Pulmonary vasodilators in patients with advanced chronic kidney disease and pre-capillary pulmonary hypertension-A case series.

Pulmonary hypertension (PH) is a prevalent complication among patients with chronic kidney disease (CKD). In these patients, pulmonary vasodilators may be useful but are underused. We describe a group of patients with precapillary PH and advanced CKD treated with pulmonary vasodilators. This was a case series of patients with CKD stage 4 and 5 and precapillary PH (isolated or combined) based on right heart catheterization (RHC) treated with pulmonary vasodilators from 2018 to 2023. Of 263 patients with isolated precapillary or combined PH and advanced CKD, only 17 (6%) were treated with pulmonary vasodilators; 53% (n = 9) with precapillary PH and 47% (n = 8) with combined PH. Most patients (94%, n = 16) received phosphodiesterase-5 antagonists, while 12% (n = 2) received endothelin receptor antagonists. Adverse clinical outcomes were seen in 35% of patients within a year. The use of pulmonary vasodilator did not prevent adverse outcomes in patients with precapillary PH and advanced CKD.

Randomized Controlled Trials of Pulmonary Vasodilator Therapy Adjunctive to Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn: A Systematic Review.

Inhaled nitric oxide (iNO) is a pulmonary vasodilator considered standard of care to treat persistent pulmonary hypertension of the newborn. However, not all infants respond to iNO. The authors performed a systematic review to examine methodology, outcomes, and challenges of randomized controlled trials testing pulmonary vasodilator medications adjunctive to iNO. The 5 trials identified showed heterogeneity in eligibility criteria and outcomes assessed. No trial achieved recruitment goals, limiting conclusions regarding efficacy, safety, and pharmacology. Trial design consensus and alternative methodologic strategies such as deferred consent, real-world controls, nonrandomized database assessments, and Bayesian statistical approaches are needed.

Short term effect of intravenous treprostinil in term and preterm infants with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition in newborns. We aimed to assess the clinical and echocardiographic responses of term and preterm infants to treprostinil. METHODS: This retrospective study included newborns diagnosed with PH and treated with treprostinil as additional therapy after inhaled nitric oxide administration in the neonatal intensive care unit of a tertiary center. Term and preterm infants were compared in terms of echocardiographic findings and clinical findings 4 weeks after treprostinil treatment. RESULTS: During the study period, 11 term and 18 preterm infants were diagnosed with PH and received treprostinil. There were no differences in the echocardiographic findings of interventricular septal deviation, direction of shunt, and ratio of estimated pulmonary artery pressure over systolic blood pressure. Congenital diaphragmatic hernia was the most common condition occurring upon PH diagnosis among term infants, while severe bronchopulmonary dysplasia was the most common in preterm infants. Improvements in echocardiographic findings were more pronounced in term infants than in preterm infants (100% vs. 55.6%, P = 0.012). The inhaled nitric oxide dose was gradually tapered for term infants and was lower than that for preterm infants at 1, 2, and 3 weeks after treprostinil. CONCLUSION: Intravenous treprostinil could be an adjuvant therapy option for term and preterm infants with PH, especially for those who cannot receive oral medication. The efficacy and safety of treprostinil in this population with PH should be investigated further.

Prostaglandin-E1 infusion in persistent pulmonary hypertension of the newborn.

BACKGROUND: Neonates with persistent pulmonary hypertension of the newborn (PPHN) can present with hypoxia and right ventricular dysfunction with resultant inadequate oxygen delivery and end-organ damage. This study describes the use of prostaglandin-E1 (PGE) for ductal patency to preserve right ventricular systolic function and limit afterload in newborns with PPHN. METHODS: This is a retrospective cohort study that follows the hemodynamics, markers of end-organ perfusion, length of therapeutics, and echocardiographic variables of 57 newborns who used prostglandin-E1 in the setting of PPHN. RESULTS: Tachycardia, lactic acidosis, and supplemental oxygen use improved following PGE initiation. Fractional area change (FAC), to assess right ventricular systolic function, and pulmonary arterial acceleration time indexed to right ventricular ejection time (PAAT/RVET), to assess right ventricular afterload, also improved over three time points relative to PGE use (before, during, and after). CONCLUSIONS: Overall, we described the safety and utility of PGE in newborns with severe PPHN for stabilization while allowing natural disease progression.

Real-world clinical practice of pulmonary arterial hypertension in Japan: Insights from a large administrative database.

Pulmonary arterial hypertension (PAH) is a fatal disease that often occurs at an early age. In recent years, aggressive treatment with multiple drugs from the early-stage diagnosis is expected to improve the prognosis. Indeed, a high rate of initial combination therapy and excellent treatment outcomes have been reported from specialized centers for PAH in Japan. However, information on PAH epidemiology, including non-PAH specialized centers in Japan, is unclear. To address the above, we conducted a retrospective observational cohort study from April 2008 to September 2020 using real-world evidence from a large-scale administrative database (Medical Data Vision) to examine baseline characteristics, comorbidities, and treatment profiles of Japanese patients with PAH. Five hundred and eighteen patients with PAH (treatment-naive PAH, age 67.2 ± 15.9) were identified through our comprehensive approach which combined PAH disease codes, medications, and diagnostic procedures. Moreover, we showed that a larger proportion of patients received monotherapy in their initial treatment (66%) compared to those receiving combination therapy (34%). During the 1-year follow-up after PAH diagnosis, 13% of patients increased their PAH medications while other patients either decreased their PAH medications (6%) or discontinued PAH treatment (27%). The 3- and 5-year event-free survival rates of all-cause death were 72% and 64%, respectively. This is the first large-scale administrative database study that provides insights into real-world PAH management in Japan. This study highlighted a different PAH clinical landscape which included a larger portion of the elderly population, higher initial monotherapy treatment, and lower survival rates than previous studies.

Pulmonary vasodilator therapy in sarcoidosis-associated pulmonary hypertension may decrease lung function decline and mortality.

The efficacy of treating sarcoidosis-associated pulmonary hypertension (SAPH) with pulmonary vasodilator therapy is unclear. The INCREASE trial showed improvement in 6-minute walk distance (6MWD) and in decline in functional vital capacity (FVC) in patients with interstitial lung disease and pulmonary hypertension. We hypothesize that patients with SAPH treated with pulmonary vasodilators have reduced decline in FVC. We retrospectively analyzed patients with SAPH who underwent lung transplantation evaluation. The primary objective was to compare change in FVC between patients with SAPH who received pulmonary vasodilators (treated) and those who did not (untreated). Secondary objectives were to compare the change in 6MWD, change in oxygen requirement, transplant rates, and mortality between treated and untreated SAPH patients. We identified 58 patients with SAPH; 38 patients received pulmonary vasodilator therapy, and 20 patients did not. Treated SAPH patients had significantly less decline in FVC than untreated SAPH patients (+54 mL vs. -357 mL, p < 0.01). Treated SAPH patients had significantly higher survival than untreated SAPH patients. Receiving PH therapy was significantly associated with a change in FVC (estimate 0.36 ± 0.07, p < 0.01) and decreased mortality (hazard ratio 0.29, confidence interval 0.12-0.67, p < 0.01). Among patients with SAPH, those who received pulmonary vasodilator therapy had significantly less decline in FVC and increased survival. Receiving pulmonary vasodilator therapy was significantly associated with FVC change and decreased mortality. These study findings point towards potential benefit of pulmonary vasodilator therapy in SAPH patients. Further prospective studies are required to fully elucidate the benefits of pulmonary vasodilator therapy in SAPH.

Inhaled Prostacyclins for Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Studies evaluating inhaled prostacyclins for the management of acute respiratory distress syndrome (ARDS) have produced inconsistent results regarding their effect on oxygenation. The purpose of this systematic review and meta-analysis was to evaluate the change in the Pao2/Fio2 ratio after administration of an inhaled prostacyclin in patients with ARDS. DATA SOURCES: We searched Ovid Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, Scopus, and Web of Science. STUDY SELECTION: We included abstracts and trials evaluating administration of inhaled prostacyclins in patients with ARDS. DATA EXTRACTION: Change in the Pao2/Fio2 ratio, Pao2, and mean pulmonary artery pressure (mPAP) were extracted from included studies. Evidence certainty and risk of bias were evaluated using Grading of Recommendations Assessment, Development, and Evaluation and the Cochrane Risk of Bias tool. DATA SYNTHESIS: We included 23 studies (1,658 patients) from 6,339 abstracts identified by our search strategy. The use of inhaled prostacyclins improved oxygenation by increasing the Pao2/Fio2 ratio from baseline (mean difference [MD], 40.35; 95% CI, 26.14-54.56; p < 0.00001; I2 = 95%; very low quality evidence). Of the eight studies to evaluate change in Pao2, inhaled prostacyclins also increased Pao2 from baseline (MD, 12.68; 95% CI, 2.89-22.48 mm Hg; p = 0.01; I2 = 96%; very low quality evidence). Only three studies evaluated change in mPAP, but inhaled prostacyclins were found to improve mPAP from baseline (MD, -3.67; 95% CI, -5.04 to -2.31 mm Hg; p < 0.00001; I2 = 68%; very low quality evidence). CONCLUSIONS: In patients with ARDS, use of inhaled prostacyclins improves oxygenation and reduces pulmonary artery pressures. Overall data are limited and there was high risk of bias and heterogeneity among included studies. Future studies evaluating inhaled prostacyclins for ARDS should evaluate their role in ARDS subphenotypes, including cardiopulmonary ARDS.

Management of Acute Right Ventricular Failure.

PURPOSE OF REVIEW: Acute right ventricular failure (RVF) is a frequent condition associated with high morbidity and mortality. This review aims to provide a current overview of the pathophysiology, presentation, and comprehensive management of acute RVF. RECENT FINDINGS: Acute RVF is a common disease with a pathophysiology that is not completely understood. There is renewed interest in the right ventricle (RV). Some advances have been principally made in chronic right ventricular failure (e.g., pulmonary hypertension). Due to a lack of precise definition and diagnostic tools, acute RVF is poorly studied. Few advances have been made in this field. Acute RVF is a complex, frequent, and life-threatening condition with several etiologies. Transthoracic echocardiography (TTE) is the key diagnostic tool in search of the etiology. Management includes transfer to an expert center and admission to the intensive care unit (ICU) in most severe cases, etiological treatment, and general measures for RVF.

Predictors of hospitalization for respiratory failure among patients with sarcoidosis-associated pulmonary hypertension.

Pulmonary hypertension leads to significant morbidity and mortality in patients with sarcoidosis. In this study, we examined clinical factors associated with the risk of respiratory failure-related hospitalization in 58 patients with sarcoidosis-associated pulmonary hypertension. Pulmonary vasodilator therapy and spirometry were associated with reduced risk of hospitalization in this cohort.

Dramatically Improved Severe Pulmonary Arterial Hypertension Caused by Qing-Dai (Chinese Herbal Drug) for Ulcerative Colitis.

Pulmonary arterial hypertension (PAH) is a rare and fatal disease for which some causative drugs have been developed. Qing-Dai is a Chinese herbal drug that is sometimes used as a specific treatment for ulcerative colitis in Asia, including Japan. Here, we report a case of severe Qing-Dai-induced PAH. A 19-year-old woman who has been taking Qing-Dai for 8 months was admitted for exertional dyspnea. Her mean pulmonary artery pressure dramatically improved from 72 to 18 mmHg with Qing-Dai discontinuation and PAH-specific therapy. After 6 years of onset, she had not relapsed with PAH with PAH-specific therapy.

Pulmonary vasodilator therapies in pulmonary arterial hypertension associated with CHD: a systematic review and network meta-analysis.

The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomes included pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD -0.33, 95% CI -0.51 to -0.14, MD -0.58, 95% CI -0.75 to -0.22 and MD -0.62, 95% CI -0.92 to -0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported; however, serious adverse event rates were relatively low (4.8-8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.

Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience.

Introduction: Phosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH). Methods and materials: This is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation. Results: Over the study period, 154 children with a median age of 1.0 (range 0.0-6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients. Conclusion: Tadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means.

Subcutaneous Treprostinil Improves Surgical Candidacy for Next Stage Palliation in Single Ventricle Patients With High-Risk Hemodynamics.

Single ventricle (SV) patients with pulmonary vascular disease (SV-PVD) are considered poor surgical candidates for Glenn or Fontan palliation. Given limited options for Stage 1 (S1) and Stage 2 (S2) SV patients with SV-PVD, we report on the use of subcutaneous treprostinil (TRE) to treat SV-PVD in this population. This single-center, retrospective cohort study examined SV patients who were not candidates for subsequent surgical palliation due to SV-PVD and were treated with TRE. The primary outcome was ability to progress to the next surgical stage; secondary outcomes included changes in hemodynamics after TRE initiation. Between 3/2014 and 8/2021, 17 SV patients received TRE for SV-PVD: 11 after S1 and 6 after S2 (median PVR 4.1 [IQR 3.2-4.8] WU*m2 and 5.0 [IQR 1.5-6.1] WU*m2, respectively). Nine of 11 (82%) S1 progressed to S2, and 2 (18%) underwent heart transplant (HTx). Three of 6 (50%) S2 progressed to Fontan, 1 underwent HTx and 2 are awaiting Fontan on TRE. TRE significantly decreased PVR in S1 patients with median post-treatment PVR of 2.0 (IQR 1.5-2.6) WU*m2. TRE can allow for further surgical palliation in select pre-Fontan patients with SV-PVD, obviating the need for HTx. Improvement in PVR was significant in S1 patients and persisted beyond discontinuation of therapy for most patients.

Novel use of riociguat in infants with severe pulmonary arterial hypertension unable to wean from inhaled nitric oxide.

Introduction: Riociguat, an oral soluble guanylate cyclase stimulator, has been approved for use in adults with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension. However, there is limited data on its therapeutic use in children. Case Presentation: We report the case of two infants with severe suprasystemic pulmonary hypertension who were successfully treated with riociguat after failure to wean off inhaled nitric oxide (iNO) despite combination PAH therapy. Case 1 is a 6-month-old term male with TBX4 deletion who presented with severe hypoxemic respiratory failure and severe PAH immediately after birth. Initial cardiac catheterization showed PVRi 15.5 WU*m2. Marked hypoxemia and PAH persisted despite aggressive therapy with sildenafil, bosentan, intravenous treprostinil, and milrinone. The infant required high doses of inhaled nitric oxide (60 ppm) and manifested significant post-ductal hypoxemia and hemodynamic instability with any attempt at weaning. After discontinuation of sildenafil, initiation, and very slow uptitration of riociguat, the patient was able to maintain hemodynamic stability and wean from nitric oxide over 6 weeks with persistently severe but not worsened pulmonary hypertension. Case 2 is a 4-month-old term male with compound heterozygous SLC25A26 mutation and severe pulmonary hypertension. Initial cardiac catheterization showed PVRi 28.2 WU*m2. After uptitration of sildenafil, bosentan, and IV treprostinil, serial echocardiograms continued to demonstrate near-systemic pulmonary hypertension. He failed multiple attempts to wean off typical doses of iNO (10-20 ppm) over the following weeks with tachypnea, hypoxemia, and worsening pulmonary hypertension on echocardiogram despite continued aggressive combination targeted therapy. After a 24-h sildenafil washout, he was initiated and uptitrated on riociguat with concomitant, successful wean of nitric oxide over one week that was well tolerated. No serious adverse effects in the titration period were observed. Conclusion: Riociguat may be considered as an adjuvant therapeutic agent in selected children with severe PAH who are poorly responsive to sildenafil therapy and unable to wean from iNO.

Chronic Thromboembolic Pulmonary Hypertension: An Observational Study.

Background and Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) has a high mortality. The treatment of CTEPH could be balloon pulmonary angioplasty (BPA), medical (MT) or pulmonary endarterectomy (PEA). This study aims to assess the clinical characteristics of CTEPH patients, surgically or medically treated, in a pulmonology referral center. Materials and Methods: A total of 124 patients with PH with suspected CTEPH (53 male subjects and 71 female subjects; mean age at diagnosis 67 ± 6) were asked to give informed consent and then were evaluated. The presence of CTEPH was ascertained by medical evaluations, radiology and laboratory tests. Results: After the evaluation of all clinical data, 65 patients met the inclusion criteria for CTEPH and they were therefore enrolled (22 males and 43 females; mean age at diagnosis was 69 ± 8). 26 CTEPH patients were treated with PEA, 32 with MT and 7 with BPA. There was a statistically significant age difference between the PEA and MT groups, at the time of diagnosis, the PEA patients were younger than the MT patients, whereas there was no statistically significant difference in other clinical characteristics (e.g., smoking habit, thrombophilia predisposition), as well as functional and hemodynamic parameters (e.g., 6-min walk test, right heart catheterization). During three years of follow-up, no patients in the PEA groups died; conversely, eleven patients in the MT group died during the same period (p < 0.05). Furthermore, a significant decrease in plasma BNP values and an increase in a meter at the six-minute walk test, 1 and 3 years after surgery, were observed in the PEA group (p < 0.05). Conclusions: This study seems to confirm that pulmonary endarterectomy (PEA) can provide an improvement in functional tests in CTEPH.

Beraprost Sodium for Pulmonary Hypertension in Dogs: Effect on Hemodynamics and Cardiac Function.

Pulmonary hypertension (PH) is a fatal condition that affects many dogs. In humans, PH is often treated with beraprost sodium (BPS). However, the effectiveness of BPS for canine PH has not been established. This study aimed to evaluate the clinical and cardiovascular response of BPS in canine patients with PH of various causes. Sixteen dogs with PH (post-capillary PH, n = 8; pre-capillary PH, n = 8) were included. BPS was continuously administered twice daily at 15 µg/kg. All dogs underwent echocardiography, including speckle-tracking analysis and blood pressure measurement, before and after BPS administration. Continuous BPS administration (range: 13.2-22.0 µg/kg) significantly decreased the pulmonary and systemic vascular impedance and increased left and right ventricular myocardial strain. In dogs with post-capillary PH, BPS administration caused no significant worsening of the left atrial pressure indicators. No side effects of BPS were observed in any dog. BPS also improved cardiac function and pulmonary circulation through pulmonary vasodilation, suggesting that BPS may be an additional treatment option for canine PH of various causes. Particularly, BPS increased left ventricular function and systemic circulation without worsening the left heart loading condition in dogs with post-capillary PH.

A systematic review of clinical study evidence for pulmonary vasodilator therapy following surgery with cardiopulmonary bypass in children with CHD.

OBJECTIVES: Complications from pulmonary hypertension are one of the leading contributors to morbidity and mortality post-cardiopulmonary bypass surgery in children with CHD. Pulmonary vasodilator therapies are commonly used post-operatively, but the optimal target patient population, therapy choice, timing of therapy initiation, and duration of therapy are not well defined. METHODS: We used PubMed and EMBASE to identify studies from 2000 to 2020 investigating the use of pulmonary vasodilator therapy post-cardiopulmonary bypass in children aged 0-18 years. To ensure eligibility criteria, studies were systematically reviewed by two independent reviewers. RESULTS: We identified 26 studies of 42,971 children across four medication classes; 23 were single centre, 14 were prospective, and 11 involved randomisation (four of which employed a placebo-control arm). A disproportionate number of children were from a single retrospective study of 41,872 patients. Definitions varied, but change in pulmonary haemodynamics was the most common primary outcome, used in 14 studies. Six studies had clinical endpoints, with mortality the primary endpoint for two studies. Treatment with inhaled nitric oxide, iloprost, and sildenafil all resulted in improved haemodynamics in specific cohorts of children with post-operative pulmonary hypertension, although improved outcomes were not consistently demonstrated across all treated children. Iloprost may be a cheaper alternative to inhaled nitric oxide with similar haemodynamic response. CONCLUSION: Studies were predominantly single-centre, a control arm was rarely used in randomised studies, and haemodynamic endpoints varied significantly. Further research is needed to reduce post-operative morbidity and mortality from pulmonary hypertension in children with CHD.

Beneficial Effects of Pulmonary Vasodilators on Pre-Capillary Pulmonary Hypertension in Patients with Chronic Kidney Disease on Hemodialysis.

BACKGROUND: In patients with chronic kidney disease (CKD) on hemodialysis, comorbid pulmonary hypertension (PH) aggravates exercise tolerance and eventually worsens the prognosis. The treatment strategy for pre-capillary PH, including combined pre- and post-capillary PH (Cpc-PH), has not been established. OBJECTIVES: This study aimed to evaluate the impact of pulmonary vasodilators on exercise tolerance and pulmonary hemodynamics in patients with CKD on hemodialysis. METHODS AND RESULTS: The medical records of 393 patients with suspected PH who underwent right heart catheterization were reviewed. Of these, seven patients had isolated pre-capillary PH and end-stage CKD on hemodialysis. Pulmonary vasodilators decreased pulmonary vascular resistance from 5.9 Wood units (interquartile range (IQR), 5.5-7.6) at baseline to 3.1 Wood units (IQR, 2.6-3.3) post-treatment (p = 0.02) as well as increased pulmonary capillary wedge pressure from 10 mmHg (IQR, 7-11) to 11 mmHg (IQR, 8-16) (p = 0.04). Pulmonary vasodilators increased the World Health Organization functional class I or II from 0% to 100% (p = 0.0002) and the 6 min walk distance from 273 m (IQR, 185-365) to 490 m (IQR, 470-550) (p = 0.03). CONCLUSIONS: Pulmonary vasodilators for PH in patients with CKD on hemodialysis decrease pulmonary vascular resistance and eventually improve exercise tolerance. Pulmonary vasodilators may help hemodialysis patients with pre-capillary PH, although careful management considering the risk of pulmonary edema is required.