小林 欣夫

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.

Background: The aimof this study is to predict the risk of coronary-arteriosclerosis and prognosis in subjects with chronic-atrial-fibrillation (CAF) using the CHADS2 and CHA2DS2-VASc scores by 320-slice-CT and invasive-coronary-angiography (ICA) in a two-center-study. Methods: 53 CAF subjects who underwent 320-slice-CT and ICA within 6-months (43 male; 69 +/- 9 years; CHADS2 score 2.2 +/- 1.3; CHA2DS2-VASc score 3.5 +/- 1.6) in the two-institutes were analyzed. CT and ICA data were transferred to the analysis-center and were analyzed by cardiologists. Results: Agatston-calcium-score and frequencies of the presence of various-kinds of plaques and >50% and >75% coronary artery stenosis were significantly higher in the subjects with CHA2DS2-VASc score >= 3 compared with thosewith score <3. However there were no-significant differences in the Agatston-calcium-score and frequencies of the presence of various-kinds of plaques and >50% and >75% coronary artery stenosis evaluated by 320-slice CT between the subjects with CHADS2 score >= 2 and <2. Frequency of N50% coronary artery stenosis by ICA was significantly higher in the subjects with CHA2DS2-VASc score >= 3 compared with those with score <3. However, there were no-significant differences in the frequencies of N50% and >75% coronary artery stenosis by ICA between the subjects with CHADS2 score >= 2 and <2. During a mean of 15.9 months, composite rate of cardiac death and heart failure did not differ between subjects with CHADS2 score >= 2 and score <2 and between subjects with CHA2DS2-VASc score >= 3 and score <3. Conclusions: The CHA2DS2-VASc score is a useful predictor of not prognosis but coronary-arteriosclerosis in subjects with CAF compared with CHADS2 score in this two-center-study. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Purpose: To compare diagnostic-accuracy of prospective and retrospective-ECG-gated acquisition in 320-slice-CT for detecting coronary-artery stenosis in subjects with chronic-atrial-fibrillation (CAF) in a two-center study. Materials and methods: 53 CAF subjects who underwent 320-slice-CT, and invasive-coronary-angiogram (ICA) within 6-months (43 male; 69 +/- 9 years; CHADS2 score 2.2 +/- 1.3; CHA2DS2-VASc score 3.5 +/- 1.6) in the two institutes were analyzed. In Institute-1, prospective-ECG-gated acquisition was routinely performed (N = 33). In Institute-2, retrospective-ECG-gated acquisition was routinely performed (N = 20). CT and ICA data were transferred to the analysis center and were analyzed by cardiologists blinded to the clinical-data. Results: Prevalence of >50 and >75% on ICA was 79 and 61% in Institute-1, and 30 and 15% in Institute-2, respectively. In a patient-by-patient analysis, Institute-2 had higher negative-predictive-value (NPV) and accuracy of >75% stenosis on CT in predicting >75% stenosis on ICA. In a vessel-by-vessel analysis, there were no significant-differences of sensitivity, specificity, positive-predictive-value (PPV) and NPV of >50% stenosis on CT in predicting >50% stenosis on ICA between both institutes. But sensitivity, specificity, and NPV of >75% stenosis on CT in predicting >75% stenosis on ICA were significantly higher in Institute-2 than in Institute-1. This is mainly because of more severe coronary-artery disease including calcification in Institute-1; there might also have been an influence of differences in scanning and reconstruction methods. Conclusions: 320-slice-CT shows relatively high diagnostic-accuracy for the detection of significant coronaryartery stenosis compared with ICA even in CAF subjects, in a two-center analysis. Retrospective-ECG-gated acquisition in 320-slice-CT shows significantly higher diagnostic-accuracy than prospective-ECG-gated acquisition for detection of >75% coronary-artery stenosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Purpose: We used bolus-tracking CT-images, which are usually used only to detect contrast-material in target organs for optimal-starting of acquisition, as virtual first pass myocardial perfusion images. Methods: Retrospective-analysis of 14 patients (10 male, 63 +/- 10 years) diagnosed with >= 75% stenosis confined to left-anterior-descending-artery (LAD) (7 patients, Group-1) or insignificant stenosis of any coronary artery (7 patients Group-2) diagnosed using invasive-coronary-angiograms (ICA) and enhanced 320-slice-CT within 3-months and without incident between examinations. Bolus-tracking CT-images were acquired at mid-level left-ventricle (LV) until CT-attenuation of descending-aorta increased to 200HU. We measured CT-attenuation (HU) in the LV anterior-wall (AW), the basal inter-ventricular-septum (BIVS), and LV basal lateral-wall (BLW) in end-systole using both bolus-tracking images and routine, enhanced, early-phase CT-images. Results: In the bolus-tracking images, the Group-1 LV AW, BIVS, BLW CT-attenuation and ratio of LV AW CT attenuation to the average of BIVS and BLW were 36 +/- 7HU, 62 +/- 11HU, 58 +/- 25HU, and 0.6 +/- 0.1 respectively. In Group-2, they were 53 +/- 14HU, 56 +/- 9HU, 54 +/- 15HU, and 1.0 +/- 0.3 respectively. LV AW CT-attenuation and the ratio of LV AW CT values to the average of BIVS and BLW, were significantly lower in Group-1 (both P < 0.05). These values were not significant using routine, enhanced, early-phase CT-images. Conclusions: Bolus-tracking CT-imagesmay be useful to detect the LAD-confined stenosis that cannot be detected using routine, enhanced, early-phase CT-images. This can be achieved by measuring the local-reduction in CT-attenuation of the LV AW compared with the average of those of the BIVS and BLW and without the need for drugs, exercise or additional radiation-exposure. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Background-Cardiac cell therapy has been proposed as one of the new strategies against myocardial infarction. Although several reports showed improvement of the function of ischemic heart, the effects of cell therapy vary among the studies and the mechanisms of the beneficial effects are still unknown. Previously, we reported that clonal stem cell antigen-1-positive cardiac progenitor cells exerted a therapeutic effect when transplanted into the ischemic heart. Our aims were to identify the cardiac progenitor-specific paracrine factor and to elucidate the mechanism of its beneficial effect. Methods and Results-By using an antibody array, we found that soluble junctional adhesion molecule-A (JAM-A) was abundantly secreted from cardiac progenitor cells. Pretreatment of neutrophils with conditioned medium from cultured cardiac progenitor cells or soluble JAM-A inhibited transendothelial migration and reduced motility of neutrophils. These inhibitory effects were attenuated by anti-JAM-A neutralizing antibody. Injection of cardiac progenitor cells into infarct heart attenuated neutrophil infiltration and expression of inflammatory cytokines. Injection of soluble JAM-A-expressing, but not of JAM-A siRNA-expressing, cardiac progenitor cells into the infarct heart prevented cardiac remodeling and reduced fibrosis area. Conclusions-Soluble JAM-A secreted from cardiac progenitor cells reduces infiltration of neutrophils after myocardial infarction and ameliorates tissue damage through prevention of excess inflammation. Our finding may lead to a new therapy for cardiovascular disease by using the anti-inflammatory effect of JAM-A.

Introduction: Antiplatelet effects of clopidogrel appear to be affected by various factors including genetic polymorphism. So far, there has been little information about the response of clopidogrel in Asians, whose prevalence of a CYP2C19 loss-of-function (LOF) allele is high. Methods and Results: We investigated background and clinical factors affecting on-clopidogrel platelet reactivity in Japanese patients undergoing coronary stent implantation (n = 114). In univariate analysis, antiplatelet effects of clopidogrel in a steady state were associated with not only CYP2C19 genotypes but also several factors including dyslipidemia. In addition, we developed an algorithm that can estimate P2Y12 Reaction Units (PRU) in a steady state by multiple regression analysis and evaluated the adequacy of the algorithm by the Akaike Information Criterion. Conclusions: We revealed several factors influencing on-clopidogrel platelet reactivity in Japanese patients. We also succeeded in developing an algorithm that estimates PRU in a steady state, although it is uncertain whether the algorithm can be applied to other populations. (C) 2014 Elsevier Ltd. All rights reserved.

Aims For successful ablation of ventricular outflow tract arrhythmia, estimation of its origin prior to the procedure can be useful. Morphology and lead placement in the right thoracic area may be useful for this purpose. Electrocardiography using synthesized right-sided chest leads (Syn-V3R, Syn-V4R, and Syn-V5R) is performed using standard leads without any additional leads. This study evaluated the usefulness of synthesized right-sided chest leads in estimating the origin of ventricular outflow tract arrhythmia. Methods and results This retrospective study included 63 patients in whom successful ablation of ventricular outflow tract arrhythmia was performed. Numbers of arrhythmias originating from the left ventricle, the septum of the right ventricle, and the free wall of the right ventricle were 11, 40, and 13, respectively. In one patient, two different left ventricular outflow tract origins were found. Electrocardiographic recordings from right-sided chest leads were divided into three types as follows: those in which an R > S concordance, a transitional zone, or an R < S concordance were detected. In all left arrhythmia cases, R > S concordance was observed. A transitional zone was evident in 34 of 40 cases of right ventricular outflow tract arrhythmia originating in the ventricular septum, and an R < S concordance was observed in 6 of the 40 cases. However, an R < S concordance was found in all cases of right ventricular outflow tract arrhythmia originating in the free wall. Conclusion Synthesized right-sided chest lead electrocardiography may be useful for estimating the origin of ventricular outflow tract arrhythmia.

Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-kappa B signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-kappa B suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses.

Evolutionarily conserved Notch signaling controls cell fate determination and differentiation during development, and is also essential for neovascularization in adults. Although recent studies suggest that the Notch pathway is associated with age-related conditions, it remains unclear whether Notch signaling is involved in vascular aging. Here we show that Notch signaling has a crucial role in endothelial cell senescence. Inhibition of Notch signaling in human endothelial cells induced premature senescence via a p16-dependent pathway. Conversely, over-expression of Notch1 or Jagged1 prolonged the replicative lifespan of endothelial cells. Notch1 positively regulated the expression of inhibitor of DNA binding 1 (Id1) and MAP kinase phosphatase 1 (MKP1), while MKP1 further up-regulated Id1 expression by inhibiting p38MAPK-induced protein degradation. Over-expression of Id1 down-regulated p16 expression, thereby inhibiting premature senescence of Notch1-deleted endothelial cells. These findings indicate that Notch1 signaling has a role in the regulation of endothelial cell senescence via a p16-dependent pathway and suggest that activation of Notch1 could be a new therapeutic target for treating age-associated vascular diseases.

Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.

In Japan, a lower maintenance dose of ticlopidine is used than in the United States and Europe. Therefore a lower maintenance dose of clopidogrel may also be considered appropriate in Japanese patients. The present randomized pilot study evaluated the efficacy and safety of 50 mg clopidogrel in Japanese patients who underwent drug-eluting stent (DES) implantation. A total of 200 patients with 277 lesions who underwent intravascular ultrasound-guided DES implantation were enrolled. The subjects were allocated to the 50- or 75-mg clopidogrel group. All patients received 100 mg aspirin daily before the procedure, and this continued indefinitely. The duration of clinical follow-up was 21.8 +/- 5.7 months in the 75-mg group and 21.9 +/- 6.1 months in the 50-mg group (P = 0.96). During follow-up, no cardiac death, myocardial infarction, or stent thrombosis was observed in either group. Side effects of clopidogrel were observed in 4 patients (4.0 %) in the 75-mg group and in 4 patients (4.0 %) in the 50-mg group. Following this randomized pilot study, it may be justified to perform a large-scale randomized study comparing 50- and 75-mg dosing of clopidogrel in Japanese patients undergoing coronary stent implantation.

Side branch compromise after stenting in bifurcation lesions is a matter of concern. It may happen that even low-profile balloon catheters do not cross stent struts after rewiring. The Corsair catheter is a hybrid catheter that has features of a microcatheter and a support catheter. The present study evaluated usefulness of the Corsair catheter to facilitate advancing a low-profile balloon catheter through stent struts in bifurcation lesions. After rewiring, low-profile balloon catheters failed to cross stent struts of 29 bifurcation lesions. The Corsair microcatheter successfully crossed stent struts in all lesions except one (97 %) where a stent was implanted to treat in-stent restenosis (stent-in-stent). Low-profile balloon catheters were able to advance into the side branch of all bifurcation lesions where the Corsair microcatheter crossed stent struts. In conclusion, the Corsair microcatheter may be utilized if low-profile balloon catheters are unable to cross stent struts in bifurcation lesions. © 2013 Japanese Association of Cardiovascular Intervention and Therapeutics.

A 78-year-old woman complained of experiencing dyspnea (New York Heart Association II) and faintness. Echocardiography revealed she had asymmetric left ventricular hypertrophy, and a dynamic left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the mitral valve. It also revealed calcification of the noncoronary cusp and a high-flow velocity in the LVOT (6.3m/s). The planimetry measurement with transesophageal echocardiography was 0.89cm2 (aortic valve area/body surface area: 0.69cm2/m2). Later, she was diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) and aortic stenosis (AS). However, during the catheterization, the transvalvular pressure gradient (PG) was only 25mmHg. In order to solve this, we performed a percutaneous transluminal septal myocardial ablation. As a result, the PG of the LVOT decreased from 152mmHg to 25mmHg.We first thought that the LVOT obstruction had reduced the flow passing through the aortic valve, and restricted the motion of the aortic valve leaflets. We also considered the possibility that the aortic valve area had been underestimated. The hemodynamic study played an important role in the decision for the treatment plan. The present case was a combination of HOCM and "mild" AS.&lt . Learning objective: We know that we can distinguish between a left ventricular outflow tract obstruction and aortic stenosis using continuous-wave Doppler according to the phase of the peak gradient. However, if both are present, it is uncertain whether we can distinguish between them. It is necessary to measure the subaortic pressure and flow passing through the aortic valve accurately by catheterization in order to know which is the chief pathology.&gt . © 2013 Japanese College of Cardiology.

心臓MRI(CMR)と12誘導Holter心電図を3ヵ月以内に受診した、肥大型心筋症(HCM)の連続患者30名(男性21名、女性9名、平均62±14歳)を対象として、HCM患者で頻繁に観察される断片化QRS波を伴う様々な形態型の心室期外収縮(VPB)の臨床的意義をレトロスペクティブに調査した。全VPBと断片化VPBの形態型数は各々4.7±3.6と2.3±1.8であった。CMR上で左室壁厚、LV重量、左室駆出率は各々17.6±3.6mm、151.6±46.3g、66.2±8.8%であった。26名の左室筋(LVM)に後期亢進(LE)が認められ、LEの平均容積は38.1±22.4mlであった。HCM患者においては、12誘導Holter心電図上の断片化VPBの形態型はCMR上のLVMにおけるLE容積と特異的な正相関を有し、その影響は全VPBよりも大きいことが示された。

3ヵ月以内に12誘導Holster心電図(ECG)と強調ECGゲートCTを受診した、肥大型心筋症(HCM)の連続患者47名(男性36名、女性11名、平均61±13歳)を対象として、冠状動脈と左室筋(LVM)の特性をレトロスペクティブに評価した。CT上で29名の患者に線維症が認められた。冠動脈狭窄を有する患者においては、無狭窄患者と比較して全心室期外収縮(VPB)と断片化VPBの形態型数は有意に低かった。CT上で線維症を有する患者においては、線維症を有しない患者と比較して全VPBと断片化VPBの形態型数は有意に高かった。全VPBまたは断片化VPBの形態型数とCT上の冠動脈内の≧50%内腔狭窄との間には負の相関係数が認められ、一方全VPBまたは断片化VPBの形態型数とCT上のLVM線維症の間には正の相関係数が認められた。

BACKGROUND: Autonomic ganglionated plexi (GPs) play a significant role in the initiation and maintenance of atrial fibrillation (AF). GPs are key targets for a maze procedure. The purpose of this study was to identify the location of the left atrial GPs based on dense epicardial mapping during a maze procedure in patients with concomitant AF. METHODS: Sixteen patients (age, 68 ± 10 years; 11 males, 69%) with heart failure and concomitant AF (duration 55 ± 86 months) underwent intraoperative epicardial electrophysiological mapping and a GP ablation using the maze procedure at our institution. Twenty-four-site, high-frequency stimulation (1,000/min; output, 18 V; pulse width, 0.75 ms) was performed by placing tweezers directly onto the potential GP sites on the left atrial epicardium. RESULTS: Active GPs were found in 13 (81%) of the 16 patients, and 12 (92%) of 13 patients had active GPs between the right pulmonary veins (PVs) and the interatrial groove. For those patients with active locations, a 7-day event-loop recording demonstrated that 12 (92%) of 13 patients were maintained in sinus rhythm 3 months after the operation. CONCLUSION: Dense epicardial mapping in the potential GP areas identified active GP locations in a high percentage of patients. GPs between the PVs and interatrial groove have a high potential as ablation targets for treatment of concomitant AF.