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MicroRNA-208 Expression is Associated With a Shift in the Balance of Myosin Heavy Chain Isoforms in Human Dilated Cardiomyopathy
The 13th Annual Scientific Meeting
020 Dysregulation of Brain MR-ENaCs Pathway Contributes to the Acquisition of Brain Na Sensitivity in Mice With LVH KOJI ITO, YOSHITAKA HIROOKA, KENJI SUNAGAWA Departement of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan Salt intake predisposes patients with left ventricular hypertrophy (LVH) to congestive heart failure. In a salt-sensitive hypertensive rat model, brain Na sensitivity is enhanced and salt augments sympathetic activity. The effects of LVH on brain Na sensitivity and salt-induced cardiac dysfunction, however, have not been clarified. We created LVH in mice with aortic banding (AB). Sham-operated mice served as controls. Four weeks after AB (AB-4), ventricular wall thickness was increased without an associated change in the percent fractional shortening (%FS). AB-4 were then fed either a high-salt (AB-H) or regular-salt (AB-R) diet for additional 4 weeks. In AB-H mice, %FS was decreased [2762 versus 3761 or 4562 (%)] and 24-h urinary norepinephrine excretion (U-NE) was increased [781657 versus 514625 or 373651 (ng/day)] compared with AB-R or Sham, respectively. Intracerebroventricular infusion of high Na induced a greater increase in blood pressure, heart rate, and U-NE in AB mice than in Sham mice. Mineralocorticoid receptor (MR) and ENaC protein levels in the brain were higher in AB mice than in Sham mice. In AB-H, intracerebroventricular infusion of the MR blocker eplerenone decreased U-NE [410621 versus 781657 (ng/day)] and improved %FS [4262 versus 2762 (%)]. Oral administration of eplerenone had similar effects. Dysregulation of the brain MR-ENaCs pathway may contribute to the acquisition of brain Na sensitivity in mice with LVH.
021 Clinical Value of Normal Thallium-201 Myocardial Perfusion Imaging in Elderly Patients YASUHIKO MITSUKE1, AKIRA NAKANO1, HIROYASU UZUI1, TOHRU GESHI1, YUZURI WADA2, REIKO NAKAYA2, KIYOHIRO TOYODA2, SATOSHI NISHIKAWA3, JONG-DAE LEE1 1 Department of Cardiovascular Medicine, University of Fukui Hospital, Fukui, Japan, 2Department of Cardiovascular Medicine, National Fukui Hospital, Fukui, Japan, 3Department of Radiology, National Fukui Hospital, Fukui, Japan The aim of this study was to evaluate long-term prognostic value of normal thallium201 myocardial perfusion imaging and implication for risk stratification by washout rate analysis in elderly patients. We studied 286 consecutive elderly CHF patients (127men, age 70-86 years) who had normal adenosine triphosphte-stress Tl myocardial scintigraphy. The mean follow up interval was 46.8 6 14.5 months (range 25.3 to 81.1 months). Among patients, only 1 cardiac death occurred (!0.1%/year) was major events, and 21 patients were required for hospitalization due to repetitive chest pain. In these 21 patients, 2 patients were diagnosed unstable angina pectoris, 7 patients were vasospastic angina, 1 patient was microvascular angina, and 11 patients were chest pain syndrome. The mean myocardial washout rate in patients who admitted due to coronary events were significantly lower than those were not.These results suggest the possibility that normal thallium-201 myocardial perfusion imaging may provide additional information for the evaluation of those elderly patients.
022 Improvement of Autonomic Nervous Activity by Waon Therapy in Patients With Chronic Heart Failure: Result of Case-control Study SO KUWAHATA, MASAAKI MIYATA, SHOJI FUJITA, TAKURO SHINSATO, TAKURO KUBOZONO, YOSHIYUKI IKEDA, SHUICHI HAMASAKI, CHUWA TEI Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan Background: The aim of this study is to evaluate the effect of Waon therapy on autonomic nervous activity in patients with chronic heart failure (CHF). Methods: 45 patients with CHF were enrolled. In Waon therapy group, 28 patients were treated with medication and Waon therapy. They are placed in a dry sauna at 60 degrees centigrade for 15 minutes and then kept on bed rest with a blanket for additional 30 minutes, once a day, for 4 weeks. In control group, 17 patients matched with Waon therapy group for age, gender, NYHA functional class were treated by conventional therapy for CHF. We analyzed RR intervals for 5 minutes in order to assess both the low frequency (LF) and the high frequency (HF). Coefficient of variance of the RR interval (CVRR) and HF were used as indices of parasympathetic nervous activity, and plasma noradrenaline level and LF/HF were used as indices of sympathetic nervous activity. These parameters were measured before, 2 and 4 weeks after treatment.
JHFS
S157
Results: Waon therapy significantly increased CVRR and HF, and decreased LF/HF and noradrenaline level 2 and 4 weeks after Waon therapy. In contrast, these parameters remained unchanged in control group. Conclusion: In patients with CHF, repeated Waon therapy improves cardiac autonomic nervous activity by increasing the parasympathetic nervous activity and decreasing the sympathetic nervous activity.
023 MicroRNA-208 Expression is Associated With a Shift in the Balance of Myosin Heavy Chain Isoforms in Human Dilated Cardiomyopathy MAMORU SATOH, YOSHITAKA MINAMI, YUJI TAKAHASHI, TSUYOSHI TABUCHI, MOTOYUKI NAKAMURA Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine Recently, microRNAs (miRs) have been discovered and regulated protein expression at the post transcription level. MiR-208, a cardiac-specific microRNA encoded by the a-myosin heavy chain (MHC) gene, is required for cardiac fibrosis and up-regulation of b-MHC expression. The purpose of this study was to determine whether miR-208 was expressed in myocardium of dilated cardiomyopathy (DCM). Endomyocardial biopsy tissues were obtained from 56 patients with DCM and 21 subjects without left ventricular (LV) dysfunction (control). Levels of miR-208, a- and b-MHC mRNAs were measured by real-time RT-PCR. Levels of miR-208 were higher in DCM patients than in controls (0.94 6 0.39 vs. 0.21 6 0.09, P ! 0.001). a-MHC levels were lower in DCM patients than in controls (P ! 0.001), whereas b-MHC levels were higher in DCM patients comparing with controls (P 5 0.03). There was negative correlation between miR-208 and a-MHC levels in DCM patients (r 5 -0.65, P ! 0.001). Levels of miR-208 were positively correlated with b-MHC levels and myocardial collagen volume. Levels of miR-208 were correlated with LV systolic function (r 5 -0.52, P ! 0.001) and LV volume (r 5 0.54, P ! 0.001) in DCM patients. This study has shown that increased myocardial expression of miR-208 is associated with MHC mRNA expression, and thus may be involved in the pathogenesis of human DCM.
024 A Case of Exercise-induced Ventricular Tachycardia After Left Ventricular Functional Improvement by Successful PCI RYO ARAKI, YOSHIKI NODA, TAKAHIRO IMANAKA, RYO MATSUTERA, TATSUYA SASAKI The cardiovascular divison, National Organization, Osaka Minami Medical Center, Osaka, Japan A 74-year-old man presented with abnormal Q wave in leads V1-4 in electrocardiography. Echocardiography showed left ventricular asynergy in anteroseptum and inferior, reduced LV funtion (EF 35% by modified Simpson), and two false tendons which were about 10 mm in width and ranged from basal anterior to apical lateral and apical septum in left ventricle. Ergometer stress myocardial scintigraphy showed redistribution in anteroseptum and inferior without symptom and significant ECG change. PCI was performed for proximal RCA and proximal LAD. Six months later, ventricular tachycardia (VT) occurred during follow-up ergometer stress myocardial scintigraphy. PCI was performed since CAG showed progression of stenosis at RCA ostium. However, VT occurred again during treadmill stress electrocardiography one month later. CAG showed no significant stenosis. Ejection fraction by modified Simpson was improved from 35% to 45%. Because it was thought that VT was caused by not ischemia but false tendons, ablation was applied to the attached part of false tendons in basal anterior in National Cardiovascular Center. VT did not occur during treadmill stress electrocardiography 4 days and 3 months after ablation. In this case, it was thought that exercise-induced VT by false tendons was caused because left ventricular function was improved by PCI. Similar cases have not been reported as far as we know and may be novel aspects of management to hybernative myocardium.
025 Noninvasive Evaluation of Left Ventricular Afterload Would Provide the Optimal Therapeutic Strategy in Patients With Acute Decompensated Heart Failure MASATAKA WATANABE, KAZUHIKO HASHIMURA, HIROYUKI TAKAHAMA, MAKOTO AMAKI, TAKAHIRO OHARA, TAKUYA
020 Dysregulation of Brain MR-ENaCs Pathway Contributes to the Acquisition of Brain Na Sensitivity in Mice With LVH KOJI ITO, YOSHITAKA HIROOKA, KENJI SUNAGAWA Departement of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan Salt intake predisposes patients with left ventricular hypertrophy (LVH) to congestive heart failure. In a salt-sensitive hypertensive rat model, brain Na sensitivity is enhanced and salt augments sympathetic activity. The effects of LVH on brain Na sensitivity and salt-induced cardiac dysfunction, however, have not been clarified. We created LVH in mice with aortic banding (AB). Sham-operated mice served as controls. Four weeks after AB (AB-4), ventricular wall thickness was increased without an associated change in the percent fractional shortening (%FS). AB-4 were then fed either a high-salt (AB-H) or regular-salt (AB-R) diet for additional 4 weeks. In AB-H mice, %FS was decreased [2762 versus 3761 or 4562 (%)] and 24-h urinary norepinephrine excretion (U-NE) was increased [781657 versus 514625 or 373651 (ng/day)] compared with AB-R or Sham, respectively. Intracerebroventricular infusion of high Na induced a greater increase in blood pressure, heart rate, and U-NE in AB mice than in Sham mice. Mineralocorticoid receptor (MR) and ENaC protein levels in the brain were higher in AB mice than in Sham mice. In AB-H, intracerebroventricular infusion of the MR blocker eplerenone decreased U-NE [410621 versus 781657 (ng/day)] and improved %FS [4262 versus 2762 (%)]. Oral administration of eplerenone had similar effects. Dysregulation of the brain MR-ENaCs pathway may contribute to the acquisition of brain Na sensitivity in mice with LVH.
021 Clinical Value of Normal Thallium-201 Myocardial Perfusion Imaging in Elderly Patients YASUHIKO MITSUKE1, AKIRA NAKANO1, HIROYASU UZUI1, TOHRU GESHI1, YUZURI WADA2, REIKO NAKAYA2, KIYOHIRO TOYODA2, SATOSHI NISHIKAWA3, JONG-DAE LEE1 1 Department of Cardiovascular Medicine, University of Fukui Hospital, Fukui, Japan, 2Department of Cardiovascular Medicine, National Fukui Hospital, Fukui, Japan, 3Department of Radiology, National Fukui Hospital, Fukui, Japan The aim of this study was to evaluate long-term prognostic value of normal thallium201 myocardial perfusion imaging and implication for risk stratification by washout rate analysis in elderly patients. We studied 286 consecutive elderly CHF patients (127men, age 70-86 years) who had normal adenosine triphosphte-stress Tl myocardial scintigraphy. The mean follow up interval was 46.8 6 14.5 months (range 25.3 to 81.1 months). Among patients, only 1 cardiac death occurred (!0.1%/year) was major events, and 21 patients were required for hospitalization due to repetitive chest pain. In these 21 patients, 2 patients were diagnosed unstable angina pectoris, 7 patients were vasospastic angina, 1 patient was microvascular angina, and 11 patients were chest pain syndrome. The mean myocardial washout rate in patients who admitted due to coronary events were significantly lower than those were not.These results suggest the possibility that normal thallium-201 myocardial perfusion imaging may provide additional information for the evaluation of those elderly patients.
022 Improvement of Autonomic Nervous Activity by Waon Therapy in Patients With Chronic Heart Failure: Result of Case-control Study SO KUWAHATA, MASAAKI MIYATA, SHOJI FUJITA, TAKURO SHINSATO, TAKURO KUBOZONO, YOSHIYUKI IKEDA, SHUICHI HAMASAKI, CHUWA TEI Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan Background: The aim of this study is to evaluate the effect of Waon therapy on autonomic nervous activity in patients with chronic heart failure (CHF). Methods: 45 patients with CHF were enrolled. In Waon therapy group, 28 patients were treated with medication and Waon therapy. They are placed in a dry sauna at 60 degrees centigrade for 15 minutes and then kept on bed rest with a blanket for additional 30 minutes, once a day, for 4 weeks. In control group, 17 patients matched with Waon therapy group for age, gender, NYHA functional class were treated by conventional therapy for CHF. We analyzed RR intervals for 5 minutes in order to assess both the low frequency (LF) and the high frequency (HF). Coefficient of variance of the RR interval (CVRR) and HF were used as indices of parasympathetic nervous activity, and plasma noradrenaline level and LF/HF were used as indices of sympathetic nervous activity. These parameters were measured before, 2 and 4 weeks after treatment.
JHFS
S157
Results: Waon therapy significantly increased CVRR and HF, and decreased LF/HF and noradrenaline level 2 and 4 weeks after Waon therapy. In contrast, these parameters remained unchanged in control group. Conclusion: In patients with CHF, repeated Waon therapy improves cardiac autonomic nervous activity by increasing the parasympathetic nervous activity and decreasing the sympathetic nervous activity.
023 MicroRNA-208 Expression is Associated With a Shift in the Balance of Myosin Heavy Chain Isoforms in Human Dilated Cardiomyopathy MAMORU SATOH, YOSHITAKA MINAMI, YUJI TAKAHASHI, TSUYOSHI TABUCHI, MOTOYUKI NAKAMURA Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine Recently, microRNAs (miRs) have been discovered and regulated protein expression at the post transcription level. MiR-208, a cardiac-specific microRNA encoded by the a-myosin heavy chain (MHC) gene, is required for cardiac fibrosis and up-regulation of b-MHC expression. The purpose of this study was to determine whether miR-208 was expressed in myocardium of dilated cardiomyopathy (DCM). Endomyocardial biopsy tissues were obtained from 56 patients with DCM and 21 subjects without left ventricular (LV) dysfunction (control). Levels of miR-208, a- and b-MHC mRNAs were measured by real-time RT-PCR. Levels of miR-208 were higher in DCM patients than in controls (0.94 6 0.39 vs. 0.21 6 0.09, P ! 0.001). a-MHC levels were lower in DCM patients than in controls (P ! 0.001), whereas b-MHC levels were higher in DCM patients comparing with controls (P 5 0.03). There was negative correlation between miR-208 and a-MHC levels in DCM patients (r 5 -0.65, P ! 0.001). Levels of miR-208 were positively correlated with b-MHC levels and myocardial collagen volume. Levels of miR-208 were correlated with LV systolic function (r 5 -0.52, P ! 0.001) and LV volume (r 5 0.54, P ! 0.001) in DCM patients. This study has shown that increased myocardial expression of miR-208 is associated with MHC mRNA expression, and thus may be involved in the pathogenesis of human DCM.
024 A Case of Exercise-induced Ventricular Tachycardia After Left Ventricular Functional Improvement by Successful PCI RYO ARAKI, YOSHIKI NODA, TAKAHIRO IMANAKA, RYO MATSUTERA, TATSUYA SASAKI The cardiovascular divison, National Organization, Osaka Minami Medical Center, Osaka, Japan A 74-year-old man presented with abnormal Q wave in leads V1-4 in electrocardiography. Echocardiography showed left ventricular asynergy in anteroseptum and inferior, reduced LV funtion (EF 35% by modified Simpson), and two false tendons which were about 10 mm in width and ranged from basal anterior to apical lateral and apical septum in left ventricle. Ergometer stress myocardial scintigraphy showed redistribution in anteroseptum and inferior without symptom and significant ECG change. PCI was performed for proximal RCA and proximal LAD. Six months later, ventricular tachycardia (VT) occurred during follow-up ergometer stress myocardial scintigraphy. PCI was performed since CAG showed progression of stenosis at RCA ostium. However, VT occurred again during treadmill stress electrocardiography one month later. CAG showed no significant stenosis. Ejection fraction by modified Simpson was improved from 35% to 45%. Because it was thought that VT was caused by not ischemia but false tendons, ablation was applied to the attached part of false tendons in basal anterior in National Cardiovascular Center. VT did not occur during treadmill stress electrocardiography 4 days and 3 months after ablation. In this case, it was thought that exercise-induced VT by false tendons was caused because left ventricular function was improved by PCI. Similar cases have not been reported as far as we know and may be novel aspects of management to hybernative myocardium.
025 Noninvasive Evaluation of Left Ventricular Afterload Would Provide the Optimal Therapeutic Strategy in Patients With Acute Decompensated Heart Failure MASATAKA WATANABE, KAZUHIKO HASHIMURA, HIROYUKI TAKAHAMA, MAKOTO AMAKI, TAKAHIRO OHARA, TAKUYA