Atrial fibrillation (AF) and atrial flutter (AFL) after heart transplantation (HT) has been associated with increased mortality. Diverse incidence rates have been reported to date, with no clear classification according to the time of onset of such arrhythmias. We determined the incidence of AF/AFL using the time of onset after HT and analyzed the associated risk factors and outcomes. We performed a retrospective study of 228 HT recipients (March 1996 to July 2007), including donor and recipient demographics, gender mismatch, ischemia time, surgical anastomosis, time of onset of AF/AFL, acute cellular rejection, left ventricular systolic function, and all-cause mortality. The mean age of the donors (81% men) was 30 ± 12 years and of the recipients (78% men) was 53 ± 11 years. AF/AFL occurred in 45 patients (20%): 24 (11%) in the first 30 days, 10 (4%) within the 31 days to 1 year, and 11 (5%) after 1 year. When the patients with AF/AFL were compared to those with sinus rhythm, the significant difference was the older mean age of the donors (p = 0.001) and the recipients (p = 0.02). The all-cause mortality rate was 43% for those with AF/AFL compared to 23% for those with sinus rhythm (hazard ratio 2.45; 95% confidence interval 1.2 to 4.8), mostly driven by the greater mortality in the later-onset AF/AFL group (>30 days after HT). In conclusion, AF and AFL have an incidence of 20% after HT and are associated with increased overall mortality compared to that in patients in sinus rhythm. AF/AFL is more common within the first 30 days of HT, with an overall incidence of 20%. Older donor and recipient age is a risk factor associated with AF/AFL.
A wide incidence range of atrial arrhythmias has been reported after heart transplantation (HT), but seldom have they been classified according to the period of onset. The incidence of atrial fibrillation (AF) and atrial flutter (AFL) after HT has decreased, over time, from 70% in 1973 to <20% in 2006. In the HT population, AF and AFL have been associated with worse outcomes. The purpose of the present single-center study was to determine the overall incidence of AF and AFL after HT; to categorize them according to onset from HT; to determine the risk factors associated with the occurrence of these arrhythmias by analyzing the characteristics of the donors and recipients, ischemia time, surgical anastomosis type, acute cellular rejection, and left ventricular systolic function; and to compare the mortality of HT recipients who developed AF and AFL with those who remained in sinus rhythm after HT.
Methods
This was a retrospective study of the incidence of AF and AFL in HT recipients with ≤11 years of follow-up. The study was conducted after approval from the institutional review board. Patients who had undergone HT from March 1996 through July 2007 were included. Of the 252 consecutive HT patients, 228 who had electrocardiograms (ECGs) available for review were selected for the present study. The baseline demographic and clinical data were retrospectively extracted from the HT database. The demographic data of the recipients and donors (i.e., age, gender, and race), donor-recipient gender mismatch, ischemia time, surgical anastomosis type (biatrial vs bicaval), interval to onset of AF and AFL from HT (in days), endomyocardial biopsy grade of acute cellular rejection, left ventricular ejection fraction, vital status, and interval to death (in days) were collected. According to our clinical protocol, all hospitalized HT recipients were monitored by continuous telemetry during the entire hospitalization. This included the period immediately after HT until discharge and all the subsequent hospitalizations. Typically, 12-lead electrocardiography was performed to evaluate any abnormal rhythms noted on telemetry or for an appropriate clinical indication. The heart rhythm (AF, AFL, or sinus rhythm) was confirmed by serial 12-lead electrocardiography. All ECGs from the date of HT to the end of the follow-up (range 2 days to 12.5 years) were collected and analyzed. Abnormal findings on an ECG were used to classify the patients into 2 categories: AF and AFL. The interval to the onset of AF or AFL was divided into 3 groups: early (<30 days after HT), intermediate (31 days to ≤1 year after HT), and late (>1 year after HT). The left ventricular ejection fraction was determined using 2-dimensional echocardiography performed during the hospitalization for AF or AFL. Surveillance endomyocardial biopsies were done according to the institutional protocol and were graded using the International Society for Heart and Lung Transplantation classification from 1990. Acute cellular rejection was defined as International Society for Heart and Lung Transplantation grade 2 or greater. A rejection episode was defined as a 28-day period starting 14 days before and ending 14 days after biopsy-proven acute cellular rejection.
Numerical values are expressed as the mean ± SD. The data had a nonparametric distribution. Differences in categorical variables were tested using Pearson’s chi-square and Fisher’s exact probability tests. Differences in the mean values were tested using Student’s t test for independent samples. Hazard ratios (from the log-rank test), with the 95% confidence intervals, were used for the mortality analysis. Kaplan-Meier survival analysis, using the log-rank test (Mantel-Cox test) was used to model the interval to an event. A significance level of p <0.05 was set for the present study.
Results
A total of 228 patients who had undergone HT from March 1996 to July 2007 were included in the present study. The mean age of the donors was 30 ± 12 years and that of the recipients was 52 ± 11 years. The demographic characteristics of the HT recipients and donors are listed in Table 1 . Most of the recipients (74%) were matched by gender to their respective donor. The mean ischemia time was 186 minutes in the sinus rhythm group and 190 minutes in the AF/AFL group (p = 0.6). Bicaval anastomosis was performed in 165 patients (72%) and biatrial anastomosis in 55 patients (24%); for 8 patients (4%), the operative report was not available. Of the 228 patients, 122 (54%) had ischemic cardiomyopathy and 106 (46%) had nonischemic cardiomyopathy.
| Characteristic | n (%) |
|---|---|
| Recipient gender | |
| Male | 179 (78%) |
| Female | 49 (22%) |
| Donor gender | |
| Male | 184 (81%) |
| Female | 44 (19%) |
| Donor race | |
| White | 143 (63%) |
| African American | 60 (26%) |
| Hispanic | 24 (10%) |
| Other, not specified | 1 (1%) |
| Gender mismatch | |
| None | 169 (74%) |
| Male donor to female recipient | 32 (14%) |
| Female donor to male recipient | 27 (12%) |
| Time of onset of atrial fibrillation and atrial flutter combined | |
| Early (0–30 days) | 24 (11%) |
| Intermediate (31 days to 1 year) | 10 (4%) |
| Late (>1 year) | 11 (5%) |
| Total | 45 (20%) |
| Time of onset of each arrhythmia | |
| Early (0–30 days) | |
| Atrial fibrillation | 18 (8%) |
| Atrial flutter | 6 (3%) |
| Intermediate (31 days to 1 year) | |
| Atrial fibrillation | 5 (2%) |
| Atrial flutter | 5 (2%) |
| Late (>1 year) | |
| Atrial fibrillation | 6 (3%) |
| Atrial flutter | 5 (2%) |
| Total | |
| Atrial fibrillation | 29 (13%) |
| Atrial flutter | 16 (7%) |
Most HT recipients (80%) were in sinus rhythm during the follow-up period. The overall incidence of AF and AFL was 20% (45 patients). Of the 45 patients who developed AF/AFL, 29 had AF and 16 AFL. More than ½ of the occurrence of AF/AFL developed in the early post-transplant period (<30 days after HT; Table 1 ). When AF and AFL were analyzed separately, AF was the predominant atrial arrhythmia, accounting for >50% of all occurrence of AF and AFL. AF was also the most common atrial arrhythmia observed in the early post-transplant period (≤30 days after HT). AFL had a similar distribution among the early, intermediate, and late periods ( Table 1 ).
The comparison of the demographic and clinical variables between the sinus rhythm and AF/AFL groups of HT recipients and their respective donors showed that they differed only by the recipient and donor age (p = 0.02 and p = 0.001, respectively; Table 2 ). An older recipient and donor age was associated with the development of AF/AFL. Endomyocardial biopsy data were available for 34 of the 45 patients who developed AF/AFL. Only 1 patient had a grade 2 or greater acute cellular rejection (International Society for Heart and Lung Transplantation 1990 grading system ). Two-dimensional echocardiography of 8 of the 11 patients who did not undergo endomyocardial biopsy showed normal left ventricular systolic function (>50%). Of the 45 patients with AF/AFL, 44 had an ejection fraction >50%, and 1 had an ejection fraction of 45%. No statistically significant association was found between the surgical anastomosis type (bicaval vs biatrial) and AF/AFL.
| Characteristic | Sinus Rhythm Group (n = 183) | AF/AFL Group (n = 45) | p Value |
|---|---|---|---|
| Recipient age (years) | 52 | 56 | 0.02 |
| Recipient gender | 0.85 | ||
| Male | 144 (78%) | 35 (80%) | |
| Female | 40 (22%) | 9 (20%) | |
| Donor age (years) | 28 | 36 | 0.0001 |
| Donor gender | 0.5 | ||
| Male | 150 (81%) | 34 (77%) | |
| Female | 34 (19%) | 10 (23%) | |
| Donor race | 0.25 | ||
| White | 110 (60%) | 33 (75%) | |
| African American | 51 (28%) | 9 (20%) | |
| Hispanic | 22 (12%) | 2 (5%) | |
| Other, not specified | 1 (1%) | ||
| Gender mismatch | 0.64 | ||
| None | 138 (75%) | 31 (70%) | |
| Male donor to female recipient | 20 (11%) | 7 (16%) | |
| Female donor to male recipient | 26 (14%) | 6 (14%) | |
| Ischemia time (min) | 186 | 190 | 0.6 |
| Anastomosis type ⁎ | 0.3 | ||
| Biatrial | 42 (24%) | 13 (31%) | |
| Bicaval | 136 (76%) | 29 (69%) |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
