Download Atrial Arrhythmias After Lung Transplantation

Atrial Arrhythmias After Lung Transplantation
Epidemiology, Mechanisms at Electrophysiology Study, and Outcomes
Vincent Y. See, MD; Kurt C. Roberts-Thomson, MBBS, PhD; William G. Stevenson, MD;
Phillip C. Camp, MD; Bruce A. Koplan, MD
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
Background—Atrial arrhythmias (AAs) including atrial fibrillation (AF) and atrial tachycardia (AT) are often observed
after cardiothoracic surgery. Our aim was to evaluate the prevalence and mechanism of AAs after lung transplantation.
Methods and Results—All patients (n⫽127) after bilateral sequential lung transplantation followed at our institution over
20 years were included. All patients received postoperative rhythm monitoring and clinic visits with ECG at 1, 3, 6, and
12 months, or as needed. AAs occurred in 40 of 127 (31.5%) patients over 4.2⫾4.1 years. AA prevalence at
postoperation and 1, 3, 6, 12, and ⬎12 months was 24%, 11%, 3%, 2%, 4%, and 11%, respectively. Early AAs were
predominantly AF, whereas all AAs ⬎12 months were AT. Time to first AF versus AT was 11⫾9 versus 1485⫾2462
days (P⫽0.09). Male sex, age, and preoperative AA predicted any early (⬍3 months) AA but did not predict late AA.
Early AA did not predict late AT. In 4 patients with drug-resistant AT, electrophysiology studies found AT involving
the pulmonary vein/left atrium anastomoses in 3 patients, including donor-to-recipient conduction in 1, border zone
macroreentry in 2, and cavotricuspid isthmus dependent flutter in 1; all patients were successfully treated with ablation.
Conclusions—AAs after lung transplantation are common. Although AF is common early, AF is rare after healing of left
atrial incisions, which probably result in surgical pulmonary vein isolation with rare exception. This raises the question
of whether additional surgical or ablation lines at the time of lung transplantation would prevent late AA. (Circ
Arrhythmia Electrophysiol. 2009;2:504-510.)
Key Words: catheter ablation 䡲 tachyarrhythmia 䡲 transplant 䡲 lung 䡲 fibrillation
A
initiation and maintenance of AF has been demonstrated.8,9
Early attempts at surgical ablation used applications of
lines of conduction block. The majority of current catheter
ablation techniques used in the treatment of AF involve
electric isolation of the PV from the left atrium (LA), with
success rates between 60% to 85%.10 –13
The surgical technique of bilateral sequential lung transplantation (LT) involves 2 separate anastomoses of donor LA
tissue cuffs surrounding both the right superior and inferior
PVs and both the left superior and inferior PVs to the
posterior wall of the recipient LA at single venous cuffs
created at the right and left PV antra, as shown in Figure 1.14
This may electrically isolate the donor PV, but residual
recipient PV tissue may persist as part of the LA anastomosis.
This LA anastomosis also forms lines of conduction block
and slow conduction that may result in electroanatomic
substrate for reentry.
The aim of this analysis was to determine the prevalence, electrophysiological substrate and mechanisms, and
management outcomes of AA in patients undergoing
bilateral sequential LT. Findings and outcomes at electrophysiology study and catheter ablation of late post–lung
trial arrhythmia (AA) is a common postoperative complication after cardiac surgery and thoracic surgery, with
respective estimated incidences of 20% to 50% and 10% to
46%, depending on methods of definition and detection.1,2
After cardiac transplantation, atrial fibrillation (AF) or atrial
flutter (AFL) are frequent in the immediate postoperative
period and are associated with acute rejection or transplant
vasculopathy, but macroreentrant or focal atrial tachycardia
(AT) are observed later after cardiac transplantation.3 AT and
AFL observed after atrial surgery are often related to surgical
lines of conduction block and regions of slow conduction.3–5
AT in the recipient atria conducting to the donor atria has also
been described after cardiac transplantation.3–5 AFL and AT
have become less frequent as cardiac transplant techniques
have evolved from biatrial to bicaval anastomoses.6
Clinical Perspective on p 510
The mechanisms underlying AF and AT initiation and
maintenance are complex and probably involve electrophysiological abnormalities that may be aggravated by
inflammation early after surgery.1,7 Over the last decade,
the importance of the pulmonary veins (PV) in both the
Received March 24, 2009; accepted August 5, 2009.
From the Cardiac Arrhythmia Service, Cardiovascular Division, Department of Medicine (V.Y.S., K.C.R.-T., W.G.S., B.A.K.), and the Division of
Thoracic Surgery, Department of Surgery (P.C.C.), Brigham and Women’s Hospital, Boston, Mass.
Guest editor for this article was Michael E. Cain, MD.
Correspondence to Bruce A. Koplan, MD, Cardiac Arrhythmia Service, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St,
Boston, MA 02115. E-mail [email protected]
© 2009 American Heart Association, Inc.
Circ Arrhythmia Electrophysiol is available at http://circep.ahajournals.org
504
DOI: 10.1161/CIRCEP.109.867978
See et al
Atrial Arrhythmia Mechanisms After Lung Transplant
505
Atrial Tachyarrhythmias
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
AAs were defined as (1) AF, (2) organized AT, or (3) sinus
rhythm (SR), as described by the AHA/ACC/ESC Guidelines for
the Management of Patients with Atrial Fibrillation and Supraventricular Tachycardia and HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial
Fibrillation.15–17 AA were identified on any 12-lead surface ECG
of each patient’s medical record. If patient records reported AA
without 12-lead ECG documentation, medical records were reviewed for telemetry monitoring or ambulatory ECG monitoring
that documented AF or AT. All atrial arrhythmias documented
beyond the postoperative period required confirmation by 12-lead
ECG. AT was defined by organized P-wave activity separated by
an isoelectric baseline with fixed cycle length. All patients were
continuously monitored in the postoperative period. Routine
clinical follow-up and 12-lead ECGs were performed at 1, 3, 6, 9,
and 12 months and then annually. The postoperative time point
was determined by the date of discharge from the hospitalization
at time of transplantation. The differentiation between early and
late time points was at ⱕ3 months versus ⬎3 months. If a patient
reported arrhythmic symptoms, ambulatory ECG monitoring was
performed. The assessment of cardiac rhythm was evaluated
independently by 3 investigators.
Electrophysiology Study
Figure 1. A, Recipient right and left pneumonectomies are performed sequentially. B, The crura between the superior and inferior PVs of the respective right and left lungs are divided to create common recipient cuffs. C, The right and left donor PVs are
cross-clamped at the respective PV antra and resected as a left
atrial tissue cuff. D, The donor LA-PV cuff is anastomosed to the
common recipient right or left LA-PV cuff. This anastomosis may
isolate donor PV tissue, but residual recipient PV tissue may be
retained as part of the surgical anastomosis.
transplant arrhythmias refractory to medical therapy are
described.
Methods
Study Population
One hundred twenty-seven consecutive patients, who underwent
bilateral sequential LT between January 9, 1987, and April 10,
2008, and were followed at our institution were included in the
study. Three patients in the study underwent a second LT surgery
(1 at another institution). Of the 130 transplants, 117 patients
underwent transplantation at Brigham and Women’s Hospital.
Patients who had undergone en bloc or single lung transplants
were excluded. This study was conducted under a general patient
record review protocol approved by the Institutional Review
Board at Brigham and Women’s Hospital.
Surgical Anastomosis
Methods of transplantation were determined on the basis of
operative records. All LA-PV anastomoses were performed in a
similar manner (Figure 1). Donor right and left PVs were isolated
as 2 LA cuffs from the donor heart at the time of organ harvest.
The recipient PV antra were cross-clamped, and the PVs were
ligated at the time of pneumonectomy. Residual PV tissue was
trimmed, and the crus between the corresponding superior and
inferior (and middle if present) PVs of the right or left side was
divided to create single right and left recipient venous cuffs that
could accommodate the combined donor right or left LA-PV cuff.
All patients who underwent electrophysiology study (EPS) and
catheter ablation provided written informed consent. Patients
were studied under light intravenous conscious sedation with
midazolam and fentanyl. Catheters used included (1): 20-pole
catheter in the right atrium and coronary sinus (Ismus Catheter,
Biosense-Webster, Diamond Bar, Calif); (2) 20-pole Lasso catheter (Optima, St Jude Medical, St Paul, Minn); and (3) externally
irrigated 3.5-mm mapping and ablation catheter (Navistar–Thermocool, Biosense-Webster, Diamond Bar, Calif). Detailed 3D
electroanatomic mapping (CARTO, Biosense-Webster, Diamond
Bar, Calif) was performed in all patients. Entrainment and
activation mapping were performed to confirm the location of
macroreentrant circuits or focal AT.18,19 LA access was obtained
by transseptal puncture; all patients received systemic anticoagulation to maintain activated clotting time 300 to 350 seconds
after LA access.
Radiofrequency ablation was performed using power applications
of 30 to 40 W with a target temperature of ⬍50°C. Successful
ablation was defined as termination of the tachycardia by radiofrequency ablation and the noninducibility of any organized tachycardia
with atrial programmed extrastimuli and burst pacing with and
without isoproterenol.
Bipolar electrograms were filtered between 30 to 500 Hz, recorded, and stored digitally on a computerized system simultaneously
with 12-lead surface ECG (Prucka CardioLab EP Systems, GE
Healthcare, Piscataway, NJ).
Statistics
Data were analyzed using SAS software version 9.1 (Cary, NC).
Data are expressed as proportions or mean⫾SD. Differences in
baseline characteristics were compared using ␹2 tests for categorical variables and Student t tests for continuous variables.
Survival curves were derived by the Kaplan–Meier method and
compared using the log-rank test. All probability values were
2-tailed, and a value of P⬍0.05 was considered significant.
Predictors of atrial arrhythmias were identified and expressed as
hazard ratios with 95% confidence intervals. Univariate predictors of atrial arrhythmia were included in a final Cox multivariable proportional hazard model.
Results
The baseline characteristics of the study cohort at the time
of transplantation are displayed in Table 1. Over a 20-year
period, 127 post-transplant patients were followed for a
506
Circ Arrhythmia Electrophysiol
October 2009
Table 1. Baseline Characteristics at the Time of Lung
Transplantation
Table 2. Predictors of Atrial Arrhythmia After Lung
Transplantation
No. of patients
127
No. of transplants
130
Age at transplant, y
Sex, male
38.2⫾13.0
54.3
Etiology of lung disease, n (%)
Cystic fibrosis
82 (64.1)
Idiopathic pulmonary fibrosis
12 (9.4)
Chronic obstructive pulmonary disease*
11 (8.6)
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
Pulmonary hypertension, primary
6 (4.7)
Pulmonary hypertension, secondary
4 (3.1)
Eosinophilic granuloma
3 (2.3)
Bronchiectasis
2 (1.6)
Sarcoidosis
2 (1.6)
Allergic bronchopulmonary aspergillosis
2 (1.6)
Bronchiolitis obliterans
2 (1.6)
Histiocytosis X
1 (0.8)
Immobile cilia syndrome
Follow-up, y
1 (0.8)
4.2⫾4.1
History of AA, %
7.9
LA diameter, mm
34.4⫾7.9
Left ventricular ejection fraction, %
60.1⫾7.4
Left ventricular hypertrophy
12.6%
*Includes ␣1–anti-trypsin deficiency.
mean of 4.2⫾4.1 years per patient. The mean age at time
of LT was 38.2⫾13.0 years, and 54% of patients were
male. The most common indications for transplantation
were cystic fibrosis (64%), idiopathic pulmonary fibrosis
(9%), and chronic obstructive pulmonary disease (9%). A
history of atrial arrhythmia before undergoing LT was
present in 7.9% of patients. Mean left atrial diameter by
echocardiography was 34.4 mm, and the mean left ventricular ejection fraction was 60.1%.
Atrial Tachyarrhythmias
Data regarding AAs are displayed in Figure 2. The
incidence of total ATs was observed to have a bimodal
Characteristic
No
Arrhythmia
Age, y
36.3⫾13.0 42.3⫾12.0
AA
Hazard
Ratio
95% CI
P
Value
1.02
1.00 –1.04
0.04
Sex, % female
56.3
22.5
0.35
0.15–0.82
0.02
LA diameter, mm
34⫾7
36⫾10
0.99
0.95–1.03
NS
Left ventricular
ejection fraction, %
61⫾7
59⫾8
0.99
0.95–1.04
NS
Left ventricular
hypertrophy
9.1%
20.5%
1.7
0.75–3.80
NS
Preoperative AF
3.5%
17.5%
2.9
1.2–7.3
0.02
NS indicates not significant.
distribution. A total of 40 patients (31.5%) had spontaneous AAs. The prevalence was greatest in the immediate
postoperative period (n⫽30, 23.8%) before hospital discharge and in the first month after surgery (n⫽18, 13.8%).
Types of AA based on 12-lead ECG at time-specific points
are shown in Figure 2. The prevalence of all AAs at
postoperative, 1, 3, 6, 12, and ⬎12 months was 24%, 11%,
3%, 2%, 4%, and 11%, respectively. In the early postoperative period, AF was more common than AT (19.7%
versus 5.5%). All atrial arrhythmias at ⬎12 months were
atrial tachycardia (AF, n⫽0 versus AT, n⫽11/104; 11%);
interestingly, no AF occurred after 1 year.
Predictors of any AA at any time after LT are shown in Table
2. Significant predictors of arrhythmia in patients included age,
male sex, and a history of AA before surgery. None of these
factors predicted late arrhythmias (after 12 months) (Table 3).
Neither the presence of early AF or AT (ⱕ1 month), nor a
preoperative history of AA predicted late AA.
Management of AAs
Among all patients with AAs, various management strategies
were pursued at the discretion of the pulmonary transplant
physicians (Table 4). A rate-control strategy with AV nodal–
blocking agents was used in 19 patients (56%). Five patients
(15%) were treated with antiarrhythmic medical therapy. Five
patients (15%) underwent DC cardioversion. In 1 patient,
transesophageal echocardiography before planned cardioversion showed extensive right atrial thrombus associated with a
Table 3. Predictors of Late Atrial Arrhythmia (>12 Months)
After Lung Transplantation
Figure 2. Both AF (blue) and organized ATs (red) are most prevalent in the early postoperative period. The prevalence of both
arrhythmias declines by 3 months. After 3 months, no AF is
observed. In contrast, organized AT prevalence increases over
the 1st year. At 1 year, all observed AAs were organized AT.
Characteristic
No
Arrhythmia
Age, y
38.0⫾13.0 42.1⫾15.0
AA
Hazard
Ratio
95% CI
P
Value
1.05
0.98 –1.10
NS
Sex, % female
46.3
36.4
1.23
0.2–8.1
NS
LA diameter, mm
35⫾8
37⫾10
0.95
0.86–1.05
NS
Left ventricular
ejection fraction, %
61⫾7
58⫾9
0.91
0.82–1.04
NS
Left ventricular
hypertrophy
10.5%
36.4%
2.52
0.48–13.3
NS
Preoperative AF
AA ⱕ30 d
6.3%
9.1%
1.47
0.11–19.5
NS
22.1%
36.4%
3.63
0.56–23.5
NS
NS indicates not significant.
See et al
Atrial Arrhythmia Mechanisms After Lung Transplant
Table 4. Management of Atrial Arrhythmias After Lung
Transplantation
Table 5.
Study
Findings and Mechanisms at Electrophysiology
Management Strategy
Patient
Mechanism
Site of Isthmus or Focal Activation
507
No.
Patients With Arrhythmia, %
Radiofrequency ablation
4
12
1
Macroreentrant
Mitral isthmus: Left inferior PV–mitral isthmus
Operative management
1
3
2
Macroreentrant
LA roof: Between right/left superior PVs
Electrical cardioversion
5
15
3
Focal
PVs: Left (1st EPS)20; right (2nd EPS)
Anti-arrhythmic medication*
5
15
4
Macroreentrant
Cavotricuspid isthmus
19
56
Acute rate-control therapy
*Vaughn-Williams class IC or class III agents.
central venous catheter; operative thrombectomy was performed with restoration of SR at the time of weaning from
cardiopulmonary bypass. Four patients with drug-refractory
AAs were referred for EPS (Table 5).
Findings at EPS
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
Findings at EPS are described in Table 5 and Figure 3. Of
the 4 patients referred for EPS, 1 (patient 4) was found to
have typical AFL by ECG and confirmed to be cavotricuspid isthmus dependent at the time of EPS and ablation.
Two patients had macroreentrant AT due to reentry in the
regions of LA anastomoses as indicated by entrainment,
activation, and voltage mapping (Figure 3, A and B). One
of these patients (patient 1) was found to have a perimitral
tachycardia circuit bounded posteriorly by the left PV
anastomosis and anteriorly by the mitral annulus that
defined an isthmus where ablation terminated the
tachycardia (Figure 3A). Patient 2 had reentry between the
left and right PV anastomoses with an isthmus at the LA
roof, where ablation terminated the tachycardia (Figure
3B). Patient 3 had AT originating from the right donor PVs
with evidence of atrioatrial conduction based on the
presence of 2:1 conduction block (Figure 3C). Patient 3
has undergone 3 EPS/ablations; the 1st at a referring
institution. At the 2nd attempt (previously reported), 2:1
AT was mapped to the left PV anastomosis with successful
ablation.20 AT recurred 16 months later, and at repeat
study he was found to have a new AT originating from the
region of the right PV anastomosis (Figure 3C). No other
ATs were inducible after ablation, and bidirectional conduction block was still present between the donor left PV
cuff and the recipient atrium. All 4 patients have remained
in SR since ablation, with 3 of the 4 patients off of all
antiarrhythmic therapy; 1 patient remains on reduced-dose
antiarrhythmic therapy without evidence of recurrence.
Discussion
This is the first and largest analysis of the epidemiology,
electrophysiological mechanisms, and outcomes of AAs
after LT in the adult population. AAs are common in the
postoperative and early post-transplant period. However,
the predominance of AF during this time is similar to the
prevalence that has been reported after both cardiac and
thoracic surgery.1,2 After 3 months, AAs are infrequent
until 12 months, at which time some organized ATs begin
to emerge. Interestingly, after 1 year, no AF was seen over
an average of 4 years of follow-up after this extensive
atrial surgery. Inflammation has been associated with AF,
and a higher inflammatory state after surgery may explain
the higher incidence of AF early but not late in our
cohort.7,21
AF, AFL, and AT have been described after thoracic
surgery and after LT.2,20,22–25 Left AFL has also been
described after LT in the pediatric population and after
orthotopic heart transplantation.25,26 The donor PV–left
atrial cuff anastomosis with the recipient LA results in
putative lines of conduction block that serve as potential
substrate for macroreentrant tachyarrhythmia while possibly also compartmentalizing the LA to reduce the incidence of AF. LT could be viewed as the ultimate form of
antral isolation of the PVs, depending on the extent of
retained recipient PV tissue. This surgical anastomosis
effectively isolates the PVs of the donor but may only
partially isolate the recipient PVs from the recipient LA.
Consistent with this is our observation of macroreentry in
the LA along surgical anastomosis lines from LT surgery.
Using entrainment, activation, and voltage mapping, critical isthmuses in the tachycardia circuits were identified
with resultant successful radiofrequency ablation. There
was 1 patient in our study in whom conduction appeared to
occur across both anastomotic suture lines. This type of
conduction across anastomotic suture lines has previously
been reported in post– cardiac transplant patients.4,5 The
mechanism of conduction across anticipated surgical lines
of block is unclear, although human cardiac fibroblasts
have been demonstrated to have an ability to interact
electrically with cardiomyocytes through gap junctions.27
This study may provide some insights into the role of the
PVs in postoperative AF. The postoperative setting is
characterized by inflammation, hemodynamic stress, and
electrolyte imbalances creating a complex milieu in which
30% to 40% of patients have AF. After the landmark report
of Haissaguerre et al,8 it has become widely recognized
that the PVs are important in the initiation and maintenance of AF. The patients in this study underwent surgical
removal of the PVs at transplantation, although small
amounts of residual PV ostial tissue may remain. In the
long term, no patients had AF consistent with effective
isolation of the PVs. Despite the surgical isolation and/or
removal of most of the PV tissue, approximately 20% of
patients still had postoperative AF. It has been suggested
that mechanisms underlying postoperative AF are multifactorial and may include pericardial inflammation, neurohormonal imbalance, and interstitial and intravascular
pressure or fluid alterations with resultant changes in atrial
conduction and refractoriness. The similar prevalence of
postoperative AF in our population may suggest that
508
Circ Arrhythmia Electrophysiol
October 2009
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
Figure 3. Activation maps and entrainment of AT from patient 1 (A), patient 2 (B), and patient 3 (C) created at the time of EPS and
catheter ablation (Carto: Biosense-Webster). Sites of entrainment are marked by asterisks with associated intracardiac electrograms, postpacing intervals, and tachycardia cycle lengths. Ablation lesions are represented by dark red sites. Dark gray regions
represent unexcitable tissue/scar. Macroreentrant circuits are highlighted by white arrows. A, Patient 1 (LAO view): Earliest activation adjoining region of latest activation identified in the region of the mitral isthmus. B, Patient 2 (PA view): Earliest activation
meeting latest activation is depicted in the region between the right and left PVs at the LA roof. AT was terminated by radiofrequency ablation at these critical isthmuses in both patients. C, Patient 3 (right posterior oblique view): Earliest activation arising
from the region of the right PVs with concentric electric activation outward from this site (blue dot). The ablation catheter is within
the right inferior PV with 2:1 conduction block across the anastomotic suture line. Ablation at the represented sites terminated the
tachycardia. Abl indicates ablation catheter; LRA, lateral right atrium; SRA, septal right atrium; CSp, proximal coronary sinus;
CSd, distal coronary sinus; Stim, stimulation channel.
postoperative AF is less dependent on triggers originating
from the PVs than AF occurring in other contexts.
Although early AAs can be predicted with commonly
associated risk factors for AF, late organized ATs are not
easily predicted with commonly identified clinical characteristics. Our analysis demonstrates that these organized
AAs can be successfully managed with catheter ablation
when standard medical therapy has failed. This is an
important management consideration in this posttransplant population that requires intensive and intricate
regimens that may be further complicated by antiarrhythmic drug therapy. The relatively high incidence of late
organized AAs in this population raises the possibility of
evaluating whether different surgical strategies including
modifications of left atrial anastomoses or even prophylactic intraoperative radiofrequency or cryoablation might
reduce the occurrence of these arrhythmias. The answer to
this latter question remains unanswered.
Study Limitations
Despite this being the largest series of post-LT patients
analyzed for postoperative arrhythmia, this retrospective and
case-control– based evaluation limits our ability to directly
compare the efficacy of treatment strategies. As the definition
of atrial arrhythmia was defined by review of medical records
and required documentation by 12-lead ECG or telemetry
tracings, it is possible that the prevalence of arrhythmia may
have been underestimated.
These data support the feasibility of SR restoration using
a catheter ablation strategy that is determined by mechanisms at EPS. However, the limited number of patients
treated by catheter ablation raises interesting mechanistic
and therapeutic questions but do not yet allow for definitive recommendations regarding operative or ablation approaches at the time of or after LT. Larger populations
would enhance the statistical power of our analyses.
Continued future analyses of post-LT patients will allow
for better elucidation of the underlying pathophysiology
and substrate of left atrial macroreentrant tachycardias
beyond the 4 patients we have described.
Conclusion
Although AF is common in the early post-LT period,
organized ATs but not AF are observed in long-term
follow-up. Clinical factors including age and prior AA
predicted postoperative AF as reported after cardiac or
thoracic surgery. EPS has defined potential mechanisms of
late ATs. Three of 4 patients were found to have AT
originating from the LA, whereas 1 patient was found to
have typical cavotricuspid isthmus– dependent AFL.
Mechanisms of left atrial tachycardia included macroreentry involving lines of conduction block associated with
See et al
Atrial Arrhythmia Mechanisms After Lung Transplant
surgical anastomoses and focal tachycardia arising from
PV anastomoses. This study further demonstrates that
catheter ablation with both targeted ablation and modification of left atrial substrate is a potentially curative
strategy in this population. Although this population is a
relatively small and specific one, observations from our
data provide insights relating to spontaneous and postoperative AF, as well as, mechanisms of left AT after
effective isolation of the PVs.
Acknowledgments
We thank Steven Boukedes of the Brigham and Women’s Hospital
Lung Transplantation Program for his assistance with
this manuscript.
Sources of Funding
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
Dr See is the recipient of the Michel Mirowski Fellowship in Cardiac
Pacing and Electrophysiology from the Heart Rhythm Society
(2007–2008). Dr Roberts-Thomson is the recipient of a Postgraduate
Research Scholarship from the National Health and Medical Research Council of Australia (NHMRC grant ID 489417) and the
Astra-Zeneca Fellowship in Medical Research from the Royal
Australian College of Physicians.
Disclosures
None.
References
1. Echahidi N, Pibarot P, O’Hara G, Mathieu P. Mechanisms, prevention,
and treatment of atrial fibrillation after cardiac surgery. J Am Coll
Cardiol. 2008;51:793– 801.
2. Materazzo C, Piotti P, Mantovani C, Miceli R, Villani F. Atrial
fibrillation after non-cardiac surgery: P-wave characteristics and
Holter monitoring in risk assessment. Eur J Cardiothorac Surg. 2007;
31:812– 816.
3. Vaseghi M, Boyle NG, Kedia R, Patel JK, Cesario DA, Wiener I,
Kobashigawa JA, Shivkumar K. Supraventricular tachycardia after
orthotopic cardiac transplantation. J Am Coll Cardiol. 2008;51:
2241–2249.
4. Lefroy DC, Fang JC, Stevenson LW, Hartley LH, Friedman PL,
Stevenson WG. Recipient-to-donor atrioatrial conduction after orthotopic
heart transplantation: surface electrocardiographic features and estimated
prevalence. Am J Cardiol. 1998;82:444 – 450.
5. Saoudi N, Redonnet M, Anselme F, Poty H, Cribier A. Catheter ablation
of atrioatrial conduction as a cure for atrial arrhythmia after orthotopic
heart transplantation. J Am Coll Cardiol. 1998;32:1048 –1055.
6. Brandt M, Harringer W, Hirt SW, Walluscheck KP, Cremer J, Sievers
HH, Haverich A. Influence of bicaval anastomoses on late occurrence of
atrial arrhythmia after heart transplantation. Ann Thorac Surg. 1997;64:
70 –72.
7. Bruins P, te Velthuis H, Yazdanbakhsh AP, Jansen PG, van Hardevelt
FW, de Beaumont EM, Wildevuur CR, Eijsman L, Trouwborst A, Hack
CE. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein
and is associated with postoperative arrhythmia. Circulation. 1997;96:
3542–3548.
8. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G,
Garrigue S, Le Mouroux A, Le Metayer P, Clementy J. Spontaneous
initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339:659 – 666.
9. Chen SA, Hsieh MH, Tai CT, Tsai CF, Prakash VS, Yu WC, Hsu TL,
Ding YA, Chang MS. Initiation of atrial fibrillation by ectopic beats
originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation.
Circulation. 1999;100:1879 –1886.
10. Ouyang F, Bansch D, Ernst S, Schaumann A, Hachiya H, Chen M, Chun
J, Falk P, Khanedani A, Antz M, Kuck KH. Complete isolation of left
atrium surrounding the pulmonary veins: new insights from the
double-lasso technique in paroxysmal atrial fibrillation. Circulation.
2004;110:2090 –2096.
509
11. Jais P, Hocini M, Sanders P, Hsu LF, Takahashi Y, Rotter M, Rostock T,
Sacher F, Clementy J, Haissaguerre M. Long-term evaluation of atrial
fibrillation ablation guided by noninducibility. Heart Rhythm. 2006;3:
140 –145.
12. Pappone C, Augello G, Sala S, Gugliotta F, Vicedomini G, Gulletta S,
Paglino G, Mazzone P, Sora N, Greiss I, Santagostino A, LiVolsi L,
Pappone N, Radinovic A, Manguso F, Santinelli V. A randomized trial of
circumferential pulmonary vein ablation versus antiarrhythmic drug
therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll
Cardiol. 2006;48:2340 –2347.
13. Arentz T, von Rosenthal J, Blum T, Stockinger J, Burkle G, Weber R,
Jander N, Neumann FJ, Kalusche D. Feasibility and safety of pulmonary
vein isolation using a new mapping and navigation system in patients
with refractory atrial fibrillation. Circulation. 2003;108:2484 –2490.
14. Pasque MK, Cooper JD, Kaiser LR, Haydock DA, Triantafillou A,
Trulock EP. Improved technique for bilateral lung transplantation:
rationale and initial clinical experience. Ann Thorac Surg. 1990;49:
785–791.
15. Fuster V, Rydén LE, Cannorn DS, Crijns HJ, Curtis AB, Ellenbogen KA,
Halperin JL, Le Heuzey J-Y, Kay GN, Lowe JE, Olsson SB, Prystowsky
EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD,
Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL,
Riegel B, Priori SG, Blanc J-J, Budaj A, Camm AJ, Dean V, Deckers JW,
Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J,
Osterspey A, Zamorano JL. ACC/AHA/ESC 2006 guideline for the
management of patients with atrial fibrillation: a report of the American
College of Cardiology/American Heart Association Task Force on
Practice Guidelines and the European Society of Cardiology Committee
for Practice Guidelines (Writing Committee to Revise the 2001
Guidelines for the Management of Patients with Atrial Fibrillation).
Circulation. 2006;114:700 –752.
16. Blomström-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins
H, Camm AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller
DD, Shaeffer CW, Stevenson WG, Tomaselli GF. ACC/AHA/ESC
guidelines for the management of patients with supraventricular arrhythmias: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the European Society
of Cardiology Committee for Practice Guidelines (Writing Committee to
Develop Guidelines for the Management of Patients with Supraventricular Arrhythmias). J Am Coll Cardiol. 2003;42:1493–1531.
17. Calkins H, Brugada J, Packer DL, Cappato R, Chen S-A, Crijns HJG,
Damiano RJ Jr, Davies W, Haines DE, Haissaguerre M, Ieseka Y,
Jackman W, Jais P, Kottkamp H, Kuck KH, Lindsay BD, Marchlinski FE,
McCarthy PM, Mont JL, Morady F, Nademanee K, Natale A, Pappone C,
Prystowsky E, Raviele A, Ruskin JN, Shemin RJ. HRS/EHRA/ECAS
Expert Consensus Statement on Catheter and Surgical Ablation of Atrial
Fibrillation: Recommendations for Personnel, Policy, Procedures and
Follow-Up (A Report of the Heart Rhythm Society Task Force on
Catheter and Surgical Ablation of Atrial Fibrillation). Heart Rhythm.
2007;4:1– 46.
18. Miyazaki H, Stevenson WG, Stephenson K, Soejima K, Epstein LM.
Entrainment mapping for rapid distinction of left and right atrial
tachycardias. Heart Rhythm. 2006;3:516 –523.
19. Jais P, Matsuo S, Knecht S, Weerasooriya R, Hocini M, Sacher F, Wright
M, Nault I, Lellouche N, Klein G, Clementy J, Haissaguerre M. A
deductive mapping strategy for atrial tachycardia following atrial fibrillation ablation: importance of localized reentry. J Cardiovasc Electrophysiol. 2008;20:480 – 491.
20. Sacher F, Vest J, Raymond JM, Stevenson WG. Incessant donor-torecipient atrial tachycardia after bilateral lung transplantation. Heart
Rhythm. 2008;5:149 –151.
21. Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju
P, Kronmal RA, Tracy RP, Van Wagoner DR, Psaty BM, Lauer MS,
Chung MK. Inflammation as risk factor for atrial fibrillation. Circulation.
2003;108:3006 –3010.
22. Gandhi SK, Bromberg BI, Mallory GB, Huddleston CB. Atrial flutter: a
newly recognized complication of pediatric lung transplantation. J Thorac
Cardiovasc Surg. 1996;112:984 –991.
23. Hoffman TM, Rhodes LA, Wieand TS, Spray TL, Bridges ND.
Arrhythmias after pediatric lung transplantation. Pediatr Transplant.
2001;5:349 –352.
24. Nielsen TD, Bahnson T, Davis RD, Palmer SM. Atrial fibrillation after
pulmonary transplant. Chest. 2004;126:496 –500.
25. Ahmari SA, Bunch TJ, Chandra A, Chandra V, Ujino K, Daly RC,
Kushwaha SS, Edwards BS, Maalouf YF, Seward JB, McGregor CG,
510
Circ Arrhythmia Electrophysiol
October 2009
Chandrasekaran K. Prevalence, pathophysiology, and clinical significance of post-heart transplant atrial fibrillation and atrial flutter. J Heart
Lung Transplant. 2006;25:53– 60.
26. Gandhi SK, Bromberg BI, Schuessler RB, Boineau JP, Cox JL, Huddleston CB. Left-sided atrial flutter: characterization of a novel compli-
cation of pediatric lung transplantation in an acute canine model. J Thorac
Cardiovasc Surg. 1996;112:992–1001.
27. Wang Y-J, Sung RJ, Lin M-W, Wu S-N. Contribution of BKCa-channel
activity in human cardiac fibroblasts to electrical coupling of cardiomyocytes-fibroblasts. J Membrane Biol. 2006;213:175–185.
CLINICAL PERSPECTIVE
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
Atrial arrhythmias after cardiothoracic surgery occur frequently, at rates of ⬇20% to 50%. Multiple studies have
demonstrated the significance of the pulmonary veins in the pathogenesis of atrial fibrillation. Bilateral lung transplantation
requires left atrial incisions that may represent the ultimate form of antral pulmonary vein isolation, depending on the extent
of retained recipient pulmonary vein tissue. In a single-center cohort of bilateral lung transplant patients, atrial arrhythmias
occurred in 31.5% of patients over 4 years. Atrial fibrillation dominated early arrhythmia prevalence (24%). All
arrhythmias past 1 year were organized atrial tachycardias (11%). Recipient age, male sex, and preoperative arrhythmia
history predicted early but not late atrial arrhythmia. Various therapies, including catheter ablation for drug-refractory
arrhythmia, were used. Electrophysiology study defined potential mechanisms including (1) macroreentry involving lines
of conduction block at surgical anastomoses and (2) focal atrial tachycardia with recovered pulmonary vein–left atrial
conduction. Catheter ablation restored sinus rhythm in all who underwent electrophysiology study. Similar rates of
postoperative fibrillation but absence of late atrial fibrillation suggest that atrial fibrillation after cardiothoracic surgery
probably has multifactorial mechanisms less dependent on pulmonary vein activity. Successful ablation of macroreentrant
circuits defined by transplant anastomoses raises the possibility that substrate modification at transplantation may modify
atrial tachycardia occurrence. Recovered pulmonary vein–left atrial conduction across suture lines raises questions
regarding mechanisms of electric “reconnection” described after cardiac transplantation and pulmonary vein isolation.
Although conclusions are limited by this small, retrospective study, these data provide mechanistic and therapeutic insights
relating to atrial fibrillation and atrial tachycardia.
Atrial Arrhythmias After Lung Transplantation: Epidemiology, Mechanisms at
Electrophysiology Study, and Outcomes
Vincent Y. See, Kurt C. Roberts-Thomson, William G. Stevenson, Phillip C. Camp and Bruce
A. Koplan
Downloaded from http://circep.ahajournals.org/ by guest on May 11, 2017
Circ Arrhythm Electrophysiol. 2009;2:504-510; originally published online August 25, 2009;
doi: 10.1161/CIRCEP.109.867978
Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville
Avenue, Dallas, TX 75231
Copyright © 2009 American Heart Association, Inc. All rights reserved.
Print ISSN: 1941-3149. Online ISSN: 1941-3084
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circep.ahajournals.org/content/2/5/504
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Circulation: Arrhythmia and Electrophysiology can be obtained via RightsLink, a service of the Copyright
Clearance Center, not the Editorial Office. Once the online version of the published article for which
permission is being requested is located, click Request Permissions in the middle column of the Web page
under Services. Further information about this process is available in the Permissions and Rights Question and
Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation: Arrhythmia and Electrophysiology is online at:
http://circep.ahajournals.org//subscriptions/