title: The prognostic impact of immunosuppression and cellular rejection on cardiac allograft vasculopathy: time for a reappraisal.
abstract: BACKGROUND
  Our current immunosuppressive strategies have made little impact on the development of cardiac allograft vasculopathy, the leading cause of long-term allograft loss. This study sought to evaluate the relationship of cellular rejection and immunosuppressive therapy with the development of morbid events resulting from cardiac allograft vasculopathy.
  
  
  METHODS
  The study population consisted of 163 consecutive patients who received heart transplants between January 1990 and May 1994. Data regarding nonimmunologic risk factors (lipids, obesity indexes, hypertension, donor age and sex, cytomegalovirus infection, diabetes mellitus, time after transplantation, and cold ischemic time), immunologic factors (histocompatibility, episodes of treated rejection, and average first-year biopsy rejection score), and immunosuppressive regimens (cumulative prednisone dose, average daily prednisone dose, mean cyclosporine level, average cyclosporine daily dose, cumulative azathioprine dose, and average daily azathioprine dose) were collected and analyzed in all patients. The diagnosis of cardiac allograft vasculopathy was established in all patients by a combination of necropsy, angiography, and intravascular ultrasound examination of the allograft vasculature. Cardiac events were defined as sudden death, myocardial infarction, and need for revascularization.
  
  
  RESULTS
  Of all variables assembled, stepwise logistic regression recognized cumulative prednisone dose > 15 gm (relative risk [RR] 5.7; p = 0.01), donor age > 35 years (RR 3.73; p < 0.05), and average biopsy rejection score > 1 (RR 2.77; p < 0.05) as independent adverse predictors of cardiac events. In distinction, average daily cyclosporine dose > 4.5 mg/kg/day was found to confer a protective effect (RR 0.16; p = 0.03).
  
  
  CONCLUSIONS
  The development of cardiac events as a result of cardiac allograft vasculopathy is influenced by the interdependence of allograft rejection and the balance of immunosuppression. The clinical implications of these findings point to the need for a reappraisal of our traditional approach to using corticosteroids (acute and maintenance) and cyclosporine (maintenance) in heart transplantation.
authors.affiliation: Advanced Heart Failure and Cardiac Transplant Program, Ochsner Medical Institutions, New Orleans, Louisiana 70121, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Mehra
authors.forename: H O
authors.initials: HO
authors.lastname: Ventura
authors.forename: R B
authors.initials: RB
authors.lastname: Chambers
authors.forename: K
authors.initials: K
authors.lastname: Ramireddy
authors.forename: F W
authors.initials: FW
authors.lastname: Smart
authors.forename: D D
authors.initials: DD
authors.lastname: Stapleton
mesh_terms: D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents