Randomized, Open-Label, Cross-Over Comparison of the Effects of Benzbromarone and Febuxostat on Endothelial Function in Patients with Hyperuricemia.

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.

Pulmonary Artery Aneurysm Associated with Bicuspid Pulmonary Valve.

A 73-year-old Japanese man was admitted with an asymptomatic pulmonary artery aneurysm. However, chest X-ray and contrast-enhanced thoracic computed tomography revealed a protrusion at the second left branch that in fact was a pulmonary artery aneurysm with a diameter of 50 mm. Transesophageal echocardiography showed a bicuspid pulmonary valve, and cardiac catheterization revealed pulmonary stenosis with a pressure gradient of 45 mmHg, but no other heart diseases were noted. An extremely rare pulmonary artery aneurysm associated with an isolated bicuspid pulmonary valve was diagnosed.

Biomarkers of Cardiac Dysfunction as Risk Factors in Cryptogenic Stroke.

BACKGROUND: It is unclear whether biomarkers of cardiac dysfunction are associated with cryptogenic stroke (CS). METHODS: We retrospectively evaluated consecutive ischemic stroke patients. Patients underwent transthoracic echocardiography to evaluate left atrial diameter and the peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e'). Patent foramen ovale (PFO) and left atrial appendage flow velocity were evaluated by transesophageal echocardiography. We compared clinical characteristics and biomarkers of cardiac dysfunction (brain natriuretic peptide [BNP], left atrial diameter, E/e', and left atrial appendage flow velocity) between CS or CS without large PFO and other causative stroke subtypes. RESULTS: Among 1,514 patients with ischemic stroke, 264 patients were classified as having CS. Of these, transesophageal echocardiography revealed 27/158 (17%) large PFOs. In comparison, for the noncardioembolic stroke group, which consisted of large artery and small vessel subtypes, patients with CS without large PFO had higher log10 BNP (adjusted OR 2.70; 95% CI 1.92-3.78; p < 0.001), higher log10 E/e' (3.41; 1.21-13.15; p = 0.019), and lower left atrial appendage flow velocity (0.98; 0.97-1.00; p = 0.031). Left atrial diameter was similar for noncardioembolic stroke and CS without large PFO (p = 0.380). Cutoff values of BNP, E/e', and left atrial appendage flow velocity capable of distinguishing CS without large PFO from noncardioembolic stroke were 65.0 pg/mL (sensitivity 55.3%; specificity 70.9%), 13.0 (45.5%; 68.0%), and 46.0 cm/s (37.1%; 87.5%), respectively. CONCLUSION: Patients with CS without large PFO could have biomarkers of cardiac dysfunction.

A score using left ventricular diastolic dysfunction to predict 90-day mortality in acute ischemic stroke: The DONE score.

PURPOSE: The aim of this study was to identify whether diastolic dysfunction predicts death at 90 days after acute ischemic stroke. METHODS: We retrospectively analyzed patients with ischemic stroke. All patients underwent transthoracic echocardiography to evaluate systolic function and diastolic function by means of assessing ejection fraction and septal E/e'. We evaluated the initial National Institute of Health Stroke Scale (NIHSS) score, arterial occlusion, and laboratory data. We used multivariate regression models to identify independent predictors of 90-day mortality. RESULTS: Among 1208 patients, the overall 90-day mortality rate was 8%. In multivariate logistic regression analysis, a higher initial NIHSS score, plasma D-dimer level and E/e', and occlusion of internal carotid artery or basilar artery were independent predictors of 90-day mortality. The DONE score derived from these valuables showed good discrimination with area under the curve (AUC) value of 0.82 (95% confidence interval [CI], 0.78-0.87) to predict 90-day mortality. The DONE score also predicted poor outcome (modified Rankin scale score, 4-6) at 90 days (AUC, 0.82; 95% CI 0.80-0.85). CONCLUSIONS: Higher E/e', indicating diastolic dysfunction, may be associated with 90-day mortality in patients with acute ischemic stroke. The DONE score could readily predict poor outcome after acute ischemic stroke.

Effectiveness and safety of oral direct factor Xa inhibitors for the treatment of venous thromboembolism in patients with cancer and/or older age.

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients' demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients' demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p < 0.001). The efficacy and safety of Xa inhibitors as VTE treatment were comparable between cancer and non-cancer patients, and in elderly and non-elderly patients. This suggests that Xa inhibitors may be promising drugs for VTE treatment, irrespective of age and comorbid cancer.

Doppler ultrasound diagnosis of transient leg malperfusion caused by dynamic obstruction in a patient with chronic aortic dissection.

Leg malperfusion caused by dynamic obstruction is a serious complication of aortic dissection. A diagnosis of the malperfusion is difficult because it is made mainly on the basis of nonspecific symptoms such as intermittent claudication and numbness on walking. In the present study, we reported on a case of a 51-year-old man with leg malperfusion in chronic aortic dissection diagnosed by Doppler ultrasound. The combination of bisferious and dampened velocity waveform changes after walking may lead us to suspect a leg malperfusion caused by dynamic obstruction.

Comparison of the effects of edoxaban, an oral direct factor Xa inhibitor, on venous thromboembolism between patients with and without cancer.

BACKGROUND: Venous thromboembolism (VTE) is a frequent and serious complication of cancer. The current guidelines in the USA and Europe recommend low-molecular weight heparin (LMWH) for the treatment of cancer-associated VTE. In Japan, LMWH is not given for the treatment of VTE; instead edoxaban, an oral direct factor Xa inhibitor, was approved for the treatment of VTE in September 2014. However, the efficacy and safety of the factor Xa inhibitor in cancer patients have not been fully elucidated. METHODS: Patients' charts were reviewed retrospectively, and 125 VTE patients (61 cancer patients) in whom edoxaban therapy was started between September 2014 and September 2016 were included in this study. Patients' demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and outcomes until February 2017 were examined. RESULTS: Patients' characteristics, including age, sex, weight, creatinine clearance, and duration of administration of edoxaban were comparable between cancer and non-cancer patients. No parenteral anticoagulant pretreatment before edoxaban was given in 37.5% and 55.7% of non-cancer and cancer patients, respectively. The incidence of pulmonary embolism was also similar in the two groups. The amount of thrombosis decreased ("improved") or disappeared ("normalized") in 89.6% and 94.1%, respectively, of non-cancer and cancer patients who underwent at least two imaging tests. The frequencies of recurrence of VTE and clinically relevant bleeding were not significantly different between the two groups (p=0.414 and 0.516, respectively). However, 21 cancer patients died, 17 of whom died of cancer, while none of the non-cancer patients died. CONCLUSION: The present study showed that the efficacy and safety of edoxaban for the treatment of VTE is comparable between cancer and non-cancer patients. Edoxaban may be a clinically useful therapy for VTE in Japanese cancer patients.

Cardiac Calcified Amorphous Tumors in a Patient with Hemodialysis for Diabetic Nephropathy.

Calcified amorphous tumor (CAT) is a rare, non-neoplastic tumor involving calcium deposition in amorphous materials. Although its etiology is unknown, cases have frequently been reported in patients with hemodialysis for chronic kidney disease. We herein describe a case of cardiac CAT in a 64-year-old woman who had been on hemodialysis for diabetic nephropathy for 20 years, and the findings of the present patient, in association with the findings of previous case reports, suggest that end-stage renal disease seems to play an important role in the onset of CAT, especially in CAT formation at the mitral annulus, which appears to differ from CAT occurring at other sites.

Afebrile Pannus-Induced Blood Culture-Negative Mechanical Valve Endocarditis.

The diagnosis of prosthetic valve endocarditis may be challenging in patients with an atypical clinical presentation. Virtually all infections associated with mechanical prosthetic valves are localized to the prosthesis-tissue junction at the sewing ring and are accompanied by tissue destruction around the prosthesis. Because the orifice of the mechanical prosthetic valve is made of metal and pyrolytic carbon, which do not enable the adherence of microorganisms, any vegetation originating from the interior of the valve orifice is usually rare. Here we present a rare case of pannus-induced mechanical prosthetic valve endocarditis that was difficult to diagnose.

Comparison of saddle-shape flexibility and elliptical-shape stability between Cosgrove-Edwards and Memo-3D annuloplasty rings using three-dimensional analysis software.

OBJECTIVE: To compare three-dimensional dynamics between implanted Cosgrove-Edwards and Sorin Memo-3D annuloplasty rings during the cardiac cycle. METHODS: We examined 11 Cosgrove-Edwards rings and 20 Sorin Memo-3D rings after mitral plasty using real-time three-dimensional transesophageal echocardiography. We evaluated ring height, ellipticity, and geometry during one cardiac cycle. Four evenly spaced phases each selected during systole and diastole were assessed using REAL VIEW software. RESULTS: The height of the Cosgrove-Edwards and Sorin Memo-3D rings was similar (2.3 ± 0.8 vs. 1.9 ± 0.9 mm, p = 0.44). The maximum difference in ring height during one cardiac cycle (change in height) was larger for the Cosgrove-Edwards than the Sorin Memo-3D rings (2.3 ± 0.8 vs. 1.5 ± 0.6 mm, p = 0.014). Ellipticity and the maximum difference in ellipticity during one cardiac cycle (change in ellipticity) were larger for Cosgrove-Edwards than Sorin Memo-3D rings (80.0 ± 9.1 vs. 72.0 ± 4.8 %, p = 0.014, respectively, and 12.0 ± 3.1 vs. 6.0 ± 1.8 %, p < 0.001). CONCLUSIONS: Cosgrove-Edwards rings were more flexible, whereas Sorin Memo-3D rings maintained the elliptical shape more effectively.

A right thoracotomy approach for mitral and tricuspid valve surgery in patients with previous standard sternotomy: comparison with a re-sternotomy approach.

BACKGROUND: To compare the outcomes of mitral and/or tricuspid valve surgery in patients with previous sternotomy between those who underwent a right thoracotomy and those who underwent re-sternotomy. METHODS: Between October 2009 and May 2015, eighteen patients underwent a right thoracotomy (R group) and 28 underwent re-sternotomy (re-S group). The right thoracotomy was prioritized for previous coronary artery bypass grafting. Follow-up was 100 % complete with a mean follow-up of 1.9 ± 1.5 years for the R group and 2.5 ± 1.4 years for the re-S group (p = 0.2137). RESULTS: Hypothermic ventricular fibrillation was applied in 33.3 % in the R group and in 7.1 % in the re-S group (p = 0.0424). Hospital mortality, the median intensive care unit stay, and the median postoperative hospital stay were 0 % versus 7.1 % (p = 0.5130), 3 days versus 2 days (p = 0.2370), and 28 days versus 29.5 days (p = 0.8043) for the R group versus the re-S group, respectively. Although the rate of major complications was comparable (R group 33.3 % versus re-S group 25.0 %, p = 0.5401), those contents were not equal. Deep sternum infection developed only in the re-S group (3.6 %) and reoperation for bleeding was required only in the R group (11.1 %). No significant difference was observed in the 2-year cardiac-related mortality-free rate (R group 93.3 ± 6.4 % versus re-S group 90.8 ± 6.4 %, p = 0.7516). CONCLUSIONS: Given study limitations, the right thoracotomy approach after previous sternotomy provided favorable outcomes as well as re-sternotomy. When selecting a right thoracotomy for re-do mitral and/or tricuspid surgery, the surgical strategy needs to be thoroughly planned.

Swinging Calcified Amorphous Tumors With Related Mitral Annular Calcification.

Among cardiac calcified amorphous tumors, the mitral annular calcification-related calcified amorphous tumor is extremely rare. We herein describe 3 surgical cases of swinging calcified amorphous tumor with related mitral annular calcification. The clinical, echocardiographic, and pathophysiologic features are reported here together with a brief review of the literature.

A cardiac hemangioma treated by a right minithoracotomy approach with thoracoscopic assistance.

Cardiac hemangiomas are extremely rare tumors, accounting for only 2.5% of all cardiac tumors. Most of these develop in the ventricles, and obtaining a good field of view is, therefore, the key to successful operation. A 40-year-old female visited a local hospital due to palpitation. Transthoracic echocardiography revealed a spherical high-echo mass (13.5 × 10.7 mm in diameter) between the papillary muscles. She was referred to our hospital to undergo close examination. Cardiac contrast-enhanced magnetic resonance imaging was performed to differentiate between malignant and benign lesions. However, this did not provide any findings leading to a definite diagnosis. To make a diagnosis and prevent embolism, the mass was excised using a right minithoracotomy approach with thoracoscopic assistance. The post-operative pathological diagnosis was a cardiac capillary-cavernous hemangioma. A right minithoracotomy approach combined with thoracoscopy allowed accurate evaluation of the mass in the left ventricle beyond the mitral valve and its accurate excision.

Coronary Artery Pseudoaneurysm due to Medial Mucoid Degeneration Mimicking an Intra-atrial Mass.

Coronary artery aneurysms are frequently asymptomatic and may be difficult to diagnose by cardiac imaging. We herein present a case of a coronary artery aneurysm of the right coronary artery due to medial mucoid degeneration mimicking an intra-atrial mass on echocardiography and magnetic resonance imaging, with the cause being diagnosed after surgery.

Rivaroxaban therapy resulting in the resolution of right atrial thrombosis resistant to ordinary control with warfarin in a patient with atrial fibrillation.

A 72-year-old man with non-valvular atrial fibrillation and metastatic liver and lung cancer after surgery for colon cancer developed thrombosis in the right atrium one month after decreasing the dose of warfarin due to the introduction of double anti-platelet therapy for coronary stent implantation. Restoring the warfarin dose with ordinary control for two months did not result in any changes in the size of the thrombus; however, the subsequent substitution of rivaroxaban (oral treatment with a direct Factor Xa inhibitor) for warfarin ultimately resolved the thrombosis.

Technical aspects of mitral valve repair in Barlow's valve with prolapse of both leaflets: triangular resection for excess tissue, sophisticated chordal replacement, and their combination (the restoration technique).

BACKGROUND: Histological degeneration in Barlow's valve mainly starts in the rough zone, frequently expands toward the chordae, and advances to the clear zone, resulting in a saccular aneurysm-like morphology in the prolapsed region. On this basis, we have repaired the prolapsed segment by triangular resection, chordal replacement and the combination (the restoration technique). The aim of this study was to report our initial findings and evaluate the efficacy of our technique. METHODS: Twelve patients diagnosed with Barlow's valve with prolapse of both leaflets (5 women; mean age, 49 years) underwent the restoration technique between January 2008 and March 2013. We retrospectively reviewed short-term clinical outcomes. The mean duration of the clinical follow-up was 2.5 ± 1.7 years. RESULTS: The restoration technique was successfully performed in all patients. Predominant repair techniques were isolated triangular resection (anterior 8, posterior 9), a combination of triangular resection with chordal replacement (anterior 1, posterior 1), and isolated chordal replacement (anterior 3, posterior 1). All patients underwent complete mitral annuloplasty, and the mean ring size was 31 ± 2 mm. In-hospital mortality was not noted. Late transthoracic echocardiography showed no or trace mitral regurgitation without significant systolic anterior motion in all patients. The New York Heart Association functional class was significantly improved from 1.3 ± 0.5 before surgery to 1.0 ± 0.0 after it (p < 0.01). There were no late thromboembolic or bleeding events. CONCLUSIONS: Initial experience with the restoration technique has provided excellent results without significant systolic anterior motion. Our technique may contribute to improve late results in Barlow's valve.

Longitudinal strain of right ventricular free wall by 2-dimensional speckle-tracking echocardiography is useful for detecting pulmonary hypertension.

AIMS: Echocardiography is widely used for screening pulmonary hypertension (PH). More recently developed two-dimensional speckle-tracking echocardiography (2D-STE) can assess regional deformation of the myocardium and is useful for detecting left ventricular dysfunction. However, its usefulness to assess right ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was to investigate the ability of peak systolic strain (PSS) and post-systolic strain index (PSI) at the RV free wall determined by 2D-STE to detect PH. MAIN METHODS: Thirty-six images (27 images from PH patients, nine from patients with connective tissue disease without PH) obtained by 2D-STE were analysed. We investigated the relationship between RV hemodynamics measured by right heart catheterization and PSS, PSI and other echocardiographic parameters reflecting RV overload including RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure gradient (TRPG). KEY FINDINGS: PSS, PSI, RVDd and TRPG were all correlated with mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Furthermore, when PSS and MPAP were measured twice, the change in PSS was correlated with the change in MPAP (r=0.633, p=0.037). Multivariate logistic regression analysis identified PSS as the only independent factor associated with MPAP ≥ 35mmHg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017-2.567; p=0.042] and PVR ≥ 400dyn·s·cm(-5) (OR, 1.804; 95% CI 1.131-2.877; p=0.013). Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was -20.75%, based on receiver operating characteristic curve analysis. SIGNIFICANCE: PSS of the RV free wall might serve as a useful non-invasive indicator of PH.