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Post-Transplant Exercise Tolerability in Japanese Heart Transplant Recipients
S174 Journal of Cardiac Failure Vol. 12 No. 8 Suppl. 2006 Conclusion: These results implicate that the infusion of carperitide have ameliorated effects in diastolic filling and inflammatory cytokines in DCM patients, which was lasting at least for one week.
1062 Post-Transplant Exercise Tolerability in Japanese Heart Transplant Recipients KAZUNOBU SHITAKURA, SHINICHI NUNODA, KIYOTAKA OKAJIMA, CHIEKO FUJII, OSAMU MATSUOKA, SACHIKO OINUMA, YUTAKA KUBO, KUNIAKI OTSUKA Department of Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan Background: Post-transplant exercise tolerability in Japanese heart transplant (HTx) recipients has not been fully elucidated. Subjects: The subjects consisted of 20 Japanese HTx recipients (7 to 53 years old at HTx, 6 females). Age matched 7 healthy volunteers were examined as control. Methods: The indices from symptom-limited treadmill exercise tests with expired gas analysis and heart-to-mediastinum ratio (HMR) of 123I labeled MIBG studies were examined. Hemodynamic parameters by using Swan-Ganz catheter and physical and mental component summary (PCS and MCS) of SF-36 were also obtained. Results: Cardiac index (CI) was correlated with peak VO2 and anaerobic threshold (AT) in HTx recipients (R50.61, 0.54, respectively). In comparison with controls, HTx recipients showed lower values in % peak VO2, % AT, peak HR and peak VO2/HR (mean controls v. HTx recipients, 119.0 v. 76.8, 133.7 v. 92.1, 190 v. 142, 17.2 v. 11.1, respectively). HMR was correlated with % Peak VO2 (R50.65) and maximum HR (R50.51). Peak VO2 and AT in HTx recipients were correlated with PCS and MCS (peak VO2: R50.55, 0.65, AT: R50.52, 0.67, respectively). Conclusions: Exercise tolerability in HTx recipients is lower than in healthy controls. The improvement of cardiac function and exercise tolerability were related to post-transplant QOL. The restoration of the sympathetic innervation was related to improved post-transplant exercise tolerability.
1063 Blockade of the 4-1BB Pathway Suppresses Graft Arterial Disease in Cardiac Allografts HITOSHI SAIKI1, HISANORI KOSUGE1, GO HARAGUCHI1, TOSHIMITSU UEDE2, MITSUAKI ISOBE1 1 Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan, 2Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan Background: 4-1BB is a member of the tumor necrosis factor receptor (TNFR) superfamily. It works as a costimulatory molecule and plays important roles in regulating the immune response. Graft arterial disease is characterized by development of neointimal hyperplasia of graft coronary arteries and it remains a major problem in clinical heart transplantation. We investigated the hypothesis that blockade of the 4-1BB pathway can suppress graft arterial disease. Methods and Results: We performed heterotopic murine cardiac transplantation. Hearts from C57BL/6 mice were transplanted into Bm 12 mice (class II mismatch). 4-1BBIg was injected intraperitoneally (100mg per injection) every 7 days for 8 weeks after transplantation. Neointimal hyperplasia was significantly attenuated by 4-1BBIg treatment (luminal occlusion: 21.663.5%) in comparison with untreated allografts (69.663.5%, p!0.001). T cell infiltration of cardiac allograft and expressions of Interferon-g and Interleukin-13 in cardiac allografts were suppressed by 4-1BBIg treatment. 4-1BB was expressed on CD4 and CD8 positive cells of splenocytes in recipient mice after transplantation. We performed mixed lymphocyte reaction using sensitized splenocytes after allograft transplantation. T cell proliferation was significantly inhibited by addition of 4-1BBIg in a dose-dependent manner. Conclusion: 4-1BBIg attenuated neointimal hyperplasia of graft coronary arteries through suppression of T cell proliferation and cytokine expression. 4-1BB could be therapeutic target of graft arterial disease in heart transplantation.
1064 Efficacy of Doppler Echocardiography in the Detection of Allograft Rejection in Heart Transplant Recipients CHIZUKO KAMIYA, TOMOKO KATOU, HATSUE UEDA, SYUUJI HASHIMOTO, AKIKO MANO, NOBORU ODA, MASAFUMI KITAKAZE, TAKESHI NAKATANI Cardiovascular Medicine, National Cardiovascular Center Purpose: Invasive screenings for acute rejection (AR) by endomyocardial biopsy (EMB) in heart transplant (HTx) recipients are still standard procedures. We investigated either right heart catheterization (RHC) or Doppler echocardiography could detect AR.
Method: We used the International Society for Heart and Lung Transplantation (ISHLT) grading system to classify EBMs; $grade 2 AR as group A, and !grade 1b AR as group B. Among 20 patients who underwent heart transplant from May 1999 to December 2005 and were followed up at National Cardiovascular Center, 8 patients (male 75%, mean age 33.7613.4 year-old) showed $grade 2 AR at any point 4 months after the post-transplant. We reviewed their hemodynamic data obtained from RHC and Doppler echocardiography. Result: Reduced deceleration time of early transmitral filling, and mitral E-wave velocity/early diastolic mitral annular motion velocity were greater in group A compared with group B (162.6612.4msec vs. 150.1620.7msec, p!0.05, and 6.862.7 vs. 6.462.5, p!0.05). None of the hemodynamic parameters obtained from RHC was significantly different between the groups. Conclusion: Detection of diastolic dysfunction by serial measurement of Doppler echocardiography would provide the time of acute rejection in HTx recipients even with stable hemodynamic conditions.
1065 High Incidence of Ventricular Recovery with Left Ventricular Assist Device for Idiopathic Cardiomyopathy in Adolescence NAOSUMI SEKIYA, MATSUMIYA GORO, NISHIMURA MOTONOBU, ICHIKAWA HAJIME, FUKUSHIMA NORIHIDE, SAWA YOSHIKI Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine Purpose: Left ventricular assist system (LVAS) implantation is an effective therapeutic modality for end-stage congestive heart failure(CHF) in pediatric patients as well as in adult population. But, because of low pump flow and poor control of anti coagulant, thrombo-embolic risk are relatively higher. For this reason, we aggressively sought for cardiac recovery especially in pediatric population. Method: From September 2003 to January 2005, five children, with age ranged from 7 to 15 (12.162.8), underwent LVAS implantation. Their diagnosis was DCM in 3, HCM in 1, and muscular dystrophy (Becker type) in 1 case. Devices implanted were exclusively Toyobo-NCVC para-corporeal LVASs. All the patients received medication for CHF including b-blocker. Result: Among the five patients, four showed significant functional recovery and had their LVAS removed. One of the recovered four patients required re-implantation of LVAS due to the recurrence of heart failure 1 week after removal of LVAS, but the other 3 patients (60% of the patients included in this study) did not have signs of recurrent heart failure and discharged home. Conclusion: LVAS patients in adolescence have chance of functional recovery and weaning from LVAS. Aggressive heart failure treatment and evaluation of cardiac function should be performed even on LVAS.
1066 Study on 35 Patients in Whom Percutaneous Cardiopulmonary Support (PCPS) was used SHIGERU KATO, SHINYA HIRAMITSU, YASUCHIKA KATO, KENJI MIYAGISHIMA, KAZUMASA MORI, HISASHI KIMURA, MASATSUGU OHTSUKI, MASATSUGU IWASE, SHIN-ICHIRO MORIMOTO, HITOSHI HISHIDA Division of Cardiology Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan Objects: PCPS has been reported to treat lethal cardiovascular disorders. However, few studies have focused on its use in large numbers of cases, which prompted us to examine this issue here. Methods: We focused on 35 patients who during the recent 10-year period were treated with PCPS. We investigated the underlying cause, outcome, weaning rate of PCPS and associated complications. Results: The underlying cause was most frequently ischemic heart disease (49%), followed by fulminant myocarditis (7%), cardiomyopathy (11%), pulmonary embolism (9%), arrhythmia (3%), sepsis (3%), and CPA (9%). Weaning from PCPS was feasible in 49% of patients. 11 of 35(31%) survived, with CABG subsequently performed in 6 patients, PCI in 4 cases, and LVAD implanted in 1 patient. Complications consisted of multiple organ failure in 14 patients (40%), hemorrhage in 3 patients, circulatory disturbances of the legs in 3 patients. The salvage rate of ischemic heart disease cases was 24%, all of which underwent emergency revascularization. The salvage rate of fulminant myocarditis was 67%. Conclusions: The use of PCPS in ischemic heart disease patients as a bridge therapy until revascularization was effective, although all of the cases in which emergency revascularization could not be performed died. The salvage rate in fulminant myocarditis was high. If the indications are considered PCPS can be a highly effective therapy.
1062 Post-Transplant Exercise Tolerability in Japanese Heart Transplant Recipients KAZUNOBU SHITAKURA, SHINICHI NUNODA, KIYOTAKA OKAJIMA, CHIEKO FUJII, OSAMU MATSUOKA, SACHIKO OINUMA, YUTAKA KUBO, KUNIAKI OTSUKA Department of Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan Background: Post-transplant exercise tolerability in Japanese heart transplant (HTx) recipients has not been fully elucidated. Subjects: The subjects consisted of 20 Japanese HTx recipients (7 to 53 years old at HTx, 6 females). Age matched 7 healthy volunteers were examined as control. Methods: The indices from symptom-limited treadmill exercise tests with expired gas analysis and heart-to-mediastinum ratio (HMR) of 123I labeled MIBG studies were examined. Hemodynamic parameters by using Swan-Ganz catheter and physical and mental component summary (PCS and MCS) of SF-36 were also obtained. Results: Cardiac index (CI) was correlated with peak VO2 and anaerobic threshold (AT) in HTx recipients (R50.61, 0.54, respectively). In comparison with controls, HTx recipients showed lower values in % peak VO2, % AT, peak HR and peak VO2/HR (mean controls v. HTx recipients, 119.0 v. 76.8, 133.7 v. 92.1, 190 v. 142, 17.2 v. 11.1, respectively). HMR was correlated with % Peak VO2 (R50.65) and maximum HR (R50.51). Peak VO2 and AT in HTx recipients were correlated with PCS and MCS (peak VO2: R50.55, 0.65, AT: R50.52, 0.67, respectively). Conclusions: Exercise tolerability in HTx recipients is lower than in healthy controls. The improvement of cardiac function and exercise tolerability were related to post-transplant QOL. The restoration of the sympathetic innervation was related to improved post-transplant exercise tolerability.
1063 Blockade of the 4-1BB Pathway Suppresses Graft Arterial Disease in Cardiac Allografts HITOSHI SAIKI1, HISANORI KOSUGE1, GO HARAGUCHI1, TOSHIMITSU UEDE2, MITSUAKI ISOBE1 1 Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan, 2Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan Background: 4-1BB is a member of the tumor necrosis factor receptor (TNFR) superfamily. It works as a costimulatory molecule and plays important roles in regulating the immune response. Graft arterial disease is characterized by development of neointimal hyperplasia of graft coronary arteries and it remains a major problem in clinical heart transplantation. We investigated the hypothesis that blockade of the 4-1BB pathway can suppress graft arterial disease. Methods and Results: We performed heterotopic murine cardiac transplantation. Hearts from C57BL/6 mice were transplanted into Bm 12 mice (class II mismatch). 4-1BBIg was injected intraperitoneally (100mg per injection) every 7 days for 8 weeks after transplantation. Neointimal hyperplasia was significantly attenuated by 4-1BBIg treatment (luminal occlusion: 21.663.5%) in comparison with untreated allografts (69.663.5%, p!0.001). T cell infiltration of cardiac allograft and expressions of Interferon-g and Interleukin-13 in cardiac allografts were suppressed by 4-1BBIg treatment. 4-1BB was expressed on CD4 and CD8 positive cells of splenocytes in recipient mice after transplantation. We performed mixed lymphocyte reaction using sensitized splenocytes after allograft transplantation. T cell proliferation was significantly inhibited by addition of 4-1BBIg in a dose-dependent manner. Conclusion: 4-1BBIg attenuated neointimal hyperplasia of graft coronary arteries through suppression of T cell proliferation and cytokine expression. 4-1BB could be therapeutic target of graft arterial disease in heart transplantation.
1064 Efficacy of Doppler Echocardiography in the Detection of Allograft Rejection in Heart Transplant Recipients CHIZUKO KAMIYA, TOMOKO KATOU, HATSUE UEDA, SYUUJI HASHIMOTO, AKIKO MANO, NOBORU ODA, MASAFUMI KITAKAZE, TAKESHI NAKATANI Cardiovascular Medicine, National Cardiovascular Center Purpose: Invasive screenings for acute rejection (AR) by endomyocardial biopsy (EMB) in heart transplant (HTx) recipients are still standard procedures. We investigated either right heart catheterization (RHC) or Doppler echocardiography could detect AR.
Method: We used the International Society for Heart and Lung Transplantation (ISHLT) grading system to classify EBMs; $grade 2 AR as group A, and !grade 1b AR as group B. Among 20 patients who underwent heart transplant from May 1999 to December 2005 and were followed up at National Cardiovascular Center, 8 patients (male 75%, mean age 33.7613.4 year-old) showed $grade 2 AR at any point 4 months after the post-transplant. We reviewed their hemodynamic data obtained from RHC and Doppler echocardiography. Result: Reduced deceleration time of early transmitral filling, and mitral E-wave velocity/early diastolic mitral annular motion velocity were greater in group A compared with group B (162.6612.4msec vs. 150.1620.7msec, p!0.05, and 6.862.7 vs. 6.462.5, p!0.05). None of the hemodynamic parameters obtained from RHC was significantly different between the groups. Conclusion: Detection of diastolic dysfunction by serial measurement of Doppler echocardiography would provide the time of acute rejection in HTx recipients even with stable hemodynamic conditions.
1065 High Incidence of Ventricular Recovery with Left Ventricular Assist Device for Idiopathic Cardiomyopathy in Adolescence NAOSUMI SEKIYA, MATSUMIYA GORO, NISHIMURA MOTONOBU, ICHIKAWA HAJIME, FUKUSHIMA NORIHIDE, SAWA YOSHIKI Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine Purpose: Left ventricular assist system (LVAS) implantation is an effective therapeutic modality for end-stage congestive heart failure(CHF) in pediatric patients as well as in adult population. But, because of low pump flow and poor control of anti coagulant, thrombo-embolic risk are relatively higher. For this reason, we aggressively sought for cardiac recovery especially in pediatric population. Method: From September 2003 to January 2005, five children, with age ranged from 7 to 15 (12.162.8), underwent LVAS implantation. Their diagnosis was DCM in 3, HCM in 1, and muscular dystrophy (Becker type) in 1 case. Devices implanted were exclusively Toyobo-NCVC para-corporeal LVASs. All the patients received medication for CHF including b-blocker. Result: Among the five patients, four showed significant functional recovery and had their LVAS removed. One of the recovered four patients required re-implantation of LVAS due to the recurrence of heart failure 1 week after removal of LVAS, but the other 3 patients (60% of the patients included in this study) did not have signs of recurrent heart failure and discharged home. Conclusion: LVAS patients in adolescence have chance of functional recovery and weaning from LVAS. Aggressive heart failure treatment and evaluation of cardiac function should be performed even on LVAS.
1066 Study on 35 Patients in Whom Percutaneous Cardiopulmonary Support (PCPS) was used SHIGERU KATO, SHINYA HIRAMITSU, YASUCHIKA KATO, KENJI MIYAGISHIMA, KAZUMASA MORI, HISASHI KIMURA, MASATSUGU OHTSUKI, MASATSUGU IWASE, SHIN-ICHIRO MORIMOTO, HITOSHI HISHIDA Division of Cardiology Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan Objects: PCPS has been reported to treat lethal cardiovascular disorders. However, few studies have focused on its use in large numbers of cases, which prompted us to examine this issue here. Methods: We focused on 35 patients who during the recent 10-year period were treated with PCPS. We investigated the underlying cause, outcome, weaning rate of PCPS and associated complications. Results: The underlying cause was most frequently ischemic heart disease (49%), followed by fulminant myocarditis (7%), cardiomyopathy (11%), pulmonary embolism (9%), arrhythmia (3%), sepsis (3%), and CPA (9%). Weaning from PCPS was feasible in 49% of patients. 11 of 35(31%) survived, with CABG subsequently performed in 6 patients, PCI in 4 cases, and LVAD implanted in 1 patient. Complications consisted of multiple organ failure in 14 patients (40%), hemorrhage in 3 patients, circulatory disturbances of the legs in 3 patients. The salvage rate of ischemic heart disease cases was 24%, all of which underwent emergency revascularization. The salvage rate of fulminant myocarditis was 67%. Conclusions: The use of PCPS in ischemic heart disease patients as a bridge therapy until revascularization was effective, although all of the cases in which emergency revascularization could not be performed died. The salvage rate in fulminant myocarditis was high. If the indications are considered PCPS can be a highly effective therapy.