- Email: [email protected]
Temporal Trends in Prevalence and Outcomes of Geriatric Patients with Acute Myocardial Infarction Complicated with Heart Failure -Miyagi AMI Registry-
The 21st Annual Scientific Meeting
•
JHFS
S15
we show that BAT dysfunction develops with heart failure and promotes cardiac remodeling by inducing systemic metabolic dysfunction. We generated a left ventricular (LV) pressure-overload model in mice with a thoracic aortic constriction (TAC). Cardiac systolic dysfunction developed in four weeks after operation, together with a reduction of the thermogenic response to acute cold exposure and an increase of TUNELpositive cells in BAT. In-vitro studies with differentiated brown adipocytes suggested that the chronic activation of adrenergic signaling reduced mitochondrial membrane potential and increased apoptotic cells. The transplantation of healthy BAT into mice undergoing TAC improved thermogenic response and ameliorated cardiac dysfunction. Studies with metabolome analyses indicated that BAT dysfunction has a causal role for accumulation of one metabolite which contributes to the progression of cardiac metabolic remodeling and dysfunction. Maintenance of BAT homeostasis would become a novel therapeutic target for heart failure. Figure C. In-hospital mortality.
YIA-BS6 Intra Venous Infusion of Nano-ONO1301 Improve Pulmonary Hypertension in Rat Model Tomomitsu Kanaya, Shigeru Miyagawa, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa; Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan Introduction: We hypothesized that intra venous infusion of newly developed nano-prostacyclin agonist, ONO1301nano, may have some potentials in targeted delivery to damaged lung and improving pulmonary hypertension in rat model. Methods & Results: PAH model rats were induced by the subcutaneous injection with SU5416 (20 g/kg), exposing to chronic hypoxia for 21 days, and normoxia after hypoxia. Treatment group was injected ONO1301nano (3 g/kg) every 7 days cycle after exposure to normoxia for 14 days in normoxia environment. In vivo, the fluorescent images showed that significantly larger number of texas red-labeled nano sized particles were detected in the damaged lung by intravenous administration compared with normal rats (P < .05). Immunostains revelaed that nano particles labeled by texas-red were detected in vimentin positive cells in the lung tissue. On catheterization, the right ventricle pressure/left ventricle pressure was significantly improved in ONO1301nano treatment group compared with the control (P < .01). Histological assessment revealed that the percent medial wall thickness in pulmonary vasculature were significantly ameliorated in treated group (P < .01). In vitro, the expression levels of VEGF and HGF in cultured fibroblasts were increased. Conclusions: Intra venous infusion of ONO1301nano improved pulmonary hemodynamically and histologically in PH model rats with selective delivery to damaged lung, suggesting Nano-prostacyclin agonist delivery system may have potential in new drug for PAH.
YIA-CS1-1 Temporal Trends in Prevalence and Outcomes of Geriatric Patients with Acute Myocardial Infarction Complicated with Heart Failure -Miyagi AMI RegistryKoichi Sato1, Jun Takahashi1, Yuanji Cui2, Kiyotaka Hao1, Satoshi Miyata1, Yasuhiko Sakata1, Hiroaki Shimokawa1; 1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Tohoku Rosai Hospital, Sendai, Japan Background: Temporal trends in the prevalence and outcomes of geriatric patients with acute myocardial infarction (AMI) complicated with heart failure (HF) remain to be elucidated. Methods and Results: We analyzed 6,648 consecutive AMI patients aged ≥70 years [70s (n = 3,576), 80s (n = 2,564), and ≥90 years (n = 508)] registered in our Miyagi AMI Registry between 2004 and 2015. Performance rate of primary percutaneous coronary intervention (PCI) significantly increased during the period in most
Figure A. Performance rate of primary PCI.
Figure B. Heart failure on admission.
age groups of both sexes (Figure A). Meanwhile, the prevalence of HF with Killip class ≥2 on admission also increased (Figure B), and in-hospital mortality remained unchanged regardless of age or sex (Figure C). Conclusions: Among geriatric AMI patients, the prevalence of HF has increased despite the increased PCI rate, which may result in the unchanged in-hospital mortality in Japan.
YIA-CS1-2 Comparison between Cardiac Magnetic Resonance and Myocardial Ultrastructural Features in Patients with Dilated Cardiomyopathy to Predict Recovery of Cardiac Function Tsunenori Saito1, Kuniya Asai2, Shigeru Sato3, Wataru Shimizu2; 1Department of Internal Med and Cardiol., Nippon Medical School Tama-Nagayama Hospital, Japan; 2 Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan; 3Tokyo Electron Microscopy Laboratory, Chiba, Japan Background: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging is a useful modality to detect myocardial fibrosis. However, some patients with dilated cardiomyopathy (DCM) are not accompanied by LGE. Methods: Endomyocardial biopsy from left ventricle (LV) was performed in 55 consecutive DCM patients (55.5 ± 13.1 years, 82% men), at their initial presentation with decompensated HF. Ultrastructural features of cardiomyocytes were detected by electron microscopy. LV functional changes over time by trans-thoracic echocardiography were examined. Definition of LV reverse remodeling (LVRR) is increasing LV ejection-fraction (EF) from >10% to a final value of >35% at 12 months. Results: During median follow-up of 2.1 years, 12 patients (22%) were readmitted for HF recurrence. Myofilament lysis, which are apparent in degenerated cardiomyocytes of DCM, were identified in 41 (72%), and autophagic vacuoles in cardiomyocytes were identified in 24 (42%). Multipleregression analysis showed that independent predictors of LVRR were higher BodyMass Index (P = .031), usage of Aldosterone-Receptor Antagonist (P = .013), autophagy (P = .003), and absence of LGE (P = .015) and myofilament lysis (P = .012). Independent predictors of readmission due to HF recurrence were C-reactive protein (hazardratio [HR], 1.995; 95% confidence-interval [CI], 1.065–3.737), myofilament lysis (HR, 14.854; 95% CI, 1.725–127.878), and absence of autophagic vacuoles (HR, 0.055; 95% CI, 0.006–0.483). Conclusions: Ultrastructural features are useful to predict not only their prognosis, but also LVRR in patients with DCM.
YIA-CS1-3 Predictor of Cardiovascular Events in Patients with Mutant Transthyretin Amyloidosis Kyoko Hirakawa1, Seiji Takashio1, Toshifumi Ishida1, Yasuhiro Izumiya1, Kouichi Kaikita1, Mitsuharu Ueda2, Yukio Ando2, Kenichi Tsujita1; 1Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Background: It is well known mutant transthyretin (mt-ATTR) amyloidosis often cause cardiac amyloidosis and cardiac involvements worsen clinical outcome. However, there is little information about predictor of cardiovascular outcome in mt-ATTR patients with long-term follow up in Japan. We analyzed the incidence poor outcome and identified the predictive factors in noninvasive risk stratification in Japanese patients with mtATTR. Method and Result: We evaluated 81 consecutive mt-ATTR patients (56.7 ± 13.7 years old). We evaluated all cause mortality and incidence of cardiovascular event. During median follow up of 7.0 years, 21 patients (25.9%) had adverse events; all cause death (n = 8), cardiac event including hospitalization due to worsening heart failure (n = 2), CRTD implantation (n = 2), ICD implantation due to ventricular tachycardia (n = 5), and pacemaker implantation due to symptomatic bradyarrhythmia (n = 5). Univaluate cox regression analysis revealed that genetic mutation (nonVal30Met), duration of mt-ATTR, IVSTd, EF, E/e, QRS width, creatinine and Ln(cardiac troponin T) levels were predictors for poor prognosis. In multivaluate cox regression analysis, IVSTd and nonVal30Met mutation were significantly and independently correlation with poor prognosis [IVSTd; hazard ratio : 1.168, 95%CI : 1.036 - 1.317; P = .01, nonVal30Met mutation; HR: 8.779, 95%CI:3.105 - 24.822; P < .01]. Conclusion: Genetic mutation and IVSTd were useful predictors of cardiovascular events. These results revealed it is important to evaluate cardiac involvement, especially nonVal30Met mt-ATTR patients.
•
JHFS
S15
we show that BAT dysfunction develops with heart failure and promotes cardiac remodeling by inducing systemic metabolic dysfunction. We generated a left ventricular (LV) pressure-overload model in mice with a thoracic aortic constriction (TAC). Cardiac systolic dysfunction developed in four weeks after operation, together with a reduction of the thermogenic response to acute cold exposure and an increase of TUNELpositive cells in BAT. In-vitro studies with differentiated brown adipocytes suggested that the chronic activation of adrenergic signaling reduced mitochondrial membrane potential and increased apoptotic cells. The transplantation of healthy BAT into mice undergoing TAC improved thermogenic response and ameliorated cardiac dysfunction. Studies with metabolome analyses indicated that BAT dysfunction has a causal role for accumulation of one metabolite which contributes to the progression of cardiac metabolic remodeling and dysfunction. Maintenance of BAT homeostasis would become a novel therapeutic target for heart failure. Figure C. In-hospital mortality.
YIA-BS6 Intra Venous Infusion of Nano-ONO1301 Improve Pulmonary Hypertension in Rat Model Tomomitsu Kanaya, Shigeru Miyagawa, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa; Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan Introduction: We hypothesized that intra venous infusion of newly developed nano-prostacyclin agonist, ONO1301nano, may have some potentials in targeted delivery to damaged lung and improving pulmonary hypertension in rat model. Methods & Results: PAH model rats were induced by the subcutaneous injection with SU5416 (20 g/kg), exposing to chronic hypoxia for 21 days, and normoxia after hypoxia. Treatment group was injected ONO1301nano (3 g/kg) every 7 days cycle after exposure to normoxia for 14 days in normoxia environment. In vivo, the fluorescent images showed that significantly larger number of texas red-labeled nano sized particles were detected in the damaged lung by intravenous administration compared with normal rats (P < .05). Immunostains revelaed that nano particles labeled by texas-red were detected in vimentin positive cells in the lung tissue. On catheterization, the right ventricle pressure/left ventricle pressure was significantly improved in ONO1301nano treatment group compared with the control (P < .01). Histological assessment revealed that the percent medial wall thickness in pulmonary vasculature were significantly ameliorated in treated group (P < .01). In vitro, the expression levels of VEGF and HGF in cultured fibroblasts were increased. Conclusions: Intra venous infusion of ONO1301nano improved pulmonary hemodynamically and histologically in PH model rats with selective delivery to damaged lung, suggesting Nano-prostacyclin agonist delivery system may have potential in new drug for PAH.
YIA-CS1-1 Temporal Trends in Prevalence and Outcomes of Geriatric Patients with Acute Myocardial Infarction Complicated with Heart Failure -Miyagi AMI RegistryKoichi Sato1, Jun Takahashi1, Yuanji Cui2, Kiyotaka Hao1, Satoshi Miyata1, Yasuhiko Sakata1, Hiroaki Shimokawa1; 1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Tohoku Rosai Hospital, Sendai, Japan Background: Temporal trends in the prevalence and outcomes of geriatric patients with acute myocardial infarction (AMI) complicated with heart failure (HF) remain to be elucidated. Methods and Results: We analyzed 6,648 consecutive AMI patients aged ≥70 years [70s (n = 3,576), 80s (n = 2,564), and ≥90 years (n = 508)] registered in our Miyagi AMI Registry between 2004 and 2015. Performance rate of primary percutaneous coronary intervention (PCI) significantly increased during the period in most
Figure A. Performance rate of primary PCI.
Figure B. Heart failure on admission.
age groups of both sexes (Figure A). Meanwhile, the prevalence of HF with Killip class ≥2 on admission also increased (Figure B), and in-hospital mortality remained unchanged regardless of age or sex (Figure C). Conclusions: Among geriatric AMI patients, the prevalence of HF has increased despite the increased PCI rate, which may result in the unchanged in-hospital mortality in Japan.
YIA-CS1-2 Comparison between Cardiac Magnetic Resonance and Myocardial Ultrastructural Features in Patients with Dilated Cardiomyopathy to Predict Recovery of Cardiac Function Tsunenori Saito1, Kuniya Asai2, Shigeru Sato3, Wataru Shimizu2; 1Department of Internal Med and Cardiol., Nippon Medical School Tama-Nagayama Hospital, Japan; 2 Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan; 3Tokyo Electron Microscopy Laboratory, Chiba, Japan Background: Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging is a useful modality to detect myocardial fibrosis. However, some patients with dilated cardiomyopathy (DCM) are not accompanied by LGE. Methods: Endomyocardial biopsy from left ventricle (LV) was performed in 55 consecutive DCM patients (55.5 ± 13.1 years, 82% men), at their initial presentation with decompensated HF. Ultrastructural features of cardiomyocytes were detected by electron microscopy. LV functional changes over time by trans-thoracic echocardiography were examined. Definition of LV reverse remodeling (LVRR) is increasing LV ejection-fraction (EF) from >10% to a final value of >35% at 12 months. Results: During median follow-up of 2.1 years, 12 patients (22%) were readmitted for HF recurrence. Myofilament lysis, which are apparent in degenerated cardiomyocytes of DCM, were identified in 41 (72%), and autophagic vacuoles in cardiomyocytes were identified in 24 (42%). Multipleregression analysis showed that independent predictors of LVRR were higher BodyMass Index (P = .031), usage of Aldosterone-Receptor Antagonist (P = .013), autophagy (P = .003), and absence of LGE (P = .015) and myofilament lysis (P = .012). Independent predictors of readmission due to HF recurrence were C-reactive protein (hazardratio [HR], 1.995; 95% confidence-interval [CI], 1.065–3.737), myofilament lysis (HR, 14.854; 95% CI, 1.725–127.878), and absence of autophagic vacuoles (HR, 0.055; 95% CI, 0.006–0.483). Conclusions: Ultrastructural features are useful to predict not only their prognosis, but also LVRR in patients with DCM.
YIA-CS1-3 Predictor of Cardiovascular Events in Patients with Mutant Transthyretin Amyloidosis Kyoko Hirakawa1, Seiji Takashio1, Toshifumi Ishida1, Yasuhiro Izumiya1, Kouichi Kaikita1, Mitsuharu Ueda2, Yukio Ando2, Kenichi Tsujita1; 1Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Background: It is well known mutant transthyretin (mt-ATTR) amyloidosis often cause cardiac amyloidosis and cardiac involvements worsen clinical outcome. However, there is little information about predictor of cardiovascular outcome in mt-ATTR patients with long-term follow up in Japan. We analyzed the incidence poor outcome and identified the predictive factors in noninvasive risk stratification in Japanese patients with mtATTR. Method and Result: We evaluated 81 consecutive mt-ATTR patients (56.7 ± 13.7 years old). We evaluated all cause mortality and incidence of cardiovascular event. During median follow up of 7.0 years, 21 patients (25.9%) had adverse events; all cause death (n = 8), cardiac event including hospitalization due to worsening heart failure (n = 2), CRTD implantation (n = 2), ICD implantation due to ventricular tachycardia (n = 5), and pacemaker implantation due to symptomatic bradyarrhythmia (n = 5). Univaluate cox regression analysis revealed that genetic mutation (nonVal30Met), duration of mt-ATTR, IVSTd, EF, E/e, QRS width, creatinine and Ln(cardiac troponin T) levels were predictors for poor prognosis. In multivaluate cox regression analysis, IVSTd and nonVal30Met mutation were significantly and independently correlation with poor prognosis [IVSTd; hazard ratio : 1.168, 95%CI : 1.036 - 1.317; P = .01, nonVal30Met mutation; HR: 8.779, 95%CI:3.105 - 24.822; P < .01]. Conclusion: Genetic mutation and IVSTd were useful predictors of cardiovascular events. These results revealed it is important to evaluate cardiac involvement, especially nonVal30Met mt-ATTR patients.