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Biomarkers for Early Diagnosis of Heart Failure
The 16th Annual Scientific Meeting
JHFS
S137
Symposium 9 S9-1 Physical Examination/Electrocardiogram SHIGERU TOYODA, TERUO INOUE The Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan Patients with heart failure have recently increased gradually and will continue to increase also in future, accompanied with upcoming aging society. It is very important to diagnose early the onset of heart failure. Since heart failure patients often adapt their symptoms, we often fail to interview a subtle change of their symptom. For early diagnosis of heart failure, it is important to “see carefully”,“hear carefully”, and “say carefully”(although there is a proverb “see no evil”, “hear no evil” and “say no evil” in Japan). We should observe patients and patients’ findings carefully. We should listen to patients’ complaints and patients’ heart sounds carefully. We should talk to patients and get information from patients carefully. Early symptoms of heart failure include dyspnea on effort, general fatigue, edema (weight gain), etc. Physical findings of early heart failure include carotid venous dilatation, third heart sound, crackles, etc. When we assess patients’ electrocardiogram, it is important to compare it with previous one. If we cannot get the previous electrocardiogram, we should carefully observe ischemic changes, arrhythmia, etc. In this symposium, we overview previous reports regarding early diagnosis of heart failure, introduce several cases who were admitted to our hospital and discuss their symptoms, physical findings, and electrocardiographic findings.
S9-2 The Echocardiographic Assessment of Subclinical Left Ventricular Dysfunction TOMOKO ISHIZU1, YOSHIHIRO SEO2, YURI KAMEDA3, TAIZO KIMURA2, DONGZHU XU2, NOBUYUKI MURAKOSHI2, SATOSHI SAKAI2, KAZUTAKA AONUMA2 1 Department of Clinical Laboratory, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan, 2Cardiovascular Division, Faculty of Medisine, University of Tsukuba, Ibaraki, Japan, 3Postgraduate School of Medical Sience, University of Tsukuba, Ibaraki, Japan Left ventricular (LV) longitudinal dysfunction has been proposed as the early echocardiographic marker of subclinical dysfunction in heart failure with persevered ejection fraction (HFpEF). Objective: To clarify the significance of longitudinal dysfunction on the cardiac performance and underlying pathology in HFpEF. Methods: Longitudinal strain (LS) was serially measured in Dahl salt-sensitive rat fed a high-salt (HT-group) or a low-salt diet (Control-group) by speckle tracking echocardiography (STE) (Vevo2100). At 12 and 14 weeks of age, cardiac hemodynamics was assessed by Miller conductance catheter and Transmural systolic wall stress was estimated and myocardial fiber angle, width, and %fibrosis were evaluated pathologically. Results: As blood pressure and LV mass elevated with aging in HTgroup, LS progressively decreased from early diastolic dysfunction, while LVEF did not differ throughout the study period. Sunendocardial layer showed longitudinal myocardial fiber orientation and increased wall stress, %fibrosis, and fiber width. LS significantly correlated with the subendocardial %fibrosis (r50.67, p!0.01) and subendocardial myocardial width (0.58, p50.02). After the adjustment by the wall stress, %fibrosis was revealed to be an independent determinant of LS. In hemodynamic evaluation, LS related with tau and end diastolic pressure volume relationship, but not with Emax. Conclusions: In hypertensive HFpEF, longitudinal function could be the early maker reflecting subendocardial fibrosis and chamber diastolic dysfunction.
S9-3 Diagnosis of Heart Failure by Biomarker YUKIHITO SATO Department of Cardiovascular Medicine, Hyogo Prefectural Amagasaki Hospital, Amagasaki, Japan In industrialized countries, chronic heart failure (HF) is a major illness and cause of death. However, because of the paucity of specific clinical manifestations of HF, its early diagnosis and management might be challenging. Therefore, biochemical markers of HF are now being closely scrutinized. An ideal biochemical marker should be a prognostic indicator, assist in the early diagnosis, reflect the therapeutic response, and help grading the risk associated with each stage of HF.B-type natriuretic peptide (BNP) and N-terminal proBNP provide additional information together with clinical symptoms for the diagnosis of acute HF in patients with presenting acute dyspnea. Slight elevation of these assays has recently been reported to be associated with future development of cardiovascular events in general population. On the other hand, cardiac troponin (cTn) has been reported to be independent prognostic biomarker in patients with both acute and chronic heart failure, though cTn is a first line biomarker of acute myocardial infarction. While conventional cTnT assays have often been used as a positive or negative categorical variable, stepwise rises in high
sensitivity (Hs)-cTn in patients presenting with chronic HF have been associated with a progressive increase in the incidence of cardiovascular events. Similar observations have been made in the general population. We here discuss potential use of these biomarkers.
S9-4 Biomarkers for Early Diagnosis of Heart Failure NORIHIKO KOTOOKA Department of Cardiovascular Medicine, Saga University, Saga, Japan Treatment of heart failure (HF) has usually focused on symptomatic stage, often after admission due to acute exacerbation. Early identification of asymptomatic or latent cardiac dysfunction is desirable to prevent the progression of HF. In addition to noninvasive imaging strategies, serological biomarkers such as N-terminal pro B-type natriuretic peptide (NT-proBNP), troponins, and C-reactive protein have been reported to be useful for estimate the severity and prognosis, and early detection of HF. For example, circulating cardiac troponin T (cTnT) is sensitive and specific markers of myocardial injury and elevated troponins in patients with HF may suggest ongoing myocardial damage. Although cTnT levels in patients with HF are often lower than those in patients with acute coronary syndrome, recently developed highly sensitive assay makes it possible to assess the association of cTnT levels with earlier stage of HF. Approximately half of patients with HF have a preserved left ventricular ejection fraction (HFpEF), and elevated plasma levels of natriuretic peptides is included guidelines for the diagnosis of HFpEF. Recently, biomarkers reflecting extracellular matrix synthesis and degradation have been reported to be more useful for predicting the presence of HFpEF than NT-pro BNP. I would like to discuss about biomarkers for early diagnosis of HF on the basis of these findings and our own experiments.
S9-5 Potential of Cardiac MRI for Predicting the Risk of Heart Failure KATSUYA ONISHI1,2, SHIRO NAKAMORI2, HIROSHI NAKAJIMA2, HAJIME SAKUMA3, MASAAKI ITO2 1 Onishi Heart Clinic, 2Department of Cardiology, Mie University Graduate School of Medicine, Tsu City, Japan, 3Department of Radiology, Mie University Graduate School of Medicine, Tsu City, Japan Cardiac magnetic resonance (CMR) is a noble method to evaluate cardiac function and myocardial perfusion. Quantitative analysis of myocardial perfusion MRI can provide noninvasive assessment of myocardial perfusion reserve (MPR). CMR tagging has been established as a technique for quantification of local intramyocardial motion measures, e.g. strain and strain rate using displacement encoding with stimulated echoes (DENSE). Accordingly, we evaluated whether MPR was impaired in patients with the risk for heart failure, and the possibility of DENSE CMR to detect wall motion abnormality. We studied 110 patients without regional myocardial ischemia, and 30 patients with heart failure with preserved ejection fraction (HFpEF). Adenosine triphosphate (ATP) stress and rest first-pass perfusion MR images were acquired with a 1.5-T MR system, and MPR was calculated as the ratio of stress to rest myocardial blood flow. MPR was associated with hypertension, age, e-GFR, hematocrit and left ventricular mass index. In multiple regression analysis, hypertension showed the strongest correlation with MPR among other risk factors after adjusting age and gender. In HFpEF patients, MPR is significantly decreased to compare with that in control subjects. Regional myocardial strain using DENSE CMR was well correlated to that using tissue Doppler imaging. In conclusion, detecting the impaired MPR may predict the risk of heart failure, and DENSE CMR may be useful method to detect wall motion abnormality.
S9-6 Importance of Assessing Sleep-disordered Breathing in Patients with Stage A/B Heart Failure YOSHIFUMI TAKATA, AKIRA YAMASHINA Department of Cardiology, Tokyo Medical University, Tokyo, Japan Sleep-disordered breathing (SDB) is known to increase the risk of developing various cardiovascular diseases in stages at risk for heart failure (HF). SDB also plays an important role in the onset and progression of HF. A recent observational cohort study showed that obstructive sleep apnea was associated with an increased risk of incident HF in community-dwelling middle-aged and older men. We have demonstrated that obstructive sleep apnea is significantly related with left ventricular diastolic dysfunction, left ventricular concentric hypertrophy and an increase of arterial stiffness, especially coexisting with metabolic syndrome. On the other hand, an existence of central sleep apnea or
JHFS
S137
Symposium 9 S9-1 Physical Examination/Electrocardiogram SHIGERU TOYODA, TERUO INOUE The Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan Patients with heart failure have recently increased gradually and will continue to increase also in future, accompanied with upcoming aging society. It is very important to diagnose early the onset of heart failure. Since heart failure patients often adapt their symptoms, we often fail to interview a subtle change of their symptom. For early diagnosis of heart failure, it is important to “see carefully”,“hear carefully”, and “say carefully”(although there is a proverb “see no evil”, “hear no evil” and “say no evil” in Japan). We should observe patients and patients’ findings carefully. We should listen to patients’ complaints and patients’ heart sounds carefully. We should talk to patients and get information from patients carefully. Early symptoms of heart failure include dyspnea on effort, general fatigue, edema (weight gain), etc. Physical findings of early heart failure include carotid venous dilatation, third heart sound, crackles, etc. When we assess patients’ electrocardiogram, it is important to compare it with previous one. If we cannot get the previous electrocardiogram, we should carefully observe ischemic changes, arrhythmia, etc. In this symposium, we overview previous reports regarding early diagnosis of heart failure, introduce several cases who were admitted to our hospital and discuss their symptoms, physical findings, and electrocardiographic findings.
S9-2 The Echocardiographic Assessment of Subclinical Left Ventricular Dysfunction TOMOKO ISHIZU1, YOSHIHIRO SEO2, YURI KAMEDA3, TAIZO KIMURA2, DONGZHU XU2, NOBUYUKI MURAKOSHI2, SATOSHI SAKAI2, KAZUTAKA AONUMA2 1 Department of Clinical Laboratory, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan, 2Cardiovascular Division, Faculty of Medisine, University of Tsukuba, Ibaraki, Japan, 3Postgraduate School of Medical Sience, University of Tsukuba, Ibaraki, Japan Left ventricular (LV) longitudinal dysfunction has been proposed as the early echocardiographic marker of subclinical dysfunction in heart failure with persevered ejection fraction (HFpEF). Objective: To clarify the significance of longitudinal dysfunction on the cardiac performance and underlying pathology in HFpEF. Methods: Longitudinal strain (LS) was serially measured in Dahl salt-sensitive rat fed a high-salt (HT-group) or a low-salt diet (Control-group) by speckle tracking echocardiography (STE) (Vevo2100). At 12 and 14 weeks of age, cardiac hemodynamics was assessed by Miller conductance catheter and Transmural systolic wall stress was estimated and myocardial fiber angle, width, and %fibrosis were evaluated pathologically. Results: As blood pressure and LV mass elevated with aging in HTgroup, LS progressively decreased from early diastolic dysfunction, while LVEF did not differ throughout the study period. Sunendocardial layer showed longitudinal myocardial fiber orientation and increased wall stress, %fibrosis, and fiber width. LS significantly correlated with the subendocardial %fibrosis (r50.67, p!0.01) and subendocardial myocardial width (0.58, p50.02). After the adjustment by the wall stress, %fibrosis was revealed to be an independent determinant of LS. In hemodynamic evaluation, LS related with tau and end diastolic pressure volume relationship, but not with Emax. Conclusions: In hypertensive HFpEF, longitudinal function could be the early maker reflecting subendocardial fibrosis and chamber diastolic dysfunction.
S9-3 Diagnosis of Heart Failure by Biomarker YUKIHITO SATO Department of Cardiovascular Medicine, Hyogo Prefectural Amagasaki Hospital, Amagasaki, Japan In industrialized countries, chronic heart failure (HF) is a major illness and cause of death. However, because of the paucity of specific clinical manifestations of HF, its early diagnosis and management might be challenging. Therefore, biochemical markers of HF are now being closely scrutinized. An ideal biochemical marker should be a prognostic indicator, assist in the early diagnosis, reflect the therapeutic response, and help grading the risk associated with each stage of HF.B-type natriuretic peptide (BNP) and N-terminal proBNP provide additional information together with clinical symptoms for the diagnosis of acute HF in patients with presenting acute dyspnea. Slight elevation of these assays has recently been reported to be associated with future development of cardiovascular events in general population. On the other hand, cardiac troponin (cTn) has been reported to be independent prognostic biomarker in patients with both acute and chronic heart failure, though cTn is a first line biomarker of acute myocardial infarction. While conventional cTnT assays have often been used as a positive or negative categorical variable, stepwise rises in high
sensitivity (Hs)-cTn in patients presenting with chronic HF have been associated with a progressive increase in the incidence of cardiovascular events. Similar observations have been made in the general population. We here discuss potential use of these biomarkers.
S9-4 Biomarkers for Early Diagnosis of Heart Failure NORIHIKO KOTOOKA Department of Cardiovascular Medicine, Saga University, Saga, Japan Treatment of heart failure (HF) has usually focused on symptomatic stage, often after admission due to acute exacerbation. Early identification of asymptomatic or latent cardiac dysfunction is desirable to prevent the progression of HF. In addition to noninvasive imaging strategies, serological biomarkers such as N-terminal pro B-type natriuretic peptide (NT-proBNP), troponins, and C-reactive protein have been reported to be useful for estimate the severity and prognosis, and early detection of HF. For example, circulating cardiac troponin T (cTnT) is sensitive and specific markers of myocardial injury and elevated troponins in patients with HF may suggest ongoing myocardial damage. Although cTnT levels in patients with HF are often lower than those in patients with acute coronary syndrome, recently developed highly sensitive assay makes it possible to assess the association of cTnT levels with earlier stage of HF. Approximately half of patients with HF have a preserved left ventricular ejection fraction (HFpEF), and elevated plasma levels of natriuretic peptides is included guidelines for the diagnosis of HFpEF. Recently, biomarkers reflecting extracellular matrix synthesis and degradation have been reported to be more useful for predicting the presence of HFpEF than NT-pro BNP. I would like to discuss about biomarkers for early diagnosis of HF on the basis of these findings and our own experiments.
S9-5 Potential of Cardiac MRI for Predicting the Risk of Heart Failure KATSUYA ONISHI1,2, SHIRO NAKAMORI2, HIROSHI NAKAJIMA2, HAJIME SAKUMA3, MASAAKI ITO2 1 Onishi Heart Clinic, 2Department of Cardiology, Mie University Graduate School of Medicine, Tsu City, Japan, 3Department of Radiology, Mie University Graduate School of Medicine, Tsu City, Japan Cardiac magnetic resonance (CMR) is a noble method to evaluate cardiac function and myocardial perfusion. Quantitative analysis of myocardial perfusion MRI can provide noninvasive assessment of myocardial perfusion reserve (MPR). CMR tagging has been established as a technique for quantification of local intramyocardial motion measures, e.g. strain and strain rate using displacement encoding with stimulated echoes (DENSE). Accordingly, we evaluated whether MPR was impaired in patients with the risk for heart failure, and the possibility of DENSE CMR to detect wall motion abnormality. We studied 110 patients without regional myocardial ischemia, and 30 patients with heart failure with preserved ejection fraction (HFpEF). Adenosine triphosphate (ATP) stress and rest first-pass perfusion MR images were acquired with a 1.5-T MR system, and MPR was calculated as the ratio of stress to rest myocardial blood flow. MPR was associated with hypertension, age, e-GFR, hematocrit and left ventricular mass index. In multiple regression analysis, hypertension showed the strongest correlation with MPR among other risk factors after adjusting age and gender. In HFpEF patients, MPR is significantly decreased to compare with that in control subjects. Regional myocardial strain using DENSE CMR was well correlated to that using tissue Doppler imaging. In conclusion, detecting the impaired MPR may predict the risk of heart failure, and DENSE CMR may be useful method to detect wall motion abnormality.
S9-6 Importance of Assessing Sleep-disordered Breathing in Patients with Stage A/B Heart Failure YOSHIFUMI TAKATA, AKIRA YAMASHINA Department of Cardiology, Tokyo Medical University, Tokyo, Japan Sleep-disordered breathing (SDB) is known to increase the risk of developing various cardiovascular diseases in stages at risk for heart failure (HF). SDB also plays an important role in the onset and progression of HF. A recent observational cohort study showed that obstructive sleep apnea was associated with an increased risk of incident HF in community-dwelling middle-aged and older men. We have demonstrated that obstructive sleep apnea is significantly related with left ventricular diastolic dysfunction, left ventricular concentric hypertrophy and an increase of arterial stiffness, especially coexisting with metabolic syndrome. On the other hand, an existence of central sleep apnea or