Sinus venosus atrial septal defect and partial anomalous pulmonary venous connection in a patient with dextrocardia.

An 85-year-old woman presenting with symptomatic pulmonary hypertension (PH) with a history of dextrocardia was referred to our facility for treatment of heart failure. Significant shunting was detected by measuring oxygen saturation during right heart catheterisation (RHC). CT with contrast revealed sinus venosus atrial septal defect (SVASD) and partial anomalous pulmonary venous connection (PAPVC), in which the left upper and middle lobar pulmonary veins returned to the superior vena cava and right atrium. Despite medical treatment, the patient died, and an autopsy was performed. SVASD and PAPVC are rare congenital anomalies. RHC with measurement of oxygen saturation and CT with contrast should be considered in patients with unexplained right atrial and ventricular enlargement or suspected PH.

Determinants of Exercise-Induced Mitral Regurgitation Using Three-Dimensional Transesophageal Echocardiography Combined With Isometric Handgrip Exercise.

Using three-dimensional (3D) transesophageal echocardiography (TEE) and isometric handgrip exercise (IHE), we investigated the determinants of exercise-induced mitral regurgitation (MR) according to MR etiologies. Seventy-six patients with more than moderate MR, 40 patients with functional MR (FMR) and 36 patients with degenerative MR (DMR), underwent 3D TEE combined with IHE. Mitral valve (MV) geometry and 3D vena contracta area (3D VCA) were simultaneously evaluated at baseline and during IHE. With regard to exercise-induced MR, Δ3D VCA was calculated as the difference between 3D VCA at baseline and 3D VCA during IHE. IHE caused different changes in MV geometry between etiologies and led to exacerbation of 3D VCA at baseline. Larger Δ3D VCA was observed in the FMR group compared with the DMR group (15.9 ± 10.3 mm2 versus 7.3 ± 4.2 mm2; p < 0.0001). In multivariate analyses, tenting height and 3D VCA were selected as independent factors associated with Δ3D VCA in the FMR group (p = 0.0135 and p = 0.0201, respectively), while flail width was selected as an independent factor associated with Δ3D VCA in the DMR group (p = 0.0066). In conclusion, IHE alters mitral valve geometry and causes exacerbation of MR regardless of MR etiology and the determinants of exercise-induced MR differed between MR etiologies.

Tricuspid valve geometry and right heart remodelling: insights into the mechanism of atrial functional tricuspid regurgitation.

AIMS: We sought to investigate tricuspid valve (TV) geometry and right heart remodelling in atrial functional tricuspid regurgitation (AF-TR) as compared with ventricular functional TR with sinus rhythm (VF-TR). METHODS AND RESULTS: Transoesophageal 3D echocardiography datasets of the TV and right ventricle were acquired in 51 symptomatic patients with severe TR (AF-TR, n = 23; VF-TR, n = 28). Three-dimensional right ventricular (RV) endocardial surfaces were reconstructed throughout the cardiac cycle and then postprocessed using semiautomated integration and segmentation software to calculate position of papillary muscle (PM) tips. Compared with VF-TR, AF-TR had more dilated and posteriorly displaced annulus and less leaflet tethering angles with more prominent right atrium and smaller RV end-systolic volume. On the XY (annular) plane, the centre of annulus was getting closer towards the anterior and posterior PM tips and was going away from the medial PM tip caused by prominent annular dilatation in AF-TR. On the Z-axis, the position of each PM tip in AF-TR was not so much displaced apically as that in VF-TR. Multiple linear regression analyses revealed that right atrial volume and right atrial/RV end-systolic volume ratio were determinants of annular area and orientation in AF-TR, respectively (both P < 0.001). Additionally, the posteromedial-directed component of posterior PM tip position and the apically directed component of the position of all three PM tips were independently associated with TV tethering angles of each leaflet in AF-TR (all P < 0.02). CONCLUSION: Right heart remodelling and its association with 3D TV geometry differ entirely between AF-TR and VF-TR, which may offer distinctive therapeutic implication.

Successful catheter ablation of persistent atrial fibrillation is associated with improvement in functional tricuspid regurgitation and right heart reverse remodeling.

Atrial fibrillation (AF) is a common disease that changes cardiac morphology, especially in the left atrium (LA). It is now known that certain categories of functional mitral regurgitation (MR) are associated with AF; however, the influence of AF on right cardiac morphology is not fully understood. Our aim in this study was to investigate the association between AF and right cardiac morphology. This was a retrospective cohort study of 86 patients with persistent AF without other cardiac disease who underwent catheter ablation (CA). Seventy-one patients had sustained sinus rhythm (SR) (SR Group) and 15 patients had sustained AF (AF Group) during the study period. We compared the changes in the right cardiac dimensions and tricuspid regurgitation (TR) between the groups 12 months after CA. Patients' baseline echocardiographic assessments revealed that the LA volume index was significantly smaller in the SR group than in the AF group (46.8 ± 11.9 ml/m2 vs 59.3 ± 12.8 ml/m2, respectively; p < 0.01). Comparing baseline data with the 12-month follow-up data, in the SR group, right atrial area (RAA, cm2), tricuspid annular diameter (mm), and tricuspid regurgitant jet area (cm2) were significantly decreased compared with the AF group (19.5 ± 4.5-15.5 ± 3.6 vs 20.7 ± 3.6-19.7 ± 2.3; 30.5 ± 4.9-26.4 ± 3.9 vs 28.7 ± 4.0-28.8 ± 3.1; and 1.4 [interquartile range (IQR) 0.7-2.6]-0.6 [IQR 0.2-1.2] vs 1.2 [IQR 1.1-1.5]-0.9 [IQR 0.4-1.3], respectively). On multivariate analysis, change in RAA correlated with the reduction in tricuspid regurgitant jet area (R = 0.51, p < 0.001). In conclusion, successful CA for persistent AF led to right heart reverse remodeling, and our findings suggested that persistent AF was associated with RAA dilatation and TR.

H2FPEF Score for the Prediction of Exercise Intolerance and Abnormal Hemodynamics in Japanese　- Evaluation by Exercise Stress Echocardiography Combined With Cardiopulmonary Exercise Testing.

BACKGROUND: Both the H2FPEF-score and nomogram-score, which consist of simple clinical parameters, can assist in diagnosing "early" heart failure with preserved ejection fraction (HFpEF) and only exertional dyspnea, but their these usefulness in Japanese remains unclear. We sought to investigate the correlation between these scores and exercise response, including the peak oxygen uptake (V̇O2), the pulmonary artery systolic pressure (PASP), the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') and stroke volume (SV) using exercise stress echocardiography (ESE) combined with cardiopulmonary exercise testing (CPET).Methods and Results:In this single-center, retrospective cross-sectional study the H2FPEF-score and nomogram-score were calculated in a total of 139 patients who underwent ESE combined with CPET. The scores correlated with peak V̇O2(r=-0.48, r=-0.44), PASP (r=0.23, r=0.29) and SV (r=-0.32, r=-0.19) at peak exercise. The nomogram-score correlated with E/e' (r=0.24). The prevalence of exercise intolerance (percent predicted peak V̇O2<75% and <50%) increased as the H2FPEF-score increased and reached 88.9% and 22.2% among the patients with high H2FPEF-score (6-9 points). CONCLUSIONS: The H2FPEF-score may be useful as the initial step to diagnosing 'early' HFpEF. The nomogram-score may be more useful in Japanese because of its more universal association with exercise response than the H2FPEF-score.

Comprehensive Evaluation of Tricuspid Regurgitation Location and Severity Using Vena Contracta Analysis: A Color Doppler Three-Dimensional Transesophageal Echocardiographic Study.

BACKGROUND: The clinical significance of three-dimensional (3D) vena contracta area (VCA) in tricuspid regurgitation (TR) is not fully elucidated. The aim of this study was to investigate the diagnostic accuracy of 3D VCA using 3D echocardiography-derived regurgitation volume as a reference standard. METHODS: One hundred sixteen patients with at least moderate TR underwent two-dimensional transthoracic and color Doppler 3D transesophageal echocardiography. The 3D vena contracta, which was located at the narrowest neck of the TR jet just above and toward the right atrial side of the flow convergence zone, was assessed for TR location and severity. RESULTS: As for TR location, patients with severe functional TR had the highest prevalence of central jet location among TR subgroups, whereas patients with severe primary TR showed a greater spatial extent of TR jet location involved compared with the moderate TR group (P < .05 for both). As for TR severity, a 3D VCA cutoff value of 0.61 cm2 discriminated severe TR with sensitivity of 78% and specificity of 97% in the total patient population (area under the curve = 0.93, P < .001). Multivariate analysis revealed that 3D VCA, a dilated right ventricle, and hepatic vein systolic reversal were independently associated with regurgitant volume (P < .001 for all). The χ2 value for the model that incorporated clinical and two-dimensional integrative parameters and 3D VCA > 0.61 cm2 to evaluate severe TR was significantly higher than that for the model that incorporated only clinical and two-dimensional integrative parameters (P = .001). CONCLUSIONS: Three-dimensional VCA has independent and incremental diagnostic value for evaluating severe TR. Comprehensive evaluation of TR location and severity using 3D vena contracta analysis may help in treatment selection for TR.

Early mitral inflow velocity to left ventricular global strain ratio predicts limited exercise capacity.

BACKGROUND: Estimation of left ventricular filling pressure (LVFP) is the essential part of the echocardiographic workup for exercise intolerance. The ratio of the mitral early filling velocity to the left ventricular global longitudinal strain (E/LVGLS) has emerged as a novel index of LVFP. This study aimed to investigate the relationship between E/LVGLS and exercise capacity. METHODS AND RESULTS: We retrospectively reviewed 90 patients with exertional dyspnea who underwent echocardiography and cardiopulmonary exercise test. Patients were classified into three groups according to their percent-predicted maximal oxygen consumption (ppVo2 ) (G â‰§ 75, ppVo2  > 75%, n = 20; G 50-75, ppVo2 75-50%, n = 57; G < 50, ppVo2  < 50%, n = 13). Measurements were (a) the relationship between ppVo2 and E/LVGLS and (b) the efficiency of integrated diastolic assessment using E/LVGLS, left ventricular volume, mitral annular early diastolic velocity (E'), and tricuspid regurgitation to identify the patient with impaired exercise capacity. Univariate linear regression analysis demonstrated that E/LVGLS had significant correlation with ppVo2 (ρ = 0.52, P < 0.001). The area under the ROC of E/LVGLS for ppVo2  < 50% was 0.86 (95%CI 0.75-0.97). The DeLong test showed that E/LVGLS was efficient to detect ppVo2  < 50% than E/E' (P = 0.007). When used in the integrated assessment of LVFP as the alternative for E/E', E/LVGLS improved risk classification for impaired exercise capacity. CONCLUSION: E/LVGLS may be a more efficient index than E/E' to identify exercise impairment as a single index and as a part of the integrated diastolic assessment.

Exercise-Stress Echocardiography and Effort Intolerance in Asymptomatic/Minimally Symptomatic Patients With Degenerative Mitral Regurgitation Combined Invasive-Noninvasive Hemodynamic Monitoring.

Background Effort intolerance, measured objectively by reduced peak oxygen consumption (Vo2), has been considered as an important prognosticator in degenerative mitral regurgitation (MR). However, its mechanism is unknown. Methods and Results In 25 asymptomatic/minimally symptomatic patients with grade III+ or greater degenerative MR undergoing semisupine invasive exercise testing, Doppler estimates and invasive measurement of systolic (SPAP) and mean pulmonary artery pressure (MPAP) and cardiac output (CO) were simultaneously obtained. Echocardiographic estimates of SPAP, MPAP, and CO correlated well with invasive measurement at peak exercise (bias, SPAP, -0.7±7.4 mm Hg; MPAP, 1.2±6.3 mm Hg; CO, 0.2±2.5 L/min). Heart rate reserve (ß, 3.997; 95% CI, 2.704-5.290 per 41.5% increase; P<0.001), MPAP/CO slope (ß, -3.846; 95% CI, -5.926 to -1.766 per 4.85 mm Hg/L per minute increase; P=0.001), and tricuspid annular plane systolic excursion/SPAP slope (ß, 4.094; 95% CI, 2.252-5.936 per 0.22 mm/mm Hg increase; P=0.003) were associated with peak Vo2 even after adjustment for increase in MR vena contracta during exercise and peak SPAP. The MPAP/CO slope of 4.13 had a sensitivity and a specificity for predicting effort intolerance (%predicted peak Vo2 <70%) of 57% and 91%, respectively, whereas the tricuspid annular plane systolic excursion/SPAP slope of 0.25 had a respective sensitivity and specificity of 86% and 82%. Conclusions The agreement between echocardiographic and invasive measures of pulmonary artery pressures and CO during exercise is acceptable. In patients with degenerative MR, effort intolerance is predominantly because of chronotropic incompetence, abnormal pulmonary vascular reserve, and limited right ventricular contractile reserve and not simply because of exercise-induced MR or pulmonary hypertension.

Mitral systolic velocity at peak exercise predicts impaired exercise capacity in patients with heart failure with preserved ejection fraction.

BACKGROUND: Nearly half of patients with heart failure have normal left ventricular ejection fraction (LVEF), but their prognosis is no better than those with reduced LVEF. Although peak oxygen consumption (VO2 ) is an independent predictor of mortality in heart failure, it is unclear how cardiac function during exercise contributes to peak VO2 . Therefore, we explored the useful parameters measured by exercise stress echocardiography to predict peak VO2 in patients with heart failure with preserved LVEF (HFpEF). METHODS AND RESULTS: We assessed 80 patients being investigated for effort intolerance or dyspnea and finally analyzed 50 patients who satisfied the HFpEF criteria. Mean peak VO2 was 16.4±2.8 mL/kg/min. Twenty-three patients (46.0%) achieved a peak VO2 <16.0 mL/kg/min (Weber class C or D). There was a significant relationship between mitral systolic velocity (S') and cardiac output (CO) at rest (R=.55, P<.0001) and peak exercise (R=.64, P<.0001). The absolute increase in S' from rest to peak exercise also correlated with the absolute increase in CO (R=.32, P=.02). Multivariate logistic regression analysis showed that S' at peak exercise independently predicted peak VO2 . Receiver-operator characteristic curve analysis identified that an S' at peak exercise of ≤8.13 cm/s predicted a peak VO2 <16.0 mL/kg/min (sensitivity 95.7%, specificity 44.4%, area under curve 0.70, 95% confidence interval 0.55-0.84, P=.004). CONCLUSIONS: Mitral systolic velocity at peak exercise accurately reflects peak VO2 and may facilitate stratification of risk in patients with HFpEF.

Inactivation of Foot-and-Mouth Disease Virus by Commercially Available Disinfectants and Cleaners.

Foot-and-mouth disease virus (FMDV) is an animal pathogen of great concern. It is contagious to cloven-hoofed animals and affects animals in extensive areas worldwide. In general, the primary eradication strategies for foot-and-mouth disease (FMD) in Japan are stamping out the disease and restriction of movement. It is also important to completely disinfect the infected area to prevent the spread of FMDV, including vehicles and people as well. However, there is no report on the effect of commercially available disinfectants against FMDV in a short contact time. In this study, we evaluated the virucidal effect of thirteen commercially available products, and got the following results: acidic ethanol disinfectants, alkaline cleaners and sodium hypochlorite had great effect (>3.0 log10 reduction in titer) against FMDV. On the other hand, neutral ethanol disinfectants, hand soaps, and quaternary ammonium compound sanitizers did not show great effect against FMDV. Therefore, it is presumed that acidic ethanol disinfectants are effective for human use and alkaline cleaners are effective for use in the infected environment for the control of a FMD outbreak.

Cucurbitane-type triterpenes from Citrullus lanatus (watermelon) seeds.

Two new cucurbitane-type triterpenes, 24-hydroperoxycucurbita-5,25-dien-3beta-ol (1) and 25-hydroperoxycucurbita-5,23-dien-3beta-ol (2), were isolated from a MeOH extract of Citrullus lanatus seeds. Compounds 1 and 2 exhibited moderate cytotoxic activities with IC50 values of 33.4-52.4 microM against HL-60 (human leukemia), P388 (murine leukemia), and L1210 (murine leukemia) cells. Compound 1 showed melanogenesis inhibitory activity (melanin content 80.0 %) with low cytotoxicity (cell viability 97.6%) at a low concentration (10 microM).

Primary clival mucocele: case report.

A 40-year-old man presented with a history of diplopia due to left abducens nerve palsy persisting for a few days. Neuroimaging examinations revealed a cystic mass in the clivus and erosion of its posterior wall. Drainage of the lesion was accomplished through a small bone defect in the anterior wall of the clivus using the endoscopic endonasal transsphenoidal approach. This procedure improved the symptoms of the patient. Intraoperative and histological findings led to a diagnosis of mucocele. A mucocele localized only in the clivus is uncommon and the pathogenesis may be closely related to pneumatization of the clivus.

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease.

Patients with Parkinson's disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN-DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold-induced and heat-induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS-on mode when compared with the DBS-off mode (P<.001), whereas the CSTs and WSTs of patients in the DBS-off mode were significantly greater than those of healthy control subjects (P<.02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P<.02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities.

Systematic evaluation of substituted cyclopentadienyl ruthenium complexes, [(eta(5)-C(5)Me(n)H(5-n))RuCl(cod)], for catalytic cycloadditions of diynes.

A series of eta(5)-cyclopentadienylruthenium complexes, [(eta(5)-C(5)Me(n)H(5-n))RuCl(cod)] (cod=1,5-cyclooctadiene), are evaluated as catalysts for the cycloaddition of 1,6-diynes with alkynes. As a result, we unexpectedly found that the complex bearing the 1,2,4-Me(3)Cp ligand is the most efficient catalyst in terms of turnover number (TON) for the cycloaddition of a bulky diiododiyne with acetylene, recording the highest TON of 970 with a catalyst loading of 0.1 mol %. To obtain insight into this result, we evaluate the electron richness of all complexes by cyclic voltammetric analyses, which indicate that the electron density of the ruthenium center increases with an increase in methyl substitution on the Cp' ligands. The initial rate (up to 10 % conversion) of the cycloaddition was then measured using (1)H NMR spectroscopy. The initial rate is found to decrease as the number of methyl substituents increases. According to these results, we assumed that the optimum catalytic performance exhibited by the 1,2,4-trimethylcyclopentadienyl complex can be attributed to its robustness under the catalytic cycloaddition conditions. The steric and electronic effects of the Cp' ligands are also investigated in terms of the regioselectivity of the cycloaddition of an unsymmetrical diyne and in terms of the chemoselectivity in the cycloaddition of a 1,6-heptadiyne with norbornene.

Intracerebral hemorrhage caused by ruptured intracavernous carotid artery aneurysm. Case report.

A 76-year-old woman presented with an enlarged right intracavernous carotid artery aneurysm first identified incidentally when she was hospitalized for thalamic hemorrhage. She was managed conservatively for 1 year, then suffered right total ophthalmoplegia associated with enlargement of the aneurysm. Two months later, she became comatose due to intracerebral hemorrhage in the right temporal lobe. Magnetic resonance imaging demonstrated further enlargement of the aneurysm. Emergency craniotomy found the lateral dural wall of the cavernous sinus was markedly expanded and torn by compression from the aneurysm. Rupture of the aneurysm into the intradural space through this dural defect was confirmed. The aneurysm was trapped after high-flow bypass, but the patient did not recover and died. Symptomatic enlarged intracavernous carotid artery aneurysm is potentially fatal and may indicate prompt surgical management.

Cu-catalyzed stereoselective conjugate addition of arylboronic acids to alkynoates.

The CuOAc-catalyzed reaction of internal alkynoates with arylboronic acids proceeded under mild conditions to yield trisubstituted cinnamates stereoselectively.

Successful treatment of tacrolimus (FK506)-related leukoencephalopathy with cerebral hemorrhage in a patient who underwent nonmyeloablative stem cell transplantation.

A 46-year-old woman with Hodgkin's disease who underwent nonmyeloablative allogeneic stem cell transplantation developed cortical blindness, seizures, and left hemiparesis on day 100 while receiving tacrolimus (FK506) and prednisone for the treatment of graft-versus-host disease (GVHD). Magnetic resonance imaging revealed multiple changes, mainly in the bilateral occipital lobes, suggesting FK506-related leukoencephalopathy. These abnormalities improved after discontinuation of FK506. However, 3 days after the episode, cerebral hemorrhage in the left occipital lobe with perforation to the left subdural space occurred. Although FK506-induced leukoencephalopathy with cerebral hemorrhage is considered the more severe form of such leukoencephalopathy, the patient's neurological symptoms almost completely resolved and radiographic findings improved after discontinuation of FK506, tapering of methylprednisolone, and initiation of mycophenolate mofetil. FK506-related leukoencephalopathy is a rare complication after allogeneic stem cell transplantation. Although the symptoms usually subside after discontinuation of FK506, therapeutic intervention in many cases may result in severe complications, including GVHD and vascular disease. We consider it important to use immunosuppressive agents without vascular endothelial toxicity for preventing the development of fatal GVHD after discontinuation of FK506.

Characteristics of prolonged afterdischarges in children with malformations of cortical development.

We investigated aberrant cortical excitability in malformations of cortical development From subdural electrodes, we recorded afterdischarges lasting > or = 6 seconds in 12 of 13 patients with malformations of cortical development and 6 of 10 pediatric patients with nonmalformations of cortical development and reviewed amperage thresholds, distribution of afterdischarges, and motor responses. In patients with malformation of cortical development, motor response thresholds were high; afterdischarge and motor response thresholds, which essentially overlapped, inversely correlated with age (P < .01); afterdischarge thresholds declined with age; and 8 patients showed afterdischarges in remote sites. In nonmalformation of cortical development, afterdischarge thresholds did not significantly correlate with age; motor response thresholds tended to decline with age; and 2 patients had remote afterdischarges. Adolescent patients with malformations of cortical development had lower afterdischarge thresholds than adolescents with nonmalformation of cortical development (P < .05). From their high afterdischarge (and motor response) thresholds, we concluded that preadolescent patients with malformation of cortical development have less excitable, immature cortices, whereas adolescent patients with malformation of cortical development with low afterdischarge thresholds have hyperexcitable cortices. Remote afterdischarges over focal dysplastic cortex suggest aberrant cortical excitability and neural circuits.