Limited guidance exists for the management of methamphetamine-associated PAH (Meth-APAH) and the experiences of physicians treating this population are not well documented. This study explored how physicians approach diagnosis and treatment and identified unmet needs in clinical care through structured interviews with 30 U.S. pulmonologists and cardiologists who manage patients with Meth-APAH. Physicians relied heavily on patient self-report to establish methamphetamine use; only 20% performed routine toxicology testing. Compared with patients with other forms of pulmonary arterial hypertension, those with methamphetamine-associated disease were younger, more likely to present in the emergency department, and more often diagnosed at advanced functional class based on physician perspectives. Physicians reported caution with initiating triple therapy and often preferred oral or subcutaneous prostacyclin agents due to concerns about adherence and risks of intravenous therapy. Socioeconomic instability and stigma were identified as major contributors to delayed diagnosis, nonadherence, and poor outcomes. Unmet needs included earlier recognition by frontline providers and greater access to addiction support resources. This study highlights critical challenges in diagnosing and managing Meth-APAH. Improving provider education, standardizing screening practices, and integrating addiction treatment into care pathways are essential to address unmet needs.

Background Combination therapy is recommended for pulmonary arterial hypertension (PAH), part of which generally includes prostanoids, which affect both the vascular tone and vessel remodeling seen in PAH. This study tested whether a dual prostacyclin treatment strategy (oral esuberaprost + inhaled treprostinil and oral background PAH therapies) would provide additional clinical benefit. Methods 271 World Health Organization functional class (FC) III/IV patients with PAH received placebo or 28.4 µg oral esuberaprost 4 times daily, in addition to newly initiated or ongoing inhaled treprostinil and background therapies. Results There was no difference between treatment groups in time to clinical worsening (primary endpoint); 49 (36.0%) patients on esuberaprost and 51 (37.8%) on placebo had a clinical worsening event. No favorable esuberaprost treatment effects were observed for the secondary or exploratory endpoints (6-minute walk distance [6MWD], Borg dyspnea score, and N-terminal pro-brain natriuretic peptide [NT-proBNP]). There were 21 all-cause deaths (esuberaprost: 8 [5.9%]; placebo: 13 [9.6%]). Post hoc exploratory analyses to investigate the effect of inhaled treprostinil on treprostinil-naïve patients (n = 151) found that the addition of inhaled treprostinil resulted in improvements in multiple components of risk status, NT-proBNP, and 6MWD from screening through week 52, irrespective of background therapy. Notably, these improvements were also seen in patients on dual background therapy. Conclusion While the study did not meet its primary endpoint, it suggested that monitoring patients based on proven risk scores may be highly beneficial. Trial Registration: Beraprost-314d Added-on to Tyvaso® (BEAT) NCT01908699; Registered 2013-07-26

RATIONALE Ralinepag, a potent, titratable, once-daily, oral prostacyclin receptor agonist is in development for the treatment of pulmonary arterial hypertension (PAH). ADVANCE EXTENSION is an ongoing open-label extension (OLE) study following ADVANCE OUTCOMES to evaluate long-term safety and tolerability of ralinepag in patients with PAH. ESC/ERS guidelines recommend low risk status as a treatment goal. Contemporary risk calculators have prognostic utility as they integrate multiple clinical parameters. In this interim analysis, we assessed REVEAL Lite 2 risk improvements with ralinepag treatment in the OLE. METHODS Participants who experienced a protocol-defined clinical worsening event (CWE) in the parent study were eligible to enroll in the OLE and included in this analysis. All participants in the OLE received ralinepag; treatment assignments in ADVANCE OUTCOMES remained blinded. Changes in REVEAL Lite 2 from OLE Baseline to Weeks 16, 28 and 52 in the OLE are presented. Only participants with ≥3 REVEAL Lite 2 parameters, two being 6MWD, WHO FC, or NT-proBNP, were included in this analysis. Extent of ralinepag exposure, dosing, and AEs are descriptively presented. RESULTS At the time of this interim analysis, 119 participants had enrolled in the OLE after a CWE in ADVANCE OUTCOMES. At OLE Baseline, 24% were low risk, 25% were intermediate risk, and 50% were high risk with an overall median (IQR) REVEAL Lite 2 score of 8 (6, 9); 72% were on dual background therapy. At Week 16 (n=95), the median (IQR) REVEAL Lite 2 score decreased to 6 (4, 8) which was maintained up to Week 28 (n=81) and Week 52 (n=62) in the OLE. At Weeks 16, 28, and 52 in the OLE 38%, 46%, and 42% of participants were low risk, respectively (Figure 1). Eighteen percent, 23%, and 15% had improved to low risk and 20%, 22%, and 27% had maintained low risk status from OLE Baseline to Weeks 16, 28, and 52, respectively. Median dose of ralinepag was 250 mcg at Week 16 and 300 mcg at Weeks 28 and 52 with a median treatment duration of 63 weeks in the OLE. AEs in the OLE were consistent with the known safety profile of prostacyclins with headache (71%), diarrhea (46%), and nausea (37%) reported most frequently. CONCLUSIONS Treatment with ralinepag in the OLE produced early and sustained REVEAL Lite 2 risk improvements after experiencing a CWE, with a substantial proportion of participants maintaining or achieving low risk status. Sponsored by United Therapeutics

Hypotension, hypoxia, and hypothermia tissue have unclear effects on postoperative outcomes. The Operating Room Black Box™ (ORBB) is a novel monitoring platform that automates “tagging” of intraoperative hypotension, hypoxia, and hypothermia. We hypothesized that intraoperative physiologic event tags would serve as predictive variables of adverse postoperative outcomes. Using the ORBB, tags were prospectively applied for moderate and severe episodes of hypotension, hypothermia, and hypoxia. Regression modeling was performed to examine the association between intraoperative tags and adverse outcomes of surgical site infection, patient safety indicator (PSI) events, length of stay, readmission, return to OR, and mortality. 2875 cases were performed and monitored with the ORBB tag system between August 17, 2020 and September 3, 2022. 567 cases (19

BACKGROUND:Early referral for lung transplantation in patients with pulmonary arterial hypertension (PAH) is recommended by multiple professional societies. We sought to use the Pulmonary Hypertension Association Registry (PHAR) to describe the current landscape of referrals for lung transplantation in patients with PAH. METHODS:PHAR is a 72-center US-based registry of patients with PAH. Participants were followed longitudinally with repeat assessments of clinical parameters, including referrals for transplantation. We compared clinical parameters between those referred for transplantation at any point, with those never referred. Next, we tested whether various clinical parameters predicted time to referral, using cox-proportional hazards modeling and stepwise backward elimination. RESULTS:Of 1,671 participants analyzed with 4,607 person-years of follow up, 199 (12%) were referred for transplantation. Of those referred, 30% underwent transplantation and 21% died without transplantation. Only 18-29% of participants with functional class 4 disease, registry to evaluate early and long-term PAH disease management Lite 2 high-risk disease, or 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) high-risk disease were referred for transplant. Rates of referral did not increase in sensitivity analyses restricting the cohort to participants without obvious contraindications based on body mass index or age. In multivariate modeling accounting for death as a competing risk, a diagnosis of pulmonary veno-occlusive disease, higher registry to evaluate early and long-term PAH disease management Lite 2 Scores, and parenteral prostacyclin use were associated with increased likelihood of referral, while older age and higher body mass index were associated with decreased likelihood of referral. CONCLUSION:Rates of referral for lung transplantation in patients with PAH remain unacceptably low and occur too late. Increased awareness of the benefit of early referral is necessary, even at expert centers.

Rationale Advancements in the management of congenital heart disease (CHD) have led to a growing population of adult CHD patients. Pulmonary arterial hypertension (PAH) is a common sequela of CHD in adults, occurring in up to 10% (30% in patients with unrepaired CHD). The treatment of PAH-CHD remains challenging, with poor outcomes in the late stages of the disease. Continuous parenteral prostanoids such as IV epoprostenol and IV/SC treprostinil are a treatment of choice for patients with advanced PAH. Although treatment with parenteral prostanoids is well-studied in the PAH population overall, there are only a limited number of small, observational studies examining their use in the subset of PAH-CHD patients. Methods We conducted a retrospective chart review study identifying all patients with CHD-PAH andtreated with IV/SC prostanoids from 2009-2024. Demographic data, comorbidities, functional class, and hemodynamics from right heart catheterizations (RHC) before and after starting prostanoids were collected. We compared changes in hemodynamics before and after prostanoids using a paired T-test. Results 15 patients with CHD-PAH were identified with a median age of 45 (range 21-74). Of these patients, 9 had atrial septal defects (2 repaired after starting therapy), 3 had both an atrial and ventricular septal defect, 1 had a repaired PDA, 1 had a repaired D-loop transposition, and 1 hadrepaired heterotaxy with left atrial isomerism, interrupted IVC, and ASD. In PAH-CHD patients, treatment with IV prostacyclins led to a statistically significant decrease in pulmonary vascular resistance (mean difference = -5.89, p = 0.0053) as well as an increase in cardiac output (mean difference = 1.36, p = 0.0193), cardiac index (mean difference = 0.62, p =0.0278), and pulmonary artery oxygen saturation (mean difference = 13.86, p = 0.0009) at the first follow-up RHC compared to measurements taken before initiating IV prostacyclins. There was no significant increase or decrease in pulmonary artery pressure, right atrial pressure, nor wedge pressure. Conclusions Treatment with IV prostacyclins is associated with statistically significant improvement in hemodynamics of patients with PAH-CHD at the first follow-up RHC. Future studies will need to explore whether this change correlates to changes in clinically significant markers of function including 6-minute walk test and functional status, as well as whether or not there are differences in effect amongst various subgroups such as type of CHD or repair status.

Background & Problem: Incorporation of a paired spontaneous awakening trial (SAT) & spontaneous breathing trial (SBT) has been well-documented to minimize ventilator days in critically ill patients. However, adherence is often subpar due to protocol complexity. The aim of this project was to improve SAT/SBT protocol adherence in a large academic medical center in Texas. Methods: Multidisciplinary interventional study employing the Plan-Do-Study-Act quality improvement methodology. Baseline data was obtained via retrospective chart review of SAT and SBT documentation. Preliminary analysis identified the following barriers to protocol completion: (1) lack of knowledge, (2) protocol variation across teams, and (3) ease of documentation. Targeted interventions were then designed to address these problems. Interventions included education materials distributed to critical care providers, changes made in the EMR to facilitate documentation, and a quality assurance and performance improvement team assembled to oversee and encourage protocol performance. Protocol planning involved literature review to obtain best practices. 1 year following protocol roll-out, post-intervention data was collected via retrospective chart review using run charts and scorecards. Protocol performance was qualitatively studied using a survey containing 27 Likert scale questions with additional prompts for comments. Descriptive statistics and inductive thematic analysis were used to summarize responses. Process measures include percent eligible patients receiving SAT screen/SAT and percent eligible patients receiving SBT screen/ SBT. Outcome measures include days spent on mechanical ventilation, and days spent in the ICU, with a balancing measure of percent ICU readmission. Results: Following the interventions, ventilator days decreased from a baseline of 6.65 to 5.87 days and ICU stay decreased from 6.36 to 6.33 days. The rate of SATs performed increased from 60.3%-73.5%, and the rate of SBTs performed increased from 78.5% to 89.6%, and the rate of ICU readmission decreased from 2.7% to 2.55%. The survey yielded fifty-two responses. 85% of participants responded positively to prompts regarding protocol knowledge, and 43% of participants responded positively to prompts regarding protocol attitudes. The survey yielded 44 comments describing barriers to completion which were divided into 7 themes. The most common barrier was difficulty applying protocol steps all eligible patients. Conclusions: A multifactorial intervention targeting staff education, efficient EMR documentation, and regular protocol surveillance led to increased adherence to the SAT/SBT protocol and consequent reductions in ventilator days and ICU stay. Additional efforts are still needed to increase adherence to 100%. Next steps are to address the barriers identified and develop appropriate interventions in future PDSA cycles.

Rationale A growing number of patients with congenital heart disease (CHD) survive into adulthood. These patients frequently develop pulmonary arterial hypertension (PAH), 30% in those with unrepaired CHD and 10% undergoing repairs. Despite advancements in the management of PAH, including continuous prostanoids, and the growing number of PAH-CHD patients, minimal research has been completed on the survival trends of this demographic. This is particularly true of patients with milder disease and unrepaired defects. Methods We conducted a retrospective chart review study of a larger PAH cohort. We identified 18 patients with PAH-CHD treated at one academic center. Dates of birth, initiation of treatment with intravenous or subcutaneous prostacyclins, and dates of death or last clinical contact were identified. We used the Kaplan-Meier method to analyze survival in this cohort. We incorporated right-censoring, accounting for losses to follow up and death. The Kaplan-Meier method was used to estimate survival function (NCSS 2024 Statistical Software) from initiation of treatment with IV/SC prostacyclins. Results We identified 18 patients with CHD-PAH from a larger PAH cohort. Median age was 47 (IQR: 18). Nine had atrial septal defects (ASD), two had ventricular septal defects (VSD), one had a patent ductus arteriosus (PDA), and the remaining six had complex CHD. Three (17%) had undergone surgical repairs prior to therapy initiation, two (11%) following therapy initiation. Over seven years (2,555 days), four patients passed away and one underwent bilateral lung transplantation with ASD repair. One-year, three-year, and five-year survival were 89%, 83%, and 83%, respectively. Both median survival time and restricted mean survival time surpassed seven years. Conclusions Survival in a group of patients with PAH-CHD receiving IV/SC prostacyclins at one academic center demonstrated both a median survival time and restricted mean survival time of greater than seven years. Further studies are needed to explore whether these survival values are replicated at other treatment centers, and to build a larger cohort. With a larger cohort, differences in survival outcomes in subgroups of type of CHD or surgical repair status could also be explored. Further investigation is needed to explain these outcomes, considering the younger median age at diagnosis and increased frequency of contact with healthcare these patients may have compared to other PAH patients.

Overnight inpatient monitoring is common following balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). We describe our institutional experience in same-day discharge (SDD) after BPA. Across 78 BPA sessions, there were only 2 (2.6%) admissions for hemoptysis with no reperfusion lung injury or deaths at 30 days.

Pulmonary hypertension (PH) is a haemodynamic condition characterised by elevation of mean pulmonary arterial pressure (mPAP) >20 mmHg, assessed by right heart catheterisation. Pulmonary arterial wedge pressure (PAWP) and pulmonary vascular resistance (PVR) distinguish pre-capillary PH (PAWP <= 15 mmHg, PVR >2 Wood Units (WU)), isolated post-capillary PH (PAWP >15 mmHg, PVR <= 2 WU) and combined post- and pre-capillary PH (PAWP >15 mmHg, PVR >2 WU). Exercise PH is a haemodynamic condition describing a normal mPAP at rest with an abnormal increase of mPAP during exercise, defined as a mPAP/cardiac output slope >3 mmHg/L/min between rest and exercise. The core structure of the clinical classification of PH has been retained, including the five major groups. However, some changes are presented herewith, such as the re-introduction of "long-term responders to calcium channel blockers" as a subgroup of idiopathic pulmonary arterial hypertension, the addition of subgroups in group 2 PH and the differentiation of group 3 PH subgroups based on pulmonary diseases instead of functional abnormalities. Mitomycin-C and carfilzomib have been added to the list of drugs with "definite association" with PAH. For diagnosis of PH, we propose a stepwise approach with the main aim of discerning those patients who need to be referred to a PH centre and who should undergo invasive haemodynamic assessment. In case of high probability of severe pulmonary vascular disease, especially if there are signs of right heart failure, a fast-track referral to a PH centre is recommended at any point during the clinical workup.

Surgical safety checklists reduce adverse events, but monitoring adherence to checklists is confounded by observation bias. The ORBB platform can monitor checklist compliance and correlate compliance with outcomes. This study aims to evaluate the association between checklist compliance and patient outcomes using the ORBB platform. This is a retrospective analysis of data from the electronic medical record of cases performed in ORBB-equipped operating rooms at a single quaternary referral center. All patients who did not opt out and underwent surgery at UT Southwestern Medical Center in ORBB-equipped rooms from August 2020 to September 2022 were included. The ORBB platform was set-up in five operating rooms and surgical safety checklist compliance was monitored by way of AI-based video review. Overall, 4581 patients were included in this analysis.. Performance on the checklist was associated with lower mortality (OR, 0.96; 95

AbstractFew studies have evaluated the effects of pulmonary arterial hypertension therapies on pericardial effusion. We evaluated hemodynamics, echocardiograms, and outcomes for 119 parenteral prostanoid‐treated patients. We discovered an increased frequency of pericardial effusions posttreatment, and that a moderate‐large pericardial effusion at initiation, but not at 1st follow‐up, was significantly associated with mortality.

BACKGROUND:Pulmonary arterial hypertension (PAH) is a life limiting disease with substantial symptom burden and healthcare utilization. Palliative care alleviates physical and emotional symptoms for patients with serious illness, and has been underutilized for these patients.OBJECTIVE:To characterize patients with PAH referred to palliative care and identify predictors of referral.METHODS:We conducted an observational study of adult patients enrolled in the Pulmonary Hypertension Association Registry from January 2015 through June 2021, performing descriptive statistics on patient characteristics at baseline for all patients and the subset referred to palliative care. These characteristics were modeled in a backwards elimination Cox regression with time to referral to palliative care as the primary outcome.RESULTS:92 of 1,578 patients were referred to palliative care (5.8%); 43% were referred at their last visit prior to death. Referrals were associated with increasing age per decade (hazard ratio 1.35 [95% confidence interval 1.16-1.58]), lower body mass index (hazard ratio 0.97 [95% confidence interval 0.94-0.998]), supplemental oxygen use (hazard ratio 2.01 [95% confidence interval 1.28-3.16]), parenteral prostanoid use (hazard ratio 2.88 [95% confidence interval 1.84-4.51]), and worse quality of life, measured via lower physical (hazard ratio 0.97 [95% confidence interval 0.95-0.99]) and mental (hazard ratio 0.98 [95% confidence interval 0.96-0.995]) scores on the 12-item Short Form Health Survey.CONCLUSION:Patients with PAH are infrequently referred to palliative care, even at centers of excellence. Referrals occur in sicker patients with lower quality of life scores, often close to the end of life.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

BACKGROUND: Echocardiographic parameters are used as prognostic markers in patients with pulmonary arterial hypertension (PAH) receiving parenteral (IV or subcutaneous [IV/SC]) prostacyclin therapy. However, data on how posttreatment echocardiographic results asso-ciate with outcomes are limited. RESEARCH QUESTION: Are echocardiographic parameters pre-and post-parenteral prostacy-clin therapy in patients with PAH associated with long-term outcomes? STUDY DESIGN AND METHODS: In this retrospective cohort study, patients with PAH initiated on IV epoprostenol or IV/SC treprostinil therapy between 2007 and 2016 were included and followed up through May 31, 2020. Survival free from transplant was assessed from the time of IV/SC prostacyclin therapy initiation and from first follow-up echocardiogram following at least 90 days of therapy. RESULTS: Patients with PAH initiated on IV/SC prostacyclin therapy (N = 118) were followed up for a median of 7.3 years. Survival was 86%, 79%, and 69% at 1, 2, and 3 years, respectively. Follow-up echocardiogram in 101 patients (median, 178 days; interquartile range, 140-273 days) showed improvement in five echocardiographic measures: right ventricular function, right ventricular systolic pressure, right ventricular diastolic diameter, left ventricular diastolic diameter, and tricuspid regurgitation (TR) severity. TR severity and pericardial effusion were associated with survival from IV/SC therapy initiation, whereas right ventricular diastolic diameter, right atrial (RA) size, TR severity, and inferior vena cava characteristics were asso-ciated with survival from first follow-up. In a multivariable analysis incorporating other prognostic measures at first follow-up, walk distance, functional class, N-terminal pro-B-type natriuretic peptide, and RA size resulted in the best fit model for survival. INTERPRETATION: Echocardiographic variables improved following IV/SC therapy, and multiple echocardiographic measures associated significantly with survival, particularly when reassessed after at least 90 days of therapy. RA size in particular may be useful in prog-nostication in follow-up of patients with PAH on IV/SC therapy.

Introduction: Parenteral prostanoids are the most potent therapies for pulmonary arterial hypertension (PAH) but are associated with complications and lifestyle limitations. Carefully selected stable patients may be considered for a transition from parenteral prostanoids to a more convenient oral regimen. We present our experience transitioning patients on parenteral prostanoids to selexipag on an outpatient basis. Methods: This was a retrospective cohort study of all group 1 PAH patients on parenteral prostanoids who transitioned to selexipag using a standardized outpatient-based protocol. Hospitalization and routine prognostic data were recorded. Results: Fourteen patients were followed for a median of 1,240 (1,052–1,528) days; all were functional class (FC) II (n = 9) or III (n = 5). Thirteen patients completed the transition, including 11 who underwent catheterization 376 (321–735) days after discontinuing parenteral therapy. Three patients had unfavorable transitions requiring reinitiation of parenteral treatment. Overall, pulmonary vascular resistance increased (3.3–4.5 WU, p = 0.01), cardiac index fell (4.0–2.8 L/min/m2, p = 0.01), N-terminal pro-hormone of brain natriuretic peptide worsened (111–205 pg/dL, p = 0.03), but PAH-related hospitalizations improved (27–8, p = 0.02). Cardiac imaging, FC, and 6-min walk distance (6MWD) were unchanged. Patients who failed were older (64 vs. 56 years old) with shorter 6MWD (274 vs. 392 m) and higher REVEAL 2.0 scores (11 vs. 3). Conclusions: Transition from parenteral prostanoids to oral selexipag in carefully selected low-risk patients was well-tolerated in many patients, with up to 5 years of follow-up. Overall, the hemodynamic response to transition is unpredictable and close monitoring, particularly in the first year of follow-up, is recommended. Additional evaluation of potential predictors of success is necessary.

Portopulmonary hypertension (POPH) is a rare complication of liver disease occurring when pulmonary arterial hypertension develops in the setting of portal hypertension. It increases the morbidity and mortality compared to patients with cirrhosis alone. POPH is classified in Group 1 pulmonary arterial hypertension, which has important implications on treatment. After aggressive treatment and in carefully selected patients, liver transplantation can be performed; this can be curative of not only their liver disease but also of their POPH. Treatment and patient selection for optimum results continues to evolve. This article provides updates on the definition, clinical course, and treatment of patients with POPH. We will also discuss the evolving data in treatment and liver transplantation in POPH.