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.

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.

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%.

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.

New Oxyhalide Solid Electrolytes with High Lithium Ionic Conductivity >10†mS cm-1 for All-Solid-State Batteries.

All-solid-state batteries (ASSBs) with inorganic solid electrolytes (SEs) have attracted significant interest as next-generation energy storage. Halides such as Li3 YCl6 are promising candidates for SE because they combine high oxidation stability and deformability. However, the ionic conductivities of halide SEs are not as high as those of other SEs, especially sulfides. Here, we discover new lithium-metal-oxy-halide materials, LiMOCl4 (M=Nb, Ta). They exhibit extremely high ionic conductivities of 10.4 mS cm-1 for M=Nb and 12.4 mS cm-1 for M=Ta, respectively, even in cold-pressed powder forms at room temperature, which are comparable to or surpass those of organic liquid electrolytes used in lithium-ion batteries. Bulk-type ASSB cells using the oxyhalides as the cathode SE demonstrate an outstanding rate capability with a capacity retention of 80 % at 5 C/0.1 C. We believe that the proposed oxyhalides are promising SE candidates for the practical applications of ASSBs.

Rehabilitation of a Patient with COVID-19 Who Underwent Right Transfemoral Amputation Due to Acute Limb Ischemia: A Case Report.

Background: Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic complications. Nonetheless, there is a paucity of clinical knowledge regarding rehabilitation of patients with COVID-19 after lower-limb amputation. Case: A 74-year-old woman with COVID-19 was admitted to a university hospital. During hospitalization, she underwent right transfemoral amputation due to acute limb ischemia. Three months after admission, the patient was transferred to a convalescent rehabilitation ward in the same hospital. A femoral prosthesis was prescribed 2 weeks after her transfer to the rehabilitation ward. It featured ischial-ramal containment with a soft liner and belt suspension, 668-g multiple linkage-type safety knee joint (Imasen Engineering; M0781 SwanS), and a solid-ankle cushioned-heel foot. The total rehabilitation time during the patient's stay in the acute-care and rehabilitation wards was 65.5 h (0.99 h/day, 66 days) and 275.0 h (3.02 h/day, 91 days), respectively. In the rehabilitation ward, the patient underwent 54.4 h (19.8%) of muscle strength training, 48.1 h (17.5%) of comprehensive assessments, and 47.1 h (17.1%) of gait training. The patient was discharged home 6 months after admission, with a total Functional Independence Measure score of 120. The patient could walk slowly [44.2 s (0.23 m/s) in the 10 m-walk test] with a femoral prosthesis and a quad cane but exhibited limited endurance (75.0 m in the 6-min walk test). Discussion: Following appropriate rehabilitation, a patient was able to walk independently after lower-limb amputation despite the complication of COVID-19, although her walking ability was limited.

Reversible Cardiac Hypertrophy in Pulmonary Arterial Hypertension Treated With High-Dose Epoprostenol.

Although current guidelines recommend the use of prostanoid infusion that includes epoprostenol for high-risk pulmonary arterial hypertension patients, epoprostenol has many adverse effects. We report a case of a heritable pulmonary arterial hypertension patient who had transient biventricular hypertrophy during high-dose administration of epoprostenol. In this case, biventricular hypertrophy with worsening of dyspnea was observed during the uptitration of epoprostenol. Inflammatory diseases and endocrine disorders were ruled out as causes of the ventricular hypertrophy. After epoprostenol was changed to intravenous treprostinil, the biventricular hypertrophy normalized, in connection with dyspnea improvement. The use of high-dose epoprostenol may contribute to cardiac hypertrophy.

Bien que les lignes directrices en vigueur recommandent les perfusions de prostanoïdes comprenant de l'époprosténol chez les patients à risque élevé atteints d'hypertension artérielle pulmonaire, les effets indésirables de l'époprosténol sont nombreux. Nous décrivons ici le cas d'un patient atteint d'hypertension artérielle pulmonaire héréditaire ayant présenté une hypertrophie biventriculaire transitoire pendant le traitement par de l'époprosténol à dose élevée. Pour ce patient, une hypertrophie biventriculaire accompagnée d'une aggravation des symptômes de dyspnée ont été observées lors de l'ajustement à la hausse de la dose d'époprosténol. Les maladies inflammatoires et les troubles endocriniens ont été écartés comme facteurs étiologiques de l'hypertrophie ventriculaire. Après le remplacement de l'époprosténol par du tréprostinil intraveineux, l'hypertrophie biventriculaire s'est résorbée, et les symptômes de dyspnée se sont atténués. Il semble donc que l'utilisation de l'époprosténol à dose élevée puisse contribuer à l'hypertrophie cardiaque.

EmPHasis-10 Health-Related Quality of Life and Exercise Capacity in Chronic Thromboembolic Pulmonary Hypertension After Balloon Angioplasty.

Background Whether pulmonary hemodynamic parameters and functional capacity are associated with quality of life in patients with chronic thromboembolic pulmonary hypertension remains unknown. This study aimed to evaluate disease-specific quality of life using the emPHasis-10 questionnaire and assess its determinants in patients with chronic thromboembolic pulmonary hypertension with normalized pulmonary hemodynamics. Methods and Results This cross-sectional study included 187 health status assessments of 143 patients with chronic thromboembolic pulmonary hypertension (median age, 68 [58-75] years; men/women, 51/136; use of home oxygen therapy, 51 patients [27%]) after balloon pulmonary angioplasty with normalized mean pulmonary artery pressure <25 mm Hg at rest. Right heart catheterization was performed, followed by assessment of 6-minute walk distance and the emPHasis-10 questionnaire. The median pulmonary artery pressure and pulmonary vascular resistance were 18 (15-21) mm Hg and 2.2 (1.7-2.9) wood units, respectively. The median emPHasis-10 score was 14 (8-24), whereas the median 6-minute walk distance was 447 (385-517) m. Univariate linear regression analysis showed that the emPHasis-10 score was associated with 6-minute walk distance (ß=-0.476 [95% CI -0.604, -0.348], P<0.001) and home oxygen therapy (ß=0.214 [95% CI, 0.072, 0.356], P=0.003) but not with hemodynamic parameters. Multiple regression analysis revealed that a higher emPHasis-10 score was associated with lower 6-minute walk distance (ß=-0.475 [95% CI, -0.631 to -0.319], P<0.001). Conclusions Health-related quality of life was associated with exercise capacity and the use of home oxygen therapy, but not with hemodynamic parameters, in patients with chronic thromboembolic pulmonary hypertension and normalized hemodynamics after balloon pulmonary angioplasty. Improvements in exercise capacity may lead to further improvements in quality of life.

High prevalence of occult left ventricular diastolic dysfunction detected by exercise stress test in systemic sclerosis.

Despite the poor prognosis of systemic sclerosis (SSc) due to the co-occurrence of left ventricular diastolic dysfunction (LVDD), presence of occult LVDD has not been sufficiently investigated. This retrospective study aimed to reveal the prevalence and determinants of occult LVDD in patients with SSc by exercise stress test. Forty-five SSc patients (age, 63 ± 13 years; men/women, 6/39) with normal pulmonary artery pressure and pulmonary artery wedge pressure (PAWP) at rest underwent a symptom-limited exercise test with right heart catheterization using a supine cycle ergometer; haemodynamic parameters at rest, leg raise and during exercise were evaluated. Occult LVDD defined PAWP ≥ 25 mmHg during exercise was seen in 13 patients (29%). Higher PAWP, lower pulmonary vascular resistance and diastolic pulmonary pressure gradient, larger left atrium at rest, and higher PAWP during leg raise (15 ± 4 vs 10 ± 4 mmHg in non-LVDD group, p < 0.001) were observed in the occult LVDD group. The area under the ROC curve for PAWP after leg raise was largest at 0.83 (95% CI: 0.70-0.95, p = 0.001). About one-third (29%) of SSc patients with normal haemodynamics at rest showed occult LVDD. A higher PAWP after leg raise could be useful for detecting occult LVDD.

Successful epoprostenol withdrawal and termination with an aid of the exercise stress test in pulmonary arterial hypertension.

Continuous infusion of intravenous epoprostenol (EPO) improves exercise capacity and survival in pulmonary arterial hypertension (PAH); however, it is associated with side effects. This study aimed to describe our experience on safe EPO withdrawal with the aid of an exercise stress test. This retrospective review included patients with PAH who were successfully withdrawn from EPO. Haemodynamic data were obtained before EPO administration, at withdrawal, and after discontinuation. After the mean pulmonary arterial pressure (mPAP) decreased to <25 mmHg for at least 1 year, an exercise test under right heart catheterisation was performed. If exercise pulmonary hypertension was not record (mPAP - cardiac output slope < 3), EPO was withdrawn. Of the 99 patients who received EPO, ten were identified as having undergone withdrawal or termination. mPAP decreased from 61 (54-71) mmHg before treatment to 19 (17-21) mmHg before withdrawal and remained unchanged, at 19 (14-23) mmHg, 1 year after EPO discontinuation. After a median follow-up of 32 months, all the patients survived. Patients with PAH who recovered their normal haemodynamic function were safely withdrawn from EPO with the aid of an exercise stress test.

Novel diagnostic and therapeutic approaches to pulmonary hypertension due to the unilateral absence of a pulmonary artery.

We report the case of a 64-year-old female diagnosed with severe pulmonary hypertension due to the unilateral absence of a pulmonary artery. The four-dimensional computed tomography scan is a useful modality for revealing detailed anatomical findings for differential diagnoses and surgical decision-making. The patient had severe pulmonary hypertension with a mean pulmonary artery pressure (PAP) of 74 mmHg and was treated with triple upfront combination therapy, leading to significant improvement in pulmonary haemodynamics (to 27 mmHg in mean PAP) and functional capacity (WHO functional class, from III to II; 6-min walk distance, from 211 to 276 m).

Factors contributing to exercise capacity in chronic thromboembolic pulmonary hypertension with near-normal hemodynamics.

BACKGROUND: Despite improved survival for patients with chronic thromboembolic pulmonary hypertension (CTEPH) due to progressive medical and interventional treatment, impaired exercise capacity remains common due to poorly understood mechanisms. We aimed to clarify the exercise capacity of CTEPH patients with near-normal pulmonary hemodynamics and evaluate its determinants among the hemodynamic, peripheral (e.g., oxygen use by the peripheral tissues), and muscular (e.g., skeletal muscle strength) factors. METHODS: Three hundred and twenty-nine patients with CTEPH (mean age, 63 ± 12 years; men/women, 73/256) with a near-normal mean pulmonary artery pressure (≤30 mm Hg) at rest were enrolled. We assessed exercise capacity by peak oxygen consumption (peak VO2) using cardiopulmonary exercise testing with a right heart catheter. We also measured the 6-minute walk distance (6MWD) and quadriceps muscle strength. RESULTS: The mean pulmonary artery pressure was 19 ± 4 mmHg and mean cardiac output was 4.8 ± 1.5 L/min at rest. The mean 6MWD was 444 ± 101 m, while the mean peak VO2 was 14.4 ± 3.9 mL/min/kg. A multivariate model that predicted 6MWD included quadriceps strength (ß = 0.45, p < 0.001) and peak arterial venous oxygen difference (ß = 0.29, p < 0.001). In contrast, the peak VO2 was best correlated with mPAP-CO slope (ß = -0.30, p < 0.001), followed by quadriceps strength and peak arterial venous oxygen difference. CONCLUSIONS: The 6MWD performance may be significantly influenced by peripheral oxygen use and muscular factors, while peak VO2 is influenced by hemodynamic and peripheral factors in CTEPH patients with near-normal hemodynamics.

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.

Pulmonary Artery Pressure as a Treatment Target to Improve the Prognosis of Idiopathic Pulmonary Arterial Hypertension　- Insight From a Cohort From Two Japanese Pulmonary Hypertension Centers.

Background: The prognosis of pulmonary arterial hypertension (PAH) has been improving since the introduction of epoprostenol (EPO). The 3-year survival of naïve idiopathic PAH (IPAH) and hereditary PAH (HPAH) was 96% in a recent prospective Japanese registry. This increase in survival in Japan may have been due to the reduction of pulmonary artery pressure (PAP) by a rapid and sufficient dosage of EPO. The aim of this retrospective study was therefore to analyze whether decreasing the PAP contributes to improving PAH prognosis. Methods and Results: Sixty-four patients with IPAH/HPAH followed up at Keio and Kyorin University Hospitals between 1999 and 2011 were enrolled and divided into 2 groups: surviving or non-surviving. Of 14 variables, EPO use, most improved mean PAP (mPAP), brain natriuretic peptide level, cardiac output, 6-min walk distance, and sex were significantly different between the 2 groups. The former 3 variables were significantly related to death on multiple regression analysis. mPAP had the highest odds ratio of 1.44 and the largest area under the receiver operating characteristic curve. The value of mPAP with the optimal combination of sensitivity and specificity was 42 mmHg. Conclusions: The best treatment target for the prognosis of IPAH/HPAH may be the reduction of mPAP; a similar large-scale study is anticipated.

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.