小林 欣夫

Introduction: Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. Intravenous administration of nicorandil can be applicable for fractional flow reserve (FFR) measurement as a hyperaemic agent and a possible alternative to adenosine. However, the effectiveness of intravenous nicorandil infusion for FFR measurement is largely unclear. Methods and analysis: This crossover randomised study is being performed to investigate the efficacy of intravenous administration of nicorandil for FFR measurement. Patients with an intermediate coronary artery stenosis who satisfy the eligibility criteria undergo FFR measurement with a consecutive randomised order of patient-blind infusions of continuous intravenous administration of adenosine and a single bolus intravenous administration of nicorandil. The primary end point of the study is the agreement between the FFR values obtained by the intravenous nicorandil and those obtained by the intravenous adenosine. Recruitment of this trial started in November 2015 and will end in March 2017, or until a total of 50 participants have been recruited. Ethics and dissemination: The protocol was approved by the Institutional Review Board at Chiba University Hospital. Study findings will be published in peer-reviewed journals.

BACKGROUND: Pulmonary vein isolation (PVI) has become an important option for treating patients with atrial fibrillation (AF). Periesophageal nerve (PEN) injury after PVI causes pyloric spasms and gastric hypomotility. This study aimed to clarify the impact of PVI on gastric motility and assess the prevalence of gastric hypomotility after PVI. METHODS: Thirty consecutive patients with AF underwent PVI under luminal esophageal temperature (LET) monitoring. The (13)C-acetate breath test was conducted before and after the procedure for all patients (PVI group). Gastric emptying was evaluated using the time to peak concentration of (13)CO2 (T max). This test was also conducted in another 20 patients who underwent catheter ablation procedures other than PVI (control group). RESULTS: The number of patients with abnormal T max (≥75 min) increased from seven (23%) to 13 (43%) and from three (15%) to five (25%) after the procedure in the PVI group and control group, respectively. The mean T max was longer after PVI than before PVI (64±14 min vs. 57±15 min, p=0.006), whereas there was no significant difference before and after the procedure in the control group. However, no significant difference in ΔT max was observed between the two groups (p=0.27). No patients suffered from symptomatic gastric hypomotility. CONCLUSIONS: Asymptomatic gastric hypomotility occurred more often after PVI. However, the average impact of PVI on gastric motility was minimal.

Purpose: We evaluated the consistency of different-assessors in estimating three-dimensional (3D) global-longitudinal-strain (GLS) of left (LV) and right ventricle (RV) using transthoracic-echocardiography (TTE) for LV and RV systolic-function. We compared results from two-independent-specialists using this-approach for 3D LV and RV parameters in a population with 74% hypertrophic-cardiomyopathy (HCM) patients. Methods: 58 patients (43 HCM(32 male; 62 +/- 15 years) and 15 controls (5 male; 53 +/- 22 years)) underwent TTE (Vivid-E9) to measure 2D and 3D GLS of the LV and RV by two-independent-specialists. Results: Consistencies of estimates of 3D LV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection-fraction (EF) between the two-assessors were 0.872 (3D LVEDV, P < 0.001), 0.797 (3D LVESV, P < 0.001), and 0.215 (3D LVEF, P = 0.105). Consistencies of 2D and 3D LV GLS between two-assessors were 0.900 (2D LVGLS, P < 0.001) and 0.874 (3D LVGLS, P < 0.001). Consistencies of estimates of 3D RVEDV, RVESV, and RVEF between two assessors were 0.781 (3D RVEDV, P < 0.001), 0.755 (3D RVESV, P < 0.001), and 0.26 (3D RVEF, P = 0.049). Consistencies of 2D and 3D GLS of whole RV and those of RV free wall only between two-assessors were 0.886 (2D GLS of whole RV, P < 0.001), 0.687 (3D GLS of whole RV, P < 0.001), 0.707 (2D GLS of RV free wall, P < 0.001), and 0.630 (3D GLS of RV free wall, P < 0.001). Conclusions: Consistencies of independent-estimates of 3D GLS of the LV and RV using TTE between two-assessors were worse than for 2D GLS of the LV and RV, but better than for 3D LVEF and RVEF in a population with 74% HCM patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Background: The pharmacodynamic effects of changing from standard-dose clopidogrel to low-dose (3.75 mg) prasugrel in Japanese patients are largely unknown. Methods and Results: A total of 53 consecutive Japanese patients with stable coronary artery disease (CAD) who received aspirin and clopidogrel were enrolled. Clopidogrel was switched to 3.75 mg prasugrel. At day 14, prasugrel was switched to 75 mg clopidogrel. Platelet reactivity was measured using the Verify Now assay at baseline, day 14, and day 28. VerifyNow P2Y12 reaction units (PRU) >208 was defined as high on-treatment platelet reactivity (HPR). The prevalence of HPR (18.9% vs. 41.5% vs. 44.2%, P<0.001) and the PRU level (154.3 +/- 54.2 vs. 196.2 +/- 55.5 vs. 194.6 +/- 55.8, P<0.001) were significantly lower on prasugrel maintenance therapy compared with the clopidogrel therapy before and after switching. The CYP2C19 genotypes that account for the 3 phenotypes (ie, extensive metabolizer, intermediate metabolizer, and poor metabolizer) had a significant impact on platelet reactivity with clopidogrel (174.9 +/- 54.0 vs. 193.1 +/- 56.5 vs. 240.6 +/- 25.4 PRU, P<0.001) but not prasugrel (147.0 +/- 51.9 vs. 147.5 +/- 58.3 vs. 184.4 +/- 38.3 PRU, P=0.15). Conclusions: Low-dose prasugrel achieves stronger platelet inhibition than clopidogrel in Japanese patients with stable CAD.

Elevated serum uric acid (SUA) level is known to be a prognostic factor in patients with acute coronary syndrome (ACS). However, the pathogenesis of the relation between SUA level and coronary plaque characteristics has not been fully evaluated. The aim of this study was to investigate the relation between SUA level and plaque composition of nonculprit lesions in patients with ACS. A total of 81 patients with ACS who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were included. They were classified into 3 groups according to tertiles of SUA level. Using integrated backscatter (IB) -IVUS system, tissue components were classified into 4 categories: calcium deposits, dense fibrosis, fibrosis, and lipid. Tertiles of SUA level were as follows: low tertile <5.0 mg/dl; intermediate tertile 5.0 to 6.4 mg/dl; and high tertile >6.4 mg/dl. There was a trend toward greater vessel volume in the high tertile group than in the low and intermediate tertile groups (19.4 +/- 3.7 vs 17.4 +/- 4.4 vs 16.7 +/- 4.1 mm(3)/mm, p = 0.05). There was no significant difference in lumen volume between the 3 groups. Plaque volume was significantly greater in the high than in the low tertile group (8.6 +/- 2.4 vs 6.7 +/- 2.2 mm(3)/mm, p = 0.01). IB-IVUS analysis demonstrated greater lipid (59.1 +/- 9.1% vs 49.7 +/- 10.9% vs 51.1 +/- 9.3%, p = 0.001) and less fibrous components (36.8 +/- 7.8% vs 44.3 +/- 7.8% vs 43.2 +/- 6.7%, p < 0.001) in the high than in the low and intermediate tertile groups. Multivariate analysis showed high SUA as an independent predictor of increasing lipid volume. In conclusion, elevated SUA level is associated with greater lipid content of coronary plaque in patients with ACS than in patients with normal levels. (C) 2015 Elsevier Inc. All rights reserved.

Background: Adipose tissue is one of the sources of mesenchymal stem cells, which have the potential to differentiate into various types of cells, including myocytes. Whether brown adipose tissue (BAT)-derived cells might differentiate into the cardiac pacemaking-conducting cells, and have the potential to regenerate the cardiac conduction system (CCS), is investigated in this study. Methods and Results: BAT was isolated from the interscapular area of mice and enzymatically digested before culture. Round or fusiform cells showed spontaneous beating at 4-7 days after culturing of BAT-derived cells. Reverse transcriptase-polymerase chain reaction analysis and immunocytochemical analysis revealed that BAT-derived cells expressed several cardiomyocytes, the CCS and pacemaker (PM) cell marker genes and proteins. Patch-clamp techniques revealed that spontaneous electrical activity and the shape of the action potential showed properties of cardiac PM cells. Next, a complete atrioventricular (AV) block was created in mice and green fluorescent protein-positive (GFP (+)) BAT-derived cells were injected intramyocardially around the AV node. At 1 week after transplantation, 50% of BAT-derived cells injected mice showed a sinus rhythm or a 2:1 AV block. Immunohistochemical analysis revealed that injected GFP (+) cells were engrafted and some GFP (+) cells co-expressed several cardiac PM cell marker proteins. Conclusions: BAT-derived cells differentiate into the CCS and PM-like cells in vitro and in vivo, and may become a useful cell source for arrhythmia therapy.

Rationale: In right ventricular hypertrophy associatedwith severe pulmonary hypertension (PH), a shift of energy metabolism toward glycolysis occurs. There are few investigations regarding fatty acid metabolism in patients with PH and right ventricular hypertrophy. Objectives: To assess whether there is fatty acid accumulation in the hypertrophied right ventricle in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether this accumulation is related to hemodynamic variables obtained by right heart catheterization. Methods: To assess fatty acid accumulation in the right ventricle, 123I-β-methyl iodophenyl pentadecanoic acid (BMIPP) analog imaging was performed in control subjects (n = 16) and patients with CTEPH (n = 13) before (n = 13) and after (n = 8) pulmonary thromboendarterectomy. Measurements and Main Results: There was increased 123IBMIPP uptake in the right ventricle of subjects with CTEPH before pulmonary endarterectomy. Right ventricular 123I-BMIPP uptake decreased significantly after thromboendarterectomy (P = 0.003) in parallel with the change of hemodynamic variables. The right ventricular BMIPP uptake was significantly correlated with the mean pulmonary artery pressure (r = 0.51, P = 0.0228) but not with pulmonary vascular resistance (r = 0.39, P = 0.0932). Conclusions: This is the first study that uses 123I-BMIPP uptake imaging to show that fatty acid accumulates in the right ventricle of patients with CTEPH and that the increased accumulation is reversible after pulmonary thromboendarterectomy. This study suggests that this imaging modality may be useful for monitoring right ventricle metabolic functions in severe PH.

Background: Late and very late stent thrombosis after drug-eluting stent implantation is a major concern. The present study evaluated difference in the effects of sirolimus, paclitaxel and zotarolimus on endothelial cells. Methods: Mouse endothelial cells were seeded in a 6-well plate. Cells were cultured with an antiproliferative drug at the expected concentrations for each well for 24 hours before making 3 scratch lines with a pipette tip. After a 4.5 hour incubation period, 3 reference scratch lines, vertically across the original scratch lines, were made in the same way. The experiment was repeated at least 6 times (6 plates). Measurements were performed at 9 crossings of each well. Wound healing ratio was calculated as 1 - (distance of the first scratch/distance of the second scratch). % cell migration was calculated as (wound healing ratio at an expected drug concentration/wound healing ratio with no drug). × 100 Average % cell migration at 54 crossings of 6 plates was calculated. Results: Paclitaxel inhibited cell migration in a concentration-dependent manner. On the other hand, concentration-dependent inhibition was not observed for sirolimus or zotarolimus. Sirolimus showed a stronger inhibitory effect on migration of endothelial cells compared to zotarolimus. Conclusions: The difference in the effect of antiproliferative drugs of drug-eluting stents on endothelial cells may be associated with relatively faster re-endothelialization of zotarolimus-eluting stent compared to the 1st generation DES.

We report a case of right ventricular (RV) diastolic dysfunction due to a large hematoma posterior to the left ventricle (LV) after cardiac surgery. An 80-year-old woman underwent cardiac surgery. After surgery, her physical findings revealed right heart failure. Localized hematoma posterior to the pericardial space and the RV compression to the sternum were shown by computed tomography. Transthoracic Doppler echocardiography demonstrated restrictive physiology of the RV although there was no evidence of constrictive pericarditis. These findings suggest that RV diastolic dysfunction could have occurred due to the hematoma posterior to the LV. Since pleural effusion had persisted despite medical therapy, the hematoma was removed surgically. Soon after surgery, dyspnea and pretibial edema were diminished bilateral pleural effusion dramatically disappeared. RV diastolic dysfunction estimated by echocardiography was improved and RV compression disappeared.We speculate that there are two physiological mechanisms for the RV compression: (1) the localized hematoma elevated the intrapericardial pressure and (2) the hematoma shifted the entire heart to the sternum. In conclusion, this is the first case report of RV diastolic dysfunction due to large hematoma posterior to the LV.&lt . Learning objective: Localized hematoma posterior to the left ventricle can be a cause of right ventricular compression that leads to onset of severe right ventricular diastolic dysfunction.&gt .

Purpose: In order to evaluate compensatory mechanisms in hypertrophic-cardiomyopathy (HCM) subjects with preserved left-ventricular (LV) ejection-fraction (EF), we measured myocardial percentage endocardial strain dependency, as represented by 2D LV global longitudinal (GLS) and circumferential-strain (GCS), using a novel, multi-layer, speckle-tracking transthoracic-echocardiography (TTE) technique. Methods: A total of 60 subjects (40 HCM with preserved LV EF (30 male; 62 +/- 15 years, all LV EF > 50%)) and 20 controls (10 male; 59 +/- 10 years) underwent TTE (Vivid-E9). Quantitative strain-measurements of: endocardial, all and epicardial layers were performed at each-site. We defined percentage endocardial strain dependency as the ratio of endocardial strain to epicardial strain. Results: Absolute GLS values at all views in all, endocardial and epicardial myocardial layers were significantly smaller in HCM subjects than in controls (all P < 0.001). There were no significant differences between both groups in absolute GCS values in the endocardial layers, at the mitral valve and papillary muscle levels. Percentage endocardial GCS dependency at all levels were greater in HCM subjects than in controls (all P < 0.01). In HCM subjects, percentage endocardial GCS dependency at the mitral valve and papillary muscle levels revealed significant, moderate, negative correlations with LV end-diastolic and systolic dimensions (correlation coefficients -0.505, -0.451 (mitral valve level) and -0.533, -0.591 (papillary muscle level), respectively). Conclusions: In HCM subjects with preserved LV EF, 2D LV GLS was lower than in controls, but endocardial GCS was maintained in compensation for reduction in endocardial GLS; thus percentage endocardial GCS dependency may increase, and the larger the LV size, the smaller this compensatory effect. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Purpose: In evaluating coronary arteries by 64-256 slice CT, atrial fibrillation (AF) is usually an exclusion criterion. We used CHADS2 score to predict coronary arteriosclerosis estimated by 320-slice CT and prognosis in AF subjects. Methods: A total of 183 consecutive subjects (148 male; 64.1 +/- 11.1 years, 97 hypertension, 60 hyperlipidemia, 21 diabetes mellitus, 76 smoking habits, body mass index 23.4 +/- 3.5) who were diagnosed previously as chronic (N=104) or paroxysmal AF (N=79), andwho underwent electrocardiogram-gated 320-slice CT were enrolled. The composite end point of cardiac death or sudden death was assessed. Results: A total of 183 AF subjects were divided into 3 groups: CHADS2 scores of 0 (N=53), 1 (N=57) and = 2 (N=73). Frequency of the presence of calcified plaque, non-calcified plaque, mixed plaque, any plaque, and N50% stenosis and Agatston calcium score was significantly lower in CHADS2 score 0 group compared with score 1 or score >= 2 groups. In logistic-regression models for prediction of calcified plaque, or any plaque on CT, the odds ratios of CHADS2 score >= 2 group to CHADS2 score 0 or 1 group were 2.03 and 2.12, respectively (both P < 0.05). During a median of 19.2 months, the composite-event-rate was significantly higher in subjects with CHADS2 score >= 2 than those with CHADS2 score 0 (P= 0.049) in Kaplan-Meier survival analysis. Conclusions: The CHADS2 score is a useful predictor of coronary arteriosclerosis on CT and may correlate with prognosis in AF subjects. Subjects with high CHADS2 score should be examined for coronary arteriosclerosis in addition to cerebral infarction. (C) 2014 Elsevier Ireland Ltd. All rights reserved.