title: Clinical significance of mild rejection of the cardiac allograft.
abstract: BACKGROUND
  The clinical status of heart transplant patients during mild rejection (lymphocytic infiltrate without myocyte necrosis) has not been previously reported. This study examined the frequency and outcome of mild rejection associated with allograft dysfunction sufficient in magnitude to be evident on clinical exam (two or more abnormal findings) and/or two-dimensional echocardiography.
  
  
  RESULTS
  The study population consisted of 59 patients, 50 men and nine women 14-61 years old (mean, 1.7 +/- 0.8 years) with a mean follow-up of 1.7 +/- 0.8 years after transplant. All were receiving cyclosporine, azathioprine, and prednisone. A total of 108 episodes of mild rejection were detected (frequency, 1.8 episodes per patient). Detailed records of clinical findings were available for 94 episodes. Thirty-five (37%) of these 94 mild rejections were associated with allograft dysfunction: hypotension, n = 4; elevated jugular venous pressure, n = 14; S3, n = 13; rales, n = 10; sinus rate > or = 110 beats per minute, n = 25; atrial fibrillation, n = 5; bradycardia < 60, n = 1; and systolic dysfunction on echo, n = 14. Treatment with high-dose steroids was clinically indicated in eight mild rejection episodes (9%) with allograft dysfunction. Of the remaining 86 untreated episodes, eight (30%) of 27 with allograft dysfunction versus six (10%) of 53 without allograft dysfunction progressed to moderate rejection on subsequent biopsy (chi 2 = 5.15, p = 0.02). Episodes with allograft dysfunction occurred earlier than those without dysfunction (15.4 +/- 2.8 weeks versus 34.4 +/- 5.5 weeks, p = 0.01) when baseline immunosuppression was higher.
  
  
  CONCLUSIONS
  Our findings indicate that 1) mild rejection is frequently associated with cardiac allograft dysfunction; 2) nine percent of mild rejection episodes may be accompanied by severe allograft dysfunction or arrhythmias, requiring aggressive treatment; 3) mild rejection associated with allograft dysfunction occurs earlier than that without allograft rejection; 4) untreated, mild rejection episodes with allograft dysfunction progress to moderate rejection more frequently than those without allograft dysfunction. These episodes require increased surveillance for progression.
authors.affiliation: Vanderbilt Transplant Center, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: T K
authors.initials: TK
authors.lastname: Yeoh
authors.forename: W H
authors.initials: WH
authors.lastname: Frist
authors.forename: T E
authors.initials: TE
authors.lastname: Eastburn
authors.forename: J
authors.initials: J
authors.lastname: Atkinson
mesh_terms: D001145:Arrhythmias, Cardiac / Q000209:etiology; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007022:Hypotension / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents