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Introduction: Heart failure (HF) especially right-heart failure causes hepatic portal system congestion. The Portal vein (PV) pulsatility can be influenced by right atrial pressure (RAP). However, the association between PV pulsatility and the condition of HF remains unclear. Hypothesis: In this study, we aim to evaluate usefulness of PV pulsatility as a prognostic marker as well as a therapeutic indicator for hospitalized acute HF patients. Methods: We enrolled 54 patients with acute HF and 17 patients without HF served as controls. PV flow velocity was measured by ultrasonography at admission and discharge phase. PV pulsatility ratio (PVPR) was calculated by dividing minimal velocity by peak velocity. The primary endpoint for prognostic analysis was cardiac death and unexpected re-hospitalization for recurrent HF. The observation period was one year from first hospitalization for HF. Results: On admission, PVPR was significantly higher in controls compared to acute HF patients (0.91±0.08 vs. 0.71±0.04, p&lt0.01).PVPR did not change during the hospitalization in controls (admission 0.91±0.08 vs discharge 0.93±0.06, p=0.31). However, in acute HF patients, PVPR was significantly elevated after the improvement of HF (admission 0.71±0.04 vs discharge 0.82±0.02, p&lt0.05) due to the increase in minimal velocity (admission 12.6±4.5 cm/s vs. discharge 14.6±4.6 cm/sec, p&lt0.05), indicating the decrease in RAP. To elucidate the association between PVPR and primary endpoint, the patients were divided into three groups according to the tertile of PVPR at discharge (PVPR-Q1:0.92&ltPVPR&lt1, PVPR-Q2: 0.73&ltPVPR&lt0.92, PVPR-Q3:PVPR&lt0.73). Kaplan-Meier analysis found that the patients with higher PV pulsatility at discharge had significantly higher event rate among the groups (Figure). Conclusions: PVPR at discharge would reflect the condition of HF. It also can be a novel prognostic marker for hospitalized acute HF patients.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are the main subgroups of pulmonary hypertension (PH). Despite differences in their etiologies, both diseases are characterized by vascular remodeling, resulting in progressive right heart failure. Noninvasive periodic evaluation of exercise tolerance has become increasingly important. Cardiopulmonary exercise testing (CPET) and a 6-minute walk test (6MWT) are now both recommended for evaluating exercise tolerance, but there is insufficient knowledge about possible differences in the associations of exercise tolerance with right heart catheterization (RHC) data for patients with PAH and CTEPH.A retrospective study was performed with 57 patients with PH (24 with PAH and 33 with CTEPH) all of whom underwent echocardiography, CPET, 6MWT, and RHC.For both patients with PAH and CTEPH, peak heart rate during CPET was significantly higher than that from 6MWT, whereas minimum peripheral oxygen saturation during CPET and 6MWT was similar. For patients with PAH, significant correlations were observed between peak (Equation is included in full-text article.)O2 and cardiac index (CI) (r = 0.59; P = .002) and between (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slopes and CI (r =-0.46, P = .02), as well as a nonsignificant correlation tendency for peak (Equation is included in full-text article.)O2 and pulmonary vascular resistance (PVR) and for (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 and PVR (r =-0.39; P = .05; and r = 0.39; P = .06, respectively). For patients with CTEPH, however, a significant correlation was observed only between (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slopes and CI (r =-0.38; P = .02).PH etiology should be considered when assessing exercise tolerance, whereas CPET can be effective in addition to hemodynamic assessment by means of RHC for periodic evaluation during followup.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary obstructive vascular disease. But there were few methods to quantify lung blood perfusion. In dual-energy CT (DECT), two image datasets are acquired in the same anatomic location using two different tube potentials. DECT can produce a more sensitive iodine distribution map image than conventional CT, which enable us to quantify blood perfusion in lung fields. There were few reports showing the clinical significance of DECT in CTEPH. Methods: We enrolled 59 consecutive CTEPH patients who underwent DECT from Jan. 2015 to Feb. 2017. We evaluated the relations between DECT parameter as lung pulmonary blood volume (PBV) and clinical parameters from 6-min walk distance (6MWD), respiratory function test, cardiopulmonary exercise test (CPX), and right heart catheterization (RHC). Results: In 59 patients (female 41, mean age 60.0±13.6 years old), two patients were WHO functional class (WHO-Fc) IV, 28 were WHO-Fc III, 23 were WHO-Fc II, six were WHO-Fc I. 28 patients were evaluated at pre-treatment, nine at post pulmonary endarterectomy (PEA), 18 at post balloon pulmonary angioplasty (BPA), and four at post hybrid therapy (PEA and BPA). The average of PBV were 25.4±7.4 Hounsfield Unit. Mean pulmonary arterial pressure (mPAP) were 29.5±12.9 mmHg, pulmonary vascular resistance (PVR) were 553±404 dyne*sec/cm5, cardiac index were 2.3±0.7 l/min/m2. The value of PBV was well reflected with WHO-Fc classification. (I/II/III/IV=31.8±6.4/27.1±7.4/22.8±6.2/23.5±13.4; ANOVA p=0.019), and was significantly correlated with mPAP (r = -0.57, p < 0.01), PVR (r = -0.60, p < 0.01), VE/VCO2 slope (r =- 0.47, p < 0.01), BNP level (r = -0.60, p < 0.01). Conclusion: PBV was positively correlated with symptom, hemodynamics, exercise capacity, and BNP level in the patients of CTEPH, suggesting that PBV by DCET can work as a new management index from a perspective of pulmonary blood perfusion.

Endothelin (ET) 1 is a potent vasoconstrictor peptide produced by vascular endothelial cells and implicated in various pathophysiologic states involving abnormal vascular tone. Homozygous ET-1 null mice have craniofacial and cardiac malformations that lead to neonatal death. To study the role of ET-1 in adult vascular physiology, we generated a mouse strain (ET-1 flox/flox ;Tie2-Cre mice) in which ET-1 is disrupted specifically in endothelial cells. ET-1 peptide levels in plasma, heart, lung, kidney, and brain homogenates were reduced by 65% to 80% in these mice. mRNA levels for ET receptors were unaltered except that the ET A receptor mRNA was upregulated in the heart. ET-1 flox/flox ;Tie2-Cre mice had mean blood pressures 10 to 12 mm Hg lower than genetic controls. In contrast, the blood pressure of mice systemically heterozygous for the ET-1 null allele (ET-1 dlox/+ mice) was unchanged compared with wild-type littermates. Despite the lower basal blood pressure, acute pharmacological responses to angiotensin II, captopril, phenylephrine, bradykinin, N G -nitro- l -arginine methyl ester, and exogenous ET-1 were normal in ET-1 flox/flox ;Tie2-Cre mice. These results support an essential role of endothelial-derived ET-1 in the maintenance of basal vascular tone and blood pressure. Normal pharmacological responses of ET-1 flox/flox ;Tie2-Cre mice suggest that the renin-angiotensin system, the adrenergic system, and NO are not significantly altered by endothelial ET-1. Taken in conjunction with other lines of genetically altered mice, our results provide evidence for a paracrine vasoregulatory pathway mediated by endothelial cell–derived ET-1 acting on the vascular smooth muscle ET A receptor.

Background Vascular calcification accompanying chronic kidney disease increases the mortality and morbidity associated with cardiovascular disorders, but no effective therapy is available. We hypothesized that glycosaminoglycans may contribute to osteoblastic differentiation of vascular smooth muscle cells during vascular calcification. Methods and Results We used exostosin‐like glycosyltranferase 2–deficient ( EXTL 2 knockout) mice expressing high levels of glycosaminoglycans in several organs including the aorta. We performed 5/6 subtotal nephrectomy and fed the mice a high‐phosphate diet to induce chronic kidney disease. Overexpression of glycosaminoglycans in the aorta enhanced aortic calcification in chronic kidney disease in EXTL 2 knockout mice. Ex vivo and in vitro, matrix mineralization in aortic rings and vascular smooth muscle cells of EXTL 2 knockout mice was augmented. Furthermore, removal of glycosaminoglycans in EXTL 2 knockout and wild‐type mice‐derived vascular smooth muscle cells effectively suppressed calcium deposition in a high‐phosphate environment. Conclusions These results illustrate an important role for glycosaminoglycans in the development of vascular calcification. Manipulation of glycosaminoglycan expression may have beneficial effects on the progression of vascular calcification in chronic kidney disease patients.

Endothelium plays important role in protective mechanism of vascular wall. The balance between endothelin-1 (ET-1) and nitric oxide provide endothelial barrier to lipoprotein retain and macrophage recruitment. In contrasts, ET-1 is also a strong vasoconstrictor. In this study, we aim to determine the role of vascular endothelial cells-derived ET-1 in the development of atherosclerosis. For that purpose, we crossbred Vascular Endothelial Cells-specific ET-1 Knockout (VEETKO) mice to ApoEKO mice. ApoE/VEET-DKO exhibited significantly lower ET-1 plasma and mRNA level as compared to ApoEKO mice. No significant differences of blood pressure, plasma cholesterol or lipid profiles were observed in both mice. Surprisingly, after 8 weeks of western diet, we found that the atherosclerotic lesion was exaggerated in the aortic sinus and brachiochepalic artery of ApoE/VEET-DKO mice (n=7) as compared to those of ApoEKO mice (n=7) (ratio/vessel wall, 0.93±0.13vs.0.49±0.09, p

Complex mechanism of the chronic inflammatory process in vascular injury and atherosclerosis involves various types of cells and cytokines. Previous in vitro studies suggest that Endothelin-1 (ET-1) is produced by those cells, induces expression of several adhesion molecules and mediates the leukocyte-endothelial interaction. In the present study, we sought to determine whether local endothelial ET-1 plays a direct effect on early inflammation and neointimal formation as a response to vascular injury in vivo . Using Cre-loxP system and Tie-2 Cre promoter, Vascular Endothelial ET-1 Knockout (VEETKO) mice was generated. The mice showed 60% reduction of ET-1 mRNA level at major organs and undetected serum ET-1 level. To induce vascular inflammation, complete ligation of the left common carotid artery was performed in 12-weeks-old male VEETKO (n=35) and Wild Type (WT) littermates (n=34). Inhibition of vascular endothelial ET-1 prevented the 4-fold increase in ET-1 mRNA level of carotid artery after ligation, in contrast to that of WT mice. This prevention resulted in lower vascular inflammation revealed by lower mRNA and protein level of PECAM-1, ICAM-1, and MCP-1 in VEETKO mice. The lack of ET-1 in endothelium further inhibited the adhesion of inflammatory cells at early days after ligation as compared to that adhered in endothelium of WT mice (cell numbers, 20.7±4.9 vs. 54.6±3.9 respectively, p

High plasma endothelin-1 (ET-1) level has been associated with diabetic cardiovascular and renal complications, which remained prevalent despite good glycemic control. Since endothelial dysfunction, which is characterized by enhanced ET-1 secretion, plays an important role in mediating diabetic complication, we hypothesized that disruption of ET-1 in endothelial cell will be protective against cardiac and renal complication of diabetes. To test this hypothesis, we injected streptozotocin to Vascular Endothelial cell Specific Endothelin-1 Knockout (VEETKO) mice, of which ET-1 expression in major organs including heart and kidney were reduced by 60%, and to their wild type (WT) littermates. Six months of diabetes increased systolic blood pressure (SBP) similarly in both genotypes, with DM-VEETKO mice have remained lower SBP than DM-WT mice (124±1.08 vs. 131.33±1.33 mmHg, p