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Recent Advances of Nuclear Cardiology in Heart Failure
S12 Journal of Cardiac Failure Vol. 23 No. 10S October 2017 SY12-1 Role of Echocardiographic Strain Imaging for Patients With Heart Failure Hidekazu Tanaka; Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan The risk stratification of patients with heart failure (HF) can be performed using echocardiographic parameters such as left ventricular (LV) ejection fraction (LVEF). Since LVEF reflects merely the change in LV volume but does not take into consideration ultrastructural changes that may occur at the myocardial level and that may impair LV systolic performance. Thus, LVEF may not truly represent LV systolic function in specific cardiac diseases or when subtle LV systolic dysfunction is present. Twodimensional speckle-tracking is a post-processing computer algorithm that uses the routine grayscale digital images, and enables assessment of myocardial strain, thereby providing detailed information on global and regional active LV deformation. Global longitudinal strain (GLS), which was defined as the average peak strain of 18 segments from standard apical views, provides the best evidence on the diagnostic and prognostic implications, and the ability of GLS to predict cardiovascular outcome may be superior to LVEF. This presentation reviews the strengths of echocardiographic speckletracking strain imaging, especially GLS, and its current potential for clinical use in patients with HF.
SY12-3 MDCT Is Useful for Comprehensive Evaluation of Organic Heart Diseases in Patients With Heart Failure Nobusada Funabashi, Hiroyuki Takaoka, Yoshio Kobayashi; The Department of Cardiology, Chiba University Hospital, Chiba, Japan Background: According to the ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/ SCMR guidelines (Circulation 2010;122:e525–55), using cardiac CT to evaluate cardiac function in subjects with heart failure is appropriate only when insufficient data are acquired by transthoracic echocardiogram and cardiac magnetic resonance. Methods and Results: In addition to its utility for evaluating cardiac function, MDCT is useful for the comprehensive evaluation of organic heart diseases in patients with heart failure. MDCT can be used for assessing the coronary arteries and myocardium to determine shunt flow, abnormal anatomy, and their spatial relationships to other organs. To date, we have reported 16 cases where MDCT was used for suspected heart failure involving organic heart diseases. The cases included 1) supracardiac type 1a total anomalous pulmonary venous return with a right-to-left shunt atrial septal defect; 2) giant pulmonary trunk with Eisenmenger-flow through the patent ductus arteriosus; 3) massive myocardial aneurysm due to an inferior-to-posterior myocardial infarction complicated by right-sided heart failure; 4) idiopathic diverticulum-type enlargement of the right atrium; 5) double-outlet right ventricle; and 6) noncompaction-like remodeling of the right ventricle in a middle-aged subject with modified transposition of the great arteries. Furthermore, we present a three-dimensional CT strain analysis to evaluate left ventricular myocardial characteristics and function using existing volumetric CT data. Conclusion: Cardiac MDCT is useful for evaluating organic heart diseases in patients with heart failure.
SY12-4 Recent Advances of Nuclear Cardiology in Heart Failure Shinro Matsuo1, Kenichi Nakajima2, Masakazu Yamagishi3; 1Nuclear Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan; 2Nuclear Medicine, Kanazawa University, Kanazawa, Japan; 3Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan Nuclear cardiology tests play a pivotal role in the assessment and management of the patients with heart failure. Non-invasive insights into pathophysiology, prognosis can be obtained by quantitative gated single positron emission computed tomography (QGS). Resting and stress myocardial perfusion imaging, with exercise or pharmacologic stress, plays a fundamental role in distinguishing ischemic from non-ischemic etiology of heart failure, and in demonstrating myocardial viability. Diastolic heart failure also termed as heart failure with a preserved left ventricular ejection fraction is readily identified by nuclear cardiology techniques. Newer techniques such as three-dimensional, wall thickening and cardiac dyssynchrony evaluation aid its assessment. Myocardial perfusion imaging, including phase analysis is also used to identify candidates for implantable cardiac defibrillator and cardiac resynchronization therapies. Neurotransmitter imaging using 123I-metaiodobenzylguanidine offers prognostic information in patients with heart failure. By adding MIBG heart-tomediastinum ratio to BNP, ROC curve AUC significantly increased from 0.756 to 0.779 in our prognostic study of patients with heart failure. MIBG HMR was usefull for risk stratification. Cardiac metabolic imaging using 123I-BMIPP is a commonly used tracer in clinical studies to diagnose metabolic heart failure. Nuclear cardiology tests, including neurotransmitter imaging and metabolic imaging, are now easily preformed with new tracers to refine heart failure diagnosis. Nuclear cardiology
studies contribute significantly to guiding management decisions for identifying cardiac risk in patients with heart failure.
SY13-2 Tyrosine Kinase Fyn Is a Novel Regulator of NADPH Oxidase 4 in Cardiac Remodeling Shouji Matsushima 1 , Junichi Sadoshima 2 , Hiroyuki Tsutsui 3 ; 1 Department of Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan; 2Department of Cardiovascular Medicine, Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey; 3Kyushu University Graduate School of Medical Science, Fukuoka, Japan NADPH oxidase 4 (Nox4) is a major sources of reactive oxygen species (ROS) in the heart and plays a crucial role in the regulation of growth and death in cardiomyocytes. Cardiac hypertrophy and dysfunction in response to pressure overload (PO) were significantly attenuated in cardiac-specific Nox4 knockout (KO) mice, and those were accompanied by preservation of mitochondrial function. Recently, we elucidated the modulation of Nox4 through post-translational mechanisms. Yeast twohybrid screening and in vitro binding assay demonstrated that Fyn, a Src family tyrosine kinase, directly interacted with Nox4. Nox4 and Fyn were co-localized in mitochondria in cardiomyocytes. Downregulation of Fyn enhanced Nox4-induced mitochondrial O2− production and apoptosis in cardiomyocytes. Fyn was activated by overexpression of Nox4. In vitro kinase assay and mass spectrometry analysis showed that Fyn directly phosphorylated tyrosine-566 of Nox4. Fyn KO mice showed exacerbated LV remodeling in response to PO compared with wild-type mice, accompanied by increases in O2− production in mitochondria and apoptosis in the heart. Deletion of Nox4 attenuated this LV remodeling in Fyn KO mice. Expression levels of Fyn and Nox4 phosphorylated at tyrosine-566 in human failing hearts were significantly decreased compared with control subjects. Fyn negatively regulates cell death as a sensor and regulator of Nox4-derived ROS in failing hearts. Fyn-Nox4 axis is a potential therapeutic target for heart failure.
SY15-1 Diagnosis of Secondary Cardiomyopathy According to Endomyocardial Cardiac Biopsy Kazufumi Nakamura, Tomonari Kimura, Hiroshi Ito; Department of Cardiovascular Medicine, Okayama University, Okayama, Japan 1. Diseases with cardiac dilatation: Chronic myocarditis and cardiac sarcoidosis are diseases similar to dilated cardiomyopathy (DCM). The diagnosis of these diseases is often difficult. · Chronic myocarditis begins in a latent fashion, but then becomes chronic. Histological findings are characterized by mononuclear cell infiltrates. · Endomyocardial biopsy (EMB) has a low sensitivity in diagnosing cardiac sarcoidosis. The use of CARTO system may be able to improve the diagnostic yield of EMB. 2. Diseases with cardiac hypertrophy: · EMB is helpful to distinguish lysosomal diseases (Fabry disease and glycogen storage disease), mitochondrial diseases and cardiac amyloidosis from hypertrophic cardiomyopathy. · Vacuolization in samples of EMB is a finding suggestive of lysosomal and mitochondrial diseases. Enzyme replacement therapy is used for the treatment of Fabry disease and Pomp disease. · As for diagnosis of cardiac amyloidosis, it is important to classify the type of amyloidosis. Drug therapy using tafamidis is considered for treatment of hereditary ATTTR amyloidosis.
SY15-2 Approach to Diagnosis of Secondary Cardiomyopathies With Left Ventricular Hypertrophy Masuteru Nakashima, Toru Kubo, Tatsuya Noguchi, Naohiro Yamasaki, Hiroaki Kitaoka; Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi, Japan Left ventricular hypertrophy (LVH) is often encountered cardiac disorder with heterogeneous clinical presentation and course. Although unexplained LVH is the hallmark of hypertrophic cardiomyopathy, differential diagnosis of secondary cardiomyopathies with LVH has been needed. Because, disease-oriented treatments have made progress. For example, the enzyme replacement therapy for Anderson-Fabry disease promises the modification of natural course of disease. In the first half of this presentation, we will overview the clinical significance of diagnostic procedures such as medical history, physical examination, laboratory data, electrocardiography, echocardiography, cardiac magnetic resonance, and cardiac catheterization including endomyocardial biopsy, in secondary cardiomyopathies with LVH. Particularly, we have been reported the clinical utility of biomarkers in differential diagnosis and risk assessment in cardiomyopathies with LVH from the regional cardiomyopathy registry named Kochi Cardiomyopathy Network. In the second half of this presentation, we will suggest the new strategy of differential diagnosis of secondary cardiomyopathies with LVH.
SY12-3 MDCT Is Useful for Comprehensive Evaluation of Organic Heart Diseases in Patients With Heart Failure Nobusada Funabashi, Hiroyuki Takaoka, Yoshio Kobayashi; The Department of Cardiology, Chiba University Hospital, Chiba, Japan Background: According to the ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/ SCMR guidelines (Circulation 2010;122:e525–55), using cardiac CT to evaluate cardiac function in subjects with heart failure is appropriate only when insufficient data are acquired by transthoracic echocardiogram and cardiac magnetic resonance. Methods and Results: In addition to its utility for evaluating cardiac function, MDCT is useful for the comprehensive evaluation of organic heart diseases in patients with heart failure. MDCT can be used for assessing the coronary arteries and myocardium to determine shunt flow, abnormal anatomy, and their spatial relationships to other organs. To date, we have reported 16 cases where MDCT was used for suspected heart failure involving organic heart diseases. The cases included 1) supracardiac type 1a total anomalous pulmonary venous return with a right-to-left shunt atrial septal defect; 2) giant pulmonary trunk with Eisenmenger-flow through the patent ductus arteriosus; 3) massive myocardial aneurysm due to an inferior-to-posterior myocardial infarction complicated by right-sided heart failure; 4) idiopathic diverticulum-type enlargement of the right atrium; 5) double-outlet right ventricle; and 6) noncompaction-like remodeling of the right ventricle in a middle-aged subject with modified transposition of the great arteries. Furthermore, we present a three-dimensional CT strain analysis to evaluate left ventricular myocardial characteristics and function using existing volumetric CT data. Conclusion: Cardiac MDCT is useful for evaluating organic heart diseases in patients with heart failure.
SY12-4 Recent Advances of Nuclear Cardiology in Heart Failure Shinro Matsuo1, Kenichi Nakajima2, Masakazu Yamagishi3; 1Nuclear Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan; 2Nuclear Medicine, Kanazawa University, Kanazawa, Japan; 3Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan Nuclear cardiology tests play a pivotal role in the assessment and management of the patients with heart failure. Non-invasive insights into pathophysiology, prognosis can be obtained by quantitative gated single positron emission computed tomography (QGS). Resting and stress myocardial perfusion imaging, with exercise or pharmacologic stress, plays a fundamental role in distinguishing ischemic from non-ischemic etiology of heart failure, and in demonstrating myocardial viability. Diastolic heart failure also termed as heart failure with a preserved left ventricular ejection fraction is readily identified by nuclear cardiology techniques. Newer techniques such as three-dimensional, wall thickening and cardiac dyssynchrony evaluation aid its assessment. Myocardial perfusion imaging, including phase analysis is also used to identify candidates for implantable cardiac defibrillator and cardiac resynchronization therapies. Neurotransmitter imaging using 123I-metaiodobenzylguanidine offers prognostic information in patients with heart failure. By adding MIBG heart-tomediastinum ratio to BNP, ROC curve AUC significantly increased from 0.756 to 0.779 in our prognostic study of patients with heart failure. MIBG HMR was usefull for risk stratification. Cardiac metabolic imaging using 123I-BMIPP is a commonly used tracer in clinical studies to diagnose metabolic heart failure. Nuclear cardiology tests, including neurotransmitter imaging and metabolic imaging, are now easily preformed with new tracers to refine heart failure diagnosis. Nuclear cardiology
studies contribute significantly to guiding management decisions for identifying cardiac risk in patients with heart failure.
SY13-2 Tyrosine Kinase Fyn Is a Novel Regulator of NADPH Oxidase 4 in Cardiac Remodeling Shouji Matsushima 1 , Junichi Sadoshima 2 , Hiroyuki Tsutsui 3 ; 1 Department of Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan; 2Department of Cardiovascular Medicine, Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, New Jersey; 3Kyushu University Graduate School of Medical Science, Fukuoka, Japan NADPH oxidase 4 (Nox4) is a major sources of reactive oxygen species (ROS) in the heart and plays a crucial role in the regulation of growth and death in cardiomyocytes. Cardiac hypertrophy and dysfunction in response to pressure overload (PO) were significantly attenuated in cardiac-specific Nox4 knockout (KO) mice, and those were accompanied by preservation of mitochondrial function. Recently, we elucidated the modulation of Nox4 through post-translational mechanisms. Yeast twohybrid screening and in vitro binding assay demonstrated that Fyn, a Src family tyrosine kinase, directly interacted with Nox4. Nox4 and Fyn were co-localized in mitochondria in cardiomyocytes. Downregulation of Fyn enhanced Nox4-induced mitochondrial O2− production and apoptosis in cardiomyocytes. Fyn was activated by overexpression of Nox4. In vitro kinase assay and mass spectrometry analysis showed that Fyn directly phosphorylated tyrosine-566 of Nox4. Fyn KO mice showed exacerbated LV remodeling in response to PO compared with wild-type mice, accompanied by increases in O2− production in mitochondria and apoptosis in the heart. Deletion of Nox4 attenuated this LV remodeling in Fyn KO mice. Expression levels of Fyn and Nox4 phosphorylated at tyrosine-566 in human failing hearts were significantly decreased compared with control subjects. Fyn negatively regulates cell death as a sensor and regulator of Nox4-derived ROS in failing hearts. Fyn-Nox4 axis is a potential therapeutic target for heart failure.
SY15-1 Diagnosis of Secondary Cardiomyopathy According to Endomyocardial Cardiac Biopsy Kazufumi Nakamura, Tomonari Kimura, Hiroshi Ito; Department of Cardiovascular Medicine, Okayama University, Okayama, Japan 1. Diseases with cardiac dilatation: Chronic myocarditis and cardiac sarcoidosis are diseases similar to dilated cardiomyopathy (DCM). The diagnosis of these diseases is often difficult. · Chronic myocarditis begins in a latent fashion, but then becomes chronic. Histological findings are characterized by mononuclear cell infiltrates. · Endomyocardial biopsy (EMB) has a low sensitivity in diagnosing cardiac sarcoidosis. The use of CARTO system may be able to improve the diagnostic yield of EMB. 2. Diseases with cardiac hypertrophy: · EMB is helpful to distinguish lysosomal diseases (Fabry disease and glycogen storage disease), mitochondrial diseases and cardiac amyloidosis from hypertrophic cardiomyopathy. · Vacuolization in samples of EMB is a finding suggestive of lysosomal and mitochondrial diseases. Enzyme replacement therapy is used for the treatment of Fabry disease and Pomp disease. · As for diagnosis of cardiac amyloidosis, it is important to classify the type of amyloidosis. Drug therapy using tafamidis is considered for treatment of hereditary ATTTR amyloidosis.
SY15-2 Approach to Diagnosis of Secondary Cardiomyopathies With Left Ventricular Hypertrophy Masuteru Nakashima, Toru Kubo, Tatsuya Noguchi, Naohiro Yamasaki, Hiroaki Kitaoka; Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University, Kochi, Japan Left ventricular hypertrophy (LVH) is often encountered cardiac disorder with heterogeneous clinical presentation and course. Although unexplained LVH is the hallmark of hypertrophic cardiomyopathy, differential diagnosis of secondary cardiomyopathies with LVH has been needed. Because, disease-oriented treatments have made progress. For example, the enzyme replacement therapy for Anderson-Fabry disease promises the modification of natural course of disease. In the first half of this presentation, we will overview the clinical significance of diagnostic procedures such as medical history, physical examination, laboratory data, electrocardiography, echocardiography, cardiac magnetic resonance, and cardiac catheterization including endomyocardial biopsy, in secondary cardiomyopathies with LVH. Particularly, we have been reported the clinical utility of biomarkers in differential diagnosis and risk assessment in cardiomyopathies with LVH from the regional cardiomyopathy registry named Kochi Cardiomyopathy Network. In the second half of this presentation, we will suggest the new strategy of differential diagnosis of secondary cardiomyopathies with LVH.