S2-4 Echo, Small Coronary Artery Stenosis in HCM

Symposia called breakthroughed aldosterone can not be ignored. These effects can be inhibited by MR anagonist at a small dose, not lower blood pressure. In this symposium, we will focus on the effectiveness of MR antagonist (aldosterone blocker) in patients with essential hypertension, with or without chronic kidney disease (CKD) in our outpatients. In patients without CKD, aldosterone blocker in addition to an ACE inhibitor or ARB, significantly lowered blood pressure and reduced urinary albumin excretion without any adverse effects. We had almost similar results in patients with CKD, however, the adverse effect of greatest concern is hyperkalemia which can occur when aldosterone blocker is combined with an inhibitor of the renin angiotensin system. If subjects are selected and followed closely, the adverse effects, especially hyperkalemia, will rarely become problematic. Symposium 2. Heart Failure 2: Assessment of Left Ventricular Function in Heart Failure S2-1 Assessment of Left Ventricular Systolic Function in Diastolic Heart Failure Using Cardiac Time Intervals Akira Kisanuki, Mihoko Kono, Chuwa Tei. Kagoshima University, Kagoshima, Japan Background and objectives: Systolic function in diastolic heart failure is defined as preserved left ventricular (LV) ejection fraction (EF). However, EF may not reflect the systolic function in DHF fully, especially the abnormalities during isovolumetric contraction time (ICT). Cardiac time interval analysis may add another information on LV systolic function which LV EF cannot provide. Methods: We examined LV systolic and diastolic function in 80 consecutive patients with DHF, 30 patients with asymptomatic diastolic dysfunction (ADD) and 30 normal subjects (Control). LV and left atrial volumes, LV EF, LV ICT and isovolumetric relaxation time (IRT), early diastolic mitral flow velocity, systolic mitral annular velocity (S ) and early diastolic mitral annular velocity were obtained using tissue and Doppler echocardiography. Results: LV ICT in DHF was significantly increased compared to those in ADD and Control. ICT in ADD were equal to that in Control. LV end - diastolic volume index in DHF was significantly increased compared to those in ADD and Control. S in DHF and ADD were significantly decreased compared to that in Control. Conclusion: LV systolic function in DHF appears to be abnormal despite preserved LV EF. S2-2 Assessment of Left Ventricular Diastolic Function by Novel Ultrasound Techniques Satoshi Nakatani. Osaka University Graduate School of Medicine, Japan Strain/strain rate imaging is the most remarkable advancement among recently developed ultrasound technologies. Strain and strain rate have been obtained based on tissue Doppler echocardiography with excellent temporal resolution but with a limitation of Doppler angle dependency. However, they can now be obtained independent of Doppler angle using speckle tracking technique. Strain and strain rate are thus obtained in longitudinal and transverse directions in the apical views and in radial and circumferential directions in the short-axis views. Longitudinal strain and strain rate well reflect global left ventricular function because most of subendocardial fibers are oriented longitudinally. Diastolic strain rate is an index of regional relaxation and has been related to global left ventricular relaxation. Further,

S13 strain rate during isovolumic relaxation time showed a good correlation with time constant of left ventricular relaxation. Speckle tracking technique can provide not only strain and strain rate but also rotational degrees and velocity at a certain short-axis image. By subtracting apical rotation from basal rotation, we can assess left ventricular twisting in systole and untwisting in diastole. The peak untwisting rate has been reported to correlate with left ventricular diastolic suction and relaxation. These new parameters are promising to assess left ventricular diastolic function independently of conventional echocardiographic parameters. S2-3 Assessment of LV Function by 3D Echo Tsui-Lieh Hsu. Taipei Veterans General Hospital, Taipei, Taiwan The advance of 3-dimensional (3D) echocardiography allows to acquiring a full volumetric dataset of the left ventricle (LV) which are using for off-line quantitative analysis of LV function. Studies have been demonstrated the accuracy of 3D method in comparison with MRI for the calculation of LV volume, ejection fraction and mass. New algorithm provides regional volume data over one cardiac cycle, which further calculation of LV dyssyncnhrony index for the selection of patients who may benefit from the cardiac resynchronization therapy. The pitfalls of current 3D technology include difficult in atrial fibrillation rhythm, loss of clear endocardium boundary in the dilated heart. The 3 layer of myocardial fiber orientation appear as a spiral, circular and longitudinal fashion. Two-dimensional speckle tracking imaging and data analysis of LV twist motion has been elucidated the importance of cardiac mechanics in normal and disease state. New modality of 3D speckle tracking technology further explores the potential clinical application of 3D volume dataset for assessing the LV function and determination of the torsion. It would have profound clinical impact for quantitative assessment of global and regional LV function. In conclusion, 3D echo could add additional diagnostic value for assessing of LV function in the diagnosis and management of failing heart. S2-4 Echo, Small Coronary Artery Stenosis in HCM Woo-Shik Kim. Kyung Hee University, Seoul, Korea The pathogenesis of myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) in the absence of epicardial coronary artery stenosis remains uncertain. Although there is growing evidence that abnormalities of the coronary microvasculature can result in myocardial ischemia in patient with HCM with normal epicardial coronary artery, clinical evaluation of the coronary microcirculation has not been fully investigated due to technical difficulties. Recent advances in transthoracic Doppler echocardiography (TTDE) allow evaluation of flow velocity not only in the left anterior descending coronary artery (LAD) but also in the intramyocardial coronary artery (IMCA, 500 1000 mm). We have observed some clinical cases of acceleration flow signal within the IMCA in patients with HCM by TTDE. Since the acceleration flow signal on color Doppler echocardiography is generally observed at the site of a segmentally narrowed portion, we hypothesized the acceleration signal observed in the IMCA might be an abnormal flow velocity which suggests a narrowed lumen in the small coronary artery. To determine whether TTDE could detect abnormal flow for a stenosis, we evaluated acceleration flow signal in IMCA. We also evaluated the

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Abstracts of the 17th Asian Pacific Congress of Cardiology

relationship between coronary flow velocity reserve in the LAD and narrowing of IMCA. Furthermore, we evaluated the characteristics of the coronary flow velocity profiles in the IMCA and to define the relationship between the coronary flow velocity pattern and clinical manifestations in patients with HCM.

arrhythmogenic action of miR-1 is likely mediated by its repression of GJA1/Cx43 and KCNJ2/Kir2.1. Conclusion: MiRNAs may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target. Acknowledgments: Supported by 973 program of China (2007CB512006) and the NSFC (30672644).

Symposium 3. Heart Failure 3: Basic Mechanism and New Therapeutic Targets in Heart Failure

S3-3 Cardiomyocyte Death and Heart Failure Kinya Otsu. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Japan

S3-1 miRNAs and Cardiac Arrhythmogenesis: Role in Atrial Fibrillation Zhiguo Wang1,2 , Baofeng Yang2 . 1 Department of Pharmacology, Harbin Medical University, Harbin, P.R. China, 2 Department of Medicine, University of Montreal, Montreal, PQ, Canada Atrial fibrillation (AF) is a highly prevalent condition associated with pronounced morbidity, mortality, and socioeconomic burden. It can cause or exacerbate heart failure that in turn promotes AF. The most important characteristics of both clinical and experimental AF is the remodeling process associated with profound reduction of L-type Ca2+ current (ICaL ) and enhancement of inward rectifier K+ current (IK1 ). We show here that microRNA-328 (miR-328) expression was aberrantly upregulated whereas miR-101, miR-133, miR-1, and miR-331 were all downregulated, in atria of experimental AF. Forced expression of miR-328 by adenovirus and transgene approaches recapitulates the phenotypes of AF, exemplified by diminished ICaL . Knockdown of miR-328 by its antisense reversed the conditions. miR-328 targets CACNA1C and CACNB1 genes encoding L-type Ca2+ channel aand b-subunits, respectively. Promoter analysis of the miR328 gene indicates that elevated NF-úB level likely underlies the aberrant upregulation of miR-328 in AF. On the other hand, we also experimentally established KCNJ2 and KCNJ4, the genes encoding Kir2.1 and Kir2.3 for IK1 , respectively, as common target genes for miR-101, miR-133, miR-1, and miR331. Downregulation of these miRNAs resulted in increase in IK1 . We conclude that multiple miRNAs are critically involved in AF remodeling. S3-2 MicroRNAs and Malignant Arrhythmias Baofeng Yang, Yanjie Lu, Yong Zhang, Yunlong Bai. Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Heilongjian, China Aim: To investigate whether MicroRNA (miRNA) is involved in pathological processes relevant to cardiomyocyte apoptosis and human cardiac disease. Methods: Animal models of myocardial infarction was performed. MiRNA levels were measured using miRNA Detection Kit. Luciferase activities were measured with a dual luciferase reporter assay kit on a luminometer. Western Blot was performed for quantification of target proteins. The currents were measured using whole-cell patch-clamp. Results: miR-1 reduced the levels of HSP60 and HSP70 proteins without changing their transcript levels. By contrast, miR-133 repressed caspase-9 expression at both the protein and mRNA levels. miR-1 and miR-133 are involved in regulating cell fate with increased miR-1 and/or decreased miR-133 levels favoring apoptosis and decreased miR-1 and/or increased miR-133 levels favoring survival. miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. The

Heart failure has become the dominant cardiovascular disorder. There is an urgent need to clarify the mechanisms governing the pathological remodeling mediated through cell death, and to identify ways to prevent and treat heart failure. There are three types of cell death: apoptosis, autophagy and necrosis. Apoptosis, a form of programmed cell death, has been well characterized and the molecular events involved in apoptotic death are well understood. We have shown that the inhibition of apoptosis signalregulating kinase 1 (ASK1), which is involved in apoptosis, results in suppression of the development of heart failure. Necrosis is often defined in a negative manner: death lacking the characteristics of programmed cell death and thus accidental and uncontrolled. However, our recent studies indicate that necrosis is tightly regulated. Cyclophilin D-dependent mitochondrial permeability transition (MTP) mediates necrotic cell death. MTP may be a therapeutic target to treat patients with heart failure. Autophagy is a cell survival mechanism that involves degradation and recycling of cytoplasmic components. In contrast, autophagy may mediate cell death under specific circumstances. In fact, damaged cardiomyocytes that show characteristics of autophagy have been observed during heart failure. However, our recent study indicated that upregulation of autophagy in failing hearts is an adaptive response. S3-4 Role of p53 in Heart Failure Tohru Minamino, Issei Komuro. Department of Cardiovascular Science and medicine, Chiba University Graduate School of Medicine, Japan Although cardiac hypertrophy is an adaptive response to hemodynamic overload caused by a large number of physiological and pathological conditions including hypertension, a number of clinical studies have shown that sustained cardiac hypertrophy is associated with a significant increase in the risk of heart failure, arrhythmia, and sudden death. At the beginning, cardiac hypertrophy has beneficial effects to maintain cardiac output by reducing wall stress. However, prolonged cardiac hypertrophy causes heart failure, and its mechanisms are largely unknown. We here demonstrate that cardiac angiogenesis is critically involved in the adaptive mechanism of cardiac hypertrophy and that p53 accumulation is crucial for the transition from cardiac hypertrophy to heart failure. Pressure overload initially promoted vascular growth in the heart by hypoxia-inducible factor-1 (HIF-1)-dependent induction of angiogenic factors, and inhibition of angiogenesis prevented the development of cardiac hypertrophy and induced systolic dysfunction. Sustained pressure overload induced accumulation of p53 that inhibited HIF-1 activity and thereby impaired cardiac angiogenesis and systolic function. Conversely, promoting cardiac angiogenesis by introducing angiogenic factors or by inhibiting p53 accumulation further developed hypertrophy and restored cardiac dysfunction under chronic pressure overload. These results suggest that inhibition of p53 activity