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Discontinuation of Corticosteroid Therapy Increases the Risk of Cardiac Mortality Associated with Progression of Left Ventricular Dysfunction in Cardiac Sarcoidosis
S146 Journal of Cardiac Failure Vol. 21 No. 10S October 2015
Young Investigators’ Awards Young Investigators’ Award 1 YA1-1 Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients with Heart Failure TOMOHIRO OTSUKI, KIMIO SATOH, KOICHIRO SUGIMURA, TATSUO AOKI, SHUNSUKE TATEBE, MASANOBU MIURA, SAORI YAMAMOTO, NOBUHIRO YAOITA, SATOSHI MIYATA, HIROAKI SHIMOKAWA Department of Cardiovascular Medicine, Tohoku University Background: Cyclophilin A (CyPA) is secreted from cardiac fibroblasts in response to angiotensin II or mechanical stretch and promotes cardiac hypertrophy and fibrosis. However, the role of CyPA as a biomarker for patients with heart failure (HF) remains to be elucidated. Methods and Results: In 143 consecutive patients who were hospitalized in Tohoku University Hospital for HF, we measured plasma levels of CyPA and BNP and examined their prognostic impacts during the follow-up (median 3.7 years). Plasma CyPA levels were significantly elevated in HF patients (15.369.6 ng/mL, n5123) than in healthy controls (5.264.5 ng/mL, n520, P!0.001). Kaplan-Meier curve showed that higher CyPA levels (S 15 ng/mL) were associated with all-cause death (HR3.7, 95% CI1.3-10.5, P!0.05) and rehospitalization (HR3.0, 95% CI1.2-7.0, P!0.05). Higher BNP levels (S 100 pg/mL) were also associated with all-cause death (HR4.3, 95% CI1.215.3, P!0.05) and rehospitalization (HR3.2, 95% CI1.2-8.9, P!0.05). Interestingly, there was no correlation between CyPA and BNP levels, suggesting different clinical implications of the 2 biomarkers. Importantly, the combination of CyPA (S 15 ng/mL) and BNP (S 100 pg/mL) was highly significantly associated with allcause death (HR12.5, 95% CI1.6-97.6, P!0.05) and rehospitalization (HR10.1, 95% CI1.2-84.2, P!0.01) compared with CyPA (!15 ng/mL) or BNP (! 100pg/mL) alone. Conclusions: These results indicate that plasma CyPA levels have prognostic impacts in HF patients, which are further enhanced when combined with BNP.
YA1-2 Discontinuation of Corticosteroid Therapy Increases the Risk of Cardiac Mortality Associated with Progression of Left Ventricular Dysfunction in Cardiac Sarcoidosis TOSHIYUKI NAGAI, NOBUTAKA NAGANO, YASUO SUGANO, TAKESHI AIBA, HIDEAKI KANZAKI, KENGO KUSANO, TERUO NOGUCHI, SATOSHI YASUDA, HISAO OGAWA, TOSHIHISA ANZAI Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Backgrounds: Corticosteroid therapy is the gold standard treatment in patients with cardiac sarcoidosis (CS). However, clinicians often have difficulty deciding the discontinuation of corticosteroids on long-term management. Methods: We examined 70 consecutive patients who were definitively diagnosed as CS by established Japanese criteria and treated with corticosteroids in our institution for over 30 years. Patients were divided into two groups based on the discontinuation of corticosteroids during longterm follow-up period (9.865.7 years). Results: Corticosteroids was discontinued in 12 patients because the improvement of clinical and/or imaging findings was observed. Patients with discontinuation had received corticosteroids for 3.463.6 years. There were no significant differences between two groups in terms of age, sex, left ventricular ejection fraction (LVEF), gallium and FDG-PET findings, incidence of ventricular arrhythmias and congestive heart failure, and dose of corticosteroids at diagnosis. After discontinuation of corticosteroids, five patients had cardiac death, and the cardiac mortality rate was significantly higher compared to patients with continuation (42% vs. 16%, P50.047). Furthermore, discontinuation of corticosteroids was associated with greater % decrease in LVEF compared to continuation (-23.1631.5% vs. 8.4631.8%, P50.019) during the follow-up period. Conclusions: In long-term management of CS patients, making the decision of discontinuation of corticosteroid therapy should be very cautious even if the temporary improvement has been observed.
YA1-3 The New Treatment Strategy Using Transcatheter Aortic Valve Implication for Decompensated Aortic Stenosis KENTA MASADA1, TORU KURATANI2, KOICHI MAEDA1, KEI TORIKAI1, TOMOAKI KUDO2, TOSHINARI OHNISHI3, YASUHIRO ICHIBORI3, SATOSHI NAKATANI3, YASUSHI SAKATA3, YOSHIKI SAWA1 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan; 2Minimally Invasive Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan; 3Department of Cardiology, Osaka University Graduate School of Medicine, Suita, Japan Background: Decompensated aortic stenosis (DAS) are extremely burdensome to treat. Unfortunately, aortic valve replacement for DAS is highly invasive, and the
results are unfavorable. So less invasive surgical techniques are necessary, and we believe transcatheter aortic valve implantation (TAVI) serves such a purpose. Objective: Our purpose of this study is to elucidate the efficacy of TAVI for DAS. Methods: We performed 256 TAVI cases from 2009 to March 2015. Among them, Edwards SAPIEN XT were used in 200 cases. We divided them into two group between LVEF !50% (LEF) (n535) and LVEFO50% (PEF) (n5165). As preoperative risk, STSscore in LEF and PEF were 19.0% and 9.5% respectively (p!0.001). There was no significant difference of co-morbility and procedural approach between both groups. PCPS rate of LEF (34.2%) was significantly higher than that of PEF (1.2%) (p!0.001). There was no significant difference of 30-day mortality (LEF/PEF52.8%/1.8%), and hospitalization period (17.1/13.9 days), and the rate of discharge home (82.8/92.7%). Freedom rate from cardiovascular death was 96.8% and 96.8% at 6 and 12 months in LEF, and 97.0% and 95.5% in PEF (p!0.66). Conclusions: We achieved satisfactory outcomes of TAVI for decompensated aortic stenosis with non-inferiority compared to cases preserved ejection fraction. Although long-term results was imperative, TAVI may become one of alternatives to AVR for decompensated aortic stenosis.
YA1-4 The Clinical Significance of Pulse Pressure in Patients with Heart Failure with Preserved Ejection Fraction TAKANORI TOKITSU, EIICHIRO YAMAMOTO, YOSHIHIRO HIRATA, HISAO OGAWA Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan Background: Although pulse pressure (PP) has been recognized as a risk factor for cardiovascular events (CVE), its association with cardiovascular outcomes in HFpEF patients remains uncertain. Methods: We enrolled 317 consecutive HFpEF patients and measured blood pressure (BP) by using ankle brachial index form at stable condition. We defined high-PP values more than 65 mmHg as reported previously. Results: PP had a positive correlation with pulse wave velocity (PWV) (p! 0.001), and negative correlations with eGFR (p!0.001) and hemoglobin levels (p!0.01) in HFpEF. In multivariatelogistic-regression analysis, age, hemoglobin, eGFR and the presence of diabetes mellitus were independently associated with high-PP. In multivariate-Cox-proportional-hazard analysis, highPP (p50.01), the presence of ischemic heart disease (p50.01), and BNP values (p50.01) were independently associated with the occurrence of CVE, but high-systolic BP was not. High-PP was also an independent predictor for HF-related events (HFE) (p!0.01). In Kaplan-Meier analysis, high-PP patients had a significant higher risk of CVE and HFE (both, log-lank test, p!0.01). We further stratified patients into four groups by combining PP values with other biomarkers, and found that high-PP+high-BNP (O100pg/dl) had the highest risk of both HFE and CVE (both, p!0.001). In combination with PP and PWV, high-PP+high-PWV (Omedian value; 1810 cm/) also had the highest risk of CVE (p!0.001). Conclusion: PP is the useful marker for risk stratification of HFpEF.
YA1-5 Relationship between Cardiac Sympathetic Hyperactivity and Myocardial Oxidative Stress in Patients with Takotsubo Cardiomyopathy TAKUMA NANNO, SHIGEKI KOBAYASHI, SEIKO ODA, HIRONORI ISHIGUCHI, TAKEKI MYOREN, TETSURO ODA, SHINICHI OKUDA, JUTARO YAMADA, TAKAYUKI OKAMURA, MASAFUMI YANO Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine We investigated the relationship between myocardial oxidative stress and cardiac sympathetic hyperactivity in patients with takotsubo cardiomyopathy (TC) compared with acute anteroseptal myocardial infarction (AMI). Methods and Results: In 8 TC patients and 8 AMI patients, ECG, echocardiography, cardiac catheterization, serial measurements of plasma catecholamines and urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage and CPK were performed for two weeks from onset. Blood sampling from coronary sinus (CS) and aorta (Ao) showed that norepinephrine (NE) levels and 8-OHdG level in CS were significantly higher than that in Ao. The peripheral plasma NE level on admission (1st day) were 2-times higher in TC than in AMI, although the max CPK value in TC was significantly lower than that in AMI. The NE level was decreased to nearly normal range in AMI at 7th, while it was still 2-times elevated in TC for a week. Dual scintigraphy of 201Tl and 123I-meta-iodobenzylguanidine (MIBG) was performed at 7th hospital day showed that sympathetic nervous injury of heart was much larger than myocardial perfusion damage in TC. Interestingly, echocardiography findings revealed that LV dysfunction in TC was improved in parallel with a decrease of U-8OHdG within 2 weeks. Conclusions: These findings suggest that elevated myocardial oxidative stress induced by catecholamines from cardiac sympathetic nerve ending may relate to transient LV dysfunction.
Young Investigators’ Awards Young Investigators’ Award 1 YA1-1 Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients with Heart Failure TOMOHIRO OTSUKI, KIMIO SATOH, KOICHIRO SUGIMURA, TATSUO AOKI, SHUNSUKE TATEBE, MASANOBU MIURA, SAORI YAMAMOTO, NOBUHIRO YAOITA, SATOSHI MIYATA, HIROAKI SHIMOKAWA Department of Cardiovascular Medicine, Tohoku University Background: Cyclophilin A (CyPA) is secreted from cardiac fibroblasts in response to angiotensin II or mechanical stretch and promotes cardiac hypertrophy and fibrosis. However, the role of CyPA as a biomarker for patients with heart failure (HF) remains to be elucidated. Methods and Results: In 143 consecutive patients who were hospitalized in Tohoku University Hospital for HF, we measured plasma levels of CyPA and BNP and examined their prognostic impacts during the follow-up (median 3.7 years). Plasma CyPA levels were significantly elevated in HF patients (15.369.6 ng/mL, n5123) than in healthy controls (5.264.5 ng/mL, n520, P!0.001). Kaplan-Meier curve showed that higher CyPA levels (S 15 ng/mL) were associated with all-cause death (HR3.7, 95% CI1.3-10.5, P!0.05) and rehospitalization (HR3.0, 95% CI1.2-7.0, P!0.05). Higher BNP levels (S 100 pg/mL) were also associated with all-cause death (HR4.3, 95% CI1.215.3, P!0.05) and rehospitalization (HR3.2, 95% CI1.2-8.9, P!0.05). Interestingly, there was no correlation between CyPA and BNP levels, suggesting different clinical implications of the 2 biomarkers. Importantly, the combination of CyPA (S 15 ng/mL) and BNP (S 100 pg/mL) was highly significantly associated with allcause death (HR12.5, 95% CI1.6-97.6, P!0.05) and rehospitalization (HR10.1, 95% CI1.2-84.2, P!0.01) compared with CyPA (!15 ng/mL) or BNP (! 100pg/mL) alone. Conclusions: These results indicate that plasma CyPA levels have prognostic impacts in HF patients, which are further enhanced when combined with BNP.
YA1-2 Discontinuation of Corticosteroid Therapy Increases the Risk of Cardiac Mortality Associated with Progression of Left Ventricular Dysfunction in Cardiac Sarcoidosis TOSHIYUKI NAGAI, NOBUTAKA NAGANO, YASUO SUGANO, TAKESHI AIBA, HIDEAKI KANZAKI, KENGO KUSANO, TERUO NOGUCHI, SATOSHI YASUDA, HISAO OGAWA, TOSHIHISA ANZAI Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Backgrounds: Corticosteroid therapy is the gold standard treatment in patients with cardiac sarcoidosis (CS). However, clinicians often have difficulty deciding the discontinuation of corticosteroids on long-term management. Methods: We examined 70 consecutive patients who were definitively diagnosed as CS by established Japanese criteria and treated with corticosteroids in our institution for over 30 years. Patients were divided into two groups based on the discontinuation of corticosteroids during longterm follow-up period (9.865.7 years). Results: Corticosteroids was discontinued in 12 patients because the improvement of clinical and/or imaging findings was observed. Patients with discontinuation had received corticosteroids for 3.463.6 years. There were no significant differences between two groups in terms of age, sex, left ventricular ejection fraction (LVEF), gallium and FDG-PET findings, incidence of ventricular arrhythmias and congestive heart failure, and dose of corticosteroids at diagnosis. After discontinuation of corticosteroids, five patients had cardiac death, and the cardiac mortality rate was significantly higher compared to patients with continuation (42% vs. 16%, P50.047). Furthermore, discontinuation of corticosteroids was associated with greater % decrease in LVEF compared to continuation (-23.1631.5% vs. 8.4631.8%, P50.019) during the follow-up period. Conclusions: In long-term management of CS patients, making the decision of discontinuation of corticosteroid therapy should be very cautious even if the temporary improvement has been observed.
YA1-3 The New Treatment Strategy Using Transcatheter Aortic Valve Implication for Decompensated Aortic Stenosis KENTA MASADA1, TORU KURATANI2, KOICHI MAEDA1, KEI TORIKAI1, TOMOAKI KUDO2, TOSHINARI OHNISHI3, YASUHIRO ICHIBORI3, SATOSHI NAKATANI3, YASUSHI SAKATA3, YOSHIKI SAWA1 1 Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan; 2Minimally Invasive Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan; 3Department of Cardiology, Osaka University Graduate School of Medicine, Suita, Japan Background: Decompensated aortic stenosis (DAS) are extremely burdensome to treat. Unfortunately, aortic valve replacement for DAS is highly invasive, and the
results are unfavorable. So less invasive surgical techniques are necessary, and we believe transcatheter aortic valve implantation (TAVI) serves such a purpose. Objective: Our purpose of this study is to elucidate the efficacy of TAVI for DAS. Methods: We performed 256 TAVI cases from 2009 to March 2015. Among them, Edwards SAPIEN XT were used in 200 cases. We divided them into two group between LVEF !50% (LEF) (n535) and LVEFO50% (PEF) (n5165). As preoperative risk, STSscore in LEF and PEF were 19.0% and 9.5% respectively (p!0.001). There was no significant difference of co-morbility and procedural approach between both groups. PCPS rate of LEF (34.2%) was significantly higher than that of PEF (1.2%) (p!0.001). There was no significant difference of 30-day mortality (LEF/PEF52.8%/1.8%), and hospitalization period (17.1/13.9 days), and the rate of discharge home (82.8/92.7%). Freedom rate from cardiovascular death was 96.8% and 96.8% at 6 and 12 months in LEF, and 97.0% and 95.5% in PEF (p!0.66). Conclusions: We achieved satisfactory outcomes of TAVI for decompensated aortic stenosis with non-inferiority compared to cases preserved ejection fraction. Although long-term results was imperative, TAVI may become one of alternatives to AVR for decompensated aortic stenosis.
YA1-4 The Clinical Significance of Pulse Pressure in Patients with Heart Failure with Preserved Ejection Fraction TAKANORI TOKITSU, EIICHIRO YAMAMOTO, YOSHIHIRO HIRATA, HISAO OGAWA Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan Background: Although pulse pressure (PP) has been recognized as a risk factor for cardiovascular events (CVE), its association with cardiovascular outcomes in HFpEF patients remains uncertain. Methods: We enrolled 317 consecutive HFpEF patients and measured blood pressure (BP) by using ankle brachial index form at stable condition. We defined high-PP values more than 65 mmHg as reported previously. Results: PP had a positive correlation with pulse wave velocity (PWV) (p! 0.001), and negative correlations with eGFR (p!0.001) and hemoglobin levels (p!0.01) in HFpEF. In multivariatelogistic-regression analysis, age, hemoglobin, eGFR and the presence of diabetes mellitus were independently associated with high-PP. In multivariate-Cox-proportional-hazard analysis, highPP (p50.01), the presence of ischemic heart disease (p50.01), and BNP values (p50.01) were independently associated with the occurrence of CVE, but high-systolic BP was not. High-PP was also an independent predictor for HF-related events (HFE) (p!0.01). In Kaplan-Meier analysis, high-PP patients had a significant higher risk of CVE and HFE (both, log-lank test, p!0.01). We further stratified patients into four groups by combining PP values with other biomarkers, and found that high-PP+high-BNP (O100pg/dl) had the highest risk of both HFE and CVE (both, p!0.001). In combination with PP and PWV, high-PP+high-PWV (Omedian value; 1810 cm/) also had the highest risk of CVE (p!0.001). Conclusion: PP is the useful marker for risk stratification of HFpEF.
YA1-5 Relationship between Cardiac Sympathetic Hyperactivity and Myocardial Oxidative Stress in Patients with Takotsubo Cardiomyopathy TAKUMA NANNO, SHIGEKI KOBAYASHI, SEIKO ODA, HIRONORI ISHIGUCHI, TAKEKI MYOREN, TETSURO ODA, SHINICHI OKUDA, JUTARO YAMADA, TAKAYUKI OKAMURA, MASAFUMI YANO Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine We investigated the relationship between myocardial oxidative stress and cardiac sympathetic hyperactivity in patients with takotsubo cardiomyopathy (TC) compared with acute anteroseptal myocardial infarction (AMI). Methods and Results: In 8 TC patients and 8 AMI patients, ECG, echocardiography, cardiac catheterization, serial measurements of plasma catecholamines and urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage and CPK were performed for two weeks from onset. Blood sampling from coronary sinus (CS) and aorta (Ao) showed that norepinephrine (NE) levels and 8-OHdG level in CS were significantly higher than that in Ao. The peripheral plasma NE level on admission (1st day) were 2-times higher in TC than in AMI, although the max CPK value in TC was significantly lower than that in AMI. The NE level was decreased to nearly normal range in AMI at 7th, while it was still 2-times elevated in TC for a week. Dual scintigraphy of 201Tl and 123I-meta-iodobenzylguanidine (MIBG) was performed at 7th hospital day showed that sympathetic nervous injury of heart was much larger than myocardial perfusion damage in TC. Interestingly, echocardiography findings revealed that LV dysfunction in TC was improved in parallel with a decrease of U-8OHdG within 2 weeks. Conclusions: These findings suggest that elevated myocardial oxidative stress induced by catecholamines from cardiac sympathetic nerve ending may relate to transient LV dysfunction.