Prevalence, Pathophysiology, and Clinical Significance of Post-heart Transplant Atrial Fibrillation and Atrial Flutter Saeed A. L. Ahmari, MD, a T. Jared Bunch, MD, a Anupam Chandra, MD, a Vidhan Chandra, MD, a Keiji Ujino, MD, a Richard C. Daly, MD, b Sudhir S. Kushwaha, MD, a Brook S. Edwards, MD, a Youssef F. Maalouf, MD, a James B. Seward, MD, a Christopher G. McGregor, MD, b and Krishnaswamy Chandrasekaran, MD a 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. Objectives: (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 demo- graphics, 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). Conclusion: 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. J Heart Lung Transplant 2006;25:53– 60. Copyright © 2006 by the International Society for Heart and Lung Transplantation. The prevalence of cardiac arrhythmias in the trans- planted heart has been reported to be between 23% and 79%. 1–4 Atrial arrhythmias are the most common, oc- curring in 18% to 65% of heart transplant recipients. 1,4,5 Despite the relatively high prevalence of atrial ar- rhythmias, the mechanisms of atrial fibrillation (AF) and atrial flutter (AFL) after cardiac transplantation have not been well elucidated in the literature. Previous reports that suggest an association with acute rejection have From the a Department of Internal Medicine, Division of Cardiology, and b Department of Surgery, Division of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota. Submitted May 12, 2005; revised May 16, 2005; accepted July 25, 2005. Reprint requests: K. Chandrasekaran, MD, Division of Cardiovas- cular Diseases, Gonda 6S, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: kchandra@mayo.edu Copyright © 2006 by the International Society for Heart and Lung Transplantation. 1053-2498/06/$–see front matter. doi:10.1016/ j.healun.2005.07.017 53