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Use of Tolvaptan in Outpatients
S204 Journal of Cardiac Failure Vol. 21 No. 10S October 2015 significantly associated with increased composite events (adjusted hazard ratio (HR), 1.38; 95% confidence interval (CI), 1.15-1.67, P50.001). Moreover, higher furosemide dose (O 40mg) was associated with incidence of composite events, especially in patients with reduced ejection fraction (!50%) (HR, 1.93; 95% CI, 1.37-2.71, P! 0.001) and in patients with lower glomerular filtration rate (!60%) (HR, 1.68; 95% CI, 1.262.24, P!0.001). Conclusions: Use of higher dose of furosemide is associated with worsened prognosis in CHF patients.
PP9-2 High Blood Urea Nitrogen to Creatinine Ratio Predicts Poor Clinical Outcome in CHF Patients with Standard Dose of Furosemide TAKUMI KONDO, TAKAHISA YAMADA, TAKASHI MORITA, SHUNSUKE TAMAKI, MASATAKE FUKUNAMI Division of Cardiology, Osaka General Medical Center, Osaka We investigated whether diuretics dose affected the prognostic value of BUN to creatinine (Cr) ratio in CHF patients. 155 euvolemic CHF pts with LVEF!40% were divided into 2 groups according to the furosemide dose, the standard dose group (SD): 40-80mg/d (n574) and low dose group (LD) !40mg/d (n581). During follow-up period of 6.264.5 years, 49 of 155 patients hospitalized for worsening heart failure (WHF) (35 pts in SD and 14 in LD). Patients with high BUN/Cr ratio had significantly higher risk of hospitalization of WHF than those with low BUN/ Cr (57% vs 38% p50.01, HR 3.4 [1.6-7.2]) in SD but not in LD. High blood urea nitrogen to creatinine ratio could predict hospitalization of worsening heart failure in CHF patients with standard dose but not in low dose of furosemide.
Figure.
PP9-3 Efficacy of Additional Administration of Vasopressin Receptor Antagonist in Acute Decompensated Heart Failure: A Prospective Randomized Study TETSUO SAKAI, GYOUITI KANAKO, SHIGETO TSUKAMOTO, MAKOTO SHOJI, YOUICHI KOBAYASHI Division of Cardiology, Department of Medicine, Showa University, School of Medicine, Tokyo, Japan Background: Vasopressin receptor antagonist (Tolvaptan) attracts attention as new diuretics for acute decompensated heart failure. One of the most characteristic effects is not to reduce serum sodium level, and expected good influence for prognosis. However, the efficacy of Tolvaptan remains unclear in real clinical situation. We performed randomized prospective study compared to conventional therapy. Methods: Thirty patients with decompensated heart failure who were not improved body fluid retention, regardless administrating 40mg Furosemide or more, were examined. Patients were randomly divided to Tolvaptan administrate group (T group: n515) and conventional therapy group (C group: n515). Changes of NYHA and NohriaStevenson classification at day 0 to day 7 were compared. Serum sodium, osmolality, creatinine, BNP, urine osmolality, sodium level, and other biomarkers at day 0, 3, and 7 were measured. Results: Changes of clinical symptoms after 7days, T group showed better improvement than C group in NYHA classification level. Urine volume was more increased in T group than C group. Changes of biomarker levels revealed no significant difference except serum sodium, urine sodium and osmolality levels. Conclusion: Additional administration of Tolvaptan maybe contributes to early improvement of heart failure symptom.
PP9-4 Use of Tolvaptan in Outpatients AKIHIRO MIZUHARA1, HIROMI AOKI2 1 Department of Cardiology and Vascular Surgery, Higashi-Washinomiya Hospital, Saitama, Japan; 2Department of Internal Medicine, Higashi-Washinomiya Hospital, Saitama, Japan Tolvaptan, a vasopressin receptor antagonist, inhibits water reabsorption in the renal collecting ducts. Tolvaptan has been found to be highly effective in treating
overhydration leading to heart failure. Subjects of the current study were 42 patients taking tolvaptan after hospital discharge. Subjects consisted of 10 patients with valvular heart disease, 9 with atrial fibrillation, 8 with dilated cardiomyopathy, 6 with overhydration, 4 with old myocardial infarction, 3 with hypertension, and 2 with some other condition (mean age: 76.3 years). Eleven patients (mean age: 81.5 years) died after discharge. For the remaining 31 patients, the mean period of observation was 12.0 months. For these patients, the mean dose of tolvaptan was 7.14 mg and mean weight was 57.9 kg. Electrolytes were gauged with sodium levels and renal function was gauged with creatine levels. Patients had Na of 138.8 mEq/l and Cre of 1.4 mg/dl. Prior to taking tolvaptan, patients were readmitted an average of 1.7 times, while after taking it they were readmitted an average of 0.5 times. A low dose 3.757.5 mg of tolvaptan was administered to outpatients, who led relatively stable lives without developing heart failure symptoms. Hypernatremia did not pose a problem in any of the patients. Continued administration of low-dose tolvaptan to outpatients is useful at combatting heart failure.
PP9-5 Tolvaptan Retains Proportion of Body Fluid Compartments during Treatment of Decompensated Heart Failure: Two Case Reports TAKESHI SUETOMI, MASAKI TAMITANI, AKIHIRO HINO, YOSUKE MIYAZAKI, MAKOTO ONO, MAMORU MOCHIZUKI, TETSURO ODA, SHIGEKI KOBAYASHI, TAKESHI YAMAMOTO, MASAFUMI YANO Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan Background: The effect of tolvaptan for body fluid compartments is still unclear. Whereas Multifrequency bioimpedance analysis (MFBIA) is non-invasive tool for body water distribution, there is considerable individual variation. Case 1: An 82year-old woman who was diagnosed as ischemic cardiomyopathy and severe mitral regurgitation was admitted due to acute decompensated heart failure (ADHF) of clinical scenario (CS) 3. Azosemide (60 mg/day), and spironolactone (12.5 mg/day) was administered. Dyspnea and hypoxia were improved but there was residual pleural effusion, and then tolvaptan (7.5 mg/day) was added. Case 2: A 40-year-old man who had congenitally corrected transposition of the great arteries was admitted due to ADHF of CS3 with atrial flutter. Cardioversion was performed, and then under noninvasive positive pressure ventilation, catecholamine, furosemide (40 mg/day), and spironolactone (25 mg/day) was administered and adequate diuresis was obtained in 6 days. Tolvaptan (7.5 mg/day) was temporarily added because of the residual systemic edema. Each case underwent MFBIA, and the amount of change in the extracellular-to-intracellular fluid Ratio (D ECF/ICF) was smaller during addition of tolvaptan than that of during only conventional diuretics administration. The amount of change in the estimated GFR (D eGFR) demonstrated same tendency. Conclusion: These cases suggest that tolvaptan tends to retain proportion of body fluid compartments compared to conventional diuretics.
PP9-6 Diuretic Response in Acute Heart Failure: Effects of Very Low Dose Tolvaptan (1.875 mg) in Old Age Patients HIROAKI MANO, KEN ARIMA, TOURU KOUNO, TOMOHIRO FURUICHI Department of cardiology, Kasukabe Municipal Hospital, Kasukabe, Japan Background: Hospitalizations for worsening heart failure due to fluid overload are common. The vasopressin antagonist Tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function. Objective: To evaluate the intermediate effects of very low dose Tolvaptan in old age patients hospitalized with heart failure. Method: We studied 16 patients (75 6 10.6 years) for heart failure with persistent signs and symptoms of systemic congestion. The serum creatinine level was 1.1 6 0.4 mg/dl. The therapeutic effects of low-dose (3.75 mg) and very low-dose (1.875 mg) once-daily Tolvaptan on hemodynamics associated with changes in fluid balance were investigated after a seven day treatment period. Results: After 7 days treatment period, body weight decreased (-5.0 6 3.7 kg); the between-group difference was not significant (p5 0.72). No significant differences were observed between very low dose group and low dose group in the urine volume (2334 ml vs. 2348 ml, p5 0.98) and Capacity of Tolvaptan required weight to decrease was significant bigger (2.8 6 2.0 kg/mg vs. 1.0 6 0.7 kg/mg, p50.03) in the very low dose Tolvaptan group. Conclusion: Very low dose Tolvaptan has been shown to reduce body weight in patients with worsening heart failure.
PP9-7 The Efficacy of Long-Term Administration of Tolvaptan for Recurrent Heart Failure RYUJI KUBOTA Department of Cardiology, Toyota Kosei Hospital, Toyota, Japan Background: There are only a few reports about the safety and efficacy of long-term administration of tolvaptan (TLV) in patients with heart failure. Therefore, we
PP9-2 High Blood Urea Nitrogen to Creatinine Ratio Predicts Poor Clinical Outcome in CHF Patients with Standard Dose of Furosemide TAKUMI KONDO, TAKAHISA YAMADA, TAKASHI MORITA, SHUNSUKE TAMAKI, MASATAKE FUKUNAMI Division of Cardiology, Osaka General Medical Center, Osaka We investigated whether diuretics dose affected the prognostic value of BUN to creatinine (Cr) ratio in CHF patients. 155 euvolemic CHF pts with LVEF!40% were divided into 2 groups according to the furosemide dose, the standard dose group (SD): 40-80mg/d (n574) and low dose group (LD) !40mg/d (n581). During follow-up period of 6.264.5 years, 49 of 155 patients hospitalized for worsening heart failure (WHF) (35 pts in SD and 14 in LD). Patients with high BUN/Cr ratio had significantly higher risk of hospitalization of WHF than those with low BUN/ Cr (57% vs 38% p50.01, HR 3.4 [1.6-7.2]) in SD but not in LD. High blood urea nitrogen to creatinine ratio could predict hospitalization of worsening heart failure in CHF patients with standard dose but not in low dose of furosemide.
Figure.
PP9-3 Efficacy of Additional Administration of Vasopressin Receptor Antagonist in Acute Decompensated Heart Failure: A Prospective Randomized Study TETSUO SAKAI, GYOUITI KANAKO, SHIGETO TSUKAMOTO, MAKOTO SHOJI, YOUICHI KOBAYASHI Division of Cardiology, Department of Medicine, Showa University, School of Medicine, Tokyo, Japan Background: Vasopressin receptor antagonist (Tolvaptan) attracts attention as new diuretics for acute decompensated heart failure. One of the most characteristic effects is not to reduce serum sodium level, and expected good influence for prognosis. However, the efficacy of Tolvaptan remains unclear in real clinical situation. We performed randomized prospective study compared to conventional therapy. Methods: Thirty patients with decompensated heart failure who were not improved body fluid retention, regardless administrating 40mg Furosemide or more, were examined. Patients were randomly divided to Tolvaptan administrate group (T group: n515) and conventional therapy group (C group: n515). Changes of NYHA and NohriaStevenson classification at day 0 to day 7 were compared. Serum sodium, osmolality, creatinine, BNP, urine osmolality, sodium level, and other biomarkers at day 0, 3, and 7 were measured. Results: Changes of clinical symptoms after 7days, T group showed better improvement than C group in NYHA classification level. Urine volume was more increased in T group than C group. Changes of biomarker levels revealed no significant difference except serum sodium, urine sodium and osmolality levels. Conclusion: Additional administration of Tolvaptan maybe contributes to early improvement of heart failure symptom.
PP9-4 Use of Tolvaptan in Outpatients AKIHIRO MIZUHARA1, HIROMI AOKI2 1 Department of Cardiology and Vascular Surgery, Higashi-Washinomiya Hospital, Saitama, Japan; 2Department of Internal Medicine, Higashi-Washinomiya Hospital, Saitama, Japan Tolvaptan, a vasopressin receptor antagonist, inhibits water reabsorption in the renal collecting ducts. Tolvaptan has been found to be highly effective in treating
overhydration leading to heart failure. Subjects of the current study were 42 patients taking tolvaptan after hospital discharge. Subjects consisted of 10 patients with valvular heart disease, 9 with atrial fibrillation, 8 with dilated cardiomyopathy, 6 with overhydration, 4 with old myocardial infarction, 3 with hypertension, and 2 with some other condition (mean age: 76.3 years). Eleven patients (mean age: 81.5 years) died after discharge. For the remaining 31 patients, the mean period of observation was 12.0 months. For these patients, the mean dose of tolvaptan was 7.14 mg and mean weight was 57.9 kg. Electrolytes were gauged with sodium levels and renal function was gauged with creatine levels. Patients had Na of 138.8 mEq/l and Cre of 1.4 mg/dl. Prior to taking tolvaptan, patients were readmitted an average of 1.7 times, while after taking it they were readmitted an average of 0.5 times. A low dose 3.757.5 mg of tolvaptan was administered to outpatients, who led relatively stable lives without developing heart failure symptoms. Hypernatremia did not pose a problem in any of the patients. Continued administration of low-dose tolvaptan to outpatients is useful at combatting heart failure.
PP9-5 Tolvaptan Retains Proportion of Body Fluid Compartments during Treatment of Decompensated Heart Failure: Two Case Reports TAKESHI SUETOMI, MASAKI TAMITANI, AKIHIRO HINO, YOSUKE MIYAZAKI, MAKOTO ONO, MAMORU MOCHIZUKI, TETSURO ODA, SHIGEKI KOBAYASHI, TAKESHI YAMAMOTO, MASAFUMI YANO Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan Background: The effect of tolvaptan for body fluid compartments is still unclear. Whereas Multifrequency bioimpedance analysis (MFBIA) is non-invasive tool for body water distribution, there is considerable individual variation. Case 1: An 82year-old woman who was diagnosed as ischemic cardiomyopathy and severe mitral regurgitation was admitted due to acute decompensated heart failure (ADHF) of clinical scenario (CS) 3. Azosemide (60 mg/day), and spironolactone (12.5 mg/day) was administered. Dyspnea and hypoxia were improved but there was residual pleural effusion, and then tolvaptan (7.5 mg/day) was added. Case 2: A 40-year-old man who had congenitally corrected transposition of the great arteries was admitted due to ADHF of CS3 with atrial flutter. Cardioversion was performed, and then under noninvasive positive pressure ventilation, catecholamine, furosemide (40 mg/day), and spironolactone (25 mg/day) was administered and adequate diuresis was obtained in 6 days. Tolvaptan (7.5 mg/day) was temporarily added because of the residual systemic edema. Each case underwent MFBIA, and the amount of change in the extracellular-to-intracellular fluid Ratio (D ECF/ICF) was smaller during addition of tolvaptan than that of during only conventional diuretics administration. The amount of change in the estimated GFR (D eGFR) demonstrated same tendency. Conclusion: These cases suggest that tolvaptan tends to retain proportion of body fluid compartments compared to conventional diuretics.
PP9-6 Diuretic Response in Acute Heart Failure: Effects of Very Low Dose Tolvaptan (1.875 mg) in Old Age Patients HIROAKI MANO, KEN ARIMA, TOURU KOUNO, TOMOHIRO FURUICHI Department of cardiology, Kasukabe Municipal Hospital, Kasukabe, Japan Background: Hospitalizations for worsening heart failure due to fluid overload are common. The vasopressin antagonist Tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function. Objective: To evaluate the intermediate effects of very low dose Tolvaptan in old age patients hospitalized with heart failure. Method: We studied 16 patients (75 6 10.6 years) for heart failure with persistent signs and symptoms of systemic congestion. The serum creatinine level was 1.1 6 0.4 mg/dl. The therapeutic effects of low-dose (3.75 mg) and very low-dose (1.875 mg) once-daily Tolvaptan on hemodynamics associated with changes in fluid balance were investigated after a seven day treatment period. Results: After 7 days treatment period, body weight decreased (-5.0 6 3.7 kg); the between-group difference was not significant (p5 0.72). No significant differences were observed between very low dose group and low dose group in the urine volume (2334 ml vs. 2348 ml, p5 0.98) and Capacity of Tolvaptan required weight to decrease was significant bigger (2.8 6 2.0 kg/mg vs. 1.0 6 0.7 kg/mg, p50.03) in the very low dose Tolvaptan group. Conclusion: Very low dose Tolvaptan has been shown to reduce body weight in patients with worsening heart failure.
PP9-7 The Efficacy of Long-Term Administration of Tolvaptan for Recurrent Heart Failure RYUJI KUBOTA Department of Cardiology, Toyota Kosei Hospital, Toyota, Japan Background: There are only a few reports about the safety and efficacy of long-term administration of tolvaptan (TLV) in patients with heart failure. Therefore, we