Hypoplastic Left Heart Syndrome with Mitral Stenosis and Aortic Atresia-Echocardiographic Findings and Early Outcomes.

BACKGROUND: Mitral stenosis/aortic atresia (MS/AA) has been reported as a high-risk variant of hypoplastic left heart syndrome (HLHS), potentially related to ventriculocoronary connections (VCCs) or endocardial fibroelastosis (EFE) and myocardial hypoperfusion. We aimed to identify echocardiographic and clinical factors associated with early death or transplant in this group. METHODS: Patients with HLHS MS/AA treated at our center between 2000 and 2020 were included. Pre-stage I palliation echocardiograms were reviewed. Certain imaging factors, such as determination of VCC, EFE, and measurement of tricuspid annular plane systolic excursion were measured from retrospective review of preoperative images; others were derived from clinical reports. Groups were compared according to primary outcome of death or transplant prior to stage II palliation. RESULTS: Of 141 patients included, 39 (27.7%) experienced a primary outcome. Ventriculocoronary connections were identified in 103 (73.0%) patients and EFE in 95 (67.4%) patients. Among imaging variables, smaller ascending aorta size (median, 2.2 [interquartile range (IQR) 1.7-2.8] vs 2.6 [2.2-3.4] mm, P = .01) was associated with primary outcome. There was similar frequency of VCC (74.4% vs 72.5%, P = .83), EFE (59.0% vs 72.5%, P = .19), moderate or greater tricuspid regurgitation (5.1% vs 5.9%, P = 1.00), and similar right ventricular systolic function (indexed tricuspid annular plane systolic excursion 32.5 ± 7.3 vs 31.4 ± 7.2 mm/m2, P = .47) in the primary outcome group compared to other patients. Clinical factors associated with primary outcome included lower birth weight (mean, 2.8 ± SD 0.8 vs 3.3 ± 0.5 kg, P = .0003), gestational age <37 weeks (31.6% vs 4.9%, P < .0001), longer cardiopulmonary bypass time (median, 112 [IQR, 93-162] vs 82 [71-119] minutes, P = .001), longer intensive care unit length of stay (median, 19 [IQR, 10-30] vs 10 [7-15] days, P = .001), and extracorporeal membrane oxygenation following stage I palliation (43.6% vs 8.8%, P < .0001). Presence of VCCs and EFE was not associated with death or transplant after controlling for birth weight and era of stage I palliation. CONCLUSIONS: In one of the largest reported single-center cohorts of HLHS MS/AA, there were few pre-stage I palliation imaging characteristics associated with primary outcome. Imaging findings evaluated in this study, including the presence of VCC and/or EFE as determined using highly sensitive echocardiogram criteria, should not preclude intervention, although impact on long-term outcomes requires further evaluation.

Consensus-Based Development of a Pediatric Echocardiography Complexity Score: Design, Rationale, and Results of a Quality Improvement Collaborative.

BACKGROUND: The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score. METHODS AND RESULTS: The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. Univariate and multivariate analyses were performed to assess for independent predictors of longer study duration. Among the 174 echocardiograms analyzed, 68.9% had underlying congenital heart disease; 44.8% were outpatient; 34.5% were performed in an intensive care setting; 61.5% were follow-up; 46.6% were initial or preoperative; and 9.8% were sedated. All studies had an assigned PEC score. In univariate analysis, longer study duration was associated with several patient and study variables (age <2 years, PEC 4 or 5, initial study, preoperative study, junior or trainee scanner, and need for additional imaging). In multivariable analysis, a higher PEC score of 4 or 5 was independently associated with longer study duration after controlling for study variables and center variation. CONCLUSIONS: The PEC scoring tool is feasible and applicable in a variety of clinical settings and can be used for correlation with diagnostic errors, allocation of resources, and assessment of physician and sonographer effort in performing, interpreting, and training in pediatric echocardiography.

Demonstration of a robust high cell density transient CHO platform yielding mAb titers of up to 2 g/L without medium exchange.

Biopharmaceuticals like therapeutic monoclonal antibodies (mAbs) and other derived proteins are popular for treating various diseases. Transient gene expression (TGE) is typically used as a fast yet efficient method to generate moderate amounts of material. It has been used to support early stage research and discovery processes. Introduction of a robust high yielding and predictive TGE platform in Chinese hamster ovary (CHO) is crucial. It maintains the consistency in cell lines and processes throughout the early drug discovery and downstream manufacturing processes. This helps researchers to identify the issues at an early stage for timely resolution. In this study, we have demonstrated a simple high-titer platform for TGE in CHO based on a dilution process of seeding cells. We achieved titers ranging from 0.8 to 1.9 g/L for eight model mAbs at three scales (1, 30, 100 mL) in 10 days using our new platform. The ability to seed by dilution significantly streamlined the process and dramatically enhanced platform throughput. We observed a modest reduction in titer ranging from 11% to 28% when cells were seeded using dilution compared to when cells were seeded using medium exchange. Further studies revealed that carry over of spent medium into transfection negatively affected the DNA uptake and transcription processes, while the translation and secretion was minimally impacted. In summary, our transient CHO platform using cells prepared by dilution at high densities can achieve high titers of up to 1.9 g/L, which can be further improved by targeting the bottlenecks of transfection and transcription.

Effects of Mitral Valve Prolapse on Quantification of Mitral Regurgitation and Ejection Fraction Using Cardiac MRI.

Purpose: To determine the impact of prolapsed volume on regurgitant volume (RegV), regurgitant fraction (RF), and left ventricular ejection fraction (LVEF) in patients with mitral valve prolapse (MVP) using cardiac MRI. Materials and Methods: Patients with MVP and mitral regurgitation who underwent cardiac MRI from 2005 to 2020 were identified retrospectively from the electronic record. RegV is the difference between left ventricular stroke volume (LVSV) and aortic flow. Left ventricular end-systolic volume (LVESV) and LVSV were obtained from volumetric cine images, with prolapsed volume inclusion (LVESVp, LVSVp) and exclusion (LVESVa, LVSVa) providing two estimates of RegV (RegVp, RegVa), RF (RFp, RFa), and LVEF (LVEFa, LVEFp). Interobserver agreement for LVESVp was assessed using intraclass correlation coefficient (ICC). RegV was also calculated independently using measurements from mitral inflow and aortic net flow phase-contrast imaging as the reference standard (RegVg). Results: The study included 19 patients (mean age, 28 years ± 16 [SD]; 10 male patients). Interobserver agreement for LVESVp was high (ICC, 0.98; 95% CI: 0.96, 0.99). Prolapsed volume inclusion resulted in higher LVESV (LVESVp: 95.4 mL ± 34.7 vs LVESVa: 82.4 mL ± 33.8; P < .001), lower LVSV (LVSVp: 100.5 mL ± 33.8 vs LVSVa: 113.5 mL ± 35.9; P < .001), and lower LVEF (LVEFp: 51.7% ± 5.7 vs LVEFa: 58.6% ± 6.3; P < .001). RegV was larger in magnitude when prolapsed volume was excluded (RegVa: 39.4 mL ± 21.0 vs RegVg: 25.8 mL ± 22.8; P = .02), with no evidence of a difference when including prolapsed volume (RegVp: 26.4 mL ± 16.4 vs RegVg: 25.8 mL ± 22.8; P > .99). Conclusion: Measurements that included prolapsed volume most closely reflected mitral regurgitation severity, but inclusion of this volume resulted in a lower LVEF.Keywords: Cardiac, MRI© RSNA, 2023See also commentary by Lee and Markl in this issue.

Appropriateness of cardiovascular computed tomography and magnetic resonance imaging in patients with conotruncal defects.

BACKGROUND: To promote the rational use of cardiovascular imaging in patients with congenital heart disease, the American College of Cardiology developed Appropriate Use Criteria (AUC), but its clinical application and pre-release benchmarks have not been evaluated. We aimed to evaluate the appropriateness of indications for cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) in patients with conotruncal defects and to identify factors associated with maybe or rarely appropriate (M/R) indications. METHODS: Twelve centers each contributed a median of 147 studies performed prior to AUC publication (01/2020) on patients with conotruncal defects. To incorporate patient characteristics and center-level effects, a hierarchical generalized linear mixed model was used. RESULTS: Of the 1753 studies (80% CMR, and 20% CCT), 16% were rated M/R. Center M/R ranged from 4 to 39%. Infants accounted for 8.4% of studies. In multivariable analyses, patient- and study-level factors associated with M/R rating included: age <1 year (OR 1.90 [1.15-3.13]), truncus arteriosus (vs. tetralogy of Fallot, OR 2.55 [1.5-4.35]), and CCT (vs. CMR, OR 2.67 [1.87-3.83]). None of the provider- or center-level factors reached statistical significance in the multivariable model. CONCLUSIONS: Most CMRs and CCTs ordered for the follow-up care of patients with conotruncal defects were rated appropriate. However, there was significant center-level variation in appropriateness ratings. Younger age, CCT, and truncus arteriosus were independently associated with higher odds of M/R rating. These findings could inform future quality improvement initiatives and further exploration of factors resulting in center-level variation.

Representation of Women and Minority Faculty and Fellows in Academic Pediatric Cardiology Training Programs.

BACKGROUND: Studies have shown that diverse care teams optimize patient outcomes. Describing the current representation of women and minorities has been a critical step in improving diversity across several fields. OBJECTIVES: To address the lack of data specific to pediatric cardiology, the authors conducted a national survey. METHODS: U.S. academic pediatric cardiology programs with fellowship training programs were surveyed. Division directors were invited (July 2021 to September 2021) to complete an e-survey of program composition. Underrepresented minorities in medicine (URMM) were characterized using standard definitions. Descriptive analyses at the hospital, faculty, and fellow level were performed. RESULTS: Altogether, 52 of 61 programs (85%) completed the survey, representing 1,570 total faculty and 438 fellows, with a wide range in program size (7-109 faculty, 1-32 fellows). Although women comprise approximately 60% of faculty in pediatrics overall, they made up 55% of fellows and 45% of faculty in pediatric cardiology. Representation of women in leadership roles was notably less, including 39% of clinical subspecialty directors, 25% of endowed chairs, and 16% of division directors. URMM comprise approximately 35% of the U.S. population; however, they made up only 14% of pediatric cardiology fellows and 10% of faculty, with very few in leadership roles. CONCLUSIONS: These national data suggest a "leaky pipeline" for women in pediatric cardiology and very limited presence of URRM overall. Our findings can inform efforts to elucidate underlying mechanisms for persistent disparity and reduce barriers to improving diversity in the field.

Is There Gender Bias in Radiology Job Postings?

BACKGROUND: Words can convey subtle cultural stereotypes and perpetuate subconscious gender biases. Wording in job advertisements that appeals to 1 gender and deters others may unintentionally skew the applicant pool and affect the early phase of the recruitment process. "Masculine" tone can lead to decreased interest among women applicants while 'feminine' wording may not affect a man's decision to apply for the job. In this study, we evaluated the presence and extent of subtle gender bias in job advertisements for radiology faculty positions. METHODS: All job postings for faculty radiologists were retrieved from the American College of Radiology Career Center website in July 2020. The complete job advertisement was analyzed using Gender Decoder, a publicly available web-based application, to determine number and percentage of female or male coded words and the overall tone of the ad. The job posts were also stratified by subspecialty, leadership positions and academic versus private practice environments. RESULTS: Of the 623 job postings reviewed, a little over half (52.0%) of job postings were feminine coded, 26.6% had a masculine tone and 21.3% had a neutral tone. Of the leadership (division director) positions, 50.0% (4/8) had a masculine tone, 37.5% had a feminine tone, and 12.5% had a neutral tone. Among various specialties, pediatric radiology had the lowest percentage of job posts with a masculine tone (10.5%) while nuclear medicine had the highest percentage (41.7%). The most commonly used feminine words were: "support," "responsible," "commitment" and the most common masculine words were: "competitive," "leader," "active." CONCLUSIONS: Most of the imaging job advertisements were feminine coded, with masculine tone in overall 26.6% posts and neutral tone in about a fifth. Leadership posts had a higher percentage of masculine tone. Awareness of these biases is important to enable diversity in recruitment and to ensure a diverse applicant pool.

The development and efficacy of a paediatric cardiology fellowship online preparatory course.

BACKGROUND: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship. METHODS: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests. RESULTS: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants' comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship. CONCLUSION: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

Cardiac Magnetic Resonance to Predict Coronary Artery Compression in Transcatheter Pulmonary Valve Implantation Into Conduits.

OBJECTIVES: The aim of this study was to evaluate the accuracy of cardiac magnetic resonance (CMR) in predicting coronary artery (CA) compression during transcatheter pulmonary valve implantation (TPVi). BACKGROUND: TPVi is a widely available option to treat dysfunctional right ventricle (RV)-to-pulmonary artery (PA) conduits, but CA compression is an absolute contraindication. CMR can evaluate coronary anatomy, but its utility in predicting CA compression is not well established. METHODS: After Institutional Review Board approval was obtained, all patients at 9 centers with attempted TPVi in RV-PA conduits and recent CMR (≤12 months) were analyzed. A core laboratory reviewed all CMR studies for the shortest orthogonal distance from a CA to the conduit, the shortest distance from a CA to the most stenotic area of the conduit, and subjective assessment of CA compression risk. RESULTS: Among 231 patients, TPVi was successful in 198 (86%); in 24 (10%), balloon testing precluded implantation (documented CA compression or high risk). Distance to the RV-PA conduit ≤2.1 mm (area under the curve [AUC]: 0.70) and distance to most stenotic area ≤13.1 mm (AUC: 0.69) predicted CA compression. Subjective assessment had the highest AUC (0.78), with 96% negative predictive value. Both distances and qualitative assessment remained independently associated with CA compression when controlling for abnormal coronary anatomy or degree of conduit calcification. CONCLUSIONS: CMR can help predict the risk for CA compression during TPVi in RV-PA conduits but cannot completely exclude CA compression. CMR may assist in patient selection and counseling families prior to TPVi, although balloon testing remains essential.

The Diagnostic Role of Echocardiographic Strain Analysis in Patients Presenting with Chest Pain and Elevated Troponin: A Multicenter Study.

BACKGROUND: Myocarditis presenting as acute chest pain with elevated troponins without significant cardiac compromise is rare in previously healthy children, often referred to as myopericarditis. Diagnosis is challenging, as conventional echocardiographic measures of systolic function can be normal. The aim of this study was to demonstrate the diagnostic utility of strain imaging in this scenario. METHODS: This was a multicenter, retrospective study including patients presenting with chest pain and elevated troponin from 10 institutions who underwent cardiac magnetic resonance imaging and transthoracic echocardiography within 30 days of each other (group 1). Findings were compared with those among 19 control subjects (group 2). Clinical data and conventional echocardiographic and cardiac magnetic resonance imaging data were collected. Echocardiography-derived strain was measured at the core laboratory. Group 1 was divided into subgroups as myocarditis positive (group 1a) or negative (group 1b) on cardiac magnetic resonance imaging on the basis of established criteria. RESULTS: Group 1 included 108 subjects (88 in group 1a, 20 in group 1b). Although all groups had normal mean fractional shortening and mean left ventricular ejection fraction, group 1 had significantly lower ejection fraction (56.8 ± 7.0%) compared with group 2 (62.3 ± 4.9%; P < .005) and fractional shortening (31.2 ± 4.9%) compared with group 2 (34.1 ± 3.5%; P < .05). Additionally, peak global longitudinal strain (GLS) was markedly abnormal in group 1 (-13.9 ± 3.4%) compared with group 2 (-19.8 ± 2.1%; P < .001). In subgroup analysis, GLS was markedly abnormal in group 1a (-13.2 ± 3.0%) compared with group 1b (-17.3 ± 2.6%; P < .001). Fifty-four subjects underwent follow-up echocardiography (46 in group 1a, eight in group 1b), with mean a follow-up time of 10 ± 11 months. At follow-up, whereas ejection fraction and fractional shortening returned to normal in all patients, abnormalities in strain persisted in group 1, with 22% still having abnormal GLS. Moreover, mean GLS was more abnormal in group 1a (-16.1 ± 2.6%) compared with group 1b (-17.4 ± 1.2%; P < .05). CONCLUSIONS: The present study demonstrates that echocardiographic GLS is significantly worse in subjects with myopericarditis presenting with chest pain and elevated troponins compared with control subjects even when conventional measures of systolic function are largely normal and that these abnormalities persisted over time.

Female Representation on Radiology Journal Editorial Boards Around the World: Geographical Differences and Temporal Trends.

RATIONALE AND OBJECTIVES: We examined the status of women's representation on radiology journal editorial boards around the world and evaluated temporal trends in female board representation. MATERIALS AND METHODS: Data on the gender of editorial board members, deputy editors, and editors-in-chief of top general radiology journals from the United States and from five continents outside North America was collected, based on listings in mastheads of each journal at 5-year intervals from 1998 to 2018. Female editorial board representation was compared to female membership in national professional radiology organizations and national physician registries. RESULTS: One of 42 editors-in-chief (2.4%), 24 of 135 deputy editors (17.8%), and 345 of 2545 (13.6%) editorial board members were female for the 20-year period. The overall percentage of female editorial board members increased from 9.7% (41 of 423) in 1998 to 17.0% (97 of 569) in 2018 (p < 0.0001). In 2018, women were less represented on the editorial boards than female professional society membership for all geographic regions except Australia/New Zealand; this difference reached statistical significance in Korea, Brazil, Europe, and China. Female editorial board representation ranged from 11.3% to 33.3%, with no significant difference between the United States (21.5%) and other countries. CONCLUSION: Although the proportion of female editorial board members of radiology journals worldwide has increased over the past two decades, female editorial board composition generally underrepresents the percentage of female radiologists. Editorial board female representation does not differ significantly between the United States and other countries.

Birth Location in Infants with Prenatally Diagnosed Hypoplastic Left Heart Syndrome.

There are conflicting data on how delivery location impacts outcomes in neonates with ductal-dependent heart disease. Our goal was to evaluate the impact of delivery location on hospital length of stay and survival in infants with prenatally diagnosed hypoplastic left heart syndrome (HLHS) after stage 1 palliation (S1P). A multicenter cohort study was performed utilizing the National Pediatric Cardiology Quality Improvement Collaborative dataset for infants with prenatally diagnosed HLHS who underwent S1P from August 2016 to December 2018. Univariate comparisons of demographics, clinical, and outcome data were made and multivariable logistic regression was performed between groups stratified by distance from surgical center. A total of 790 patients from 33 centers were analyzed: 85% were born < 5 miles from the surgical center with 72% of those (486/673) born at the surgical center. Infants born < 5 miles from the surgical center were significantly (p < 0.05) more likely to be male, white, full term, have no non-cardiac anomaly, and have commercial health insurance; they were significantly more likely to breastfeed pre-operatively, and less likely to have pre-operative cardiac catheterizations, pre-operative mechanical ventilation, or delayed surgery. There was no significant difference between groups in hospital length of stay, 30-day survival, or survival to hospital discharge. In this multicenter dataset, hospital length of stay and survival after S1P did not differ based on distance from birth location to surgical center. However, neonates born < 5 miles from the surgical center had lower rates of potentially modifiable pre-operative risk factors including mechanical ventilation and delays to surgery.

Accuracy of Cardiac Magnetic Resonance Imaging in Diagnosing Pediatric Cardiac Masses: A Multicenter Study.

BACKGROUND: After diagnosis of a cardiac mass, clinicians must weigh the benefits and risks of ascertaining a tissue diagnosis. Limited data are available on the accuracy of previously developed noninvasive pediatric cardiac magnetic resonance (CMR)-based diagnostic criteria. OBJECTIVES: The goals of this study were to: 1) evaluate the CMR characteristics of pediatric cardiac masses from a large international cohort; 2) test the accuracy of previously developed CMR-based diagnostic criteria; and 3) expand diagnostic criteria using new information. METHODS: CMR studies (children 0-18 years of age) with confirmatory histological and/or genetic diagnosis were analyzed by 2 reviewers, without knowledge of prior diagnosis. Diagnostic accuracy was graded as: 1) single correct diagnosis; 2) correct diagnosis among a differential; or 3) incorrect diagnosis. RESULTS: Of 213 cases, 174 (82%) had diagnoses that were represented in the previously published diagnostic criteria. In 70% of 174 cases, both reviewers achieved a single correct diagnosis (94% of fibromas, 71% of rhabdomyomas, and 50% of myxomas). When ≤2 differential diagnoses were included, both reviewers reached a correct diagnosis in 86% of cases. Of 29 malignant tumors, both reviewers indicated malignancy as a single diagnosis in 52% of cases. Including ≤2 differential diagnoses, both reviewers indicated malignancy in 83% of cases. Of 6 CMR sequences examined, acquisition of first-pass perfusion and late gadolinium enhancement were independently associated with a higher likelihood of a single correct diagnosis. CONCLUSIONS: CMR of cardiac masses in children leads to an accurate diagnosis in most cases. A comprehensive imaging protocol is associated with higher diagnostic accuracy.

Mycoplasma pneumoniae CARDS toxin exploits host cell endosomal acidic pH and vacuolar ATPase proton pump to execute its biological activities.

Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia among hospitalized children in the United States. It is also responsible for a spectrum of other respiratory tract disorders and extrapulmonary manifestations in children and adults. The main virulence factor of M. pneumoniae is a 591 amino acid multifunctional protein called Community Acquired Respiratory Distress Syndrome (CARDS) toxin. The amino terminal region of CARDS toxin (N-CARDS) retains ADP-ribosylating activity and the carboxy region (C-CARDS) contains the receptor binding and vacuolating activities. After internalization, CARDS toxin is transported in a retrograde manner from endosome through the Golgi complex into the endoplasmic reticulum. However, the mechanisms and criteria by which internalized CARDS toxin is transported and activated to execute its cytotoxic effects remain unknown. In this study, we used full-length CARDS toxin and its mutant and truncated derivatives to analyze how pharmacological drugs that alter pH of intracellular vesicles and electrical potential across vesicular membranes affect translocation of CARDS toxin in mammalian cells. Our results indicate that an acidic environment is essential for CARDS toxin retrograde transport to endoplasmic reticulum. Moreover, retrograde transport facilitates toxin clipping and is required to induce vacuole formation. Additionally, toxin-mediated cell vacuolation is strictly dependent on the function of vacuolar type-ATPase.

Longitudinal Assessment of Right Ventricular Function in Hypoplastic Left Heart Syndrome.

Overall survival of patients with hypoplastic left heart syndrome (HLHS) has shown continued improvement. Right ventricular (RV) dysfunction, in the long term, adversely affects prognosis in these patients. This study examines changes in echocardiographic markers of RV function in a longitudinal cohort. We retrospectively reviewed patients with HLHS managed at our institution from 7/1994 to 1/2016. Follow-up included surgical and clinical data, and echocardiographic measures. Measures of RV function preceding and following all three stages of single ventricular palliation were collected. Freedom from transplant-free survival was assessed by Kaplan-Meier analysis. Multivariable associations with time to death or transplant were explored using the Cox proportional hazards model. A total of 120 patients with HLHS were identified. Norwood operation was performed in all patients. The probability of survival for the cohort was 71 ± 4.4%, 69 ± 4.5% and 66 ± 4.7% at 1, 2 and 5 years respectively after stage I Norwood operation. RV fractional area change (FAC), compared to post-Norwood was decreased at all subsequent stages with the greatest change noted post-superior cavo-pulmonary shunt from 40.7 ± 9.3% to 31.1 ± 8.3% (p < 0.001). Similarly, tricuspid valve annular systolic excursion (TAPSE) Z-score declined from -2.9 ± 1.3 to -9.7 ± 1.3 (p < 0.001) with a decrement at every stage of evaluation. In comparison to patients with post-Norwood RV FAC >35% and TAPSE Z-score > -5, patients with RV FAC ≤ 35% and TAPSE Z-score ≤ -5 had a significantly lower transplant-free survival (p < 0.0001). In patients with HLHS undergoing staged palliation, decrement in RV function manifests longitudinally. Post-Norwood RV FAC and TAPSE Z-score appear to be early markers of poor outcome in this population.

Accelerating and de-risking CMC development with transposon-derived manufacturing cell lines.

The development of highly productive, genetically stable manufacturing cell lines is on the critical path to IND filing for protein-based biologic drugs. Here, we describe the Leap-In Transposase® platform, a novel transposon-based mammalian (e.g., Chinese hamster ovary) cell line development system that produces high-titer stable pools with productivity and product quality attributes that are highly comparable to clones that are subsequently derived therefrom. The productivity distributions of clones are strongly biased toward high producers, and genetic and expression stability is consistently high. By avoiding the poor integration rates, concatemer formation, detrimental transgene recombination, low average expression level, unpredictable product quality, and inconsistent genetic stability characteristic of nonhomologous recombination methods, Leap-In provides several opportunities to de-risk programs early and reduce timelines and resources.

Improving adherence to echocardiogram reporting guidelines in patients with repaired tetralogy of fallot: A quality improvement initiative.

BACKGROUND: In patients with repaired tetralogy of Fallot (TOF), key echocardiogram report elements have been identified, but poor adherence has been demonstrated, particularly for quantitative assessment. We report a quality improvement effort to improve adherence at our institution, with a focus on increasing quantitative assessment of right ventricular (RV) function. METHODS: Baseline compliance was established by a 3-month retrospective review of outpatient echocardiogram reports. Intervention 1 included presenting baseline data and reviewing the guidelines with echocardiogram laboratory staff (physicians and sonographers). Intervention 2, chosen to focus on quantitative assessment of RV function, involved recommending measurement of tricuspid annular plane systolic excursion (TAPSE) for all echocardiograms. Reporting rates were prospectively analyzed for 1 month after each intervention. To evaluate sonographer versus physician compliance, both study images (acquisition of TAPSE images) and reports were reviewed. RESULTS: At baseline, adherence was poor (median 65% of elements reported), with lower rates for measurements versus descriptive elements (median 40% vs 78%, p<.0001). Following intervention 1, total reported elements improved (median 71% vs 65%, p=0.02) due to increase in measurements (median 50% vs 40%, p=0.02). Reports of quantitative RV function did not significantly change after either intervention, but sonographer compliance improved after intervention 1 (33% vs 14%, p=0.03), with further improvement after intervention 2 (53% vs 14%, p=0.001). CONCLUSION: While education on lesion-specific guidelines may modestly improve adherence, standardization has a greater effect. However, interventions may have differential impact on sonographers versus attendings, and iterative interventions may be required to change practice patterns.