Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Exercise intolerance in chronic thromboembolic pulmonary hypertension after pulmonary angioplasty.

INTRODUCTION: Exercise pulmonary hypertension is common in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who experience shortness of breath during exercise and reduced exercise capacity despite normalised pulmonary arterial pressure (PAP) at rest; however, the relationship between exercise pulmonary hypertension and exercise capacity remains unclear. Here we aimed to determine whether exercise pulmonary hypertension is related to exercise capacity and ventilatory efficiency in CTEPH patients with normalised resting haemodynamics after pulmonary balloon angioplasty (BPA). PATIENTS AND METHODS: In total, 249 patients with CTEPH treated with BPA (mean±sd age 63±14 years; male:female 62:187) with normal mean PAP (mPAP) (<25 mmHg) and pulmonary arterial wedge pressure (≤15 mmHg) at rest underwent cardiopulmonary exercise testing with right heart catheterisation. mPAP-cardiac output (CO) during exercise was plotted using multipoint plots. Exercise pulmonary hypertension was defined by a mPAP-CO slope >3.0. RESULTS: At rest, pulmonary vascular resistance was significantly higher in the exercise pulmonary hypertension group (n=116) than in the non-exercise pulmonary hypertension group (n=133). Lower peak oxygen consumption (13.5±3.8 versus 16.6±4.7 mL·min-1·kg-1; p<0.001) was observed in the former group. The mPAP-CO slope was negatively correlated with peak oxygen consumption (r= -0.45, p<0.001) and positively correlated with the minute ventilation versus carbon dioxide output slope (r=0.39, p<0.001). CONCLUSIONS: Impaired exercise capacity and ventilatory efficiency were observed in patients with CTEPH who had normalised PAP at rest but exercise pulmonary hypertension.

Etiology of Exercise-Induced Pulmonary Hypertension Can Be Differentiated by Echocardiography　- Insight From Patients With Chronic Pulmonary Thromboembolism With Normal Resting Hemodynamics by Balloon Pulmonary Angioplasty.

BACKGROUND: Exercise-induced pulmonary hypertension (PH) is often seen in chronic thromboembolic PH (CTEPH) patients with normalized resting hemodynamics, but it is difficult to differentiate precapillary PH as pulmonary vascular dysfunction and post-capillary PH from occult-left ventricular dysfunction (LVD). The aim of this study was to examine whether the exercise-induced elevation of pulmonary arterial wedge pressure (PAWP) can be predicted by the echocardiographic index at rest.Methods and Results:A total of 71 CTEPH patients (67±11 years old, male/female=15/56) treated by pulmonary angioplasty with near-normal pulmonary arterial pressure (PAP) and normal PAWP at rest underwent symptom-limited exercise test using supine cycle ergometer with right heart catheterization. Exercise-induced elevation in PAWP of >20 mmHg during exercise was defined as occult-LVD. Resting echocardiography was performed within 3 months. In the occult-LVD (n=28), PAWP at rest after leg raising for exercise (14±4 vs. 11±3 mmHg, P<0.001), and mean PAP during exercise were higher compared with the non-LVD (n=43). Peak oxygen consumption, cardiac output, and pulmonary vascular resistance at peak exercise did not differ between groups. Left atrial volume index (LAVi) in the occult-LVD was significantly larger (39.7±8.1 vs. 34.4±9.6 mL/m2, P=0.017). LAVi correlated with exercise PAWP (r=0.356, P=0.002), but not resting PAWP (r=0.161, P=0.179). CONCLUSIONS: Larger left atrial volume may reflect the exercise-induced PAWP elevation as occult-LVD in CTEPH patients.

Giant Fold Gastritis Induced by Epoprostenol Infusion in Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Epoprostenol infusion is the strongest and most convincing therapeutic strategy for severe pulmonary arterial hypertension (PAH). This study investigated the gastrointestinal side effects of epoprostenol. Methods and Results: The study group of 12 patients treated with epoprostenol (epoprostenol group) and 4 patients without epoprostenol (control group) underwent stomach barium examination, which revealed that the prevalence of giant fold gastritis was significantly higher in the patients treated with epoprostenol (75% in epoprostenol group vs. 0% in control group; P=0.019). CONCLUSIONS: Giant fold gastritis may be an important side effect of epoprostenol infusion.

Nocturnal Hypoxemia, But Not Sleep Apnea, Is Associated With a Poor Prognosis in Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Sleep apnea (SA) can cause repeated nocturnal arterial oxygen desaturation and result in acute increase in pulmonary arterial pressure (PAP). The presence of SA is associated with a poor prognosis in patients with chronic left-sided heart failure, but little is known for patients with pulmonary arterial hypertension (PAH). Methods and Results: We enrolled 151 patients with PAH (44±16 years old, male/female=37/114). They were all in the Nice Classification group 1 (idiopathic PAH/associated PAH=52/48%, mean PAP of 46±16 mmHg). They underwent right-heart catheterization and a sleep study with simplified polysomnography. Averaged percutaneous oxygen saturation (SpO2) during sleep was measured and an apnea-hypopnea index >5 was defined as SA. SA was noted in 58 patients (obstructive SA/central SA: 29/29). Over an average follow-up of 1,170±763 days, 32 patients died. By Kaplan-Meier analysis, there was no significant difference in deaths of patients with and without SA (χ2=2.82, P=0.093). On the other hand, the mortality in patients with lower averaged SpO2 was significantly higher than in those with higher averaged SpO2 (χ2=14.7, P<0.001) and that was the only independent variable related to death in multivariate Cox proportional hazards analysis. CONCLUSIONS: SA in patients with PAH was not associated with worse prognosis, unlike left ventricular heart failure, but nocturnal hypoxemia was related to poor prognosis.

Sorafenib as a potential strategy for refractory pulmonary arterial hypertension.

Sorafenib is an inhibitor of multi-kinases including tyrosine and serine/threonine kinases. We investigated the efficacy and safety of sorafenib for the treatment of patients with refractory pulmonary arterial hypertension (PAH). Sorafenib was started in 9 patients (7 with idiopathic PAH, 2 with pulmonary veno-occlusive disease) who had severe PAH and right heart failure, in spite of treatment with vasodilators specific for PAH. Sorafenib was started as an add-on therapy at a dose of 50 or 100 mg/day, and increased to 100-400 mg/day. New York Heart Association functional class improved in 8 patients and did not change in 1. Mean pulmonary arterial pressure improved in 6 patients (14-28% decrease) and did not apparently change in 2 (follow-up catheterization was not performed in 1 patient). The main adverse effects of sorafenib were skin reactions on the hands and feet, which appeared in 5 patients. They were tolerable in 4 patients, but discontinuation of sorafenib was needed in only 1 patient. In conclusion, sorafenib had favorable effects to improve symptoms and objective variables in patients with refractory PAH, with tolerable adverse events. Sorafenib is an alternative strategy for patients with refractory PAH.

Depressive Status in Patients With Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: The present comparative study with healthy volunteers was conducted to investigate the depressive status and temperament in patients with chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:The results of the temperament and personality scale test, and the Quick Inventory of Depressive Symptomatology-Self Report revealed that CTEPH patients have a significantly higher depressive status than healthy volunteers. CONCLUSIONS: It may be that CTEPH patients are more likely to have a depressive temperament in origin. It is expected that the relationship between the biological traits of CTEPH (e.g., genetics) and patients' depressive temperament will be elucidated in the future.

Successful Treatment of Severe Right-Sided Heart Failure Due to Postoperative Constrictive Pericarditis With Tolvaptan.

The prognosis of inoperative constrictive pericarditis is poor due to subsequent severe right-sided heart failure that is refractory to conventional medical treatment. This case report describes the long-term treatment with tolvaptan, a new selective vasopression V2-receptor antagonist, was remarkably effective for inoperative constrictive pericarditis. Despite that tolvaptan was approved for the treatment of hyponatremia in Europe and the United States, the indications and treatment duration of it are not yet well established clinically. We propose that tolvaptan could offer an alternative option for the treatment of medically refractory severe right-sided heart failure such as constrictive pericarditis.

A case report of limitation of transcatheter hepatic arterial embolization for hereditary hemorrhagic telangiectasia type 2 with pulmonary arterial hypertension.

INTRODUCTION AND IMPORTANCE: Arteriovenous malformations (AVMs) in the liver caused by hereditary hemorrhagic telangiectasia (HHT) influence pulmonary artery hypertension (PAH). Liver transplantation (LT) is the most common treatment for HHT-induced hepatic AVMs. However, LT is contraindicated for patients with severe PAH. There is controversy regarding the ideal therapeutic approach for HHT with PAH and hepatic AVMs. CASE PRESENTATION: We present the case of a 48-year-old female with PAH and HHT. After the initiation of PAH-targeted drugs, we considered that the PAH was mainly caused by high cardiac output secondary to multiple diffuse AVMs in the liver. LT was contraindicated due to high mean pulmonary arterial pressure (mPAP), and we opted to perform transcatheter embolization as an alternative treatment for the AVM. Multiple-stage embolization sessions did not effectively improve the shunt in the liver or the pulmonary hemodynamics. The patient died of an uncontrolled gastrointestinal hemorrhage. CLINICAL DISCUSSION: LT was considered in our case; it was contraindicated because of pulmonary hypertension that was in line with the model for end-stage liver disease exception criteria. Repeated embolization did not reduce the liver shunt or improve pulmonary hemodynamics, possibly due to the diffuse distribution of AVMs in the liver and the rapid development of new collateral vessels with each embolization. Recently, pulmonary vascular resistance (PVR) has been proposed as a more appropriate index for stratifying perioperative risk. CONCLUSION: Based on previous reports and our experience, rapid decision-making regarding LT may be needed based on mPAP and PVR after the initiation of PAH-targeted drugs.

Understanding Patient Perspectives Toward Shared Decision-Making in Patients With Pulmonary Hypertension.

Clinical guidelines for pulmonary hypertension (PH) recommend shared decision-making and individualized treatment. However, patient perspectives on PH treatment goals, preference toward a decision-making style of treatment, and adoption of shared decision-making remain unclear. This cross-sectional questionnaire-based study assessed the patients' preferred and actual participation role in treatment decision-making, rated on 5 scales (ranging from passive [patients leave all decisions to physicians] to active [patients make the decision after physicians show patients several options]) and evaluated the concordance between preferred and actual participation roles. The important factors underlying patients' perspectives in treatment decision-making (i.e., prognosis; symptom, financial, family, and social burdens; patient values; and physician recommendation) were evaluated. Univariate logistic regression analysis was performed to determine the patients with a positive preference toward "physician recommendation" in treatment decision-making. Among 130 patients with PH (median age: 58 years; mean pulmonary arterial pressure: 23 mm Hg; 27.7% were males), 59.2% preferred that "physicians make the decision regarding treatment after showing patients therapeutic options (i.e., intermediate between passive and active roles)." The patient-preferred and actual participation roles in decision-making had moderate agreement (Cohen's kappa = 0.46). The most important factor in treatment decisions was "symptom burden reduction" (93.8%). Although 85.0% of patients chose "physician recommendation" as an important factor, 49.6% chose "alignment with my values." The determinants of patients who chose "physician recommendation" were less severe hemodynamics and better functional capacity. In conclusion, patients with PH preferred that the "physicians make the decision after showing patients therapeutic options" and prioritized physician recommendation over their values.

Exercise pulmonary hypertension in patients with systemic sclerosis based on updated guidelines.

Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis (SSc) remains unknown. We aimed to investigate the characteristics of exercise pulmonary hypertension (ex-PH) in patients with systemic sclerosis (SSc), which are unknown. We retrospectively examined 77 patients with SSc who underwent symptom-limited exercise testing using a cycle ergometer with right heart catheterization at our hospital. Nineteen patients with postcapillary PH were excluded. Fifty-eight patients (median age, 63 years; 55 women) were divided into the overt-PH (n = 18, mean pulmonary arterial pressure [PAP] > 20 mmHg and pulmonary vascular resistance > 2 Wood units at rest), ex-PH (n = 19, mean PAP/cardiac output slope > 3), and non-PH (n = 21) groups. Exercise tolerance and echocardiography results were compared among the groups. Peak oxygen consumption was high in the non-PH group, intermediate in the ex-PH group, and low in the overt-PH group (14.5 vs. 13.0 vs. 12.5 mL/kg/min, p = 0.043), and the minute ventilation/peak carbon dioxide production slope was also intermediate in the ex-PH group (32.2 vs. 32.4 vs. 43.0, p = 0.003). The tricuspid annular plane systolic excursion/systolic PAP ratio decreased from non-PH to ex-PH to overt-PH (0.73 vs. 0.69 vs. 0.55 mm/mmHg, p = 0.018). In patients with SSc, exercise PH may represent an intermediate condition between not having PH and overt PH, according to the new guidelines.

Determinants of physical quality of life in patients with chronic thromboembolic pulmonary hypertension after treatment: Insights from invasive exercise stress test.

BACKGROUND: Impaired quality of life (QoL) is prevalent among patients with chronic thromboembolic pulmonary hypertension (CTEPH) despite improved survival due to medical advances. We clarified the physical QoL of patients with CTEPH with mildly elevated pulmonary hemodynamics and evaluated its determinants using a database of patients with CTEPH evaluated for hemodynamics during exercise. METHODS: The QoL was measured in 144 patients with CTEPH (age, 66 (58-73) years; men/women, 48/96) with mildly elevated mean pulmonary artery pressure (<30 mm Hg) at rest after treatment with balloon pulmonary angioplasty and/or pulmonary endarterectomy using the Short-Form 36 (SF-36) questionnaire. The enrolled patients were divided into 2 groups: physical component summary (PCS) scores in the SF-36 over 50 as PCS-good and those under 50 as PCS-poor. RESULTS: The median PCS in SF-36 score was 43.4 (IQR 32.4-49.5) points. The PCS-poor group (n = 110) was older and had lower exercise capacity and SaO2 during exercise. PCS scores were correlated with 6-minute walk distance (rs=0.40, p < 0.001), quadriceps strength (rs=0.34, p < 0.001), peak VO2 (rs=0.31, p < 0.001), SaO2 at rest (rs=0.35, p < 0.001) and peak exercise (rs=0.33, p < 0.001), home oxygen therapy usage (rs=-0.28, p = 0.001), and pulmonary vascular resistance at peak exercise (rs=-0.26, p = 0.002). CONCLUSIONS: The impairment of physical QoL was common in patients with CTEPH with improved hemodynamics; exercise capacity, hypoxemia, and hemodynamic status during exercise were related to the physical QoL.

Switching from Beraprost to Selexipag in the Treatment of Pulmonary Arterial Hypertension: Insights from a Phase IV Study of the Japanese Registry (The EXCEL Study: EXChange from bEraprost to seLexipag Study).

Pulmonary arterial hypertension (PAH) remains a significant challenge in cardiology, necessitating advancements in treatment strategies. This study explores the safety and efficacy of transitioning patients from beraprost to selexipag, a novel selective prostacyclin receptor agonist, within a Japanese cohort. Employing a multicenter, open-label, prospective design, 25 PAH patients inadequately managed on beraprost were switched to selexipag. Key inclusion criteria included ongoing beraprost therapy for ≥3 months, a diagnosis of PAH confirmed by mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, and current treatment with endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors. Outcomes assessed were changes in hemodynamic parameters (mPAP, cardiac index, pulmonary vascular resistance) and the 6 min walk distance (6-MWD) over 3-6 months. The study found no statistically significant changes in these parameters post-switch. However, a subset of patients, defined as responders, demonstrated improvements in all measured hemodynamic parameters, suggesting a potential benefit in carefully selected patients. The transition was generally well-tolerated with no serious adverse events reported. This investigation underscores the importance of personalized treatment strategies in PAH, highlighting that certain patients may benefit from switching to selexipag, particularly those previously on higher doses of beraprost. Further research is needed to elucidate the predictors of positive response to selexipag and optimize treatment regimens for this complex condition.

Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry.

Background: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group. Objectives: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema. Methods: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders. Results: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis. Conclusions: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541).

Transition from Intravenous Epoprostenol to Treprostinil Due to Intolerable Side Effects in Patients With Pulmonary Arterial Hypertension.

Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension (PAH); however, it has side effects. Reviewing the side effects associated with epoprostenol and treprostinil is essential for improving the long-term treatment strategies for PAH. This retrospective review included patients with PAH who transitioned from intravenous epoprostenol to intravenous treprostinil owing to intolerable side effects, including high cardiac output symptoms, ascites, and thrombocytopenia. Of the 85 patients who received epoprostenol at our hospital between 2013 and 2021, 16 (11 women), with a median age of 33 (range 26 to 40) years (including 12 with idiopathic PAH, 3 with hereditary PAH, and 1 with connective tissue disease pulmonary hypertension), had to switch from intravenous epoprostenol to treprostinil owing to the side effects. After transitioning, epoprostenol-associated intolerable side effects, such as high cardiac output symptoms, ascites, and thrombocytopenia, were ameliorated. In conclusion, for patients with PAH who have intolerable side effects from epoprostenol and have difficulty in continuing treatment, switching from epoprostenol to treprostinil may be an option. Switching treatment leads to better adherence and improved long-term prostacyclin therapy.

Pulmonary artery pressure-perfusion relation during exercise in patients with chronic thromboembolic pulmonary hypertension using pulmonary arteriography and right-heart catheterization.

Background: In pulmonary hypertension (PH), pulmonary artery pressure (PAP) does not increase to pulmonary perfusion (PP) < 50%. During exercise, PAP may be increased even at PP > 50% for the early detection of PP disorders. The relationship between PP estimated by pulmonary angiography (PAG) and PAP was evaluated in patients with chronic thromboembolic PH (CTEPH) treated by balloon pulmonary angioplasty with near-normal PH. Methods: Thirty-one patients (age 60 ± 11 years) with CTEPH underwent catheterization at rest and during exercise. Each segmental PP was determined by visualization of its segmental pulmonary artery and graded from 0 to 3 in the PAG. PP was estimated as the percentage PAG (%PAG) score-%summed total of all segmental PP/the full score-54. Results: The mean PAP (mPAP) increased from 28 ± 6 mmHg to 46 ± 10 mmHg during exercise. Transpulmonary pressure gradient, the value of mPAP with the pulmonary artery wedge pressure substituted at peak exercise, was negatively correlated with %PAG score (rs = -0.56, p < 0.001) and elevated at > 50% PP. Conclusions: The PAP-PP relationship at peak exercise was correlated, shifting from the relationship at rest, and the PAP started to rise with PP > 50%.

Protocol for a multicentre, double-blind, randomised, placebo-controlled trial of riociguat on peak cardiac index during exercise in patients with chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty (THERAPY-HYBRID-BPA trial).

OBJECTIVES: Balloon pulmonary angioplasty (BPA) and medical therapy, such as soluble guanylate cyclase stimulators, are recommended treatments for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA). However, monotherapy with BPA or medical therapy cannot always eliminate symptoms such as exertional dyspnoea. Thus, this study aims to clarify the efficacy of continuous treatment with riociguat in inoperable CTEPH patients with normalised haemodynamics after BPA. METHODS AND ANALYSIS: This is a double-blind, multicentre, randomised, placebo-controlled trial. Participants with CTEPH who are ineligible for PEA will receive riociguat followed by BPA. Subsequently, participants will be randomised (1:1) into either riociguat continuing or discontinuing groups and will be observed for 16 weeks after randomisation. The primary endpoint will be the change in peak cardiac index (CI) during the cardiopulmonary exercise test. In the primary analysis, the least square mean differences and 95% CIs for the change in peak CI at 16 weeks between the groups will be estimated by a linear mixed-effects model with baseline value as a covariate, treatment group as a fixed effect and study institution as a random effect. ETHICS AND DISSEMINATION: National Hospital Organisation Review Board for Clinical Trials (Nagoya) and each participating institution approved this study and its protocols. Written informed consent will be obtained from all participants. The results will be disseminated at medical conferences and in journal publications. REGISTRATION DETAILS: Japan Registry of Clinical Trials: jRCT no. 041200052. CLINICALTRIALS: gov by National Library of Medicine Registry ID: NCT04600492. TRIAL REGISTRATION NUMBER: NCT04600492.

Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Arterial Hypertension.

Background The symptom for identification of pulmonary arterial hypertension (PAH) is dyspnea on exertion, with a concomitant decrease in exercise capacity. Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to exercise capacity and ventilatory efficiency in patients with hemodynamically normalized PAH after medical treatment. Methods and Results In total, 82 patients with PAH (age: median 46 [interquartile range, 39-51] years; male:female, 23:59) and mean pulmonary arterial pressure ≤30 mm Hg at rest were enrolled. The exercise capacity, indicated by the 6-minute walk distance and peak oxygen consumption, and the ventilatory efficiency, indicated by the minute ventilation versus carbon dioxide output slope, were assessed using cardiopulmonary exercise testing with a right heart catheter. The mean pulmonary arterial pressure was 21 (17-25) mm Hg, and the 6-minute walk distance was 530 (458-565) m, whereas the peak oxygen consumption was 18.8 (14.8-21.6) mLꞏmin-1ꞏkg-1. The multivariate model that best predicted 6-minute walk distance included peak arterial mixed venous oxygen content difference (ß=0.46, P<0.001), whereas the best peak oxygen consumption predictors included peak cardiac output (ß=0.72, P<0.001), peak arterial mixed venous oxygen content difference (ß=0.56, P<0.001), and resting mean pulmonary arterial pressure (ß=-0.25, P=0.026). The parameter that best predicted minute ventilation versus carbon dioxide output slope was the resting mean pulmonary arterial pressure (ß=0.35, P=0.041). Quadriceps muscle strength was moderately correlated with exercise capacity (6-minute walk distance; ρ=0.57, P<0.001; peak oxygen consumption: ρ=0.56, P<0.001) and weakly correlated with ventilatory efficiency (ρ=-0.32, P=0.007). Conclusions Central and peripheral factors are closely related to impaired exercise tolerance in patients with hemodynamically normalized PAH.

Characteristics of cardiopulmonary exercise testing in patients with combined post- and pre-capillary pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease (LHD), comprising two subtypes: (1) isolated post-capillary pulmonary hypertension (Ipc-PH) and (2) combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Knowledge regarding the physiological characteristics that distinguish Cpc-PH, which has a worse prognosis, from Ipc-PH remains limited. Therefore, this study aimed to assess the utility of cardiopulmonary exercise testing (CPET) variables in detecting Cpc-PH. METHODS AND RESULTS: Among 105 consecutive patients with LHD (age: 55 ± 13 years; male/female = 79/26) who underwent right heart catheterization and CPET, 45 (43%) were classified as PH-LHD (mean pulmonary artery pressure >20 mmHg). Ipc-PH (n = 24) was defined as pulmonary vascular resistance (PVR) ≤ 3 WU and Cpc-PH (n = 21) as PVR > 3 WU. Patients with Cpc-PH had a significantly lower peak partial pressure of carbon dioxide (PETCO2) (Non-PH/Ipc-PH/Cpc-PH = 38.2 ± 6.6 vs. 38.3 ± 6.0 vs 33.0 ± 4.4 mmHg, p = 0.006), higher VE vs. VCO2 slope (Non-PH/Ipc-PH/Cpc-PH = 33.0 [28.3, 36.6] vs. 32.5 [28.1, 37.8] vs. 40.6 [33.6, 46.1], p = 0.007), and lower ΔVO2/ΔWR (Non-PH/Ipc-PH/Cpc-PH = 8.5 ± 1.4 vs. 8.0 ± 1.7 vs. 6.8 ± 2.0 mL/min/watt, p = 0.001) than those with Ipc-PH and non-PH. Using multivariable logistic regression analysis, CPET variables were found to be independent predictors of Cpc-PH (lower peak PETCO2: odds ratio, 0.728 [95% confidence interval {CI}: 0.616-0.840], p = 0.003 and lower ΔVO2/ΔWR: odds ratio, 0.747 [95% CI: 0.575-0.872], p = 0.003). CONCLUSION: From our exploratory analysis, CPET variables, especially in the lower peak PETCO2 and lower ΔVO2/ΔWR, were associated with Cpc-PH in patients with left heart disease.