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As health care consumes a growing share of GDP, the demand for better evidence regarding the effects of health care treatments and how these vary across individuals is increasing. Estimating this with observational data is difficult given the endogeneity of treatment decisions. But because the random assignment clinical trials (RACTs) used in the FDA approval process only estimate average health effects and do not consider spending, there is no good alternative. In this study we use administrative data from California's Medicaid program to estimate the impact of HIV antiretroviral treatments (ARVs). We use data on health care utilization to proxy for health status and exploit the rapid takeup of ARVs following their FDA approval. Our estimate of a 68 percent average mortality rate reduction is in line with the results from RACTs. We also find that the ARVs lowered short-term health care spending by reducing expenditures on other categories of medical care. Combining these two effects we estimate the cost per life year saved at $19,000. Our results suggest an alternative method for estimating the real-world effects of new treatments that is especially well-suited to those treatments that diffuse rapidly following their approval. [ABSTRACT FROM AUTHOR]

Objective: To report our recent experience with prenatal detection of significant cardiovascular malformations (CVMs) in Nevada's state-wide maternal population receiving prenatal care., Methods: We queried our databases for those with significant CVMs diagnosed pre- or postnatally between May 1, 2021, and April 30, 2024. We defined CVMs as those that required, would have required, or will likely require a therapeutic procedure in the first 12 months. Additionally, we included those with atrioventricular and ventriculoarterial discordance and left isomeric situs, both unaccompanied by additional CVMs, and congenital complete heart block. We defined routine prenatal care as obstetric care, which included at least one fetal anatomical survey ultrasound., Results: We identified 390 cases of significant CVMs. Of the 390 cases, 359 (92%) had prenatal care over the three-year observation period, with prenatal detection rates for the three 12-month intervals: 76% (87/115), 87% (94/108), and 95% (129/136) respectively (p < 0.001 by chi-square). A total of 310 prenatal diagnoses were made from comprehensive fetal echocardiograms performed on 8397 pregnant women at maternal-fetal-medicine centers., Conclusion: To our knowledge, these results represent the highest prenatal detection rate for significant CVMs, in a state-wide maternal population in the United States., (© 2025 John Wiley & Sons Ltd.)

Importance: Chronic absenteeism among kindergarten through grade 12 students has increased considerably after the COVID-19 pandemic., Objective: To examine the association between virtual learning during the 2020-2021 school year and chronic absenteeism during the 2021-2022 school year at the school district level., Design, Setting, and Participants: This cross-sectional study used a panel of 11 017 school districts throughout the US comprising kindergarten through grade 12 for the 2018-2019 and 2021-2022 school years., Exposures: The key covariates were the percentage of hybrid and virtual school days in the previous school year, with an assumption that these values in the 2018-2019 school year were zero., Main Outcome and Measures: Chronic absenteeism rates at the district level, which were regressed on the percentage of school days in a learning mode in the previous school year, demographic characteristic and socioeconomic status controls, plus district and year fixed effects. Observations were weighted by district enrollment, and SEs were clustered at the district level., Results: The dataset includes 11 017 school districts for 2 years and 22 034 observations. Chronic absenteeism rates increased by 13.5 percentage points, from a mean (SD) of 15.9% (8.1%) in the 2018-2019 school year to 29.4% (13.2%) in the 2021-2022 school year. Students whose schools had 100% virtual instruction during the COVID-19 pandemic had chronic absenteeism rates that were 6.9 percentage points (95% CI, 4.8-8.9 percentage points) higher than those that were 100% in person. Hybrid instruction was not associated with increased absenteeism. The association between virtual learning and chronic absenteeism varied by socioeconomic status, with the conditional correlation much larger for at-risk students; chronic absenteeism rates were 10.6 percentage points (95% CI, 7.2-14.1 percentage points) higher among students with 100% of days in virtual learning from districts in the top quintile of poverty rates compared with 100% in-persion districts., Conclusions and Relevance: In this cross-sectional study, chronic absenteeism rates were substantially higher in school districts that used virtual learning during the COVID-19 pandemic compared with in person. Understanding how to reduce chronic absenteeism and use virtual learning without potentially negative consequences are key policy questions moving forward.

Background: Optimal pharmacological therapy for pulmonary arterial hypertension (PAH) remains unclear, as pathophysiological heterogeneity may affect therapeutic outcomes. A ranking methodology based on pulmonary vascular genetic expression analysis could assist in medication selection and potentially lead to improved prognosis., Objective: To describe a bioinformatics approach for ranking currently approved pulmonary arterial antihypertensive agents based on gene expression data derived from percutaneous endoarterial biopsies in an animal model of pulmonary hypertension., Methods: We created a chronic PAH model in Micro Yucatan female swine by surgical anastomosis of the left pulmonary artery to the descending aorta. A baseline catheterization, angiography and pulmonary endoarterial biopsy were performed. We obtained pulmonary vascular biopsy samples by passing a biopsy catheter through a long 8 French sheath, introduced via the carotid artery, into 2- to 3-mm peripheral pulmonary arteries. Serial procedures were performed on days 7, 21, 60, and 180 after surgical anastomosis. RNA microarray studies were performed on the biopsy samples., Results: Utilizing the medical literature, we developed a list of PAH therapeutic agents, along with a tabulation of genes affected by these agents. The effect on gene expression from pharmacogenomic interactions was used to rank PAH medications at each time point. The ranking process allowed the identification of a theoretical optimum three-medication regimen., Conclusion: We describe a new potential paradigm in the therapy for PAH, which would include endoarterial biopsy, molecular analysis and tailored pharmacological therapy for patients with PAH., Competing Interests: David Mann is the CEO of Vascular Biosciences (VBS). Roy Williams is an employee and warrant holder of VBS, and Jose Nunez and Reinhardt Tarmidi are employees of VBS. All other authors have nothing to declare., (© 2023 Rothman et al.)

We reviewed patients with chromosome 22q11.2 deletion syndrome. We analyzed cardiovascular findings in patients with confirmed chromosome 22q11.2 deletion syndrome live-born in Nevada between March 2007 and September 2020. We identified 60 patients. Of the 60 patients, 32 (53%) were female. Of the 60, 48 (80%) had a conotruncal abnormality (including isolated vascular rings): 23 of 32 (72%) for females versus 25 of 28 (89%) for males, P = .41. However, 11 (34%) of 32 females had a right aortic arch; whereas, 21 (75%) of 28 males had a right aortic arch, P = .007. In conclusion, in our patient cohort, we found conotruncal malformations were common. However, we noted males were statistically more likely to have a right aortic arch than females. To the best of our knowledge, this male-female aortic arch laterality difference in patients with chromosome 22q11.2 deletion syndrome has not been previously noted.

Objective: We reviewed our experience with transvenous liver biopsy-derived hepatic fibrosis scores and possible associated risk factors in those postextracardiac Fontan patients. Methods: We identified extracardiac-Fontan patients with postoperative durations <20 years who underwent cardiac catheterizations with transvenous hepatic biopsies between April 2012 and July 2022. If a patient underwent two liver biopsies, we averaged the two total fibrosis scores and concurrent time, pressure, and oxygen saturation data. We grouped patients by the following factors: (1) sex , (2) venovenous collaterals, and (3) type of functionally univentricular heart. We identified potential hepatic fibrosis risk factors as the following: female, presence of venovenous collaterals, and a functional univentricle of right-ventricular type. For statistical analysis, we used Kruskal-Wallis nonparametric testing. Results: We identified 127 patients who underwent 165 transvenous biopsies, with 38 patients undergoing 2 biopsies. We found that females with two additional risk factors had the highest median total fibrosis scores, 4 (1-8); males with <2 risk factors had the lowest median total fibrosis scores, 2 (0-5); and females with <2 additional risk factors and males with two risk factors were in the middle, median total fibrosis score 3 (0-6), P =.002; and there were no statistical differences for the other demographic or hemodynamic variables. Conclusions: For extracardiac-Fontan patients with similar demographic and hemodynamic variables, identifiable risk factors are associated with the degree of hepatic fibrosis.

Background: Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications., Objectives: This study aimed to assess whether the homing peptide CAR (CARSKNKDC) improves the vasodilatory selectivity of fasudil in the pulmonary circulation or systemic circulation in a porcine pulmonary hypertension model., Materials and Methods: Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19.9 kg, mean age 4.3 months). Fasudil (0.3 mg/kg) was administered without and with CAR (1.5 mg/kg), and the effect on aortic (Ao) and right ventricular (RV) pressure was recorded with indwelling catheters., Results: Immediately after fasudil administration, there was a decrease in Ao pressure followed by prompt recovery to baseline. The RV pressure decrease was progressive and sustained. Fasudil alone resulted in a 12% decrease in RV pressure, whereas co-administration of CAR with fasudil resulted in a 22% decrease in RV pressure (p < 0.0001). Fasudil alone caused an average decrease of 34% in the RV/Ao pressure ratio, and fasudil + CAR caused an average decrease of 40% in the RV/Ao pressure ratio (p < 0.0001)., Conclusion: The homing peptide CAR selectively enhanced the acute vasodilatory effects of fasudil on the pulmonary vascular bed in a porcine experimental model of pulmonary hypertension., Competing Interests: All authors, except David Mann, declared no conflicts of interest with respect to the research, authorship, and/or publication of this article. David Mann is a shareholder, patent holder, and employee of Vascular Biosciences., (© 2023 Rothman et al.)

We analyzed patients with isolated, balanced complete atrioventricular septal defects. We identified 71 patients born in Nevada, between January 2008 and December 2020. We also analyzed prenatal detection rates. Of the 71, 61 (85%) had trisomy 21, 1 (1%) had CHARGE syndrome and 22q.11 deletion, and 10 (14%) had no chromosomal abnormalities. Of the 71, 67 had prenatal care, and 43/67 (64%) were prenatally diagnosed. Prenatal detection rate for 2008-2012 was 9/20 (45%) and 18/21 (86%) for 2018-2020, P = .03. Of the 71, 67 underwent surgical repair with 1 current postpulmonary artery banding and 0 surgical deaths. Of the 67, 3 (4%) had heart block. Only 1 (1.5%) patient had reoperation for a mitral valve replacement. Of the 71, 67 (94%) are alive during a 6-year average (range = 0-12 years) follow-up. In conclusion, surgical and long-term outcomes were excellent. Also, high state-wide, general population prenatal detection rates were achieved.

We examine the impact of the US drug crisis on children's living arrangements. Because factors that lead to drug use could also alter family structure, we instrument for the intensity of the drug crisis with cross-state exposure to marketing of the prescription opioid at the epicenter of the crisis. We find that the crisis increased the likelihood that a child lives away from a parent or in a household headed by a grandparent. Our results suggest that if drug use had remained at 1996 levels, 1.5 million fewer children aged 0-16 would have lived away from a parent in 2015., (Copyright © 2022. Published by Elsevier B.V.)

Objective: We investigated the prevalence of isolated vascular rings in the general population of Southern Nevada., Methods: We identified those prenatally and postnatally diagnosed with an isolated vascular ring between January 2014 and December 2021. We included only those with vascular or ligamentous structures completely encircling the trachea and esophagus. To investigate the prevalence of isolated vascular rings, we included only those with situs solitus, levocardia, and no significant intracardiac malformations., Results: We identified 112 patients. Of the 112, 66 (59%) were female. There were approximately 211,000 total live births in Southern Nevada for the study period, for an overall prevalence of 5.3 isolated vascular rings per 10 000 live births. However, for the years 2014 to 2017, the average prevalence figure was 3.5 per 10 000 live births, and for the years 2018 to 2021, the average prevalence figure was 7.1 (range 6.5-8.0) per 10 000 live births. Simultaneously, the prenatal detection rate rose from 66% to 86%., Conclusions: Isolated vascular rings are common cardiovascular malformations. As prenatal detection rates in the Southern Nevada general population approach 90%, the prevalence figures for isolated vascular rings appear to asymptote at about 7 per 10 000 live births.

Objective: We investigated the relationship between prenatal detection of significant congenital heart disease and elective termination of pregnancy over time in Nevada., Methods: We identified those prenatally or post-natally diagnosed with significant congenital cardiovascular malformations in Nevada with birth dates or estimated delivery dates between July 2012 and June 2021., Results: We identified 1246. Of 1246, 69 underwent fetal demise, 42 had elective termination, and 1135 were live-born. Of the 1135 live-born, 1090 had prenatal care, of which 718 (66%) overall had a prenatal diagnosis of significant congenital heart disease. However, prenatal detection statistically significantly increased over time from 45 to 82%, p  = .00001. Termination of pregnancy averaged 10% of those identified within the legal timeframe, and the rate did not statistically significantly increase with increasing prenatal detection rates, p  = .56. Of the 42 undergoing elective termination, 23 (55%) had syndromes or comorbidities vs. 280 (25%) of the 1135 live-births, p = .0003., Conclusions: In Nevada, despite a statistically significant increase in prenatal detection of significant congenital heart disease over time, termination of pregnancy rates did not increase. Nevertheless, those undergoing elective termination were more likely to have associated syndromes or comorbidities.

Objective: We retrospectively analyzed our center's experience with the prenatal diagnosis of isolated perimembranous ventricular septal defects that underwent primary surgical repair in infancy., Methods: We identified patients born in Southern Nevada, between October 2012 and October 2020, with prenatal care that underwent surgical closure of an isolated large perimembranous ventricular septal defect between 1 and 12 months of age. The description at surgery defined ventricular septal defect morphology. We included only those with situs solitus, levocardia without dextroposition, and without any other cardiovascular abnormality. We analyzed prenatal detection rates for each of the eight years., Results: We identified 81 patients. Of the 81, 35 (43%) had trisomy 21. We identified no other aneuploidies in those that underwent surgical repair; however, 1 had a 15q13.3 deletion syndrome, and 1 had a 22 q11.2 deletion syndrome. Of the 81, 27 (33%) overall were prenatally diagnosed. Increasing prenatal detection rates strongly correlated with time ( R  = 0.92, p  = .002)., Conclusions: Trisomy 21 is common in isolated perimembranous ventricular septal defects undergoing primary repair in infancy. Further, prenatal detection rates significantly improved over time, up to 65% detection in the current years.

A 12-year-old with a history of critical pulmonary stenosis and moderate right ventricular hypoplasia underwent neonatal pulmonary valve dilation, an aortopulmonary shunt, and an infant cavopulmonary anastomosis with aortopulmonary shunt takedown. During a diagnostic cardiac catheterization at 12 years of age, angiography showed interruption in the midportion of the coronary sinus, which required no intervention.

Objective: We reviewed our center's experience with neonatal and infant hypoplastic aortic arch, unassociated with intracardiac malformations, and investigated changes in prenatal detection rates over time for those requiring therapeutic procedures., Methods: We identified all prenatal diagnoses of hypoplastic aortic arch with situs solitus, unassociated with intracardiac malformations, made in Nevada between May 2017 and April 2022. In addition, we identified all those 0-180 days old, with prenatal care, that underwent a surgical or interventional cardiac catheterization aortic arch procedure, whether prenatally or postnatally diagnosed. We excluded those with ventricular septal defects, functionally univentricular hearts, interrupted aortic arches, or any associated malformation requiring an additional surgical or interventional procedure ≤6 months old. Additionally, we calculated prenatal detection rates for those undergoing a surgical or interventional catheterization procedure for each of the 5 years., Results: We identified 107 patients prenatally and postnatally. Of the 107 patients, 56 (34 prenatally diagnosed and 22 postnatally diagnosed) underwent an aortic arch procedure, and 51 additionally prenatally diagnosed, live-born infants did not undergo a procedure. Of the 56 procedures, 2 were by interventional catheterization, and 54 underwent a surgical repair. Prenatal detection for those undergoing a procedure statistically significantly increased over the 5 years from 38% to 82%, rho = 0.95 (p = .04)., Conclusions: Currently in Nevada, our prenatal detection rate is >80% in the general population for those between 0 and 6 months old who require a therapeutic procedure for aortic arch obstruction without intracardiac malformations., (© 2022 Wiley Periodicals LLC.)

Objective: We investigated possible gender differences for hepatic fibrosis in extracardiac-Fontan patients., Methods: We identified extracardiac Fontan, performed between 2000 and 2016, who underwent cardiac catheterizations with transvenous hepatic biopsies between April 2012 and June 2022. We divided the patients by gender for analysis., Results: We identified 116 patients who underwent 145 transvenous biopsies, with 29 patients undergoing 2 biopsies at an average interval of 5 ± 1 years. We divided the 145 biopsies into two groups: 1) 98/145 (68%) males and 2) 47/145 (32%) females. For the 47 female liver biopsy specimens, the median total fibrosis score was 3 (0-8), and for the 98 male liver biopsy specimens, the median total fibrosis score was 2 (0-6), p = .007. The average age at surgery for females was 3 ± 1 years and for males 3 ± 1 years, p = .99. Average Fontan duration at biopsy for females was 11 ± 5 years and for males, 10 ± 4 years, p = .23. No other demographic, anatomic, echocardiographic, laboratory, or hemodynamic findings demonstrated statistically significant gender differences., Conclusions: Females had statistically significantly higher median total fibrosis scores than males for the similar average age at extracardiac Fontan and average Fontan duration., (© 2022 Wiley Periodicals LLC.)

Objective: We reviewed our center's surgical mortality rates for those who underwent a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) category 4 or 5 neonatal cardiovascular surgery., Methods: We identified all patients who underwent a STAT category 4 or 5 neonatal index cardiovascular surgical procedure between July 2015 and July 2021., Results: We identified 239 patients. We divided them into two groups: (1) 42 (17.6%) ≤2.5 kg, and (2) 197 (82.4%) were >2.5 kg at the time of neonatal surgery. Of those ≤2.5 kg, 18/42 (42.9%) had syndromes or associated noncardiac malformations versus 34/197 (17.3%) of those >2.5 kg, p = .0093. Thirty-day discharge mortality for those ≤2.5 kg was 3/42 (7.1%) versus l0/197 (5.1%) for those >2.5 kg, p = .83., Conclusions: Weight at the time of surgery, presence of syndromes, and associated noncardiac malformations did not affect mortality in those undergoing complex neonatal STAT 4 or 5 category cardiovascular surgery., (© 2022 Wiley Periodicals LLC.)

Our objective was to review our experience with isomerism associated with univentricular hearts and evaluate the prevalence of pulmonary versus systemic outflow obstruction. We identified those prenatally or postnatally diagnosed, between September 2004 and October 2021, with right and left isomerism and a functionally univentricular heart. We identified 62, 51 prenatally and 11 postnatally. Of the 62, 61 had prenatal care for an 84% (51/61) prenatal detection rate. Of the 62, 36 (58%) had right isomerism. Of the 51 prenatally diagnosed, 36 were live-born, 13 had fetal demise, and two underwent elective termination. Of the total 62, 43 had pulmonary outflow obstruction, 14 had systemic outflow obstruction, three had no outflow obstruction, and two had a common arterial trunk. However, between September 2004 and December 2019, 41 of 52 (79%) had pulmonary outflow obstruction, and between January 2000 and October 2021, 2 of 10 (20%) had pulmonary outflow obstruction (p = 001). We noted a statistically significant temporal change in the prevalence of pulmonary versus systemic outflow obstruction in those with isomeric situs and a functionally univentricular heart. Further, prenatal diagnosis exceeded 80% in the general population of Nevada., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Our objective was to investigate whether a relationship existed between our center's STAT 4 and 5 category surgical mortality and general-population prenatal detection rates in Nevada. Methods: We identified patients who underwent STAT 4 and 5 neonatal index cardiovascular surgeries at our center between October 2012 and September 2021. Additionally, we calculated prenatal detection rates for each of the 9 retrospective study years. We used descriptive statistics and nonparametric testing, including the Spearman Rho correlation ( R ) and the Mann-Whitney U -tests, with a significant P -value set at < .05. Results: We identified 356 patients. We noted a statistically significant increasing trend in prenatal detection percentages (rho = 0.79, P  = .01), concurrent with a statistically significant decreasing trend in surgical mortality (rho = -0.82, P  = .007). Conclusions: Despite encouraging results, we could not establish a cause-and-effect relationship between concurrent decreased surgical mortality and increased prenatal detection rates for patients undergoing STAT 4 and 5 surgical procedures at our center.

Overdose deaths involving opioids have increased dramatically since the 1990s, leading to the worst drug overdose epidemic in U.S. history, but there is limited empirical evidence about the initial causes. In this article, we examine the role of the 1996 introduction and marketing of OxyContin as a potential leading cause of the opioid crisis. We leverage cross-state variation in exposure to OxyContin's introduction due to a state policy that substantially limited the drug's early entry and marketing in select states. Recently unsealed court documents involving Purdue Pharma show that state-based triplicate prescription programs posed a major obstacle to sales of OxyContin and suggest that less marketing was targeted to states with these programs. We find that OxyContin distribution was more than 50% lower in "triplicate states" in the years after the drug's launch. Although triplicate states had higher rates of overdose deaths prior to 1996, this relationship flipped shortly after the launch and triplicate states saw substantially slower growth in overdose deaths, continuing even 20 years after OxyContin's introduction. Our results show that the introduction and marketing of OxyContin explain a substantial share of overdose deaths over the past two decades.

The COVID-19 pandemic in the US has been particularly devastating for nursing home residents. A key question is how have some nursing homes been able to effectively protect their residents, while others have not? Using data on the universe of US nursing homes, we examine whether establishment quality is predictive of COVID-19 mortality. Higher-quality nursing homes, as measured by CMS overall five-star rating, have substantially lower COVID-19 mortality through September of 2020. Quality does not predict the ability to prevent any COVID-19 resident or staff cases, but higher-quality establishments prevent the spread of resident infections conditional on having one. Preventing COVID-19 cases and deaths may come at some cost, as high-quality homes have substantially higher non-COVID deaths. The positive correlation between establishment quality and non-COVID mortality is strong enough that high-quality homes also have more total deaths than their low-quality counterparts and this relationship has grown with time. As of late April 2021, five-star homes have experienced 8.4 percent more total deaths than one-star homes., (Copyright © 2022. Published by Elsevier B.V.)

Objective: We reviewed our center's experience with prenatal detection in Nevada's general population for young infants undergoing cardiovascular surgery., Methods: We identified patients born in Nevada that underwent an initial cardiovascular surgery between 0 and 6 months old with birth dates between August 2012 and July 2021. Additionally, we calculated prenatal congenital cardiovascular malformation detection rates for each of the 9 years., Results: We identified 660 patients. For the 660 patients, 649 (98%) mothers underwent prenatal care, which included at least one anatomical-survey obstetric ultrasound. Of the 649 with prenatal care, 395 (61%) had a prenatal diagnosis overall. However, prenatal diagnosis improved over the 9 years from 44% in 2012 to 79% in 2021 (correlation coefficient of 0.93, p = .00024)., Conclusions: Our results demonstrated a progressive rise in prenatal detection rates for young infants undergoing cardiovascular surgery in Nevada., (© 2021 Wiley Periodicals LLC.)

Objective: We reviewed our center's experience with common arterial trunk., Methods: We included those with common arterial trunk in Nevada with estimated delivery dates or birth dates between June 2006 and May 2021. We excluded patients with functionally univentricular hearts., Results: We identified a total of 39: 32 prenatally and 7 postnatally. Of the 32 prenatally detected, 2 had elective termination, 2 had fetal demise, and 28 were live-born. Of the 7 postnatally diagnosed, 6 had prenatal care without a fetal echocardiogram, and 1 had no prenatal care. Overall, live-born prenatal detection was 28/34 (82%). Prenatal detection for 2006-2009 was 2/6 (33%) and for 2010-2021 was 26/28 (93%) p = .049. Of the 35 live-born infants, 1 died preoperatively, and 34 underwent neonatal surgery. Of the 34, 8 had palliation (birth weight 1.9±0.7 kg, range 0.8-2.6 kg), and 26 had a primary repair (birth weight 3.0±0.3 kg, range 2.6-4.0 kg) p = .0004. For all 34 neonatal surgical procedures, there were 2 (5.9%) deaths; however, there were no subsequent surgical or interventional catheterization mortalities., Conclusions: In Nevada, current state-wide, general population prenatal detection of the common arterial trunk was more than 90%. By employing a combination of neonatal palliation and primary repair, surgical mortality was less than 6% in a cohort that included those with birth weights less than 2.5 kg, truncal valve surgery, and interrupted aortic arches., (© 2021 Wiley Periodicals LLC.)

Objective: We reviewed our center's prenatal detection and surgical experience with high-risk, 2-ventricle patients, with complex congenital heart disease that underwent stage-1 hybrid palliation., Methods: We retrospectively identified those born between March 2008 and March 2021 with 2-ventricle hearts, complex congenital cardiovascular malformations, and ductal-dependent systemic circulation that underwent stage-1 hybrid palliation consisting of surgical bilateral pulmonary artery banding and interventional catheterization placed ductus arteriosus stents., Results: We identified 30 patients. Of the 30, 19 (63%) were male. For the 30, median gestational age was 35 weeks (29-39 weeks), and median birth weight was 2.2 kg (0.6-4.5 kg). Of the 30, 1 was transferred from an adjacent state, and 29 were born in Nevada. Of the 29 born in Nevada, overall statewide prenatal detection was 18 of 29 (62%); however, for 2008 to 2011 the prenatal detection rate was 3 of 10 (30%) and 15 of 19 (79%) for 2012 to 2021, P  = .03. For the last 5 years, prenatal detection for Nevada-born patients was 8 of 8 (100%). Two full-term newborns, without a prenatal diagnosis, presented postnatally in extremis. For the 30 patients, there were 0 stage-1 hybrid palliation mortalities, 1 subsequent repair mortality, and 3 late nonsurgical deaths., Conclusions: Stage-1 hybrid palliation may result in excellent surgical outcomes for high-risk, 2-ventricle patients. Additionally, high rates of population-wide prenatal detection are possible for high-risk congenital heart disease, allowing prenatal planning and possibly reducing postnatal extremis presentations.

We report a newborn with truncus arteriosus and a very unusual variant of "crossed" pulmonary arteries. The left pulmonary artery arose anterior and slightly to the right side of the common trunk and the right pulmonary artery arose from the posterior and left side of the common trunk. Computed tomographic images and a diagram are provided., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Pediatric Cardiology.)

The 2020 US mortality totaled 2.8 million after early March, which is 17.3% higher than age-population-weighted mortality over the same time interval in 2017 to 2019, for a total excess death count of 413,592. We use data on weekly death counts by cause, as well as life tables, to quantify excess mortality and life years lost from both COVID-19 and non-COVID-19 causes by race/ethnicity, age, and gender/sex. Excess mortality from non-COVID-19 causes is substantial and much more heavily concentrated among males and minorities, especially Black, non-Hispanic males, than COVID-19 deaths. Thirty-four percent of the excess life years lost for males is from non-COVID-19 causes. While minorities represent 36% of COVID-19 deaths, they represent 70% of non-COVID-19 related excess deaths and 58% of non-COVID-19 excess life years lost. Black, non-Hispanic males represent only 6.9% of the population, but they are responsible for 8.9% of COVID-19 deaths and 28% of 2020 excess deaths from non-COVID-19 causes. For this group, nearly half of the excess life years lost in 2020 are due to non-COVID-19 causes., Competing Interests: The authors declare no competing interest.

We examine the impact of early state and local COVID-19 policies to encourage social distancing. Outcomes are daily foot traffic at establishments spanning ten key industries, across which transmission risk varies substantially. Policies include state of emergency declarations, blunt general restrictions such as stay-at-home (SAH) orders, and targeted rules such as restrictions on bars, restaurants, entertainment venues, and schools. Exploiting variation in the timing of policies in difference-in-difference models, we show that much of the decline in foot traffic early in the pandemic was due to private precautionary behavior. SAH orders explain almost none of the foot traffic decline in industries with high risk of virus transmission, but they do explain a substantial share of the decline in moderate- to low-risk industries such as outdoor sports and visits to parks. Targeted restrictions tend to impact intended industries, as well as complementary ones. We show that the impact of targeted restrictions is largest in counties with no SAH restrictions, suggesting that better targeting of public restrictions can have important efficiency gains., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: We investigated a relationship between a composite index comprised of Fontan-circuit anatomical features and hepatic fibrosis scores from biopsy., Methods: We identified living extracardiac Fontan patients, ≥7 years old and ≥5 but <20 years postoperative, that underwent cardiac catheterization and transvenous liver biopsy between March 2012 and September 2020. We divided patients into anatomical groups and applied a risk score to each patient. We compared average anatomical risk scores with average hepatic total fibrosis scores by group., Results: We identified 111 patients that met inclusion criteria. After excluding four patients, we assigned 107 to one of 12 anatomical variant groups (n ≥ 3). For the 107, the average age at liver biopsy was 14 ± 6 years old. Of the 107, 105 (98%) were New York Heart Association Class 1. We found average anatomical risk scores by group correlated with average total fibrosis scores by group (R = 0.8; p = .005). An average Fontan duration to biopsy of 10 ± 1 years was similar for all 12 anatomical groups. We found no other clinical variables, laboratory, or hemodynamic values that trended with anatomical risk scores or hepatic total fibrosis scores., Conclusions: In a cohort of relatively young, stable extracardiac Fontan patients, average composite anatomical risk scores strongly correlated with average hepatic total fibrosis scores by anatomical group. These findings suggest that some anatomical variants in extracardiac Fontan patients are associated with higher Fontan-associated liver disease (FALD)-related hepatic total fibrosis scores than others, despite similar Fontan durations., (© 2021 Wiley Periodicals LLC.)

Objective: We reviewed our center's isolated vascular ring data., Methods: Inclusion criteria were patients born in Nevada between June 2015 and July 2020 with situs solitus, levocardia, atrioventricular and ventriculoarterial concordance, and no significant intracardiac malformations., Results: We identified 95 patients. Of the 95, 56 (59%) were female (p = .033). For the study period, there were approximately 180,000 live births, for a prevalence of 5.3 isolated vascular rings per 10,000 live births. Of the 95, 78 (82%) were prenatally diagnosed. Of the 95, 63 (66%) were products of high-risk pregnancies (p = .0001). Additionally, we found advanced maternal age was an isolated vascular ring risk factor (relative risk ratio, 2.7; 95% confidence interval, 1.8, 4.1; p < .00001)., Conclusions: Isolated vascular rings are relatively common cardiovascular malformations and more common in females. High prenatal detection rates are achievable. Further, the majority with isolated vascular rings are products of high-risk pregnancies, and advanced maternal age is a statistically significant occurrence risk factor., (© 2021 Wiley Periodicals LLC.)

Objective: We hypothesized that a relationship between post-Fontan hepatic fibrosis and anatomical variants might exist., Methods: Attempting to limit confounding variables, we analyzed data from living, stable, post-extracardiac Fontan patients who underwent cardiac catheterization and transvenous hepatic biopsy procedures between March 2012 and June 2020., Results: We identified 120 patients who met the inclusion criteria. Of the 120, 35 (29%) had pulmonary artery stents. For the 35 with pulmonary artery stents, the average total fibrosis score was 3.2 ± 1.9 and the fibrosis progression rate was 0.36 ± 0.33, and for those with no pulmonary artery stents, the total fibrosis score was 2.6 ± 1.8 and the fibrosis progression rate was 0.27 ± 0.33 ( P = .13 and P = .11, respectively). Of the 120, 65 had functional univentricles of right ventricular type. Of these 65, 27 had pulmonary artery stents. For the 27 with pulmonary artery stents, the average total fibrosis score was 3.4 ± 1.8 and the average fibrosis progression rate was 0.39 ± 0.30, and for the 38 without pulmonary artery stents, the average fibrosis score was 2.3 ± 1.5 and the average fibrosis progression rate was 0.23 ± 0.21 ( P = .01 for comparison of both values)., Conclusions: This study's findings suggest that a post-extracardiac Fontan with a functional univentricle of right ventricular type plus a pulmonary artery stent may have more advanced liver pathology than those without a pulmonary artery stent at similar Fontan duration years and ages at liver biopsy.

Objective: We hypothesized that a relationship might exist between angiographically demonstrable, post-Fontan venovenous collaterals, and hepatic fibrosis., Methods: We analyzed data from post-Fontan patients that underwent cardiac catheterization and transvenous-hepatic biopsy procedures between March 2012 and March 2020. From innominate vein angiography, we determined those that either had or lacked venovenous collaterals. Additionally, we examined data from post-Fontan patients that underwent hepatic ultrasound, shear-wave elastography between January 2017 and March 2020., Results: We identified 164 patients that met inclusion criteria. Of the 164, 101 (62%) had venovenous collaterals. Of the 101 with collaterals, average total fibrosis score (TFS) was 3.2 and the average rate of fibrosis progression was 0.28 vs an average TFS of 2.1 and an average fibrosis progression rate of 0.22 for those without collaterals (P = .00001 and P = .01, respectively). Of the 101 with collaterals, oxygen saturation was 91% ± 4% vs 93% ± 3% (P = .048) without collaterals. Of the 164, 86 (52%) underwent ultrasound shear-wave elastography. Of the 86 patients undergoing elastography, 50 (58%) were performed in those with collaterals, and 36 (42%) in those without collaterals. For the 50 with collaterals, average elastography values were 13.3 vs 11.2 kPa for the 36 without collaterals (P = .006). We found no statistically significant differences for age at biopsy, Fontan duration, Fontan-type, type of functional univentricle, laboratory, clinical, or hemodynamic values between those with or without collaterals., Conclusions: The presence of angiographically demonstrated venovenous collaterals was associated with statistically, significantly more advanced liver fibrosis than those without collaterals., (© 2020 Wiley Periodicals LLC.)

A 57-year-old man, with a history of coarctation patch repair at three years of age, presented with left ventricular dilatation and moderate to severe dysfunction. A computed tomographic angiogram of the chest revealed moderate residual stenosis of the distal arch and proximal descending aorta and a large aneurysm adjacent to the origin of the left subclavian artery. Due to high surgical risk, a hybrid approach was undertaken with temporary balloon occlusion of the left subclavian artery, followed by surgical left common carotid to left subclavian artery graft and percutaneous covered stent implantation to relieve the obstruction and exclude the aneurysm.

This investigation analyzed the rate of hepatic fibrosis progression in post-Fontan patients that underwent hepatic biopsy. The study cohort comprised post-Fontan patients that underwent cardiac catheterization and transvenous liver biopsy between March 2012 and September 2019. We identified 126 patients that met inclusion criteria. Of the 126, 27 (21%) had a lateral tunnel Fontan, and 99 (79%) had an extracardiac Fontan. For the 27 lateral tunnel Fontan patients, age at Fontan was 4 ± 2 years, and for the 99 extracardiac Fontan patients age at Fontan was 4 ± 2 years (p = 0.98). For the 27 lateral tunnel Fontan patients, the average total fibrosis score was 3.0 ± 1.5; and for the 99 extracardiac Fontan patients, the average total fibrosis was 2.7 ± 1.7 (p = 0.48). For the lateral tunnel Fontan patients, the average Fontan duration was 20 ± 6 years; and for the 99 extracardiac Fontan patients, the average Fontan duration was 11 ± 5 years (p < 0.001). For the 27 lateral tunnel Fontan patients, the average rate of fibrosis progression was 0.16 ± 0.10 total fibrosis score/year; and for the 99 extracardiac Fontan patients, the average rate of fibrosis progression was 0.30 ± 0.23 total fibrosis score/year (p < 0.001). In conclusion, our findings suggest that those with extracardiac Fontans have a faster rate of hepatic fibrosis progression than those with lateral tunnel Fontans. More extensive or multi-institutional studies will be needed to confirm these findings and define the clinical significance of discrepant rates of hepatic fibrosis in post-Fontan patients.

Selexipag is an oral prostacyclin receptor agonist; it was recently approved for use in adults with pulmonary arterial hypertension. The safety and efficacy of selexipag has not yet been determined in the pediatric population. We describe short-term hemodynamic and clinical data with selexipag therapy in four pediatric patients with pulmonary hypertension. We reviewed clinical, echocardiographic, and hemodynamic data. One patient was transitioned from subcutaneous treprostinil to selexipag, and in three patients, selexipag was added as a third agent. Drug dosing was attained empirically based on patient body size. A follow-up catheterization was performed 12-18 months after initiation of selexipag therapy. All four patients tolerated selexipag well, without significant side effects. One patient transitioned successfully from subcutaneous treprostinil to selexipag. None of the four patients had clinical deterioration. In three patients who were able to perform a 6-minute walk test, pre and post selexipag distances were 350 and 400, 409 and 390, and 300 and 360 m, respectively. Echocardiograms showed no significant changes. Catheterization showed a variable change in pulmonary vascular resistance (small decrease in three patients and increase in one patient). Brain natriuretic peptide levels before and after selexipag in the four patients were 38 and 49, 33 and 54, 29 and 25, and 12 and 14 pg/mL, respectively. Selexipag use for 16-28 months was safe in four pediatric patients; none of them had clinical deterioration. Larger number of patients and longer follow-up intervals are necessary before further recommendations can be made., (© The Author(s) 2020.)

Background: Premature infants often require long-term indwelling intravascular catheters. Occasionally, catheters fracture and migrate into cardiovascular structures, risking perforation, infection, thrombosis, and interference with cardiac and valve function. This case series describes our experience with percutaneous retrieval of broken intravascular catheters., Methods: A gooseneck micro-snare was used to retrieve fractured catheters in four premature infants, weighing between 840 and 1930 grams., Results: All procedures were successful without complications., Conclusions: Gooseneck-snare retrieval of broken indwelling intravascular catheters can be performed safely and successfully in premature infants even those that weigh less than 1000 grams.

Objective: Our objective was to evaluate the incidence of a persistent right umbilical vein in isomerism versus situs solitus., Methods: For this retrospective, observational, nonrandomized report, we identified fetuses with confirmed right umbilical veins from all patients referred for fetal echocardiography in Southern Nevada between January 2006 and January 2019., Results: For the period January 2006 to January 2019, we identified 89 fetuses with situs solitus and a right umbilical vein from 16 320 women undergoing prenatal cardiac evaluation, resulting in a right umbilical vein incidence of 0.5% in situs solitus. For the same period, we identified 36 fetuses with isomerism and confirmatory umbilical vein imaging. Of the 36, 15 (42%) had right umbilical veins. Of the 15, four of 11 (19%) had left isomerism, and 11 of 15 (73%) had right isomerism (P = .006)., Conclusions: A right umbilical vein is rare with situs solitus and common with isomerism. A right umbilical vein is more common in right isomerism than left isomerism and should alert the clinician to check for isomeric situs, especially right isomerism., (© 2019 John Wiley & Sons, Ltd.)

Background: We reviewed data on patients born with critical congenital heart disease in the state of Nevada and analyzed detection via prenatal diagnosis versus newborn pulse oximetry screening, location of birth, and gestational age at birth., Methods: We inquired our databases and electronic health records for all patients with critical congenital heart disease born in Nevada between January 2016 and May 2019., Results: We identified 218 live born patients. Of the 218, average gestational age was 38 weeks (±2.2 weeks). Of the 218, 171 (78%) were prenatally diagnosed, 37 (17%) were diagnosed by immediate postnatal signs and symptoms, 8 (4%) had false-negative pulse oximetry screens that resulted in post-hospital discharge presentations, and 2 (1%) had positive pulse oximetry screens. The eight post-hospital discharge presentations included four in extremis, two with extreme cyanosis, and two dying at home. Of the 171 prenatally diagnosed patients, 157 (92%) were born at the Nevada hospital with the congenital cardiac unit., Conclusion: To the best of our knowledge, our results represent the highest statewide, general population prenatal detection of critical congenital heart disease in the United States. Our high prenatal detection rate led to the majority of patients being born at the Nevada facility with the congenital heart unit, limiting intrastate neonatal transports. On average, patients were born at term. Further, in Nevada, state-mandated, universal pulse oximetry screening resulted in more false-negative results than positive results.

Objectives. To determine what role the 88 000 Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) vouchers for permanent supportive housing among US veterans distributed between 2008 and 2017 played in the significant fall in veterans' homelessness over the same time period. Methods. Using a panel data set at the Continuum of Care level over the 2007 to 2017 period, we correlated changes in vouchers with permanent supportive housing units and measures of homelessness. To reduce concerns about omitted variables bias, we used a 2-stage least-squares procedure. The instrument is a Bartik-type shift-share variable. Specifically, for the cumulative vouchers received at the local level, we used the share of the nation's homeless veterans from the local level in the year before the HUD-VASH program multiplied by the cumulative number of vouchers distributed at the national level up to that point. Results. For each additional voucher, permanent supportive housing units increased by 0.9 and the number of homeless veterans decreased by 1. Conclusions. Our results indicate the HUD-VASH program worked as intended and veterans' homelessness would have risen substantially over the past decade without the program.

Patients: We reviewed all patients evaluated at our center with situs solitus, levocardia, and a right aortic arch that were born between January 2000 and January 2018., Results: From our databases, we identified 204 patients. We excluded patients with a double aortic arch from analysis. Of the 204 patients, 103 (50%) were male. Of the 204 patients, 95 (47%) had an isolated right aortic arch. Of the 95 with an isolated right aortic arch, 4 (4%) had chromosome 22q11.2 deletion syndrome, and 89 (94%) had a vascular ring. Of the 204 patients, 109 (53%) had a surgical intracardiac malformation. Of the 109, with an associated surgical intracardiac malformation, 38 (35%) had chromosome 22q11.2 deletion syndrome, and 28 (26%) had a vascular ring. Overall, of the 204 patients, 200 (98%) had a vascular ring, an associated intracardiac malformation, or both. Prenatal detection was 85% (40/47) for the subset of patients born in Southern Nevada between January 2015 and January 2018., Conclusion: this review, to best of our knowledge, reports one of largest series of right aortic arches in the literature. Data from our cohort demonstrates that a right aortic arch in situs solitus is almost always associated with pathology. Further, our center's right aortic arch prenatal detection rate exceeds previous reports., (© 2018 Wiley Periodicals, Inc.)

Objectives: Children with comorbid asthma and obesity present with more severe and harder-to-control disease than asthmatic children at healthy weight. Weight loss has been shown to improve asthma symptoms, yet physical activity may be difficult due to exercise-induced bronchospasm. Children with asthma have lower exercise rates than non-asthmatics. The objective of this study was to retrospectively evaluate attrition rates and program outcome measures (Body Mass Index [BMI] and maximum oxygen consumption [VO 2 max]) among asthmatic and non-asthmatic participants., Study Design: Clinical data were collected from the Healthy Hearts Program, a 12-week nutrition and activity intervention program for children who are overweight, obese, or at risk for heart disease and other conditions, and used for the study., Methods: Intervention data and demographics were obtained from medical records at the Children's Heart Center Nevada. Descriptive statistics, paired t-tests, Cox regression analysis, and analysis of covariance were conducted., Results: The mean age of this population (N = 232) was 11 years; 54% were male, 64% were Hispanic, and 37% had asthma. Median time in the program was 9 weeks, and 58% of the population completed the program. Unadjusted analyses showed significant BMI decreases in asthmatic (P = 0.002) and non-asthmatic (P = 0.001) participants and increases in cardiorespiratory function for asthmatic males and females (P = 0.003, P = 0.004) and non-asthmatic males and females (P < 0.001 for both). Asthmatic and non-asthmatic children both had improved exercise intensity (P = 0.033, P < 0.001)., Conclusions: This program is both beneficial and practical for obese children with asthma for losing weight and improving cardiorespiratory function., (Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: We hypothesized that clinic-based, hepatic-ultrasound, elastography measurements, either alone or in combination with other noninvasive variables, might correlate with liver-biopsy fibrosis scores in patients post-Fontan., Methods: Between March 2012 and February 2017, we identified patients post-Fontan that underwent elective cardiac catheterization and simultaneous transvenous hepatic biopsy. From this group, we selected patients that met inclusion criteria for liver-ultrasound, shear-wave elastography. Utilizing the results of elastography, laboratory testing, and time post-Fontan, we constructed a composite Fontan hepatic index as a sum of elastography measurements in kilopascals, model for end-stage liver disease excluding INR scores, and the square root of the number of years post-Fontan. Further, we analyzed correlations between Fontan hepatic index values and fibrosis scores from hepatic biopsy., Results: We identified a total of 79 post-Fontan patients that underwent cardiac catheterization and liver biopsy. Of the 79 patients, 53 met inclusion criteria, and 32 consented to undergo hepatic-ultrasound elastography. Of the 32 that underwent elastography, data from 30 patients was used for analysis. We found no statistically significant differences in demographics, laboratory values, or cardiac catheterization data between the 30 included patients and the 21 that did not participate. Utilizing data from the 30 included patients, we found a strong, highly statistically significant correlation between the Fontan hepatic index values and total fibrosis scores (R = 0.8, P < .00001). However, the cohort size prevented reliable discriminating cut-off values for the range of total fibrosis scores., Conclusions: In a small cohort of patients post-Fontan, preliminary findings suggest that the composite Fontan hepatic index might be a clinically useful, noninvasive method of serially monitoring for hepatic fibrosis. Further studies, with large patient cohorts, are necessary to validate our findings and develop clinically useful discriminatory cutoff values., (© 2017 Wiley Periodicals, Inc.)

We treated two patients with unexplained cyanosis, an atrial septal defect and an unusual form of non-obstructive double-chambered right ventricle, with device closure of the atrial septal defect.

Objective: We hypothesized that a right aortic arch in situs solitus, with or without an associated cardiovascular malformation, is often associated with a vascular ring., Methods: From those born in Southern Nevada between March 2012 and March 2017, we identified 50 (3.6 per 10,000 live births) with a right aortic arch and situs solitus. From the 50 patients, 6 did not meet inclusion criteria for further analysis., Results: Of the 44 remaining, 33 (75%) had a vascular ring. Of the 33 with a vascular ring, 26 (79%) occurred with an isolated right aortic arch, and 7 (21%) had an associated cardiovascular malformation. Of the total 44 patients with a right aortic arch in situs solitus, 34 (79%) were diagnosed prenatally., Conclusions: In conclusion, we found a right aortic arch in situs solitus was often associated with a vascular ring. Further, to the best of our knowledge, no previous general population study has demonstrated an equal or higher right aortic arch, prenatal detection rate of 79%., (© 2017 Wiley Periodicals, Inc.)

MicroRNAs (miRNAs) may regulate a number of genes, each of which may have a variety of functions. We utilized an endoarterial biopsy catheter to assess the dysregulation of miRNAs in a porcine shunt model of pulmonary hypertension (PH). Two Yucatan micropigs underwent surgical anastomosis of the left pulmonary artery to the descending aorta. Endoarterial biopsy samples were obtained at baseline, and at regular intervals during the progression of PH. RNA, isolated from biopsy samples, was analyzed by Illumina miRNA expression microarrays (containing ∼1200 human miRNAs), Affymetrix Porcine GeneChips, Bioconductor, and GeneSpring. We examined a total of 925 genes in a PH whole genome microarray. Biopsy samples showed that 39 miRNAs were downregulated and 34 miRNAs were upregulated compared to baseline. The number of PH-associated genes reported to be controlled by each of the dysregulated miRNAs was in the range of 1-113. The five miRNAs that had the largest number of PH-associated genes were: miR-548c-3p, miR-520d-3p, miR-130a-5p, miR-30a-3p, and miR-let-7g-3p. Several of the dysregulated miRNAs have been associated with molecular pathways and biologic processes involved in PH. Among 29 miRNAs, which were predicted to be dysregulated by a systems biology approach, we found four that were dysregulated in our porcine shunt model. An endoarterial biopsy technique was successful in showing that a large number of miRNAs are dysregulated in a porcine shunt model of PH. Many of these miRNAs control multiple PH-associated genes, molecular pathways, and biologic processes. Endoarterial biopsy offers potential experimental and clinical diagnostic value.

Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH's mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one canine and one swine) utilized repeated infusions of ceramic microspheres into the pulmonary vascular bed, and the third model employed a surgical aorto-pulmonary shunt. In the canine model, seven dogs underwent microsphere infusions that resulted in progressive elevation of pulmonary arterial pressure over a few months. In this model, pulmonary endoarterial tissue was obtained for histology. In the aorto-pulmonary shunt swine model, 17 pigs developed systemic level pulmonary pressures after 2-3 months. In this model, pulmonary endoarterial tissue was sequentially obtained to assess for changes in gene and microRNA expression. In the swine microsphere infusion model, three pigs developed only a modest chronic increase in pulmonary arterial pressure, despite repeated infusions of microspheres (up to 40 in one animal). The main purpose of this model was for vasodilator testing, which was performed successfully immediately after acute microsphere infusions. Chronic PH in large animal models can be successfully created; however, a model's characteristics need to match the investigational goals.