sample size, and using standardized methodology for measurements and data normalization are warranted. The availability of robust nomograms may encourage the use of personalized rather than generic cutoff values.

Nomograms for mitral inflow Doppler and tissue Doppler velocities in Caucasian children.

BACKGROUND: Pediatric echocardiographic nomograms for systolic/diastolic functional indices are limited by small sample size and inconsistent methodologies. Our aim was to establish pediatric nomograms for mitral valve (MV) pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI) velocities. METHODS: We performed PWD/TDI measurements of MV velocities and generated models testing for linear/logarithmic/exponential/square root relationships. Heteroscedasticity was accounted for by White test or Breusch-Pagan test. Age, weight, height, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. RESULTS: In all, 904 Caucasian Italian healthy children (age 0 days-17 years; 45.5% females; BSA 0.12-2.12m(2)) were prospectively studied. No individual variable provided equations with an acceptable coefficient of determination (R(2)) and even the inclusion of multiple variables in the model resulted in only a partial amelioration of the R(2). Higher R(2) were obtained for PWD-E deceleration time (0.53), septal (Se') and lateral (Le') MV-TDI e' velocity (Se': 0.54; Le': 0.55). Variability was higher at lower age and BSA. In older children patterns were more reproducible; however, the exclusion of neonates did not substantially improve the final models. The low R(2) hampered building of z-scores and calculation of estimated percentiles. Thus normative data have been presented as observed percentile according to age for all measurements. CONCLUSIONS: We report normal ranges for PWD and TDI mitral velocities derived from a large population of Caucasian children. Variability of diastolic patterns especially at lower ages needs to be taken into account.

Review and status report of pediatric left ventricular systolic strain and strain rate nomograms.

Interest in strain (ε) and strain rate (SR) for the assessment of pediatric left ventricular (LV) myocardial function has increased. However, the strengths and limitations of published pediatric nomograms have not been critically evaluated. A literature search was conducted accessing the National Library of Medicine using the keywords myocardial velocity, strain, strain rate, pediatric, reference values, and nomograms. Adding the following keywords, the results were further refined: neonates, infants, adolescents, range/intervals, and speckle tracking. Ten published studies evaluating myocardial velocities, ε, or SR nomograms were analyzed. Sample sizes were limited in most of these studies, particularly in terms of neonates. Heterogeneous methods-tissue Doppler imaging, two- and three-dimensional speckle tracking-were used to perform and normalize measurements. Although most studies adjusted measurements for age, classification by specific age subgroups varied. Few studies addressed the relationships of ε and SR measurements to body size and heart rate. Data have been generally expressed by mean values and standard deviations; Z scores and percentiles that are commonly employed for pediatric echocardiographic quantification have been never used. Reference values for ε and SR were found to be reproducible in older children; however, they varied significantly in neonates and infants. Pediatric nomograms for LV ε and SR are limited by (a) small sample sizes, (b) inconsistent methodology used for derivation and normalization, and (c) scarcity of neonatal data. Some of the studies demonstrate reproducible patterns for systolic deformation in older children. There is need for comprehensive nomograms of myocardial ε and SR involving a large population of normal children obtained using standardized methodology.

Strengths and limitations of current pediatric blood pressure nomograms: a global overview with a special emphasis on regional differences in neonates and infants.

The availability of robust nomograms is essential for the correct evaluation of blood pressure (BP) values in children. A literature search was conducted by accessing the National Library of Medicine by using the keywords BP, pediatric and reference values/nomograms. A total of 43 studies that evaluated pediatric BP nomograms were included in this review. Despite the accuracy of the latest studies, many numerical and methodological limitations still remain. The numerical limitations include the paucity of data for neonates/infants and for some geographic areas (Africa/South America/East Europe/Asia) and ethnicities. Furthermore, the data on ambulatory BP and response to exercise are extremely limited, and the criteria for stress-test interruption are lacking. There was heterogeneity in the methodologies employed to perform the measurements, in the inclusion/exclusion criteria (often not reported), in the data normalization and the data expression (Z-scores/percentiles/mean values). Although most studies adjusted the measurements for age and/or height, the classification by specific age/height subgroups varied. Gender differences were generally considered, whereas other confounders (that is, ethnicity/geographic area/environment) were seldom evaluated. As a result, nomograms were heterogeneous, and when comparable, at times showed widely different confidence intervals. These differences are most likely because of both methodological limitations and differences among the populations studied. Some robust nomograms exist (particularly those from the USA); however, it has been demonstrated that if adopted in other countries/continents, they may generate an unpredictable bias in the evaluation of BP values in children. Actual pediatric BP nomograms present consistent limitations that affect the evaluation of BP in children. Comprehensive nomograms, which are based on a large population of healthy children (including neonates/infants) and use standardized methodology, are warranted for every country/region.

BNP in children with congenital cardiac disease: is there now sufficient evidence for its routine use?

Interest in brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the management of children with CHD has increased. There are, however, no current guidelines for their routine use. The aim of this review article is to provide an update on the data regarding the use of BNP/NT-proBNP in the evaluation and surgical treatment of children with CHD. BNP/NT-proBNP levels in children with CHD vary substantially according to age, laboratory assay methods, and the specific haemodynamics associated with the individual congenital heart lesion. The accuracy of BNP/NT-proBNP as supplemental markers in the integrated screening, diagnosis, management, and follow-up of CHD has been established. In particular, the use of BNP/NT-proBNP as a prognostic indicator in paediatric cardiac surgery has been widely demonstrated, as well as its role in the subsequent follow-up of surgical patients. Most of the data, however, are derived from single-centre retrospective studies using multivariable analysis; prospective, randomised clinical trials designed to evaluate the clinical utility and cost-effectiveness of routine BNP/NT-proBNP use in CHD are lacking. The results of well-designed, prospective clinical trials should assist in formulating guidelines and expert consensus recommendations for its use in patients with CHD. Finally, the use of new point-of-care testing methods that use less invasive sampling techniques - capillary blood specimens - may contribute to a more widespread use of the BNP assay, especially in neonates and infants, as well as contribute to the development of screening programmes for CHD using this biomarker.

Echocardiographic nomograms for chamber diameters and areas in Caucasian children.

BACKGROUND: Although a quantitative evaluation of cardiac chamber dimensions in pediatric echocardiography is often important, nomograms for these structures are limited. The aim of this study was to establish reliable echocardiographic nomograms of cardiac chamber diameters and areas in a wide population of children. METHODS: A total of 1,091 Caucasian Italian healthy children (age range, 0 days to 17 years; 44.8% female) with body surface areas (BSAs) ranging from 0.12 to 1.8 m(2) were prospectively enrolled. Twenty-two two-dimensional and M-mode measurements of atrial and ventricular chamber diameters and areas were performed. Models using linear, logarithmic, exponential, and square-root relationships were tested. Heteroscedasticity was tested by the White test and the Breusch-Pagan test. Age, weight, height, and BSA, calculated by the Haycock formula, were used as the independent variables in different analyses to predict the mean value of each echocardiographic measurement. The influence of various confounders, including gender, type of delivery, prematurity, and interobserver variability, was also evaluated. Structured Z scores were then computed. RESULTS: The Haycock formula provided the best fit and was used when presenting data as predicted values (mean ± 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. Confounders were not included in the final models, because they did not show significant effects for most of the measurements. CONCLUSIONS: Echocardiographic reference values are presented for chamber area and diameters, derived from a large population of healthy children. These data partly cover a gap in actual pediatric echocardiographic nomograms. Further studies are required to reinforce these data, as well as to evaluate other parameters and ethnicities.

The potential and limitations of plasma BNP measurement in the diagnosis, prognosis, and management of children with heart failure due to congenital cardiac disease: an update.

The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with heart failure caused by various acquired and congenital heart diseases (CHD). In January 2013, we performed a computerized literature search in the National Library of Medicine (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included a mix of Medical Subject Headings and free-text terms for the key concepts, starting from BNP assay and 'NT-proBNP assay', children, CHD. The search was further refined by adding the keywords neonate/s, newborn/s, heart failure, cardiomyopathy, screening, prognosis, follow-up, and management. BNP values are age and method dependent, even in pediatric populations. Regardless of age, there is great variability in BNP/NT-proBNP values within CHD characterized by different hemodynamic and clinical conditions. There is enough evidence to support the use of BNP/NT-proBNP as an adjunctive marker in the integrated evaluation of patients with congenital and acquired heart disease to help define severity and progression of heart failure as well in the monitoring of response to treatment. BNP/NT-proBNP can also be used for the screening of heart failure and as a prognostic marker in children undergoing cardiac surgery; however, to date, there are studies with heterogeneous patient groups, and diverse outcome measures selected are still few. BNP/NT-proBNP can be used as adjunctive markers in the integrated screening, diagnosis, management, and follow-up of children with heart failure caused by various acquired and congenital heart disease.

Echocardiographic nomograms for ventricular, valvular and arterial dimensions in caucasian children with a special focus on neonates, infants and toddlers.

BACKGROUND: A quantitative echocardiographic assessment is often essential for the management of congenital heart disease, especially in the first months of life. Despite this, pediatric echocardiographic nomograms are limited and heterogeneous, particularly for neonates and infants. The aim of this study was to establish reliable echocardiographic nomograms in a broad population of healthy Caucasian children. METHODS: Two-dimensional and M-mode measurements of 22 cardiovascular structures were performed. Models using linear, logarithmic, exponential, and square root relationships were tested. Heteroscedasticity was tested using the White and Breusch-Pagan tests. Age, weight, height, and body surface area (BSA; calculated using seven different formulas) were used as the independent variables in different analyses to predict the mean value of each echocardiographic measurement. Structured Z scores were then computed. RESULTS: A total of 445 consecutive Caucasian Italian healthy subjects (age range, 0 days to 36 months; 49% female subjects) with BSAs ranging from 0.12 to 0.67 m(2) were prospectively enrolled. The calculation of BSA using the Haycock formula provided the best results, while other formulas either underestimated (DuBois, Mosteller, Dreyer, and Meban) or overestimated (Boyd and Gehan) BSA. The Haycock formula has been used when presenting data as predicted values (mean ± 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. For all the measurements, there was no significant intraobserver or interobserver variability. CONCLUSIONS: The investigators report new, reliable echocardiographic Z scores derived from a large population of Caucasian neonates, infants, and toddlers calculated using a rigorous statistical design. These nomograms represent a valid diagnostic tool for echocardiographic quantification in this age group.

Controversies in the prophylaxis and treatment of postsurgical pericardial syndromes: a critical review with a special emphasis on paediatric age.

Postsurgical pericardial syndromes are common complications after cardiac surgery; however, their treatment is not well established yet. We reviewed the accuracy and limits of clinical trials of prophylaxis and treatment of these diseases to identify an evidence-based therapeutic approach. We performed a literature search in the National Library of Medicine using the keywords pericardial effusion, cardiac surgery and paediatric/congenital. The research was then redefined adding separately the keywords postpericardiotomy syndrome, NSAIDs, steroids and colchicine. We found 12 clinical trials (eight for the prophylaxis and four regarding treatment), testing three major agent classes: NSAIDs, corticosteroids and colchicine. Therapy is generally based on NSAID with or without steroids with the adjunct of colchicine for recurrences. Only a few randomized controlled trials (RCTs) in adults support NSAID therapy. Efficacy of steroids has been proved only in small paediatric works, whereas no studies are available for colchicine. Studies furthermore presented some limitations: not univocal endpoints (not allowing for a meta-analysis), a limited sample size, scarce attention to confounders (such as the underlying cardiac disease and diuretic/analgesic regimen). Moreover, different agents were not assessed, nor when to start therapy. More evidence (two wide RCT plus a meta-analysis) supports the role of colchicine for prophylaxis in adults. Prophylaxis with NSAID/corticosteroids instead failed to have significant advantage in children, whereas a few data are available for adults. Evidence for the treatment of postsurgical pericardial syndromes is incomplete, making it difficult to understand when to treat and which agent to employ, especially in children.

Response of cardiac endocrine function to surgery stress is age dependent in neonates and children with congenital heart defects: consequences in diagnostic and prognostic accuracy of brain natriuretic peptide measurement.

OBJECTIVE: The aim of this study was to evaluate the diagnostic and prognostic accuracy of brain natriuretic peptide assay in neonates and children undergoing surgery for congenital heart disease. DESIGN: Prospective, observational study. SETTING: Single center. PATIENTS: We enrolled 336 consecutive children (median age, 6 mo [range, 0-37 mo]) undergoing cardiac surgery (87 neonates; age, 7 d [5-12]; median, 25th-75th percentile; 24 infants and children; age, 11 mo [4-60]) and 436 healthy controls. INTERVENTIONS: Brain natriuretic peptide was measured preoperatively, on every postoperative day in the ICU, and at discharge. Intubation time was the primary outcome. MEASUREMENTS AND MAIN RESULTS: Preoperative brain natriuretic peptide values in patients with congenital heart disease were higher than those in controls (p < 0.01). Brain natriuretic peptide had a good diagnostic accuracy in discriminating between patients with congenital heart disease and healthy controls with an area under the curve = 0.918 for neonates and area under the curve = 0.894 for older children. The best cutoff values, calculated by receiver operating characteristic analysis, were different for the two age subgroups with cutoff values of 363.5 ng/L for neonates and 23.5 ng/L for older children. At 24 hours after surgery, although brain natriuretic peptide decreased in neonates (baseline 2723 vs 1290 ng/L, p < 0.001), it increased in children (60 vs 365 ng/L at 24 hours, p < 0.001). Multivariable analysis identified the preoperative level of brain natriuretic peptide in infant/children and the difference in brain natriuretic peptide value (baseline 24 hours) in neonates, as independent predictors of intubation time. Furthermore, body surface area, Aristotle score, and cardiopulmonary bypass time had an independent significant effect on the endpoint in either group. CONCLUSIONS: Baseline cardiac endocrine function and its response to surgical stress are dependent on age in neonates and children, undergoing cardiac surgery for congenital heart disease. Brain natriuretic peptide shows a good diagnostic and prognostic accuracy in this setting, with different features in either neonates or infants/children subsets.

Thyroid and brain natriuretic Peptide response in children undergoing cardiac surgery for congenital heart disease- age-related variations and prognostic value.

BACKGROUND: Interest in hormonal response after pediatric cardiac surgery is growing, but many aspects remain unclear. The aim of this study was to test age-related variations and prognostic values of thyroid hormones, and brain natriuretic peptide (BNP) levels before and after surgery. METHODS AND RESULTS: A total of 162 children undergoing cardiac surgery were divided into 3 age groups (group 1, n=57 neonates; group 2, n=58 infants; group 3, n=47 toddlers). Free thyroid hormones (fT3 and fT4), thyrotropin (thyroid-stimulating hormone [TSH]) and BNP were measured preoperatively, daily postoperatively in the intensive care unit and after 15 days. The primary outcome was time to extubation (TTE; variable used as time to event by survival analysis). The hormonal response differed among age groups. In older children the TSH nadir occurred at 6-12h after surgery (0.42 mIU/L, P<0.001), with a progressive recovery thereafter, while in neonates the TSH nadir occurred later, at 36-60 h (0.14 mIU/L, P<0.001), followed by a much slower recovery. In neonates, BNP also dropped after surgery (from 2,899 to 824.0 ng/L, P<0.001) while increased in older children (from 71.00 to 527.00 ng/L, P<0.001). On multivariate analysis independent predictors of TTE were fT3 nadir in all age groups, together with TSH nadir and Aristotle score in neonates, and body surface area and BNP peak in older children. CONCLUSIONS: BNP and thyroid response after pediatric cardiac surgery differs widely according to age. Beside Aristotle score, combined measurement of fT3 and TSH are the strongest predictors of TTE, especially in neonates.

Diagnostic accuracy of B-type natriuretic hormone for congenital heart disease in the first month of life.

BACKGROUND: The goal of the present study was to evaluate the diagnostic accuracy of B-type natriuretic hormone (BNP) assay in children with congenital heart disease (CHD) in the first month of life. METHODS: BNP was measured in 152 neonates with CHD; 154 healthy children matched for age were used as controls. BNP was measured with a fully automated platform (Triage BNP reagents, Access Immunoassay Systems, Beckman Coulter, Inc., Fullerton, CA, USA). RESULTS: BNP values were significantly higher (p<0.0001) in newborns and infants with CHD compared with control (CHD patients: median 1167.5 ng/L, range 25-54,447 ng/L; healthy children: median 150.5 ng/L, range 5-866 ng/L). The diagnostic accuracy of BNP was assessed using the receiver operating characteristic (ROC) analysis, taking into account the three different groups divided according to age. Group 1: all CHD patients and healthy newborns and infants as a whole (i.e., from birth to the 30th day of life); Group 2: from the 1st to 3rd day of life; Group 3: from the 4th to 30th day of life. The area under the curve (AUC) of the ROC curve for Group 3 (0.935) was significantly higher than that for Group 1 (0.843, p=0.009) and Group 2 (0.769, p=0.0003), while the AUC values of Group 1 and Group 2 were not significantly different (p=0.191). CONCLUSIONS: BNP may be considered a useful marker for screening in the integrated approach of newborns, infants and children with suspected CHD. However, the accuracy of the BNP assay varies greatly during the first month of extra-uterine life, showing the lowest diagnostic accuracy in the first 3 days after birth. After the second week of life, the biomarker becomes more accurate in ruling in CHD.