Hemoglobin and serum creatinine before LVAD implantation predict myocardial recovery and eventual LVAD weaning

The 12th Annual Scientific Meeting outcomes including cardiac rupture, left ventricular (LV) remodeling and cardiac death. Recent experimental studies have shown that CRP per se has some biological properties including proinflammatory and proapoptotic effects. Here we tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI using transgenic mice with human CRP expression (CRP-Tg). Methods & Results: CRP-Tg and their nontransgenic littermates (Control) underwent proximal ligation of left coronary artery. The baseline phenotype was similar in CRP-Tg and control mice. Although the mortality after MI was not different between groups, echocardiography indicated that CRP-Tg mice had more LV dilation and worse LV function at one week and five weeks after MI. Hemodynamic studies showed that LV dP/dt and dP/dt were significantly lower in the CRP-Tg group than in the Control group, although infarct size was comparable. Histological evaluation showed a higher rate of apoptosis in the border zone of infarcted hearts from CRP-Tg mice compared with controls. Quantitative RT-PCR showed that angiotensin II type 1a receptor and interleukin-6 were upregulated in viable LV samples from CRP-Tg mice. Conclusion: Increased CRP expression exacerbates LV dysfunction and remodeling after MI, suggesting a pathogenetic role of CRP in the remodeling process after MI.

105 Mitochondrial transcription factors, Tfam and Tfb2 m regulate the SERCA2 gene transcription. A coordinate regulatory mechanism of energy production and expenditure ATAI WATANABE, MASASHI ARAI, MASAHIKO KURABAYASHI Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Japan Background: The heart consumes ATP, which is mainly produced in mitochondria. Mitochondrial enzymes are produced under the control of mitochondrial specific transcription factor, Tfam and its enhancer, Tfb2 m. SERCA2 plays a central role in cardiac function by using ATP. Therefore, we tested if Tfam and Tfb2 m activate SERCA2 gene transcription as well as mitochondrial gene in the normal and diseased heart. Results: Localization of Tfam/Tfb2 m in the nucleus was demonstrated by immunostaining. ChIP assay revealed Tfam and Tfb2 m bound to the 479 to 1nt region of the SERCA2 gene promoter. Fluorescence correlation spectroscopy further revealed Tfam and Tfb2 m bound to the 122 to 114nt and the 122 to 117nt region, respectively. Overexpression of Tfam and Tfb2 m increased the SERCA2 gene transcription by 96% and their ablation diminished the SERCA2 transcription by 65 %. In the rat myocardial infarction model, SERCA2 mRNA level was significantly correlated with Tfam(r 5 0.52, p ! 0.001) and Tfb2m(r 5 0.72, p ! 0.001) mRNA. In the neonatal rat cultured myocytes, mutation of either Tfam or Tfb2 m binding sites decreased basal SERCA2 luciferase activity. Norepinephrine, an inducer of heart failure, decreased SERCA2 luciferase activity and its effect was further enhanced when mutations were induced. Conclusion: Our study revealed a novel machanism of the coordinate regulation of the transcription of genes for ATP production and expenditure. This mechanism will become a therapeutic target for heart failure.

106 Plasma concentration of brain natriuretic peotide in stable outpatients: How much chage should be consider hazardous? YUTAKA TAKEDA, SHOGO SUZUKI, SHUICHI KITADA, KOJI YAMAMOTO, SHOGO SUZUKI, YASUAKI DOHI, NOBUYUKI OHTE, GENJIRO KIMURA Department of Cardio-Renal Medicine and Hypertension, Nagoya City University, Nagoya, Japan Background: The plasma concentration of B-type natriuretic peptide (BNP) in outpatients is hard to interpret due to lack of knowledge of the natural within-person variation of BNP. Methods: In a prospective historical cohort study, 6 consecutive measurements of the plasma concentration of BNP were made at 4-week intervals in 24 patients with dilated cardiomyopathy (DCM), 25 with hypertensive heart disease (HHD), and 29 with myocardial infarction (MI). Critical difference at the 95% confidence level (CD) were calculated with a log-normal approach, and the results were back-transformed to a normal scale. Results: The within-person distribution of BNP was right-skewed and a Gaussian distribution was achieved by logtransformation. The up and down CD were 238% and -70% in patients with DCM, 220% and -69% in those with HHD, and 297% and -75% in those with MI, respectively. Conclusion: The plasma concentration of BNP may triple or fall by one-third without a change in the status of heart failure either in patients with DCM or MI. In monitoring of patients with heart failure, BNP should be interpreted in the context of the skewed within-person distribution.



JHFS

S171

107 Hemoglobin and serum creatinine before LVAD implantation predict myocardial recovery and eventual LVAD weaning NOBORU ODA1, YUKIKO NAKANO1, YASUKI KIHARA1, TOMOKO KATO2, MASANOBU YANASE2, TAKESHI NAKATANI2, MASAFUMI KITAKAZE2, KAZUHIKO HASHIMURA2, HITONOBU TOMOIKE2, SOICHIRO KITAMURA2 1 Department of Caediology, University of Hiroshima, Hiroshima, Japan, 2National Cardiovascular Center, Suita Osaka, Japan Background: Some patients have shown successful weaning from left ventricular assist device (LVAD) due to myocardial amelioration by the chronic mechanical unloading. However, factors that determine the myocardial recovery during LVAD leading to its weaning have not been clarified. Methods: The clinical courses of 85 consecutive patients who underwent LVAD implantations between 1994 and 2007 were retrospectively reviewed. The patients were divided into group A (N 5 23 cardiac recovery to the level of LVEF O 45% was shown within 6 months since LVAD implantation) and group B (N 5 62 cardiac recovery was not shown, LVEF ! 45%). The laboratory data and cardiac function before and after LVAD were compared. Results: The ratio of patients who eventually obtained successful LVAD explantation was significantly higher in group A than in group B (39.1% vs. 0%, p ! 0.001). LVEF before LVAD was not difference between group A and B (19.0 6 7.3 vs. 17.9 6 9.1%). In contrast, hemoglobin and serum creatinine levels before LVAD showed significant differences between the 2 groups (12.0 6 1.3 vs. 9.15 6 1.27 g/dl, p ! 0.01; 1.05 6 0.38 vs. 2.24 6 1.64 mg/dl, p ! 0.01, respectively), while these levels after LVAD were similar. Any other laboratory data and medications were not different between the groups. Conclusion: Preoperative hemoglobin level and serum creatinine level are the predictors of myocardial recovery leading to LVAD explantation.

108 Persistent elevation in troponin T level during convalescence is associated with inflammatory response in patients with decompensated heart failure KIMI KOIDE1, TSUTOMU YOSHIKAWA1, YUJI NAGATOMO1, TOSHIHISA ANZAI1, TOMOMI MEGURO2, SATOSHI OGAWA1 1 Cardiology Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan, 2Tokyo Electric Power Company Hospital, Tokyo, Japan Purpose: Persistent elevation in cardiac troponin T (cTnT) predicts adverse clinical outcome in patients with chronic heart failure. We sought to determine the association between persistent elevation in cTnT and coexistent pathophysiology in patients with decompensated heart failure (dHF). Method: Plasma cTnT levels were determined before discharge in 151 patients with dHF, and divided into patients who showed positive [cTnT( )] (n 5 37) and those who showed negative [cTnT(-)] (n 5 114). Result: Patients with diabetes were more common in cTnT( ) than cTnT(-) (p 5 0.0046). Echocardiographic left ventricular end-diastolic and end-systolic diameter was smaller in cTnT( ) (p 5 0.0214, p 5 0.0556). Blood hemoglobin concentration on discharge was lower in cTnT( ) (p 5 0.0018). Brain natriuretic peptide level (BNP) and high sensitivity C-reactive protein levels (hsCRP) were higher in cTnT( ) (p 5 0.036, 0.0065). Multivariate analysis showed that predischarge BNP (p 5 0.0354) and hsCRP (p 5 0.0477) were independently associated with positive cTnT. During mean follow-up period of 347 days after discharge, total mortality (p 5 0.0056), cardiac death (p 5 0.028), and worsening heart failure requiring admission (p 5 0.0169) were more common in cTnT( ) than cTnT(-). Cox proportional hazard analysis showed positive cTnT was an independent predictors of total mortality (p 5 0.0063) and cardiac death (p 5 0.0180). Conclusions: Persistent elevation in cTnT during convalescence was associated with anemia, hsCRP and BNP elevations, and worse clinical outcome in patients with dHF. Prolonged inflammatory response may play a role in mediating such phenomena.

109 Diversity of Molecular Forms of Plasma Brain Natriuretic Peptide (BNP) in Patients with Heart Failure (HF) KAZUYOSHI TADOKORO1, TOSHIO NISHIKIMI1, KIMIHIKO ISHIMURA1, CHIKAKO IEMURA1, HIROAKI MATSUOKA1, MASASHI KEDA2, MASAKO MATSUBARA3, NAOTO MINAMINO3 1 The Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan, 2The Institute of International Education and Research, Dokkyo Medical University, Mibu, Tochigi, Japan, 3The Department of Pharmacology, National Cardiovascular Center, Research Institute, Osaka, Japan Background: Recent studies revealed the diversity of molecular forms of plasma BNP in patients with HF. However, the mechanism of diversity of molecular form of plasma BNP remains unknown. Methods: The normal age-matched control (n 5