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Diagnosis and Treatment of Isolated Cardiac Sarcoidosis
The 18th Annual Scientific Meeting
JHFS
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VT were observed in 13 patients (38%), and they had significantly lower LVEF compared to no-VT patients. (43 6 14% vs. 58 6 10% p50.02) We found an optimal cut off value of 44% in ROC analysis, this value identified 7 of 13 patients with VT, resulting in sensitivity and specificity levels of 0.54 and 0.91. Conclusion: In this study, lower LVEF was associated with VT in cardiac sarcoidosis.
with occurrence of heart failure (p ! 0.05). This association was still significant after adjustment for age, gender, incidence of hypertension, diabetes mellitus and kidney function. Conclusion: Parathyroid hormone is associated with future heart failure. Our results suggest that treatment to reduced PTH level is helpful to prevent future cardiac event.
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P-127
Diagnosis and Treatment of Isolated Cardiac Sarcoidosis DAISUKE TEZUKA, TARO SASAOKA, MITSUAKI ISOBE Department of Cardiovascular Medicine, Tokyo Medical and Dental University
Relationship between Indoxyl Sulfate and Fibroblast Growth Factor 23 in Heart Failure Patients with Preserved Renal Function MIKI IMAZU1, MASANORI ASAKURA1, HIROYUKI TAKAHAMA1, HIROSHI ASANUMA2, AKIRA FUNADA1, YASUO SUGANO1, TAKAHIRO OHARA1, TAKUYA HASEGAWA1, HIDEAKI KANZAKI1, TOSHIHISA ANZAI1, MASAFUMI KITAKAZE1 1 National Cerebral and Cardiovascular Center, Osaka, Japan, 2Kyoto Prefectural University School of Medicine
Background: Long term survival data and the therapeutic significance of prednisolone for isolated cardiac sarcoidosis (iCS) has not been established, particularly in the cases with left ventricular (LV) dysfunction (EF ! 50%). Moreover, it is difficult to diagnose iCS patients without histological evidence of granulomas. The aim of this study was to assess therapeutic effect and prognosis of iCS. Methods: According to clinical criteria, sarcoidosis with CS (sCS) and iCS were diagnosed. iCS cases were examined using cardiac magnetic resonance imaging or 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography. Results: Baseline of brain natriuretic peptide (BNP) were not different between sCS (n517) and iCS (n57). After prednisolone treatment, BNP decreased significantly in both groups (sCS: before, 157.36130.3 pg/ml; after, 108.8693.7, p50.01; iCS: before, 317.86331.2; after, 138.66161.6, p50.043). The prognosis demonstrated by Kaplan -Meier curve (40651.1 months) was not different between sCS (n530) and iCS (n511). CS cases not treated by prednisolone showed poorer prognosis (p50.0069). The patients with LV dysfunction which was not treated by prednisolone had the worst outcome among the all groups (p50.0011). Conclusion: iCS cases with LV dysfunction initially those suspected with the noninvasive imaging modalities, prednisolone treatment should be considered.
P-125 Heterogeneity of Sympathetic Nervous Density in the Left Ventricular Wall in Dilated Cardiomyopathy SHOHEI KIKUCHI, SHUICHI KITADA, NOBUYUKI OHTE Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose: We assessed presynaptic sympathetic nervous function in patients with dilated cardiomyopathy (DCM) using positron emission tomography (PET) with Carbon-11 hydroxyephedrine (HED). Methods: In 15 patients with DCM in stable conditions and 15 healthy controls, left ventricular (LV) myocardial global blood flow (MBF) was measured using N-13 ammonia PET and then global HED retention index (HED-RI) was determined as myocardial tracer activity between 30-40 minutes divided by the integral of the activity input function. The polar maps of the tracers were divided into 17 segments, and each segmental tracer activity of MBF and HED-RI were normalized to the highest values in each patients. Coefficients of variation (CV) were calculated to assess heterogeneity of MBF and HED-RI in the LV wall. Results: MBF and HED-RI were significantly lower in patients with DCM than in healthy subjects (0.5960.10 vs 0.7860.10 mL/min/g, p50.0003; 6.961.9 vs 8.862.0 %/min, p50.02, respectively). CV of both MBF and HED-RI were significantly higher in patients with DCM than in healthy subjects (24.767.9 vs 17.564.1 %, p50.004; 16.465.4 vs 10.362.2%, p50.0004, respectively). The CVs of HED-RI were significantly correlated with logBNP (r50.65, p50.0001). Conclusion: In addition to the global reduction of cardiac sympathetic activity, heterogeneous sympathetic presynaptic tracer uptake in the LV wall was demonstrated in patients with DCM. The degree of heterogeneity was correlated to severity of heart failure.
P-126 Impact of Parathyroid Hormone on Future Occurrence of Heart Failure in Patients without History of Cardiovascular Disease SATORU SAKURAGI, KEIJI YAMADA Department of Cardiology, Iwakuni Clinical Center Parathyroid hormone (PTH) plays an important role in bone metabolism. High PTH level increases intracellular calcium in arterial wall, which causes hypertension and left ventricular hypertrophy. However, information on the association of PTH level with cardiovascular event in general population is still lacking. Methods and Results: 174 subjects (84male, 68years) without history of cardiovascular disease were enrolled from September 2012 to April 2013. At baseline, parathyroid function was assessed with intact PTH (iPTH). Subjects were classified into tertiles of intact PTH and clinical characteristics were compared. Association of intact PTH with future cardiovascular event was also evaluated. Subjects with highest tertile of iPTH was older, and had higher ratio of female and prevalence of hypertension (p ! 0.05 for all). In blood test, markers of kidney function such as creatinine and cystatin C were increaed in subjects with highest tertile of iPTH. NT-proBNP increased with iPTH (p ! 0.01). During the follow-up period of 115days, 7 subjects developed congestive heart failure. Serum intact iPTH was significantly associated
Backgrounds: Both indoxyl sulfate (IS) known as one of a uremic toxin and fibroblast growth factor 23 (FGF23) which is one of a phosphate-regulating hormone are known to be prognostic markers with chronic kidney disease. Recently it was reported that IS suppressed Klotho expression which need to FGF23 signaling in kidney, but it is less known the relationship between IS and FGF23. We aimed to determine the relationship in heart failure patients without advanced renal dysfunction. Methods: We investigated 726 subjects from a community population, and prospectively enrolled 79 patients who have history of heart failure with more than 60 ml/min/1.73 m2 of eGFR and without albuminuria (HF group). We matched community population with gender and eGFR of HF patients (Control group). The plasma IS levels and the serum FGF23 levels were measured at the same time. Results: IS levels significantly correlated with FGF23 levels in HF group (r50.35, p50.002), but not in Control group (r50.07, p50.521), and IS did not correlate with phosphorous and intact parathyroid hormone which relate to FGF23 in these groups. IS and FGF23 levels of HF group were significantly higher than of Control group, and BNP levels, too. Conclusion: IS related to FGF23 in HF patients without obvious renal dysfunction. IS might influence regulating the serum FGF23 levels.
P-128 Serum Brain-derived Neurotrophic Factor Level Predicts Adverse Clinical Outcomes in Patients with Heart Failure MASATO KUDO, SHINTARO KINUGAWA, ARATA FUKUSHIMA, TAKASHI YOKOTA, SHOUJI MATSUSHIMA, TAKAAKI FURIHATA, MASAYA TSUDA, JUNICHI MATSUMOTO, SHINGO TAKADA, HIROYUKI TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Aims: Exercise intolerance as well as depressive symptoms are prevalent and associated with adverse outcomes in patients with heart failure (HF). Brain-derived neurotrophic factor (BDNF) is involved in cardiovascular diseases as well as skeletal muscle energy metabolism and depression. We recently reported that serum BDNF level was decreased in HF patients and was closely related to their exercise capacity. We thus investigated whether serum BDNF level was associated with their outcomes. Methods and Results: We measured serum BDNF level in 58 HF patients (59.2613.7 years, NYHA I-III) at baseline and adverse events including all cause death and HF rehospitalization were registered during the mean follow-up of 18.2 months. The multivariate analysis demonstrated that serum BDNF level was an independent prognostic factor of adverse events (hazard ratio 2.32, 95% confidence interval 1.20-4.47, P50.008). Cutoff value of serum BDNF determined by receiver operating characteristic curve analysis predicted adverse events with sensitivity, specificity, and positive and negative predictive values of 75%, 79%, 60%, and 85%, respectively. Kaplan-Meier analysis demonstrated that low level of BDNF was associated with higher rates of adverse events than high level of BDNF (P50.001). Conclusion: Decreased serum BDNF levels were significantly associated with adverse outcomes in HF patients, suggesting that they can be a useful prognostic biomarker.
P-129 Serum Irisin Levels Provide Prognostic Information in Patients with Heart Failure with Reduced Ejection Fraction SHINSUKE HANATANI, YASUHIRO IZUMIYA, YUICHI KIMURA, YOSHIRO ONOUE, SATOSHI ARAKI, HISAO OGAWA Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan Introduction: Irisin is a newly identified myokine found in human serum. The gene expression of irisin precursor in skeletal muscle is associated with exercise tolerance in heart failure patients. Hypothesis: In patients with heart failure with reduced ejection fraction (HFrEF), irisin could be a useful biomarker to predict future cardiovascular events. Methods and Results: We measured serum irisin levels in 84 patients with HFrEF. Serum irisin concentrations were measured by an ELISA. The endpoint was a composite of total mortality, cardiovascular hospitalization and coronary revascularization. These patients were divided into 2 groups according to irisin levels.
JHFS
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VT were observed in 13 patients (38%), and they had significantly lower LVEF compared to no-VT patients. (43 6 14% vs. 58 6 10% p50.02) We found an optimal cut off value of 44% in ROC analysis, this value identified 7 of 13 patients with VT, resulting in sensitivity and specificity levels of 0.54 and 0.91. Conclusion: In this study, lower LVEF was associated with VT in cardiac sarcoidosis.
with occurrence of heart failure (p ! 0.05). This association was still significant after adjustment for age, gender, incidence of hypertension, diabetes mellitus and kidney function. Conclusion: Parathyroid hormone is associated with future heart failure. Our results suggest that treatment to reduced PTH level is helpful to prevent future cardiac event.
P-124
P-127
Diagnosis and Treatment of Isolated Cardiac Sarcoidosis DAISUKE TEZUKA, TARO SASAOKA, MITSUAKI ISOBE Department of Cardiovascular Medicine, Tokyo Medical and Dental University
Relationship between Indoxyl Sulfate and Fibroblast Growth Factor 23 in Heart Failure Patients with Preserved Renal Function MIKI IMAZU1, MASANORI ASAKURA1, HIROYUKI TAKAHAMA1, HIROSHI ASANUMA2, AKIRA FUNADA1, YASUO SUGANO1, TAKAHIRO OHARA1, TAKUYA HASEGAWA1, HIDEAKI KANZAKI1, TOSHIHISA ANZAI1, MASAFUMI KITAKAZE1 1 National Cerebral and Cardiovascular Center, Osaka, Japan, 2Kyoto Prefectural University School of Medicine
Background: Long term survival data and the therapeutic significance of prednisolone for isolated cardiac sarcoidosis (iCS) has not been established, particularly in the cases with left ventricular (LV) dysfunction (EF ! 50%). Moreover, it is difficult to diagnose iCS patients without histological evidence of granulomas. The aim of this study was to assess therapeutic effect and prognosis of iCS. Methods: According to clinical criteria, sarcoidosis with CS (sCS) and iCS were diagnosed. iCS cases were examined using cardiac magnetic resonance imaging or 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography. Results: Baseline of brain natriuretic peptide (BNP) were not different between sCS (n517) and iCS (n57). After prednisolone treatment, BNP decreased significantly in both groups (sCS: before, 157.36130.3 pg/ml; after, 108.8693.7, p50.01; iCS: before, 317.86331.2; after, 138.66161.6, p50.043). The prognosis demonstrated by Kaplan -Meier curve (40651.1 months) was not different between sCS (n530) and iCS (n511). CS cases not treated by prednisolone showed poorer prognosis (p50.0069). The patients with LV dysfunction which was not treated by prednisolone had the worst outcome among the all groups (p50.0011). Conclusion: iCS cases with LV dysfunction initially those suspected with the noninvasive imaging modalities, prednisolone treatment should be considered.
P-125 Heterogeneity of Sympathetic Nervous Density in the Left Ventricular Wall in Dilated Cardiomyopathy SHOHEI KIKUCHI, SHUICHI KITADA, NOBUYUKI OHTE Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Purpose: We assessed presynaptic sympathetic nervous function in patients with dilated cardiomyopathy (DCM) using positron emission tomography (PET) with Carbon-11 hydroxyephedrine (HED). Methods: In 15 patients with DCM in stable conditions and 15 healthy controls, left ventricular (LV) myocardial global blood flow (MBF) was measured using N-13 ammonia PET and then global HED retention index (HED-RI) was determined as myocardial tracer activity between 30-40 minutes divided by the integral of the activity input function. The polar maps of the tracers were divided into 17 segments, and each segmental tracer activity of MBF and HED-RI were normalized to the highest values in each patients. Coefficients of variation (CV) were calculated to assess heterogeneity of MBF and HED-RI in the LV wall. Results: MBF and HED-RI were significantly lower in patients with DCM than in healthy subjects (0.5960.10 vs 0.7860.10 mL/min/g, p50.0003; 6.961.9 vs 8.862.0 %/min, p50.02, respectively). CV of both MBF and HED-RI were significantly higher in patients with DCM than in healthy subjects (24.767.9 vs 17.564.1 %, p50.004; 16.465.4 vs 10.362.2%, p50.0004, respectively). The CVs of HED-RI were significantly correlated with logBNP (r50.65, p50.0001). Conclusion: In addition to the global reduction of cardiac sympathetic activity, heterogeneous sympathetic presynaptic tracer uptake in the LV wall was demonstrated in patients with DCM. The degree of heterogeneity was correlated to severity of heart failure.
P-126 Impact of Parathyroid Hormone on Future Occurrence of Heart Failure in Patients without History of Cardiovascular Disease SATORU SAKURAGI, KEIJI YAMADA Department of Cardiology, Iwakuni Clinical Center Parathyroid hormone (PTH) plays an important role in bone metabolism. High PTH level increases intracellular calcium in arterial wall, which causes hypertension and left ventricular hypertrophy. However, information on the association of PTH level with cardiovascular event in general population is still lacking. Methods and Results: 174 subjects (84male, 68years) without history of cardiovascular disease were enrolled from September 2012 to April 2013. At baseline, parathyroid function was assessed with intact PTH (iPTH). Subjects were classified into tertiles of intact PTH and clinical characteristics were compared. Association of intact PTH with future cardiovascular event was also evaluated. Subjects with highest tertile of iPTH was older, and had higher ratio of female and prevalence of hypertension (p ! 0.05 for all). In blood test, markers of kidney function such as creatinine and cystatin C were increaed in subjects with highest tertile of iPTH. NT-proBNP increased with iPTH (p ! 0.01). During the follow-up period of 115days, 7 subjects developed congestive heart failure. Serum intact iPTH was significantly associated
Backgrounds: Both indoxyl sulfate (IS) known as one of a uremic toxin and fibroblast growth factor 23 (FGF23) which is one of a phosphate-regulating hormone are known to be prognostic markers with chronic kidney disease. Recently it was reported that IS suppressed Klotho expression which need to FGF23 signaling in kidney, but it is less known the relationship between IS and FGF23. We aimed to determine the relationship in heart failure patients without advanced renal dysfunction. Methods: We investigated 726 subjects from a community population, and prospectively enrolled 79 patients who have history of heart failure with more than 60 ml/min/1.73 m2 of eGFR and without albuminuria (HF group). We matched community population with gender and eGFR of HF patients (Control group). The plasma IS levels and the serum FGF23 levels were measured at the same time. Results: IS levels significantly correlated with FGF23 levels in HF group (r50.35, p50.002), but not in Control group (r50.07, p50.521), and IS did not correlate with phosphorous and intact parathyroid hormone which relate to FGF23 in these groups. IS and FGF23 levels of HF group were significantly higher than of Control group, and BNP levels, too. Conclusion: IS related to FGF23 in HF patients without obvious renal dysfunction. IS might influence regulating the serum FGF23 levels.
P-128 Serum Brain-derived Neurotrophic Factor Level Predicts Adverse Clinical Outcomes in Patients with Heart Failure MASATO KUDO, SHINTARO KINUGAWA, ARATA FUKUSHIMA, TAKASHI YOKOTA, SHOUJI MATSUSHIMA, TAKAAKI FURIHATA, MASAYA TSUDA, JUNICHI MATSUMOTO, SHINGO TAKADA, HIROYUKI TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Aims: Exercise intolerance as well as depressive symptoms are prevalent and associated with adverse outcomes in patients with heart failure (HF). Brain-derived neurotrophic factor (BDNF) is involved in cardiovascular diseases as well as skeletal muscle energy metabolism and depression. We recently reported that serum BDNF level was decreased in HF patients and was closely related to their exercise capacity. We thus investigated whether serum BDNF level was associated with their outcomes. Methods and Results: We measured serum BDNF level in 58 HF patients (59.2613.7 years, NYHA I-III) at baseline and adverse events including all cause death and HF rehospitalization were registered during the mean follow-up of 18.2 months. The multivariate analysis demonstrated that serum BDNF level was an independent prognostic factor of adverse events (hazard ratio 2.32, 95% confidence interval 1.20-4.47, P50.008). Cutoff value of serum BDNF determined by receiver operating characteristic curve analysis predicted adverse events with sensitivity, specificity, and positive and negative predictive values of 75%, 79%, 60%, and 85%, respectively. Kaplan-Meier analysis demonstrated that low level of BDNF was associated with higher rates of adverse events than high level of BDNF (P50.001). Conclusion: Decreased serum BDNF levels were significantly associated with adverse outcomes in HF patients, suggesting that they can be a useful prognostic biomarker.
P-129 Serum Irisin Levels Provide Prognostic Information in Patients with Heart Failure with Reduced Ejection Fraction SHINSUKE HANATANI, YASUHIRO IZUMIYA, YUICHI KIMURA, YOSHIRO ONOUE, SATOSHI ARAKI, HISAO OGAWA Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan Introduction: Irisin is a newly identified myokine found in human serum. The gene expression of irisin precursor in skeletal muscle is associated with exercise tolerance in heart failure patients. Hypothesis: In patients with heart failure with reduced ejection fraction (HFrEF), irisin could be a useful biomarker to predict future cardiovascular events. Methods and Results: We measured serum irisin levels in 84 patients with HFrEF. Serum irisin concentrations were measured by an ELISA. The endpoint was a composite of total mortality, cardiovascular hospitalization and coronary revascularization. These patients were divided into 2 groups according to irisin levels.