[Hemorrhagic Colon Cancer with Left Atrial Thrombus Formation after Anticoagulant Therapy Discontinuation-A Case Report].

The patient was a 72-year-old female. She had been taking rivaroxaban for chronic atrial fibrillation; however, she stopped taking it due to anemia and was hospitalized urgently. A contrast-enhanced computed tomography(CT)scan showed a 30 mm mass in the ascending colon, and a colonoscopy revealed ascending colon cancer(cT3, cN0, cM0, cStage Ⅱa). The tumor was hemorrhagic and was thought to have caused the anemia. On day 6 of hospitalization, another contrast- enhanced CT scan showed a poorly contrast-enhanced area in the left atrium, and transesophageal echocardiography revealed 2 left atrial thrombi(27 mm and 17 mm). Since early induction of anticoagulation therapy was considered, an emergency open right colectomy was performed to remove the cause of the bleeding. Intravenous heparin therapy was started the day after surgery and was switched to oral apixaban therapy on the fourth postoperative day. The postoperative course was good, and she was discharged home on the 17th postoperative day. This patient had conflicting clinical problems simultaneously; however, immediate decision-making and initiation of treatment were effective.

Effects of Dual Initial Combination Therapy With Macitentan Plus Riociguat or Macitentan Plus Selexipag on Hemodynamics in Patients With Pulmonary Arterial Hypertension (SETOUCHI-PH Study)　- Protocol of a Multicenter Randomized Control Trial.

Background: The latest guideline from the European Society of Cardiology and European Respiratory Society recommends initial combination therapy with oral pulmonary arterial hypertension (PAH)-specific drugs in PAH patients with World Health Organization functional class (WHO-FC) II or III. However, whether this initial combination therapy improves hemodynamics and clinical failure events regardless of the combination of PAH-specific drugs remains unknown. This study was designed to evaluate whether the initial combination therapy with macitentan plus riociguat or macitentan plus selexipag showed equal efficacy in reducing pulmonary vascular resistance (PVR) 8 months after administration. Methods and Results: This study is a multicenter randomized control trial. PAH subjects with WHO-FC II or III will be randomized (1 : 1) into initial combination therapy with either macitentan plus riociguat or macitentan plus selexipag, and will be observed 8 months after the initiation of treatment. The primary endpoint will be the difference in the change ratio of PVR from baseline to after 8 months of treatment. Conclusions: The SETOUCHI-PH study will clarify whether initial combination therapy with macitentan plus riociguat or macitentan plus selexipag results in equal reductions in PVR 8 months after administration.

Non-Invasive Central Venous Pressure Measurement Using Enclosed-Zone Central Venous Pressure (ezCVPTM).

BACKGROUND: Central venous pressure (CVP) is measured to assess intravascular fluid status. Although the clinical gold standard for evaluating CVP is invasive measurement using catheterization, the use of catheterization is limited in a clinical setting because of its invasiveness. We developed novel non-invasive technique, enclosed-zone (ezCVPTM) measurement for estimating CVP. The purpose of this study was to assess the feasibility of ezCVP and the relationship between ezCVP and CVP measured by a catheter.Methods and Results:We conducted 291 measurements in 97 patients. Linear regression analysis revealed that ezCVP was significantly correlated with CVP (r=0.65, P<0.0001). The Bland-Altman analysis showed that ezCVP had an underestimation bias of -2.5 mmHg with 95% limits of agreement of -14.1 mmHg and 9.6 mmHg for CVP (P<0.0001). The areas under the curves of receiver operating curve with ezCVP to detect the CVP ≥12 cmH2O (8.8 mmHg) and CVP >10 mmHg were 0.81 or 0.88, respectively. The sensitivity, specificity and positive likelihood ratio of ezCVP for the CVP ≥8.8 mmHg and CVP >10 mmHg were 0.59, 0.96 and 14.8 with a cut-off value of 11.9 and 0.79, 0.97 and 26.3 with a cut-off value of 12.7. CONCLUSIONS: These findings suggest that ezCVP measurement is feasible and useful for assessing CVP.

Prognostic significance of oscillatory ventilation at rest in patients with advanced heart failure undergoing cardiopulmonary exercise testing.

BACKGROUND: Among heart failure patients diagnosed as having exertional oscillatory ventilation (OV), some present with OV at rest that persists during exercise, and others develop OV only after the onset of exercise during cardiopulmonary exercise (CPX) testing. We tested whether or not there was any difference in the prognostic significance between the two abnormal breathing patterns. METHODS: Patients with New York Heart Association class III-heart failure were categorized into the following 3 groups according to their ventilation pattern during the CPX: patients with an OV pattern at rest that persisted for ≥60% of the exercise test at an amplitude of ≥15% of the average resting value (group 1), patients with the same abnormal ventilatory pattern as group 1 that was observed only during exercise (group 2), and patients without any OV (group 3). The patients were followed-up for at least 2 years to assess the composite outcome of cardiac death or hospitalization for worsening heart failure. RESULTS: The occurrence of the composite outcome differed significantly across the groups with its highest occurrence in group 1 (21/29 [72.4%], 15/38 [39.5%] and 48/167 [28.7%]; log-rank P < 0.001). In multivariate hazard analyses, an N-terminal pro-brain natriuretic peptide of >900 pg/mL (hazard ratio [HR] = 1.72, P = 0.04), and group 1 (HR 2.03, P = 0.02) were independently associated with the composite outcome. CONCLUSIONS: Checking for the resting OV prior to incremental exercise during CPX testing may be helpful in risk-stratification among subjects with advanced heart failure.

Reliability and responsiveness of a goniometric device for measuring the range of motion in the dart-throwing motion plane.

Background: Dart-throwing motion (DTM) is an important component of wrist function and, consequently, has the potential to become an evaluation tool in rehabilitation. However, no measurement method is currently available to reliably measure range of motion (ROM) of the wrist in the DTM plane. Objectives: To determine the reliability and responsiveness of a goniometric device to measure wrist ROM in the DTM plane. Methods: ROM of the wrist in the DTM plane was measured in 70 healthy participants. The intra-class correlation coefficient (ICC) was used to evaluate the relative reliability of measurement, and a Bland-Altman analysis conducted to establish its absolute reliability, including the 95% limits of agreement (95% LOA). The standard error of the measurement (SEM) and minimal detectable change at the 95% confidence level (MDC95) were calculated as measures of responsiveness. Results: The intra-rater ICC was 0.87, and an inter-rater ICC of 0.71. There was no evidence of a fixed or proportional bias. For intra- and inter-rater reliability, 95% LOA ranged from -13.83 to 11.12 and from -17.75 to 16.19, respectively. The SEM and MDC95 were 4.5° and 12.4°, respectively, for intra-rater reliability, and 6.0° and 16.6°, respectively, for inter-rater reliability. Conclusion: The ROM of the wrist in the DTM plane was measured with fair-to-good reliability and responsiveness and, therefore, has the potential to become an evaluation tool for rehabilitation.

Predictive value of plaque morphology assessed by frequency-domain optical coherence tomography for impaired microvascular perfusion after elective stent implantation: the intracoronary electrocardiogram study.

Aims: This study was undertaken to assess the association between plaque features at culprit lesions assessed by frequency-domain optical coherence tomography (FD-OCT) and impaired microvascular perfusion estimated by intracoronary electrocardiogram (IcECG) after elective percutaneous coronary intervention (PCI). Furthermore, we investigated whether IcECG could predict future cardiac events. Methods and results: This study consisted of 84 patients who underwent both FD-OCT and IcECG during PCI. Patients were classified into two groups based on ST-segment elevation (ST-E) on IcECG after the procedure; ST-E (-) group (n = 53) and ST-E (+) group (n = 31). Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (-) group (240 µm [IQR 180 to 310] vs. 100 µm [IQR 60 to 120], P < 0.001). Plaque rupture (7.5% vs. 35.5%, P = 0.001), lipid-rich plaque (75.5% vs. 100%, P < 0.001), the thin cap fibroatheroma (0% vs. 25.8%, P < 0.001) on pre-FD-OCT, protrusion (18.9% vs. 56.7%, P < 0.001), and intra-stent dissection (15.1% vs. 50.0%, P < 0.001) on post-FD-OCT were significantly more frequently found in the ST-E (+) group than in the ST-E (-) group. The incidence of MACE (cardiac death, myocardial infarction, revascularization, hospitalization for heart failure) during 1-year was significantly higher in the ST-E (+) group than in the ST-E (-) group (5.7% vs. 19.4%, P < 0.05). Conclusion: Plaque features assessed by FD-OCT might be associated with impaired microvascular perfusion and ST-segment elevation on IcECG after the procedure could predict 1-year cardiac events after elective PCI.

Evaluation of end-tidal CO2 pressure at the anaerobic threshold for detecting and assessing pulmonary hypertension.

Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO2) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P < 0.01). Multiple regression analysis showed that PETCO2 at the AT was independently associated with an elevated mPAP (P = 0.04). The sensitivity and specificity of CPET for PH were 80 and 86%, respectively, when the cut-off value identified by receiver operating characteristic curve analysis for PETCO2 at the AT was ≤34.7 mmHg. A combination of echocardiography and CPET improved the sensitivity in detecting PH without markedly reducing specificity (sensitivity 87%, specificity 85%). Evaluation of PETCO2 at the AT is useful for estimating pulmonary pressure. A combination of CPET and previous screening algorithms for PH may enhance the diagnostic ability of PH.

Use of the augmentation index from applanation tonometry of the radial artery for assessing the extent of coronary artery calcium as assessed by coronary computed tomography.

BACKGROUND: The augmentation index (AI) obtained from applanation tonometry of the radial artery is technically the easiest and quickest of available methods for assessing arterial stiffness. We tested the hypothesis that the radial AI is associated with the extent of coronary artery calcium (CAC) as assessed by coronary computed tomography (CCT). METHODS AND RESULTS: This study included 161 patients with known or suspected coronary artery disease undergoing central hemodynamic measurements and CCT. Radial AI was recorded and was corrected in accordance with heart rate (radial AI@75). Thirty-seven patients had no CAC (CAC score = 0), 85 had low-grade CAC (CAC score = 1-399), and 39 had high-grade CAC (CAC score ≥400). Coronary risk factors, except for age and serum creatinine, were similar among the three groups. There were significant differences in brachial systolic blood pressure (SBP) (p = 0.011) and radial AI@75 (%) (p = 0.006). Multivariate analysis showed that age (ß = 0.27, p = 0.001), serum creatinine (ß = 0.18, p = 0.03), and radial AI@75 (ß = 0.24, p = 0.005) were significantly associated with ln (CAC score + 1), whereas brachial SBP was not. Additionally, serum creatinine (odds ratio: 11.91, 95% confidence interval: 1.46-112.0, p = 0.02) and radial AI@75 (per 10%) (odds ratio: 1.76, 95% confidence interval: 1.22-2.64, p = 0.002) were independent factors associated with high-grade CAC. CONCLUSIONS: Our results suggest that the radial AI is better for estimating CAC than brachial SBP in patients with known or suspected coronary artery disease.

Effects of hemoglobin level on myocardial washout rate of thallium-201 in patients with normal myocardial perfusion assessed by single-photon emission computed tomography.

Myocardial perfusion single-photon emission computed tomography (SPECT) is often performed even in patients with suspected coronary artery disease complicated by anemia. We assessed the effects of hemoglobin level on myocardial washout rate of Thallium-201 (Tl-201) in patients with normal myocardial perfusion assessed by SPECT. The study population consisted of 231 patients with summed stress score of zero on SPECT. The mean myocardial washout rate of Tl-201 in the left ventricle was calculated from the stress and the redistribution Bull's eye map. Hematological test was performed within 2 weeks before gated SPECT. There were 135 male and 96 female patients with a mean age of 72.6 ± 9.0 years. The mean hemoglobin was 12.9 ± 1.9 mg/dl; the median was 13.2 mg/dl and the range was 8.0-16.5 mg/dl. There was a significant inverse correlation between hemoglobin level and myocardial washout rate of Tl-201 (r = -0.45, p < 0.001). Univariate linear regression analysis showed that age, female, body mass index, serum creatinine, hemoglobin, end-diastolic volume, and ejection fraction were associated with myocardial washout rate of Tl-201. Multivariate analysis showed that only hemoglobin was the independent predictor of myocardial washout rate of Tl-201 (ß = -0.35, p < 0.001). Our data suggested that anemia was a major determinant of increased myocardial washout rate of Tl-201 in patients with normal myocardial perfusion on SPECT.

Aortic knob width reflects left ventricular diastolic function assessed by gated myocardial perfusion single photon emission computed tomography in patients with normal myocardial perfusion.

BACKGROUND: Aortic knob width on chest radiography represents the extent of aortic dialation and tortuosity of the aortic arch. We tested the hypothesis that aortic knob width reflected left ventricular (LV) diastolic function assessed by gated myocardial perfusion single photon emission computed tomography (SPECT) in patients with normal myocardial perfusion. METHODS: One hundred and thirty patients with preserved LV ejection fraction and normal myocardial perfusion were enrolled in this study. Aortic knob width was measured along the horizontal line from the point of the lateral edge of the trachea to the left lateral wall of the aortic knob. The peak filling rate (PFR) and the one-third mean filling rate (1/3 MFR) were obtained as LV diastolic parameters. RESULTS: There were 114 male and 16 female patients. Age ranged from 43 to 88 years (69.9 ± 8.9 years). Aortic knob width ranged from 24.2 to 53.4 mm (37.6 ± 5.7 mm). There was a significant correlation between age and aortic knob width (r = 0.34, p < 0.001). Aortic knob width was inversely correlated with both PFR (r = -0.53, p < 0.001) and 1/3 MFR (r = -0.42, p < 0.001). Multivariate linear regression analysis revealed that serum creatinine (ß = -0.16, p = 0.045) and aortic knob width (ß = -0.45, p < 0.001) were significant predictors of PFR, and that age (ß = -0.20, p = 0.02) and aortic knob width (ß = -0.33, p < 0.001) were significant predictors of 1/3 MFR. CONCLUSIONS: Our data suggested that aortic knob width on chest radiography was a simple marker of LV diastolic function in patients with normal myocardial perfusion.

Comparison of 8-frame and 16-frame thallium-201 gated myocardial perfusion SPECT for determining left ventricular systolic and diastolic parameters.

The myocardial perfusion single photon emission computed tomography synchronized with the electrocardiogram (gated SPECT) has been widely used for the assessment of left ventricular (LV) systolic and diastolic functions using Quantitative gated SPECT. The aim of this study was to compare the effects of 8-frame and 16-frame thallium-201 (Tl-201) gated SPECT for determining LV systolic and diastolic parameters. The study population included 42 patients with suspected coronary artery disease who underwent gated SPECT by clinical indication. LV systolic and diastolic parameters were assessed on 8-frame and 16-frame gated SPECT. There were good correlations in end-diastolic volume (r = 0.99, p < 0.001), end-systolic volume (ESV) (r = 0.97, p < 0.001) and ejection fraction (EF) (r = 0.95, p < 0.001) between 8-frame and 16-frame gated SPECT. Bland-Altman plot showed a significant negative slope of -0.08 in EDV indicating a larger difference for larger EDV. Eight-frame gated SPECT overestimated ESV by 2.3 ml, and underestimated EF by -4.2% than 16-frame gated SPECT. There were good correlations in peak filling rate (PFR) (r = 0.87, p < 0.001), one third mean filling rate (r = 0.87, p < 0.001) and time to PFR (r = 0.61, p < 0.001) between 8-frame and 16-frame gated SPECT. Eight-frame gated SPECT underestimated PFR by -0.22 than 16-frame gated SPECT. Eight-frame gated SPECT estimated as much MFR/3 and TPFR as 16-frame gated SPECT. According to the data, the study suggested that 8-frame Tl-201 gated SPECT could underestimate systolic and/or diastolic parameter when compared with 16-frame gated SPECT.

Selvester QRS score and total perfusion deficit calculated by quantitative gated single-photon emission computed tomography in patients with prior anterior myocardial infarction in the coronary intervention era.

Selvester QRS scoring system has an advantage of being inexpensive and easily accessible for estimating myocardial infarct (MI) size. We assessed the correlation and agreement between QRS score and total perfusion deficit (TPD) calculated by quantitative gated single-photon emission computed tomography (QGS) in patients with prior anterior MI undergoing coronary intervention. Sixty-six patients with prior anterior MI and 66 age- and sex-matched control subjects were enrolled. QRS score was obtained using a 50-criteria and 31-point system. QRS score was significantly higher in patients with prior anterior MI than control subjects (12.8 ± 8.9 vs 1.1 ± 2.7 %, p < 0.001). In overall patients (n = 132), QRS score was correlated well with TPD (r = 0.81, p < 0.001). This good correlation was found even in patients with TPD ≤40 % (n = 126) or in patients with TPD ≤30 % (n = 117). In overall patients, MI size estimated by QRS score was 7.0 ± 8.8 %, which was significantly smaller than TPD, 11.4 ± 14.0 % (p < 0.001). Bland-Altman plot showed that there was an increasing difference between QRS score and TPD with increasing MI size. When Blant-Altman plots were applied to patients with TPD ≤40 % and further in patients with TPD ≤30 %, the difference between QRS score and TPD became smaller, and the agreement became better. In overall patients, QRS score was correlated well with QGS measurements, such as end-diastolic volume (r = 0.62, p < 0.001), end-systolic volume (r = 0.67, p < 0.001), or ejection fraction (r = -0.73, p < 0.001). Our results suggest that QRS score reflects TPD well in patients with prior anterior MI, whose TPD is less than approximately 30 % even in the coronary intervention era.

Implications of World Health Organization classification for body mass index on the correlations between common electrocardiographic indexes for left ventricular hypertrophy and left ventricular mass.

BACKGROUND: Some electrocardiographic indexes such as Cornell index, Cornell product index, or Sokolow-Lyon index remain to be used in the clinical setting. We assessed the effects of body mass index (BMI) on the correlations between these ECG indexes and left ventricular mass (LVM). METHODS: One hundred ninety-six outpatients who underwent both ECG and echocardiography on the same day were included in this study. In accordance with the World Health Organization (WHO) classification of BMI, the patients were classified into the four groups: underweight (<18.5 kg/m2, n = 30), normal weight (18.5-24.9 kg/m2, n = 83), overweight (25-29.9 kg/m2, n = 43), and obese (≥30 kg/m2, n = 40). RESULTS: With increasing WHO classification of BMI, Cornell index (RaVL+SV3), Cornell product index [(RaVL+SV3)RQRS duration], and LVM increased. On the other hand, Sokolow-Lyon index (SV1+RV5) decreased. Cornell index correlated with LVM in normal weight group (r = 0.27, p = 0.015), but did not in the other groups. Cornell product index also correlated with LVM in normal weight group (r = 0.30, p = 0.006), but did not in the other groups. Sokolow-Lyon index correlated with LVM well in normal weight group (r = 0.32, p = 0.004) and better in underweight group (r = 0.61, p = 0.0004). However, no correlations were found in overweight and obese groups. CONCLUSIONS: Our results suggest that BMI influences the correlations between these ECG indexes and LVM, and should be taken into consideration when assessing LVH.

Impact of Malondialdehyde-Modified Low-Density Lipoprotein on Tissue Characteristics in Patients With Stable Coronary Artery Disease　- Integrated Backscatter-Intravascular Ultrasound Study.

BACKGROUND: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is considered to play an essential role in plaque destabilization. We aimed to investigate the association between the tissue characteristics of culprit plaque assessed by integrated backscatter (IB)-intravascular ultrasound (IVUS) and the serum MDA-LDL levels in patients with stable coronary artery disease. METHODS AND RESULTS: The study group consisted of 179 patients undergoing IB-IVUS during elective percutaneous coronary intervention. Patients were classified into 2 groups based on serum MDA-LDL level: low MDA-LDL group (<102 U/L, n=88) and high MDA-LDL group (≥102 U/L, n=91). Plaques in the high MDA-LDL group had higher %lipid (45.2±12.5% vs. 54.9±14.5%, P<0.001) and lower %fibrosis (43.0±9.1% vs. 36.4±11.4%, P<0.001) than did plaques in the low MDA-LDL group. Lipid-rich plaque (%lipid >60% or %fibrosis <30%) was significantly more frequently found in the high MDA-LDL group than in the low MDA-LDL group (14.3% vs. 39.8%, P<0.001). The incidence of MACE (cardiac death, myocardial infarction and/or hospitalization for heart failure) during 3 years was significantly higher in the high MDA-LDL group than in the low MDA-LDL group (6.6% vs. 15.9%, P=0.02). CONCLUSIONS: Higher MDA-LDL might be associated with greater lipid and lower fibrous content, contributing to coronary plaque vulnerability. (Circ J 2016; 80: 2173-2182).

Effects of left ventricular size on the accuracy of diastolic parameters derived from myocardial perfusion SPECT: comparison with tissue Doppler echocardiography.

BACKGROUND: Impaired left ventricular (LV) diastolic function is a sensitive and early sign of myocardial ischemia. We evaluated the effects of LV size on the accuracy of diastolic parameters derived from SPECT. METHODS: The study population consisted of 151 patients with known or suspected coronary artery disease who underwent both SPECT and transthoracic echocardiography. Peak filling rate (PFR), one-third mean filling rate (1/3 MFR) and the ratio of time to PFR to the RR interval (TPFR/RR) were calculated by quantitative gated SPECT. Peak early mitral annular velocity (e') was used as the reference standard of LV diastolic function. RESULTS: There were 43 patients with end-systolic volume (ESV) of ≤10 ml, 43 patients with ESV of 11-20 ml and 65 patients with ESV of >20 ml. There were significant differences in PFR (p < 0.001), 1/3 MFR (p < 0.001) or TPFR/RR (p = 0.01) among the 3 groups. These diastolic parameters were increased with decreased LV size. In overall patients, PFR (r = 0.24, p = 0.003) and 1/3 MFR (r = 0.31, p < 0.001) were positively, and TPFR/RR (r = -0.23, p = 0.004) was inversely correlated with e'. Multivariate linear regression analyses showed that male gender (ß = -0.14, p = 0.07; ß = -0.16, p = 0.04), ESV (ß = -0.63, p < 0.001; ß = -0.45, p < 0.001) and e' (ß = 0.36, p < 0.001; ß = 0.40, p < 0.001) were significant factors associated with PFR or 1/3 MFR. Multivariate linear regression analysis also showed that ESV (ß = -0.17, p = 0.03) and e' (ß = -0.21, p = 0.01) were significant factors associated with TPFR/RR. CONCLUSIONS: Our data suggest that PFR, 1/3 MFR and TPFR/RR derived from SPECT are correlated with e' as the reference standard of LV diastolic function, but are overestimated in small-sized heart. LV size should be taken into consideration when interpreting these diastolic parameters.

Iliac Artery Stenting Combined with Open Iliofemoral Endarterectomy Facilitated by a Novel Ultrasonic Ablation Instrument for Diffuse Iliofemoral Occlusive Disease.

An 81-year-old male complained of intermittent claudication of the right leg. Computed tomography (CT) revealed a right external iliac artery (EIA) stenosis with severe calcification extending to the common femoral artery. A hybrid procedure of endarterectomy and stenting was performed. EIA endarterectomy was performed using a novel Cavitron Ultrasonic Surgical Aspirator which ablated the inside of the distal EIA without arterial injury. A stent graft was placed in the proximal EIA covering the margin of endarterectomized distal EIA. Postoperative CT showed no stenosis, and symptoms in the leg disappeared. This could be an alternative procedure for iliofemoral occlusive disease.

Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension.

Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p < 0.05). Of the three subsets, the proportion of non-Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p < 0.01), whereas those of rTregs and aTregs were not different between the two groups. Moreover, the expression levels of cytotoxic T lymphocyte antigen 4, a functional cell surface molecule, in aTregs (p < 0.05) and non-Tregs (p < 0.05) were significantly higher in PAH patients compared with controls. These results suggested the non-Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH.

Prognostic Factors for Survival in Pulmonary Hypertension Due to Left Heart Disease.

BACKGROUND: The epidemiological data of pulmonary hypertension (PH) due to left heart disease (LHD) are limited. This study investigated hemodynamic and clinical factors associated with mortality in patients with PH due to LHD. METHODS AND RESULTS: We conducted a retrospective review in 243 patients with PH due to LHD, defined as mean pulmonary arterial pressure ≥25 mmHg and pulmonary wedge pressure >15 mmHg at rest in right heart catheterization. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Seventy-five patients died during an average follow-up of 52 months (range, 20-73 months). On multivariate analysis, only diastolic pulmonary vascular pressure gradient (DPG) ≥7 mmHg among hemodynamic measurements was a predictor of mortality. Elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), more severe New York Heart Association (NYHA) class, anemia, and renal dysfunction were more strongly associated with mortality. Mean right atrial pressure (RAP) and currently available markers of pulmonary vascular remodeling including transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) had no effect on survival. CONCLUSIONS: DPG is weakly associated with mortality in PH due to LHD. Clinical factors such as NT-pro BNP, NYHA class, anemia and renal dysfunction are superior predictors. The prognostic ability of hemodynamic factors such as mean RAP, TPG, PVR and DPG is limited.

Influence of dual antiplatelet therapy on mean platelet volume in patients with coronary artery disease undergoing percutaneous coronary intervention.

Mean platelet volume (MPV) is a well-established marker of platelet activation, and recent studies have shown that platelet activation is central to the processes in the pathophysiology of coronary artery disease (CAD). The study population consisted of 45 patients with stable CAD who underwent successful percutaneous coronary intervention (PCI) with drug-eluting stents. We selected 45 age- and sex-matched control subjects without cardiovascular diseases who did not require antiplatelet therapy. Hematological test was performed 3 times within 1 month before DAPT (baseline), at 2 weeks after PCI (post PCI) and at 9 months after PCI (follow-up). Compared to control subjects, MPV was significantly larger in patients with CAD (10.0 ± 0.6 vs 10.7 ± 0.8 fl, p < 0.01) although there was no significant difference in white blood cell count, hemoglobin, and platelet count between the 2 groups. In patients with CAD, DAPT did not affect platelet count (19.3 ± 4.8 × 10(4)-18.9 ± 4.6 × 10(4)/µl) or MPV (10.7 ± 0.8-10.5 ± 0.9 fl) during the follow-up period. MPV remained to be higher at follow-up in patients with CAD despite DAPT compared to control subjects (10.1 ± 0.7 vs 10.5 ± 0.9 fl, p < 0.05). Our data suggested that MPV might not be suitable for monitoring the effects of DAPT on platelet activity in patients with CAD undergoing PCI.