title: Effects of mineralocorticoid receptor antagonist spironolactone on cardiac sympathetic nerve activity and prognosis in patients with chronic heart failure.
abstract: BACKGROUND
  Aldosterone prevents norepinephrine uptake and promotes structural remodeling of the heart. Spironolactone is well known to have an anti-aldosteronergic effect, and this agent could improve cardiac sympathetic nerve activity (CSNA) in patients with chronic heart failure (CHF). On the other hand, we previously reported that the delta washout rate (WR) determined from serial (123)I-MIBG scintigraphic studies is the best currently available prognostic value in patients with CHF.
  
  
  METHODS
  In total 208 patients with CHF (left ventricular ejection fraction [LVEF] <45%), but no cardiac events for at least 5 months, were identified on the basis of a history of decompensated acute heart failure requiring hospitalization. These patients underwent (123)I-MIBG scintigraphy and echocardiography just before leaving the hospital and after 6 months of treatment. The patients were retrospectively divided into a spironolactone (n=82) and a non-spironolactone (n=126) group.
  
  
  RESULTS
  The extents of changes in (123)I-MIBG scintigraphic and echocardiographic parameters in the spironolactone group were significantly better than those in the non-spironolactone group. Of the 208 patients, 56 experienced fatal cardiac events during the study. The mean follow-up period was 4.45+/-1.82 years. On Kaplan-Meier analysis, the rate freedom from cardiac death was 81.7% (67/82) in the spironolactone group and 67.5% (85/126) in the non-spironolactone group (P<0.05). Moreover, stepwise multivariate analyses showed spironolactone therapy to have the most independent and significant negative relationship with delta-WR, during the period from hospital discharge until 6 months after starting treatment, in patients with CHF (P<0.001).
  
  
  CONCLUSIONS
  Spironolactone treatment improves CSNA and prevents LV remodeling in patients with CHF. Furthermore, this agent is potentially effective for reducing the incidence of fatal cardiac events in CHF patients.
authors.affiliation: Department of Medicine and Biological Science, Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan. s-kasama@bay.wind.ne.jp
authors.forename: Shu
authors.initials: S
authors.lastname: Kasama
authors.forename: Takuji
authors.initials: T
authors.lastname: Toyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sumino
authors.forename: Hisao
authors.initials: H
authors.lastname: Kumakura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takayama
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Minami
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone