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Intravenous Vagal Nerve Stimulation in Acute Myocardial Infarction (AMI) Strikingly Reduces Infarction Size and Improves Chronic Cardiac Failure
S150 Journal of Cardiac Failure Vol. 20 No. 10S October 2014 O-022 Long-term Effect of Tolvaptan in Patient with Chronic Heart Failure TORU SHIBAHARA1, KEN IKEDA1, TOSHIYA FUJIWARA1, MASAYASU NAKAGAWA1, SATOSHI KIBIRA2, HIROSHI ITO3 1 Cardiorogy, Akita city hospital, Akita, Japan, 2Cardiology, Kibira Medical Clinic, Akita, Japan, 3Cardiovascular and Raspiratory Medicine, Akita University Graduate School of Medicine, Akita, Japan Background: Tolvaptan, a selective vasopressin V2-receptor antagonist, has clinical efficacy in reducing volume overload in patients with heart failure. However, it is still unclear whether Tolvaptan improves long-term prognos is or not. In this study, we investigated the long-term effect of Tolvaptan in patients with diuretic-resistant heart failure. Methods: Between February 2012 and April 2014, 39 patients with heart failure were hospitalized in our hospital and were treated with Tolvaptan. Tolvaptan was continued with 17 patients (10 male and 7 female, 74611 years old) after discharge. Results: Tolvaptan therapy improved NYHA class and avoided readmission. However 2 patients died within 6 month after induction of tolvaptan therapy because of sudden death. Conclusions: These results suggest tolvaptan therapy improves prognosis and quality of life in patients with severe heart failure.
O-023 The Chronic Administration of Tolvaptan Controls Advance of Renal Dysfunction in Patients with Chronic Heart Failure YOHEI ONO1, HIROTO TAKAMATSU1, MASASHI ARAI2, HITOSHI ADACHI3 1 Division of Cardiology, Fujioka General Hospital, Fujioka, Gunma, Japan, 2Division of Cardiology, Tatebayashi Kosei Hospital, Tatebayashi, Gunma, Japan, 3Division of Cardiology, Gunma Prefectural Cardiovascular Center Background: Effectiveness of tolvapton in chronic heart failure has not been fully studied yet. In this study, we investigated the effect of tolvaptan on prognosis and renal function in chronic heart failure. Methods: We enrolled consecutive 32 patients with acute heart failure who were responders to tolvaptan. We classified the patients who took tolvaptan only in acute phase into Group-A (n513), and the patients who took tolvaptan in chronic phase as well as acute phase into Group-C (n519). We compared outcomes and renal function at chronic phase between two groups. Results: There were no significant differences in age, medications and the echocardiographic data between two groups. eGFR in acute phase was significantly (p50.02) lower in Group-C (38.0619.6) than Group-A (56.4622.6). BNP was significantly (p50.048) higher in Group-C (1608.161286.5pg/ dl) than Group-A (857.36588.3pg/dl). As for the outcomes of heart failure, there were no significant differences in the mortality (8% in Group-A vs. 16% in Group-C, p50.41) and re-hospitalization rate (23% vs. 37%, p50.50). When we compared the alternation of eGFR from acute to chronic phase, it was improved in Group-C (2.869.9), while worsened in Group-A (-9.2613.5), and there was significant difference in the improving ratio between two groups (p50.01). Conclusion: The chronic administration of tolvaptan prevented deterioration of renal function in heart failure patients without worsening the clinical outcome and heart failure.
O-024 Association Factor Affecting Diuresis of Intravenous Salt Supplementation with Low-dose Furosemide for Treatment of Acute Decompensated Heart Failure TOMOTAKA ANDO, SHINICHI HIROTANI, HISASHI SAWADA, MASATAKA SUGAHARA, SHOHEI FUJIWARA, AKIYO EGUCHI, YOSHITAKA OKUHARA, DAISUKE MORISAWA, TOSHIHIRO IWASAKU, TOHRU MASUYAMA Department of Internal Medicine, Cardiovascular Division Hyogo College of Medicine, Nishinomiya, Japan Background: We have reported that supplementation of salt to furosemide enhances the diuretic effectiveness in treatment of acute decompensated heart failure (ADHF). However, there are some cases in that intravenous salt supplementation with low-dose furosemide (HTS therapy) does not work effectively. In this study, we investigated association factor affecting diuresis of HTS therapy. Method: Fifteen patients in ADHF with volume over were analyzed. We examined 24-hour urinary volume, biochemical value and parameters of cardiac ultrasonography before treatment. We investigated the correlation between urinary volume and biochemical value. Result: There were no correlation between urinary volume and serum sodium concentration, urine sodium concentration, and plasma brain natriuretic Peptide. There is negative correlation between urinary volume and urine potassium concentration (r250.35). There were no correlation between urinary volume and parameters of cardiac ultrasonography. Conclusion: Our date showed that urine potassium concentration can be a predictive factor on diuretic effectiveness of HTS therapy for treatment of ADHF.
O-030
clinical applications. We developed a simple and practical percutaneous intravenous VNS (iVNS) and examine its clinical impact on ischemia-reperfusion (I/R) model. Method: We used 16 mongrel dogs. For I/R we ligated the left anterior descending coronary artery for 3 hours then reperfused. For iVNS we performed the field electrical stimulation by pacing catheter in the superior vena cava. One month after ischemiareperfusion, we compared the infarct size, hemodynamics and ventricular function by end-systolic elastance (Ees, Millar pressure and sonomicrometric volumetry) among 3 groups, sham (N53), iVNS (N56) and no iVNS (N57). Results: Compared to no VNS, iVNS strikingly decreased the infarction size (0.960.9 vs. 6.462.0cm2, p! 0.05), LVEDP (4.161.7 vs. 15.867.6 mmHg, p!0.05), and NT-pro BNP (1282690 vs. 366761637 pmol/ml, p!0.05) and increased Ees (16.066.2 vs. 6.363.3 mmHg/ ml, p!0.05). Conclusion: Intravenous VNS reduced the infarct size and improved chronic cardiac function (4 weeks) after AMI. Intravenous VNS could be a clinically useful device therapy for AMI and prevent heart failure in the long term.
O-031 Activation of Baroreflex Instantly Reduces Left Atrial Pressure and Increases Cardiac Output in Dogs with Pacing Induced Heart Failure TAKAFUMI SAKAMOTO, TAKAMORI KAKINO, KEITA SAKU, KENJI SUNAGAWA Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan Background: In heart failure, excessive activation of sympathetic nerve activity (SNA) constricts both resistance and capacitance vessels and worsens pulmonary congestion. Pulmonary congestion induces hypoxia and hypoxia induced sympathoexcitation initiates the vicious cycle of decompensated heart failure. Baroreflex is known as one of the strongest and quickest modulators of SNA. We hypothesized that activation of baroreflex suppresses SNA and quickly improves hemodynamics in heart failure. Methods: In 5 mongrel dogs with pacing induced heart failure (ejection fraction520w30%), we isolated both carotid sinuses and connected them to a servo-controlled piston pump to control carotid sinus pressure (CSP). After maintaining CSP at 80mmHg, we activated baroreflex by increasing CSP to 160 mmHg and suppressed SNA. We measured right atrial pressure (RAP), left atrial pressures (LAP) and aortic flow (CO). Results: Activation of baroreflex significantly lowered the LAP (23 6 2 mmHg vs. 9 6 4 mmHg, p!0.005), RAP (7.9 6 1.6 mmHg vs. 5.9 6 1.9 mmHg, p!0.005), while increased CO by 15% (40 6 10 ml/kg/min vs. 46 6 10 ml/kg/min, p!0.005). All hemodynamic variables reached a steady state in a few minutes. Conclusion: Activation of baroreflex strikingly and instantly reduces the left atrial pressure, while increases cardiac output in dogs with pacing induced heart failure. This mechanism can serve as a novel therapeutic strategy for acute decompensated heart failure.
O-032 Fibroblast-specific TGFb Receptor Inhibition Promotes Smooth Muscle Proliferation in Coronary Artery of Pressure-overloaded Mouse Heart NORIMICHI KOITABASHI1, MASARU OBOKATA1, MITSURU SEKI1, SIMON CONWAY2, DAVID KASS3, MASAHIKO KURABAYASHI1 1 Department of Cardiovascular Medicine, Gunma University, Maebashi, Japan, 2 Indiana University School of Medicine, Indianapolis, USA, 3Johns Hopkins University, Baltimore, USA Transforming Growth Factor beta (TGFb) is a key factor which regulates proliferation of fibroblasts and collagen production. Since TGFb signaling also has critical roles on inflammatory response, cellular hypertrophy and angiogenesis, the net effect on injured organ is sometimes controversial. To dissect the role of TGFb signaling in pathological cardiac remodeling, cell-specific conditional gene manipulation models would be necessary. Previously we have shown that cardiomyocyte-specific TGFb inhibition prevents cardiac pathological remodeling. Here, we tested the role of cell-specific TGFb signaling in chronic pressure-overload using fibroblast (FB)-specific gene suppression of TGFb type1 receptor (Tgfbr1) in mice. We created periostin-promoter Cre x Tgfbr1 floxed mice. Transverse aortic constriction (TAC) promotes progressive cardiac hypertrophy and ventricular dysfunction. FB-specific TGFb inhibition attenuated cardiac dysfunction induced by TAC. Surprisingly, perivascular fibrosis was enhanced in FB-specific TGFb inhibition. In addition, intimal smooth muscle cells in epicardial coronary artery showed marked proliferation. On the other hand, systemic inhibition of TGFb signalingby neutralizing antibody administration failed to attenuate cardiac remodeling in spite of suppressing effect on fibrosis. Our results revealed the TGFb-mediated complex interaction in heart cells to control cardiac function and structure against pathological stress.
O-033
Intravenous Vagal Nerve Stimulation in Acute Myocardial Infarction (AMI) Strikingly Reduces Infarction Size and Improves Chronic Cardiac Failure TAKAHIRO ARIMURA1, KEITA SAKU1, TAKAMORI KAKINO1, TAKUYA AKASHI1, YOSHINORI MURAYAMA1, TAKAKO TAKEHARA1, TOMOMI IDE1, TAKUYA KISHI1,2, KENJI SUNAGAWA1 1 Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan, 2 Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University, Fukuoka, Japan
p53-induced Cardio - Bone Marrow Axis Remodeling Deteriorates Cardiac Function During Pressure Overload YOHKO YOSHIDA1,2, IPPEI SHIMIZU1,2, GORO KATSUUMI2, MASAYOSHI SUDA2, YUKA HAYASHI2, RYUTARO IKEGAMI2, HIROMI KAYAMORI2, SHUANG JIAO2, TOHRU MINAMINO2 1 Department of Molecular Aging and Cell Biology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, 2Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Background: Although vagal nerve stimulation (VNS) is known to reduce infarct size and improve chronic heart failure, technical difficulties associated with VNS prevents it from
The death rate related to severe heart failure is still unacceptably high. Accumulating evidence has demonstrated the role of sterile inflammatory responses in the progression
O-023 The Chronic Administration of Tolvaptan Controls Advance of Renal Dysfunction in Patients with Chronic Heart Failure YOHEI ONO1, HIROTO TAKAMATSU1, MASASHI ARAI2, HITOSHI ADACHI3 1 Division of Cardiology, Fujioka General Hospital, Fujioka, Gunma, Japan, 2Division of Cardiology, Tatebayashi Kosei Hospital, Tatebayashi, Gunma, Japan, 3Division of Cardiology, Gunma Prefectural Cardiovascular Center Background: Effectiveness of tolvapton in chronic heart failure has not been fully studied yet. In this study, we investigated the effect of tolvaptan on prognosis and renal function in chronic heart failure. Methods: We enrolled consecutive 32 patients with acute heart failure who were responders to tolvaptan. We classified the patients who took tolvaptan only in acute phase into Group-A (n513), and the patients who took tolvaptan in chronic phase as well as acute phase into Group-C (n519). We compared outcomes and renal function at chronic phase between two groups. Results: There were no significant differences in age, medications and the echocardiographic data between two groups. eGFR in acute phase was significantly (p50.02) lower in Group-C (38.0619.6) than Group-A (56.4622.6). BNP was significantly (p50.048) higher in Group-C (1608.161286.5pg/ dl) than Group-A (857.36588.3pg/dl). As for the outcomes of heart failure, there were no significant differences in the mortality (8% in Group-A vs. 16% in Group-C, p50.41) and re-hospitalization rate (23% vs. 37%, p50.50). When we compared the alternation of eGFR from acute to chronic phase, it was improved in Group-C (2.869.9), while worsened in Group-A (-9.2613.5), and there was significant difference in the improving ratio between two groups (p50.01). Conclusion: The chronic administration of tolvaptan prevented deterioration of renal function in heart failure patients without worsening the clinical outcome and heart failure.
O-024 Association Factor Affecting Diuresis of Intravenous Salt Supplementation with Low-dose Furosemide for Treatment of Acute Decompensated Heart Failure TOMOTAKA ANDO, SHINICHI HIROTANI, HISASHI SAWADA, MASATAKA SUGAHARA, SHOHEI FUJIWARA, AKIYO EGUCHI, YOSHITAKA OKUHARA, DAISUKE MORISAWA, TOSHIHIRO IWASAKU, TOHRU MASUYAMA Department of Internal Medicine, Cardiovascular Division Hyogo College of Medicine, Nishinomiya, Japan Background: We have reported that supplementation of salt to furosemide enhances the diuretic effectiveness in treatment of acute decompensated heart failure (ADHF). However, there are some cases in that intravenous salt supplementation with low-dose furosemide (HTS therapy) does not work effectively. In this study, we investigated association factor affecting diuresis of HTS therapy. Method: Fifteen patients in ADHF with volume over were analyzed. We examined 24-hour urinary volume, biochemical value and parameters of cardiac ultrasonography before treatment. We investigated the correlation between urinary volume and biochemical value. Result: There were no correlation between urinary volume and serum sodium concentration, urine sodium concentration, and plasma brain natriuretic Peptide. There is negative correlation between urinary volume and urine potassium concentration (r250.35). There were no correlation between urinary volume and parameters of cardiac ultrasonography. Conclusion: Our date showed that urine potassium concentration can be a predictive factor on diuretic effectiveness of HTS therapy for treatment of ADHF.
O-030
clinical applications. We developed a simple and practical percutaneous intravenous VNS (iVNS) and examine its clinical impact on ischemia-reperfusion (I/R) model. Method: We used 16 mongrel dogs. For I/R we ligated the left anterior descending coronary artery for 3 hours then reperfused. For iVNS we performed the field electrical stimulation by pacing catheter in the superior vena cava. One month after ischemiareperfusion, we compared the infarct size, hemodynamics and ventricular function by end-systolic elastance (Ees, Millar pressure and sonomicrometric volumetry) among 3 groups, sham (N53), iVNS (N56) and no iVNS (N57). Results: Compared to no VNS, iVNS strikingly decreased the infarction size (0.960.9 vs. 6.462.0cm2, p! 0.05), LVEDP (4.161.7 vs. 15.867.6 mmHg, p!0.05), and NT-pro BNP (1282690 vs. 366761637 pmol/ml, p!0.05) and increased Ees (16.066.2 vs. 6.363.3 mmHg/ ml, p!0.05). Conclusion: Intravenous VNS reduced the infarct size and improved chronic cardiac function (4 weeks) after AMI. Intravenous VNS could be a clinically useful device therapy for AMI and prevent heart failure in the long term.
O-031 Activation of Baroreflex Instantly Reduces Left Atrial Pressure and Increases Cardiac Output in Dogs with Pacing Induced Heart Failure TAKAFUMI SAKAMOTO, TAKAMORI KAKINO, KEITA SAKU, KENJI SUNAGAWA Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan Background: In heart failure, excessive activation of sympathetic nerve activity (SNA) constricts both resistance and capacitance vessels and worsens pulmonary congestion. Pulmonary congestion induces hypoxia and hypoxia induced sympathoexcitation initiates the vicious cycle of decompensated heart failure. Baroreflex is known as one of the strongest and quickest modulators of SNA. We hypothesized that activation of baroreflex suppresses SNA and quickly improves hemodynamics in heart failure. Methods: In 5 mongrel dogs with pacing induced heart failure (ejection fraction520w30%), we isolated both carotid sinuses and connected them to a servo-controlled piston pump to control carotid sinus pressure (CSP). After maintaining CSP at 80mmHg, we activated baroreflex by increasing CSP to 160 mmHg and suppressed SNA. We measured right atrial pressure (RAP), left atrial pressures (LAP) and aortic flow (CO). Results: Activation of baroreflex significantly lowered the LAP (23 6 2 mmHg vs. 9 6 4 mmHg, p!0.005), RAP (7.9 6 1.6 mmHg vs. 5.9 6 1.9 mmHg, p!0.005), while increased CO by 15% (40 6 10 ml/kg/min vs. 46 6 10 ml/kg/min, p!0.005). All hemodynamic variables reached a steady state in a few minutes. Conclusion: Activation of baroreflex strikingly and instantly reduces the left atrial pressure, while increases cardiac output in dogs with pacing induced heart failure. This mechanism can serve as a novel therapeutic strategy for acute decompensated heart failure.
O-032 Fibroblast-specific TGFb Receptor Inhibition Promotes Smooth Muscle Proliferation in Coronary Artery of Pressure-overloaded Mouse Heart NORIMICHI KOITABASHI1, MASARU OBOKATA1, MITSURU SEKI1, SIMON CONWAY2, DAVID KASS3, MASAHIKO KURABAYASHI1 1 Department of Cardiovascular Medicine, Gunma University, Maebashi, Japan, 2 Indiana University School of Medicine, Indianapolis, USA, 3Johns Hopkins University, Baltimore, USA Transforming Growth Factor beta (TGFb) is a key factor which regulates proliferation of fibroblasts and collagen production. Since TGFb signaling also has critical roles on inflammatory response, cellular hypertrophy and angiogenesis, the net effect on injured organ is sometimes controversial. To dissect the role of TGFb signaling in pathological cardiac remodeling, cell-specific conditional gene manipulation models would be necessary. Previously we have shown that cardiomyocyte-specific TGFb inhibition prevents cardiac pathological remodeling. Here, we tested the role of cell-specific TGFb signaling in chronic pressure-overload using fibroblast (FB)-specific gene suppression of TGFb type1 receptor (Tgfbr1) in mice. We created periostin-promoter Cre x Tgfbr1 floxed mice. Transverse aortic constriction (TAC) promotes progressive cardiac hypertrophy and ventricular dysfunction. FB-specific TGFb inhibition attenuated cardiac dysfunction induced by TAC. Surprisingly, perivascular fibrosis was enhanced in FB-specific TGFb inhibition. In addition, intimal smooth muscle cells in epicardial coronary artery showed marked proliferation. On the other hand, systemic inhibition of TGFb signalingby neutralizing antibody administration failed to attenuate cardiac remodeling in spite of suppressing effect on fibrosis. Our results revealed the TGFb-mediated complex interaction in heart cells to control cardiac function and structure against pathological stress.
O-033
Intravenous Vagal Nerve Stimulation in Acute Myocardial Infarction (AMI) Strikingly Reduces Infarction Size and Improves Chronic Cardiac Failure TAKAHIRO ARIMURA1, KEITA SAKU1, TAKAMORI KAKINO1, TAKUYA AKASHI1, YOSHINORI MURAYAMA1, TAKAKO TAKEHARA1, TOMOMI IDE1, TAKUYA KISHI1,2, KENJI SUNAGAWA1 1 Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan, 2 Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University, Fukuoka, Japan
p53-induced Cardio - Bone Marrow Axis Remodeling Deteriorates Cardiac Function During Pressure Overload YOHKO YOSHIDA1,2, IPPEI SHIMIZU1,2, GORO KATSUUMI2, MASAYOSHI SUDA2, YUKA HAYASHI2, RYUTARO IKEGAMI2, HIROMI KAYAMORI2, SHUANG JIAO2, TOHRU MINAMINO2 1 Department of Molecular Aging and Cell Biology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, 2Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Background: Although vagal nerve stimulation (VNS) is known to reduce infarct size and improve chronic heart failure, technical difficulties associated with VNS prevents it from
The death rate related to severe heart failure is still unacceptably high. Accumulating evidence has demonstrated the role of sterile inflammatory responses in the progression