title: Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality.
abstract: OBJECTIVE
  This study examined the hypothesis that patients who develop angiotensin-converting enzyme inhibitor intolerance attributable to circulatory-renal limitations (CRLimit) have more severe underlying disease and worse outcome.
  
  
  BACKGROUND
  Although the renin-angiotensin system contributes to the progression of heart failure (HF), it also supports the failing circulation. Patients with the most severe disease may not tolerate inhibition of this system.
  
  
  METHODS
  Consecutive inpatient admissions to the cardiomyopathy service of the Brigham and Women's Hospital between 2000 and 2002 were reviewed retrospectively for initial profiles, discharge medications, and documented reasons for discontinuation of angiotensin-converting enzyme inhibitors. Outcomes of death and transplantation were determined.
  
  
  RESULTS
  Of the 259 patients, 86 were not on an angiotensin-converting enzyme inhibitor at discharge. Circulatory-renal limitations of symptomatic hypotension, progressive renal dysfunction, or hyperkalemia were documented in 60 patients (23%); other adverse effects, including cough, in 24 patients; and absent reasons in 2 patients. Compared with patients on angiotensin-converting enzyme inhibitors, patients with CRLimit were older (60 vs. 55 years; p = 0.006), with longer history of HF (5 vs. 2 years; p = 0.009), lower systolic blood pressure (104 vs. 110 mm Hg; p = 0.05), lower sodium (135 vs. 138 mEql/l; p = 0.002), and higher initial creatinine (2.5 vs. 1.2 mg/dl; p = 0.0001). Mortality was 57% in patients with CRLimit and 22% in the patients on angiotensin-converting enzyme inhibitors during a median 8.5-month follow-up (p = 0.0001).
  
  
  CONCLUSIONS
  Development of CRLimit to angiotensin-converting enzyme inhibitor intolerance identifies patients with severe disease who are likely to die during the next year. New treatment strategies should be targeted to this population.
authors.affiliation: Departments of Medicine and Cardiology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kittleson
authors.forename: Shelley
authors.initials: S
authors.lastname: Hurwitz
authors.forename: Monica R
authors.initials: MR
authors.lastname: Shah
authors.forename: Anju
authors.initials: A
authors.lastname: Nohria
authors.forename: Eldrin
authors.initials: E
authors.lastname: Lewis
authors.forename: Michael
authors.initials: M
authors.lastname: Givertz
authors.forename: James
authors.initials: J
authors.lastname: Fang
authors.forename: John
authors.initials: J
authors.lastname: Jarcho
authors.forename: Gilbert
authors.initials: G
authors.lastname: Mudge
authors.forename: Lynne W
authors.initials: LW
authors.lastname: Stevenson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001581:Benzothiadiazines; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001900:Boston / Q000453:epidemiology; D003404:Creatinine / Q000378:metabolism; D004232:Diuretics; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D015995:Prevalence; D012079:Renal Circulation / Q000187:drug effects*; D012720:Severity of Illness Index; D012964:Sodium / Q000097:blood; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D016019:Survival Analysis; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001581:Benzothiadiazines; D015415:Biomarkers; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D012964:Sodium; D003404:Creatinine; D011188:Potassium