- Email: [email protected]
The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation
The 18th Annual Scientific Meeting many lymphocytes, despite the absence of myocarditis. Purpose: We hypothesized there might be concerned with autoimmune responce, therefore evaluated relationship between autoimmunity and severe heart hailure. Methods and Results: We collected blood serum from 37 heart failure patients and 10 VAD patients along with 100 healthy normal subjects. Using homogenated normal human heart lysate, we performed western blot analysis by their serum. We could find several specific auto-antigens and to identify the protein, we next made purification of these proteins by an anion exchange and reverse phase HPLC. We finally identified 4 proteins as auto-antigen candidates by MS analysis. For example, one out of antigen X were detected against the serum from 4 out of 10 VAD implantation patients, which could find only one out of a hundred healthy normal subjects (P!0.01). Conclusion: In this study, we identified specific auto-antigens in severe heart failuer patients. It will be a marker of severe heart failure and useful for us to decide VAD implantation.
P-013 The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation KYUNG-HEE KIM1, YONG-JIN KIM2, SEUNG-PYO LEE2, HYUNG-KWAN KIM2, DAE-WON SOHN2 1 Division of Cardiology, Department of Internal Medicine, Sejong General Hospital & Sejong Heart Institute, 2Department of Internal Medicine, Cardiovascular Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea Introduction: Degenerative mitral regurgitation (MR) is often accompanied by left ventricular hypertrophy (LVH) and diastolic dysfunction. Objectives: This study determined the contribution of LVH and associated diastolic dysfunction on LV remodeling and exercise capacity in rats with significant MR. Method: LVH and diastolic dysfunction were created by suprarenal aortic constriction (SAC) in SD rats. Serial echocardiographic studies and exercise were performed at 2-week intervals and invasive hemodynamic examination by a pressure-volume catheter system was done at 14 weeks after SAC. To test the effect of LVH and diastolic dysfunction on LV remodeling and exercise capacity, the rats were divided into 3 groups [SAC+MR 5SAC followed by MR operation, MR5laparotomy followed by MR operation, Control]. MR was created by introducing a needle through LV apex under the guidance of TEE and making a hole on anterior mitral leaflet. MR was considered significant if a regurgitant jet area occupied more than 45% of the left atrium. SAC was done at 2 weeks before MR formation in SAC+MR group. Results: During the LVH and diastolic dysfunction experiment, LV wall thickness increased in LVH group compared to control group whereas LV ejection fraction (EF) and E/E’ did not change. In hemodynamic analysis, LV end diastolic pressure and the EDPVR slope were greater in LVH group than in control group. Next, when we compared LV remodeling and exercise capacity between above 3 groups, LV dilatation and exercise intolerance were developed first in SAC+MR group. However, MR group showed a catch-up of remodeling and exercise intolerance at 10 weeks after MR formation (LV ESD at 10 weeks after MR formation, 4.3360.26 vs. 6.5060.40 vs. 6.5961.38 mm for control vs. MR vs. SAC+MR, P!0.05; LV EDD, 7.6860.15 vs. 10.4860.46 vs. 10.2061.26 mm, P!0.05; exercise duration, 765.36130.1 vs. 487.8649.0 vs. 434.0680.3 seconds, P!0.05; no statistical differences between SAC+MR and MR). In neurohormonal activity, the level of BNP was not different between 3 groups. However interstitial fibrosis is greater in SAC+MR compared with MR and control. Conclusion: We successfully set up two small animal models of LVH accompanied with diastolic dysfunction and significant MR. LVH and associated diastolic dysfunction did not affect LV remodeling and exercise capacity over time in rats with significant MR.
P-020 Relationships Between Nutritional Status and Markers of Congestion in Patients with Pulmonary Arterial Hypertension AKIRA KAWAMOTO1,3, TAKAO KATO2, YOSHIAKI OKANO3, TETSUO SHIOI3, TAKESHI KIMURA3 1 Hamamatsu Rosai Hospital, 2Cardiovascular Center, the Tazuke Kofukai Medical Research Institute, Kitano Hospital, 3Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University Purpose: Right ventricular (RV) dysfunction and cachexia often coexist; however, there are few studies investigating pulmonary arterial hypertension (PAH) and nutritional status. This study sought to examine the relationships among nutritional status, markers of congestion, and echocardiographic parameters in patients with stable PAH. Methods: In this prospective study, subjects with stable PAH (n58) underwent the subjective global assessment (SGA) for nutritional status, blood tests, and comprehensive echocardiography. Results: Estimated systolic pulmonary artery pressure (ePAP) and BNP levels were 82.7615.7 (mean6SD) mmHg and 1766146 ng/L, respectively. Left ventricular diastolic diameter (LVDd) was negatively correlated with ePAP (r5-0.70, p50.04), implying a dilated RV and compressed left ventricle (LV). Blood urea nitrogen, a marker of protein catabolism, was positively correlated with SGA scores (r50.81, p!0.01) and BNP (r50.68, p50.04) and negatively with LV diameter (r5-0.87, p!0.01). Serum pre-albumin, a rapid turnover hepatic protein, was positively correlated with ePAP (r50.70, p50.01) and negatively with serum sodium concentrations
JHFS
S191
(r5-0.56, p50.02). In multiple regression analyses, BMI was determined by WBC count, ePAP, serum sodium and AST concentrations, and IVC diameter. Conclusion: There were strong correlations between markers of nutritional status, markers of congestion, and PAH severity. These results suggest that poor nutritional status and cachexia may be surrogate markers for PAH severity and potential therapeutic targets for PAH.
P-021 Changes of Metabolomic Profiling are Associated with Reduced Exercise Capacity in Patients with Heart Failure MASAYA TSUDA, SHINTARO KINUGAWA, ARATA FUKUSHIMA, TAKASHI YOKOTA, SHOJI MATSUSHIMA, TAKAAKI FURIHATA, SHINGO TAKADA, MASATO KUDO, JUNICHI MATSUMOTO, HIROYUKI TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Background: Exercise intolerance is a major clinical manifestation, and closely related to poor prognosis in heart failure (HF) patients. Metabolic derangements have been shown to be involved in this phenomenon. We thus investigated the metabolites associated with exercise capacity by using global metabolomic analysis of plasma samples in HF patients. Methods and Results: Ten consecutive HF patients with reduced ejection fraction (57 6 12 years, NYHA class II-III) and 5 agematched healthy subjects as controls (56 6 3 years) were studied. Charged metabolites in plasma samples were measured by capillary electrophoresis mass spectrometry. Peak oxygen uptake (peak VO2), anaerobic threshold (AT), and VE/ VCO2 slope were measured by cardiopulmonary exercise test. A total of 233 charged metabolites were identified. Significant increases in arginine methylation, phospholipid metabolites, and urea cycle metabolites were observed in HF patients compared to controls. Methylarginine including asymmetric dimethylarginine (ADMA) (r5-0.77, P!0.001) and symmetric dimethylarginine (SDMA) (r5-0.65, P50.040) levels, and phospholipid metabolites including choline (r5-0.63, P50.049) and N,N-dimethylglycine (r5-0.75, P50.011) levels were negatively correlated to both peak VO2 and AT in HF patients. N,N-dimethylglycine (r50.72, P50.026) and Urea (r50.82, P50.006) levels were positively correlated to VE/VCO2 slope. Conclusions: Increases in metabolites of arginine methylation, phospholipid metabolism, and urea cycle are associated with exercise intolerance in HF. These results provide mechanistic insights into exercise intolerance associated with HF.
P-022 The Fischer Ratio in Patients with Chronic Heart Failure SHUHEI TSUJI, YUKIHITO SATOU Hyogo Prefectual Amagasaki Hospital, Hyogo, Japan Background: Cachexia is a common complication in severe chronic heart failure (HF). Patients with HF complicated with cachexia showed increased mortality, but its pathophysiology is not fully understood. Hence, this study aimed at identifying malnutrition in HF patients from the viewpoint of amino acid concentration. Methods: To clarify the relationship between amino acids and HF, we collected blood samples from 113 HF patients (male, 61 (54%); mean age, 73.968.8 years; mean ejection fraction, 53616%; median serum B-type natriuretic peptide (BNP) concentration, 229.6pg/ml), and measured the serum amino acid composition. Result: The median Fischer ratio (the molar ratio of branched chain amino acids to aromatic amino acids) was 2.7. Patients with higher Fischer ratio were younger (P!0.001), and had higher body mass index (P!0.001), hemoglobin (P!0.001), and albumin (P!0.001), and lower high density lipoprotein (HDL) cholesterol (P50.003), and BNP (P!0.001). In the multivariable analysis, the Fischer ratio was positively correlated with albumin (correlation coefficient (CC)50.489; 95% confidence interval (CI), 0.183w0.795; P50.002), and negatively correlated with HDL cholesterol (CC5-0.025; 95% CI, -0.008w-0.025; P!0.001), and BNP (CC5-0.695; 95% CI, -1.111w-0.277; P50.001). Conclusion: In the patients with HF, the Fischer ratio was paralleled with poor control of HF represented as a high BNP concentration. Thus, HF patients may have poor nutritional status.
P-023 Prognostic Impact of Preexisting Hypertension in Hospitalized Patient with Established Systolic Heart Failure BYUNG-SU YOO1, SEOK-MIN KANG2, EUN-SEOK JEON3, DONG-JU CHOI4, MYEONG-CHAN CHO5, KYU-HYUNG RYU6 1 Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Korea, 2Division of Cardiology, Yonsei University Severance Hospital, Seoul, Korea, 3Division of Cardiology, Sungkyunkwan University Samsung Medical Center, Seoul, Korea, 4Division of Cardiology, Seoul National University Bundang Hospital, Seongnam, Korea, 5Chungbuk National University College of Medicine, Cheongju, Korea, 6Division of Cardiology, Hallym University Medical Center, Korea Background: Hypertension is the most common risk factor and co-morbidity for heart failure. However the prognostic value of the hypertension in established heart failure has
P-013 The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation KYUNG-HEE KIM1, YONG-JIN KIM2, SEUNG-PYO LEE2, HYUNG-KWAN KIM2, DAE-WON SOHN2 1 Division of Cardiology, Department of Internal Medicine, Sejong General Hospital & Sejong Heart Institute, 2Department of Internal Medicine, Cardiovascular Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea Introduction: Degenerative mitral regurgitation (MR) is often accompanied by left ventricular hypertrophy (LVH) and diastolic dysfunction. Objectives: This study determined the contribution of LVH and associated diastolic dysfunction on LV remodeling and exercise capacity in rats with significant MR. Method: LVH and diastolic dysfunction were created by suprarenal aortic constriction (SAC) in SD rats. Serial echocardiographic studies and exercise were performed at 2-week intervals and invasive hemodynamic examination by a pressure-volume catheter system was done at 14 weeks after SAC. To test the effect of LVH and diastolic dysfunction on LV remodeling and exercise capacity, the rats were divided into 3 groups [SAC+MR 5SAC followed by MR operation, MR5laparotomy followed by MR operation, Control]. MR was created by introducing a needle through LV apex under the guidance of TEE and making a hole on anterior mitral leaflet. MR was considered significant if a regurgitant jet area occupied more than 45% of the left atrium. SAC was done at 2 weeks before MR formation in SAC+MR group. Results: During the LVH and diastolic dysfunction experiment, LV wall thickness increased in LVH group compared to control group whereas LV ejection fraction (EF) and E/E’ did not change. In hemodynamic analysis, LV end diastolic pressure and the EDPVR slope were greater in LVH group than in control group. Next, when we compared LV remodeling and exercise capacity between above 3 groups, LV dilatation and exercise intolerance were developed first in SAC+MR group. However, MR group showed a catch-up of remodeling and exercise intolerance at 10 weeks after MR formation (LV ESD at 10 weeks after MR formation, 4.3360.26 vs. 6.5060.40 vs. 6.5961.38 mm for control vs. MR vs. SAC+MR, P!0.05; LV EDD, 7.6860.15 vs. 10.4860.46 vs. 10.2061.26 mm, P!0.05; exercise duration, 765.36130.1 vs. 487.8649.0 vs. 434.0680.3 seconds, P!0.05; no statistical differences between SAC+MR and MR). In neurohormonal activity, the level of BNP was not different between 3 groups. However interstitial fibrosis is greater in SAC+MR compared with MR and control. Conclusion: We successfully set up two small animal models of LVH accompanied with diastolic dysfunction and significant MR. LVH and associated diastolic dysfunction did not affect LV remodeling and exercise capacity over time in rats with significant MR.
P-020 Relationships Between Nutritional Status and Markers of Congestion in Patients with Pulmonary Arterial Hypertension AKIRA KAWAMOTO1,3, TAKAO KATO2, YOSHIAKI OKANO3, TETSUO SHIOI3, TAKESHI KIMURA3 1 Hamamatsu Rosai Hospital, 2Cardiovascular Center, the Tazuke Kofukai Medical Research Institute, Kitano Hospital, 3Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University Purpose: Right ventricular (RV) dysfunction and cachexia often coexist; however, there are few studies investigating pulmonary arterial hypertension (PAH) and nutritional status. This study sought to examine the relationships among nutritional status, markers of congestion, and echocardiographic parameters in patients with stable PAH. Methods: In this prospective study, subjects with stable PAH (n58) underwent the subjective global assessment (SGA) for nutritional status, blood tests, and comprehensive echocardiography. Results: Estimated systolic pulmonary artery pressure (ePAP) and BNP levels were 82.7615.7 (mean6SD) mmHg and 1766146 ng/L, respectively. Left ventricular diastolic diameter (LVDd) was negatively correlated with ePAP (r5-0.70, p50.04), implying a dilated RV and compressed left ventricle (LV). Blood urea nitrogen, a marker of protein catabolism, was positively correlated with SGA scores (r50.81, p!0.01) and BNP (r50.68, p50.04) and negatively with LV diameter (r5-0.87, p!0.01). Serum pre-albumin, a rapid turnover hepatic protein, was positively correlated with ePAP (r50.70, p50.01) and negatively with serum sodium concentrations
JHFS
S191
(r5-0.56, p50.02). In multiple regression analyses, BMI was determined by WBC count, ePAP, serum sodium and AST concentrations, and IVC diameter. Conclusion: There were strong correlations between markers of nutritional status, markers of congestion, and PAH severity. These results suggest that poor nutritional status and cachexia may be surrogate markers for PAH severity and potential therapeutic targets for PAH.
P-021 Changes of Metabolomic Profiling are Associated with Reduced Exercise Capacity in Patients with Heart Failure MASAYA TSUDA, SHINTARO KINUGAWA, ARATA FUKUSHIMA, TAKASHI YOKOTA, SHOJI MATSUSHIMA, TAKAAKI FURIHATA, SHINGO TAKADA, MASATO KUDO, JUNICHI MATSUMOTO, HIROYUKI TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Background: Exercise intolerance is a major clinical manifestation, and closely related to poor prognosis in heart failure (HF) patients. Metabolic derangements have been shown to be involved in this phenomenon. We thus investigated the metabolites associated with exercise capacity by using global metabolomic analysis of plasma samples in HF patients. Methods and Results: Ten consecutive HF patients with reduced ejection fraction (57 6 12 years, NYHA class II-III) and 5 agematched healthy subjects as controls (56 6 3 years) were studied. Charged metabolites in plasma samples were measured by capillary electrophoresis mass spectrometry. Peak oxygen uptake (peak VO2), anaerobic threshold (AT), and VE/ VCO2 slope were measured by cardiopulmonary exercise test. A total of 233 charged metabolites were identified. Significant increases in arginine methylation, phospholipid metabolites, and urea cycle metabolites were observed in HF patients compared to controls. Methylarginine including asymmetric dimethylarginine (ADMA) (r5-0.77, P!0.001) and symmetric dimethylarginine (SDMA) (r5-0.65, P50.040) levels, and phospholipid metabolites including choline (r5-0.63, P50.049) and N,N-dimethylglycine (r5-0.75, P50.011) levels were negatively correlated to both peak VO2 and AT in HF patients. N,N-dimethylglycine (r50.72, P50.026) and Urea (r50.82, P50.006) levels were positively correlated to VE/VCO2 slope. Conclusions: Increases in metabolites of arginine methylation, phospholipid metabolism, and urea cycle are associated with exercise intolerance in HF. These results provide mechanistic insights into exercise intolerance associated with HF.
P-022 The Fischer Ratio in Patients with Chronic Heart Failure SHUHEI TSUJI, YUKIHITO SATOU Hyogo Prefectual Amagasaki Hospital, Hyogo, Japan Background: Cachexia is a common complication in severe chronic heart failure (HF). Patients with HF complicated with cachexia showed increased mortality, but its pathophysiology is not fully understood. Hence, this study aimed at identifying malnutrition in HF patients from the viewpoint of amino acid concentration. Methods: To clarify the relationship between amino acids and HF, we collected blood samples from 113 HF patients (male, 61 (54%); mean age, 73.968.8 years; mean ejection fraction, 53616%; median serum B-type natriuretic peptide (BNP) concentration, 229.6pg/ml), and measured the serum amino acid composition. Result: The median Fischer ratio (the molar ratio of branched chain amino acids to aromatic amino acids) was 2.7. Patients with higher Fischer ratio were younger (P!0.001), and had higher body mass index (P!0.001), hemoglobin (P!0.001), and albumin (P!0.001), and lower high density lipoprotein (HDL) cholesterol (P50.003), and BNP (P!0.001). In the multivariable analysis, the Fischer ratio was positively correlated with albumin (correlation coefficient (CC)50.489; 95% confidence interval (CI), 0.183w0.795; P50.002), and negatively correlated with HDL cholesterol (CC5-0.025; 95% CI, -0.008w-0.025; P!0.001), and BNP (CC5-0.695; 95% CI, -1.111w-0.277; P50.001). Conclusion: In the patients with HF, the Fischer ratio was paralleled with poor control of HF represented as a high BNP concentration. Thus, HF patients may have poor nutritional status.
P-023 Prognostic Impact of Preexisting Hypertension in Hospitalized Patient with Established Systolic Heart Failure BYUNG-SU YOO1, SEOK-MIN KANG2, EUN-SEOK JEON3, DONG-JU CHOI4, MYEONG-CHAN CHO5, KYU-HYUNG RYU6 1 Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Korea, 2Division of Cardiology, Yonsei University Severance Hospital, Seoul, Korea, 3Division of Cardiology, Sungkyunkwan University Samsung Medical Center, Seoul, Korea, 4Division of Cardiology, Seoul National University Bundang Hospital, Seongnam, Korea, 5Chungbuk National University College of Medicine, Cheongju, Korea, 6Division of Cardiology, Hallym University Medical Center, Korea Background: Hypertension is the most common risk factor and co-morbidity for heart failure. However the prognostic value of the hypertension in established heart failure has