title: Prevalence, pathophysiology, and clinical significance of post-heart transplant atrial fibrillation and atrial flutter.
abstract: BACKGROUND
  Atrial rhythm disturbances, in particular atrial fibrillation (AF) and flutter (AFL), are common in the denervated transplanted heart. However, there is a relative paucity of data in the prevalence, mechanism of arrhythmia, and long-term significance.
  
  
  OBJECTIVE
  (1) Determine the prevalence of AF and AFL in heart transplant patients, (2) define the echo/Doppler features associated with arrhythmia, and (3) evaluate the impact of arrhythmia on long-term survival.
  
  
  METHODS
  All patients who received an orthotopic heart transplant at the Mayo Clinic, Rochester, Minnesota, between 1988 and 2000 were included. Analysis of serial electrocardiograms and Holter monitor records provided evidence of AF or AFL development. Variables including general patient demographics, histology-proven rejection numbers and grades, results of serial coronary angiography, endomyocardial biopsy specimens, and echocardiographic studies performed at 6 weeks and 3 years after transplant were obtained to determine variables predictive of arrhythmia development.
  
  
  RESULTS
  There were 167 heart transplant recipients, of which 16 (9.5%) developed AF and another 25 (15.0%) developed AFL over 6.5 +/- 3.4 years. Patients who developed AF or AFL had lower left ventricular (LV) ejection fractions (56.6% +/- 1.6% vs 62.5% +/- 1.5%, p < 0.05), higher LV end-systolic dimensions (LVESD) (33.6 +/- 1.12 mm vs 29.7 +/- 0.97 mm, p < 0.01), higher right atrial volume indexes (43.2 +/- 12.3 ml vs 35 +/- 5.3 ml, p < 0.03), lower mitral deceleration time (145 +/- 8 msec vs 160 +/- 12 msec, p < 0.05), and lower late mitral annulus tissue a' velocities (0.06 +/- 0.005 cm/sec vs 0.08 +/- 0.01 cm/sec, p < 0.02) compared with an age- and gender-matched Sinus Rhythm Group. Grade 3 rejection was a time-dependent covariate predictor of AFL risk (hazard ratio [HR], 2.95; 95% confidence interval [CI], 1.3-6.6, p < 0.008) but not AF (HR, 2.264; 95% CI, 0.72-7.1; p = 0.10). Thirty-nine of 167 patients died: 13 in the arrhythmia group and 26 in the normal sinus rhythm group. Development of atrial dysrhythmia adversely affected the outcome in the first 5 years (p < 0.001) compared with normal sinus rhythm. Predictors of long-term mortality included AF/AFL (HR, 2.88; 95% CI, 1.38-5.96; p < 0.004), age at transplant (HR, 1.04; 95% CI, 1.00-1.07, p < 0.03), coronary artery disease (HR, 2.655; 95% CI, 1.25-5.64; p = 0.01), pre-transplant cardiac amyloidosis (HR, 5.02; 95% CI 2.37-10.62; p < 0.001), right atrial volume index (HR, 1.03; 95% CI, 1.00-10.7; p = 0.03), mitral deceleration time <160 msec (p < 0.01), and LVESD >30 mm (p < 0.04).
  
  
  CONCLUSIONS
  Development of AF/AFL post-heart transplantation is not uncommon and is associated with decreased long-term survival. Cumulative effects of repeated moderate-to-severe (grade 3 or more) rejections that result in increased cardiac fibrosis are associated with the development of AFL, but not AF. Similarly advanced restrictive diastolic dysfunction caused by fibrosis from repeated moderate-to-severe (grade 3 or more) rejections was predominant in the patients with arrhythmia and was a marker of poor long-term outcome.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Saeed A L
authors.initials: SA
authors.lastname: Ahmari
authors.forename: T Jared
authors.initials: TJ
authors.lastname: Bunch
authors.forename: Anupam
authors.initials: A
authors.lastname: Chandra
authors.forename: Vidhan
authors.initials: V
authors.lastname: Chandra
authors.forename: Keiji
authors.initials: K
authors.lastname: Ujino
authors.forename: Richard C
authors.initials: RC
authors.lastname: Daly
authors.forename: Sudhir S
authors.initials: SS
authors.lastname: Kushwaha
authors.forename: Brook S
authors.initials: BS
authors.lastname: Edwards
authors.forename: Youssef F
authors.initials: YF
authors.lastname: Maalouf
authors.forename: James B
authors.initials: JB
authors.lastname: Seward
authors.forename: Christopher G
authors.initials: CG
authors.lastname: McGregor
authors.forename: Krishnaswamy
authors.initials: K
authors.lastname: Chandrasekaran
mesh_terms: D000328:Adult; D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000503:physiopathology*; D001282:Atrial Flutter / Q000453:epidemiology* / Q000503:physiopathology*; D001706:Biopsy; D017023:Coronary Angiography; D003971:Diastole; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011183:Postoperative Complications; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000209:etiology