- Email: [email protected]
Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia
S180 Journal of Cardiac Failure Vol. 18 No. 10S October 2012 were performed with left coronary artery ligation and randomized to treatment with HFD alone (control group) or HFD plus DPP-4 inhibitor (MK-626, 3mg/kg/day) (MK group). Left ventricular function was assessed using echocardiography at day 5. Infarct size, the number of vessels, and myocardial ischemia were assessed at day 5. Serum DPP-4 activity was assessed at day 3. Results: Serum DPP-4 activity was increased in control mice compared to sham mice, but it was significantly decreased by DPP-4 inhibitor (sham 360693RLU, control 8536114RLU, MK 104678RLU, p!0.05) at day 3. The treatment with DPP-4 inhibitor significantly improved left ventricular function (EF: sham 71.263.6%, control 20.866.7%, MK 40.664.3%, p!0.05) and decreased the infarction size. DPP-4 inhibitor also increased the ratio of PECAM-positive endothelial cells to dystrophin-positive cardiomyocytes (sham 0.8260.03, control 0.8260.04, MK 1.1660.07, p!0.05) and decreased the area of hypoxiprobe-1-positive ischemia in the border area (sham 0.2660.11%, control 8.7160.28%, MK 5.8360.56%, p!0.05). Conclusion: DPP-4 inhibitors may have cardioprotective effects through the decrease in myocardial ischemia in post-myocardial infarction heart.
P-079 Infarct Size and Ventricular Dilatation for 4 Weeks After the Onset of Acute Myocardial Infarction Determines Prominent Left Ventricular Remodeling YUKI IKEDA, TAKAYUKI INOMATA, TOSHIMI KOITABASHI, TAKASHI NARUKE, ICHIRO WATANABE, SHUNSUKE ISII, ICHIROU TAKEUCHI, TOHRU IZUMI Department of Cardio-angiology, Kitasato University School of Medicine, Kanagawa, Japan Background: Although the long-term prognosis of acute myocardial infarction (AMI) depends on left ventricular remodeling (LVR), which may lead to chronic heart failure, the chronological transition of LVR after AMI has not been well elucidated. Methods & Results: We studied 39 consecutive patients with AMI due to obstruction of the left anterior descending artery (LAD) in 2009-2011. A gated single photon emission computed tomography (SPECT) was performed at 1, 4, and 24 weeks after the onset of AMI. Patients were stratified into two groups according to the median LV end-diastolic volume index (LVEDVI; 71 ml/m2) at the 24th week. Compared to the group with the lower LVEDVI (L; 55 6 11 ml/m2), the group with the higher LVEDVI (H; 94 6 22 ml/m2) showed significantly higher levels of serum creatine phosphokinase (2307 6 1700 IU/L vs. 5960 6 2867 respectively, P ! 0.0001) on admission together with a significantly higher summed rest score (SRS; 15 6 10 IU/L vs. 25 6 9 respectively P50.003) in the 1st week. The H group presented extensively impaired myocardium. In the H group, the increase in SRS was prominent in the area outside the territory supplied by LAD during the period between the 1st and 4th weeks. Conclusion: SRS calculated using SPECT during the first month after AMI may predict subsequent LVR.
P-080 The Optimal Timing of Coronary Revascularization in Patients with Acute Heart Failure Syndrome and Coronary Artery Disease YASUTAKA INUZUKA1, TAKESHI KIMURA2 1 Department of Cardiology, Shiga Medical Center for Adults, Shiga, Japan, 2 Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Background: The optimal timing for coronary revascularization in patients with acute heart failure syndrome and coronary artery disease (CAD) except for acute coronary syndrome (ACS) is unclear. Methods: Among 13,087 patients undergoing first percutaneous coronary intervention (PCI) in the CREDO-Kyoto registry Cohort-2 from January 2005 to December 2007, we identified 849 non-ACS patients with AHFS and CAD. One hundred eighty-one patients underwent PCI within 3 days of hospitalization (early PCI group), and 668 patients underwent PCI after 4days of hospitalization (late PCI group). Results: The early PCI group had a higher ejection fractions (52% versus 45%, PO0.01) and fewer cardiovascular comorbidities. Angiographical characteristics were compatible between the two groups. At three years, all-cause mortality was not different between the groups (18% versus 23%, log rank P50.59). After adjusting confounders, the hazard ratio (HR) for early PCI versus late PCI was 1.01 (95% confidence interval [CI], 0.64-1.52; P50.98) for all-cause death. The incidence of rehospitalization for heart failure through three years was significantly lower in early PCI group (14% versus 27%, log rank PO0.01; adjusted HR 0.57 [95% CI, 0.34-0.89], PO0.01). Conclusions: In patients with AHFS and CAD, the strategy of early PCI was associated with similar long-term mortality and a lower risk of rehospitalization compared with the strategy of late PCI.
P-081 Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia KENICHIRO HANAWA1, KENTA ITO1, KENTARO AIZAWA1, TOMOHIKO SHINDO1, KENSUKE NISHIMIYA1, YUHI HASEBE1, HIDEYUKI HASEGAWA2, SATOSHI YASUDA3, HIROSHI KANAI2, HIROAKI 1 SHIMOKAWA 1 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Graduate Schools of Engineering and Biomedical
Engineering, Tohoku University, Japan, 3National Cerebral and Cardiovascular Center, Osaka, Japan Background: The number of patients with severe ischemic heart failure is increasing worldwide. Recently, the low-intensity pulsed ultrasound (LIPUS) has been reported to induce angiogenesis. In this study, we aimed to develop the LIPUS for the treatment of ischemic heart failure. Methods and Results: In cultured human endothelial cells, the LIPUS up-regulated mRNA expression of vascular endothelial growth factor with a peak noted at 32-cycle LIPUS 3 hours after irradiation (P50.02). Based on this in vitro study, the effect of LIPUS was studied in a porcine model of chronic myocardial ischemia with an ameroid constrictor placed around the coronary artery (n517). The ischemic region was treated with either sham treatment (n58) or LIPUS (32-cycle with intensity of 100 mW/cm2 for 20 min) at 3 different short axis levels (n59). Four weeks after the treatment, left ventricular ejection fraction significantly improved in the LIPUS group (4764 to 5765%, P!0.05) without any adverse effects, whereas it remained unchanged in the control group (4665 to 4766%, P50.33). Capillary density was significantly increased, and regional myocardial blood flow was improved only in the LIPUS group. Conclusions: These results indicate that the LIPUS is a new, effective and safe therapeutic strategy for ischemic heart failure.
P-082 Effectiveness of Emergent CRT-D Treatment in a Case with Intractable Severe Ischemic Heart Failure AKIKO KAWANA, YUHI HASEBE, MASATERU KONDO, MAKOTO NAKANO, MOHAMED A SHAFEE, YUJI WAKAYAMA, KOJI HUKUDA, HIROAKI SHIMOKAWA Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan A 58 year-old man was transferred to our hospital for intensive treatment of his severe heart failure. He suffered from a sustained chest pain for more than 8 hours and was transferred to a municipal hospital 6 month before admission. Emergent coronary angiography showed total occlusion of his left anterior descending coronary artery and successful reperfusion of the coronary artery was achieved by subsequent percutaneous coronary intervention (PCI) at 11 hours after the onset of acute myocardial infarction (AMI). The CK levels increased up to 10,724 IU/L, resulting in severe global LV dysfunction with atrial fibrillation (AF) tachycardia and catecholamine-dependent conditions. Introduction of bblocker was unsuccessful due to repetitive worsening heart failure for 6 months. He was finally referred to our hospital for further treatment, including possible heart transplantation. After admission, low-dose amiodarone (50mg) for AF tachycardia was started, but resulted in complete AV block and slow junctional beats with left bundle branch block. He fell into a hemodynamic shock, and needed a temporary pacing and intra-aortic balloon pumping (IABP). We then performed emergent CRT-D implantation the next day, and were finally able to wean IABP and control AF tachycardia with restarting amiodarone. This is a unique case where emergent CRT-D was effective to control intractable severe ischemic heart failure.
P-083 Long-term Effects of Tolvaptan in Patients with Heart Failure HAYATO OGAWA, MASAYOSHI AJIOKA, NAOYA OTAKA, TERUHIRO SAKAGUCHI, YOSHIHISA NAKANO, AKITOSHI HARA, YOSUKE MURASE, HIROYUKI OSANAI, YOSHIHITO NAKASHIMA, HIROSHI ASANO Cardiovascular Medicine, Tosei General Hospital, Seto, Japan Tolvaptan has never been proved to be effective on long-term mortality or morbidity for patients with heart failure. However, continuous use of tolvaptan dramatically reduces frequency of admission in some cases. In this study, we report long-term effects of tolvaptan in patients with heart failure. Sixteen patients (6 male and 10 female) had received tolvaptan in addition to standard heart failure therapy for more than one year. Mean age was 75.3 6 6.1 years, mean ejection fraction was 56.3 6 16.4%, mean serum brain natriuretic peptide (BNP) levels were 322 6 243 pg/ml, and mean serum creatinine levels were 1.24 6 0.48 mg/dL. The frequency of admission during one year was significantly reduced between before and after treatment with tolvaptan (1.69 times to 0.75 times, P 5 0.011). After one-year administration of tolvaptan, mean serum BNP levels decreased, but the difference was not significant (322 6 243 to 223 6 184 pg/ml). Mean serum creatinine, sodium and potassium levels did not change significantly. These findings indicate that long-term tolvaptan treatment prevent hospitalization in patients having heart failure, without worsening renal function.
P-084 Short-term Effects of Tolvaptan in Elderly Patients with Acute Heart Failure JUNKO OHASHI, MINAKO OIKAWA-WAKAYAMA Department of Cadiovascular Medicine, Japanese Red Cross Sendai Hospital, Miyagi, Japan Background: Tolvaptan is a new approach for the treatment of heart failure without affecting renal function. The purpose of this study was to demonstrate the short-term
P-079 Infarct Size and Ventricular Dilatation for 4 Weeks After the Onset of Acute Myocardial Infarction Determines Prominent Left Ventricular Remodeling YUKI IKEDA, TAKAYUKI INOMATA, TOSHIMI KOITABASHI, TAKASHI NARUKE, ICHIRO WATANABE, SHUNSUKE ISII, ICHIROU TAKEUCHI, TOHRU IZUMI Department of Cardio-angiology, Kitasato University School of Medicine, Kanagawa, Japan Background: Although the long-term prognosis of acute myocardial infarction (AMI) depends on left ventricular remodeling (LVR), which may lead to chronic heart failure, the chronological transition of LVR after AMI has not been well elucidated. Methods & Results: We studied 39 consecutive patients with AMI due to obstruction of the left anterior descending artery (LAD) in 2009-2011. A gated single photon emission computed tomography (SPECT) was performed at 1, 4, and 24 weeks after the onset of AMI. Patients were stratified into two groups according to the median LV end-diastolic volume index (LVEDVI; 71 ml/m2) at the 24th week. Compared to the group with the lower LVEDVI (L; 55 6 11 ml/m2), the group with the higher LVEDVI (H; 94 6 22 ml/m2) showed significantly higher levels of serum creatine phosphokinase (2307 6 1700 IU/L vs. 5960 6 2867 respectively, P ! 0.0001) on admission together with a significantly higher summed rest score (SRS; 15 6 10 IU/L vs. 25 6 9 respectively P50.003) in the 1st week. The H group presented extensively impaired myocardium. In the H group, the increase in SRS was prominent in the area outside the territory supplied by LAD during the period between the 1st and 4th weeks. Conclusion: SRS calculated using SPECT during the first month after AMI may predict subsequent LVR.
P-080 The Optimal Timing of Coronary Revascularization in Patients with Acute Heart Failure Syndrome and Coronary Artery Disease YASUTAKA INUZUKA1, TAKESHI KIMURA2 1 Department of Cardiology, Shiga Medical Center for Adults, Shiga, Japan, 2 Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Background: The optimal timing for coronary revascularization in patients with acute heart failure syndrome and coronary artery disease (CAD) except for acute coronary syndrome (ACS) is unclear. Methods: Among 13,087 patients undergoing first percutaneous coronary intervention (PCI) in the CREDO-Kyoto registry Cohort-2 from January 2005 to December 2007, we identified 849 non-ACS patients with AHFS and CAD. One hundred eighty-one patients underwent PCI within 3 days of hospitalization (early PCI group), and 668 patients underwent PCI after 4days of hospitalization (late PCI group). Results: The early PCI group had a higher ejection fractions (52% versus 45%, PO0.01) and fewer cardiovascular comorbidities. Angiographical characteristics were compatible between the two groups. At three years, all-cause mortality was not different between the groups (18% versus 23%, log rank P50.59). After adjusting confounders, the hazard ratio (HR) for early PCI versus late PCI was 1.01 (95% confidence interval [CI], 0.64-1.52; P50.98) for all-cause death. The incidence of rehospitalization for heart failure through three years was significantly lower in early PCI group (14% versus 27%, log rank PO0.01; adjusted HR 0.57 [95% CI, 0.34-0.89], PO0.01). Conclusions: In patients with AHFS and CAD, the strategy of early PCI was associated with similar long-term mortality and a lower risk of rehospitalization compared with the strategy of late PCI.
P-081 Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia KENICHIRO HANAWA1, KENTA ITO1, KENTARO AIZAWA1, TOMOHIKO SHINDO1, KENSUKE NISHIMIYA1, YUHI HASEBE1, HIDEYUKI HASEGAWA2, SATOSHI YASUDA3, HIROSHI KANAI2, HIROAKI 1 SHIMOKAWA 1 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Graduate Schools of Engineering and Biomedical
Engineering, Tohoku University, Japan, 3National Cerebral and Cardiovascular Center, Osaka, Japan Background: The number of patients with severe ischemic heart failure is increasing worldwide. Recently, the low-intensity pulsed ultrasound (LIPUS) has been reported to induce angiogenesis. In this study, we aimed to develop the LIPUS for the treatment of ischemic heart failure. Methods and Results: In cultured human endothelial cells, the LIPUS up-regulated mRNA expression of vascular endothelial growth factor with a peak noted at 32-cycle LIPUS 3 hours after irradiation (P50.02). Based on this in vitro study, the effect of LIPUS was studied in a porcine model of chronic myocardial ischemia with an ameroid constrictor placed around the coronary artery (n517). The ischemic region was treated with either sham treatment (n58) or LIPUS (32-cycle with intensity of 100 mW/cm2 for 20 min) at 3 different short axis levels (n59). Four weeks after the treatment, left ventricular ejection fraction significantly improved in the LIPUS group (4764 to 5765%, P!0.05) without any adverse effects, whereas it remained unchanged in the control group (4665 to 4766%, P50.33). Capillary density was significantly increased, and regional myocardial blood flow was improved only in the LIPUS group. Conclusions: These results indicate that the LIPUS is a new, effective and safe therapeutic strategy for ischemic heart failure.
P-082 Effectiveness of Emergent CRT-D Treatment in a Case with Intractable Severe Ischemic Heart Failure AKIKO KAWANA, YUHI HASEBE, MASATERU KONDO, MAKOTO NAKANO, MOHAMED A SHAFEE, YUJI WAKAYAMA, KOJI HUKUDA, HIROAKI SHIMOKAWA Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan A 58 year-old man was transferred to our hospital for intensive treatment of his severe heart failure. He suffered from a sustained chest pain for more than 8 hours and was transferred to a municipal hospital 6 month before admission. Emergent coronary angiography showed total occlusion of his left anterior descending coronary artery and successful reperfusion of the coronary artery was achieved by subsequent percutaneous coronary intervention (PCI) at 11 hours after the onset of acute myocardial infarction (AMI). The CK levels increased up to 10,724 IU/L, resulting in severe global LV dysfunction with atrial fibrillation (AF) tachycardia and catecholamine-dependent conditions. Introduction of bblocker was unsuccessful due to repetitive worsening heart failure for 6 months. He was finally referred to our hospital for further treatment, including possible heart transplantation. After admission, low-dose amiodarone (50mg) for AF tachycardia was started, but resulted in complete AV block and slow junctional beats with left bundle branch block. He fell into a hemodynamic shock, and needed a temporary pacing and intra-aortic balloon pumping (IABP). We then performed emergent CRT-D implantation the next day, and were finally able to wean IABP and control AF tachycardia with restarting amiodarone. This is a unique case where emergent CRT-D was effective to control intractable severe ischemic heart failure.
P-083 Long-term Effects of Tolvaptan in Patients with Heart Failure HAYATO OGAWA, MASAYOSHI AJIOKA, NAOYA OTAKA, TERUHIRO SAKAGUCHI, YOSHIHISA NAKANO, AKITOSHI HARA, YOSUKE MURASE, HIROYUKI OSANAI, YOSHIHITO NAKASHIMA, HIROSHI ASANO Cardiovascular Medicine, Tosei General Hospital, Seto, Japan Tolvaptan has never been proved to be effective on long-term mortality or morbidity for patients with heart failure. However, continuous use of tolvaptan dramatically reduces frequency of admission in some cases. In this study, we report long-term effects of tolvaptan in patients with heart failure. Sixteen patients (6 male and 10 female) had received tolvaptan in addition to standard heart failure therapy for more than one year. Mean age was 75.3 6 6.1 years, mean ejection fraction was 56.3 6 16.4%, mean serum brain natriuretic peptide (BNP) levels were 322 6 243 pg/ml, and mean serum creatinine levels were 1.24 6 0.48 mg/dL. The frequency of admission during one year was significantly reduced between before and after treatment with tolvaptan (1.69 times to 0.75 times, P 5 0.011). After one-year administration of tolvaptan, mean serum BNP levels decreased, but the difference was not significant (322 6 243 to 223 6 184 pg/ml). Mean serum creatinine, sodium and potassium levels did not change significantly. These findings indicate that long-term tolvaptan treatment prevent hospitalization in patients having heart failure, without worsening renal function.
P-084 Short-term Effects of Tolvaptan in Elderly Patients with Acute Heart Failure JUNKO OHASHI, MINAKO OIKAWA-WAKAYAMA Department of Cadiovascular Medicine, Japanese Red Cross Sendai Hospital, Miyagi, Japan Background: Tolvaptan is a new approach for the treatment of heart failure without affecting renal function. The purpose of this study was to demonstrate the short-term