title: Efficacy and safety of tolvaptan for pediatric patients with congestive heart failure. Multicenter survey in the working group of the Japanese Society of PEdiatric Circulation and Hemodynamics (J-SPECH).
abstract: BACKGROUND
  Tolvaptan, a vasopressin V2-receptor antagonist, has been reported to improve congestion in adult patients with heart failure. However, it has not been fully clarified whether tolvaptan is also effective and safe for pediatric patients as well as adult.
  
  
  METHODS
  This trial was a multicenter, retrospective, observational study, and was led by the Japanese Society of PEdiatric Circulation and Hemodynamics (J-SPECH). Thirty-four pediatric patients who received tolvaptan to treat congestive heart failure were enrolled in this study.
  
  
  RESULTS
  An increment in the urinary volume and decrease in the body weight from baseline were significant at day 1 (+106.7 ± 241.5%, p = 0.008 and -2.30 ± 4.17%, p = 0.01), day 3 (+113.5 ± 261.9%, p = 0.02 and -2.30 ± 4.17%, p = 0.01), week 1 (+56.3 ± 163.5%, p = 0.01 and -1.55 ± 4.09%, p = 0.03) and month 1 (+91.1 ± 171.6%, p = 0.01 and -2.95 ± 5.98, p = 0.03). The significant predictive factors in responders, who was defined as patients who achieved an increase in the urinary volume at day 1, were older age (p = 0.03), larger body weight before exacerbation (p = 0.04), higher weight at one day before the first administration of tolvaptan (p = 0.03), higher aspartate aminotransferase levels (p = 0.03) and higher urinary osmolality levels (p = 0.03). A logistic regression analysis showed that the urinary osmolality was the only significant predictive factor for responders to tolvaptan. Adverse drug reactions were observed in 7 patients (20.6%). Six patients had thirst and a dry month, and 1 had a mild increase in the alanine aminotransferase and aspartate aminotransferase.
  
  
  CONCLUSIONS
  Tolvaptan can be effectively and safely administered in pediatric patients. Because the kidneys in neonates and infants are resistant to arginine vasopressin, the efficacy of tolvaptan may be less effective compared to older children.
authors.affiliation: Department of Cardiology, Chiba Children's Hospital, Japanese Society of PEdiatric Circulation and Hemodynamics, Japan; Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Department of Cardiology, Chiba Children's Hospital, Japanese Society of PEdiatric Circulation and Hemodynamics, Japan; Japanese Society of PEdiatric Circulation and Hemodynamics, Japan. Electronic address: murat@seagreen.ocn.ne.jp.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Itoi
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohuchi
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Masutani
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Yamazawa
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Senzaki
authors.affiliation: Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ishikawa
mesh_terms: D000293:Adolescent; D065092:Antidiuretic Hormone Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D010372:Pediatrics / Q000379:methods; D012189:Retrospective Studies; D012955:Societies, Medical; D011795:Surveys and Questionnaires; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan
keywords: Arginine vasopressin; Child; Congestive heart failure; Diuretics; Hyponatremia; Tolvaptan