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Background: A prolonged QRS duration ( ≥ 120 milliseconds) predicts outcomes in patients with left-sided heart failure, but the impact in idiopathic pulmonary arterial hypertension (IPAH) and right-sided heart failure is unknown. We assessed the prognostic value of a prolonged ECG QRS duration in patients with IPAH in China.Methods: We retrospectively analyzed the initial 12-lead ECG for QRS duration in 212 consecutive patients with IPAH seen at our center between 2007 and 2009. Patients were divided according to QRS duration < 120 milliseconds or ≥ 120 milliseconds. The baseline characteristics and survival of the two groups were compared.Results: Thirty-five patients with IPAH (16.5%) had a QRS duration ≥ 120 milliseconds, including 21 (9.9%) with right bundle-branch block and 14 (6.6%) with nonspecific intraventricular conduction delay. Prolongation of the QRS duration was associated with a worse World Health Organization functional class and 6-min walk test distance and higher serum uric acid when compared with patients with normal QRS duration (P < .05). Prolonged QRS duration was an independent predictor of mortality and was associated with a 2.5-fold increased risk of death (P = .024).Conclusion: Prolongation of the QRS duration is associated with clinical severity in patients with IPAH. In addition, QRS prolongation has an independent association with cardiopulmonary mortality and could be a new predictor of adverse outcome in patients with IPAH. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disease for which both continuous IV epoprostenol and continuous subcutaneous treprostinil have proven effective. With continuous IV treprostinil having potential advantages over both of the above therapies, we investigated the safety and efficacy of this regimen in patients with PAH. METHODS: We conducted a 12-week, prospective, open-label, uncontrolled, multicenter study of continuous IV treprostinil in 16 patients with PAH that was idiopathic (n = 8), related to connective tissue disease (n = 6), or related to congenital heart disease (n = 2). The primary end point was change from baseline to week 12 in exercise capacity assessed by the 6-min walk (6MW) test. RESULTS: Continuous IV treprostinil increased 6MW distance (mean +/- SE) by 82 m from baseline (319 +/- 22 m) to week 12 (400 +/- 26 m) [n = 14; p = 0.001]. There were also significant improvements in the secondary end points of Naughton-Balke treadmill time (p = 0.007), Borg dyspnea score (p = 0.008), and hemodynamics (mean pulmonary artery pressure, p = 0.03; cardiac index, p = 0.002; pulmonary vascular resistance, p = 0.001) at week 12 compared with baseline. Side effects were mild and consistent with those reported with prostacyclin treatment. One death, unrelated to study drug, occurred during the 12-week study in a patient who received 3 days of treprostinil and died 2 weeks later. CONCLUSIONS: Long-term IV infusion of treprostinil is safe and appears to be effective for the treatment of patients with PAH. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary microvasculature leading to elevated precapillary pulmonary hypertension. Pulmonary vascular remodeling, a characteristic of PAH, is driven by dysfunctions in the signaling between the pulmonary smooth muscle and endothelial cells with abnormalities that affect cell proliferation and immune dysregulation. Sotatercept, an activin signaling inhibitor, has recently been approved by the US Food and Drug Administration for the treatment of PAH based on two pivotal clinical trials. Evidence-based clinical trials have provided a framework to guide clinicians treating the disease; however, they are not tailored to the individual patient. Often, recommendations from these data are unclear or too general, due to remaining gaps in knowledge. In this edition of "How I Do It," we provide a case-based discussion of common clinical decisions regarding diagnostic testing, choice of first-line agents, escalation of therapy, potential timing of sotatercept, safety awareness, practical use, potential management changes, and the future use of sotatercept in other pulmonary hypertension cohorts., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: I. R. P. is a consultant for Acceleron/Merck, Aerovate, Gossamer, Keros, Janssen, Liquidia, Respira, and United Therapeutics. Tufts Medical Center receives grant support to allow I. R. P. to be Principal Investigator for Acceleron/Merck, Janssen, Keros, Tenax, and United Therapeutics. D. W. has served on the advisory board for Gossamer, Liquidia, and Merck Roivant; and has been a speaker for Janssen and United Therapeutics. M. G.-M. is a consultant for Acceleron/Merck, Aerami (ended), Bayer (ended), Janssen, JucaBio, Keros, and United Therapeutics. George Washington Medical Faculty Associates receives grant support to allow M. G.-M. to be a Principal Investigator from Acceleron/Merck, Aerovate, Gossamer, and Keros (pending). M. G.-M.’s husband is an employee of Intellia Therapeutics., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Multiparametric risk assessment tools determine mortality risk in patients with pulmonary arterial hypertension (PAH) by combining invasive and noninvasive variables so management strategies can be tailored to individuals., Research Question: Can a risk score based on common echocardiographic parameters risk-stratify patients with PAH?, Study Design and Methods: A Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) echocardiographic risk score (REVEAL-ECHO) was derived using retrospective echocardiographic data from 2,400 adult patients with PAH enrolled in the REVEAL registry database. A stepwise Cox regression model identified echocardiographic parameters significantly predictive of survival. Values were assigned to each selected parameter based on survival at 12 months' follow-up (Kaplan-Meier estimates). The REVEAL-ECHO risk score was the sum of individual values. Patients were categorized as having low, intermediate, or high risk based on Kaplan-Meier-predicted 12-month survival., Results: The risk score included four echocardiographic parameters-right ventricular (RV) chamber enlargement, reduced RV systolic function, tricuspid regurgitation severity, and pericardial effusion-and accounted for PAH etiology. Higher REVEAL-ECHO risk scores signaled lower probability of 12-month survival. Statistically significant separation of mortality risk was observed among the risk strata: intermediate vs low (hazard ratio [HR], 1.43; 95% CI, 1.17-1.75; P = .0004) and high vs low (HR, 2.60; 95% CI, 2.19-3.10; P < .0001). Augmentation of the REVEAL Lite 2 risk calculator with REVEAL-ECHO risk scores achieved separation of REVEAL Lite 2 into four risk groups and identified a subgroup of patients with a low REVEAL Lite 2 risk score who were at higher risk (intermediate-low risk) and a subgroup of patients with an intermediate REVEAL Lite 2 risk score who also were at higher risk (intermediate-high risk)., Interpretation: A REVEAL-ECHO risk score, derived using four echocardiographic parameters, may discriminate risk further when used as an adjunct to current risk assessment scores. Further validation is required., (Copyright © 2023. Published by Elsevier Inc.)

Background: Pulmonary arterial hypertension is a progressive, fatal disease. Published treatment guidelines recommend treatment escalation on the basis of regular patient assessment with the goal of achieving or maintaining low-risk status. Various strategies are available to determine risk status. This analysis describes an update of the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator (REVEAL 2.0) and compares it with recently published European Society of Cardiology/Respiratory Society guideline-derived risk assessment strategies., Methods: A subpopulation from the US-based registry REVEAL that survived ≥ 1 year postenrollment (baseline for this cohort) was analyzed. For REVEAL 2.0, point values and cutpoints were reassessed, and new variables were evaluated. The Kaplan-Meier method was used to estimate survival at 12 months postbaseline; discrimination was quantified using the c-statistic. Mortality estimates and discrimination were compared between REVEAL 2.0 and Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and French Pulmonary Hypertension Registry (FPHR) risk assessment strategies. For this comparison, a three-category REVEAL 2.0 score was computed in which patients were classified as low-, intermediate-, or high-risk., Results: REVEAL 2.0 demonstrated similar discrimination as the original calculator in this subpopulation (c-statistic = 0.76 vs 0.74), provided excellent separation of risk among the risk categories, and predicted clinical worsening as well as mortality in patients who were followed ≥ 1 year. The REVEAL 2.0 three-category score had greater discrimination (c-statistic = 0.73) than COMPERA (c-statistic = 0.62) or FPHR (c-statistic = 0.64). Compared with REVEAL 2.0, COMPERA and FPHR both underestimated and overestimated risk., Conclusions: REVEAL 2.0 demonstrates greater risk discrimination than the COMPERA and FPHR risk assessment strategies in patients enrolled in REVEAL. After external validation, the REVEAL 2.0 calculator can assist clinicians and patients in making informed treatment decisions on the basis of individual risk profiles., Trial Registry: ClinicalTrials.gov; No. NCT00370214; URL: www.clinicaltrials.gov., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Disease-specific patient-reported outcome (PRO) instruments are important in assessing the impact of disease and treatment. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is the first instrument for quantifying pulmonary arterial hypertension (PAH) symptoms and impacts developed according to the 2009 US Food and Drug Administration PRO guidance; previous qualitative research in patients with PAH supported its initial content validity., Methods: Content finalization and psychometric validation were conducted by using data from A Study of Macitentan in Pulmonary Arterial Hypertension to Validate the PAH-SYMPACT (SYMPHONY), a single-arm, 16-week trial with macitentan 10 mg in US patients with PAH. Item performance, Rasch analysis, and factor analyses were used to select the final item content of the PRO and to define its domain structure. Internal consistency, test-retest reliability, known-group and construct validity, sensitivity to change, and influence of oxygen on item performance were evaluated., Results: Data from 278 patients (79% female; mean age: 60 years) were analyzed. Following removal of redundant/misfitting items, the final questionnaire has 11 symptom items across two domains (cardiopulmonary and cardiovascular symptoms) and 11 impact items across two domains (physical and cognitive/emotional impacts). Differential item function analysis confirmed that PRO scoring is unaffected by oxygen use. For all four domains, internal consistency reliability was high (Cronbach's alpha > 0.80), and scores were highly reproducible in stable patients (intraclass correlation coefficient: 0.84-0.94). Correlations with the Cambridge Pulmonary Hypertension Outcome Review questionnaire and the 36-item Medical Outcomes Study Short Form Survey were moderate to high ([r] = 0.34-0.80). The questionnaire differentiated well between patients with varying disease severity levels and was sensitive to improvements in clinician- and patient-reported disease severity., Conclusions: The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire is a brief, disease-specific PRO instrument possessing good psychometric properties that can be administered in clinical practice and clinical studies., Trial Registry: ClinicalTrials.gov; No.: NCT01841762; URL: www.clinicaltrials.gov., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prostacyclins improve symptoms and survival in pulmonary arterial hypertension (PAH). In response to risks associated with external delivery systems, an implantable IV infusion system was developed. A multicenter, prospective, single-arm, clinical trial (DelIVery for PAH) was conducted to evaluate this system for treprostinil in PAH. This analysis describes the findings related to the implant procedure., Methods: Patients (N = 64) with PAH (World Health Organization group 1) receiving stable IV treprostinil were enrolled. Patients were transitioned to a temporary peripheral IV infusion catheter prior to the procedure. System implantation was performed at 10 centers under general anesthesia or deep IV sedation by clinicians from various specialties. Central venous access was via the cephalic, subclavian, jugular, or axillary vein. Using an introducer and fluoroscopic guidance, the distal tip of the infusion catheter was placed at the superior caval-atrial junction. The catheter was tunneled from the venous access site to an abdominal subcutaneous pocket, where the pump was placed., Results: Of the 64 patients enrolled, four exited prior to implantation. All 60 implant procedures were successful. At baseline, all patients were receiving treprostinil via an external pump at a mean dose of 71.4 ± 27.8 ng/kg/min (range: 22-142 ng/kg/min). The implant averaged 102 ± 32 min (range: 47-184 min). Clinically significant implant procedure-related complications included one pneumothorax, two infections, and one episode of atrial fibrillation. There were three postimplantation catheter dislocations in two patients. Common implant-related events that were not complications included implant site pain (83%) and bruising (17%)., Conclusions: The procedure for inserting a fully implantable system for treprostinil was successfully performed, with few complications., Trial Registry: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion., Methods: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature., Results: Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 ± 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 ± 1.7 hours per week preimplantation, and this time decreased to 0.6 ± 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions., Conclusions: The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction., Trial Registry: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Trastuzumab emtansine (T-DM1) is a Food and Drug Administration-approved novel agent for the treatment of HER-2 positive advanced breast cancer. We report a case of pulmonary arterial hypertension (PAH) that we attribute to the use of T-DM1. A 43-year-old woman with stage IV breast cancer presented with dyspnea on exertion. After excluding other secondary causes of pulmonary hypertension, a diagnosis of moderately severe PAH was made based on right heart catheterization. History revealed that the patient had been on T-DM1 before presentation. During T-DM1 treatment, the patient experienced hereditary hemorrhagic telangiectasia-like symptoms consisting of spider angiomata-skin lesions, epistaxis, and hematochezia, which resolved with discontinuation of T-DM1. Temporal associations of T-DM1 use with the development of PAH in the patient, and the reported association between hereditary hemorrhagic telangiectasia and PAH via genetic linkage, led us to suspect T-DM1 as the cause of PAH., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether recent advances in pulmonary arterial hypertension therapy can be safely applied to sarcoidosis-associated pulmonary hypertension (SAPH). Evidence for prostacyclin (PG) therapy in SAPH is limited., Methods: We conducted a single-center, retrospective review of 46 patients with sarcoidosis, 26 of whom had SAPH. Thirteen received PG as monotherapy or in combination with oral vasodilators., Results: Follow-up right-sided heart catheterization at a mean of 12.7 months revealed improved cardiac output, cardiac index, and pulmonary vascular resistance. Functional class and N-terminal pro-brain natriuretic peptide levels also improved in patients treated with PG. No significant change in oxygen requirement was seen with vasodilator therapy initiation. At 2 years, 15 patients with SAPH survived, including eight on PG, and at 5 years, seven survived, including five on PG. Survival was significantly reduced in patients with SAPH compared with patients who had sarcoidosis without pulmonary hypertension. Multivariate analysis demonstrated that the use of PG therapy in SAPH is not associated with increased mortality., Conclusions: Many patients with severe SAPH showed significant hemodynamic and clinical improvement on long-term IV or subcutaneous PG therapy and had survival outcomes similar to patients with moderate SAPH on oral vasodilator therapy.

Objective: The pulmonary hypertension connection (PHC) equation predicts contemporary survival in idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension (PAH). The aim of this study is to validate the PHC equation in a prospective PAH population cohort and compare its predictability with the French equation., Methods: We compared the rates of actual survival in patients prospectively followed for up to 3.5 years in four double-blind, randomized trials and their open-label extension studies with predicted survival calculated using the PHC equation [(P(t) = e((-A(x,y,z)t)), A(x,y,z) = e((-1.270-0.0148x + 0.0402y - 0.361z)), where P(t) is the probability of survival, t the time interval in years, x the mean pulmonary artery pressure, y the mean right atrial pressure, and z the cardiac index] and the French equation in patients with idiopathic, heritable, and anorexigen-associated PAH (n = 449)., Results: Mean age was 44 ± 15 years, 77% were women, and 80% had World Health Organization (WHO) functional class III/IV symptoms. The mean 6-min walk distance (6MWD) was 354 ± 95 m. The baseline hemodynamics were as follows: mean right atrial pressure 10 ± 6 mm Hg, mean pulmonary artery pressure 59 ± 15 mm Hg, and cardiac output 4.1 ± 1.5 L/min. The 1-, 2-, and 3-year Kaplan-Meier survival rates were 89%, 80%, and 70%, respectively; the nonadjusted survival rates were 91%, 87%, and 84%, respectively. The expected survival predicted by both the PHC and the French equations was similar to the actual observed Kaplan-Meier survival and was within its 95% confidence limits. The PHC equation also performed well when used in patients with WHO functional class III/IV, cardiac output < 4 L/min, or 6MWD < 380 m., Conclusion: Risk prediction equations (PHC and French) accurately predicted survival and may be useful for risk estimation in patients with idiopathic, heritable, and anorexigen-associated PAH in large cohort studies. Their use for survival prediction for individual patients needs further study.

Background: In pulmonary arterial hypertension (PAH), survival predictions can be important for optimization of therapeutic strategies. The present study aimed to validate a quantitative algorithm for predicting survival derived from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) and develop a simplified calculator for everyday clinical use., Methods: Prospectively collected data from patients with newly diagnosed (< 3 months) World Health Organization group I pulmonary hypertension enrolled in the REVEAL Registry were used to validate a predictive algorithm for 1-year survival. Model calibration was evaluated by comparing algorithm-predicted survival with observed Kaplan-Meier estimates for the overall validation cohort and for five risk groups. Similarly, the risk discriminators for the simplified calculator were compared with those of the quantitative algorithm., Results: The validation cohort comprised 504 individuals with mean ± SD 6-min walk distance 308 ± 128 m, and 61.5% were functional class III. The proportion of patients surviving 1 year fell within the range predicted by the model (95.1%, 91.5%, 84.6%, 76.3%, and 58.2%, respectively) among patients in the low (predicted survival ≥ 95%), average (90% to < 95%), moderate (85% to < 90%), high (70% to < 85%), and very high (< 70%) risk strata. Predicted and observed 1-year survival were similar across risk stratum, and the c-index indicated good discrimination for both the full equation (0.726) and the simplified risk calculator (0.724)., Conclusions: The REVEAL Registry predictive algorithm and simplified risk score calculator are well calibrated and demonstrate good discriminatory ability in patients with newly or previously diagnosed PAH., Trial Registry: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.

Background: Recent studies have reported an increase in catheter-related bloodstream infections (BSIs) and gram-negative BSIs among patients with pulmonary arterial hypertension treated with IV treprostinil. One possible explanation is the neutral pH of the treprostinil diluent compared with the basic pH of epoprostenol. We hypothesized that administering IV treprostinil with epoprostenol diluent will lower the rate of gram-negative BSI., Methods: We prospectively enrolled patients treated with IV treprostinil and changed the diluent from native diluent to epoprostenol diluent. We compared the incidence of BSI and gram-negative BSI between those receiving IV treprostinil with epoprostenol diluent (n = 25) and those actively receiving IV epoprostenol (n = 61), as well as with a cohort of patients who received IV treprostinil in native diluent (n = 34). Incidence rates of BSI were expressed as a fraction of 1,000 medicine treatment days., Results: There were similar rates of BSI in those treated with treprostinil with epoprostenol diluent and those treated with epoprostenol (0.32 of 1,000 vs 0.40 of 1,000; P = .79). Also, there were similar rates of gram-negative BSI in these two cohorts (0.08 of 1,000 vs 0.20 of 1,000; P = .46). BSI rates were not statistically different between those treated with treprostinil with epoprostenol diluent and those treated with treprostinil (0.32 of 1,000 vs 0.90 of 1,000; P = .06). However, gram-negative BSIs were significantly lower in patients treated with treprostinil with epoprostenol diluent than in those treated with treprostinil (0.08 of 1,000 vs 0.71 of 1,000, respectively; P = .01)., Conclusions: Patients treated with treprostinil with epoprostenol diluent have a lower incidence of gram-negative BSI than do those treated with treprostinil and a similar rate to those treated with epoprostenol. Changing the diluent of treprostinil to epoprostenol diluent, in combination with the use of water-tight seals throughout the delivery system, appears to be an effective safety measure.

The current treatment of pulmonary arterial hypertension (PAH) uses vasodilator drugs. Although they improve symptoms associated with PAH, their chronic effects on the pulmonary vasculature and the right ventricle (RV) in humans remain unknown. We report the autopsy findings from a patient with idiopathic PAH treated with epoprostenol successfully for 18 years. The patient died of colon cancer. The pulmonary vasculature surprisingly showed extensive changes of a proliferative vasculopathy. Immunohistochemical studies confirmed ongoing cellular proliferation. Studies of the RV demonstrated concentric hypertrophy with seemingly preserved contractility. The myocardium shifted to glycolytic metabolism. Although the long-term use of epoprostenol contributed to the patient's increased survival, it did not prevent progression of the underlying vascular disease. Remarkably, the RV was able to sustain a normal cardiac output in the face of advanced vascular pathology. The mechanisms by which the RV adapts to chronic PAH need further study.

Pulmonary arterial hypertension (PAH) is a fatal orphan disease. The global epidemiology of PAH is not well known and encourages combined national and international efforts to enhance understanding of the disease. A global database will help unify investigators and patients to foster collaboration and knowledge.

Background: Selective serotonin reuptake inhibitors (SSRIs) prevent the development of and reverse pulmonary hypertension (PH) in animal models. We sought to determine whether SSRIs are associated with a decreased incidence of PH in at-risk patients and whether SSRIs are associated with decreased mortality in patients with established PH., Methods: In a case-control study of patients enrolled in the Surveillance of Pulmonary Hypertension in America (SOPHIA) registry, we tested whether patients without PH (no-PH group; n = 155) were more likely to be receiving SSRIs when compared to those with confirmed PH (n = 1,180). In a separate cohort study of adults with documented PH in the referral-based Pulmonary Hypertension Connection (PHC) registry (n = 542), we classified patients into categories by SSRI use, and we examined whether SSRI use was associated with decreased mortality., Results: In SOPHIA, the confirmed PH group was less likely to be receiving SSRIs compared with the no-PH group (univariate odds ratio [OR], 0.56 [95% confidence interval (CI), 0.39 to 0.82]; p = 0.003; multivariate OR, 0.71l [95% CI, 0.48 to 1.06]; p = 0.09). In the PHC, 69 of 542 patients (13%) were receiving SSRIs at the time of referral. During a mean (+/- SD) follow-up period of 4.0 +/- 3.1 years, 12% of patients receiving SSRIs vs 23% of patients not receiving SSRIs died (hazard ratio [HR], 0.35; 95% CI, 0.14 to 0.87; p = 0.023). The association between SSRI use and decreased mortality persisted after adjusting for age, gender, etiology of PH, and obesity (HR, 0.35; 95% CI, 0.14 to 0.88; p = 0.026)., Conclusions: SSRIs appear to be associated with a decreased development of PH and a decreased mortality in PH. These findings provide a rationale for clinical trials of SSRIs in PH.