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Clinical Characteristics of Hospitalized Patients with Dilated Cardiomyopathy: Results from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)
The 11th Annual Scientific Meeting
JHFS
S15
Symposium 10 S10-1 Cardiomyopathies and Myocarditis AKIRA MATSUMORI Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
S10-4 Cardiac Fabry Disease: Diagnosis, Clinical Manifestations and Management TOSHIHIRO TAKENAKA Division of Cardiac Repair and Regeneration, Kagoshima University, Kagoshima, Japan
Cardiomyopathies and myocarditis are major causes of heart failure death worldwide. The roles of viruses, immunity, cytokines and genetics as sources of cardiomyopathies have been relatively understated in the rapidly developing world of clinical cardiology. We have demonstrated that hepatitis C virus (HCV) is one of the main viral sources of human cardiomyopathies, and HCV causes different phenotypes of cardiomyopathies. NT-proBNP was elevated in high percentage of patients with myocarditis and heart failure, and of asymptomatic individuals infected with HCV suggesting that HCV causes frequently myocardial injury. Recent our work have shown that autoantibodies against cardiac troponin I were detected in patients with myocarditis, and their titers were high in patients with HCV infection. We have also shown that immunoglobulin free light chains are new biomarkers of heart failure, and that they may be useful for differentiating diastolic and systolic heart failure due to cardiomyopathies. These observations introduce a new concept in which inflammation provides a functional link between immune activation and development of cardiomyopathies and heart failure, and points to new investigations directed toward their pathogenesis and treatment.
Fabry disease is an X-linked lysosomal storage disorder resulting from a deficiency of a-galactosidase A. This enzymatic defect leads to the progressive accumulation of glycosphingolipids in all organs including the heart. Various cardiac manifestations such as left ventricular hypertrophy (LVH), valvular involvement, ischemic heart disease and arrhythmias have been reported. On the other hand, cardiac variant of Fabry disease, with manifestations limited to the heart, has been reported. Cardiac Fabry disease has been detected with several percent incidence rates in male patients with unexplained LVH among different ethnic population. In the initial-stage of the disease, concentric LVH with diastolic dysfunction is seen in most of the patients. ECG abnormalities including arrhythmias can be also seen. As the disease progresses, patients begin to suffer from congestive heart failure owing not only to LV diastolic dysfunction but also to systolic dysfunction. Fatal arrhythmias also develop in the end-stage of the disease. Enzyme replacement therapy as a specific therapy for the disease is now available and first studies have shown their efficacy to cardiac lesions. Thus, cardiac Fabry disease should be considered in the differential diagnosis of patients with unexplained LVH.
S10-2
S10-5
Genomic Analysis of Cardiomyopathies HIROYUKI MORITA Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan
Recent Advancement of Transthoracic Doppler Echocardiography in Noninvasive Assessment of Cardiac Function and Coronary Circulation in Cardiomyopathies TAKESHI HOZUMI1, KENICHI SUGIOKA1, HIROKI OE1, YOSHIKI MATSUMURA1, KOTARO ARAI1, KEITARO OGAWA1, SHINICHI IWATA1, RYO OTSUKA1, YASUHIKO TAKEMOTO1, MINORU YOSHIYAMA1, JUNICHI YOSHIKAWA2 1 Osaka City University Medical School, Osaka, Japan, 2Ekisaikai Hospital, Osaka, Japan
A plenty of gene mutations causing cardiomyopathies have been identified and their relationship with the clinical outcomes is being discussed. At least in hypertrophic cardiomyopathy (HCM), genomic analysis of sarcomere protein gene mutations could convince us of the diagnosis of the disease. The variety of sarcomere protein gene mutations can partly explain the great diversity of clinical manifestation of HCM. Even in HCM, however, there remain some limitations that retard practical application of genetic diagnosis. For example, the same mutation could not necessarily induce the same clinical manifestation. The gene-environment interactions and/or genetic modifiers should be further examined. In dilated cardiomyopathy (DCM), the number of causing gene mutations identified to date remains limited and many more will undoubtedly defied, however, the current repertoire of mutations suggest a multiplicity of pathways by which the heart can fail. Further genomic analysis of DCM will show us a variety of pathways. The identification of the critical nodal points in these pathways is expected to provide new opportunities for the targeting of drug therapy and/or gene therapy. In this presentation, significance and limitations of genomic analysis in cardiomyopathies will be discussed.
S10-3 Potential Role of AT1 Receptor Blocker in Treatment of Cardiomyopathy SHOKEI MITSUYAMA Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan Cardiomyopathy is one of the causative diseases of heart failure. Regardless of the cause of heart failure, heart failure is generally characterized by not only hemodynamic disorder but also the activation of neurohormonal factors. Particularly, the activation of renin-angiotensin system and sympathetic nervous system play a major role in the pathophysiology of heart failure, which is confirmed by various clinical evidence. Thus, blockers of renin-angiotesnin system such as ACE inhibitors and AT1 receptor blockers (ARB), and b-blockers, are the useful agents for treatment of heart failure caused by cardiomyopathy as well as other cardiac diseases. ARB is known to have differential pharmacological effects from ACE inhibitors. Accumulating experimental evidence indicates that ARB improve cardiac systolic and diastolic dysfunction in heart failure, mainly by ameliorating cardiac hypertrophy and remodeling. Furthermore, ARB exert multiple pleiotropic cardiac effects, including the inhibition of reactive oxygen species by suppressing NADPH oxidase, xanthine oxidase, and eNOS uncoupling, the inhibiton of inflammation, and the increase in NO bioavailability etc. However, in terms of treatment of heart failure, the potential difference between ARB and ACE inhibitors remains to be elucidated.
Recent tranthoracic Doppler echocardiography (TTDE) enables us to assess global and segmental cardiac function by real-time three-dimensional (RT-3D) method and several strain techniques, and coronary circulation by coronary flow imaging in caridomyopathies. (1) Hypertrophic cardiomyopathy (HCM): Accurate left ventricular mass can be assessed without any hypothesis by RT-3D echocardiography in HCM patients. Left ventricular (LV) segmental analysis can be evaluated by tissue Doppler or tissue tracking techniques. Characteristic coronary flow velocity waveform and decreased CFR are obtained by coronary flow imaging in HCM patients. (2) Dilated cardiomyopathy (DCM): LVEF can be accurately evaluated by RT-3D echocardiography. Segmental LV analysis by RT-3D or strain techniques may be used for the follow-up of LV dyssynrchony in DCM patients. Impaired CFR is obtained by coronary flow imaging in DCM patients before beta-blocker therapy. Early change in CFR after treatment with beta-blocker is associated with subsequent improvement in LV ejection fraction (LVEF), suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with DCM. Thus, recent echocardiographic techniques including RT-3D method, LV strain analysis, and coronary flow imaging can be used for noninvasive assessment of cardiac function and coronary circulation in HCM and DCM patients.
S10-6 Clinical Characteristics of Hospitalized Patients with Dilated Cardiomyopathy: Results from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) HIROYUKI TSUTSUI1, MIYUKI MAKAYA2, SHINTARO KINUGAWA1, AKIRA TAKESHITA3 1 Hokkaido University Graduate School of Medicine, Sapporo, Japan, 2International Medical Center of Japan, Tokyo, Japan, 3Aso Iizuka Hospital, Iizuka, Japan The characteristics and outcome of patients with idiopathic dilated cardiomyopathy have been described by a number of previous epidemiological studies and large scale clinical trials, which have been performed mainly in the United States and Europe. However, very little information is available on this issue in Japan. JCARE-CARD is designed to study prospectively the characteristics, treatment, and outcomes in
S16 Journal of Cardiac Failure Vol. 13 No. 6 Suppl. 2007 a broad sample of patients hospitalized with heart failure (HF) at teaching hospitals throughout Japan between January 2004 to June 2005 and the outcomes will be followed through 2006 (mean follow-up at least 1 year). As of June 2005, baseline data on 2676 patients with HF have been registered from 169 participating hospitals. Ischemic heart disease was the leading etiology of HF (32%) and dilated cardiomyopathy was identified as the cause of HF in 18% of patients. Compared to ischemic etiology, the patients with dilated cardiomyopathy were younger and had less comorbid factors including hypertension, diabetes, hyperlipidemia, and stroke, but higher prevalence of atrial fibrillation. The JCARE-CARD will provide important insights into patients with HF due to dilated cardiomyopathy in routine clinical practice in Japan.
JHFS
S15
Symposium 10 S10-1 Cardiomyopathies and Myocarditis AKIRA MATSUMORI Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
S10-4 Cardiac Fabry Disease: Diagnosis, Clinical Manifestations and Management TOSHIHIRO TAKENAKA Division of Cardiac Repair and Regeneration, Kagoshima University, Kagoshima, Japan
Cardiomyopathies and myocarditis are major causes of heart failure death worldwide. The roles of viruses, immunity, cytokines and genetics as sources of cardiomyopathies have been relatively understated in the rapidly developing world of clinical cardiology. We have demonstrated that hepatitis C virus (HCV) is one of the main viral sources of human cardiomyopathies, and HCV causes different phenotypes of cardiomyopathies. NT-proBNP was elevated in high percentage of patients with myocarditis and heart failure, and of asymptomatic individuals infected with HCV suggesting that HCV causes frequently myocardial injury. Recent our work have shown that autoantibodies against cardiac troponin I were detected in patients with myocarditis, and their titers were high in patients with HCV infection. We have also shown that immunoglobulin free light chains are new biomarkers of heart failure, and that they may be useful for differentiating diastolic and systolic heart failure due to cardiomyopathies. These observations introduce a new concept in which inflammation provides a functional link between immune activation and development of cardiomyopathies and heart failure, and points to new investigations directed toward their pathogenesis and treatment.
Fabry disease is an X-linked lysosomal storage disorder resulting from a deficiency of a-galactosidase A. This enzymatic defect leads to the progressive accumulation of glycosphingolipids in all organs including the heart. Various cardiac manifestations such as left ventricular hypertrophy (LVH), valvular involvement, ischemic heart disease and arrhythmias have been reported. On the other hand, cardiac variant of Fabry disease, with manifestations limited to the heart, has been reported. Cardiac Fabry disease has been detected with several percent incidence rates in male patients with unexplained LVH among different ethnic population. In the initial-stage of the disease, concentric LVH with diastolic dysfunction is seen in most of the patients. ECG abnormalities including arrhythmias can be also seen. As the disease progresses, patients begin to suffer from congestive heart failure owing not only to LV diastolic dysfunction but also to systolic dysfunction. Fatal arrhythmias also develop in the end-stage of the disease. Enzyme replacement therapy as a specific therapy for the disease is now available and first studies have shown their efficacy to cardiac lesions. Thus, cardiac Fabry disease should be considered in the differential diagnosis of patients with unexplained LVH.
S10-2
S10-5
Genomic Analysis of Cardiomyopathies HIROYUKI MORITA Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan
Recent Advancement of Transthoracic Doppler Echocardiography in Noninvasive Assessment of Cardiac Function and Coronary Circulation in Cardiomyopathies TAKESHI HOZUMI1, KENICHI SUGIOKA1, HIROKI OE1, YOSHIKI MATSUMURA1, KOTARO ARAI1, KEITARO OGAWA1, SHINICHI IWATA1, RYO OTSUKA1, YASUHIKO TAKEMOTO1, MINORU YOSHIYAMA1, JUNICHI YOSHIKAWA2 1 Osaka City University Medical School, Osaka, Japan, 2Ekisaikai Hospital, Osaka, Japan
A plenty of gene mutations causing cardiomyopathies have been identified and their relationship with the clinical outcomes is being discussed. At least in hypertrophic cardiomyopathy (HCM), genomic analysis of sarcomere protein gene mutations could convince us of the diagnosis of the disease. The variety of sarcomere protein gene mutations can partly explain the great diversity of clinical manifestation of HCM. Even in HCM, however, there remain some limitations that retard practical application of genetic diagnosis. For example, the same mutation could not necessarily induce the same clinical manifestation. The gene-environment interactions and/or genetic modifiers should be further examined. In dilated cardiomyopathy (DCM), the number of causing gene mutations identified to date remains limited and many more will undoubtedly defied, however, the current repertoire of mutations suggest a multiplicity of pathways by which the heart can fail. Further genomic analysis of DCM will show us a variety of pathways. The identification of the critical nodal points in these pathways is expected to provide new opportunities for the targeting of drug therapy and/or gene therapy. In this presentation, significance and limitations of genomic analysis in cardiomyopathies will be discussed.
S10-3 Potential Role of AT1 Receptor Blocker in Treatment of Cardiomyopathy SHOKEI MITSUYAMA Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan Cardiomyopathy is one of the causative diseases of heart failure. Regardless of the cause of heart failure, heart failure is generally characterized by not only hemodynamic disorder but also the activation of neurohormonal factors. Particularly, the activation of renin-angiotensin system and sympathetic nervous system play a major role in the pathophysiology of heart failure, which is confirmed by various clinical evidence. Thus, blockers of renin-angiotesnin system such as ACE inhibitors and AT1 receptor blockers (ARB), and b-blockers, are the useful agents for treatment of heart failure caused by cardiomyopathy as well as other cardiac diseases. ARB is known to have differential pharmacological effects from ACE inhibitors. Accumulating experimental evidence indicates that ARB improve cardiac systolic and diastolic dysfunction in heart failure, mainly by ameliorating cardiac hypertrophy and remodeling. Furthermore, ARB exert multiple pleiotropic cardiac effects, including the inhibition of reactive oxygen species by suppressing NADPH oxidase, xanthine oxidase, and eNOS uncoupling, the inhibiton of inflammation, and the increase in NO bioavailability etc. However, in terms of treatment of heart failure, the potential difference between ARB and ACE inhibitors remains to be elucidated.
Recent tranthoracic Doppler echocardiography (TTDE) enables us to assess global and segmental cardiac function by real-time three-dimensional (RT-3D) method and several strain techniques, and coronary circulation by coronary flow imaging in caridomyopathies. (1) Hypertrophic cardiomyopathy (HCM): Accurate left ventricular mass can be assessed without any hypothesis by RT-3D echocardiography in HCM patients. Left ventricular (LV) segmental analysis can be evaluated by tissue Doppler or tissue tracking techniques. Characteristic coronary flow velocity waveform and decreased CFR are obtained by coronary flow imaging in HCM patients. (2) Dilated cardiomyopathy (DCM): LVEF can be accurately evaluated by RT-3D echocardiography. Segmental LV analysis by RT-3D or strain techniques may be used for the follow-up of LV dyssynrchony in DCM patients. Impaired CFR is obtained by coronary flow imaging in DCM patients before beta-blocker therapy. Early change in CFR after treatment with beta-blocker is associated with subsequent improvement in LV ejection fraction (LVEF), suggesting the potential predictive value of coronary circulation for subsequent LV reverse remodeling after beta-blocker therapy in patients with DCM. Thus, recent echocardiographic techniques including RT-3D method, LV strain analysis, and coronary flow imaging can be used for noninvasive assessment of cardiac function and coronary circulation in HCM and DCM patients.
S10-6 Clinical Characteristics of Hospitalized Patients with Dilated Cardiomyopathy: Results from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) HIROYUKI TSUTSUI1, MIYUKI MAKAYA2, SHINTARO KINUGAWA1, AKIRA TAKESHITA3 1 Hokkaido University Graduate School of Medicine, Sapporo, Japan, 2International Medical Center of Japan, Tokyo, Japan, 3Aso Iizuka Hospital, Iizuka, Japan The characteristics and outcome of patients with idiopathic dilated cardiomyopathy have been described by a number of previous epidemiological studies and large scale clinical trials, which have been performed mainly in the United States and Europe. However, very little information is available on this issue in Japan. JCARE-CARD is designed to study prospectively the characteristics, treatment, and outcomes in
S16 Journal of Cardiac Failure Vol. 13 No. 6 Suppl. 2007 a broad sample of patients hospitalized with heart failure (HF) at teaching hospitals throughout Japan between January 2004 to June 2005 and the outcomes will be followed through 2006 (mean follow-up at least 1 year). As of June 2005, baseline data on 2676 patients with HF have been registered from 169 participating hospitals. Ischemic heart disease was the leading etiology of HF (32%) and dilated cardiomyopathy was identified as the cause of HF in 18% of patients. Compared to ischemic etiology, the patients with dilated cardiomyopathy were younger and had less comorbid factors including hypertension, diabetes, hyperlipidemia, and stroke, but higher prevalence of atrial fibrillation. The JCARE-CARD will provide important insights into patients with HF due to dilated cardiomyopathy in routine clinical practice in Japan.