Mortality, Recurrent Thromboembolism and Major Bleeding in Cancer-Associated and Non-Cancer Pulmonary Embolism Patients Treated With Direct Oral Anticoagulants.

BACKGROUND: Pulmonary embolism (PE) is a potentially fatal form of venous thromboembolism (VTE). This study compares the mortality, incidence of recurrent VTE, and incidence of major bleeding between non-cancer and cancer-associated PE patients treated with direct oral anticoagulants (DOACs).Methods and Results:This was a retrospective, observational, single-center study involving 130 consecutive patients (87 with active cancer; 43 without cancer) who received DOAC treatment for PE between January 2016 and December 2019. Kaplan-Meier analysis showed significantly higher mortality in cancer-associated PE patients than in non-cancer patients (35/87 [40%] vs. 1/43 [2%], P<0.001, log-rank test, HR 18.6 [95% CI: 2.5-136.0]). In contrast, the cumulative incidences of recurrent VTE and major bleeding were comparable between the 2 groups. Among the cancer-associated PE patients, the incidence for the composite outcome of recurrent VTE or major bleeding was significantly higher in patients undergoing chemotherapy than in those not undergoing chemotherapy (9/37 [24%] vs. 2/50 [4%], P=0.004, log-rank test, HR 6.9 [95% CI: 1.5-32.0]). CONCLUSIONS: Although cancer-associated PE patients treated with DOACs showed higher mortality compared with non-cancer patients, presumably because of the presence of cancer, the risk of recurrent VTE or major bleeding was comparable between the 2 groups. Thus, DOAC is an important treatment option for cancer-associated PE, although underlying cancer-related risks (e.g., chemotherapy) remain.

Assessment of Severity in Chronic Thromboembolic Pulmonary Hypertension by Quantitative Parameters of Dual-Energy Computed Tomography.

OBJECTIVE: The objective of this study was to assess the correlation between dual-energy computed tomography quantitative parameters and hemodynamics in patients with chronic thromboembolic pulmonary hypertension. METHODS: Dual-energy computed tomography of 52 chronic thromboembolic pulmonary hypertension patients were evaluated retrospectively. The mean lung perfused blood volume (lung PBV) and the mean pulmonary artery (PA) enhancement measured at pulmonary parenchymal phase were compared with the hemodynamics by Spearman rank correlation coefficient (rs) and receiver operating characteristic analysis. RESULTS: Lung PBV was correlated with mean pulmonary arterial pressure (rs = 0.47, P < 0.001). Pulmonary artery enhancement was correlated with cardiac index (rs = -0.49, P < 0.001) and pulmonary vascular resistance (rs = 0.48, P < 0.001). The areas under the curves were 0.86 for lung PBV to predict mean pulmonary arterial pressure of >50 mm Hg and 0.86 for PA enhancement to predict pulmonary vascular resistance of >1000 dyne·s/cm. CONCLUSIONS: Lung PBV and PA enhancement could be indicators of hemodynamics.

Single-center prognostic validation of the risk assessment of the 2015 ESC/ERS guidelines in patients with pulmonary arterial hypertension in Japan.

The 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension include a multidimensional risk assessment for patients with pulmonary arterial hypertension (PAH). However, prognostic validations of this risk assessment are limited, especially outside Europe. Here, we validated the risk assessment strategy in PAH patients in our institution in Japan. Eighty consecutive PAH patients who underwent right heart catheterization between November 2006 and December 2018 were analyzed. Patients were classified as low, intermediate, or high risk by using a simplified version of the risk assessment that included seven variables: World Health Organization functional class, 6-min walking distance, peak oxygen consumption, brain natriuretic peptide, right atrial pressure, mixed venous oxygen saturation, and cardiac index. The high-risk group showed significantly higher mortality than the low- or intermediate-risk group at baseline (P < 0.001 for both comparisons), and the mortalities in the intermediate- and low-risk groups were both low (P = 0.989). At follow-up, patients who improved to or maintained a low-risk status showed better survival than those who did not (P = 0.041). Our data suggest that this risk assessment can predict higher mortality risk and long-term survival in PAH patients in Japan.

Automatic Remasking of Digital Subtraction Angiography Images in Pulmonary Angiography.

In pulmonary angiography, the heartbeat creates artifacts that hinder extraction of blood vessel images in digital subtraction angiography. Remasking according to the cardiac phase of the angiogram may be effective but has yet to be automated. Here, automatic remasking was developed and assessed according to the cardiac phase from electrocardiographic information collected simultaneously with imaging. Manual remasking, fixed remasking, and our proposed automatic remasking were applied to 14 pulmonary angiography series from five participants with either chronic thromboembolic pulmonary hypertension or pulmonary arteriovenous malformation. The processing time and extent of artifacts from the heartbeat were compared. In addition, the peak signal-to-noise ratio (PSNR) was measured from differential images between mask image groups before the injection of the contrast medium to investigate optimal mask images. The mean time required for automatic remasking was 4.7 s/series, a significant reduction in processing time compared with the mean of 266 s/series for conventional manual processing. A visual comparison of the different approaches showed virtually no misregistration artifacts from the heartbeat in manual or automatic remasking according to cardiac phase. The results from measuring the PSNR for differential images between mask image groups also showed that smaller cardiac phase difference and time difference between two images ensure higher PSNR (p < 0.01). Automatic remasking according to the cardiac phase was fast and easy to implement and reduced misregistration artifacts from heartbeat.

Effects of Tobacco Smoking on Cardiovascular Disease.

Tobacco smoking continues to be a major risk factor for cardiovascular disease (CVD) and the leading avoidable cause of death worldwide. Tobacco smoking has declined in high-income countries, but the average smoking rate in Japan remains high: 29.4% for men and 7.2% for women in 2017. Of note, the average smoking rate among middle-aged men remains approximately 40%, indicating that a high incidence of smoking-related CVD will continue for a couple of decades in Japan. The adverse effects of tobacco smoking on CVD are more extensive than previously thought. Physicians should be particularly alert to the development and progression of heart failure, atrial fibrillation, and venous thromboembolism, as well as ischemic CVD among tobacco smokers. Increasing use of heat-not-burn tobacco as cigarette alternatives is an emerging issue. Harmful effects do not disappear just by changing the delivery system of tobacco.

Medium-term health-related quality of life in patients with pulmonary arterial hypertension treated with goal-oriented sequential combination therapy based on exercise capacity.

BACKGROUND: Pulmonary arterial hypertension (PAH) remains a life-threatening condition, despite modern therapies. We prospectively investigated the therapeutic health-related quality of life (HRQOL) effects of goal-oriented sequential combination therapy based on exercise capacity in patients newly diagnosed with PAH. METHODS: To examine the changes in HRQOL in PAH patients, we treated 30 patients newly diagnosed with PAH with goal-oriented sequential combination therapy based on exercise capacity. We monitored exercise capacity by cardiopulmonary exercise testing and observed the benefit of using a peak VO2 cut-off of 15 mL/kg/min to guide combination therapy. First-line treatment was an endothelin receptor antagonist (ERA); second-line treatment was the addition of a phosphodiesterase-5 inhibitor (PDE-5I). At baseline and at 3, 6, and 12 months, HRQOL was evaluated by using the eight-item Medical Outcomes Survey Short Form Health Survey. RESULTS: At 12 months, 100% of PAH patients were receiving an ERA, and 82% an ERA + PDE-5I. The mean physical component summary (PCS) score was 33.5 at baseline, 41.2 at 3 months, 40.8 at 6 months, and 42.0 at 12 months, and the mean mental component summary (MCS) scores were 45.6, 47.0, 50.0, and 50.1, respectively. PCS score was significantly greater at 3 months than at baseline (P = 0.035). MCS score was comparable at 3 months and at baseline, but was significantly greater at 6 and 12 months than at baseline (P = 0.033, P = 0.028, respectively). Thus, PCS score improved soon after initiation of therapy, and MCS score improved later. CONCLUSIONS: Together, these results suggest that goal-oriented sequential combination therapy based on exercise capacity improves HRQOL in patients with PAH.

Usefulness of scoring right ventricular function for assessment of prognostic factors in patients with chronic thromboembolic pulmonary hypertension.

Right ventricular (RV) function is associated with prognosis in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to establish an RV dysfunction score using RV echocardiographic parameters to clarify the clinical characteristics in patients with CTEPH and to compare RV dysfunction score with parameters such as World Health Organization (WHO) functional class, hemodynamics, exercise capacity, and plasma BNP level. We enrolled 35 inpatients with CTEPH (mean age, 62 ± 15 years, 15 males). We constructed 'an RV dysfunction score' calculated as the summation of each point awarded for the presence of four parameters: tricuspid annular plane systolic excursion (TAPSE) < 16 mm, 1 point; tissue Doppler-derived tricuspid lateral annular systolic velocity (S') < 10 cm/s, 1 point; right ventricular fractional area change (RVFAC) < 35%, 1 point; and right ventricular myocardial performance index (RV-MPI) > 0.4, 1 point. TAPSE, S', RVFAC, and RV-MPI was 18.7 ± 4.8 mm, 11.9 ± 3.1 cm/s, 33.5 ± 13.9%, and 0.39 ± 0.2, respectively. The RV dysfunction score was associated with symptom [WHO functional class (p = 0.026)], hemodynamics [mean PAP (p = 0.01), cardiac index (p = 0.009), pulmonary vascular resistance (p = 0.001), and SvO2 (p = 0.039)], exercise capacity [6-min walk distance (p = 0.046), peakVO2 (p = 0.016), and VE/VCO2 slope (p = 0.031)], and plasma BNP level (p = 0.005). This RV dysfunction score using the four RV echocardiographic parameters could be a simple and useful scoring system to evaluate prognostic factors in patients with CTEPH.

Left ventricular end-diastolic dimension and septal e' are predictors of cardiac index at rest, while tricuspid annular plane systolic excursion is a predictor of peak oxygen uptake in patients with pulmonary hypertension.

Little is known regarding a correlation of hemodynamics at rest or exercise capacity with echocardiographic parameters in patients with pulmonary hypertension (PH). To clarify these potential correlations, we performed transthoracic echocardiography, right heart catheterization, and cardiopulmonary exercise testing in 53 patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Left ventricular end-diastolic dimension (LVDd), early diastolic velocity of the septal mitral annulus (septal e'), tricuspid regurgitation peak gradient (TRPG), and tricuspid annular plane systolic excursion (TAPSE) were significantly correlated with cardiac index (LVDd; r = 0.477, P < 0.001, septal e'; r = 0.463, P = 0.001, TRPG; r = - 0.455, P = 0.001 and TAPSE; r = 0.406, P = 0.003, respectively). Multiple regression analysis revealed that LVDd and septal e' were significantly associated with cardiac index (CI) and stroke volume index at rest. Among the exercise capacity markers evaluated, TAPSE, TRPG, and LVDd were significantly correlated with peak oxygen uptake (TAPSE; r = 0.534, P < 0.001, TRPG; r = - 0.466, P = 0.001 and LVDd; r = 0.411, P = 0.002, respectively). Multiple regression analysis showed that TAPSE was significantly associated with peak oxygen uptake (VO2). In PAH and CTEPH patients, LVDd and septal e' were significantly associated with CI at rest, whereas TAPSE was significantly associated with peak VO2. Echocardiographic parameters may predict the prognostic factors of PAH and CTEPH patients.

Serum uric acid as a predictor of future hypertension: Stratified analysis based on body mass index and age.

BACKGROUND: Serum uric acid level is a predictor of future hypertension. However, its dependence on body mass index or age is unclear. METHODS: We examined 26,442 Japanese males aged 18-60years free from hypertension or diagnosed cardiovascular disease at baseline followed up between 2000 and 2010. Participants were categorized into three groups according to the tertile of serum uric acid levels [mg/dL; 1st (reference): 0.1-5.3; 2nd: 5.4-6.2; 3rd: 6.3-11.6]. Incident hypertension was defined as newly detected blood pressure≥140/90mmHg and/or antihypertensive drugs initiation. Body mass index (<25kg/m(2) vs. ≥25kg/m(2)) and age (<40years vs. ≥40years) were stratified into two groups. RESULTS: During a mean follow-up of 7.2years, there were 11,361 (43%) hypertension cases. Mean serum uric acid levels (mg/dL) at baseline in each group were 1st tertile, 4.6; 2nd tertile, 5.8; and 3rd tertile, 7.0. The cumulative incident hypertension rate was significantly higher in the 3rd tertile (50.8%) than in the 1st (37.4%). Multiple-adjusted hazard ratios (95% confidence interval) for incident hypertension compared with 1st tertile were 1.01 (0.96-1.05) and 1.15 (1.10-1.21) in the 2nd and 3rd tertile, respectively. There was a significant interaction between age and serum uric acid level (p for interaction=0.035). In subjects aged ≥40years, the 3rd serum uric acid group showed higher hazard ratios [1.48 (1.38-1.59)]. CONCLUSION: High serum uric acid level was associated with future hypertension in young and middle-aged Japanese males. This association was stronger among subjects ≥40years old.

Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Macitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH. METHODS AND RESULTS: Macitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN-terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667±293 to 417±214 dyn·sec·cm(-5)(P<0.0001). 6MWD increased from 427±128 to 494±116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH. CONCLUSIONS: Macitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. ( TRIAL REGISTRATION: JAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478-1483).

Impact of preoperative regular physical activity on postoperative course after open abdominal aortic aneurysm surgery.

Early ambulation after open abdominal aortic aneurysm (AAA) surgery is assumed to play a key role in preventing postoperative complications and reducing hospital length of stay. However, the factors predicting early ambulation after open AAA surgery have not yet been sufficiently investigated. Here, we investigated which preoperative and intraoperative variables are associated with start time for ambulation in patients after open AAA surgery. A total of 67 consecutive patients undergoing open AAA surgery were included in the study [male, 62 (92 %); mean age, 68 years (range, 47-82 years), mean AAA diameter, 53 mm (range, 28-80 mm)]. Preoperative physical activity was examined by means of 6-min walk distance (6MWD) and a medical interview. Patients were divided into two groups, according to when independence in walking was attained: early group <3 days (n = 36) and late group ≥3 days (n = 31), and the pre-, intra-, and postoperative recovery data were compared. There were no significant differences in patient baseline characteristics or intraoperative data between the two groups. The number of patients engaging in preoperative regular physical activity and 6MWD were significantly greater (p = 0.042 and p = 0.034, respectively) in the early group than in the late group. In addition, time to hospital discharge was significantly shorter in the early group than in the late group (p = 0.031). Binary logistic regression analysis showed that preoperative regular physical activity was the only independent factor for identifying patients in the early group (odds ratio 2.769, 95 % confidence interval 1.024-7.487, p = 0.045). These results suggest that engaging in regular physical activity is an effective predictor of early ambulation after open AAA surgery.

Cardiopulmonary Exercise Testing as a Tool for Diagnosing Pulmonary Hypertension in Patients with Dilated Cardiomyopathy.

BACKGROUND: Recently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly threatening result of left-sided heart disease. However, there have been few investigations of the impact of cardiopulmonary exercise testing (CPX) variables on PH in dilated cardiomyopathy (DCM). We evaluated the usefulness of crucial CPX variables for detecting elevated pulmonary arterial pressure (PAP) in patients with DCM. METHODS: Ninety subjects with DCM underwent cardiac catheterization and CPX at our hospital. Receiver operator characteristic (ROC) analysis was performed to assess the ability of CPX variables to distinguish between the presence and absence of PH. RESULTS: Overall mean values were: mean PAP (mPAP), 18.0 ± 9.6 mmHg; plasma brain natriuretic peptide, 233 ± 295 pg/mL; and left ventricular ejection fraction, 30.2 ± 11.0%. Patients were allocated to one of two groups on the basis of mean PAP, namely DCM without PH [mean PAP (mPAP) <25 mmHg; n = 75] and DCM with PH (mPAP ≥25 mmHg; n = 15). A cutoff achieved percentage of predicted peak VO2 (%PPeak VO2 ) of 52.5% was the best predictor of an mPAP ≥25 mmHg in the ROC analysis (area under curve: 0.911). In the multivariate analysis, %PPeak VO2 was the only significant independent predictor of PH (Wald 6.52, odds ratio 0.892, 95% CI 0.818-0.974; P = 0.011). CONCLUSIONS: %PPeak VO2 was strongly associated with the presence of PH in patients with DCM. Taken together, these findings indicate that CPX variables could be important for diagnosing PH in patients with DCM.

Endomyocardial radial strain rate imaging during dobutamine stress echocardiography for the evaluation of contractile reserve in patients with dilated cardiomyopathy.

PURPOSE: Myocardial contractile reserve is associated with clinical prognosis in patients with dilated cardiomyopathy (DCM). We assessed myocardial contractile reserve using tissue Doppler strain rate imaging with dobutamine stress echocardiography in DCM patients. METHODS: Simultaneous echocardiography and left ventricular (LV) catheterization during dobutamine stress were performed in 20 patients with DCM, and echocardiography was performed in 31 control subjects. Dobutamine was infused at a starting dose of 5 µg/kg/min for 5 minutes and then at 10 µg/kg/min. Peak endomyocardial radial strain (ɛ) and systolic strain rate (SRsys ) measured with echocardiography and the maximum first derivative of LV pressure (LV dP/dtmax ) derived from catheterization were used as indices of contractility. Their percentage change from baseline to the dose of 10 µg/kg/min was calculated. RESULTS: The ɛ and SRsys were significantly smaller in DCM patients than in controls. The LV dP/dtmax , ɛ, and SRsys were significantly higher at the dose of 10 µg/kg/min than at baseline. The percentage change in SRsys was significantly correlated with the percentage change in LV dP/dtmax . CONCLUSIONS: Strain rate imaging during dobutamine stress in DCM might prove noninvasively informative for the evaluation of myocardial contractile reserve and provide insight into LV systolic dysfunction. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:555-560, 2016.

Prognostic impact of combined late gadolinium enhancement on cardiovascular magnetic resonance and peak oxygen consumption in ambulatory patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Peak oxygen consumption (peak VO2) and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) are prognostic in heart failure. We investigated whether LGE-CMR and peak VO2combined had additive value in risk stratifying patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Fifty-seven DCM patients underwent CMR and cardiopulmonary exercise testing. Cardiac events were cardiac death, hospitalization for decompensated heart failure, or lethal arrhythmia. Twenty-five (44%) were LGE-positive. The median peak VO2was 18.5 mL·kg(-1)·min(-1). On multivariate analysis, positive LGE (P = .048) and peak VO2(P = .003) were independent cardiac event predictors. Cardiac event risk was significantly higher with positive LGE and peak VO2< 18.5 mL ·kg⁻¹ ·min⁻¹ than with negative LGE and peak VO2≥ 18.5 mL · kg⁻¹ · min⁻¹ (hazard ratio 12.5; 95% CI 1.57-100; P = .017). In 3 patient groups (group A: no LGE, peak VO2≥ 18.5 mL · kg⁻¹ · min⁻¹, n = 18; group B: positive LGE or peak VO2< 18.5 mL · kg⁻¹ · min⁻¹, n = 24; group C: positive LGE and peak VO2< 18.5 mL · kg⁻¹ · min⁻¹, n = 15) during follow-up (71 ± 32 months), group C had higher cardiac event rates than the others. CONCLUSIONS: Combined assessment of LGE-CMR and peak VO2provides additive prognostic information in ambulatory DCM.

Associations of proteinuria and the estimated glomerular filtration rate with incident hypertension in young to middle-aged Japanese males.

OBJECTIVE: To investigate the independent associations of proteinuria and the estimated glomerular filtration rate (eGFR) with incident hypertension. METHODS: We investigated 29,181 Japanese males 18-59years old without hypertension in 2000 and examined whether proteinuria and the eGFR predicted incident hypertension independently over 10years. Incident hypertension was defined as a newly detected blood pressure of ≥140/90mmHg and/or the initiation of antihypertensive drugs. Proteinuria and the eGFR were categorized as dipstick negative (reference), trace or ≥1+ and ≥60 (reference), 50-59.9 or <50ml/min/1.73m(2), respectively. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of incident hypertension. RESULTS: At baseline, 236 (0.8%) and 477 (1.6%) participants had trace and ≥1+ dipstick proteinuria, while 1416 (4.9%) and 129 (0.4%) participants had an eGFR of 50-59.9 and <50ml/min/1.73m(2), respectively. The adjusted HRs were significant for proteinuria ≥1+ (HRs 1.20, 95% CI: 1.06-1.35) and an eGFR of <50ml/min/1.73m(2) (1.29, 1.03-1.61). When two non-referent categories were combined (dipstick≥trace vs. negative and eGFR<60 vs. ≥60ml/min/1.73m(2)), the association was more significant for proteinuria (1.15, 1.04-1.27) than for eGFR (0.99, 0.92-1.07). CONCLUSIONS: Proteinuria and a reduced eGFR are independently associated with future hypertension in young to middle-aged Japanese males.

Prognostic value of pulmonary hypertension in ambulatory patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Pulmonary hypertension (PH) because of left-sided heart disease carries a poor prognosis. We investigated whether non-ischemic dilated cardiomyopathy (DCM) with PH is associated with poor prognosis. METHODS AND RESULTS: A total of 256 consecutive DCM patients were enrolled. We measured the ratio of the maximum first derivative of left ventricular pressure (LVdP/dtmax)/systolic blood pressure and pressure half-time (T1/2) as cardiac function. Patients were allocated to 2 groups on the basis of mean pulmonary arterial pressure (mPAP), namely DCM without PH group (mPAP <25 mmHg; n=225) and DCM with PH group (mPAP ≥25 mmHg; n=31). We followed all patients for a mean of 4.3 years for the occurrence of cardiac events, defined as cardiac death or hospitalization for worsening heart failure. Cardiac events were significantly more frequent in the DCM with PH group than in the DCM without PH group (P<0.001). Multivariate Cox regression analysis revealed that mPAP ≥25 mmHg and LV end-systolic volume index were significant independent risk factors for cardiac death. Incidence of cardiac death was significantly higher in patients with DCM with PH than in those without PH [hazard ratio 11.79 (3.18-43.7), P<0.0001]. CONCLUSIONS: The presence of PH was independently associated with an increased incidence of cardiac death in ambulatory patients with DCM.

Clinical usefulness of endothelial progenitor cells in predicting the efficacy of riociguat in chronic thromboembolic pulmonary hypertension.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients.