Impact of Treatment Strategy on Outcomes in Isolated Pulmonary Artery of Ductal Origin.

Isolated pulmonary artery (PA) of ductal origin (IPADO) is a rare cardiac defect which requires surgical repair, with or without preceding palliation. We sought to determine the impact of treatment strategy on outcomes. Retrospective study of consecutive patients with IPADO that underwent staged or primary repair from 1/05 to 9/16 at 6 Congenital Cardiac Research Collaborative centers. Patients with single ventricle physiology, major aortopulmonary collaterals, or bilateral IPADO were excluded. Primary outcome was isolated PA z-score at late follow-up. Secondary outcomes included PA symmetry index (isolated:confluent PA diameter) and reintervention burden. Propensity score adjustment was used to account for baseline differences. Of 60 patients in the study cohort, 26 (43%) underwent staged and 34 (57%) primary repair. The staged and primary repair groups differed in weight at diagnosis and presence of other heart disease but not in baseline PA dimensions. Staged patients underwent ductal stent (n = 16) or surgical shunt (n = 10) placement followed by repair at 210 vs. 21 days in the primary repair group (p < 0.001). At median follow-up of 4.5 years post-repair, after adjustment, isolated PA z-score (- 0.74 [- 1.75, - 0.26] vs. - 1.95 [- 2.91, - 1.59], p = 0.012) and PA symmetry index (0.81 [0.49, 1.0] vs. 0.55 [0.48, 0.69], p = 0.042) significantly favored the staged repair group. Freedom from PA reintervention was not different between groups (adjusted HR 0.78 [0.41, 1.48]; p = 0.445). A staged approach to repair of IPADO is associated with superior isolated PA size and symmetry at late follow-up. Consideration should be given to initial palliation in IPADO patients, when feasible.

Diagnostic Accuracy of Fetal Echocardiography in Congenital Heart Disease.

BACKGROUND: The accuracy of fetal echocardiography (FE) is not well defined, and reporting of diagnostic discrepancies (DDs) is not standardized. The authors applied a categorization scheme developed by the American College of Cardiology Quality Metric Working Group and applied it to FE. METHODS: A retrospective single-center study was conducted of prenatally diagnosed major structural congenital heart disease, defined as expected need for intervention within the first year of life. DDs between pre- and postnatal findings were identified and categorized. Minor DDs had no clinical impact, moderate DDs had impact without harm, and severe DDs resulted in adverse events. Multivariate regression analysis was used to determine factors associated with discrepancy. RESULTS: From December 2008 to September 2017, 17,096 fetal echocardiograms were obtained, among which 222 fetuses with a median gestational age at first FE of 24 weeks were included. There were 30 DDs (13.5%), of which the majority were false negatives (56.7%). Most were minor or moderate in severity, with one severe DD. The majority were possibly preventable (90%), with the most common contributing factor being technical limitations (43.3%). The most common anatomic segment involved was the ventricular septum (23%), primarily missed septal defects. Comparing cases with DDs versus those without, those with DDs were more likely to have high anatomic complexity (16.7% vs 3.6%, P = .01), maternal comorbidities (40.0% vs 22.1%, P = .03), and a younger maternal age (median, 27 vs 30 years, P = .02). They were also more likely to have later gestation at initial FE (median, 29.5 vs 24 weeks, P = .003), to have fewer total fetal echocardiograms (median, 2 vs 3, P = .002), and to have a fellow as the initial sonographer (36.7% vs 16.7%, P = .03). There were no significant differences in maternal race/ethnicity, fetal comorbidities, and interpreting physician experience between cases with DDs and those without. On multivariate analysis, variables associated with DD included high anatomic complexity, maternal comorbidities, and fellow as initial imager. A greater number of fetal echocardiograms was associated with reduced DD. CONCLUSIONS: FE had a DD rate of 13.5%, mostly minor and moderate in severity. Factors associated with DD included high anatomic complexity, maternal comorbidities, fellow as the initial sonographer, and fewer fetal echocardiograms. Strategies to reduce DD could include a regular secondary review and repeat FE, particularly when anatomic complexity is high.

Technical factors are associated with complications and repeat intervention in neonates undergoing transcatheter right ventricular decompression for pulmonary atresia and intact ventricular septum: results from the congenital catheterisation research collaborative.

BACKGROUND: Transcatheter right ventricle decompression in neonates with pulmonary atresia and intact ventricular septum is technically challenging, with risk of cardiac perforation and death. Further, despite successful right ventricle decompression, re-intervention on the pulmonary valve is common. The association between technical factors during right ventricle decompression and the risks of complications and re-intervention are not well described. METHODS: This is a multicentre retrospective study among the participating centres of the Congenital Catheterization Research Collaborative. Between 2005 and 2015, all neonates with pulmonary atresia and intact ventricular septum and attempted transcatheter right ventricle decompression were included. Technical factors evaluated included the use and characteristics of radiofrequency energy, maximal balloon-to-pulmonary valve annulus ratio, infundibular diameter, and right ventricle systolic pressure pre- and post-valvuloplasty (BPV). The primary end point was cardiac perforation or death; the secondary end point was re-intervention. RESULTS: A total of 99 neonates underwent transcatheter right ventricle decompression at a median of 3 days (IQR 2-5) of age, including 63 patients by radiofrequency and 32 by wire perforation of the pulmonary valve. There were 32 complications including 10 (10.5%) cardiac perforations, of which two resulted in death. Cardiac perforation was associated with the use of radiofrequency (p=0.047), longer radiofrequency duration (3.5 versus 2.0 seconds, p=0.02), and higher maximal radiofrequency energy (7.5 versus 5.0 J, p<0.01) but not with patient weight (p=0.09), pulmonary valve diameter (p=0.23), or infundibular diameter (p=0.57). Re-intervention was performed in 36 patients and was associated with higher post-intervention right ventricle pressure (median 60 versus 50 mmHg, p=0.041) and residual valve gradient (median 15 versus 10 mmHg, p=0.046), but not with balloon-to-pulmonary valve annulus ratio, atmospheric pressure used during BPV, or the presence of a residual balloon waist during BPV. Re-intervention was not associated with any right ventricle anatomic characteristics, including pulmonary valve diameter. CONCLUSION: Technical factors surrounding transcatheter right ventricle decompression in pulmonary atresia and intact ventricular septum influence the risk of procedural complications but not the risk of future re-intervention. Cardiac perforation is associated with the use of radiofrequency energy, as well as radiofrequency application characteristics. Re-intervention after right ventricle decompression for pulmonary atresia and intact ventricular septum is common and relates to haemodynamic measures surrounding initial BPV.

A Comparison of Anterograde Versus Retrograde Approaches for Neonatal Balloon Aortic Valvuloplasty.

In neonates requiring balloon aortic valvuloplasty, both anterograde and retrograde approaches are feasible. A recent comparison of these two approaches is lacking. A retrospective cohort study of neonates at a single center undergoing BAV from 9/00 to 7/14 was performed. Records were reviewed including pre- and post-intervention echocardiograms and catheterization data. Comparisons of acute efficacy and procedural safety were made based on type of approach utilized. Forty-two neonates underwent BAV. Eleven cases utilized exclusively an anterograde approach, while 31 included a retrograde approach (including 4 with both approaches used). There were no significant differences between groups in baseline demographic and clinical characteristics. Additionally, by both pre-intervention echocardiogram and catheterization, there were no differences based on approach in aortic valve gradient, degree of aortic insufficiency (AI), or degree of mitral regurgitation (MR). Both approaches were equally efficacious in gradient reduction (45 ± 17 vs. 44 ± 21 mmHg, p = 0.97), and there was no difference in post-intervention AI as assessed by both catheterization and echocardiogram (52% vs. 64% none or trivial, p = 0.74). Additionally, there was no difference in the proportion of patients with an increased severity of MR after BAV (15% vs. 22%, p = 0.52). The retrograde approach required a larger arterial catheter and was associated with a higher rate of arterial thrombosis (61% vs. 18%, p = 0.014). Both anterograde and retrograde approaches to neonatal BAV appear to be equally efficacious in the short term. The anterograde approach avoids the need for a larger arterial catheter and may reduce the risk of arterial thrombosis.

Outcomes After Decompression of the Right Ventricle in Infants With Pulmonary Atresia With Intact Ventricular Septum Are Associated With Degree of Tricuspid Regurgitation: Results From the Congenital Catheterization Research Collaborative.

BACKGROUND: Outcomes after right ventricle (RV) decompression in infants with pulmonary atresia with intact ventricular septum vary widely. Descriptions of outcomes are limited to small single-center studies. METHODS AND RESULTS: Neonates undergoing RV decompression for pulmonary atresia with intact ventricular septum were included from 4 pediatric centers. Primary end point was reintervention post-RV decompression; secondary end points included circulation type at latest follow-up. Ninety-nine patients (71 with pulmonary atresia with intact ventricular septum and 28 with virtual atresia) underwent RV decompression at median 3 (25th-75th, 2-5) days of age. Seventy-one patients (72%) underwent at least 1 reintervention after decompression. Median duration of follow-up was 3 years (range, 1-10). Freedom from reintervention was 51% at 1 month and 23% at 3 years. In multivariable analysis, reintervention was associated with virtual atresia (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.28-091; P=0.027), smaller RV length (HR, 0.94; 95% CI, 0.89-0.99; P=0.027), and ≤mild tricuspid regurgitation (TR; HR, 3.58; 95% CI, 2.04-6.30; P<0.001). Patients undergoing surgical shunt or ductal stent were less likely to have virtual atresia (HR, 0.36; 95% CI, 0.15-0.85; P=0.02) and more likely to have higher RV end-diastolic pressure (HR, 1.07; 95% CI, 1.00-1.15; P=0.057) and ≤mild TR (HR, 3.50; 95% CI, 1.75-7.0; P<0.001). Number of reinterventions was associated with ≤mild TR (rate ratio, 1.87; 95% CI, 1.23-2.87; P=0.0037). Multivariable analysis indicated that <2-ventricle circulation status was associated with ≤mild TR (odds ratio, 18.6; 95% CI, 5.3-65.2; P<0.001) and lower RV area (odds ratio, 0.81; 95% CI, 0.72-0.91; P<0.001). CONCLUSIONS: Patients with pulmonary atresia with intact ventricular septum deemed suitable for RV decompression have a high reintervention burden although most achieve 2-ventricle circulation. TR ≤mild at baseline is strongly associated with reintervention and <2-ventricle circulation at medium-term follow-up. Degree of baseline TR may be an important marker of long-term outcomes in this population.

Determination and application of empirically derived detergent phase boundaries to effectively crystallize membrane proteins.

Elucidating the structures of membrane proteins is essential to our understanding of disease states and a critical component in the rational design of drugs. Structural characterization of a membrane protein begins with its detergent solubilization from the lipid bilayer and its purification within a functionally stable protein-detergent complex (PDC). Crystallization of the PDC typically occurs by changing the solution environment to decrease solubility and promote interactions between exposed hydrophilic surface residues. As membrane proteins have been observed to form crystals close to the phase separation boundaries of the detergent used to form the PDC, knowledge of these boundaries under different chemical conditions provides a foundation to rationally design crystallization screens. We have carried out dye-based detergent phase partitioning studies using different combinations of 10 polyethylene glycols (PEG), 11 salts, and 11 detergents to generate a significant amount of chemically diverse phase boundary data. The resulting curves were used to guide the formulation of a 1536-cocktail crystallization screen for membrane proteins. We are making both the experimentally derived phase boundary data and the 1536 membrane screen available through the high-throughput crystallization facility located at the Hauptman-Woodward Institute. The phase boundary data have been packaged into an interactive Excel spreadsheet that allows investigators to formulate grid screens near a given phase boundary for a particular detergent. The 1536 membrane screen has been applied to 12 membrane proteins of unknown structures supplied by the structural genomics and structural biology communities, with crystallization leads for 10/12 samples and verification of one crystal using X-ray diffraction.