Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

[Unmet Needs from the Cancer Patient Perspective].

An unmet needs survey was conducted among cancer patients, their families, and others affected by cancer during the 10-year period from 2011 to 2022 to clarify the actual situation regarding access to information, treatment choices, daily quality of life, and psychosocial support from the perspective of cancer patients, and to explore characteristics, problems, and issues in the categories of common cancers, rare cancers, and pediatric cancers. The desire for successful treatment itself is the same regardless of the type of cancer. However, economic and psychological burdens are closely related to age and life stage, and second opinions and necessary information differ by cancer type. Aspects of daily living difficulties, hospital visits, and financial burdens are also apparent. In addition, a comparison with a survey of clinical trials taken exclusively with rare cancer patients in 2018 was discussed. We believe that focusing on these differences will lead to measures to address unmet needs so that no one is left behind.

Automatic segmentation of bladder cancer on MRI using a convolutional neural network and reproducibility of radiomics features: a two-center study.

This study aimed to develop a versatile automatic segmentation model of bladder cancer (BC) on MRI using a convolutional neural network and investigate the robustness of radiomics features automatically extracted from apparent diffusion coefficient (ADC) maps. This two-center retrospective study used multi-vendor MR units and included 170 patients with BC, of whom 140 were assigned to training datasets for the modified U-net model with five-fold cross-validation and 30 to test datasets for assessment of segmentation performance and reproducibility of automatically extracted radiomics features. For model input data, diffusion-weighted images with b = 0 and 1000 s/mm2, ADC maps, and multi-sequence images (b0-b1000-ADC maps) were used. Segmentation accuracy was compared between ours and existing models. The reproducibility of radiomics features on ADC maps was evaluated using intraclass correlation coefficient. The model with multi-sequence images achieved the highest Dice similarity coefficient (DSC) with five-fold cross-validation (mean DSC = 0.83 and 0.79 for the training and validation datasets, respectively). The median (interquartile range) DSC of the test dataset model was 0.81 (0.70-0.88). Radiomics features extracted from manually and automatically segmented BC exhibited good reproducibility. Thus, our U-net model performed highly accurate segmentation of BC, and radiomics features extracted from the automatic segmentation results exhibited high reproducibility.

Microvasculopathy Evaluated by Dual-Energy Computed Tomography in Patients with Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension.

Background: Poor subpleural perfusion (PSP) on dual-energy computed tomography (DE-CT) suggests microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH). However, whether the microvasculopathy findings are equivalent to those in pulmonary arterial hypertension (PAH) remains unclear. The aim of this study was to elucidate the characteristics of microvasculopathy in CTEPH compared to those of that in PAH. Methods: We retrospectively reviewed subpleural perfusion on DE-CT and the hemodynamics of 23 patients with PAH and 113 with inoperable CTEPH. Subpleural perfusion on DE-CT was classified as poor (subpleural spaces in all segments with little or no perfusion) or normal. Results: PSP was observed in 51% of patients with CTEPH and in 4% of those with PAH (p < 0.01). CTEPH patients with PSP had poorer baseline hemodynamics and lower diffusing capacity for carbon monoxide divided by the alveolar volume (DLCO/VA) than those with CTEPH with normal perfusion (pulmonary vascular resistance [PVR]: 768 ± 445 dynes-sec/cm5 vs. 463 ± 284 dynes-sec/cm5, p < 0.01; DLCO/VA, 60.4 ± 16.8% vs. 75.9 ± 15.7%, p < 0.001). Despite the existence of PSP, hemodynamics improved to nearly normal in both groups after balloon pulmonary angioplasty. Conclusions: PSP on DE-CT, which is one of the specific imaging findings in CTEPH, might suggest a different mechanism of microvasculopathy from that in PAH.

RC time (resistance × compliance) is related to residual symptom after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

Background: Right ventricular (RV) afterload is widely assessed by pulmonary vascular resistance (PVR). However, RV afterload is underestimated because PVR does not account for the pulsatile load. The pulsatile load is often evaluated by pulmonary arterial compliance (PAC). The RC (resistance-compliance) time, which is calculated from the product of PVR and PAC, is considered to remain constant under medical therapy. However, little is known on how RC time is affected by invasive therapy in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to evaluate change of RC time in patients underwent pulmonary endarterectomy (PEA). Furthermore, we investigated the clinical relevance of RC time. Methods: We reviewed consecutive 50 patients except for death case underwent PEA. Baseline clinical parameters including RC time before performing PEA and follow-up were evaluated. Patients was classified as decrease or non-decrease according to change of RC time. Furthermore, we classified patients into a NYHA I group who had no symptom after treatment and a residual symptom group in order to investigate the relationship of RC time to residual symptoms. Results: RC time was significantly decreased after PEA (0.54 ± 0.16 to 0.45 ± 0.12 sec, p < 0.001). Residual symptom after PEA of Decrease group were significantly better than that of Non-decrease group in RC time (12 patients, 40% vs. 11 patients, 78.6%, p < 0.02). Furthermore, multivariate analysis revealed that only RC time after PEA was independently associated with residual symptom (OR 1.026, 95% CI 1.005-1.048; p = 0.017). Conclusions: RC time was decreased after PEA, and might be a possible indicator for predicting PEA success.

Progression from normal vessel wall to atherosclerotic plaque: lessons from an optical coherence tomography study with follow-up of over 5 years.

The initial process of atherosclerotic development has not been systematically evaluated. This study aimed to observe atherosclerotic progression from normal vessel wall (NVW) to atherosclerotic plaque and examine local factors associated with such progression using > 5-year long-term follow-up data obtained by serial optical coherence tomography (OCT). A total of 49 patients who underwent serial OCT for lesions with NVW over 5 years (average: 6.9 years) were enrolled. NVW was defined as a vessel wall with an OCT-detectable three-layer structure and intimal thickness ≤ 300 µm. Baseline and follow-up OCT images were matched, and OCT cross sections with NVW > 30° were enrolled. Cross sections were diagnosed as "progression" when the NVW in these cross sections was reduced by > 30° at > 5-year follow-up. Atherogenic progression from NVW to atherosclerotic plaque was observed in 40.8% of enrolled cross sections. The incidence of microchannels in an adjacent atherosclerotic plaque within the same cross section (6.7 vs. 3.3%; p = 0.046) and eccentric distribution of atherosclerotic plaque (25.0 vs. 12.6%; p < 0.001) at baseline was significantly higher in cross sections with progression than in those without. Cross sections with progression exhibited significantly higher NVW intimal thickness at baseline than cross sections without progression (200.1 ± 53.7 vs. 180.2 ± 59.6 µm; p < 0.001). Multivariate analysis revealed that the presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness at baseline were independently associated with progression at follow-up. The presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness were potentially associated with initial atherosclerotic development from NVW to atherosclerotic plaque.

Assessment of oxygenation after balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: The efficacy of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension would be promising. However, some patients showed residual dyspnea or symptoms, despite normalized hemodynamics. We aimed to clarify the clinical impact of oxygenation parameters on BPA outcome. METHOD: Ninety-nine consecutive patients who underwent BPA from September 2011 to December 2019 were enrolled. We evaluated hemodynamics with right heart catheterization, arterial blood gas examination, New York Heart Association functional class (NYHA-FC), respiratory function tests, nocturnal oximetry, and exercise capacity (6-min walk test and cardiopulmonary exercise testing) at baseline and after BPA. RESULT: Nearly normal hemodynamics was achieved after BPA (mean pulmonary artery pressure (PAP): 37.5 ± 10.0 to 20.6 ± 4.9 mmHg, p < 0.01). Oxygenation slightly improved (partial pressure of arterial oxygen; 61.5 ± 12.3 to 67.7 ± 12.7 mmHg, p < 0.01). Exertional desaturation remained unchanged (-8.1 ± 4.8 to -7.8 ± 5.1, p = 0.59), and this was associated with residual symptom (NYHA-FC ≥ 2) after BPA (OR 0.591, 95% CI 0.416-0.840, p = 0.003) in multivariate regression analyses. Lower vital capacity (r2 = 0.03, p = 0.01), higher mean PAP (r2 = 0.08, p = 0.02), and higher minute ventilation/carbon dioxide production (VE/VCO2) slope (r2 = 0.18, p < 0.01), the marker of ventilatory inefficiency, were correlated with exertional desaturation after BPA in multivariate linear analyses. CONCLUSION: Although hemodynamics nearly normalized, oxygenation did not. Moreover, exertional desaturation remained unchanged. This might cause residual symptom after BPA. Residual pulmonary hypertension suggesting incurable arteriopathy, and higher VE/VCO2 slope suggesting ventilation-perfusion mismatch might be related to exertional desaturation. Domiciliary oxygen therapy should be continued, if necessary.

Evaluation of microvasculopathy using dual-energy computed tomography in patients with chronic thromboembolic pulmonary hypertension.

The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension has been suggested. Recently, dual-energy computed tomography has been used to produce a sensitive iodine distribution map in lung fields to indicate microvasculopathy according to poor subpleural perfusion. Our aim was to evaluate the impact of microvasculopathy on pathophysiology in chronic thromboembolic pulmonary hypertension. According to the extent of poor subpleural perfusion, ninety-three interventional treatment-naïve patients were divided into poorly perfused (n = 49) or normally perfused group (n = 44). We assessed cardiopulmonary exercise test, right heart catheterization, and dual-energy computed tomography parameters for quantitative evaluation of lung perfusion of blood volume score. Lung perfusion of blood volume score in normally perfused group was significantly inversely correlated with pulmonary vascular resistance (pulmonary vascular resistance = 6816.1 × lung perfusion of blood volume score-0.793, R2 = 0.225, p < 0.01), but lung perfusion of blood volume score in poorly perfused group was not. Poorly perfused group had higher pulmonary vascular resistance (879 ± 409 dynes-s/cm5 vs. 574 ± 279 dynes-s/cm5, p < 0.01) and lower lung perfusion of blood volume score (22.1 ± 5.4 vs. 26.4 ± 6.6, p < 0.01) and % diffusing capacity for carbon monoxide divided by the alveolar volume (59.9 ± 15.4% vs. 78.8 ± 14.2%, p < 0.01). Perfusion of blood volume score in the normally perfused group showed an inverse correlation with pulmonary vascular resistance; however, that in poorly perfused group did not. Microvasculopathy might contribute to severe hemodynamics, apart from pulmonary vascular obstruction. In our experience, more than half of treatment-naïve chronic thromboembolic pulmonary hypertension patients have microvasculopathy.

[COST ANALYSIS OF ANDROGEN DEPRIVATION THERAPY AND DRUGS FOR CASTRATION-RESISTANT PROSTATE CANCER].

(Purpose) Recently, new effective drugs for the treatment of castration-resistant prostate cancer (CRPC) have been developed. Although they are expected to prolong the survival time of patients with advanced prostate cancer, they may result in an economic burden. In this study, we determined the treatment results and the cost of CRPC drugs. (Methods) From 2014 to 2017, patients who were unfit for curative therapy were enrolled in this study. First, they received androgen deprivation therapy (ADT) by surgical or chemical castration. Once castration-sensitive cancer progressed to castration-resistant cancer, CRPC drugs, such as docetaxel, cabazitaxel, abiraterone and enzalutamide, were administered sequentially. In elderly or fragile patients, drug doses were often reduced to minimize their toxicity. The total costs of drugs for castration-sensitive and castration-resistant cancers were calculated, and the results were evaluated. (Results) Prostate biopsies detected prostate cancer in 257 patients. Eighty-one patients were treated with ADT, and 56 of the cancers were metastatic or showed a high prostate specific antigen level (>100 ng/ml). Thirty patients out of the 56 with advanced cancers developed CRPC, and the median time to CRPC was 10 months (range, 3-39). Drugs targeting CRPC were administered in 25 patients for a median duration of 20 months (range, 3-50). During the median observation period of 48 months (range, 13-75), 15 patients died of prostate cancer. The median annual cost of drugs for castration-sensitive cancer was 234,000 Japanese yen (2,187 US dollars) [range, 50,000-315,000 yen (467-2,943 US dollars) ]. In contrast, the median annual cost of drugs for CRPC was 2,041,000 yen (19,075 US dollars) [range, 346,000-5,017,000 yen (3,230-46,886 US dollars) ]. (Conclusions) Advanced prostate cancer tended to rapidly progress to CRPC, which required a sequence of expensive drugs for treatment. Early diagnosis preventing the development of advanced prostate cancer is desirable to reduce the economic burden for the health insurance system.

The role of balloon pulmonary angioplasty and pulmonary endarterectomy: Is chronic thromboembolic pulmonary hypertension still a life-threatening disease?

BACKGROUND: The management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched the BPA program in 2011. The aim was to analyze the survival and treatment efficacy of our CTEPH treatment program in the modern management era. METHODS AND RESULTS: We retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed from January 2011 (i.e. after the availability of BPA) to December 2019. Of forty-one patients who underwent pulmonary endarterectomy (PEA), 25 underwent additional BPA (Combination group) and the others were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group). The remaining 12 patients did not undergo any interventional treatments. The 1- and 5-year survival rates of operated patients (n = 41) were 97.4% and 90.0%, compared to 96.9% and 86.9% in not-operated patients (n = 102), respectively (p = 0.579). There was no mortality in the Combination group. Mean pulmonary artery pressure after treatments in the PEA only, Combination, and BPA only groups was 20.5 ± 6.7, 17.9 ± 4.9, and 20.7 ± 4.6 mmHg, respectively (p = 0.067, one-way ANOVA). Percent decrease of pulmonary vascular resistance in each treatment groups was -73.7 ± 11.3%, -74.3 ± 11.8%, and - 54.9 ± 22.5%, respectively (p < 0.01, one-way ANOVA). CONCLUSION: There was no significant difference in long-term survival between operated and not-operated CTEPH. Moreover, the Combination approach might have the potential to introduce notable improvements in the prognosis of CTEPH. BPA and PEA appear to be mutually complementary therapies in the modern management era.

Impaired Cholesterol-Uptake Capacity of HDL Might Promote Target-Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation.

Background We evaluated the importance of high-density lipoprotein (HDL) functionality for target-lesion revascularization in patients treated with coronary stents using a rapid cell-free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol-uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow-up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow-up was performed to assess target-lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P<0.001). The CUC showed a significant inverse correlation with incidence of target-lesion revascularization (odds ratio, 0.887; P=0.003) and with lipid accumulation inside stents, suggesting that neoatherosclerosis contributes to the association between CUC and target-lesion revascularization. Conclusions Impaired HDL functionality, detected as decreased CUC, might lead to future stent failure by provoking atherogenic changes of the neointima within stents. Both quantitative and qualitative assessments of HDL might enable the improved prediction of clinical outcomes after stent implantation.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

Efficacy of alirocumab for reducing plaque vulnerability: Study protocol for ALTAIR, a randomized controlled trial in Japanese patients with coronary artery disease receiving rosuvastatin.

BACKGROUND: Although a recent clinical trial demonstrated that alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, significantly reduces the incidence of acute coronary events, the impact of alirocumab on plaque stabilization remains uncertain. The Efficacy of ALirocumab for Thin-cap fibroatheroma in patients with coronary Artery disease estImated by optical coherence tomogRaphy (ALTAIR) study will investigate the effect of alirocumab on thin-cap fibroatheroma (TCFA) in Japanese patients who underwent recent percutaneous coronary intervention (PCI). METHODS AND DESIGN: ALTAIR is a phase IV, open-label, randomized, parallel-group, single-center study involving blinded optical coherence tomography (OCT) image analysis in Japanese adults hospitalized for PCI and having suboptimal control of low-density lipoprotein cholesterol (LDL-C) levels (>70mg/dL) despite statin therapy. Patients will be randomized (1:1) to the alirocumab arm (alirocumab 75mg every 2 weeks added to rosuvastatin 10mg/day) or the standard-of-care arm (rosuvastatin 10mg/day, with initiation and/or dose adjustment of non-statin lipid-lowering to achieve an LDL-C target of <70mg/dL). OCT imaging will be conducted at baseline and at week 36 (post-treatment). The primary objective is to compare the alirocumab and standard-of-care arms regarding the change in TCFA fibrous-cap thickness after 9 months of treatment. CONCLUSION: The outcomes of ALTAIR (ClinicalTrials.gov identifier: NCT03552432) will provide insights into the effect of alirocumab on plaque vulnerability following PCI in patients with suboptimal LDL-C control despite stable statin therapy.

Pulmonary Endarterectomy and Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension　- Similar Effects on Health-Related Quality of Life.

Background: While hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH) can be improved by invasive therapy such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA), there has been little data on the health-related quality of life (HRQOL) in such patients. Methods and Results: This single-center and observational study compared the impact of invasive therapy on HRQOL. We utilized the Medical Outcome Study 36-Item Short Health Survey (SF-36) to measure HRQOL and compared HRQOL changes after PEA and BPA. A total of 48 patients were diagnosed with CTEPH. Of these, 39 patients completed questionnaires before and after invasive therapy. The PEA group (n=15) and the BPA group (n=24) had similar improvements in clinical parameters. With regard to HRQOL score, both groups had fairly low scores in physical functioning (PF), role physical (RP), general health (GH), social functioning (SF), role emotional (RE), and physical component summary (PCS) at baseline. PF, GH, vitality (VT), mental health (MH), and PCS had significant improvements in the PEA group while PCS and all subscales except for bodily pain (BP) had significant improvements in the BPA group. Furthermore, changes between baseline and follow-up were not significantly different between the 2 groups. Conclusions: BPA for patients who are ineligible for PEA can recover HRQOL to a similar level to that achieved by PEA.

"Anagrelide-induced pulmonary arterial hypertension": a rare case of drug-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension can be associated with exposure to certain drugs or toxins. However, only a few cases of drug-induced pulmonary arterial hypertension have been previously reported. Anagrelide is an oral imidazoquinazoline agent that is prescribed for reducing elevated platelet counts in patients with myeloproliferative disorders. We report the case of a 70-year-old female patient who developed pulmonary arterial hypertension after taking anagrelide for the treatment of polycythemia vera. Pulmonary arterial hypertension promptly improved after the discontinuation of anagrelide. Anagrelide-induced pulmonary arterial hypertension is a very rare disease, and our case shows that it might be reversible.

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Residual symptoms after pulmonary endarterectomy (PEA) remain as the clinical issues to be solved. Additional balloon pulmonary angioplasty (BPA) after PEA showed its efficacy with symptoms in a case series, although long-term spontaneous recovery of exercise ability after PEA was also reported. However, no studies have validated the clinical efficacy of additional BPA by directly comparing PEA with and without BPA. The aim of this study was to retrospectively evaluate the efficacy of additional BPA as a sequential hybrid therapy for chronic thromboembolic pulmonary hypertension after PEA. METHODS AND RESULTS: Among 44 patients with chronic thromboembolic pulmonary hypertension, 20 patients had residual symptoms after PEA. Of those, 10 patients underwent additional BPA (hybrid group) and were compared with the other 10 patients, who were followed up without BPA (PEA group). The period from PEA to additional BPA was 7.3±2.3 months. In hybrid group, mean pulmonary arterial pressure was significantly improved by PEA (40.6±1.8 to 26.9±3.1 mm Hg, P=0.001) and improved further (to 16.7±1.8 mm Hg, P=0.002) with additional BPA, which resulted in remarkable improvement in World Health Organization (WHO) functional class (pre- to post-BPA: class I/II/III/IV, 0/5/4/1 to 7/3/0/0; P<0.001). Compared with the PEA group at follow-up, the hybrid group achieved better mean pulmonary arterial pressure (18.7±1.7 versus 30.2±3.2 mm Hg, P=0.008), WHO functional class (class I/II/III/IV, 7/3/0/0 versus 0/8/2/0; P=0.001), and 6-minute walking distance (429±38 versus 319±22 m, P=0.028). CONCLUSIONS: A sequential hybrid strategy improved residual symptoms and exercise capacity compared with single-PEA therapy.