- Email: [email protected]
Safety and outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease: A multicenter registry study
Safety and outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease: A multicenter registry study Jackson J. Liang, DO,* David S. Frankel, MD, FHRS,* Valay Parikh, MD,† Dhanujaya Lakkireddy, MD, FHRS,† Sanghamitra Mohanty, MD, MS, FHRS,‡ J. David Burkhardt, MD, FHRS,‡ Andrea Natale, MD, FHRS,‡ Judit Szilagyi, MD,x Edward P. Gerstenfeld, MD, FHRS,x Jeremy P. Moore, MD, MS, FHRS,{ Kathryn K. Collins, MD, FHRS,k Joseph D. Kay, MD,** Pasquale Santangeli, MD, PhD,* Francis E. Marchlinski, MD, FHRS,* William H. Sauer, MD, FHRS,** Duy T. Nguyen, MD, FHRS** From the *Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, †Kansas University Medical Center, Kansas City, Kansas, ‡Texas Cardiac Arrhythmia Institute, Austin, Texas, xUCSF, San Francisco, California, {UCLA, Los Angeles, California, kChildren’s Hospital Colorado, University of Colorado, Aurora, Colorado, and **University of Colorado, Aurora, Colorado. BACKGROUND An increasing number of adults with congenital heart disease (CHD) are undergoing catheter ablation for atrial fibrillation (AF). Data on ablation strategy and outcomes in CHD are limited. Rhythm control is often believed to be of greater importance among patients with complex CHD. OBJECTIVE The purpose of this study was to examine the safety and efficacy of AF ablation in adult patients with CHD. METHODS A multicenter retrospective analysis was performed of CHD patients undergoing AF ablation. Clinical data were collected, including AF and CHD type, procedural data, and outcomes. Patients were divided into 3 groups (simple, moderate, and severe) based on CHD complexity, as defined by the 2014 PACES/HRS (Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society) consensus statement. One-year procedural success was defined as freedom from recurrent AF, off antiarrhythmic drugs (complete) or off/on previously failed antiarrhythmic drugs (partial).
Introduction With advances in medical, interventional, and surgical therapies, more patients with congenital heart disease (CHD) are surviving to adulthood. Patients with CHD are frequently hospitalized for cardiac issues, and 80% of deaths in these patients are related to heart failure (HF), sudden death, arrhythmias, and vascular complications.1–3
RESULTS Overall, 84 CHD patients (mean age 51.5 6 12.1 years; 65.5% male; 45.2% with paroxysmal AF) undergoing AF ablation (51 simple, 22 moderate, 11 severe complexity) were included. Pulmonary vein isolation was performed in 80 (95.2%), of whom 30 (35.7%) underwent pulmonary vein isolation alone. Overall, complete and complete/partial freedom was achieved at 1 year in 53.1% and 71.6%, respectively, with no significant differences between those with simple, moderate, or severe complexity. There were no major complications and 7 minor complications, and 2 patients died during follow-up. CONCLUSION There are dramatic differences in the degree of CHD complexity among patients referred for AF ablation. When performed at experienced centers, AF ablation is safe and effective even among patients with the most complex forms of CHD. KEYWORDS Atrial fibrillation; Catheter ablation; Complexity; Congenital heart disease (Heart Rhythm 2019;16:846–852) All rights reserved.
© 2018 Heart Rhythm Society.
The prevalence of atrial arrhythmias, such as atrial fibrillation (AF), is higher among CHD patients compared to the general population. The incidence of AF increases with age and is associated with significantly increased risk of adverse events.4 There is a significant amount of heterogeneity in the structural heart disease (SHD) complexity in CHD patients, which may predispose them to develop AF. AF may also
Drs Sauer and Nguyen receive significant research grants from Biosense Webster and CardioNXT; and educational grants from St Jude Medical, Boston Scientific, and Medtronic. Drs Sauer and Nguyen have a provisional patent on partially insulated focused catheter ablation. Drs Nguyen and Sauer have non-public equity interests/stock options in CardioNXT. All other authors have reported that they have no conflicts relevant to the contents of this paper to disclose. Address reprint requests and correspondence: Dr Duy T. Nguyen, Section of Cardiac Electrophysiology, Division of Cardiology, University of Colorado, UB-132, Leprino Bldg, 12401 E. 17th Ave, Aurora, CO 80045. E-mail address: [email protected].
1547-5271/$-see front matter © 2018 Heart Rhythm Society. All rights reserved.
https://doi.org/10.1016/j.hrthm.2018.12.024
Liang et al
AF Ablation in Patients With Adult CHD
have a hemodynamically significant detrimental effect in patients with more complex CHD vs the general population. Although antiarrhythmic drugs (AADs) usually are attempted as first-line therapy in this complex population, they are frequently poorly tolerated or ineffective.5 As such, AF ablation has been increasingly used as a treatment strategy. Data examining optimal AF ablation strategies in CHD patients remain limited. Furthermore, although rhythm control is often believed to be of greater importance among more complex CHD patients, the safety and efficacy of AF ablation remain unknown. We aimed to examine the safety and efficacy of AF ablation in patients with different degrees of CHD complexity.
Methods We retrospectively identified consecutive adult patients with CHD who were treated with catheter ablation for symptomatic AF at 6 study centers (Hospital of the University of Pennsylvania, Philadelphia, PA; University of Colorado, Aurora, CO; Texas Cardiac Arrhythmia Institute, Austin, TX; University of Kansas Medical Center, Kansas City, KA; University of California San Francisco, San Francisco, CA; University of California Los Angeles, Los Angeles, CA) between 2008 and 2016. Etiologies of CHD among study patients are shown in Figure 1. All participants provided written informed consent for the ablation procedure as well as inclusion in medical research at the time of the procedure. Collection of data was approved by the institutional review boards of each of the respective participating centers. Ablations were performed per the operator’s discretion at each study center. Details of the AF ablation procedure and follow-up are described in the Supplementary Methods. Patients were followed-up in the outpatient setting per each institution’s routine postablation protocol. The dates of AF recurrence (after 3-month postablation blanking period) and death as well as continued use of AADs after ablation were identified from review of the medical records. Recurrent atrial arrhythmias during follow-up were managed by the treating electrophysiologist. Typically, treatment of AF recurrence consisted of anticoagulation, cardioversion, adjustment or initiation of AAD, and/or repeat AF ablation.
AF complexity For the purposes of analysis, patients were divided into 3 groups based on CHD complexity (simple, moderate, or severe) as defined by the 2014 PACES/HRS (Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society) expert consensus statement (Figure 1).6 Patients with multiple CHD abnormalities were classified based on the most severe abnormality.
Statistical analysis Baseline demographics, medications, comorbidities, clinical details regarding CHD type, imaging study findings, details from the ablation procedure including ablation strategies and complications, and outcomes after ablation were abstracted
847 from the medical records for each patient and summarized using percentages and means. Demographic and clinical measures were compared based on CHD complexity at enrollment using t tests, c2 tests, or Fisher tests, as appropriate. Proportional hazards models were used to evaluate clinical and demographic predictors of AF recurrence during follow-up. The proportional hazards assumption was examined for all variables before model inclusion. All analyses were performed using SPSS Statistics (IBM, Armonk, NY) and Microsoft Excel (Microsoft, Seattle, WA). P ,.05 was considered significant.
Results Patient population Between January 2008 and October 2016, a total of 84 adult CHD patients treated with AF ablation were included. Table 1 lists the baseline clinical characteristics of the patients. Mean age at time of ablation was 51.5 6 12.1 years, 65% were male, and 38 (45.2%) had paroxysmal AF. Nineteen patients (22.6%) had undergone at least 1 previous ablation at another institution for AF, and 21 (25.0%) had undergone previous ablation for intra-atrial reentrant tachycardia (IART). Mean CHADS2 score was 1.25 6 1.07, and mean CHA2DS2VASc score was 1.80 6 1.50. The majority of patients (77.4%) had failed or were intolerant of at least 1 AAD before ablation, and 55 (65.5%) were taking an AAD at the time of ablation. Of 84 patients, the degree of complexity of CHD was considered to be simple in 51 (60.7%), moderate in 22 (26.2%), and severe in 11 (13.1%) (Figure 1). Other than a higher likelihood of clinical HF in the severe complexity group (P 5 .001), there were no significant differences in baseline characteristics between the simple, moderate, and severe complexity groups (Table 1).
AF ablation procedural information Overall mean procedure time was 299.1 6 111.5 minutes, and there was a trend toward longer procedure times in patients with increasing CHD complexity (simple: 275.9 6 99.2 minutes; intermediate: 328.0 6 122.8 minutes; severe: 342.8 6 125.3 minutes; P 5 .07). Total mean fluoroscopy time was 51.3 6 28.5 minutes (simple: 48.7 6 27.1 minutes; intermediate: 49.6 6 33.4 minutes; severe: 63.9 6 23.5 minutes; P 5 .27). Ablation strategies performed during AF ablation are listed in Table 2. Left atrial (LA) ablation was performed in 82 patients (97.6%), and 2 patients (2.4%) underwent ablation of triggers and complex fractionated atrial electrogram ablation in the right atrium (RA) alone. Overall, ablation within the RA was performed in 40 patients (47.6%) . Pulmonary vein isolation (PVI) was performed in 80 patients (95.2%). Thirty patients underwent PVI alone, and the remaining 50 patients underwent ablation lesions in addition to PVI. The most frequent additional ablation lesion sets included targeting of non-PV triggers in 38 (45.2%), cavotricuspid isthmus ablation in 31 (36.9%), creation of a roof line in 20 (23.8%), mitral annular linear ablation in 17 (20.3%), and complex fractionated atrial electrogram ablation in 16
848
Heart Rhythm, Vol 16, No 6, June 2019
Figure 1 Classification of the complexity of congenital heart disease (CHD) of patients undergoing atrial fibrillation ablation. ASD 5 atrial septal defect; IVC 5 inferior vena cava; PV 5 pulmonary vein; SVC 5 superior vena cava; TGA 5 transposition of the great arteries; VSD 5 ventricular septal defect.
(19.1%). Focal impulse or rotor ablation was performed in 3 patients (3.6%). Aside from an increased prevalence of RA atriotomy ablation in the severe group (P 5 .02), there was no statistically significant difference in ablation strategies between groups with different CHD complexity (Table 2).
Non-PV triggers A total of 65 distinct non-PV triggers were identified among the 38 patients with at least 1 non-PV trigger targeted (Table 2). The most common sites of non-PV triggers were superior vena cava (SVC; including persistent left SVC) in 14 (16.7%), anterior LA in 10 (11.9%), crista terminalis or eustachian ridge in 8 (9.5%), LA roof in 8 (9.5%), coronary sinus in 7 (8.3%), LA septum in 7 (9.3%), and LA appendage in 3 (3.6%).
54.0% (70.0%) for simple, 57.1% (81.0%) for moderate, and 40.0% (60.0%) for severe CHD complexity (P 5 .66 for complete and P 5 .44 for complete/partial freedom between groups).
Improvement in left ventricular ejection fraction Baseline mean left ventricular ejection fraction (LVEF) of the 72 patients with available echocardiograms for LVEF quantification was 53.0% 6 11.8% at the time of ablation (no difference between groups). A total of 21 patients (29.1%) had reduced LVEF (,50%) before ablation. Of these 21 patients with reduced baseline LVEF, the last available follow-up echocardiogram revealed any degree of LVEF improvement in 19 (90.5%), whereas 16 (76.2%) had normalization of LV function (LVEF 50%).
Efficacy: Ablation success and AF recurrence AF ablation was considered acutely successful in all patients, and successful isolation of PVs was achieved in all 80 patients in whom PVI was attempted. Mean follow-up for 81 patients with available follow-up data was 708.6 6 807.7 days (3 patients lost to follow-up after ablation were excluded from outcome analysis). Early AF recurrence within the 3-month postablation blanking period occurred in 21 of the 73 patients (28.8%) with available data. Outcomes were defined with regard to the index ablation performed at the 6 participating centers. Complete freedom (off AADs) from recurrent AF out to 1 year after ablation (excluding the 3-month blanking period) was achieved in 43 of 81 patients (53.1%), and partial freedom (on previously ineffective AADs) was achieved in an additional 15 patients (overall partial or complete freedom achieved in 58/81 patients [71.6%]). One-year complete (and including partial) success rates were
Safety: Complications and long-term mortality No major complications occurred. Supplemental Table 1 lists the 7 procedure-related minor complications that occurred during AF ablation (1 simple, 4 moderate, 2 severe CHD). The 2 patients who died during follow-up had severe complexity CHD. One death was due to progressive biventricular HF 380 days after AF ablation in a patient with Shone syndrome and previous coarctation repair (age 3 weeks), aortic valvulotomy (age 10 months), patch-plasty of supravalvular aortic stenosis (age 1 year), Ross procedure, and mosaic aortic valve replacement. The other death was due to an unknown cause 14 days after ablation in a patient with hypoplastic LV, dextrocardia with L-transposition of the great arteries, atretic mitral valve and pulmonary artery, and secundum atrial septal defect with discontinuous pulmonary arteries who had previously undergone Potts shunt (age 2 days) and Blalock-Taussig shunt (age 10 years).
Liang et al Table 1
AF Ablation in Patients With Adult CHD
849
Baseline characteristics of CHD adults undergoing AF ablation
Characteristic
Overall (N 5 84)
Simple (n 5 51)
Intermediate (n 5 22)
Severe (n 5 11)
P value
Age (y) Male gender Paroxysmal AF type 1 Previous AF ablation Height (cm) Weight (kg) Body mass index (kg/m2) Heart failure Hypertension Diabetes mellitus Transient ischemic attack or stroke CHADS2 score CHA2DS2-VASc score Baseline LVEF (%) (n 5 72) LVEF ,50% (n 5 72) Failed 1 antiarrhythmic drug No. of failed antiarrhythmic drugs Medication at time of ablation Beta-blocker Any antiarrhythmic drug Amiodarone Sotalol Dofetilide Dronedarone Class 1A or 1C antiarrhythmic drug ACE inhibitor or ARB Diuretic Digoxin Calcium channel blocker Any antiplatelet agent Warfarin Non–vitamin K antagonist oral anticoagulant
51.5 6 12.1 55 (65.5) 38 (45.2) 19 (22.6) 173.5 6 11.2 89.2 6 25.1 29.5 6 6.9 31 (36.9) 36 (42.9) 12 (14.3) 8 (9.5) 1.25 6 1.07 1.80 6 1.50 53.0 6 11.8 21/72 (29.1%) 65 (77.4) 1.5 6 1.3
51.8 6 16.1 37 (72.5) 29 (56.9) 10 (19.6) 174.5 6 12.2 91.2 6 24.1 29.9 6 6.3 12 (23.5) 25 (49.0) 7 (13.7) 5 (9.8) 1.20 6 1.13 1.61 6 1.48 52.5 6 13.2 12/44 (27.2%) 41 (80.4) 1.6 6 1.3
55.1 6 13.2 13 (59.3) 9 (40.9) 8 (36.4) 172.4 6 10.3 87.5 6 27.6 29.2 6 8.0 10 (45.5) 8 (36.47) 4 (18.2) 1 (4.5) 1.14 6 0.89 1.95 6 1.43 54.7 6 10.0 6/19 (31.6%) 17 (77.3) 1.6 6 1.3
48.2 6 15.2 5 (45.5) 8 (72.7) 1 (9.1) 171.4 6 8.1 83.3 6 25.7 28.2 6 7.7 9 (81.8) 3 (27.3) 1 (9.1) 2 (18.2) 1.73 6 1.10 2.36 6 1.69 51.5 6 6.5 3/9 (33.3%) 7 (63.6) 1.5 6 1.6
.30 .18 .20 .15 .61 .60 .74 .001 .32 .77 .45 .47 .80 .74 .93 .48 .60
9 (81.8) 6 (54.5) 4 (36.4) 0 (0.0) 1 (9.1) 0 (0.0) 1 (9.1) 5 (45.5) 6 (54.5) 2 (18.2) 3 (27.3) 4 (36.4) 8 (72.7) 1 (9.1)
.93 .09 .06 .46 .12 .71 .10 .55 .10 .90 .43 .87 .59 .10
65 (77.4) 55 (65.5) 14 (16.7) 6 (7.1) 14 (16.7) 4 (4.8) 21 (25.0) 26 (31.0) 26 (31.0) 17 (20.2) 14 (16.7) 34 (40.5) 54 (64.3) 21 (25.0)
40 (78.4) 38 (74.5) 5 (9.8) 5 (9.8) 12 (23.5) 3 (5.9) 17 (33.3) 15 (29.4) 12 (23.5) 10 (19.6) 9 (17.6) 22 (43.1) 31 (60.8) 17 (33.3)
16 (76.2) 11 (50.0) 5 (23.8) 1 (4.8) 1 (4.8) 1 (4.8) 3 (14.3) 6 (28.6) 8 (38.1) 5 (23.8) 2 (9.5) 8 (38.1) 15 (71.4) 3 (14.3)
Values are given as mean 6 SD or n (%) unless otherwise indicated. ACE 5 angiotensin-converting enzyme; AF 5 atrial fibrillation; ARB 5 aldosterone receptor blocker; CHD 5 congenital heart disease; LVEF 5 left ventricular ejection fraction.
Discussion To our knowledge, this study represents the largest and only multicenter series to date of adult CHD patients with symptomatic AF treated with catheter ablation. We report the safety and efficacy of catheter ablation in a population of patients with CHD who underwent catheter ablation at 6 high-volume, experienced ablation centers that is comparable to that of historical reports for patients without CHD.7,8 At 1 year after AF ablation, 53.1% of patients were free from any AF recurrence off AADs, whereas 71.6% achieved freedom from AF recurrence either off AADs or on previously ineffective AADs only. There were no significant differences in complete or partial freedom from recurrent AF at 1 year after ablation between patients with simple, moderate, or severe CHD. Although PVI was performed in nearly all patients, additional ablation was also performed in the majority of patients. The high incidence of non-PV triggers (45.2%) reported in this series may have been due in part to the institution-dependent variability in defining non-PV triggers or to a higher incidence of non-PV triggers in this population for whom the PVs may not be the primary or only triggers of AF. Previous studies have reported a wide
range (11%–69%) in the incidence of non-PV triggers in patients undergoing initial and repeat ablation.9–11 CHD affects .1% of newborns, and CHD prevalence in the United States in 2010 was estimated to be approximately 2.4 million, with 1.4 million cases being adults over age 18.12 Historically, most deaths in CHD patients occurred early in childhood. However, advances in medical and surgical therapies for CHD patients over the past 40 years have led to a marked decline in infant and childhood deaths.13 As such, the number of CHD patients will likely continue to grow. One study found that more than half of severe CHD patients who reached age 18 developed atrial arrhythmias by age 65.4 The hemodynamic consequences of SHD in CHD can increase the risk of developing AF over time. Long-standing volume and pressure overload can lead to adverse anatomic structural changes and development of fibrosis, predisposing patients to AF. It is well known that onset of AF in patients with SHD not due to CHD is an independent predictor of worsening HF, hospitalization, stroke, and death. Similarly, the presence of AF in CHD patients is associated with increased mortality, stroke, HF, and need for cardiac
850 Table 2
Heart Rhythm, Vol 16, No 6, June 2019 Procedural characteristics and outcomes based on CHD complexity
Total procedure time (min) Total fluoroscopy time (min) Ablation strategy Any RA ablation Any LA ablation PVI PVI alone CFAE (RA or LA) Roof line Mitral annular line (anterior or septal) Mitral annular line (lateral) CTI line RA atriotomy ablation Other RA flutter ablation Other LA flutter ablation Focal impulse or rotor ablation Non-PV triggers (RA or LA) Non-PV trigger sites Crista terminalis or eustachian ridge SVC (including persistent left SVC) Coronary sinus LA roof Anterior LA LA septum LA appendage Complications Major Minor Outcomes 1-year complete freedom 1-year complete or partial freedom
Overall (N 5 84)
Simple (n 5 51)
Intermediate (n 5 22)
Severe (n 5 11)
P value
299.1 6 111.5 51.3 6 28.5
275.9 6 99.2 48.7 6 27.1
328.0 6 122.8 49.6 6 33.4
342.8 6 125.3 63.9 6 23.5
.07 .27
40 (47.6) 82 (97.6) 80 (95.2) 30 (35.7) 16 (19.1) 20 (23.8) 12 (14.3) 5 (6.0) 31 (36.9) 4 (4.8) 13 (15) 4 (4.8) 3 (3.6) 38 (45.2)
22 (43.1) 51 (100) 49 (96.1) 18 (35.3) 9 (17.6) 12 (23.5) 11 (23.9) 3 (6.5) 20 (41.7) 0 (0.0) 10 (19.6) 3 (5.8) 2 (7.8) 24 (47.1)
14 (63.6) 20 (90.9) 20 (90.9) 7 (31.8) 6 (27.3) 5 (22.7) 1 (4.5) 2 (9.1) 9 (40.9) 3 (13.6) 3 (13.6) 1 (4.5) 1 (4.5) 11 (50.0)
4 (36.4) 11 (100) 11 (100) 5 (45.5) 1 (9.1) 3 (27.3) 0 (0.0) 0 (0.0) 4 (36.4) 1 (9.1) 0 (0.0) 0 (0.0) 0 (0.0) 3 (27.3)
.06 .06 .46 .74 .37 .97 .05 .55 .93 .02 .26 .71 .72 .43
8 (9.5) 14 (16.7) 7 (8.3) 8 (9.5) 10 (11.9) 7 (8.3) 3 (3.6)
4 (7.8) 8 (15.7) 4 (7.8) 6 (11.8) 10 (19.6) 5 (9.8) 2 (3.9)
3 (13.6) 5 (22.7) 1 (4.5) 2 (9.1) 0 (0.0) 1 (4.5) 1 (4.5)
1 (9.1) 1 (9.1) 2 (18.2) 0 (0.0) 0 (0.0) 1 (9.1) 0 (0.0)
.74 .53 .46 .47 .02 .74 .92
0 (0.0) 7 (8.3)
0 (0.0) 1 (2.0)
0 (0.0) 4 (18.2)
0 (0.0) 2 (18.2)
— .05
27 (54.0) 35 (70.0)
12 (57.1) 17 (81.0)
4 (40.0) 6/10 (60.0)
.66 .44
43 (53.1) 58/81 (71.6)
Values are given as mean 6 SD or n (%) unless otherwise indicated. CFAE 5 complex fractionated atrial electrogram; CHD 5 congenital heart disease; CTI 5 cavotricuspid isthmus; LA 5 left atrium; PV 5 pulmonary vein; PVI 5 pulmonary vein isolation; RA 5 right atrium; SVC 5 superior vena cava.
intervention compared to CHD patients who do not have atrial arrhythmias.4 Because of the anatomic complexity in patients with CHD (Figure 2 shows 2 examples of the anatomic complexity of patients undergoing AF ablation in the series), physicians may be hesitant to proceed with catheter ablation. As such, many patients may be referred later in the disease process, after multiple failed AADs and frequently after AF has progressed from paroxysmal to persistent forms. The PACES/HRS expert consensus statement on the use of catheter ablation in children and patients with congenital heart disease states that a “catheter-based procedure centered on electrically isolating pulmonary veins can be useful in adults with CHD and symptomatic drug-refractory atrial fibrillation (Class IIa, Level of evidence C).”14 Many published series have examined the efficacy and safety of catheter ablation for atrial tachycardias, particularly IART, among CHD patients.15–17 Despite high rates of acute success, recurrent arrhythmias are common, and repeat ablations are often necessary to achieve long-term success. However, data for AF ablation in this same patient population remain limited. Philip et al compared outcomes after AF ablation in 36 CHD patients vs 355 non-CHD patients with SHD.18 They found that single-procedure complete freedom
(off AADs) from recurrent AF was similar between groups at both 300 days (42% vs 53%) and 4 years (27% vs 36%; P 5 .42) with similar rates of complications (15% vs 11%; P 5 .42).18 Two additional series examining ablation in patients with repaired atrial septal defect or patent foramen ovale have shown AF ablation to be safe and effective in these patients.19,20 The current study shows that AF ablation can be safe and effective even in patients with the most complex forms of CHD if performed by experienced operators at high-volume centers. It is important to adopt a multidisciplinary approach with collaboration from anesthesia, adult CHD, cardiac surgery, and HF departments when performing AF ablation in CHD patients. In our series, nontraditional techniques were frequently performed to achieve successful AF ablation because of the anatomic complexity in many patients. For example, a retrograde aortic approach was used in 2 patients (1 with D-transposition of the great arteries status post Mustard repair and the other with single ventricle status post Fontan surgery) to access the pulmonary venous atrium for mapping and ablation, including PVI using a robotic magnetic navigation system (Niobe; Stereotaxis, St. Louis, MO). In another patient with anomalous right superior PV draining into the SVC, epicardial access was obtained, and a balloon
Liang et al
AF Ablation in Patients With Adult CHD
was inflated in the epicardial space to deflect the phrenic nerve to permit safe SVC isolation (Figure 2A). Preprocedural imaging including echocardiography, computed tomographic scanning, and magnetic resonance imaging can help to guide the ablation procedure. Furthermore, 3-dimensional printing has been increasingly used by adult and pediatric cardiothoracic surgeons to prepare for surgical repairs in patients with CHD, and this technology also can be considered in patients being considered for AF ablation.21 CHD complexity may affect success and recurrence after AF ablation. In our study, there were numerically lower
851 success rates (both complete and complete/partial freedom from AF) in the severe CHD group, but it was not statistically different from the other 2 groups. This was likely due to the smaller number of patients in the severe CHD group, resulting in a lack of power to detect a statistical difference. There was also no difference seen in the type of AF for the 3 groups of CHD complexity, but this analysis was only for CHD patients coming for an AF ablation and likely reflects a referral bias. It is well known that AF and HF are closely related conditions; one may lead to the other, and vice versa. A predominance of the evidence suggests that restoration of sinus
Figure 2 Complex anatomy in patients with congenital heart disease undergoing atrial fibrillation ablation. A, left: Electroanatomic right atrial (RA) and left atrial (LA) maps of a patient with anomalous right superior pulmonary vein (RSPV) draining into the superior vena cava (SVC)/RA. The RSPV could not be isolated during the ablation procedure because of proximity to the phrenic nerve. A, right: Electroanatomic RA map at repeat procedure showing lesions delivered to achieve SVC/RSPV isolation via a combined endo/epicardial approach with use of a balloon in the epicardial space to deflect the phrenic nerve. B, left: Computed tomographic (CT) scan (axial view) of a patient with D-transposition of the great arteries status post Mustard repair with SVC and inferior vena cava baffles. B, right: CT-merged electroanatomic map used to guide ablation showing patient’s complex LA and RA anatomy. LCPV 5 left common pulmonary vein; LIPV 5 left inferior pulmonary vein; LSPV 5 left superior pulmonary vein; LV 5 left ventricle; RIPV 5 right inferior pulmonary vein; RV 5 right ventricle.
852 rhythm with successful AF ablation in non-CHD patients with HF with reduced LVEF is associated with improved outcomes, including HF hospitalizations and mortality.22–26 However, whether AF ablation in patients with HF in the setting of CHD (often with preserved LVEF) has a similar positive impact on long-term outcomes remains poorly studied. To confirm our findings, additional large prospective studies are necessary to ascertain the safety and efficacy of catheter AF ablation in this patient population.
Study limitations There are several limitations and inherent biases involved in this retrospective, observational registry study. There was likely a component of referral bias as patients were often referred late in their AF course, and many had failed multiple AADs as well as previous AF and IART ablations before they were referred for ablation at the study centers. Because of the retrospective and multicenter nature of this study, some clinical, procedural, and follow-up data were not available for all patients. Finally, not all anatomies categorized as “anatomically simple” in terms of adult CHD complexity are also considered “procedurally simple” in terms of AF ablation. For example, “anatomically simple” anatomies such as interrupted inferior vena cava and persistent left SVC may actually represent unique challenges during an AF ablation.
Conclusion As the population of adults with CHD continues to age, the incidence of AF will continue to increase. Catheter ablation is a viable, safe, and effective treatment option for adult CHD patients with symptomatic AF, a population of relatively young patients in whom maintenance of sinus rhythm may be more important and in whom long-term AAD use is of concern. Dramatic differences in the degree of anatomic complexity exist among adult CHD patients referred for AF ablation. However, when performed at experienced centers, AF ablation is both safe and effective even among patients with the most complex forms of CHD.
Appendix Supplementary data Supplementary data associated with this article can be found in the online version at https://doi.org/10.1016/j.hrthm.2 018.12.024.
References 1. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. The emerging burden of hospital admissions of adults with congenital heart disease. Heart 2010;96:872–878. 2. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. Mortality in adult congenital heart disease. Eur Heart J 2010;31:1220–1229. 3. Bhatt AB, Foster E, Kuehl K, et al. Congenital heart disease in the older adult: a scientific statement from the American Heart Association. Circulation 2015; 131:1884–1931. 4. Bouchardy J, Therrien J, Pilote L, et al. Atrial arrhythmias in adults with congenital heart disease. Circulation 2009;120:1679–1686. 5. El-Assaad I, Al-Kindi SG, Abraham J, et al. Use of dofetilide in adult patients with atrial arrhythmias and congenital heart disease: a PACES collaborative study. Heart Rhythm 2016;13:2034–2039.
Heart Rhythm, Vol 16, No 6, June 2019 6. Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS expert consensus statement on the recognition and management of arrhythmias in adult congenital heart disease: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD). Heart Rhythm 2014; 11:e102–e165. 7. Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015;372:1812–1822. 8. Kuck KH, Brugada J, Furnkranz A, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med 2016;374:2235–2245. 9. Gokoglan Y, Mohanty S, Gunes MF, et al. Pulmonary vein antrum isolation in patients with paroxysmal atrial fibrillation: more than a decade of follow-up. Circ Arrhythm Electrophysiol 2016;9:e003660. 10. Lin D, Santangeli P, Zado ES, et al. Electrophysiologic findings and long-term outcomes in patients undergoing third or more catheter ablation procedures for atrial fibrillation. J Cardiovasc Electrophysiol 2015;26:371–377. 11. Santangeli P, Zado ES, Hutchinson MD, et al. Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation. Heart Rhythm 2016;13:374–382. 12. Gilboa SM, Devine OJ, Kucik JE, et al. Congenital heart defects in the United States: estimating the magnitude of the affected population in 2010. Circulation 2016;134:101–109. 13. Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli AJ. Changing mortality in congenital heart disease. J Am Coll Cardiol 2010; 56:1149–1157. 14. Philip Saul J, Kanter RJ, Abrams D, et al. PACES/HRS expert consensus statement on the use of catheter ablation in children and patients with congenital heart disease: developed in partnership with the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American Academy of Pediatrics (AAP), the American Heart Association (AHA), and the Association for European Pediatric and Congenital Cardiology (AEPC). Heart Rhythm 2016;13:e251–e289. 15. de Groot NM, Atary JZ, Blom NA, Schalij MJ. Long-term outcome after ablative therapy of postoperative atrial tachyarrhythmia in patients with congenital heart disease and characteristics of atrial tachyarrhythmia recurrences. Circ Arrhythm Electrophysiol 2010;3:148–154. 16. Klehs S, Schneider HE, Backhoff D, Paul T, Krause U. Radiofrequency catheter ablation of atrial tachycardias in congenital heart disease: results with special reference to complexity of underlying anatomy. Circ Arrhythm Electrophysiol 2017;10:e005451. 17. Yap SC, Harris L, Silversides CK, Downar E, Chauhan VS. Outcome of intraatrial re-entrant tachycardia catheter ablation in adults with congenital heart disease: negative impact of age and complex atrial surgery. J Am Coll Cardiol 2010;56:1589–1596. 18. Philip F, Muhammad KI, Agarwal S, Natale A, Krasuski RA. Pulmonary vein isolation for the treatment of drug-refractory atrial fibrillation in adults with congenital heart disease. Congenit Heart Dis 2012;7:392–399. 19. Lakkireddy D, Rangisetty U, Prasad S, et al. Intracardiac echo-guided radiofrequency catheter ablation of atrial fibrillation in patients with atrial septal defect or patent foramen ovale repair: a feasibility, safety, and efficacy study. J Cardiovasc Electrophysiol 2008;19:1137–1142. 20. Santangeli P, Di Biase L, Burkhardt JD, et al. Transseptal access and atrial fibrillation ablation guided by intracardiac echocardiography in patients with atrial septal closure devices. Heart Rhythm 2011;8:1669–1675. 21. Valverde I, Gomez-Ciriza G, Hussain T, et al. Three-dimensional printed models for surgical planning of complex congenital heart defects: an international multicentre study. Eur J Cardiothorac Surg 2017;52:1139–1148. 22. Khan MN, Jais P, Cummings J, et al. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med 2008;359:1778–1785. 23. Jones DG, Haldar SK, Hussain W, et al. A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure. J Am Coll Cardiol 2013;61:1894–1903. 24. Hunter RJ, Berriman TJ, Diab I, et al. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial). Circ Arrhythm Electrophysiol 2014;7:31–38. 25. Di Biase L, Mohanty P, Mohanty S, et al. Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: results from the AATAC multicenter randomized trial. Circulation 2016;133:1637–1644. 26. Marrouche NF, Brachmann J, Andresen D, et al. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med 2018;378:417–427.
Introduction With advances in medical, interventional, and surgical therapies, more patients with congenital heart disease (CHD) are surviving to adulthood. Patients with CHD are frequently hospitalized for cardiac issues, and 80% of deaths in these patients are related to heart failure (HF), sudden death, arrhythmias, and vascular complications.1–3
RESULTS Overall, 84 CHD patients (mean age 51.5 6 12.1 years; 65.5% male; 45.2% with paroxysmal AF) undergoing AF ablation (51 simple, 22 moderate, 11 severe complexity) were included. Pulmonary vein isolation was performed in 80 (95.2%), of whom 30 (35.7%) underwent pulmonary vein isolation alone. Overall, complete and complete/partial freedom was achieved at 1 year in 53.1% and 71.6%, respectively, with no significant differences between those with simple, moderate, or severe complexity. There were no major complications and 7 minor complications, and 2 patients died during follow-up. CONCLUSION There are dramatic differences in the degree of CHD complexity among patients referred for AF ablation. When performed at experienced centers, AF ablation is safe and effective even among patients with the most complex forms of CHD. KEYWORDS Atrial fibrillation; Catheter ablation; Complexity; Congenital heart disease (Heart Rhythm 2019;16:846–852) All rights reserved.
© 2018 Heart Rhythm Society.
The prevalence of atrial arrhythmias, such as atrial fibrillation (AF), is higher among CHD patients compared to the general population. The incidence of AF increases with age and is associated with significantly increased risk of adverse events.4 There is a significant amount of heterogeneity in the structural heart disease (SHD) complexity in CHD patients, which may predispose them to develop AF. AF may also
Drs Sauer and Nguyen receive significant research grants from Biosense Webster and CardioNXT; and educational grants from St Jude Medical, Boston Scientific, and Medtronic. Drs Sauer and Nguyen have a provisional patent on partially insulated focused catheter ablation. Drs Nguyen and Sauer have non-public equity interests/stock options in CardioNXT. All other authors have reported that they have no conflicts relevant to the contents of this paper to disclose. Address reprint requests and correspondence: Dr Duy T. Nguyen, Section of Cardiac Electrophysiology, Division of Cardiology, University of Colorado, UB-132, Leprino Bldg, 12401 E. 17th Ave, Aurora, CO 80045. E-mail address: [email protected].
1547-5271/$-see front matter © 2018 Heart Rhythm Society. All rights reserved.
https://doi.org/10.1016/j.hrthm.2018.12.024
Liang et al
AF Ablation in Patients With Adult CHD
have a hemodynamically significant detrimental effect in patients with more complex CHD vs the general population. Although antiarrhythmic drugs (AADs) usually are attempted as first-line therapy in this complex population, they are frequently poorly tolerated or ineffective.5 As such, AF ablation has been increasingly used as a treatment strategy. Data examining optimal AF ablation strategies in CHD patients remain limited. Furthermore, although rhythm control is often believed to be of greater importance among more complex CHD patients, the safety and efficacy of AF ablation remain unknown. We aimed to examine the safety and efficacy of AF ablation in patients with different degrees of CHD complexity.
Methods We retrospectively identified consecutive adult patients with CHD who were treated with catheter ablation for symptomatic AF at 6 study centers (Hospital of the University of Pennsylvania, Philadelphia, PA; University of Colorado, Aurora, CO; Texas Cardiac Arrhythmia Institute, Austin, TX; University of Kansas Medical Center, Kansas City, KA; University of California San Francisco, San Francisco, CA; University of California Los Angeles, Los Angeles, CA) between 2008 and 2016. Etiologies of CHD among study patients are shown in Figure 1. All participants provided written informed consent for the ablation procedure as well as inclusion in medical research at the time of the procedure. Collection of data was approved by the institutional review boards of each of the respective participating centers. Ablations were performed per the operator’s discretion at each study center. Details of the AF ablation procedure and follow-up are described in the Supplementary Methods. Patients were followed-up in the outpatient setting per each institution’s routine postablation protocol. The dates of AF recurrence (after 3-month postablation blanking period) and death as well as continued use of AADs after ablation were identified from review of the medical records. Recurrent atrial arrhythmias during follow-up were managed by the treating electrophysiologist. Typically, treatment of AF recurrence consisted of anticoagulation, cardioversion, adjustment or initiation of AAD, and/or repeat AF ablation.
AF complexity For the purposes of analysis, patients were divided into 3 groups based on CHD complexity (simple, moderate, or severe) as defined by the 2014 PACES/HRS (Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society) expert consensus statement (Figure 1).6 Patients with multiple CHD abnormalities were classified based on the most severe abnormality.
Statistical analysis Baseline demographics, medications, comorbidities, clinical details regarding CHD type, imaging study findings, details from the ablation procedure including ablation strategies and complications, and outcomes after ablation were abstracted
847 from the medical records for each patient and summarized using percentages and means. Demographic and clinical measures were compared based on CHD complexity at enrollment using t tests, c2 tests, or Fisher tests, as appropriate. Proportional hazards models were used to evaluate clinical and demographic predictors of AF recurrence during follow-up. The proportional hazards assumption was examined for all variables before model inclusion. All analyses were performed using SPSS Statistics (IBM, Armonk, NY) and Microsoft Excel (Microsoft, Seattle, WA). P ,.05 was considered significant.
Results Patient population Between January 2008 and October 2016, a total of 84 adult CHD patients treated with AF ablation were included. Table 1 lists the baseline clinical characteristics of the patients. Mean age at time of ablation was 51.5 6 12.1 years, 65% were male, and 38 (45.2%) had paroxysmal AF. Nineteen patients (22.6%) had undergone at least 1 previous ablation at another institution for AF, and 21 (25.0%) had undergone previous ablation for intra-atrial reentrant tachycardia (IART). Mean CHADS2 score was 1.25 6 1.07, and mean CHA2DS2VASc score was 1.80 6 1.50. The majority of patients (77.4%) had failed or were intolerant of at least 1 AAD before ablation, and 55 (65.5%) were taking an AAD at the time of ablation. Of 84 patients, the degree of complexity of CHD was considered to be simple in 51 (60.7%), moderate in 22 (26.2%), and severe in 11 (13.1%) (Figure 1). Other than a higher likelihood of clinical HF in the severe complexity group (P 5 .001), there were no significant differences in baseline characteristics between the simple, moderate, and severe complexity groups (Table 1).
AF ablation procedural information Overall mean procedure time was 299.1 6 111.5 minutes, and there was a trend toward longer procedure times in patients with increasing CHD complexity (simple: 275.9 6 99.2 minutes; intermediate: 328.0 6 122.8 minutes; severe: 342.8 6 125.3 minutes; P 5 .07). Total mean fluoroscopy time was 51.3 6 28.5 minutes (simple: 48.7 6 27.1 minutes; intermediate: 49.6 6 33.4 minutes; severe: 63.9 6 23.5 minutes; P 5 .27). Ablation strategies performed during AF ablation are listed in Table 2. Left atrial (LA) ablation was performed in 82 patients (97.6%), and 2 patients (2.4%) underwent ablation of triggers and complex fractionated atrial electrogram ablation in the right atrium (RA) alone. Overall, ablation within the RA was performed in 40 patients (47.6%) . Pulmonary vein isolation (PVI) was performed in 80 patients (95.2%). Thirty patients underwent PVI alone, and the remaining 50 patients underwent ablation lesions in addition to PVI. The most frequent additional ablation lesion sets included targeting of non-PV triggers in 38 (45.2%), cavotricuspid isthmus ablation in 31 (36.9%), creation of a roof line in 20 (23.8%), mitral annular linear ablation in 17 (20.3%), and complex fractionated atrial electrogram ablation in 16
848
Heart Rhythm, Vol 16, No 6, June 2019
Figure 1 Classification of the complexity of congenital heart disease (CHD) of patients undergoing atrial fibrillation ablation. ASD 5 atrial septal defect; IVC 5 inferior vena cava; PV 5 pulmonary vein; SVC 5 superior vena cava; TGA 5 transposition of the great arteries; VSD 5 ventricular septal defect.
(19.1%). Focal impulse or rotor ablation was performed in 3 patients (3.6%). Aside from an increased prevalence of RA atriotomy ablation in the severe group (P 5 .02), there was no statistically significant difference in ablation strategies between groups with different CHD complexity (Table 2).
Non-PV triggers A total of 65 distinct non-PV triggers were identified among the 38 patients with at least 1 non-PV trigger targeted (Table 2). The most common sites of non-PV triggers were superior vena cava (SVC; including persistent left SVC) in 14 (16.7%), anterior LA in 10 (11.9%), crista terminalis or eustachian ridge in 8 (9.5%), LA roof in 8 (9.5%), coronary sinus in 7 (8.3%), LA septum in 7 (9.3%), and LA appendage in 3 (3.6%).
54.0% (70.0%) for simple, 57.1% (81.0%) for moderate, and 40.0% (60.0%) for severe CHD complexity (P 5 .66 for complete and P 5 .44 for complete/partial freedom between groups).
Improvement in left ventricular ejection fraction Baseline mean left ventricular ejection fraction (LVEF) of the 72 patients with available echocardiograms for LVEF quantification was 53.0% 6 11.8% at the time of ablation (no difference between groups). A total of 21 patients (29.1%) had reduced LVEF (,50%) before ablation. Of these 21 patients with reduced baseline LVEF, the last available follow-up echocardiogram revealed any degree of LVEF improvement in 19 (90.5%), whereas 16 (76.2%) had normalization of LV function (LVEF 50%).
Efficacy: Ablation success and AF recurrence AF ablation was considered acutely successful in all patients, and successful isolation of PVs was achieved in all 80 patients in whom PVI was attempted. Mean follow-up for 81 patients with available follow-up data was 708.6 6 807.7 days (3 patients lost to follow-up after ablation were excluded from outcome analysis). Early AF recurrence within the 3-month postablation blanking period occurred in 21 of the 73 patients (28.8%) with available data. Outcomes were defined with regard to the index ablation performed at the 6 participating centers. Complete freedom (off AADs) from recurrent AF out to 1 year after ablation (excluding the 3-month blanking period) was achieved in 43 of 81 patients (53.1%), and partial freedom (on previously ineffective AADs) was achieved in an additional 15 patients (overall partial or complete freedom achieved in 58/81 patients [71.6%]). One-year complete (and including partial) success rates were
Safety: Complications and long-term mortality No major complications occurred. Supplemental Table 1 lists the 7 procedure-related minor complications that occurred during AF ablation (1 simple, 4 moderate, 2 severe CHD). The 2 patients who died during follow-up had severe complexity CHD. One death was due to progressive biventricular HF 380 days after AF ablation in a patient with Shone syndrome and previous coarctation repair (age 3 weeks), aortic valvulotomy (age 10 months), patch-plasty of supravalvular aortic stenosis (age 1 year), Ross procedure, and mosaic aortic valve replacement. The other death was due to an unknown cause 14 days after ablation in a patient with hypoplastic LV, dextrocardia with L-transposition of the great arteries, atretic mitral valve and pulmonary artery, and secundum atrial septal defect with discontinuous pulmonary arteries who had previously undergone Potts shunt (age 2 days) and Blalock-Taussig shunt (age 10 years).
Liang et al Table 1
AF Ablation in Patients With Adult CHD
849
Baseline characteristics of CHD adults undergoing AF ablation
Characteristic
Overall (N 5 84)
Simple (n 5 51)
Intermediate (n 5 22)
Severe (n 5 11)
P value
Age (y) Male gender Paroxysmal AF type 1 Previous AF ablation Height (cm) Weight (kg) Body mass index (kg/m2) Heart failure Hypertension Diabetes mellitus Transient ischemic attack or stroke CHADS2 score CHA2DS2-VASc score Baseline LVEF (%) (n 5 72) LVEF ,50% (n 5 72) Failed 1 antiarrhythmic drug No. of failed antiarrhythmic drugs Medication at time of ablation Beta-blocker Any antiarrhythmic drug Amiodarone Sotalol Dofetilide Dronedarone Class 1A or 1C antiarrhythmic drug ACE inhibitor or ARB Diuretic Digoxin Calcium channel blocker Any antiplatelet agent Warfarin Non–vitamin K antagonist oral anticoagulant
51.5 6 12.1 55 (65.5) 38 (45.2) 19 (22.6) 173.5 6 11.2 89.2 6 25.1 29.5 6 6.9 31 (36.9) 36 (42.9) 12 (14.3) 8 (9.5) 1.25 6 1.07 1.80 6 1.50 53.0 6 11.8 21/72 (29.1%) 65 (77.4) 1.5 6 1.3
51.8 6 16.1 37 (72.5) 29 (56.9) 10 (19.6) 174.5 6 12.2 91.2 6 24.1 29.9 6 6.3 12 (23.5) 25 (49.0) 7 (13.7) 5 (9.8) 1.20 6 1.13 1.61 6 1.48 52.5 6 13.2 12/44 (27.2%) 41 (80.4) 1.6 6 1.3
55.1 6 13.2 13 (59.3) 9 (40.9) 8 (36.4) 172.4 6 10.3 87.5 6 27.6 29.2 6 8.0 10 (45.5) 8 (36.47) 4 (18.2) 1 (4.5) 1.14 6 0.89 1.95 6 1.43 54.7 6 10.0 6/19 (31.6%) 17 (77.3) 1.6 6 1.3
48.2 6 15.2 5 (45.5) 8 (72.7) 1 (9.1) 171.4 6 8.1 83.3 6 25.7 28.2 6 7.7 9 (81.8) 3 (27.3) 1 (9.1) 2 (18.2) 1.73 6 1.10 2.36 6 1.69 51.5 6 6.5 3/9 (33.3%) 7 (63.6) 1.5 6 1.6
.30 .18 .20 .15 .61 .60 .74 .001 .32 .77 .45 .47 .80 .74 .93 .48 .60
9 (81.8) 6 (54.5) 4 (36.4) 0 (0.0) 1 (9.1) 0 (0.0) 1 (9.1) 5 (45.5) 6 (54.5) 2 (18.2) 3 (27.3) 4 (36.4) 8 (72.7) 1 (9.1)
.93 .09 .06 .46 .12 .71 .10 .55 .10 .90 .43 .87 .59 .10
65 (77.4) 55 (65.5) 14 (16.7) 6 (7.1) 14 (16.7) 4 (4.8) 21 (25.0) 26 (31.0) 26 (31.0) 17 (20.2) 14 (16.7) 34 (40.5) 54 (64.3) 21 (25.0)
40 (78.4) 38 (74.5) 5 (9.8) 5 (9.8) 12 (23.5) 3 (5.9) 17 (33.3) 15 (29.4) 12 (23.5) 10 (19.6) 9 (17.6) 22 (43.1) 31 (60.8) 17 (33.3)
16 (76.2) 11 (50.0) 5 (23.8) 1 (4.8) 1 (4.8) 1 (4.8) 3 (14.3) 6 (28.6) 8 (38.1) 5 (23.8) 2 (9.5) 8 (38.1) 15 (71.4) 3 (14.3)
Values are given as mean 6 SD or n (%) unless otherwise indicated. ACE 5 angiotensin-converting enzyme; AF 5 atrial fibrillation; ARB 5 aldosterone receptor blocker; CHD 5 congenital heart disease; LVEF 5 left ventricular ejection fraction.
Discussion To our knowledge, this study represents the largest and only multicenter series to date of adult CHD patients with symptomatic AF treated with catheter ablation. We report the safety and efficacy of catheter ablation in a population of patients with CHD who underwent catheter ablation at 6 high-volume, experienced ablation centers that is comparable to that of historical reports for patients without CHD.7,8 At 1 year after AF ablation, 53.1% of patients were free from any AF recurrence off AADs, whereas 71.6% achieved freedom from AF recurrence either off AADs or on previously ineffective AADs only. There were no significant differences in complete or partial freedom from recurrent AF at 1 year after ablation between patients with simple, moderate, or severe CHD. Although PVI was performed in nearly all patients, additional ablation was also performed in the majority of patients. The high incidence of non-PV triggers (45.2%) reported in this series may have been due in part to the institution-dependent variability in defining non-PV triggers or to a higher incidence of non-PV triggers in this population for whom the PVs may not be the primary or only triggers of AF. Previous studies have reported a wide
range (11%–69%) in the incidence of non-PV triggers in patients undergoing initial and repeat ablation.9–11 CHD affects .1% of newborns, and CHD prevalence in the United States in 2010 was estimated to be approximately 2.4 million, with 1.4 million cases being adults over age 18.12 Historically, most deaths in CHD patients occurred early in childhood. However, advances in medical and surgical therapies for CHD patients over the past 40 years have led to a marked decline in infant and childhood deaths.13 As such, the number of CHD patients will likely continue to grow. One study found that more than half of severe CHD patients who reached age 18 developed atrial arrhythmias by age 65.4 The hemodynamic consequences of SHD in CHD can increase the risk of developing AF over time. Long-standing volume and pressure overload can lead to adverse anatomic structural changes and development of fibrosis, predisposing patients to AF. It is well known that onset of AF in patients with SHD not due to CHD is an independent predictor of worsening HF, hospitalization, stroke, and death. Similarly, the presence of AF in CHD patients is associated with increased mortality, stroke, HF, and need for cardiac
850 Table 2
Heart Rhythm, Vol 16, No 6, June 2019 Procedural characteristics and outcomes based on CHD complexity
Total procedure time (min) Total fluoroscopy time (min) Ablation strategy Any RA ablation Any LA ablation PVI PVI alone CFAE (RA or LA) Roof line Mitral annular line (anterior or septal) Mitral annular line (lateral) CTI line RA atriotomy ablation Other RA flutter ablation Other LA flutter ablation Focal impulse or rotor ablation Non-PV triggers (RA or LA) Non-PV trigger sites Crista terminalis or eustachian ridge SVC (including persistent left SVC) Coronary sinus LA roof Anterior LA LA septum LA appendage Complications Major Minor Outcomes 1-year complete freedom 1-year complete or partial freedom
Overall (N 5 84)
Simple (n 5 51)
Intermediate (n 5 22)
Severe (n 5 11)
P value
299.1 6 111.5 51.3 6 28.5
275.9 6 99.2 48.7 6 27.1
328.0 6 122.8 49.6 6 33.4
342.8 6 125.3 63.9 6 23.5
.07 .27
40 (47.6) 82 (97.6) 80 (95.2) 30 (35.7) 16 (19.1) 20 (23.8) 12 (14.3) 5 (6.0) 31 (36.9) 4 (4.8) 13 (15) 4 (4.8) 3 (3.6) 38 (45.2)
22 (43.1) 51 (100) 49 (96.1) 18 (35.3) 9 (17.6) 12 (23.5) 11 (23.9) 3 (6.5) 20 (41.7) 0 (0.0) 10 (19.6) 3 (5.8) 2 (7.8) 24 (47.1)
14 (63.6) 20 (90.9) 20 (90.9) 7 (31.8) 6 (27.3) 5 (22.7) 1 (4.5) 2 (9.1) 9 (40.9) 3 (13.6) 3 (13.6) 1 (4.5) 1 (4.5) 11 (50.0)
4 (36.4) 11 (100) 11 (100) 5 (45.5) 1 (9.1) 3 (27.3) 0 (0.0) 0 (0.0) 4 (36.4) 1 (9.1) 0 (0.0) 0 (0.0) 0 (0.0) 3 (27.3)
.06 .06 .46 .74 .37 .97 .05 .55 .93 .02 .26 .71 .72 .43
8 (9.5) 14 (16.7) 7 (8.3) 8 (9.5) 10 (11.9) 7 (8.3) 3 (3.6)
4 (7.8) 8 (15.7) 4 (7.8) 6 (11.8) 10 (19.6) 5 (9.8) 2 (3.9)
3 (13.6) 5 (22.7) 1 (4.5) 2 (9.1) 0 (0.0) 1 (4.5) 1 (4.5)
1 (9.1) 1 (9.1) 2 (18.2) 0 (0.0) 0 (0.0) 1 (9.1) 0 (0.0)
.74 .53 .46 .47 .02 .74 .92
0 (0.0) 7 (8.3)
0 (0.0) 1 (2.0)
0 (0.0) 4 (18.2)
0 (0.0) 2 (18.2)
— .05
27 (54.0) 35 (70.0)
12 (57.1) 17 (81.0)
4 (40.0) 6/10 (60.0)
.66 .44
43 (53.1) 58/81 (71.6)
Values are given as mean 6 SD or n (%) unless otherwise indicated. CFAE 5 complex fractionated atrial electrogram; CHD 5 congenital heart disease; CTI 5 cavotricuspid isthmus; LA 5 left atrium; PV 5 pulmonary vein; PVI 5 pulmonary vein isolation; RA 5 right atrium; SVC 5 superior vena cava.
intervention compared to CHD patients who do not have atrial arrhythmias.4 Because of the anatomic complexity in patients with CHD (Figure 2 shows 2 examples of the anatomic complexity of patients undergoing AF ablation in the series), physicians may be hesitant to proceed with catheter ablation. As such, many patients may be referred later in the disease process, after multiple failed AADs and frequently after AF has progressed from paroxysmal to persistent forms. The PACES/HRS expert consensus statement on the use of catheter ablation in children and patients with congenital heart disease states that a “catheter-based procedure centered on electrically isolating pulmonary veins can be useful in adults with CHD and symptomatic drug-refractory atrial fibrillation (Class IIa, Level of evidence C).”14 Many published series have examined the efficacy and safety of catheter ablation for atrial tachycardias, particularly IART, among CHD patients.15–17 Despite high rates of acute success, recurrent arrhythmias are common, and repeat ablations are often necessary to achieve long-term success. However, data for AF ablation in this same patient population remain limited. Philip et al compared outcomes after AF ablation in 36 CHD patients vs 355 non-CHD patients with SHD.18 They found that single-procedure complete freedom
(off AADs) from recurrent AF was similar between groups at both 300 days (42% vs 53%) and 4 years (27% vs 36%; P 5 .42) with similar rates of complications (15% vs 11%; P 5 .42).18 Two additional series examining ablation in patients with repaired atrial septal defect or patent foramen ovale have shown AF ablation to be safe and effective in these patients.19,20 The current study shows that AF ablation can be safe and effective even in patients with the most complex forms of CHD if performed by experienced operators at high-volume centers. It is important to adopt a multidisciplinary approach with collaboration from anesthesia, adult CHD, cardiac surgery, and HF departments when performing AF ablation in CHD patients. In our series, nontraditional techniques were frequently performed to achieve successful AF ablation because of the anatomic complexity in many patients. For example, a retrograde aortic approach was used in 2 patients (1 with D-transposition of the great arteries status post Mustard repair and the other with single ventricle status post Fontan surgery) to access the pulmonary venous atrium for mapping and ablation, including PVI using a robotic magnetic navigation system (Niobe; Stereotaxis, St. Louis, MO). In another patient with anomalous right superior PV draining into the SVC, epicardial access was obtained, and a balloon
Liang et al
AF Ablation in Patients With Adult CHD
was inflated in the epicardial space to deflect the phrenic nerve to permit safe SVC isolation (Figure 2A). Preprocedural imaging including echocardiography, computed tomographic scanning, and magnetic resonance imaging can help to guide the ablation procedure. Furthermore, 3-dimensional printing has been increasingly used by adult and pediatric cardiothoracic surgeons to prepare for surgical repairs in patients with CHD, and this technology also can be considered in patients being considered for AF ablation.21 CHD complexity may affect success and recurrence after AF ablation. In our study, there were numerically lower
851 success rates (both complete and complete/partial freedom from AF) in the severe CHD group, but it was not statistically different from the other 2 groups. This was likely due to the smaller number of patients in the severe CHD group, resulting in a lack of power to detect a statistical difference. There was also no difference seen in the type of AF for the 3 groups of CHD complexity, but this analysis was only for CHD patients coming for an AF ablation and likely reflects a referral bias. It is well known that AF and HF are closely related conditions; one may lead to the other, and vice versa. A predominance of the evidence suggests that restoration of sinus
Figure 2 Complex anatomy in patients with congenital heart disease undergoing atrial fibrillation ablation. A, left: Electroanatomic right atrial (RA) and left atrial (LA) maps of a patient with anomalous right superior pulmonary vein (RSPV) draining into the superior vena cava (SVC)/RA. The RSPV could not be isolated during the ablation procedure because of proximity to the phrenic nerve. A, right: Electroanatomic RA map at repeat procedure showing lesions delivered to achieve SVC/RSPV isolation via a combined endo/epicardial approach with use of a balloon in the epicardial space to deflect the phrenic nerve. B, left: Computed tomographic (CT) scan (axial view) of a patient with D-transposition of the great arteries status post Mustard repair with SVC and inferior vena cava baffles. B, right: CT-merged electroanatomic map used to guide ablation showing patient’s complex LA and RA anatomy. LCPV 5 left common pulmonary vein; LIPV 5 left inferior pulmonary vein; LSPV 5 left superior pulmonary vein; LV 5 left ventricle; RIPV 5 right inferior pulmonary vein; RV 5 right ventricle.
852 rhythm with successful AF ablation in non-CHD patients with HF with reduced LVEF is associated with improved outcomes, including HF hospitalizations and mortality.22–26 However, whether AF ablation in patients with HF in the setting of CHD (often with preserved LVEF) has a similar positive impact on long-term outcomes remains poorly studied. To confirm our findings, additional large prospective studies are necessary to ascertain the safety and efficacy of catheter AF ablation in this patient population.
Study limitations There are several limitations and inherent biases involved in this retrospective, observational registry study. There was likely a component of referral bias as patients were often referred late in their AF course, and many had failed multiple AADs as well as previous AF and IART ablations before they were referred for ablation at the study centers. Because of the retrospective and multicenter nature of this study, some clinical, procedural, and follow-up data were not available for all patients. Finally, not all anatomies categorized as “anatomically simple” in terms of adult CHD complexity are also considered “procedurally simple” in terms of AF ablation. For example, “anatomically simple” anatomies such as interrupted inferior vena cava and persistent left SVC may actually represent unique challenges during an AF ablation.
Conclusion As the population of adults with CHD continues to age, the incidence of AF will continue to increase. Catheter ablation is a viable, safe, and effective treatment option for adult CHD patients with symptomatic AF, a population of relatively young patients in whom maintenance of sinus rhythm may be more important and in whom long-term AAD use is of concern. Dramatic differences in the degree of anatomic complexity exist among adult CHD patients referred for AF ablation. However, when performed at experienced centers, AF ablation is both safe and effective even among patients with the most complex forms of CHD.
Appendix Supplementary data Supplementary data associated with this article can be found in the online version at https://doi.org/10.1016/j.hrthm.2 018.12.024.
References 1. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. The emerging burden of hospital admissions of adults with congenital heart disease. Heart 2010;96:872–878. 2. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. Mortality in adult congenital heart disease. Eur Heart J 2010;31:1220–1229. 3. Bhatt AB, Foster E, Kuehl K, et al. Congenital heart disease in the older adult: a scientific statement from the American Heart Association. Circulation 2015; 131:1884–1931. 4. Bouchardy J, Therrien J, Pilote L, et al. Atrial arrhythmias in adults with congenital heart disease. Circulation 2009;120:1679–1686. 5. El-Assaad I, Al-Kindi SG, Abraham J, et al. Use of dofetilide in adult patients with atrial arrhythmias and congenital heart disease: a PACES collaborative study. Heart Rhythm 2016;13:2034–2039.
Heart Rhythm, Vol 16, No 6, June 2019 6. Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS expert consensus statement on the recognition and management of arrhythmias in adult congenital heart disease: developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD). Heart Rhythm 2014; 11:e102–e165. 7. Verma A, Jiang CY, Betts TR, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med 2015;372:1812–1822. 8. Kuck KH, Brugada J, Furnkranz A, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med 2016;374:2235–2245. 9. Gokoglan Y, Mohanty S, Gunes MF, et al. Pulmonary vein antrum isolation in patients with paroxysmal atrial fibrillation: more than a decade of follow-up. Circ Arrhythm Electrophysiol 2016;9:e003660. 10. Lin D, Santangeli P, Zado ES, et al. Electrophysiologic findings and long-term outcomes in patients undergoing third or more catheter ablation procedures for atrial fibrillation. J Cardiovasc Electrophysiol 2015;26:371–377. 11. Santangeli P, Zado ES, Hutchinson MD, et al. Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation. Heart Rhythm 2016;13:374–382. 12. Gilboa SM, Devine OJ, Kucik JE, et al. Congenital heart defects in the United States: estimating the magnitude of the affected population in 2010. Circulation 2016;134:101–109. 13. Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli AJ. Changing mortality in congenital heart disease. J Am Coll Cardiol 2010; 56:1149–1157. 14. Philip Saul J, Kanter RJ, Abrams D, et al. PACES/HRS expert consensus statement on the use of catheter ablation in children and patients with congenital heart disease: developed in partnership with the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American Academy of Pediatrics (AAP), the American Heart Association (AHA), and the Association for European Pediatric and Congenital Cardiology (AEPC). Heart Rhythm 2016;13:e251–e289. 15. de Groot NM, Atary JZ, Blom NA, Schalij MJ. Long-term outcome after ablative therapy of postoperative atrial tachyarrhythmia in patients with congenital heart disease and characteristics of atrial tachyarrhythmia recurrences. Circ Arrhythm Electrophysiol 2010;3:148–154. 16. Klehs S, Schneider HE, Backhoff D, Paul T, Krause U. Radiofrequency catheter ablation of atrial tachycardias in congenital heart disease: results with special reference to complexity of underlying anatomy. Circ Arrhythm Electrophysiol 2017;10:e005451. 17. Yap SC, Harris L, Silversides CK, Downar E, Chauhan VS. Outcome of intraatrial re-entrant tachycardia catheter ablation in adults with congenital heart disease: negative impact of age and complex atrial surgery. J Am Coll Cardiol 2010;56:1589–1596. 18. Philip F, Muhammad KI, Agarwal S, Natale A, Krasuski RA. Pulmonary vein isolation for the treatment of drug-refractory atrial fibrillation in adults with congenital heart disease. Congenit Heart Dis 2012;7:392–399. 19. Lakkireddy D, Rangisetty U, Prasad S, et al. Intracardiac echo-guided radiofrequency catheter ablation of atrial fibrillation in patients with atrial septal defect or patent foramen ovale repair: a feasibility, safety, and efficacy study. J Cardiovasc Electrophysiol 2008;19:1137–1142. 20. Santangeli P, Di Biase L, Burkhardt JD, et al. Transseptal access and atrial fibrillation ablation guided by intracardiac echocardiography in patients with atrial septal closure devices. Heart Rhythm 2011;8:1669–1675. 21. Valverde I, Gomez-Ciriza G, Hussain T, et al. Three-dimensional printed models for surgical planning of complex congenital heart defects: an international multicentre study. Eur J Cardiothorac Surg 2017;52:1139–1148. 22. Khan MN, Jais P, Cummings J, et al. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med 2008;359:1778–1785. 23. Jones DG, Haldar SK, Hussain W, et al. A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure. J Am Coll Cardiol 2013;61:1894–1903. 24. Hunter RJ, Berriman TJ, Diab I, et al. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial). Circ Arrhythm Electrophysiol 2014;7:31–38. 25. Di Biase L, Mohanty P, Mohanty S, et al. Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: results from the AATAC multicenter randomized trial. Circulation 2016;133:1637–1644. 26. Marrouche NF, Brachmann J, Andresen D, et al. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med 2018;378:417–427.