Rational design of base, sugar and backbone modifications improves ADAR-mediated RNA editing.

AIMers are short, chemically modified oligonucleotides that induce A-to-I RNA editing through interaction with endogenous adenosine deaminases acting on RNA (ADAR) enzymes. Here, we describe the development of new AIMer designs with base, sugar and backbone modifications that improve RNA editing efficiency over our previous design. AIMers incorporating a novel pattern of backbone and 2' sugar modifications support enhanced editing efficiency across multiple sequences. Further efficiency gains were achieved through incorporation of an N-3-uridine (N3U), in place of cytidine (C), in the 'orphan base' position opposite the edit site. Molecular modeling suggests that N3U might enhance ADAR catalytic activity by stabilizing the AIMer-ADAR interaction and potentially reducing the energy required to flip the target base into the active site. Supporting this hypothesis, AIMers containing N3U consistently enhanced RNA editing over those containing C across multiple target sequences and multiple nearest neighbor sequence combinations. AIMers combining N3U and the novel pattern of 2' sugar chemistry and backbone modifications improved RNA editing both in vitro and in vivo. We provide detailed N3U synthesis methods and, for the first time, explore the impact of N3U and its analogs on ADAR-mediated RNA editing efficiency and targetable sequence space.

Pulmonary Artery Wedge Pressure Can Underestimate Direct Pulmonary Vein Pressure in Pediatric Pulmonary Vein Stenosis.

Background: Pulmonary artery wedge pressure (PAWP) can underestimate directly measured pulmonary vein pressure (PVP) as demonstrated in animal studies and human case reports. This concept has not been validated in a larger cohort of pediatric patients with pulmonary vein stenosis (PVS). Methods: Pediatric patients who underwent cardiac catheterization for PVS at a single center from January 1, 2018, to March 31, 2023, were retrospectively reviewed. Mismatch between the PAWP and directly measured PVP or LA pressure was defined as >3 mm Hg. Preintervention angiography was reviewed and percent stenosis calculated. Results: Twenty-six patients met inclusion criteria; 51 lower pulmonary veins (34 left, 17 right) from 42 catheterizations were evaluated. Significant PVS (≥30% stenosis) was seen in 38/51 (75%) veins, and 9/51 (18%) veins had no angiographic narrowing (0% stenosis). PAWP-PVP mismatch occurred in 37/51 (73%) veins with a median difference of 8 mm Hg (IQR, 6-12). Of these, PAWP was equal to LA pressure in 26 instances, all of which had significant PVS (median % stenosis 54 [IQR, 45-60]). Six of the cases with PAWP-PVP mismatch, PVS (range, 41%-70% stenosis), and no PAWP-LA mismatch reported both a proximal and distal segmental PAWP. In all 6 instances, there was no distal PAWP-PVP mismatch (median difference 1 mm Hg [range, 0-3]). Conclusions: In this single-center study of pediatric patients with PVS, PAWP significantly underestimated directly measured PVP in lower pulmonary veins. Balloon wedge or end hole catheter position in a distal lobar segment may more accurately estimate the PVP.

Intubation and Lower Saturation in the Delivery Room are Associated with Balloon Atrial Septostomy in Neonates with Transposition of the Great Arteries.

OBJECTIVE: To identify delivery room (DR) characteristics of patients with transposition of the great arteries (TGA) who underwent preoperative balloon atrial septostomy (BAS). STUDY DESIGN: Retrospective cohort study of all patients with prenatally diagnosed TGA delivered at our center between 2013 and 2023 who underwent arterial switch operation during the newborn admission. RESULTS: A total of 168 patients were included (median gestational age 39.5 weeks, 64% male, 33% with ventricular septal defect [VSD], 8% with aortic arch hypoplasia). BAS was performed in 84 patients (50%). Patients who underwent BAS had higher proportion of intubation in the DR (87% vs. 33%, p<0.001), lower maximum oxygen saturation in the first 10 minutes (64% vs. 74%, p<0.001) and 20 minutes (71% vs. 81%, p<0.001) of life, and lower maximum oxygen saturation at any point in the DR (79% vs. 87%, p<0.001). Adjusting for confounders (VSD, aortic arch anomaly, 5-minute Apgar, birth weight), intubation in the DR (adjusted odds ratio [aOR] 9.5, 95% CI 3.9, 25.0) and lower maximum oxygen saturation in the DR (aOR 0.9, 95% CI 0.8, 0.9) were independently associated with BAS. By receiver operating characteristic analysis, a maximum oxygen saturation of less than 86% at any timepoint in the DR discriminated for BAS with a specificity of 0.88, sensitivity of 0.70, and area under the curve of 0.82. CONCLUSIONS: Intubation and lower oxygen saturation in the DR are independently associated with BAS in patients with TGA born at our center. A maximum DR saturation of less than 86% best discriminates patients who undergo BAS in our population.

Incidence, Management, and Outcomes of Pulmonary Embolism at Tertiary Pediatric Hospitals in the United States.

Background: Pediatric pulmonary embolism (PE) is rare and potentially life-threatening. Though thrombolysis and thrombectomy are increasingly used in adult PE, trends in pediatric treatment and outcomes remain incompletely described. Objectives: The purpose of this study was to describe the incidence of PE, proportion of cases treated with anticoagulation alone, systemic thrombolysis, and directed therapy (local thrombolysis and thrombectomy), clinical outcomes, and total costs. Methods: A multicenter observational study was performed using administrative data from the Pediatric Health Information System database to study PE treated at U.S. pediatric hospitals from 2015 to 2021. Outcomes by treatment were evaluated using multivariable generalized linear mixed effects models. Results: Of 3,136 subjects, 70% were at least 12 years of age, and 46% were male. Sixty-two percent had at least 1 comorbidity, and congenital heart disease of any kind was the most prevalent (20%). Eighty-eight percent of subjects received anticoagulation alone, 7% received systemic thrombolysis, and 5% received directed therapy. Overall in-hospital mortality was 7.5%. Treatment approach did not change over time (P = 0.98). After adjusting for patient characteristics, directed therapy was associated with a lower risk of mortality (adjusted percentage -3%, [95% CI: -5% to 0%]) than anticoagulation alone. Systemic thrombolysis was associated with a greater total cost of hospitalization ($113,043 greater [95% CI: $62,866, $163,219]). Length of hospital stay did not differ by treatment. Conclusions: Pediatric patients with PE have a high incidence of underlying chronic disease. Anticoagulation alone remains the mainstay of treatment, with thrombolysis and thrombectomy rarely being used. Given the relative rarity of pediatric PE, additional research requiring innovative study designs is paramount.

Fundamentals of wildlife dosimetry and lessons learned from a decade of measuring external dose rates in the field.

Methods for determining the radiation dose received by exposed biota require major improvements to reduce uncertainties and increase precision. We share our experiences in attempting to quantify external dose rates to free-ranging wildlife using GPS-coupled dosimetry methods. The manuscript is a primer on fundamental concepts in wildlife dosimetry in which the complexities of quantifying dose rates are highlighted, and lessons learned are presented based on research with wild boar and snakes at Fukushima, wolves at Chornobyl, and reindeer in Norway. GPS-coupled dosimeters produced empirical data to which numerical simulations of external dose using computer software were compared. Our data did not support a standing paradigm in risk analyses: Using averaged soil contaminant levels to model external dose rates conservatively overestimate the dose to individuals within a population. Following this paradigm will likely lead to misguided recommendations for risk management. The GPS-dosimetry data also demonstrated the critical importance of how modeled external dose rates are impacted by the scale at which contaminants are mapped. When contaminant mapping scales are coarse even detailed knowledge about each animal's home range was inadequate to accurately predict external dose rates. Importantly, modeled external dose rates based on a single measurement at a trap site did not correlate to actual dose rates measured on free ranging animals. These findings provide empirical data to support published concerns about inadequate dosimetry in much of the published Chernobyl and Fukushima dose-effects research. Our data indicate that a huge portion of that literature should be challenged, and that improper dosimetry remains a significant source of controversy in radiation dose-effect research.

Outcomes Associated with Giant Coronary Artery Aneurysms after Kawasaki Disease: A Single-Center United States Experience.

OBJECTIVES: To determine the long-term outcomes among a cohort of patients with Kawasaki disease (KD) and a history of giant coronary artery aneurysms (CAAs) at a single US center. STUDY DESIGN: Medical records for all patients with KD and giant CAAs at a pediatric academic institution were reviewed. Primary outcomes included major adverse cardiovascular events (MACE) and normalization of CA luminal diameter, using Kaplan-Meier analyses. RESULTS: There were 60 patients with KD and giant CAAs identified between 1989 and 2023. The majority of patients were male (71.7%) with a median age at diagnosis of 0.9 years (range, 0.2-13.3 years). Patients were followed for a median of 11 years, up to 34.5 years. MACE occurred in 13 patients (21.7%) at a median of 1.4 years (range, 0.04-22.6 years) after KD diagnosis. The 10-, 20-, and 30-year MACE-free rates were 75%, 75%, and 60%. Patients with maximal CA z scores of ≥20 or bilateral CAA were more likely to have MACE. During follow-up, 26.7% of CAA regressed to a normal luminal diameter at a median of 3.6 years (range, 0.6-12.0 years). The 10-, 20- and 30-year likelihood of CA regression to normal luminal diameter was 36%, 46%, and 46%. CONCLUSIONS: Over 30 years, MACE occurred in nearly 22% of patients, more often in those with bilateral CAA or CA z scores of ≥20. Despite regression to a normal luminal diameter in >25% of CAAs, patients with a history of KD-associated giant CAA require ongoing surveillance for cardiac complications, even years after the initial disease.

Outcomes of Neonates Born with Symptomatic Tetralogy of Fallot and Absent Ductus Arteriosus.

OBJECTIVE: To test the hypothesis that neonates with symptomatic tetralogy of Fallot (TOF) and absent ductus arteriosus (ADA) have worse clinical outcomes compared with those with a ductus arteriosus (DA), and that this difference is driven by those born with ADA and with critically deficient pulmonary blood flow (CDPBF). STUDY DESIGN: We performed a retrospective, multicenter cohort study of neonates who underwent intervention for symptomatic TOF comparing death and reintervention between subjects with and without a DA identified on fetal echocardiogram or on echocardiogram performed in the first postnatal day. Exclusion criteria were as follows: inability to define DA status, collaterals supplying pulmonary blood flow, atrioventricular septal defect, and absent pulmonary valve. We defined CDPBF as undergoing a procedure to augment pulmonary blood flow on the date of birth or extracorporeal membrane oxygenation prior to such a procedure. RESULTS: The study cohort included 519 patients, among whom 11% had ADA. Patients with ADA were more likely to have a genetic syndrome and had smaller branch pulmonary artery size. In analyses adjusting for center, interventional treatment strategy, genetic syndrome, and minimum branch pulmonary artery size, ADA was associated with higher mortality risk (adjusted hazard ratio of 2.37 (95% CI: 1.07,5.27; P = .034). Seven patients had CDPBF (1.3% of the entire cohort and 12% of patients with ADA). CONCLUSIONS: A minority of symptomatic TOF neonates have ADA, which is associated with higher adjusted mortality risk compared with those with a DA. CDPBF appears to be a rare but important entity in this population.

Male mating season range expansion results from an increase in scale of daily movements for a polygynous-promiscuous bird.

Males of species with promiscuous mating systems are commonly observed to use larger ranges during the mating season relative to non-mating seasons, which is often attributed to a change in movements related to reproductive activities. However, few studies link seasonal range sizes to variation in daily space use patterns to provide insight into the behavioral mechanisms underlying mating season range expansion. We studied 20 GPS-tagged male wild turkeys (Meleagris gallopavo), a large upland gamebird, during the mating and summer non-mating seasons to test the hypothesis that larger mating season ranges resulted from male wild turkeys expanding the scale of daily movement activities to locate and court females. We delineated mating and non-mating seasons based on intensity of gobbling, a vocalization tied to courtship behavior, recorded by autonomous recording units distributed across the study area. Mating season ranges were significantly larger than non-mating season ranges. Daily ranges were larger in the mating season, as were distances between roost sites used on consecutive nights. Variance in daily range size was greater in the mating season, but low temporal autocorrelation suggested considerable daily variability in both seasons. We found no evidence that male wild turkeys changed how they distributed daily movements within seasonal ranges, or differences in habitat use, suggesting larger mating season ranges result from male wild turkeys increasing the scale of their daily movements, rather than a systematic shift to a nomadic movement strategy. Likely, the distribution of females is more dynamic and ephemeral compared to other resources, prompting males to traverse larger daily ranges during the mating season to locate and court females. Our work illustrates the utility of using daily movement to understand the behavioral process underlying larger space use patterns.

Distinguishing ASH clinical practice guidelines from other forms of ASH clinical advice.

ABSTRACT: The American Society of Hematology (ASH) develops a variety of resources that provide guidance to clinicians on the diagnosis and management of blood diseases. These resources include clinical practice guidelines (CPGs) and other forms of clinical advice. Although both ASH CPGs and other forms of clinical advice provide recommendations, they differ with respect to the methods underpinning their development, the principal type of recommendations they offer, their transparency and concordance with published evidence, and the time and resources required for their development. It is crucial that end users be aware of the differences between CPGs and other forms of clinical advice and that producers and publishers of these resources use clear and unambiguous terminology to facilitate their distinction. The objective of this article is to highlight the similarities and differences between ASH CPGs and other forms of ASH clinical advice and discuss the implications of these differences for end users.

Influence of artificial intelligence on the diagnostic performance of endoscopists in the assessment of Barrett's esophagus: a tandem randomized and video trial.

BACKGROUND: This study evaluated the effect of an artificial intelligence (AI)-based clinical decision support system on the performance and diagnostic confidence of endoscopists in their assessment of Barrett's esophagus (BE). METHODS: 96 standardized endoscopy videos were assessed by 22 endoscopists with varying degrees of BE experience from 12 centers. Assessment was randomized into two video sets: group A (review first without AI and second with AI) and group B (review first with AI and second without AI). Endoscopists were required to evaluate each video for the presence of Barrett's esophagus-related neoplasia (BERN) and then decide on a spot for a targeted biopsy. After the second assessment, they were allowed to change their clinical decision and confidence level. RESULTS: AI had a stand-alone sensitivity, specificity, and accuracy of 92.2%, 68.9%, and 81.3%, respectively. Without AI, BE experts had an overall sensitivity, specificity, and accuracy of 83.3%, 58.1%, and 71.5%, respectively. With AI, BE nonexperts showed a significant improvement in sensitivity and specificity when videos were assessed a second time with AI (sensitivity 69.8% [95%CI 65.2%-74.2%] to 78.0% [95%CI 74.0%-82.0%]; specificity 67.3% [95%CI 62.5%-72.2%] to 72.7% [95%CI 68.2%-77.3%]). In addition, the diagnostic confidence of BE nonexperts improved significantly with AI. CONCLUSION: BE nonexperts benefitted significantly from additional AI. BE experts and nonexperts remained significantly below the stand-alone performance of AI, suggesting that there may be other factors influencing endoscopists' decisions to follow or discard AI advice.

Effect of patient factors, center, and era on Fontan timing: An observational study using the Pediatric Health Information Systems Database.

BACKGROUND: There are no consensus guidelines defining optimal timing for the Fontan operation, the last planned surgery in staged palliation for single-ventricle heart disease. OBJECTIVES: Identify patient-level characteristics, center-level variation, and secular trends driving Fontan timing. METHODS: A retrospective observational study of subjects who underwent Fontan from 2007 to 2021 at centers in the Pediatric Health Information Systems database was performed using linear mixed-effects modeling in which age at Fontan was regressed on patient characteristics and date of operation with center as random effect. RESULTS: We included 10,305 subjects (40.4% female, 44% non-white) at 47 centers. Median age at Fontan was 3.4 years (IQR 2.6-4.4). Hypoplastic left heart syndrome (-4.4 months, 95%CI -5.5 to -3.3) and concomitant conditions (-2.6 months, 95%CI -4.1 to -1.1) were associated with younger age at Fontan. Subjects with technology-dependence (+4.6 months, 95%CI 3.1-6.1) were older at Fontan. Black (+4.1 months, 95%CI 2.5-5.7) and Asian (+8.3 months, 95%CI 5.4-11.2) race were associated with older age at Fontan. There was significant variation in Fontan timing between centers. Center accounted for 10% of variation (ICC 0.10, 95%CI 0.07-0.14). Center surgical volume was not associated with Fontan timing (P = .21). Operation year was associated with age at Fontan, with a 3.1 month increase in age for every 5 years (+0.61 months, 95%CI 0.48-0.75). CONCLUSIONS: After adjusting for patient-level characteristics there remains significant inter-center variation in Fontan timing. Age at Fontan has increased. Future studies addressing optimal Fontan timing are warranted.

Catheterization for Congenital Heart Disease Adjustment for Risk Method II.

BACKGROUND: Current metrics used to adjust for case mix complexity in congenital cardiac catheterization are becoming outdated due to the introduction of novel procedures, innovative technologies, and expanding patient subgroups. This study aims to develop a risk adjustment methodology introducing a novel, clinically meaningful adverse event outcome and incorporating a modern understanding of risk. METHODS: Data from diagnostic only and interventional cases with defined case types were collected for patients ≤18 years of age and ≥2.5 kg at all Congenital Cardiac Catheterization Project on Outcomes participating centers. The derivation data set consisted of cases performed from 2014 to 2017, and the validation data set consisted of cases performed from 2019 to 2020. Severity level 3 adverse events were stratified into 3 tiers by clinical impact (3a/b/c); the study outcome was clinically meaningful adverse events, severity level ≥3b (3bc/4/5). RESULTS: The derivation data set contained 15 224 cases, and the validation data set included 9462 cases. Clinically meaningful adverse event rates were 4.5% and 4.2% in the derivation and validation cohorts, respectively. The final risk adjustment model included age <30 days, Procedural Risk in Congenital Cardiac Catheterization risk category, and hemodynamic vulnerability score (C statistic, 0.70; Hosmer-Lemeshow P value, 0.83; Brier score, 0.042). CONCLUSIONS: CHARM II (Congenital Heart Disease Adjustment for Risk Method II) risk adjustment methodology allows for equitable comparison of clinically meaningful adverse events among institutions and operators with varying patient populations and case mix complexity performing pediatric cardiac catheterization.

Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial.

ABSTRACT: Guadecitabine is a novel hypomethylating agent (HMA) resistant to deamination by cytidine deaminase. Patients with relapsed/refractory acute myeloid leukemia (AML) were randomly assigned to guadecitabine or a preselected treatment choice (TC) of high-intensity chemotherapy, low-intensity treatment with HMAs or low-dose cytarabine, or best supportive care (BSC). The primary end point was overall survival (OS). A total of 302 patients were randomly assigned to guadecitabine (n = 148) or TC (n = 154). Preselected TCs were low-intensity treatment (n = 233 [77%; mainly HMAs]), high-intensity chemotherapy (n = 63 [21%]), and BSC (n = 6 [2%]). The median OS were 6.4 and 5.4 months for guadecitabine and TC, respectively (hazard ratio 0.88 [95% confidence interval, 0.67-1.14]; log-rank P = .33). Survival benefit for guadecitabine was suggested in several prospective subgroups, including age <65 years, Eastern Cooperative Oncology Group performance status 0 to 1, refractory AML, and lower peripheral blood blasts ≤30%. Complete response (CR) + CR with partial hematologic recovery rates were 17% for guadecitabine vs 8% for TC (P < .01); CR+CR with incomplete count recovery rates were 27% for guadecitabine vs 14% for TC (P < .01). Safety was comparable for the 2 arms, but guadecitabine had a higher rate of grade ≥3 neutropenia (32% vs 17%; P < .01). This study did not demonstrate an OS benefit for guadecitabine. Clinical response rates were higher for guadecitabine, with comparable safety to TC. There was an OS benefit for guadecitabine in several prespecified subgroups. This study was registered at www.clinicaltrials.gov as #NCT02920008.

Calculating Relative Lung Perfusion Using Fluoroscopic Sequences and Image Analysis: The Fluoroscopic Flow Calculator.

BACKGROUND: Maldistribution of pulmonary blood flow in patients with congenital heart disease impacts exertional performance and pulmonary artery growth. Currently, measurement of relative pulmonary perfusion can only be performed outside the catheterization laboratory. We sought to develop a tool for measuring relative lung perfusion using readily available fluoroscopy sequences. METHODS: A retrospective cohort study was conducted on patients with conotruncal anomalies who underwent lung perfusion scans and subsequent cardiac catheterizations between 2011 and 2022. Inclusion criteria were nonselective angiogram of pulmonary vasculature, oblique angulation ≤20°, and an adequate view of both lung fields. A method was developed and implemented in 3D Slicer's SlicerHeart extension to calculate the amount of contrast that entered each lung field from the start of contrast injection and until the onset of levophase. The predicted perfusion distribution was compared with the measured distribution of pulmonary blood flow and evaluated for correlation, accuracy, and bias. RESULTS: In total, 32% (79/249) of screened studies met the inclusion criteria. A strong correlation between the predicted flow split and the measured flow split was found (R2=0.83; P<0.001). The median absolute error was 6%, and 72% of predictions were within 10% of the true value. Bias was not systematically worse at either extreme of the flow distribution. The prediction was found to be more accurate for either smaller and younger patients (age 0-2 years), for right ventricle injections, or when less cranial angulations were used (≤20°). In these cases (n=40), the prediction achieved R2=0.87, median absolute error of 5.5%, and 78% of predictions were within 10% of the true flow. CONCLUSIONS: The current study demonstrates the feasibility of a novel method for measuring relative lung perfusion using conventional angiograms. Real-time measurement of lung perfusion at the catheterization laboratory has the potential to reduce unnecessary testing, associated costs, and radiation exposure. Further optimization and validation is warranted.

Racial and Ethnic Variation in ECMO Utilization and Outcomes in Pediatric Cardiac ICU Patients.

Background: Previous studies have reported racial disparities in extracorporeal membrane oxygenation (ECMO) utilization in pediatric cardiac patients. Objectives: The objective of this study was to determine if there was racial/ethnic variation in ECMO utilization and, if so, whether mortality was mediated by differences in ECMO utilization. Methods: This is a multicenter, retrospective cohort study of the Pediatric Cardiac Critical Care Consortium clinical registry. Analyses were stratified by hospitalization type (medical vs surgical). Logistic regression models were adjusted for confounders and evaluated the association between race/ethnicity with ECMO utilization and mortality. Secondary analyses explored interactions between race/ethnicity, insurance, and socioeconomic status with ECMO utilization and mortality. Results: A total of 50,552 hospitalizations from 34 hospitals were studied. Across all hospitalizations, 2.9% (N = 1,467) included ECMO. In medical and surgical hospitalizations, Black race and Hispanic ethnicity were associated with severity of illness proxies. In medical hospitalizations, race/ethnicity was not associated with the odds of ECMO utilization. Hospitalizations of other race had higher odds of mortality (adjusted odds ratio [aOR]: 1.61; 95% CI: 1.22-2.12; P = 0.001). For surgical hospitalizations, Black (aOR: 1.24; 95% CI: 1.02-1.50; P = 0.03) and other race (aOR: 1.50; 95% CI: 1.17-1.93; P = 0.001) were associated with higher odds of ECMO utilization. Hospitalizations of Hispanic patients had higher odds of mortality (aOR: 1.31; 95% CI: 1.03-1.68; P = 0.03). No significant interactions were demonstrated between race/ethnicity and socioeconomic status indicators with ECMO utilization or mortality. Conclusions: Black and other races were associated with increased ECMO utilization during surgical hospitalizations. There were racial/ethnic disparities in outcomes not explained by differences in ECMO utilization. Efforts to mitigate these important disparities should include other aspects of care.

Evaluating Procedural Performance: A Composite Outcome for Aortic and Pulmonary Valvuloplasty in Congenital Cardiac Catheterization.

Background: Safety events and technical success (TS) have been previously reported for aortic and pulmonary valvuloplasty, but a composite performance measure as a novel, patient-centered strategy has neither been developed nor been studied. This study aims to refine a procedural performance (PP) variable, a composite of TS and procedural safety, for isolated, standard-risk aortic and pulmonary valvuloplasty. Methods: A multicenter review was performed using data from the Congenital Cardiac Catheterization Project on Outcomes registry. Data were collected for all cases of isolated balloon aortic and pulmonary valvuloplasty from 2014 through 2017. Patients were excluded if they were aged <1 month, were inpatient at the time of the procedure, or had significant comorbidities, such as Williams or Noonan syndrome. Criteria for TS were developed and categorized (optimal, satisfactory, and unsatisfactory) by expert consensus based on previous outcome research. Adverse events (AE) were categorized by severity (level 1-5) using established criteria. Level 4 and 5 severity AE were considered high-severity AE. Using criteria of TS and AE severity, PP was divided into 3 composite outcome classes. Factors correlating with class III (suboptimal) PP were analyzed. Results: There were 169 cases of aortic and 270 cases of pulmonary valvuloplasty in the cohorts. In the aortic valvuloplasty cohort, a suboptimal PP (class III) occurred in 14% of cases, mostly due to high-severity AE (7%). No significant correlation between patient or case characteristics and PP was demonstrated. In the pulmonary valvuloplasty cohort, class III PP occurred in 9% of cases, predominantly due to residual valve gradient, which correlated with lower weight (P = .02). Conclusions: We designed a composite variable of PP consisting of TS and safety as a comprehensive measure of outcome. Incorporating both TS and AE may better reflect patient outcome than each metric measured separately. PP indices may identify areas for further investigation and quality improvement.