Early treatment with tolvaptan improves diuretic response in acute heart failure with renal dysfunction

Yuya Matsue, Jozine M. Ter Maaten, Makoto Suzuki, Sho Torii, Satoshi Yamaguchi, Seiji Fukamizu, Yuichi Ono, Hiroyuki Fujii, Takeshi Kitai, Toshihiko Nishioka, Kaoru Sugi, Yuko Onishi, Makoto Noda, Nobuyuki Kagiyama, Yasuhiro Satoh, Kazuki Yoshida, Peter van der Meer, Kevin Damman, Adriaan A. Voors, Steven R. Goldsmith

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Background: Poor response to diuretics is associated with worse prognosis in patients with acute heart failure (AHF). We hypothesized that treatment with tolvaptan improves diuretic response in patients with AHF. Methods: We performed a secondary analysis of the AQUAMARINE open-label randomized study in which a total of 217 AHF patients with renal impairment (eGFR < 60 mL/min/1.73 m2) were randomized to either tolvaptan or conventional treatment. We evaluated diuretic response to 40 mg furosemide or its equivalent based on two different parameters: change in body weight and net fluid loss within 48 h. Results: The mean time from patient presentation to randomization was 2.9 h. Patients with a better diuretic response showed greater relief of dyspnea and less worsening of renal function. Tolvaptan patients showed a significantly better diuretic response measured by diuretic response based both body weight [−1.16 (IQR −3.00 to −0.57) kg/40 mg vs. −0.51 (IQR −1.13 to −0.20) kg/40 mg; P < 0.001] and net fluid loss [2125.0 (IQR 1370.0–3856.3) mL/40 mg vs. 1296.3 (IQR 725.2–1726.5) mL/40 mg; P < 0.001]. Higher diastolic blood pressure and use of tolvaptan were independent predictors of a better diuretic response. Conclusions: Better diuretic response was associated with greater dyspnea relief and less WRF. Early treatment with tolvaptan significantly improved diuretic response in AHF patients with renal dysfunction.

Original languageEnglish (US)
Pages (from-to)802-812
Number of pages11
JournalClinical Research in Cardiology
Issue number10
StatePublished - Oct 1 2017

Bibliographical note

Funding Information:
AQUAMARINE study was funded by Japan Heart Foundation Multicenter Study Grant. Dr.Yuya Matsue is supported by JSPS (Japan Society for the Promortion of Science) Overseas Research Fellowship, and received a honorarium from Otsuka Pharmaceutical Co. Dr. Makoto Suzuki received lectures honoraria from Bayer, Otsuka Pharmaceutical Co., Biotronik Japan Co., Daiichi-Snakyo, Medtronic Japan Co., Ltd., St. Jude Medical Japan, and Fukuda Denshi. Dr. Yuichi ono received lectures honoraria from Medtronic Japan Co., Ltd. Dr. Kazuki Yoshida receives tuition support jointly from the Japan Student Services Organization and Harvard T. H. Chan School of Public Health (partially supported by training Grants from Pfizer, Takeda, Bayer, and PhRMA). Dr. Kaoru Sugi received scholarship fund from Daiichi-Sankyo Pharmaceutical and lectures honoraria from Bayer. Dr. Steven R. Goldsmith received consulting fees, speaking fees, and research support from Otsuka USA and Otsuka-Japan. The other authors have nothing to disclose related to this paper.

Funding Information:
Funding AQUAMARINE study was funded by Japan Heart Foundation Multicenter Study Grant.

Publisher Copyright:
© 2017, The Author(s).


  • Acute heart failure
  • Diuretics
  • Dyspnea relief
  • Worsening renal function


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