Nadia Assanta

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

Abstract 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.

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

Abstract 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. Clin Chem Lab Med 2010;48:1333–8.

Controversies in the definition and management of insignificant left-to-right shunts

Haemodynamically insignificant left-to-right shunts are frequently discovered when screening for congenital heart disease, resulting in significant economic and psychosocial impact. A literature search was performed within the National Library of Medicine using the keywords small/insignificant/silent atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA) and patent foramen ovale (PFO). The search was refined by adding the keywords definition, classification and follow-up. Our analysis revealed significant heterogeneity in the evaluation and management of innocent left-to-right shunts. The definitions for small defects vary greatly, making it difficult to distinguish between physiologic and pathologic lesions (eg, a PFO vs a true ASD). Most small defects will partially or completely resolve spontaneously early in life. If spontaneous resolution does not occur, the risk for long-term complications (such as embolic events and endocarditis) is low but poses several practical and ethical issues: immediate discharge versus long-term follow-up, duration and frequency of follow-up, and content and method of discussions with the parents. Additionally, there is controversy pertaining to treatment for PDAs and VSDs, particularly among interventional cardiologists, even though risk/benefit analyses are lacking. Standards and guidelines using consensus opinion for the management of insignificant left-to-right shunts are needed to address the heterogeneity in diagnosis and management as well as use of resources, ethical and psychosocial issues.

Diagnostic accuracy and clinical relevance of brain natriuretic peptide assay in pediatric patients with congenital heart diseases.

Background The clinical usefulness of B-type natriuretic peptide (BNP) assay in congenital heart diseases is still controversial. We evaluated the diagnostic accuracy and clinical relevance of this assay in different cardiovascular hemodynamic conditions in pediatric patients with congenital heart diseases. Materials and methods BNP was measured in 173 healthy individuals and in 382 pediatric patients with congenital heart diseases. We identified five subgroups of hemodynamic conditions: left ventricular volume overload, right ventricular volume overload, left ventricular pressure overload, right ventricular pressure overload, and biventricular volume overload. Results BNP was higher (P < 0.0001) in patients (median 49.0 ng/l, range 0.45–14363 ng/l) than in the reference population (median 6.1 ng/l, range 1.0–29.7 ng/l). BNP assay showed a good diagnostic accuracy in discriminating between healthy individuals and patients (area under the receiver operating characteristic curve 0.95, SE 0.009). Lower BNP values were found in right ventricular pressure overload than in left ventricular pressure overload, left ventricular volume overload, or biventricular volume overload. In the left ventricular volume overload subgroup, BNP significantly correlated with peak systolic gradients (ρ = 0.622, P < 0.001) and left ventricular dilatation (ρ = 0.35, P = 0.03). In the right ventricular volume overload subgroup, BNP correlated with right ventricular pressure (ρ = 0.622, P < 0.001) and right ventricular dilatation (ρ = 0.377, P = 0.0077). Moreover, in cyanotic defects, BNP showed a significant correlation with O2 saturation (ρ = 0.204 P = 0.0128). Conclusion BNP assay showed a good diagnostic accuracy in discriminating between healthy individuals and patients. Congenital heart disease with left ventricular pressure overload and biventricular volume overload has higher BNP values than that with right ventricular pressure overload.

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.

Lung ultrasound in adult and paediatric cardiac surgery: is it time for routine use?

Respiratory complications are common causes of morbidity and the need of repeated X-ray examinations after cardiac surgery. Ultrasound of the chest, including the lung parenchyma, has been recently introduced as a new tool to detect many pulmonary abnormalities. Despite this, the use of lung ultrasound (LUS) in adult and congenital cardiac surgery remains limited. In particular, lung ultrasound has been mainly used in the evaluation of pleural effusion (PLE), but no consensus exists on methods to quantify the volume of the effusion. Usefulness of LUS for the assessment of diaphragmatic motion in children has also been highlighted, but no clear recommendation exists regarding its routine use. Accuracy of LUS in detecting pulmonary congestion after adult cardiac surgery has been demonstrated, whereas studies in children are still scarce, and data on pneumothorax and lung consolidations are limited in the paediatric population. There are methodological and practicality issues regarding diagnostic protocols (i.e. image views and their sequential order) and instrumentation (transducers and their setting) used in different studies. It also remains unclear which practitioner-the cardiologist, intensivist, pulmonologist or the radiologist, should perform the examination. Cost analysis pertaining to extensive clinical application of lung ultrasound in cardiac surgery has never been performed. Guidelines and recommendations are warranted for a systematic and extensive use of this technique in cardiac surgery at different ages, as it could serve as a useful, versatile tool that could potentially decrease time, radiation exposure and costs.

Acro‐cardio‐facial syndrome: A microdeletion syndrome?

Acro‐cardio‐facial syndrome (ACFS) is an infrequently reported, variable condition characterized by split‐hand and split‐foot malformation and congenital heart defect (CHD), along with cleft lip and palate, genital anomalies, unusual face and intellectual disability. An autosomal recessive pattern of inheritance has been suggested because of affected sibs born to unaffected parents and parental consanguinity; the cause is unknown. We describe a newborn with the clinical manifestations of ACFS in whom a deletion of the region 6q21‐q22.3 was detected by array CGH. We compare the clinical features of the present patient with earlier reported patients with similar 6q deletions and patients diagnosed with ACFS. The similarities between these patient groups suggest that ACFS may be a microdeletion syndrome caused by loss of the 6q21‐22.3 region. The recurrence in families may be explained by prenatal germline mosaicism. Alternatively, ACFS may be a genetically heterogeneous disorder which can also be caused by biallelic mutations of an autosomal recessive gene.

Nomograms for two-dimensional echocardiography derived valvular and arterial dimensions in Caucasian children.

BACKGROUND Despite recent advances, current pediatric echocardiographic nomograms for valvular and arterial dimensions remain limited. METHODS We prospectively studied healthy Caucasian Italian children by two-dimensional (2D) echocardiography. Echocardiographic measurements for 18 valvular and arterial dimensions were performed and models were generated testing for linear, logarithmic, exponential, and square root relationships. Heteroscedasticity was accounted for by White or Breusch-Pagan test. Age, weight, height, heart rate, and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Structured Z-scores were then computed. RESULTS In all, 1151 subjects (age 0 days to 17 years; 45% females; BSA 0.12-2.12m2) were studied. The Haycock formula was used when presenting data as predicted values (mean±2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. The predicted values and Z-score boundaries for all measurements are presented. CONCLUSIONS We report echocardiographic nomograms for valvular and arterial dimensions derived from a large population of children. Integration of these data with those of previous reports would allow for a comprehensive coverage of pediatric 2D echocardiographic nomograms for measurement of 2D cardiac structures.

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.

Decision levels for plasma B-type natriuretic peptide assay to diagnose significant cardiovascular disease in children.

We read with interest the paper of Law et al. ([1][1]) regarding the accuracy of B-type natriuretic peptide (BNP) to diagnose significant cardiovascular disease in children. In their prospective study the authors enrolled 100 children (including 42 neonates) presenting with signs and symptoms that