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Objective: Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve "seamless" management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery., Methods: This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups., Results: A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1-3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP,  heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p < 0.001), and in group 2 from 17 ± 2 mmHg to 14 ± 2 mmHg (p < 0.001), with no difference between groups. In the postoperative recovery, patients in Group 2 exhibited a reduced duration of mechanical ventilation, 19 (11, 25) hours vs 69 (23, 189) hours, p = 0.001; a shorter stay in the ICU, 8 (6, 12) days vs 16 (9,26) days, p = 0.006; and a shorter postoperative length of stay, 27 (17,55) days vs 39 (29,58) days, p = 0.032. Patients in Group 2 also exhibited a lower incidence of thromboembolic events, 0 (0/26) vs 26% (9/35), p = 0.043; and the need for renal replacement therapy, 0 (0/26) vs 31% (11/35), p = 0.011., Conclusion: Treprostinil reduces pulmonary artery pressure after TCPC procedure. The standardized application of treprostinil may improve the postoperative recovery which should be proven by randomized controlled trials or matched cohort studies in the future., (© 2024. The Author(s).)

Background: Interventional therapies for severe pulmonary arterial hypertension (PAH) can provide right ventricular (RV) decompression and preserve cardiac output. Transcatheter stent placement in a residual ductus arteriosus (PDA) is one potentially effective option in critically ill infants and young children with PAH. We sought to assess recovery of RV function by echocardiographic strain in infants and young children following PDA stenting for acute PAH., Methods: Retrospective review of patients < 2 years old who underwent PDA stenting for acute PAH. Clinical data were abstracted from the electronic medical record. RV strain (both total and free wall components) was assessed from echocardiographic images at baseline and 3, 6, and 12 months post-intervention, as well as at last echocardiogram., Results: Nine patients underwent attempted ductal stenting for PAH. The median age at intervention was 38 days and median weight 3.7 kg. One-third (3of 9) of patients had PAH associated with a congenital diaphragmatic hernia. PDA stents were successfully deployed in eight patients. Mean RV total strain was - 14.9 ± 5.6% at baseline and improved to - 23.8 ± 2.2% at 6 months post-procedure (p < 0.001). Mean free wall RV strain was - 19.5 ± 5.4% at baseline and improved to - 27.7 ± 4.1% at 6 months (p = 0.002). Five patients survived to discharge, and four patients survived 1 year post-discharge., Conclusion: PDA stenting for severe, acute PAH can improve RV function as assessed by strain echocardiography. The quantitative improvement is more prominent in the first 6 months post-procedure and stabilizes thereafter., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta-analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies., Methods and Results: According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta-analyses. Data were extracted and curated for Bayesian network meta-analysis. The primary outcome was the change in the 6-min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (-77.76 m, 95% CI: -102.04 to -54.34 m), Macitentan (-65.32 m, 95% CI: -95.34 to -36.1 m), Bosentan (-64.5 m, 95% CI: -94.7 to -35.07 m), Iloprost (-62.66 m, 95% CI: -99.48 to -27.13 m), Oxygen (-62.42 m, 95% CI: -100.01 to -25.78 m), Treprostinil (-62.01 m, 95% CI: -89.04 to -35.61 m), Riociguat (-60.59 m, 95% CI: -86.11 to -35.98 m), Selexipag (-47.2 m, 95% CI: -85.61 to -10.19 m), Sildenafil (-44.92 m, 95% CI: -74.43 to -16.15 m), or Sitaxsentan (-39.53 m, 95% CI: -78.99 to -0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re-hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions., Conclusions: Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual-drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Reverse Potts shunt (RPS) and lung or heart-lung transplantation are life-extending surgical interventions for pediatric patients with severe pulmonary arterial hypertension (PAH). Robust criteria for identifying patients who will benefit from these procedures remain elusive. Based on 30 years of experience, we sought to refine the surgical indications., Methods: This single-center retrospective cohort study included 61 consecutive pediatric patients with PAH managed by RPS (2004-2020) or transplantation (1988-2020). Their mid-term outcomes were assessed., Results: Compared with the 20 patients managed by RPS, the 41 transplant waitlist patients, of whom 28 were transplanted, were older (14.9 vs 8.0 years, P = .0001), had worse right ventricular impairment (tricuspid annular plane systolic excursion, 12.5 mm vs 18.0 mm, P = .03), and were managed later in the evolution of the disease (6.0 vs 1.7 years, P = .002). After implementation of a high-priority allocation program in 2007, waitlist mortality decreased from 52.6% to 13.6% (P = .02) and 5-year survival increased from 57.1% to 74.7% after RPS and 55.6% to 77.2% after transplantation. At a median follow-up of 8.6 years after RPS and 5.9 years after transplantation, functional capacity had improved significantly, and PAH-specific drug requirements had diminished markedly in the RPS group. Two patients successfully underwent double-lung transplant 6 and 9 years after RPS., Conclusions: In selected children with suprasystemic PAH, RPS is associated with functional capacity improvements and decreased pharmacotherapy needs over the midterm. RPS deserves consideration earlier in the course of pediatric PAH, with transplantation being performed in the event of refractory RV failure., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls. NC-Measurements were repeated after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in CTEPH patients. We examined whether NC-measurements were related to markers of disease severity and predictive of time to clinical worsening (TTCW) as tested by univariate linear/logistic regression and cox-regression analysis, respectively. Capillary density was significantly lower in PAH (7.5 ± 1.1, p < 0.001) and in CTEPH (8.4 ± 1.5, p < 0.001) compared to asymptomatic controls (10.3 ± 1.0 capillaries/mm). Capillary density was similar in iPAH and hPAH and unrelated to hemodynamics in either PAH or CTEPH. A lower capillary density was predictive of clinical worsening in PAH (p 0.05). After normalization of pulmonary artery pressures by PEA or BPA, capillary density remained reduced in CTEPH patients. Capillary loop apex, capillary and venous- and arterial limb diameter were increased in patients with PAH and CTEPH compared to controls. Nailfold capillary density is reduced to a similar extent in iPAH, hPAH and CTEPH. Normalization of hemodynamics by PEA or BPA does not lead to a restoration of capillary density in CTEPH. Capillary dimensions were increased in both patients with PAH and CTEPH. Lower capillary density was predictive of clinical worsening in PAH. Our findings indicate that a loss of peripheral capillaries is not specific to PAH and is not related to the hemodynamic disturbance per se, but that shared mechanisms may account for a simultaneous development of a systemic microangiopathy and pulmonary vascular remodeling., (© 2024. The Author(s).)

Pulmonary arterial hypertension (PAH) associated with congenital heart disease (PAH-CHD) is a complication that occurs after unrepaired significant systemic-to-pulmonary shunt. Treatment options for PAH-CHD-predominantly left-to-right (L-R) shunt in children with borderline-high pulmonary vascular resistant index (PVRi) have been debated. We aimed to assess the treatment and survival of children with PAH-CHD-predominantly L-R shunt with borderline to high PVRi, using Eisenmenger syndrome (ES) for comparison. In 1995-2021, a total of 142 patients with ES and 192 children with PAH-CHD-predominantly L-R shunt were eligible for our analysis. The PVRi in ES patients was 26.7 ± 16.8 WU m 2 . Most patients (91%) received PAH-targeted therapy. Of the 192 children with PAH-CHD-predominantly L-R shunt, the baseline PVRi was 9.2 ± 5.8 WU m 2 . A total of 64 patients (33.3%) had borderline PVRi (4-8 WU m 2 ) and 98 patients (51%) had high PVRi (> 8 WU m 2 ). Most patients (88.5%) responded to acute pulmonary vasodilatory testing and underwent repair, with 158 undergoing defect closure and 12 having fenestrated closure. A treat-and-repair strategy was used in 33 children (17.1%). The 10- and 15-year survival rates for patients with ES were 79.3% and 72.4%, respectively, which was significantly inferior to children with borderline PVRi [97.3% and 87.8% (p = 0.02)]; and high PVRi [91.6% and 89.5% (p = 0.06)], respectively. The survival rate of children receiving treat-and-repair was slightly higher than that of ES (p = 0.16). The independent mortality risk in children with PAH-CHD-predominantly L-R shunt was persistent PAH following the defect correction (adjusted hazard ratio 5.8, 95% CI 1.7-19.9, p = 0.005).Trial registration: TCTR20200420004., (© 2024. The Author(s).)

Background: In patients with pulmonary arterial hypertension (PAH), refractory to medical therapy, lung transplantation emerges as an option. This study describes the outcomes of 8 PAH patients who underwent lung transplantation., Methods: A retrospective, single-center study was conducted among patients with PAH who underwent lung transplantation in our center., Results: Patients had a median age of 46 years, with female sex predominance (75%). Causes of HAP were pulmonary veno-occlusive disease (n = 5, 62.5%), idiopathic PAH (n = 2, 25%), and heritable PAH (n = 1, 12.5%). Pre-transplant hemodynamics revealed a median mean pulmonary artery pressure of 58.5 mm Hg (48-86). All patients received bilateral lung transplants with extracorporeal membrane oxygenation support, displaying immediate post-transplant hemodynamic improvement. Primary graft dysfunction grade 3 (PGD 3) was observed in 75% of patients. Five patients (62.5%) died, with a 72.9% survival at 12 months and 29.2% at 24 months post-transplantation., Conclusion: Our study reveals the complexity and challenges of lung transplants in patients with PAH. Despite notable immediate hemodynamic improvements, high rates of PGD 3 and the survival rate remain a concern. Further research to define optimal peri and post-transplant management to improve survival is required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-term clinical outcomes after pulmonary artery denervation (PADN) in patients with Group 1 pulmonary arterial hypertension (PAH) have not been reported., Aims: We aimed to investigate the effect of PADN on 1-year outcomes in patients with PAH., Methods: In the multicentre PADN-CFDA trial, 128 patients with Group 1 PAH were randomly assigned to PADN plus a phosphodiesterase-5 inhibitor (PDE-5i) versus a sham PADN procedure plus a PDE-5i. The principal endpoint of interest for the present study was clinical worsening at 1 year after randomisation, the composite of worsening of PAH (increase in WHO functional class, need for additional PAH treatments or PAH-related hospitalisation), atrial septostomy, listing for lung transplantation, or all-cause death., Results: One-year clinical follow-up was available in all patients. At 1 year, clinical worsening had occurred in 3 (4.8%) patients in the PADN plus PDE-5i group and in 15 patients (23.1%) in the sham plus PDE-5i group (adjusted hazard ratio: 0.17; 95% confidence interval [CI]: 0.05-0.60; p=0.006), driven by significantly increased rates of PAH-related hospitalisations, worsening functional class and the requirement for additional PAH treatments in the sham group. Results were consistent in high-risk, intermediate-risk and low-risk patients (p interaction =0.186). Patients treated with PADN plus PDE-5i had an improvement in the between-group change in the six-minute walking distance (6MWD) from baseline to 1 year of 81.2 m (95% CI: 50.3-112.2; p<0.001) compared with PDE-5i treatment alone., Conclusions: In this multicentre sham-controlled randomised trial, PADN treatment for Group 1 PAH significantly reduced clinical worsening and improved the 6MWD during 1-year follow-up in patients treated with a PDE-5i.

Background: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients., Methods: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months., Results: In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up., Conclusions: In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a progressive, life-limiting disease. Despite significant medical progress over the last three decades, the prognosis of PAH remains poor. PAH is associated with sympathetic nervous system over-stimulation and baroreceptor-mediated vasoconstriction, leading to pathologic pulmonary artery (PA) and right ventricular remodeling. PA denervation is a minimally-invasive intervention that ablates local sympathetic nerve fibers and baroreceptors to modulate pathologic vasoconstriction. Preliminary animal and clinical studies have shown improvements in short-term pulmonary hemodynamics and PA remodeling. However, future studies are needed to elucidate appropriate patient selection, timing of intervention, and long-term efficacy before integration into standard of care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Portopulmonary hypertension (POPH) is a type of pulmonary arterial hypertension occurring exclusively in those with portal hypertensive liver disease. Liver transplantation (LT) can significantly improve outcomes. Current guidelines counsel against immediate adjustments to targeted therapy after LT and suggest routine echocardiography as sufficiently informative to guide therapeutic adjustments. Current practice patterns for adjusting targeted therapy after LT in POPH, and how they compare with guidelines, are not well established. To answer this question, we performed an institutional review board-approved, cross-sectional mixed-methods survey-based study of US POPH providers. Anonymized requests to complete the survey were sent through professional networks between January 20, 2022, and April 20, 2022. Responses were compared between cardiologists and pulmonologists using Fisher's exact tests, at a significance of 0.05. A total of 85 POPH physicians were included in the final analysis (66% pulmonologists and 34% cardiologists). Following LT, the majority of respondents routinely used a combination of standard cardiopulmonary assessment modalities to guide adjustment of targeted therapy following LT. Most respondents (69%) started by adjusting parenteral prostacyclins with small titrations and frequent reassessments within 3 months of LT, but some (19.7%) adjusted targeted therapy immediately after LT. Our results showed that the majority of respondents favored serial integrated cardiopulmonary testing (including routine right heart catheterization) to guide the adjustment of targeted therapy in POPH after LT, and almost one-fifth of respondents weaned therapy immediately after LT. Our study demonstrates heterogeneity in POPH practice patterns after LT, highlights differences between current practice patterns and the most recent guidelines, emphasizes the need for additional research, and supports a team-based approach to standardize care for these high-risk patients and optimize post-LT outcomes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Lung transplantation (LT) is the only option for patients with pulmonary arterial hypertension (PAH) refractory to maximal medical therapy. However, some patients referred for LT could survive without LT, and its determinants remain unclear. This study aimed to elucidate prognostic factors of severe PAH at the referral time. We retrospectively analyzed 34 patients referred for LT evaluation. The primary outcome was a composite of death or LT. Over a median follow-up period of 2.56 years, eight patients received LT and eight died. Compared with LT-free survival group, pulmonary arterial systolic pressure (PASP) was higher (p = 0.042), and the ratio of tricuspid annular plane systolic excursion (TAPSE) to PASP (TAPSE/PASP) was lower (p = 0.01) in LT or death group. In receiver operating characteristic analysis, the area under the curve was 0.759 (95% confidence interval 0.589-0.929) for TAPSE/PASP to predict primary outcome, and the optimal cut-off value was 0.30 mm/mmHg (sensitivity 0.875 and specificity 0.667). In a multivariate analysis, TAPSE/PASP was independently associated with death or LT. Kaplan-Meier analysis showed a better LT-free survival in patients with TAPSE/PASP ≧0.30 mm/mmHg than in those with < 0.30 mm/mmHg (p = 0.001). Low-level TAPSE/PASP could be a poor prognostic factor in PAH patients referred for LT evaluation., (© 2023. The Author(s).)

Lung volume reduction surgery (LVRS) represents a standard surgical approach for patients with severe pulmonary emphysema. One of the relevant risk factors for LVRS is the presence of pulmonary arterial hypertension (PAH). The aim of this study is to assess the postoperative changes in pulmonary arterial pressure (PAP) after LVRS for patients with severe pulmonary emphysema compared with preoperative measures. N = 61 consecutive patients with severe pulmonary emphysema and preoperative evidence for PAH (pulmonary arterial systolic pressure [PASP] ≥ 35 mmHg) were prospectively included into this study. In all patients, thoracoscopic LVRS was performed. PASP was assessed by echocardiography before surgery, early postoperatively, and 3 months after surgery. Data were prospectively recorded and analyzed retrospectively. Primary end points were the postoperative changes in PASP as well as the 90 day mortality rate. Secondary endpoints included: pulmonary function test, exercise capacity, quality of life, and dyspnea symptoms (Borg scale). Early after surgery, a significant reduction in PASP was observed at the day of discharge and at 3 month follow-up. In n = 34 patients, no tricuspid valve regurgitation was detectable anymore suggesting normal PAP. In n = 3 patients, venovenous extracorporeal lung support (VV ECLS) was already implemented preoperatively. In the remaining cases, VV ECLS was applied intraoperatively and continued postoperatively. Mean duration of postoperative ECLS support was 2 days. Four patients died due to acute right heart failure, two patients from sepsis with multiorgan failure, and one patient from acute pulmonary embolism. Ninety day mortality was 11.5 %. A significant improvement was postoperatively observed regarding the performance status, dyspnea scale, as well as quality of life. This study suggests a beneficial effect of LVRS on PAP, which may ultimately help to protect and stabilize right ventricular function. Further studies, implementing pre- and postoperative right heart catheterizations including invasive PAP evaluation, are necessary to support the findings in this study in greater detail., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Rationale: The lung allocation score (LAS) was revised in 2015 to improve waiting list mortality and rate of transplant for patients with pulmonary arterial hypertension (PAH). Objectives: We sought to determine if the 2015 revision achieved its intended goals. Methods: Using the Standard Transplant Analysis and Research file, we assessed the impact of the 2015 LAS revision by comparing the pre- and postrevision eras. Registrants were divided into the LAS diagnostic categories: group A-chronic obstructive pulmonary disease; group B-pulmonary arterial hypertension; group C-cystic fibrosis; and group D-interstitial lung disease. Competing risk regressions were used to assess the two mutually exclusive competing risks of waiting list death and transplant. Cumulative incidence plots were created to visually inspect risks. Measurements and Main Results: The LAS at organ matching increased by 14.2 points for registrants with PAH after the 2015 LAS revision, the greatest increase among diagnostic categories (other LAS categories: Δ, -0.9 to +2.8 points). Before the revision, registrants with PAH had the highest risk of death and lowest likelihood of transplant. After the 2015 revision, registrants with PAH still had the highest risk of death, now similar to those with interstitial lung disease, and the lowest rate of transplant, now similar to those with chronic obstructive pulmonary disease. Conclusions: Although the 2015 LAS revision improved access to transplant and reduced the risk of waitlist death for patients with PAH, it did not go far enough. Significant differences in waitlist mortality and likelihood of transplant persist.

Background: World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial., Objectives: The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH., Methods: Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months., Results: Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up., Conclusions: In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266)., Competing Interests: Funding Support and Author Disclosures This trial was supported by the National Scientific Foundation of China (grants NSFC 91639303, and NSFC 81770441, and NSFC 82121001). Nanjing First Hospital funded this trial, and Pulnovo Medical provided all PADN catheters through the study period. Dr Stone has received speaker honoraria from Medtronic, Pulnovo Medical, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity or options in Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, has received research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, and V-Wave. Dr S.-L. Chen is the inventor of PADN but not the owner of the PADN patent; has received speaker honoraria from Microport, Pulnovo Medical, Boston Scientific, Medtronic, Sanofi, and BioMed; is a fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University; and has received grants from the National Scientific Foundation of China. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is unknown whether pulmonary arterial hypertension (PAH) risk stratification instruments could be helpful to support the decision to list a patient for lung transplantation (LT). Our aim was to evaluate contemporary risk assessment tools in a cohort of PAH patients listed for LT., Methods: Consecutive PAH patients (without pulmonary veno-occlusive disease or unrepaired congenital heart disease) listed for LT at the French Pulmonary Hypertension Reference Center between January 2006 and December 2018 were included. At the time of listing, risk stratification was assessed using the ESC/ERS criteria, the REVEAL Lite 2 score and the COMPERA 2.0 method. The primary end point was overall survival after LT listing. Secondary outcome measures were mortality on waiting list and posttransplant survival., Results: One hundred and two patients were enrolled (mean age 38 ± 13 years, 69% females). Overall survival after listing was 72%, 58% and 46% at 1, 3 and 5 years respectively. Survival after LT listing was lower in "high-risk" patients according to the ESC/ERS criteria (p = 0.0001) and the REVEAL Lite 2 score (p = 0.04). The COMPERA 2.0 method discriminated post-listing survival of patients at high-risk, intermediate-high and intermediate-low risk (p = 0.04). The proportion of patients requiring urgent transplantation and extracorporeal life support as a bridge to transplantation was higher in the "high-risk" patients. Posttransplant survival was significantly lower in "high-risk" patients according to the ESC/ERS criteria (p = 0.0004)., Conclusions: High-risk PAH patients at the time of LT listing have poor outcomes, suggesting that LT should be considered earlier in the course of PAH remaining refractory to triple combination therapy with a parenteral prostacyclin., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD-PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO 3 ), bicarbonate in superior vena cava (svcHCO 3 ), and the partial pressure of dissolved CO 2 gas in radial artery (aPCO 2 ) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO 3 , svcHCO 3 , and aPCO 2 , would be of great value in disease monitoring and evaluating future therapeutic interventions., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Background: Severe pulmonary arterial hypertension (PAH) is a contraindication for heart transplantation (HT). It has been correlated with increased early and late mortality, mainly associated with right ventricular failure. Ventricular assistance devices (VADs) can promote reduction of intracardiac pressures and consequent reduction of PAH over the medium and long terms, thus enabling future candidature for HT. The diminution of early pulmonary pressure within this scenario remains unclear., Objective: To evaluate the reduction of PAH and correlate data from right catheterization with the earliness of this reduction., Design and Setting: Cross-sectional study in a general hospital in São Paulo, Brazil., Methods: This was a retrospective analysis on the medical records of patients undergoing VAD implantation in a single hospital. Patients for whom VAD had been indicated as a bridge to candidature for HT due to their condition of constant PAH were selected., Results: Four patients with VADs had constantly severe PAH. Their mean pulmonary artery systolic pressure (PASP) before VAD implantation was 66 mmHg. Over the 30-day period after the procedure, all the patients evolved with a drop in PASP to below 60 mmHg. Their new average was 36 mmHg, which was a drop of close to 50% from baseline values. The one-year survival of this sample was 100%., Conclusion: VAD implantation can reduce PAH levels. Early reduction occurred in all patients. Thus, use of VAD is an important bridge tool for enabling candidature for HT among patients with constantly severe PAH.

Background and Aim: Giant aneurysm of the pulmonary artery (PAA) is an extremely rare condition that may develop in patients with pulmonary arterial hypertension (PAH) which may be complicated by rupture, dissection or intravascular thrombus formation. The aim of this study was to examine available literature with regard to surgical strategies in patients undergoing transplantation for PAH with PAA., Results: These patients were traditionally considered for heart-lung transplantation but more recently, there have been reports of successful lung transplantation with reconstruction of the pulmonary artery., Conclusions: Unless there is a mandatory indication for heart-lung transplantation, patients with PAH and PAA can undergo lung transplantation and reconstruction of the pulmonary artery without compromising the outcome., (© 2022 Wiley Periodicals LLC.)

Background: We investigated whether RV function recovers in children with pulmonary arterial hypertension (PAH) and RV failure undergoing lung transplantation (LuTx)., Methods: Prospective observational study of 15 consecutive children, 1.9 to 17.6 years old, with PAH undergoing bilateral LuTx. We performed advanced echocardiography (Echo) and cardiac magnetic resonance imaging (MRI), followed by conventional and strain analysis, pre- and ∼6 weeks post-LuTx., Results: After LuTx, RV/LV end-systolic diameter ratio (Echo), RV volumes and systolic RV function (RVEF 63 vs 30 %; p < 0.05) by MRI completely normalized, even in children with severe RV failure (RVEF < 40%). The echocardiographic end-systolic LV eccentricity index nearly normalized post-LuTx (1.0 vs 2.0, p < 0.0001) while RV hypertrophy regressed more slowly and was still evident. We found especially the end-systolic RV/LV ratios by Echo (diameter: 0.6 vs 2.6) or MRI (volumes: 0.8 vs 3.4) excellent diagnostic tools (p < 0.05): Together with RVEF by MRI, these ratios were superior to tricuspid annular plane systolic excursion (TAPSE; p = 0.4551) in assessing global systolic RV dysfunction. Moreover, children with severe PAH had reduced RV 2D longitudinal strain (Echo, MRI; p = 0.0450) and decreased RV 2D radial and circumferential strain (MRI; p = 0.0026 and p = 0.0036 respectively), all of which greatly improved following LuTx., Conclusion: We demonstrate full recovery of RV systolic function in children within two months after LuTx for severe PAH, independently of the patients' age, weight, and hemodynamic compromise preceding the LuTx. Even in end-stage pediatric PAH with poor RV function and low cardiac output, LuTx should be preferred over heart-lung transplantation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates., Methods: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes., Results: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001)., Conclusions: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT)., Methods: Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in 3 transplant centers from 1996 to 2019., Results: From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pretransplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1-, 3-, and 5-y unadjusted survival rates after LT were 72%, 63%, and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR, 1.91; 95% CI, 1.07-3.74, P = 0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010., Conclusions: Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Pulmonary arterial hypertension (PAH) is rare but remains fatal in infants and children despite the advance of targeted therapies. Lung transplantation (LTx), first performed in pediatric patients in the 1980s, is, with the Potts shunt, the only potentially life-extending option in patients with end-stage PAH but is possible only in tightly selected patients. Size-matching challenges severely restrict the donor organ pool, resulting-together with peculiarities of PAH in infants-in high waitlist mortality. We aimed to investigate survival when using a high-priority allocation program (HPAP) in children with PAH listed for double-LTx or heart-LTx., Methods: We conducted a single-center, retrospective, before-after study of consecutive children with severe Group 1 PAH listed for double-LTx or heart-LTx between 1988 and 2019. The HPAP was implemented in France in 2006 and 2007 for heart-LTx and double-LTx, respectively., Results: Fifty-five children with PAH were listed for transplantation. Mean age at transplantation was 15.8±2.8 years and 72% had heart-lung transplantation. PAH was usually idiopathic (65%) or due to congenital heart disease (25%). HPAP implementation resulted in the following significant benefits: Decreased cumulative incidence of waitlist death within 1 and 2 years (p < 0.0001); increased cumulative incidence of transplantation within 6 months, from 44% to 67% (p < 0.01); and improved survival after listing (at 1, 3, and 5 years: 61%, 50%, and 44% vs. 92%, 84%, and 72% before and after HPAP implementation, respectively; p = 0.02)., Conclusion: HPAP implementation was associated with significant improvements in access to transplantation and in survival after listing in children with end-stage PAH., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension remains a progressive, life-limiting disease despite optimal medical therapy. Pulmonary artery denervation has arisen as a novel intervention in the treatment of pulmonary arterial hypertension, and other forms of pulmonary hypertension, with the aim of reducing the sympathetic activity of the pulmonary circulation. Pre-clinical studies and initial clinical trials have demonstrated that the technique can be performed safely with some positive effects on clinical, haemodynamic and echocardiographic markers of disease. The scope of the technique in current practice remains limited given the absence of well-designed, large-scale, international randomised controlled clinical trials. This review provides an overview of this exciting new treatment modality, including pathophysiology, technical innovations and recent trial results., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Despite advances in treatment of idiopathic pulmonary arterial hypertension (IPAH), there remains no medical cure, and patients can experience disease progression leading to right heart failure, progressive exercise intolerance, and death. The reversed Potts shunt (left pulmonary artery to descending aorta) was reintroduced for treatment of end-stage IPAH to permit decompression of the suprasystemic right ventricle by right to left shunting, with preservation of upper body oxygenation. The shunt has the potential to delay the need for lung transplantation and offer a treatment for those who are transplant ineligible. To optimize shunt design and avoid the potential complications of bidirectional shunting, we developed a novel approach using a unidirectional-valved shunt (UVS) in patients with IPAH with suprasystemic pulmonary arterial pressure and poor right ventricular function., Methods: A single-center retrospective review was performed of UVS cases done at Columbia University Medical Center-New York Presbyterian between November 1, 2016, and May 1, 2019., Results: Five patients (4 female; ages 12-22 years) underwent UVS. All had suprasystemic pulmonary arterial pressure, poor right ventricular function, and World Health Organization functional class IV symptoms at baseline. All patients are alive and transplant-free at latest follow-up (range 3-33 months; median 6 ± 11 months)., Conclusions: The UVS may offer an alternative solution to lung transplantation in adolescents and young adults with IPAH. Longer-term follow-up is needed to determine the ultimate impact of unidirectional unloading of the right ventricle in these patients and to determine whether the UVS will enable a broader approach to the treatment of patients with IPAH., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to explore the relationship between the neutrophil to lymphocyte ratio (NLR) and the early clinical outcomes in children with congenital heart disease (CHD) associated with pulmonary arterial hypertension (PAH) after cardiac surgery., Methods: A retrospective observational study involving 190 children from January 2013 to August 2019 was conducted. Perioperative clinical and biochemical data were collected., Results: We found that pre-operative NLR was significantly correlated with AST, STB, CR and UA (P < 0.05), while post-operative NLR was significantly correlated with ALT, AST, BUN (P < 0.05). Increased post-operative neutrophil count and NLR as well as decreased lymphocyte count could be observed after cardiac surgery (P < 0.05). Level of pre-operative NLR was significantly correlated with mechanical ventilation time, ICU stay time and total length of stay (P < 0.05), while level of post-operative NLR was only significantly correlated to the first two (P < 0.05). By using ROC curve analysis, relevant areas under the curve for predicting prolonged mechanical ventilation time beyond 24 h, 48 h and 72 h by NLR were statistically significant (P < 0.05)., Conclusion: For patients with CHD-PAH, NLR was closely related to early post-operative complications and clinical outcomes, and could act as a novel marker to predict the occurrence of prolonged mechanical ventilation.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction and vascular remodeling. Despite significant advancement in our understanding of the pathogenesis of PAH in recent years, treatment options for PAH are limited and their prognosis remains poor. PAH is now seen as a severe pulmonary arterial vasculopathy with structural changes driven by excessive vascular proliferation and inflammation. Perturbations of a number of cellular and molecular mechanisms have been described, including pathways involving growth factors, cytokines, metabolic signaling, elastases, and proteases, underscoring the complexity of the disease pathogenesis. Interestingly, emerging evidence suggests that stem/progenitor cells may have an impact on disease development and therapy. In preclinical studies, stem/progenitor cells displayed an ability to promote endothelial repair of dysfunctional arteries and induce neovascularization. The stem cell-based therapy for PAH are now under active investigation. This review article will briefly summarize the updates in the research field, with a special focus on the contribution of stem/progenitor cells to lesion formation via influencing vascular cell functions and highlight the potential clinical application of stem/progenitor cell therapy to PAH.

This study investigated the efficacy and safety of intravenous treprostinil during the perioperative period in infants with non-restrictive ventricular septal defect (VSD) and severe pulmonary arterial hypertension (PAH) undergoing surgical VSD repair. This was a retrospective study. There were 79 infants with non-restrictive VSD and severe PAH receiving surgical treatment from January to December 2019 in our cardiac center. The patients were divided into the treprostinil group and control group according to whether intravenous treprostinil was used during the perioperative period. There were no significant differences in the preoperative characteristics, including age, sex, weight, ventricular size, or preoperative pulmonary artery pressure, between the two groups. Although the pulmonary artery pressure in both groups was significantly lower postoperatively than preoperatively, the postoperative pulmonary artery systolic pressure was significantly lower in group T than in group C. The postoperative mechanical ventilation time, ICU stay, and hospital stay in group T were shorter than those in group C. Treprostinil can be used effectively and safely to reduce the perioperative pulmonary artery pressure in infants with non-restrictive VSD and severe PAH undergoing surgical VSD repair.

The increase in thickening of the arterial wall of pulmonary arterial hypertension (PAH) includes cellular proliferation as well as matrix deposition and interrupted internal elastic lamina (IEL) consisting of a thick homogeneous sheet of elastin. Little is, although, known about the detail of IEL formation in PAH. Endothelin-1 is overexpressed in pulmonary arterioles of PAH. We aimed to examine the expression of genes contributing to IEL formation in pulmonary artery smooth muscle cells (PASMCs) especially focused on lysyl oxidase (LOx), an exreacellular matrix enzyme that catalyzes the cross-linking of collagens or elastin. We quantified mRNA expressions of genes contributing to IEL formation including LOx in PASMCs using real-time quantitative polymerase chain reaction. We stimulated human PASMCs with endothelin-1 with prostacyclin or trapidil. Endothelin-1 significantly increased LOx expression. Prostacyclin and trapidil restored endothelin-1-induced LOx expression to the basal level. Endothelin-1 increased LOx expression strongly in PASMCs from PAH patients compared to those from controls. Trapidil reduced LOx expression only in PASMCs from PAH patients. Overexpressed endothelin-1 in PAH patients can increase expression of LOx and agitate cross-linking of elastin and collagen, resulting in ectopic deposition of these in the vascular media.

Background: Aneurysm of the main pulmonary artery trunk (PAA) is a rare but severe complicating factor in patients suffering from pulmonary arterial hypertension (PAH). Many centers consider PAA an indication for a heart-lung transplantation. We aimed to summarize our institutional experience with a lung-only strategy in this complex group of patients., Methods: We performed a retrospective single-center analysis of patients with PAH and a severe PAA who underwent lung transplantation between January 1996 and November 2018., Results: A total of 127 patients with PAH underwent lung transplantation during the study period. Seven patients presented with severe PAA (mean diameter, 70.4 mm). Donor lungs were procured together with the main pulmonary artery (PA). In the recipient, cardiopulmonary bypass with bicaval cannulation was established, and bilateral pneumonectomy together with resection of the entire PA trunk was performed. The right donor lung was implanted, and the attached PA trunk was pulled through behind the superior vena cava and ascending aorta. Anastomosis was performed just above the level of the pulmonary valve. Thereafter, the left lung was implanted by reconnecting the left PA to the main PA trunk. All but 1 patient, who died from sepsis on postoperative day 13, were successfully discharged., Conclusions: To the best of our knowledge, this is the largest published experience of patients with PAH and severe PAA who underwent lung transplantation. We show that these patients are eligible for double lung transplantation and do not require heart-lung transplantation., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The use of extracorporeal membrane oxygenator instead of standard cardiopulmonary bypass during lung transplantation is debatable. Moreover, recently, the concept of prolonged postoperative extracorporeal membrane oxygenator (ECMO) support has been introduced in many transplant centers to prevent primary graft dysfunction (PGD) and improve early and long-term results. The objective of this study was to review the results of our extracorporeal life support strategy during and after bilateral sequential lung transplantation (BSLT) for pulmonary artery hypertension. We review retrospectively our experience in BSLT for pulmonary artery hypertension between January 2010 and August 2018. A total of 38 patients were identified. Nine patients were transplanted using cardiopulmonary bypass (CPB), in eight cases CPB was followed by a prolonged ECMO (pECMO) support, 14 patients were transplanted on central ECMO support, and seven patients were transplanted with central ECMO support followed by a pECMO assistance. The effects of different support strategies were evaluated, in particular in-hospital morbidity, mortality, incidence of PGD, and long-term follow-up. The use of CPB was associated with poor postoperative results and worse long-term survival compared with ECMO-supported patients. Predictive preoperative factors for the need of intraoperative CPB instead of ECMO were identified. The pECMO strategy had a favorable effect to mitigate postoperative morbidity and mortality, not only in intraoperative ECMO-supported patients, but even in CPB-supported cases. In our experience, ECMO may be considered as the first choice circulatory support for lung transplantation. Sometimes, in very complex cases, CBP is still necessary. The pECMO strategy is very effective to reduce incidence of PGD even in CPB-supported patients., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objectives: The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) on a minimum of dual oral therapy., Background: Early studies have suggested that PDN can reduce PVR in patients with PAH., Methods: TROPHY1 (Treatment of Pulmonary Hypertension 1) was a multicenter, international, open-label trial undertaken at 8 specialist centers. Patients 18 to 75 years of age with PAH were eligible if taking dual oral or triple nonparenteral therapy and not responsive to acute vasodilator testing. Eligible patients underwent PDN (TIVUS System). The primary safety endpoint was procedure-related adverse events at 30 days. Secondary endpoints included procedure-related adverse events, disease worsening and death to 12 months, and efficacy endpoints that included change in pulmonary hemodynamic status, 6-min walk distance, and quality of life from baseline to 4 or 6 months. Patients were to remain on disease-specific medication for the duration of the study., Results: Twenty-three patients underwent PDN, with no procedure-related serious adverse events reported. The reduction in PVR at 4- or 6-month follow-up was 94 ± 151 dyn·s·cm -5 (p = 0.001) or 17.8%, which was associated with a 42 ± 63 m (p = 0.02) increase in 6-min walk distance and a 671 ± 1,555 step (p = 0.04) increase in daily activity., Conclusions: In this multicenter early feasibility study, PDN with an intravascular ultrasound catheter was performed without procedure-related adverse events and was associated with a reduction in PVR and increases in 6-min walk distance and daily activity in patients with PAH on background dual or triple therapy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary arterial hypertension (PAH) is frequently complicated by sleep disordered breathing (SDB), and previous studies have largely focused on hypoxemic SDB. Even though nocturnal hypercapnia was shown to exacerbate pulmonary hypertension, the clinical significance of nocturnal hypercapnia among PAH patients has been scarcely investigated., Method: Seventeen patients with PAH were identified from 246 consecutive patients referred to Kyoto University Hospital for the evaluation of lung transplant registration from January 2010 to December 2017. Included in this study were 13 patients whose nocturnal transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring data were available. Nocturnal hypercapnia was diagnosed according to the guidelines of the American Academy of Sleep Medicine. Associations of nocturnal PtcCO2 measurements with clinical features, the findings of right heart catheterization and pulmonary function parameters were evaluated., Results: Nocturnal hypercapnia was diagnosed in six patients (46.2%), while no patient had daytime hypercapnia. Of note, nocturnal hypercapnia was found for 5 out of 6 patients with idiopathic PAH (83.3%). Mean nocturnal PtcCO2 levels correlated negatively with the percentage of predicted total lung capacity (TLC), and positively with cardiac output and cardiac index., Conclusion: Nocturnal hypercapnia was prevalent among advanced PAH patients who were waiting for lung transplantation, and associated with %TLC. Nocturnal hypercapnia was associated with the increase in cardiac output, which might potentially worsen pulmonary hypertension especially during sleep. Further studies are needed to investigate hemodynamics during sleep and to clarify whether nocturnal hypercapnia can be a therapeutic target for PAH patients., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Yoshinari Nakatsuka and Naomi Takahashi reports grants from Philips-Respironics, grants from ResMed Japan, grants from Fukuda Denshi, grants from Fukuda Lifetec Keiji. Kimihiko Murase and Hirofumi Takeyama reports grants from Philips-Respironics, grants from Teijin Pharma, grants from Fukuda Denshi, grants from Fukuda Lifetec Keiji. Kazuo Chin reports grants and personal fees from Philips-Respironics, grants and personal fees from Teijin Pharma, grants and personal fees from Fukuda Denshi, grants and personal fees from Fukuda Lifetec Keiji, grants from KYORIN Pharmaceutical Co., Ltd, grants from Nippon Boehringer Ingelheim Co., Ltd, grants and personal fees from GlaxoSmithKline, personal fees from MSD, personal fees from ResMed, personal fees from Astellas Pharma, personal fees from Eisai Co., Ltd. Hideyuki Kinoshita reports personal fees from Actelion Pharmaceuticals Japan Ltd., Nippon Shinyaku Co., Ltd, Bayer Yakuhin, Ltd., and research grant from Bayer Yakuhin, Ltd. Toyofumi Chen-Yoshikawa, Akihiro Aoyama, Hiroyasu Kubo, Satoshi Hamada, Takuma Minami, Kiminobu Tanizawa, Tomohiro Handa, Toyohiro Hirai and Hiroshi Date declare no potential conflict of interests. The Department of Respiratory Care and Sleep Control Medicine is funded by endowments from Philips-Respironics, ResMed, Fukuda Denshi and Fukuda Lifetec-Keiji to Kyoto University. These competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Ventricle catheterization in the rat is widely practiced in cardiopulmonary research. The catheters deployed are either fluid filled or solid tip pressure or pressure-volume catheters. The access to the right ventricle is through the right jugular vein, most commonly without direct visualization such as fluoroscopy. Advancement of the catheter tip is aided by visualizing the pressure signals of the monitoring/recording systems used. This approach may present challenges due to various reasons, including the stiffness of new catheters, their dimensions or anatomical changes associated with the animal disease model. In this article, we present a novel approach, which has been optimized, successfully validated surgically and adopted in current projects. It has been shown to improve both the overall quality of the signals recorded and the time to access the right ventricle, thus reducing the overall time of surgery. The method presented in this article is safe, easy to reproduce and does not require additional skills compared to a more 'standard' approach., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Management of a giant pulmonary trunk aneurysm in lung transplantation is a challenge. Herein, we present a patient undergoing replacement of the giant pulmonary artery aneurysm with a donor's aorta in bilateral lung transplantation for idiopathic pulmonary arterial hypertension. A plastic three-dimensional model of the pulmonary artery aneurysm created accurately based on computed tomography data allowed us to simulate the procedure on the back table. Our intraoperative findings and management are discussed in this article., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Cor triatriatum is an exceedingly rare congenital heart defect which can present at any age depending upon the presence of associated cardiac anomalies and the size of communication between the common chamber and the left atrium. Our aim is to present 10 years surgical outcome of cor triatriatum repair in patients who present beyond infancy., Methods: On going through our institute's surgical database from January 2009 to June 2019 for cor triatriatum, 14 patients were found to have undergone the surgical correction. Their demographic profile and midterm outcome in terms of mortality, functional status, and cardiac function was assessed., Results: There were total 14 patients with slight female predominance (57.14%) who underwent cor triatriatum surgical repair. The mean age at the time of surgery was 12.14 ± 9.97 years ranging from 1 to 29 years. Associated congenital cardiac defects were seen in 12 (85.71%) patients with atrial septal defect being the most common. Partial anomalous pulmonary venous connection was seen in 4 (28.57%) patients. Eight (57.14%) patients had severe pulmonary hypertension preoperatively. All but two patients showed marked reduction in pulmonary artery pressures postoperatively. All the patients underwent excision of the membrane and repair of associated cardiac defects simultaneously. There was no early or midterm mortality or any reintervention over a mean follow-up period of 58.06 ± 30.73 months (range 20-120 months)., Conclusion: The early and midterm surgical outcome of cor triatriatum is excellent even in patients who present beyond infancy with reversible pulmonary artery hypertension., (© 2019 Wiley Periodicals, Inc.)