Relation between Hemodynamic Parameters on Admission and Worsening Renal Function in Early Phase in Patients with Acute Decompensated Heart Failure

S180 Journal of Cardiac Failure Vol. 21 No. 10S October 2015 strain pattern. Results: LVRR was observed in 38 patients (55%). D QRS voltage, D QRS duration, and D QTc duration were significantly smaller in the positive LVRR group (P!0.001, P50.042 and P50.010, respectively). The percentage of STT normalization was higher in the positive LVRR group (P50.005). Multivariate analysis revealed that D QRS voltage was a significant determinant of LVRR (odds ratio50.192, P!0.001). D QRS voltage was inversely related to the change of LVEF (R5-0.512, P!0.001) and LVDd (R5-0.559, P!0.001). In addition, Kaplan-Meier survival analysis indicated that D QRS voltage!-0.440 subgroup have a favorable prognosis (P50.001). Conclusion: The change of RV5+SV1 voltage in ECG is associated with LVRR in DCM.

OP23-4 A Case of Dilated Cardiomyopathy and Severe Heart Failure with Repetitive Coma Due to Hepatic Encephalopathy TOYOJI KAIDA, TAKAYUKI INOMATA, TEPPEI FUJITA, YUICHIRO IIDA, YUUKI IKEDA, TAKERU NABETA, TOMOYOSHI YANAGISAWA, EMI MAEKAWA, TOSHIMI KOITABASHI, JUNYA AKO Department of Cardio-angiology, Kitasato University, School of Medicine, Kanagawa, Japan A 48-year-old man had suffered from heart failure (HF) based on idiopathic dilated cardiomyopathy since over 20 years. In spite of guideline-directed medical therapy including angiotensinconverting enzyme inhibitor and beta-blocker, he repeated hospitalization for exacerbated HF. On admission, he had repeatedly coma and tremor. Although abdominal ultrasonography demonstrated no typical findings of liver cirrhosis such as irregular surface and atrophy together with splenomegaly, he was diagnosed as hepatic encephalopathy according to hyperammoniemia as well as the increased levels of serum hyaluronic acid and collagen type 4 after excluding other organic diseases including viral, autoimmune and alcoholic liver disorder. By relieving systemic congestion by conventional HF management, he could easily recover from coma, leading to the idea that hepatic encephalopathy must be caused by liver congestion. There have been few reports so far regarding hepatic encephalopathy derived from exacerbated HF, considering some specific pathogenesis involved in this case.

OP23-5 Indication for Mitral Valve Surgery in Advanced Non-ischemic Dilated Cardiomyopathy: Molecular Biological Analysis in Histone Modification Process in Distressed Cardiomyocytes NORIYUKI KASHIYAMA, SHIGERU MIYAGAWA, KOICHI TODA, TERUYA NAKAMURA, YASUSHI YOSHIKAWA, SATSUKI FUKUSHIMA, SHUNSUKE SAITO, DAISUKE YOSHIOKA, YOSHIKI SAWA Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan Background: It has been reported that methylation or acetylation of histone H3, is closely related to distressed cardiomyocytes during the development of heart failure. In this study, we investigated whether reduced histone modification in the left ventricle (LV) would be associated with poor outcome after mitral valve (MV) replacement in advanced NIDCM with mitral regurgitation (MR). Methods: Poor outcome was defined as the need for left ventricular assist device (LVAD) implantation following MV surgery. The LV tissues in 13 patients with NIDCM (LV ejection fraction (LVEF & 35%)) with MR who underwent MV replacement from 2012 to 2015 were stained immunochemically with histone H3 lysine 9 tri-methylation (H3K9me3) and acetylation (H3K9ac), and scores were assigned as intensity and percentage of positive staining cardiac cell nuclei. Result: Four patients (31%) presenting poor outcome underwent LVAD implantation after MV surgery. In the both group, preoperative LVEF (p50.49) and LV end-systolic volume index (p50.42) were comparable, whereas LV stroke work index (LVSWI) was significantly lower in the patients with poor outcome (p50.02). Immunohistochemical scores of H3K9me3 and H3K9ac were significantly lower in the patients with poor outcome (p!0.01 and p!0.01, respectively) and closely correlated with LVSWI (p50.028, p!0.01, respectively). Conclusions: Reduced H3K9 methylation and acetylation in cardiomyocytes were closely related to poor LV performance and may represent poor clinical outcome after MV surgery in advanced NIDCM.

OP24-2 Relationships between Brain Natriuretic Peptide and Left Ventricular End Diastolic Pressure at Rest and during Exercise in Patients after AMI MICHINARI HIEDA1, SHINJI YASUNO2, NORITOSHI NAGAYA3, REIKO FUJIWARA1, REON KUMASAKA1, TETSUO ARAKAWA1, MICHIO NAKANISHI1, HIROSHI TAKAKI1,4, YOICHI GOTO1 1 Department of Cardiovascular Rehabilitation, National Cerebral and Cardiovascular Center, Suita, Osaka; 2EBM Center, Kyoto University; 3Nagaya Clinic; 4Takaki Clinic Background: The aim of this study was to clarify relationships between brain natriuretic peptide (BNP) and left ventricular end-diastolic pressure (LVEDP) at rest and during exercise in patients after acute myocardial infarction (AMI). Methods: We studied a total of 72 male patients after AMI (mean6SD of age: 6069 yr; peak

CPK 293161954 IU/L; ejection fraction (EF) 4769%). They underwent an invasive haemodynamic exercise test with simultaneous left (micromanometer) and right heart catheterization on a supine ergometer (work rate: 60-90W) at initiation of cardiovascular rehabilitation. The ratio of LVEDP to workload at peak exercise (LVEDP/W) was calculated as a measure of normalized LVEDP during exercise. Results: In the whole patients, LVEDP markedly increased during exercise (average; 1263 to 32610 mmHg, P!0.0001) without any adverse events. CPX demonstrated that LVEDP/W was significantly and negatively correlated with peak VO2 (r5-0.32, P50.008). Log-transformed BNP (Log-BNP) at initiation of cardiovascular rehabilitation (R50.39, P50.025) and 3-month (R50.16, P50.039) was correlated with LVEDP at rest. Log-BNP at 3-month was significantly correlated with LVEDP/W (R50.39, P50.028), but Log-BNP at initiation (R50.32, P50.076). Furthermore, D LVEDP was correlated with log-BNP at 3-month (R50.37, P50.037). Conclusion: Our data indicate that BNP is associated with left ventricular filling pressure at rest and during exercise, and that exercise-induced elevation of LVEDP is associated with reduced exercise capacity in post AMI non-failing patients.

OP24-3 A Combination of Anemia and High Levels of BNP is Indicative of In-Hospital Mortality of Patients with Acute Myocardial Infarction TADASHI SUGIE, SHIGETO NAMIUCHI, TORU TAKII, KENYA SAJI, ATSUSHI KATO Department of Cardiovascular Medicine, Sendai Open Hospital Background: Anemia is an important factor negatively affecting the prognosis of patients with ischemic heart disease. B-type natriuretic peptide (BNP), a marker of heart failure, is also closely associated with mortality in patients with acute myocardial infarction (AMI). However, few studies have assessed the relationship between hemoglobin (Hb) and BNP levels in AMI patients with regard to inhospital prognosis. Methods and Results: This study included 474 patients with AMI; their Hb concentrations were determined on admission; their BNP levels, approximately 7 days after the onset of AMI. The combined effect of these values on in-hospital mortality was evaluated. Patients were classified into 4 groups according to the presence of anemia and their median BNP values. The incidences of in-hospital mortality in the 4 groups were as follows: nonanemic patients with low BNP levels, 0.5%; nonanemic patients with high BNP levels, 5.5%; anemic patients with low BNP levels, 0%; and anemic patients with high BNP levels, 12%. Our results indicated that inhospital mortality was higher in anemic patients with high BNP levels than in nonanemic patients with low BNP levels. Conclusions: Classification based on the presence of anemia and BNP levels is useful for predicting in-hospital mortality in patients with AMI.

OP24-4 Enlargement of Infarct Size by CKD is Preventable by Consistent Activation of the Erythropoietin Receptor KEITARO NISHIZAWA1, TOSHIYUKI YANO1, TAKAYUKI MIKI1, MASAYA TANNO1, ATSUSHI KUNO2, HIDEMICHI KOUZU1, TOSHIYUKI TOBISAWA1, TETSUJI MIURA1 1 Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, Sapporo, Japan; 2Department of Pharmacology, Sapporo Medical Univercity Purpose: We examined if epoetin beta pegol (continuous erythropoietin receptor activator, CERA) reverses increased myocardial susceptibility to ischemia/reperfusion (I/ R) injury in chronic kidney disease (CKD). Methods and Results: The rats underwent 5/6 nephrectomy (subtotal nephrectomy, SNx) or a sham operation (Sham). Subcutaneous administration of CERA at a dose of 0.6 mg/kg or saline every 7 days was commenced at a week after the operation. At 5 weeks after the operation, development of CKD in SNx was confirmed by 2.4-fold increase in serum creatinine level. Treatment with CERA did not affect creatinine level in SNx. Hemoglobin level was lower in SNx than those in Sham (14.260.2 vs. 17.560.2 mg/dl), which was preserved in SNx by CERA (16.460.7 mg/dl). Infarct size, induced by 20-min coronary artery occlusion/2h reperfusion, was larger in SNx than in Sham (60.064.0 vs. 43.962.2% of risk area). CERA significantly reduced infarct size in SNx (36.963.9%) but not Sham (31.864.6%). In contrast, single injection of CERA a day before I/R did not reduce infarct size in SNx (58.163.0%). Infarct size was negatively correlated with hemoglobin level (r5-0.55, p!0.01), indicating that consistent, but not acute, activation of erythropoietin receptors plays a role in CERA-induced infarct size reduction in SNx. Conclusions: Consistent erythropoietin receptor activation prevents CKD-induced increase in myocardial susceptibility to I/R injury.

OP24-5 Relation between Hemodynamic Parameters on Admission and Worsening Renal Function in Early Phase in Patients with Acute Decompensated Heart Failure YUICHI KAWASE, LEO HATA, KEIICHIRO IWASAKI, TAKESHI TADA, KAZUSHIGE KADOTA, KAZUAKI MITSUDO Department of Cardiology, Kurashiki Central Hospital Background: In patients admitted for acute decompensated heart failure (ADHF), the relation between hemodynamic parameters on admission and worsening renal

The 19th Annual Scientific Meeting function (WRF, an increase in serum creatinine by O0.3 mg/dl from baseline) in early phase remains insufficiently evaluated. Methods: We retrospectively investigated the predictors of WRF within 24 hours in 80 patients admitted for ADHF and treated by pulmonary artery catheter-guided therapy between January 2006 and July 2007 (mean age, 78.4610.9 years). Result: WRF within 24 hours occurred in 9 patients (11.3%). There were no significant differences between patients with and without WRF in left ventricular ejection fraction (41.369.4% vs. 41.4612.6%, p50.98), pulmonary capillary wedge pressure (22.368.8 mmHg vs. 18.268.3 mmHg, p50.25), and cardiac index (3.361.3 l/min/m2 vs. 2.961 l/min/ m2, p50.3) on admission. By multivariate adjustment analysis, independent predictors of WRF within 24 hours were serum creatinine on admission (odds ratio, 7.1; 95% confidence interval, 2.2-33.9; p50.0007), men (odds ratio, 11.2; 95% confidence interval, 1.3-307.9; p50.024), and central venous pressure on admission (odds ratio, 1.3; 95% confidence interval, 1.1-1.6; p50.006). Conclusions: Central venous pressure on admission is an independent predictors of WRF in early phase, while other hemodynamic parameters on admission were not.

OP25-1 Clinical and Hemodynamic Effects of Simple Add-on Tolvaptan Therapy and Their Predictors in Patients with Heart Failure YUICHI SATO1, KAORU DOHI1, TETSUSHIRO TAKEUCHI1, MUNEYOSHI TANIMURA1, EMIYO SUGIURA1, NAOTO KUMAGAI1, SHIRO NAKAMORI1, NAOKI FUJIMOTO2, NORIKAZU YAMADA1, MASAAKI ITO1 1 Department of Cardiology and Nephrology, Mie University Graduate School of Medicine; 2Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine Purpose: We evaluated the clinical and hemodynamic effects of simple add-on tolvaptan (TLV) therapy and identified their predictors in patients with heart failure (HF). Methods: We retrospectively enrolled 60 HF patients with excess fluid retention despite receiving adequate medical therapy including oral diuretics. All patients received TLV (median of 7.5 mg/day). They underwent right heart catheterization at baseline and after 7-day treatment. Results: The majority of patients were successfully treated with simple add-on TLV therapy (Group 1), but 22% of patients (Group 2) were defined as being unsuccessfully treated because 1) HF symptom score worsened or 2) HF symptom score O6, and mean pulmonary capillary wedge pressure (PCWP) O18 mmHg and mean right atrial pressure (RAP) O10 mmHg after TLV therapy. The group 2 had lower urine sodium/creatinine ratio (UNa/UCr) and higher plasma BNP level than group 1 at baseline, and the combination with UNa/UCr !46.5 mEq/gCr and plasma BNP level O778 pg/ ml best predicted unsuccessful simple add-on TLV therapy with sensitivity of 54%, specificity of 100%, positive predictive value of 100%, negative predictive value of 89%, and accuracy of 90%. Conclusion: Combination of UNa/UCr and plasma BNP level best predicted clinical and hemodynamic effects of simple add-on TLV therapy.

OP25-2 The FE-K-guided Therapy May Lead a Better Outcome in Heart Failure Treated with Tolvaptan KEN-ICHI HIASA, TAKEO FUJINO, TAKAFUMI SAKAMOTO, KISHO OHTANI, YASUSHI MUKAI, TAIKI HIGO, TOMOMI IDE Department of Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan Background: Hyponatremia has prognostic significance for heart failure, however, tolvaptan (TLV) has no clinical evidence of survival improvement in hyponatremic heart failure. Our clinical data also revealed no beneficial effect on survival or re-hospitalization rate, especially in prolonged usage of, even though serum sodium tended to normalize in almost all cases. We hypothesised TLV may induce GFR reduction or activate renin-angiotensin-aldosterone (RAAS) system via intravascular free water clearance. Methods: A retrospective cohort design was used to assess 82 patients who treated TLV. We analyzed intravascular free water clearance, serum Na, and increase of fractional excretion of potassium (FE-K), which reflects RAAS activation or GFR reduction. Results: After administration of TLV, FE-K significantly increased compared short-term administration group with other groups, especially in poor prognostic groups as follows: need to mechanical support or valve replacement surgery (ex. VAD, PCPS or TAVI) and death, 5.5-O5.7%, 25.3-O35.3%, 28.9-O106.2%, respectively. However, there was not significant exacerbation in mortality rate in the long-term treated patients without FE-K elevation. Conclusion: Long-term administration of TLV may worsen rehospitalization and survival rate due to activation of reninangiotensinaldosterone system or GRF reduction via free water clearance of intravascular space. FE-K can be a helpful marker for early detection of RAAS activation or GFR reduction treated with TLV and FE-K-guided therapy may lead a better outcome for patients using TLV.



JHFS

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OP25-3 Right-Sided Dominant Heart Failure is a Predictor of Response to Tolvaptan TAKEO FUJINO, TAIKI HIGO, TAKAFUMI SAKAMOTO, KEN-ICHI HIASA, TOMOMI IDE Department of Cardiovascular Medicine, Kyushu University Hospital Background: Tolvaptan is effective to improve symptoms of patients with congestive heart failure (HF). However, the response to tolvaptan from the viewpoint of hemodynamics is not fully understood. Ratio of mean right atrial pressure (mRAP) to mean pulmonary capillary wedge pressure (mPCWP) is a robust parameter independent of volume condition, representing the balance of right and left ventricular functions. In this study we investigated the usefulness of ratio of mRAP to mPCWP (mRAP/ mPCWP) to predict responders to tolvaptan. Methods and Results: We retrospectively analyzed 48 patients whom we newly started tolvaptan for congestive HF since 2011. We defined responders (n521) as patients whose urine volume increased !500 ml or those whose body weight decreased !0.5 kg after initiation of tolvaptan, and defined others as non-responders (n527). Mean age was 59619 years old, and 54% were male. Serum total bilirubin was significantly elevated in responders. Right heart catheterization showed mRAP was significantly higher in responders (1466 vs 965 mmHg, P!0.01). Ratio of mRAP to mPCWP (mRAP/mPCWP) was also higher in responders (1.060.7 vs 0.660.5, P!0.05). Receiveroperating curve analysis showed the sensitivity and specificity to predict responders were 0.57 and 0.78, respectively, by the cutoff of mRAP/mPCWP 0.75. Conclusion: mRAP/mPCWP is useful for predicting responders to tolvaptan. Our result also suggest tolvaptan is useful for rightsided dominant heart failure.

OP25-4 Effect of Long-term Treatment of Tolvaptan in Patients with Acute Decompensated Heart Failure and Chronic Kidney Disease YUSUKE UEMURA, RYO IMAI, AYAKO MIURA, TAKAYUKI MITSUDA, SHINJI ISHIKAWA, MASAYOSHI KOYASU, TOMOHIRO UCHIKAWA, KENJI TAKEMOTO, MASATO WATARAI Cardiovascular Center, Anjo Kosei Hospital, Anjo, Japan Background: Tolvaptan has an aquaretic effect without affecting renal function. We investigated the effect of long-term treatment of tovaptan on clinical outcome and kidney function in patients with acute decompensated heart failure and advanced chronic kidney disease (CKD). Methods and Results: We compared a total of 33 patients who took tolvaptan for more than two months for the treatment of heart failure and had advanced CKD (defined by eGFR at admission ! 45 ml/min/1.73m2) between June 2012 and May 2015 (TLV group) with a historical control of 36 patients who had a need for increase of loop diuretics dosage or maintenance of high dose of loop diuretics (60mg or more) without tolvaptan for the control of heart failure between April 2010 and March 2012 (LD group). Patients were followed up for 6 months after discharge. A Kaplan-Meier analysis demonstrated that readmission rate for the treatment of heart failure was significantly lower in TLV group. Furthermore, in TLV group, changes in serum creatinine and eGFR after discharge were more favorable for kidney function. Conclusions: In patients admitted by acute decompensated heart failure with advanced CKD, oral tolvaptan decreased readmission caused by heart failure worsening and had renal protective effects during 6-month after discharge. Tolvaptan could be an effective agent for long-term management of heart failure and CKD.

OP25-5 Left Ventricular Systolic Function Affects the Renal Functions after Tolvaptan Treatment in Congestive Heart Failure Patients KENTARO JUJO1,2, NATSUKO SHIOZAKI1, NOBUHISA HAGIWARA1 1 Department of Cardiology, Tokyo Women’s Medical University, Tokyo, Japan; 2 Department of Cardiology, Nishiarai Heart Center Hospital, Tokyo, Japan Background: Tolvaptan exerts potent fluid excretion effects and preserves renal function in patients with congestive heart failure (CHF). However, the impact of their left ventricular ejection fraction (LVEF) on the effect of tolvaptan is unclear. Methods and Results: Sixty consecutive patients urgently hospitalized due to worsening of CHF were randomly assigned to receive either daily 40 mg of intravenous furosemide or 7.5 mg of oral tolvaptan in addition to standard CHF treatment. Then we classified the study population in each group by LVEF (cut-off: 40%) into patients with preserved LVEF (HFpEF) and reduced LVEF (HFrEF). Patient baseline profiles were significantly different among 4 groups, because HFpEF population more frequently included older patients with lower hemoglobin. Although total 5-day urine volume was similar among groups, serum creatinine was significantly increased only in furosemide-treated HFpEF patients. Incidence of worsening renal function was greater than 40% in furosemide-treated HFpEF patients, and it was significantly higher than other groups. One possible reason was that systolic blood pressure in furosemide-treated HFpEF patients greatly decreased compared to other groups, leading to impaired renal blood flow. Reductions in CVP, BNP, and plasma aldosterone