Design and implementation of multicenter pediatric and congenital studies with cardiovascular magnetic resonance: Big data in smaller bodies.

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts.

Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood: Results From a National Population-Based Study.

BACKGROUND: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy. METHODS: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0-10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation. RESULTS: There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0-92.0) 1 year after presentation, 80% (95% CI, 69.0-87.0) at 10 years, and 78% (95% CI, 67.0-86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60-11.05; P=0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02-8.08; P=0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22-1.73; P<0.001), and lower fractional shortening z score (hazard ratio, 0.84; 95% CI, 0.74-0.95; P=0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with ß-blocker, and 13 (21%) had an implantable cardioverter-defibrillator. CONCLUSIONS: The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.

Unplanned Repeat Echocardiography with Sedation in Children: Patient Risk Factors.

Patient selection criteria for echocardiography with sedation in children are not well defined. We attempted to identify predictors of unplanned repeat echocardiography with sedation. This was a single-center, case-control study of echocardiograms performed in children aged 1-36 months. Cases underwent unplanned repeat examinations with sedation, while controls did not. Patient variables and study indications were compared. Logistic regression identified the most significant predictors. Cases (n = 104, median time to repeat echocardiogram 17 days, median age 12.9 months) were older than controls (n = 212, median age 5.0 months, P < 0.001). Significantly more cases than controls had structural cardiac disease (64 vs. 23 %) and anatomic complexity ≥moderate (38 vs. 5 %, P < 0.001 for both). Cases more often had Kawasaki disease (11 vs. 2 %), and controls more often had murmur (56 vs. 11 %, P < 0.001 for both). Logistic regression identified age 6 months to <2 years (OR 3.26, 95 % CI 1.70-6.28, P < 0.001), Kawasaki disease (OR 5.20, 95 % CI 1.46-18.50, P = 0.01), and known pre-echocardiogram anatomic complexity ≥moderate (OR 3.99, 95 % CI 1.64-9.66, P = 0.002) as significant risk factors. An indication for murmur was protective (OR 0.32, 95 % CI 0.13-0.76, P = 0.01). We identified several risk factors for unplanned repeat echocardiography with sedation in children, including age 6 months to <2 years, higher anatomic complexity, and Kawasaki disease. Murmur was a protective factor. These results may help pediatric echocardiography laboratories establish criteria for sedation.

Reduced Systolic Function and Not Genetic Variants Determine Outcome in Pediatric and Adult Left Ventricular Noncompaction Cardiomyopathy.

Background: Left ventricular noncompaction cardiomyopathy (LVNC CMP) is a genetic cardiomyopathy. Genotype-phenotype correlation and clinical outcome of genetic variants in pediatric and adult LVNC CMP patients are still unclear. Methods: The retrospective multicenter study was conducted in unrelated index patients with LVNC CMP, diagnosed between the years 1987 and 2017, and all available family members. All index patients underwent next-generation sequencing for genetic variants in 174 target genes using the Illumina TruSight Cardio Sequencing Panel. Major adverse cardiac events (MACE) included mechanical circulatory support, heart transplantation, survivor of cardiac death, and/or all-cause death as combined endpoint. Results: Study population included 149 LVNC CMP patients with a median age of 27.8 (9.2-44.8) years at diagnosis; 58% of them were symptomatic, 18% suffered from non-sustained and sustained arrhythmias, and 17% had an implantable cardioverter defibrillator (ICD) implanted. 55/137 patients (40%) were ≤ 18 years at diagnosis. A total of 134 variants were identified in 87/113 (77%) index patients. 93 variants were classified as variant of unknown significance (VUS), 24 as likely pathogenic and 15 as pathogenic. The genetic yield of (likely) pathogenic variants was 35/113 (31%) index patients. Variants occurred most frequently in MYH7 (n=19), TTN (n = 10) and MYBPC3 (n = 8). Altogether, sarcomere gene variants constituted 42.5% (n = 57) of all variants. The presence or absence of (likely) pathogenic variants or variants in specific genes did not allow risk stratification for MACE. Reduced left ventricular (LV) systolic function and increased left ventricular end-diastolic diameter (LVEDD) were risk factors for event-free survival in the Kaplan-Meier analysis. Through multivariate analysis we identified reduced LV systolic function as the main risk factor for MACE. Patients with reduced LV systolic function were at a 4.6-fold higher risk for MACE. Conclusions: Genetic variants did not predict the risk of developing a MACE, neither in the pediatric nor in the adult cohort. Multivariate analysis emphasized reduced LV systolic function as the main independent factor that is elevating the risk for MACE. Genetic screening is useful for cascade screening to identify family members at risk for developing LVNC CMP.

Neutrophil-to-lymphocyte ratio is prognostic factor of prolonged pleural effusion after pediatric cardiac surgery.

OBJECTIVES: Postoperative pleural effusion (PE) is common after pediatric cardiac surgery, and if prolonged can lead to the deterioration of the general condition due to malnutrition and result in death. This study aims at identifying the prognostic factors of prolonged PE after pediatric cardiac surgery.Design and settings: Patients were divided into the effective (with chest tube removal within 10 days after medical therapy) and ineffective (with chest tube in place for more than 10 days) groups. The factors were compared between the two groups retrospectively. PARTICIPANTS: Participants included patients who had prolonged PE after cardiac surgery in national center for child and health development between October 2014 and October 2017. MAIN OUTCOME MEASURES: Baseline characteristics and procedure details were compared between the two groups to determine the predictor of prolonged PE. White blood cell count, platelet count, neutrophil-to-lymphocyte ratio, hemoglobin level, serum total protein level, serum albumin level, blood fibrinogen level, serum creatinine level, etc. were examined. RESULTS: Twenty patients were included. Between the two groups, no significant differences in baseline characteristics, such as age, weight, and sex were found, and significant differences were observed only in the NLR change ratio (effective group, 5.1 [4.1-8.0] versus ineffective group, 11.9 [9.9-14.1]; P = 0.01). CONCLUSIONS: NLR change ratio is a potential prognostic factor of prolonged PE, including chylothorax, after pediatric cardiac surgery.

Magnetic resonance imaging planning in children with complex congenital heart disease - A new approach.

OBJECTIVES: To compare a standard sequential 2D Planning Method (2D-PM) with a 3D offline Planning Method (3D-PM) based on 3D contrast-enhanced magnetic resonance angiography (CE-MRA) in children with congenital heart disease (CHD). DESIGN: In 14 children with complex CHD (mean: 2.6 years, range: 3 months to 7.6 years), axial and coronal cuts were obtained with single slice spin echo sequences to get the final double oblique longitudinal cut of the targeted anatomical structure (2D-PM, n = 31). On a separate workstation, similar maximal intensity projection (MIP) images were generated offline from a 3D CE-MRA. MIP images were localizers for repeated targeted imaging using the previous spin echo sequence (3D-PM). Finally, image coverage, spatial orientation and acquisition time were compared for 2D-PM and 3D-PM. MAIN OUTCOME MEASURES: 2D-PM and 3D-PM images were similar: both perfectly covered the selected anatomic regions and no spatial differences were found (p>0.05). The mean time for creation of the final imaging plane was 241 ± 31 s (2D-PM) compared to 71 ± 18 s (3D-PM) (p<0.05). CONCLUSIONS: 3D-PM shows similar results compared to 2D-PM, but allows faster and offline planning thereby reducing the scan time significantly. As newly developed high-resolution 3D datasets can also be used further improvement of this technology is expected.

The impact of procedural sedation on diagnostic errors in pediatric echocardiography.

BACKGROUND: Infants and young children frequently have difficulty remaining still for an echocardiographic examination, potentially leading to poor study quality, increasing the likelihood of diagnostic errors. Sedation is believed to improve echocardiographic quality, but its effectiveness has not been demonstrated. The aim of this study was to test the hypothesis that sedation would improve study quality and reduce diagnostic errors. METHODS: Outpatient echocardiograms from children aged ≤36 months obtained from January 2008 to June 2009 were examined. Variables related to image quality, report completeness, and sedation use were collected. Diagnostic errors were identified and categorized. Multivariate analysis identified the odds ratios (OR) and 95% confidence intervals (CI) for risk factors for potentially preventable diagnostic errors and the impact of sedation on these errors. RESULTS: Among 2,003 echocardiographic examinations, sedation was used in 498 (25%). The overall diagnostic error rate was 6.5%. Most errors (66%) were potentially preventable. Multivariate analysis identified the following risk factors for potentially preventable errors: precardiac procedure (OR, 2.19; 95% CI, 1.05-4.59; P = .04), moderate anatomic complexity (OR, 3.91; 95% CI, 2.25-6.81; P < .001), and high anatomic complexity (OR, 8.36; 95% CI, 3.57-19.6; P < .001). Sedation was independently associated with lower odds of potentially preventable diagnostic errors (OR, 0.47; 95% CI, 0.27-0.80; P = .006). Echocardiographic examinations with sedation had fewer image quality concerns (22% vs 60%) and fewer incomplete reports (3% vs 20%) (P < .001). CONCLUSIONS: Most echocardiographic diagnostic errors among infants and young children are potentially preventable. Sedation is associated with a lower likelihood of these diagnostic errors, fewer imaging quality concerns, and fewer incomplete reports.