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Background: The Lung Allocation Score (LAS) is used in the U.S. to prioritize lung transplant candidates. Selection bias, induced by dependent censoring of waitlisted candidates and prediction of posttransplant survival among surviving, transplanted patients only, is only partially addressed by the LAS. Recently, a modified LAS (mLAS) was designed to mitigate such bias. Here, we estimate the clinical impact of replacing the LAS with the mLAS., Methods: We considered lung transplant candidates waitlisted during 2016 and 2017. LAS and mLAS scores were computed for each registrant at each observed organ offer date; individuals were ranked accordingly. Patient characteristics associated with better priority under the mLAS were investigated via logistic regression and generalized linear mixed models. We also determined whether differences in rank were explained more by changes in predicted pre- or posttransplant survival. Simulations examined how 1-year waitlist, posttransplant, and overall survival might change under the mLAS., Results: Diagnosis group, 6-minute walk distance, continuous mechanical ventilation, functional status, and age demonstrated the highest impact on differential allocation. Differences in rank were explained more by changes in predicted pretransplant survival than changes in predicted posttransplant survival, suggesting that selection bias has more impact on estimates of waitlist urgency. Simulations suggest that for every 1000 waitlisted individuals, 12.8 (interquartile range: 5.2-24.3) fewer waitlist deaths per year would occur under the mLAS, without compromising posttransplant and overall survival., Conclusions: Implementing a mLAS that mitigates selection bias into clinical practice can lead to important differences in allocation and possibly modest improvement in waitlist survival., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Electroencephalographic seizures (ESs) after neonatal cardiac surgery are often subclinical and have been associated with poor outcomes. An accurate ES prediction model could allow targeted continuous electroencephalographic monitoring (CEEG) for high-risk neonates., Methods: ES prediction models were developed and validated in a multicenter prospective cohort where all postoperative neonates who underwent cardiopulmonary bypass (CPB) also underwent CEEG., Results: ESs occurred in 7.4% of neonates (78 of 1053). Model predictors included gestational age, head circumference, single-ventricle defect, deep hypothermic circulatory arrest duration, cardiac arrest, nitric oxide, extracorporeal membrane oxygenation, and delayed sternal closure. The model performed well in the derivation cohort (c-statistic, 0.77; Hosmer-Lemeshow, P = .56), with a net benefit (NB) over monitoring all and none over a threshold probability of 2% in decision curve analysis (DCA). The model had good calibration in the validation cohort (Hosmer-Lemeshow, P = .60); however, discrimination was poor (c-statistic, 0.61), and in DCA there was no NB of the prediction model between the threshold probabilities of 8% and 18%. By using a cut point that emphasized negative predictive value in the derivation cohort, 32% (236 of 737) of neonates would not undergo CEEG, including 3.5% (2 of 58) of neonates with ESs (negative predictive value, 99%; sensitivity, 97%)., Conclusions: In this large prospective cohort, a prediction model of ESs in neonates after CPB had good performance in the derivation cohort, with an NB in DCA. However, performance in the validation cohort was weak, with poor discrimination, poor calibration, and no NB in DCA. These findings support CEEG of all neonates after CPB., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The optimal approach to identify SARS-CoV-2 infection among college students returning to campus is unknown. Recommendations vary from no testing to two tests per student. This research determined the strategy that optimizes the number of true positives and negatives detected and reverse transcription polymerase chain reaction (RT-PCR) tests needed., Methods: A decision tree analysis evaluated five strategies: (1) classifying students with symptoms as having COVID-19, (2) RT-PCR testing for symptomatic students, (3) RT-PCR testing for all students, (4) RT-PCR testing for all students and retesting symptomatic students with a negative first test, and (5) RT-PCR testing for all students and retesting all students with a negative first test. The number of true positives, true negatives, RT-PCR tests, and RT-PCR tests per true positive (TTP) was calculated., Results: Strategy 5 detected the most true positives but also required the most tests. The percentage of correctly identified infections was 40.6%, 29.0%, 53.7%, 72.5%, and 86.9% for Strategies 1-5, respectively. All RT-PCR strategies detected more true negatives than the symptom-only strategy. Analysis of TTP demonstrated that the repeat RT-PCR strategies weakly dominated the single RT-PCR strategy and that the thresholds for more intensive RT-PCR testing decreased as the prevalence of infection increased., Conclusion: Based on TTP, the single RT-PCR strategy is never preferred. If the cost of RT-PCR testing is of concern, a staged approach involving initial testing of all returning students followed by a repeat testing decision based on the measured prevalence of infection might be considered., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Research on genomic medicine integration has focused on applications at the individual level, with less attention paid to implementation within clinical settings. Therefore, we conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in implementation of genomic medicine within Implementing GeNomics In PracTicE (IGNITE) Network projects., Methods: Up to four study personnel, including principal investigators and study coordinators from each of six IGNITE projects, were interviewed using a semistructured interview guide that asked interviewees to describe study site(s), progress at each site, and factors facilitating or impeding project implementation. Interviews were coded following CFIR inner-setting constructs., Results: Key barriers included (1) limitations in integrating genomic data and clinical decision support tools into electronic health records, (2) physician reluctance toward genomic research participation and clinical implementation due to a limited evidence base, (3) inadequate reimbursement for genomic medicine, (4) communication among and between investigators and clinicians, and (5) lack of clinical and leadership engagement., Conclusion: Implementation of genomic medicine is hindered by several system-level barriers to both research and practice. Addressing these barriers may serve as important facilitators for studying and implementing genomics in practice.

PurposeImplementation research provides a structure for evaluating the clinical integration of genomic medicine interventions. This paper describes the Implementing Genomics in Practice (IGNITE) Network's efforts to promote (i) a broader understanding of genomic medicine implementation research and (ii) the sharing of knowledge generated in the network.MethodsTo facilitate this goal, the IGNITE Network Common Measures Working Group (CMG) members adopted the Consolidated Framework for Implementation Research (CFIR) to guide its approach to identifying constructs and measures relevant to evaluating genomic medicine as a whole, standardizing data collection across projects, and combining data in a centralized resource for cross-network analyses.ResultsCMG identified 10 high-priority CFIR constructs as important for genomic medicine. Of those, eight did not have standardized measurement instruments. Therefore, we developed four survey tools to address this gap. In addition, we identified seven high-priority constructs related to patients, families, and communities that did not map to CFIR constructs. Both sets of constructs were combined to create a draft genomic medicine implementation model.ConclusionWe developed processes to identify constructs deemed valuable for genomic medicine implementation and codified them in a model. These resources are freely available to facilitate knowledge generation and sharing across the field.

Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI)., Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI., Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights., Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60)., Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics., Methods: The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use., Results: Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use., Conclusions: Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Increasing epidemiological evidence suggests independent associations between psoriasis and cardiovascular and metabolic disease. Our objective was to test the hypothesis that directly assessed psoriasis severity relates to the prevalence of metabolic syndrome and its components. A population-based, cross-sectional study was undertaken using computerized medical records from the Health Improvement Network Study population including individuals in the age group of 45-65 years with psoriasis and practice-matched controls. The diagnosis and extent of psoriasis were determined using provider-based questionnaires. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. A total of 44,715 individuals were included: 4,065 with psoriasis and 40,650 controls. In all, 2,044 participants had mild psoriasis (2% body surface area (BSA)), 1,377 had moderate psoriasis (3-10% BSA), and 475 had severe psoriasis (>10% BSA). Psoriasis was associated with metabolic syndrome, adjusted odds ratio (adj. OR 1.41, 95% confidence interval (CI) 1.31-1.51), varying in a "dose-response" manner, from mild (adj. OR 1.22, 95% CI 1.11-1.35) to severe psoriasis (adj. OR 1.98, 95% CI 1.62-2.43). Psoriasis is associated with metabolic syndrome and the association increases with increasing disease severity. Furthermore, associations with obesity, hypertriglyceridemia, and hyperglycemia increase with increasing disease severity independently of other metabolic syndrome components. These findings suggest that screening for metabolic disease should be considered for psoriasis, especially when it is severe.

Patients receiving hemodialysis have high rates of cardiovascular morbidity and mortality that may be related to the hemodynamic effects of rapid ultrafiltration. Here we tested whether higher dialytic ultrafiltration rates are associated with greater all-cause and cardiovascular mortality, and hospitalization for cardiovascular disease. We used data from the Hemodialysis Study, an almost-7-year randomized clinical trial of 1846 patients receiving thrice-weekly chronic dialysis. The ultrafiltration rates were divided into three categories: up to 10 ml/h/kg, 10-13 ml/h/kg, and over 13 ml/h/kg. Compared to ultrafiltration rates in the lowest group, rates in the highest were significantly associated with increased all-cause and cardiovascular-related mortality with adjusted hazard ratios of 1.59 and 1.71, respectively. Overall, ultrafiltration rates between 10-13 ml/h/kg were not associated with all-cause or cardiovascular mortality; however, they were significantly associated among participants with congestive heart failure. Cubic spline interpolation suggested that the risk of all-cause and cardiovascular mortality began to increase at ultrafiltration rates over 10 ml/h/kg regardless of the status of congestive heart failure. Hence, higher ultrafiltration rates in hemodialysis patients are associated with a greater risk of all-cause and cardiovascular death.

Background: This study tested the discriminant validity of International Society for Heart and Lung Transplantation (ISHLT) primary graft dysfunction (PGD) grades with lung injury biomarker profiles and survival., Methods: The study samples consisted of a multicenter prospective cohort study for the biomarker analysis and a cohort study of 450 patients for the mortality analyses. PGD was defined according to ISHLT consensus at 24, 48, and 72 hours after transplantation. We compared the changes in plasma markers of acute lung injury between PGD grades using longitudinal data models. To test predictive validity, we compared differences in the 30-day mortality and long-term survival according to PGD grade., Results: PGD Grade 3 demonstrated greater differences between plasma intercellular adhesion molecule 1 (ICAM-1), protein C, and plasminogen activator inhibitor type 1 (PAI-1) levels than did PGD Grades 0 to 2 at 24, 48, and 72 hours after lung transplantation (p < 0.05 for each). Grade 3 had the highest 30-day (test for trend p < 0.001) and overall mortality (log rank p < 0.001), with PGD Grades 1 and 2 demonstrating intermediate risks of mortality. The ability to discriminate both 30-day and overall mortality improved as the time of grading moved away from the time of transplantation (test for trend p < 0.001)., Conclusions: The ISHLT grading system has good discriminant validity, based on plasma markers of lung injury and mortality. Grade 3 PGD was associated with the most severely altered plasma biomarker profile and the worst outcomes, regardless of the time point of grading. PGD grade at 48 and 72 hours discriminated mortality better than PGD grade at 24 hours., (Copyright © 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Warfarin-dosing algorithms incorporating CYP2C9 and VKORC1 -1639G>A improve dose prediction compared with algorithms based solely on clinical and demographic factors. However, these algorithms better capture dose variability among whites than Asians or blacks. Herein, we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1 -1639G>A among Asians (n = 1103), blacks (n = 670), and whites (n = 3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 single nucleotide polymorphisms (SNPs) and haplotypes on warfarin dose used both univariate and multi variable linear regression. VKORC1 -1639G>A and 1173C>T individually explained the greatest variance in dose in all 3 racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among whites than blacks and Asians. Differences in the percentage of variance in dose explained by VKORC1 across race were largely accounted for by the frequency of the -1639A (or 1173T) allele. Thus, clinicians should recognize that, although at a population level, the contribution of VKORC1 toward dose requirements is higher in whites than in nonwhites; genotype predicts similar dose requirements across racial groups.

Background: Warfarin is the primary therapy to prevent stroke and venous thromboembolism. Significant periods of nonadherence frequently go unreported by patients and undetected by providers. Currently, no comprehensive screening tool exists to help providers assess the risk of nonadherence at the time of initiation of warfarin therapy., Methods: This article reports on a prospective cohort study of adults initiating warfarin therapy at two anticoagulation clinics (university- and Veterans Affairs-affiliated). Nonadherence, defined by failure to record a correct daily pill bottle opening, was measured daily by electronic pill cap monitoring. A multivariable logistic regression model was used to develop a point system to predict daily nonadherence to warfarin., Results: We followed 114 subjects for a median of 141 days. Median nonadherence of the participants was 14.4% (interquartile range [IQR], 5.8-33.8). A point system, based on nine demographic, clinical, and psychosocial factors, distinguished those demonstrating low vs high levels of nonadherence: four points or fewer, median nonadherence 5.8% (IQR, 2.3-14.1); five points, 9.1% (IQR, 5.9-28.6); six points, 14.5% (IQR, 7.1-24.1); seven points, 14.7% (IQR, 7.0-34.7); and eight points or more, 29.3% (IQR, 15.5-41.9). The model produces a c-statistic of 0.66 (95% CI, 0.61-0.71), suggesting modest discriminating ability to predict day-level warfarin nonadherence., Conclusions: Poor adherence to warfarin is common. A screening tool based on nine demographic, clinical, and psychosocial factors, if further validated in other patient populations, may help to identify groups of patients at lower risk for nonadherence so that intensified efforts at increased monitoring and intervention can be focused on higher-risk patients.

Objective: We sought to examine the validity of specific hospital discharge codes in identifying drug toxicity precipitating hospitalization, among elderly users of high-risk medications., Study Design and Setting: We conducted a cross-sectional evaluation assessing the diagnostic test characteristics of International Classification of Diseases-9 External-Cause-of-Injury codes (E-codes) compared with a reference standard of medical record review. This study was nested within a prospective cohort of elders using warfarin, digoxin, or phenytoin as identified in the Pharmaceutical Assistance Contract for the Elderly benefit program., Results: We identified 4,803 subjects contributing 11,409 person-years of exposure to at least one of three drug groups. Subjects experienced 8,756 hospitalizations, of which 304 were deemed, by expert review, to be a result of an adverse event of warfarin, digoxin, or phenytoin. The sensitivity, specificity, and positive (PPVs) and negative predictive values for drug-specific E-codes were warfarin--25.5%, 98.3%, 46.6%, and 95.7%; digoxin--84.0%, 99.1%, 56.8%, and 99.8%; and phenytoin--86.7%, 98.7%, 59.1%, and 99.7%., Conclusions: E-codes for digoxin and phenytoin have a high sensitivity, but E-codes for all three medications have poor PPVs, a result that might produce misclassification in studies based solely on discharge coding. Investigators should confirm such rare events via medical record review.

Background: Current atrial fibrillation (AF) ablation involves isolation of all pulmonary veins (PVs) with or without additional linear lesions. However, whether such extensive ablation is necessary is unclear., Objective: The purpose of this study was to assess the efficacy of different ablation strategies on long-term AF control., Methods: We prospectively randomized patients to undergo isolation of all versus arrhythmogenic PVs (identified by standardized stimulation protocol). PV isolation was guided by circular mapping catheter. The endpoint was entry/exit block persisting for > or = 20 minutes. Patients were evaluated at three clinic visits (at 6 weeks, 6 months, and 1 year) and multiple transtelephonic monitoring periods. Antiarrhythmic drugs were discontinued at 6 weeks. Primary study endpoint was long-term AF control (freedom or >90% reduction in AF burden off or on previously ineffective antiarrhythmic drugs at 1 year after a single ablation procedure)., Results: Over a 20-month period, 105 patients (76 men and 29 women, age 57 +/- 9 years; paroxysmal AF = 77) were randomized, and 103 patients completed 1-year follow-up (51 patients in all-PV arm, 52 patients in arrhythmogenic PV arm). The primary endpoint was achieved in 75 (73%) patients and was similar in patients randomized to all-PV arm versus arrhythmogenic PV arm [38 (75%) patients vs 37 (71%) patients, respectively; odds ratio 1.18, 95% confidence interval 0.50, 2.83, P = .70]. Secondary study endpoints, including freedom from AF off antiarrhythmic drugs, total procedure/fluoroscopy times, and occurrence of serious adverse events, were not different between the two groups., Conclusion: In a randomized comparison, isolation of arrhythmogenic veins was as efficacious as empiric isolation of all veins in achieving long-term AF control.

Study Objectives: Primary graft failure (PGF) is a severe acute lung injury syndrome that occurs following lung transplantation. We compared the clinical outcomes of patients who developed PGF with those who did not., Methods: We conducted a retrospective cohort study including 255 consecutive lung transplant procedures. PGF was defined as (1) diffuse alveolar opacities developing within 72 h of transplantation, (2) an arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio of < 200 beyond 48 h postoperatively, and (3) no other secondary cause of graft dysfunction. PGF was tested for acceptance with 30-day and all-cause hospital mortality rates, overall survival, hospital length of stay (HLOS), duration of mechanical ventilation, and best 6-min walk test (6MWT) distance achieved within 12 months., Setting: Academic medical center., Results: The overall incidence of PGF was 11.8% (95% confidence interval [CI], 7.9 to 15.9%). The all-cause mortality rate at 30 days was 63.3% in patients with PGF and 8.8% in patients without PGF (relative risk [RR], 7.15; 95% CI, 4.34 to 11.80%; p < 0.001). A total of 73.3% of patients with PGF died during hospitalization vs 14.2% of patients without PGF (RR, 5.18%; 95% CI, 3.51 to 7.63; p < 0.001). The median HLOS in 30-day survivors was 47 days in patients with PGF vs 15 days in those without PGF (p < 0.001), and the mean duration of mechanical ventilation was 15 days in patients with PGF vs 1 day in those without PGF (p < 0.001). By 12 months, a total of 28.5% of survivors with PGF achieved a normal age-appropriate 6MWT distance vs 71.4% of survivors without PGF at 12 months (p = 0.014). The median best 6MWT distance achieved within the first 12 months was 1,196 feet in patients with PGF vs 1,546 feet in those without PGF (p = 0.009)., Conclusions: PGF has a significant impact on mortality, HLOS, and duration of mechanical ventilation following lung transplantation. Survivors of PGF have a protracted recovery with impaired physical function up to 1 year following transplantation.

Study Objective: s: Primary graft failure (PGF) is a devastating acute lung injury syndrome following lung transplantation. We sought to identify donor, recipient, and operative risk factors for its development., Design: We conducted a cohort study of 255 consecutive lung transplant procedures performed between October 1991 and July 2000. We defined PGF as follows: (1) diffuse alveolar opacities exclusively involving allograft(s) and developing within 72 h of transplant, (2) a ratio of PaO(2) to fraction of inspired oxygen < 200 beyond 48 h postoperatively, and (3) no other secondary cause of graft dysfunction identified. Risk factors were assessed individually and adjusted for confounding using multivariable logistic regression models., Setting: Tertiary-care academic medical center., Results: The overall incidence was 11.8% (95% confidence interval [CI], 7.9 to 15.9). Following multivariable analysis, the risk factors independently associated with development of PGF were as follows: a recipient diagnosis of primary pulmonary hypertension (PPH; adjusted odds ratio [OR], 4.52; 95% CI, 1.29 to 15.9; p = 0.018), donor female gender (adjusted OR, 4.11; 95% CI, 1.17 to 14.4; p = 0.027), donor African-American race (adjusted OR, 5.56; 95% CI, 1.57 to 19.8; p = 0.008), and donor age < 21 years (adjusted OR, 4.06; 95% CI, 1.34 to 12.3; p = 0.013) and > 45 years (adjusted OR, 6.79; 95% CI, 1.61 to 28.5; p = 0.009)., Conclusions: Recipient diagnosis of PPH, donor African-American race, donor female gender, and donor age are independently and strongly associated with development of PGF.

Study Objectives: The goal of this study was to determine whether the survival of patients with pulmonary hypertension related to systemic sclerosis (SScPH) was different from that of patients with other forms of pulmonary arterial hypertension., Design: Retrospective cohort study., Setting: Tertiary care medical center., Patients: Our cohort was composed of 33 patients with pulmonary hypertension that is sporadic, familial, or related to anorexigen use (PPH) and 22 patients with SScPH who underwent initial pulmonary artery catheterization and vasodilator study at our center between January 1997 and June 2001., Measurements and Results: Patients with SScPH had somewhat lower percentage of predicted lung volumes than patients with PPH (total lung capacity, 80% vs 92%; p = 0.06) and had lower percentage of predicted diffusion capacity of the lung for carbon monoxide (42% vs 68%; p = 0.0002). Right atrial pressure, pulmonary artery pressure, and cardiac index were similar between the groups. Patients with SScPH and PPH were treated with usual medical therapies, such as digoxin, warfarin, and continuous IV epoprostenol. Despite these similarities, the risk of death in patients with SScPH was higher than in patients with PPH (unadjusted hazard ratio, 2.9; 95% confidence interval, 1.1 to 7.8; p = 0.03). This increased risk appeared to persist after adjustment for a variety of demographic, hemodynamic, or treatment variables., Conclusions: Despite having similar hemodynamics, patients with SScPH have a higher risk of death than patients with PPH. Future studies of the mechanism and therapy of pulmonary arterial hypertension should focus on the distinctions between the different forms of this disease.