- Email: [email protected]
Inappropriate Expression of Hepcidin by Liver Congestion may Play an Important Role in Anemia and Iron Deficiency in Heart Failure
The 16th Annual Scientific Meeting with a heightend risk of the primary endpoint in a total population [HR1.69; 95%CI 0.953.00; p50.073]. In HFpEF (LVEF$45%, n5209), BUN-to-creatinine ratio was associated with a heightend risk of the primary endpoint [HR2.99;95%CI, 1.28-6.99; p5 0.012]. In HFrEF (EF!45%, n5107), BUN-to-creatinine ratio was not associated with the primary endpoint [HR0.90;95%CI 0.40-2.06; p50.81]. Conclusion: In patients with HFpEF, elevated BUN-to-creatinine ratio was a marker of poor prognosis.
O-070 Carolic Restriction Ameliorates Cardiac Steatosis by Activation of Autophagy via Cyclic AMP/AMPK/PKA Axis AKIO MONJI, YASUKO K. BANDO, MORIHIKO AOYAMA, TOKO MITSUI, TOYOAKI MUROHARA Department of Cardiology, Nagoya University, Nagoya, Japan Introduction: Caloric restriction (CR) promotes beneficial cardiovascular effects and enhances autophagy partly via the cyclic-AMP elevation. Cardiac steatosis impairs cardiac function associated with myocardial lipid accumulation and lipotoxic injury. However, the impact of CR on the cardiac steatosis remains unclear. Hypothesis: Cardiac steatosis-induced remodeling may be reversed by CR via activation of autophagy through the cyclic AMP/AMPkinase axis. Methods: High-fat-diet-induced obese mice (DIO) and age-matched counterparts (CTL) were allocated into CR and ad libitum (AL) group. Results: DIO-CR exhibited 32.661.58% reduction in body weight. DIO-AL exhibited reduced systolic left-ventricular function (EF(%); 66.262.9 for DIO-AL versus 76.862.3 for CTL-AL) and increased left-ventricular wall thickness (LVPWd(mm); 0.9360.08 versus 0.7360.03). CR reversed the systolic dysfunction and LV hypertrophy observed in DIO-AL groups (EF(%); 72.361.7 for DIO-CR versus 65.662.0 for DIOAL, LVPWd(mm); 0.8160.06 versus 0.9060.06). DIO-AL exhibited enhanced interstitial fibrosis compared to CTL-AL, that was reduced in DIO-CR (0.5860.10-fold versus DIOAL). Oil-red-O staining revealed that CR ameliorated cardiac lipid accumulation in DIOAL. CR reduced cardiac oxidative stress detected by DHE staining. Cardiac autophagy and cyclic AMP-AMPK activity were enhanced in DIO-CR group. The increased levels of PINK1 and parkin (the cooperative indicators for the damaged mitochondria) in DIOAL were reversed by CR. Conclusions: CR ameliorates cardiac dysfunction remodeling in cardiac steatosis via activation of autophagy through the cyclic AMP-AMPkinase axis.
O-071 Losartan/hydrochlorothiazide Combination Therapy Improved Diastolic Dysfunction in Patients with Uncontrolled Hypertension in Comparison with a High-dose Therapy of Losartan KAZUHIDE OGINO1, MASAYUKI HIRAI2, YOSHIHARU KINUGASA2, MASAHIKO KATO2, KAZUHIRO YAMAMOTO2 1 Center for Clinical Residency Program, Tottori University Hospital, Tottori, Japan, 2 Division of Molecular Medicine and Therapeutics, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Tottori, Japan Purpose and Methods: Diastolic dysfunction is common in hypertensive patients, however, it is remains unknown if a combination therapy of angiotensin II receptor blocker and thiazide diuretics improves diastolic dysfunction in hypertensive patients. In this study, therefore, we evaluated the effects of a combination therapy of losartan and hydrochlorothiazide (HCTZ) on diastolic function in hypertensive patients. Uncontrolled hypertensive patients with diastolic dysfunction (n536) treated by losartan (50mg/day) were evaluated before and after the 16-week therapy of a combination of losartan (50mg/day)/HCTZ (12.5mg/day) or a high-dose of losartan (100mg/day). Results: Left ventricular dimension (LV) and E/E’ were significantly decreased with the combination therapy compared with the high-dose therapy of losartan (p!0.05), however, there were no significant differences in LV ejection fraction or % fractional shortening between 2 therapies. BNP were significantly decreased with both therapies (p!0.05) but it was not statistically different between the 2 therapies. Serum uric acid level was decreased and eGFR was increased with the high-dose therapy of losartan (p!0.05). Matrix metalloproteinase 2 (MMP2) level was significantly decreased with the combination therapy (p!0.05), but MMP9 was not changed. Conclusions: The combination therapy of losartan and HCTZ improved diastolic dysfunction in uncontrolled hypertensive patients. On the other hand, the high-dose therapy of losartan did not change diastolic function although this therapy decreased serum uric acid level and improved eGFR.
O-072 Adaptive Servo Ventilation Improves Long-term Prognosis in Heart Failure Patients with Preserved Left Ventricular Ejection Fraction and Sleep Disordered Breathing AKIOMI YOSHIHISA1, SATOSHI SUZUKI1, TAKAMASA SATO2, KOICHI SUGIMOTO2, TAKAYOSHI YAMAKI2, HIROYUKI KUNII2, KAZUHIKO NAKAZATO2, HITOSHI SUZUKI2, SHU-ICHI SAITOH2, YASUCHIKA TAKEISHI1 1 Department of Advanced Cardiac Therapeutics, Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan, 2Department of Cardiology and Hematology Fukushima Medical University, Fukushima, Japan Background: Effective pharmaco-therapy for heart failure with preserved left ventricular ejection fraction (HFpEF) is still unclear. High prevalence of SDB has been
JHFS
S161
documented in HFpEF. Adaptive servo ventilation (ASV) improves SDB. However, it still remains unclear whether ASV improves cardiac function and long-term prognosis of HFpEF with SDB. Methods: Twenty five patients with HFpEF (defined as LVEF of O 45%) and moderate-severe SDB (defined as apnea hypopnea index O 15 /h) were enrolled and divided into two groups: 10 patients treated with conventional medications and ASV (ASV group) and 15 patients treated with conventional medications alone (Non-ASV group). BNP, LVEF, and right ventricular systolic pressure (RVPs) were determined before and 6 months after treatments. Patients were followed to register cardiac events after discharge (average follow up period 728 days). Results: Although, LVEF did not improve in both groups, BNP and RVPs significantly reduced in ASV group (BNP: 285.9 to 161.8 pg/ml, RVPs: 40.5 to 32.1 mmHg, P!0.05, respectively), but not in Non-ASV group. Eight events (death 5, re-hospitalization 3) ocurred in this follow up period. Importantly, event free rate was significantly higher in ASV group than in Non-ASV group (90.0% vs. 53.3%, logrank P!0.05). Conclusions: ASV decreased cardiac overload and improved long-term prognosis in patients with HFpEF and SDB. ASV might be a promissing useful tool for HFpEF and SDB.
O-073 Inappropriate Expression of Hepcidin by Liver Congestion may Play an Important Role in Anemia and Iron Deficiency in Heart Failure TOMOYASU SUZUKI, HARUO HANAWA, SHUANG JIAO, MASAHIRO ITO, TAKESHI KASHIMURA, HIROAKI OBATA, MAKOTO KODAMA Division of Cardiology, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan Background: Anemia and iron deficiency are common in congestive heart failure. Hepcidin produced primarily by hepatocytes plays a central role in the maintenance of systemic iron homeostasis and recent studies have suggested that hepcidin play an important role in anemia and iron deficiency in heart failure. Purpose: We investigated that in liver congestion, anemia, iron kinetics, expression of hepcidin and expression of proinflammatory cytokines and BMP-6, which are known to induce hepcidin. Method: We prepared rat models of liver congestion by ligating inferior vena cava in the space between the diaphragm and liver (IVC stenosis) and compared with sham operation and phlebotomy model. Result: In IVC stenosis rats, persistent anemia, congestion of centrilobular sinusoid, hemosiderin laden macrophages and myofibroblast proliferation were observed and expression of inflammatory cytokines and BMP-6 increased in liver. Hepcidin expression in liver of IVC stenosis rats did not decrease differently from marked down-regulation of hepcidin in phlebotomy model. Conclusion: Inappropriate expression of hepcidin by tissue iron overload or up-regulation of proinflammatory cytokines and BMP-6 due to liver congestion may play an important role in anemia and iron deficiency in right-side heart failure.
O-074 The Impact of the Dilatation of Right Ventricle on Effects of Adaptive Servoventilation in Patients with Acute Heart Failure SHIGEFUMI FUKUI, AKIHIRO NAKAMURA, KENJIRO SATO, SOTA NAKAJIMA, HIDEAKI ENDO, TORU TAKAHASHI, EIJI NOZAKI, KENJI TAMAKI Division of Cardiology, Iwate Prefectural Central Hospital, Morioka, Japan Purpose: To elucidate whether the dilatation of right ventricle infuences the effects of adaptive servo-ventilation (ASV) in patients with acute heart failure (AHF). Methods: Thirteen patients (mean age, 77 6 9) with AHF treated with ASV were retrospectively examined. Results: There were two in-hospital deaths (one; sudden death, the other; ventricular fibrillation due to ischemic heart disease). After ASV treatment, brain natriuretic peptide (BNP) levels were significantly decreased in the whole of patients (1120 6 679 pg/ml to 472 6 514 pg/ml, P!0.05). There was not significant but mildly positive correlation between the extent of the dilatation of right ventricle and that of changes in BNP levels (R50.32). Conclusions: It is possible that right ventricular dysfunction may affect effectiveness of ASV treatment in patients with AHF.
O-075 Clinical Characteristics and Prognosis of Right to Left Filling Pressure Mismatch in the Patients with Acute Decompensated Heart Failure TAKAHIRO NAKASHIMA, HIROYUKI YOKOYAMA, HIROYUKI TAKAHAMA, HIDEAKI KANZAKI, TAKAFUMI YAMANE, TAICHI ADACHI, JUNICHI KOTANI, SATOSHI YASUDA, YOICHI GOTO, MASAFUMI KITAKAZE Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan Background: The prognosis of right-left filling pressure (R-LFP) mismatch diagnosed by pulmonary artery catheter (PAC) in acute decompensated heart failure (ADHF) is unknown. Method: To address this issue, we studied 124 patients performed PAC among 757 ADHF patients who admitted in our hospital. R-LFP mismatch was defined as pulmonary capillary wedge pressure (PCWP) !5 right atrial pressure (RAP) or PCWP!51.5RAP if RAPO510mmHg. Results: Patients were categorized into two groups with (Group R-L; n511) and without R-LFP mismatch. Group R-L showed significantly lower systolic blood pressure at admission, higher serum total bilirubin and lower prevalence of congestion in chest X-ray,
O-070 Carolic Restriction Ameliorates Cardiac Steatosis by Activation of Autophagy via Cyclic AMP/AMPK/PKA Axis AKIO MONJI, YASUKO K. BANDO, MORIHIKO AOYAMA, TOKO MITSUI, TOYOAKI MUROHARA Department of Cardiology, Nagoya University, Nagoya, Japan Introduction: Caloric restriction (CR) promotes beneficial cardiovascular effects and enhances autophagy partly via the cyclic-AMP elevation. Cardiac steatosis impairs cardiac function associated with myocardial lipid accumulation and lipotoxic injury. However, the impact of CR on the cardiac steatosis remains unclear. Hypothesis: Cardiac steatosis-induced remodeling may be reversed by CR via activation of autophagy through the cyclic AMP/AMPkinase axis. Methods: High-fat-diet-induced obese mice (DIO) and age-matched counterparts (CTL) were allocated into CR and ad libitum (AL) group. Results: DIO-CR exhibited 32.661.58% reduction in body weight. DIO-AL exhibited reduced systolic left-ventricular function (EF(%); 66.262.9 for DIO-AL versus 76.862.3 for CTL-AL) and increased left-ventricular wall thickness (LVPWd(mm); 0.9360.08 versus 0.7360.03). CR reversed the systolic dysfunction and LV hypertrophy observed in DIO-AL groups (EF(%); 72.361.7 for DIO-CR versus 65.662.0 for DIOAL, LVPWd(mm); 0.8160.06 versus 0.9060.06). DIO-AL exhibited enhanced interstitial fibrosis compared to CTL-AL, that was reduced in DIO-CR (0.5860.10-fold versus DIOAL). Oil-red-O staining revealed that CR ameliorated cardiac lipid accumulation in DIOAL. CR reduced cardiac oxidative stress detected by DHE staining. Cardiac autophagy and cyclic AMP-AMPK activity were enhanced in DIO-CR group. The increased levels of PINK1 and parkin (the cooperative indicators for the damaged mitochondria) in DIOAL were reversed by CR. Conclusions: CR ameliorates cardiac dysfunction remodeling in cardiac steatosis via activation of autophagy through the cyclic AMP-AMPkinase axis.
O-071 Losartan/hydrochlorothiazide Combination Therapy Improved Diastolic Dysfunction in Patients with Uncontrolled Hypertension in Comparison with a High-dose Therapy of Losartan KAZUHIDE OGINO1, MASAYUKI HIRAI2, YOSHIHARU KINUGASA2, MASAHIKO KATO2, KAZUHIRO YAMAMOTO2 1 Center for Clinical Residency Program, Tottori University Hospital, Tottori, Japan, 2 Division of Molecular Medicine and Therapeutics, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Tottori, Japan Purpose and Methods: Diastolic dysfunction is common in hypertensive patients, however, it is remains unknown if a combination therapy of angiotensin II receptor blocker and thiazide diuretics improves diastolic dysfunction in hypertensive patients. In this study, therefore, we evaluated the effects of a combination therapy of losartan and hydrochlorothiazide (HCTZ) on diastolic function in hypertensive patients. Uncontrolled hypertensive patients with diastolic dysfunction (n536) treated by losartan (50mg/day) were evaluated before and after the 16-week therapy of a combination of losartan (50mg/day)/HCTZ (12.5mg/day) or a high-dose of losartan (100mg/day). Results: Left ventricular dimension (LV) and E/E’ were significantly decreased with the combination therapy compared with the high-dose therapy of losartan (p!0.05), however, there were no significant differences in LV ejection fraction or % fractional shortening between 2 therapies. BNP were significantly decreased with both therapies (p!0.05) but it was not statistically different between the 2 therapies. Serum uric acid level was decreased and eGFR was increased with the high-dose therapy of losartan (p!0.05). Matrix metalloproteinase 2 (MMP2) level was significantly decreased with the combination therapy (p!0.05), but MMP9 was not changed. Conclusions: The combination therapy of losartan and HCTZ improved diastolic dysfunction in uncontrolled hypertensive patients. On the other hand, the high-dose therapy of losartan did not change diastolic function although this therapy decreased serum uric acid level and improved eGFR.
O-072 Adaptive Servo Ventilation Improves Long-term Prognosis in Heart Failure Patients with Preserved Left Ventricular Ejection Fraction and Sleep Disordered Breathing AKIOMI YOSHIHISA1, SATOSHI SUZUKI1, TAKAMASA SATO2, KOICHI SUGIMOTO2, TAKAYOSHI YAMAKI2, HIROYUKI KUNII2, KAZUHIKO NAKAZATO2, HITOSHI SUZUKI2, SHU-ICHI SAITOH2, YASUCHIKA TAKEISHI1 1 Department of Advanced Cardiac Therapeutics, Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan, 2Department of Cardiology and Hematology Fukushima Medical University, Fukushima, Japan Background: Effective pharmaco-therapy for heart failure with preserved left ventricular ejection fraction (HFpEF) is still unclear. High prevalence of SDB has been
JHFS
S161
documented in HFpEF. Adaptive servo ventilation (ASV) improves SDB. However, it still remains unclear whether ASV improves cardiac function and long-term prognosis of HFpEF with SDB. Methods: Twenty five patients with HFpEF (defined as LVEF of O 45%) and moderate-severe SDB (defined as apnea hypopnea index O 15 /h) were enrolled and divided into two groups: 10 patients treated with conventional medications and ASV (ASV group) and 15 patients treated with conventional medications alone (Non-ASV group). BNP, LVEF, and right ventricular systolic pressure (RVPs) were determined before and 6 months after treatments. Patients were followed to register cardiac events after discharge (average follow up period 728 days). Results: Although, LVEF did not improve in both groups, BNP and RVPs significantly reduced in ASV group (BNP: 285.9 to 161.8 pg/ml, RVPs: 40.5 to 32.1 mmHg, P!0.05, respectively), but not in Non-ASV group. Eight events (death 5, re-hospitalization 3) ocurred in this follow up period. Importantly, event free rate was significantly higher in ASV group than in Non-ASV group (90.0% vs. 53.3%, logrank P!0.05). Conclusions: ASV decreased cardiac overload and improved long-term prognosis in patients with HFpEF and SDB. ASV might be a promissing useful tool for HFpEF and SDB.
O-073 Inappropriate Expression of Hepcidin by Liver Congestion may Play an Important Role in Anemia and Iron Deficiency in Heart Failure TOMOYASU SUZUKI, HARUO HANAWA, SHUANG JIAO, MASAHIRO ITO, TAKESHI KASHIMURA, HIROAKI OBATA, MAKOTO KODAMA Division of Cardiology, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan Background: Anemia and iron deficiency are common in congestive heart failure. Hepcidin produced primarily by hepatocytes plays a central role in the maintenance of systemic iron homeostasis and recent studies have suggested that hepcidin play an important role in anemia and iron deficiency in heart failure. Purpose: We investigated that in liver congestion, anemia, iron kinetics, expression of hepcidin and expression of proinflammatory cytokines and BMP-6, which are known to induce hepcidin. Method: We prepared rat models of liver congestion by ligating inferior vena cava in the space between the diaphragm and liver (IVC stenosis) and compared with sham operation and phlebotomy model. Result: In IVC stenosis rats, persistent anemia, congestion of centrilobular sinusoid, hemosiderin laden macrophages and myofibroblast proliferation were observed and expression of inflammatory cytokines and BMP-6 increased in liver. Hepcidin expression in liver of IVC stenosis rats did not decrease differently from marked down-regulation of hepcidin in phlebotomy model. Conclusion: Inappropriate expression of hepcidin by tissue iron overload or up-regulation of proinflammatory cytokines and BMP-6 due to liver congestion may play an important role in anemia and iron deficiency in right-side heart failure.
O-074 The Impact of the Dilatation of Right Ventricle on Effects of Adaptive Servoventilation in Patients with Acute Heart Failure SHIGEFUMI FUKUI, AKIHIRO NAKAMURA, KENJIRO SATO, SOTA NAKAJIMA, HIDEAKI ENDO, TORU TAKAHASHI, EIJI NOZAKI, KENJI TAMAKI Division of Cardiology, Iwate Prefectural Central Hospital, Morioka, Japan Purpose: To elucidate whether the dilatation of right ventricle infuences the effects of adaptive servo-ventilation (ASV) in patients with acute heart failure (AHF). Methods: Thirteen patients (mean age, 77 6 9) with AHF treated with ASV were retrospectively examined. Results: There were two in-hospital deaths (one; sudden death, the other; ventricular fibrillation due to ischemic heart disease). After ASV treatment, brain natriuretic peptide (BNP) levels were significantly decreased in the whole of patients (1120 6 679 pg/ml to 472 6 514 pg/ml, P!0.05). There was not significant but mildly positive correlation between the extent of the dilatation of right ventricle and that of changes in BNP levels (R50.32). Conclusions: It is possible that right ventricular dysfunction may affect effectiveness of ASV treatment in patients with AHF.
O-075 Clinical Characteristics and Prognosis of Right to Left Filling Pressure Mismatch in the Patients with Acute Decompensated Heart Failure TAKAHIRO NAKASHIMA, HIROYUKI YOKOYAMA, HIROYUKI TAKAHAMA, HIDEAKI KANZAKI, TAKAFUMI YAMANE, TAICHI ADACHI, JUNICHI KOTANI, SATOSHI YASUDA, YOICHI GOTO, MASAFUMI KITAKAZE Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan Background: The prognosis of right-left filling pressure (R-LFP) mismatch diagnosed by pulmonary artery catheter (PAC) in acute decompensated heart failure (ADHF) is unknown. Method: To address this issue, we studied 124 patients performed PAC among 757 ADHF patients who admitted in our hospital. R-LFP mismatch was defined as pulmonary capillary wedge pressure (PCWP) !5 right atrial pressure (RAP) or PCWP!51.5RAP if RAPO510mmHg. Results: Patients were categorized into two groups with (Group R-L; n511) and without R-LFP mismatch. Group R-L showed significantly lower systolic blood pressure at admission, higher serum total bilirubin and lower prevalence of congestion in chest X-ray,