Increased Urine Aquaporin-2 Levels Relative to Plasma Arginine ...

S174 Journal of Cardiac Failure Vol. 20 No. 10S October 2014 4h, 8h, and 24h after tolvaptan administration. Patients were divided into 3 groups according to the change of sodium level (D-group: decrease of sodium level vs. M-group: mild increase (1-4Meq/L) vs. I-group: increase (5-13Meq/L). Results: Hypernatremia (O149Meq/L) was observed in 3 patients (4.2%). Timing of reaching maximum sodium level was 4h in 2 (2.7%) and 24h in 35 (48.6%) patients, while sodium level did not increase after tolvaptan treatment in 35 (48.6%) patients. The level of baseline serum sodium was significantly different among the three groups (D-group: 139.263.6 vs. M-group: 135.966.7 vs. I-group:134.5 65.5Meq/L, respectively, p50.03). The age, potassium level, creatinine level, decrease of body weight, or tolvaptan dose was not associated with change of sodium level. Extreme sodium elevation (O12Meq/L) was observed in 1 (1.4%) patient, and the elevation timing was at 24h after tolvaptan administration. Conclusions: Rapid sodium elevation was rare, although prevalence of mild sodium elevation within 24h was about 50%. In future, we must check how frequently the serum sodium level should be measured according to the patient characteristics.

O-172 Baseline Urine Sodium Concentration Best Predicts the Response to Short-term Tolvaptan Treatment in Patients with Heart Failure YUICHI SATO1, KAORU DOHI1, TETSUSHIRO TAKEUCHI1, MUNEYOSHI TANIMURA1, EMIYO SUGIURA1, NAOTO KUMAGAI1, SHIRO NAKAMORI1, NAOKI FUJIMOTO2, MASHIO NAKAMURA3, 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, 3Department of Clinical Cardiovascular Research, Mie University Graduate School of Medicine Purpose: We identified predictor of response to tolvapan (TLV) in patients with heart failure (HF). Methods: We enrolled 48 patients with HF with excess fluid retention despite receiving oral diuretics. All patients received low-dose TLV (7.5 mg/day) for 7 days, and underwent right heart catheterization at baseline and after 7-day treatment period. Patients were defined as non-responder only if they require specific intervention including intravenous vasodilator and inotropic therapy beyond simply holding diuretic after TLV treatment. Results: Responders (77%) had higher urine sodium concentration, lower plasma BNP levels, lower mean pulmonary capillary wedge pressure (mPCWP) and mean right atrial pressure (mRAP) than non-responders at baseline. However, serum sodium levels and urine osmolality at baseline were similar between the two groups. Responders had greater reduction in mPCWP and mRAP than non-responders after 7-day treatment period. Multivariable logistic regression analysis confirmed that plasma BNP levels and urinary sodium concentration were the independent predictors of responders to TLV (BNP: OR 0.943, 95% CI 0.900-0.988, P50.010, urine sodium concentration: OR 1.006, 95% CI 1.001-1.010, P50.013). ROC curve analysis showed that urine sodium concentration was the best predictor of responders to TLV with cut-off point of O46.5 mEq/gCre (AUC 0.883, 95% CI; 0.768-0.999, sensitivity 79%, specificity 91%, PO0.001). Conclusion: Urinary sodium concentration is the most important predictor of responders to TLV in patients with HF.

O-173 Serum Creatinine and Estimated GFR Predict Long-term Efficacy of Vasopressin Receptor Antagonist in Patients with Decompensated Heart Failure SHIGETO TSUKAMOTO, TETSUO SAKAI, TERUO SEKIMOTO, TARO ADACHI, YUJI HAMAZAKI, YOUICHI KOBAYASHI Division of Caldiology, Department of Medicine, Showa University School of Medicine Background: To prevent re-hospitalization due to recurring decompensated heart failure, long-term administration of the vasopressin type 2 receptor antagonist

Variable Age, yrs Male, n (%) Tolvaptan dosage (mg) Left ventricular ejection fraction (%) Clinical scenario classification (2/3/5) Serum sodium (mEq/L) Serum creatinine (mg/dL) Estimated GFR (mL/ min/1.73m2) B-type natriuretic peptide (pg/mL) Loop diuretics dosage (mg)

Not rehospitalized (n58)

Rehospitalized (n59)

Pvalue

65.5 6 17.8 5 (62.5) 7.97 6 4.4 39 6 15.2

73.9 6 8.2 7 (77.8) 10.0 6 3.5 38 6 11.7

0.251 0.490 0.336 0.888

6/2/0

6/2/1

137.8 6 2.6 1.16 6 0.53

135.2 6 4.9 1.79 6 0.59

0.220 0.048

56.9 6 26.2

33.2 6 15.4

0.047

906.3 6 750.9

1226.8 6 816.5

0.463

77.5 6 55.2

128.9 6 63.2

0.121

(Tolvaptan) is often provided. However, their efficacy and indications are not to be determined. We retrospectively examined the patients treated with Tolvaptan for long term. Methods: Tolvaptan was administrated to 102 patients during hospitalization from October 2010 to May 2014. Long-term treatment of Tolvaptan after discharge was provided to 22 patients. Among 22 patients, 17 patients were followed-up for six months. We divided them into two groups whether re-hospitalized within six months after discharge or not, and compared clinical characteristics at the time of Tolvaptan administration. Results: Results are showed in Table. Conclusion: Serum creatinine and estimated GFR at the time of administration may predict long-term efficacy of Tolvaptan.

O-174 Increased Urine Aquaporin-2 Levels Relative to Plasma Arginine Vasopressin is a Novel Marker of Response to Tolvaptan TERUHIKO IMAMURA1, KOICHIRO KINUGAWA1, TAKEO FUJINO2, TOSHIRO INABA2, HISATAKA MAKI2, MASARU HATANO2, ATSUSHI YAO2, ISSEI KOMURO2 1 Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 2Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Background: Preserved function of collecting duct may be essential for the response to vasopressin V2 receptor antagonist, tolvaptan (TLV), but the relationship with responses to TLV has been unknown. Methods and Results: Consecutive 60 patients with stage D decompensated heart failure (HF) who had received TLV on a de novo basis were retrospectively enrolled [TLV(+) group]. Among them, 41 patients were responders defined by urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma levels of arginine vasopressin (P-AVP) had a close correlation (r50.843, p!0.001) with urine aquaporin-2 (U-AQP2) levels (5.42 6 3.54 ng/mL). In contrast, 19 were the UV-defined non-responders, and they had extremely low UAQP2 levels (0.76 6 0.59 ng/mL, p!0.001 vs. responders) regardless of P-AVP levels. Calculated by the ROC analysis, U-AQP2/P-AVP O0.5 103 completely separated the UV-defined responders from the non-responders. Then, we determined the AQPdefined responders as having U-AQP2/P-AVP O0.5 103. Propensity score-matched 60 HF patients without TLV treatment were examined, and exactly the same numbers of patients (N541) were selected as the AQP-defined responders. These patients had a poorer survival without TLV than the TLV-treated responders over 2-year observation period (73.8% vs. 94.8%, p50.034). Conclusions: U-AQP2/P-AVP is a novel predictor for the response to TLV in patients with decompensated HF. The AQP-defined responders may enjoy a better prognosis by TLV treatment.

O-175 BNP Level Predicts Clinical Efficacy of Tolvaptan in Patients with Heart Failure SEIICHIROU YOSHIMURA1, YOSHITAKA SUGAWARA1, YASUYUKI MARUYAMA2, TAKAAKI SHIONO3, TOSHIKAZU FUNAZAKI4, YOSHIHIKO SAKAI5, NORIHUMI KUBO6, HIROSHI WADA1, TAKESHI MITSUHASHI1, SHIN-ICHI MOMOMURA1 1 Cardiovascular Division Saitama Medical Center, Jichi Medical University, Saitama city, Saitama, Japan, 2Iwatsuki Minami Hospital, 3Kitazato Medical Center, 4 Kawaguchi Saiseikai Hospital, 5Koshigaya Hospital, Dokkyo Medical University, 6 Saitama Medical Center Objective: We examined the effectiveness and safety of tolvaptan in patients hospitalized for heart failure in multi center. Method: Clinical parameters including urine volume, body weight, serum sodium level and renal function, were obtained from in hospital patients with heart failure who had received tolvaptan at 3.75 to 15 mg daily. Results: Tolvaptan was administered in 66 patients (male 48/female18, age 70.3+/ 14.1, NYHA2:3:457:42:15). During hospitalization, urinary volume increase (pre12526684 ml, post18426877ml, p ! 0.0001) and body weight decreased significantly(pre 64.1617.6Kg, post 59.8616.3Kg, p ! 0.0001), without significant changes in blood pressure, heart rate, serum Na level and serum creatine level. BNP level had correlations with change of urine volume. Conclusions: Patients BNP level predicts changes of urine volume.

O-176 RV Dysfunction Plays an Important Role in Predicting Non-response to Tolvaptan in Patients with Heart Failure with Reduced Ejection Fraction NORIAKI IWAHASHI, TOSHIAKI EBINA, KAZUO KIMURA Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan We explored the role of RV function for the prediction of Tolvaptan (TLV) in patients with heart failure with reduced EF(HFrEF). Methods: 55 patients admitted for acute decompensated HF were enrolled (Age73 years, 35male). EF were uniformly reduced (LVEF532%). They were administered TLV at 7.5-15 mg/day for one week. Non-response was defined as no evidence of a 1 kg decrease in body weight (BW) during a week. Blood sampling and echocardiography, including strain imaging, were performed just prior to starting TLV. Vivid-q