Challenges and lessons learned from the Pediatric Heart Network Normal Echocardiogram Database study.

BACKGROUND: The Pediatric Heart Network Normal Echocardiogram Database Study had unanticipated challenges. We sought to describe these challenges and lessons learned to improve the design of future studies. METHODS: Challenges were divided into three categories: enrolment, echocardiographic imaging, and protocol violations. Memoranda, Core Lab reports, and adjudication logs were reviewed. A centre-level questionnaire provided information regarding local processes for data collection. Descriptive statistics were used, and chi-square tests determined differences in imaging quality. RESULTS: For the 19 participating centres, challenges with enrolment included variations in Institutional Review Board definitions of "retrospective" eligibility, overestimation of non-White participants, centre categorisation of Hispanic participants that differed from National Institutes of Health definitions, and exclusion of potential participants due to missing demographic data. Institutional Review Board amendments resolved many of these challenges. There was an unanticipated burden imposed on centres due to high numbers of echocardiograms that were reviewed but failed to meet submission criteria. Additionally, image transfer software malfunctions delayed Core Lab image review and feedback. Between the early and late study periods, the proportion of unacceptable echocardiograms submitted to the Core Lab decreased (14 versus 7%, p < 0.01). Most protocol violations were from eligibility violations and inadvertent protected health information disclosure (overall 2.5%). Adjudication committee reviews led to protocol changes. CONCLUSIONS: Numerous challenges encountered during the Normal Echocardiogram Database Study prolonged study enrolment. The retrospective design and flaws in image transfer software were key impediments to study completion and should be considered when designing future studies collecting echocardiographic images as a primary outcome.

Quantitative echocardiographic measures in the assessment of single ventricle function post-Fontan: Incorporation into routine clinical practice.

BACKGROUND: Quantitative echocardiographic measurements of single ventricular (SV) function have not been incorporated into routine clinical practice. METHODS: A clinical protocol, which included quantitative measurements of SV deformation (global circumferential and longitudinal strain and strain rate), standard deviation of time to peak systolic strain, myocardial performance index (MPI), dP/dT from an atrioventricular valve regurgitant jet, and superior mesenteric artery resistance index, was instituted for all patients with a history of Fontan procedure undergoing echocardiography. All measures were performed real time during clinically indicated studies and were included in clinical reports. RESULTS: A total of 100 consecutive patients (mean age = 11.95±6.8 years, range 17 months-31.3 years) completed the protocol between September 1, 2014 to April 29, 2015. Deformation measures were completed in 100% of the studies, MPI in 93%, dP/dT in 55%, and superior mesenteric artery Doppler in 82%. The studies were reviewed to assess for efficiency in completing the protocol. The average time for image acquisition was 27.4±8.8 (range 10-62 minutes). The average time to perform deformation measures was 10.8±5.5 minutes (range 5-35 minutes) and time from beginning of imaging to report completion was 53.4±13.7 minutes (range 27-107 minutes). There was excellent inter-observer reliability when deformation indices were blindly repeated. Patients with a single left ventricle had significantly higher circumferential strain and strain rate, longitudinal strain and strain rate, and dP/dT compared to a single right ventricle. There were no differences in quantitative indices of ventricular function between patients <10 vs. >10 years post-Fontan. CONCLUSION: Advanced quantitative assessment of SV function post-Fontan can be consistently and efficiently performed real time during clinically indicated echocardiograms with excellent reliability.

Variable Myocardial Response to Load Stresses in Infants with Single Left Ventricular Anatomy: Influence of Initial Physiology and Surgical Palliative Strategy.

Initial surgical strategies in neonates with single left ventricular (LV) anatomy vary based on adequacy of pulmonary and systemic blood flow. Differing myocardial responses to these strategies, as reflected in indices of systolic function, ventricular size, and mass have not been well defined. We sought to evaluate single LV myocardial response to varied physiology and initial palliation and determine whether the response is consistent and predictable. Infants with single LV physiology were divided based on neonatal palliation: no palliation/PA band (NO); BT shunt only (BT); or Norwood procedure (NP). Echo measures were obtained at presentation, early post-bidirectional Glenn (BDG), late post-BDG follow-up, and post-Fontan procedure. Measures included ejection fraction, LV mass indexed to height2.7 and end diastolic volume indexed to body surface area, and mass/volume ratio. The cohort included 38 children (13 NO, 13 BT, 12 NP). Ejection fraction was similar but depressed in all groups at all stages. LV mass was higher in the NP group than the BT group at early post-BDG (p = 0.03) and higher than both BT and NO groups (p < 0.01) at late post-BDG, but the difference was resolved by post-Fontan follow-up. The NP group had the most remarkable remodeling in LV size from BDG to Fontan, suggesting that volume unloading is most valuable in this subgroup. Ventricular remodeling can be identified by echocardiography in children with single LV physiology, despite variable initial surgical palliative strategies. Importantly, these initial surgical strategies do not result in significant differences after Fontan palliation during early childhood.

Echocardiographic assessment of single-ventricle diastolic function and its correlation to short-term outcomes after the Fontan operation.

BACKGROUND/HYPOTHESIS/OBJECTIVES: Postoperative complications after the Fontan operation for single ventricle heart disease are common and include persistent pleural drainage and prolonged length of hospital stay (LOS). Diastolic ventricular dysfunction may increase risk for postoperative complications by raising central venous pressures. We sought to determine the relationship between preoperative echocardiographic measurements of diastolic function, including myocardial deformation imaging, on (a) preoperative invasive catheterization measurements and (b) postoperative outcomes after the Fontan procedure. DESIGN/METHODS: All patients that underwent Fontan procedure from 2011 to 2017 were included. Echocardiograms performed within 6 months prior to Fontan operation were evaluated. Measurements of ventricular global and diastolic strain and strain rate were performed offline with TomTec speckle tracking software. Other diastolic function measurements included atrioventricular valve inflow and annular tissue Doppler imaging. Diastolic function measurements were correlated with pre-Fontan catheterization measurements and postoperative Fontan outcomes using Spearman's rho. Multivariable logistic regression for a prolonged LOS (>75%ile for postoperative LOS) was performed to adjust for preoperative risk factors. RESULTS: A total of 141 patients were included in the study. Majority had single morphologic right ventricle (58.9%). Median age at time of Fontan was 3.4 years (IQR 2.9-4). Median hospital LOS was 9 days (IQR 7-11). Circumferential diastolic strain rate weakly correlated with LOS (rho = -0.21, P = .01). There was no correlation between any other diastolic strain measurements and pre-Fontan end-diastolic pressure or postoperative LOS. In multivariable analysis, E/E' was the only echo measurement that predicted prolonged hospital LOS (OR 1.4, 95%CI: 1.1-1.8, P = .003). CONCLUSION: Preoperative diastolic strain measurements did not have a strong association with postoperative Fontan outcomes. Increased E/E' ratio, however, did predict greater LOS after Fontan procedure, and may be useful in preoperative risk stratification. Future studies are needed to further assess the utility of diastolic strain imaging in the single-ventricle population.

Impact of Initial Shunt Type on Echocardiographic Indices in Children After Single Right Ventricle Palliations.

Background Heart size and function in children with single right ventricle (RV) anomalies may be influenced by shunt type at the Norwood procedure. We sought to identify shunt-related differences during early childhood after staged surgical palliations using echocardiography. Methods We compared echocardiographic indices of RV, neoaortic, and tricuspid valve size and function at 14 months, pre-Fontan, and 6 years in 241 subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt or RV-to-pulmonary-artery shunt. Results At 6 years, the shunt groups did not differ significantly in any measure except for increased indexed neoaortic area in the modified Blalock-Taussig shunt. RV ejection fraction improved between pre-Fontan and 6 years in the RV-to-pulmonary artery shunt group but was stable in the modified Blalock-Taussig shunt group. For the entire cohort, RV diastolic and systolic size and functional indices were improved at 6 years compared with earlier measurements, and indexed tricuspid and neoaortic annular area decreased from 14 months to 6 years. The prevalence of ≥moderate tricuspid and neoaortic regurgitation was uncommon and did not vary by group or time period. Diminished RV ejection fraction at the 14-month study was predictive of late death/transplant; the hazard of late death/transplant when RV ejection fraction was <40% was tripled (hazard ratio, 3.18; 95% CI, 1.41-7.17). Conclusions By 6 years after staged palliation, shunt type has not impacted RV size and function, and RV and valvar size and function show beneficial remodeling. Poor RV systolic function at 14 months predicts worse late survival independent of the initial shunt type. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00115934.

Challenges With Left Ventricular Functional Parameters: The Pediatric Heart Network Normal Echocardiogram Database.

BACKGROUND: The reliability of left ventricular (LV) systolic functional indices calculated from blinded echocardiographic measurements of LV size has not been tested in a large cohort of healthy children. The objective of this study was to estimate interobserver variability in standard measurements of LV size and systolic function in children with normal cardiac anatomy and qualitatively normal function. METHODS: The Pediatric Heart Network Normal Echocardiogram Database collected normal echocardiograms from healthy children ≤18 years old distributed equally by age, gender, and race. A core lab used two-dimensional echocardiograms to measure LV dimensions from which a separate data coordinating center calculated LV volumes and systolic functional indices. To evaluate interobserver variability, two independent expert pediatric echocardiographic observers remeasured LV dimensions on a subset of studies, while blinded to calculated volumes and functional indices. RESULTS: Of 3,215 subjects with measurable images, 552 (17%) had a calculated LV shortening fraction (SF) < 25% and/or LV ejection fraction (EF) < 50%; the subjects were significantly younger and smaller than those with normal values. When the core lab and independent observer measurements were compared, individual LV size parameter intraclass correlation coefficients were high (0.81-0.99), indicating high reproducibility. The intraclass correlation coefficients were lower for SF (0.24) and EF (0.56). Comparing reviewers, 40/56 (71%) of those with an abnormal SF and 36/104 (35%) of those with a normal SF based on core lab measurements were calculated as abnormal from at least one independent observer. In contrast, an abnormal EF was less commonly calculated from the independent observers' repeat measures; only 9/47 (19%) of those with an abnormal EF and 8/113 (7%) of those with a normal EF based on core lab measurements were calculated as abnormal by at least one independent observer. CONCLUSIONS: Although blinded measurements of LV size show good reproducibility in healthy children, subsequently calculated LV functional indices reveal significant variability despite qualitatively normal systolic function. This suggests that, in clinical practice, abnormal SF/EF values may result in repeat measures of LV size to match the subjective assessment of function. Abnormal LV functional indices were more prevalent in younger, smaller children.

Impact of initial norwood shunt type on right ventricular deformation: the single ventricle reconstruction trial.

BACKGROUND: The Single Ventricle Reconstruction trial demonstrated a transplantation-free survival advantage at 12-month follow-up for patients with right ventricle-pulmonary artery shunts (RVPAS) with the Norwood procedure compared with modified Blalock-Taussig shunts but similar survival and decreased global right ventricular (RV) function on longer term follow-up. The impact of the required ventriculotomy for the RVPAS remains unknown. The aim of this study was to compare echocardiography-derived RV deformation indices after stage 2 procedures in survivors with single RV anomalies enrolled in the Single Ventricle Reconstruction trial. METHODS: Global and regional RV systolic longitudinal and circumferential strain and strain rate, ejection fraction, and short-axis percentage fractional area change were all derived by speckle-tracking echocardiography from protocol echocardiograms obtained at 14.3 ± 1.2 months. Student t tests or Wilcoxon rank sum tests were used to compare groups. RESULTS: The cohort included 275 subjects (129 in the modified Blalock-Taussig shunt group and 146 in the RVPAS group). Longitudinal deformation could be quantified in 214 subjects (78%) and circumferential measures in 182 subjects (66%). RV ejection fraction and percentage fractional area change did not differ between groups. There were no significant differences between groups for global or regional longitudinal deformation. Circumferential indices showed abnormalities in deformation in the RVPAS group, with decreased global circumferential strain (P = .05), strain rate (P = .09), and anterior regional strain rate (P = .07) that approached statistical significance. CONCLUSIONS: RV myocardial deformation at 14 months, after stage 2 procedures, was not significantly altered by the type of initial shunt placed. However, abnormal trends were appreciated in circumferential deformation for the RVPAS group in the area of ventriculotomy that may represent early myocardial dysfunction. These data provide a basis for longer term RV deformation assessment in survivors after Norwood procedures.