Author + information
- Received December 19, 2016
- Revision received April 5, 2017
- Accepted April 11, 2017
- Published online December 4, 2017.
- Michelle Samuel, MPHa,
- Mohammad Almohammadi, MDb,
- Meytal Avgil Tsadok, PhDa,
- Jacqueline Joza, MDc,
- Cynthia A. Jackevicius, BScPhm, PharmD, MScd,e,
- Maria Koh, MScd,
- Hassan Behlouli, PhDa,
- Atul Verma, MDc,
- Louise Pilote, MD, MPH, PhDa,b,∗ ( and )
- Vidal Essebag, MD, PhDc
- aDivision of Clinical Epidemiology, McGill University Health Centre Research Institute, Montreal, Quebec, Canada
- bDivision of General Internal Medicine, McGill University Health Centre Research Institute, Montreal, Quebec, Canada
- cDivision of Cardiology, McGill University Health Centre Research Institute, Montreal, Quebec, Canada
- dInstitute of Clinical Evaluative Sciences, University Health Network, University of Toronto, Toronto, Ontario, Canada
- eVeterans Administration Greater Los Angeles Health System, Western University of Health Sciences, Los Angeles, California
- ↵∗Address for correspondence:
Dr. Louise Pilote, Division of General Internal Medicine, McGill University Health Centre, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada.
Objectives The purpose of this study was to evaluate the safety and incidence of periprocedural adverse events (AEs) among patients who underwent catheter ablation (CA) for atrial fibrillation (AF) in Quebec and Ontario, Canada.
Background CA is evolving into the mainstay therapy for patients with symptomatic AF refractory to antiarrhythmic medication. However, the safety of CA at the population level over time requires further evaluation.
Methods A population-based cohort was constructed using administrative databases of all patients who underwent CA between 1999 and 2014 in Quebec and Ontario, Canada. Incidence and predictors of AEs were assessed within 30 days of CA. Major AEs included all-cause mortality, cerebrovascular accident (CVA) including transient ischemic attack, pericardial effusion requiring drainage (PERD), vascular AEs, hemorrhage/hematoma, and pulmonary embolism.
Results Of 6,388 patients who had a CA (mean age 57.3 years; mean CHA2DS2-VASc 1.1 ± 1.4; 27.6% female), 221 (3.5%) patients developed major AEs within 30 days of index CA. Hemorrhage/hematoma was the most frequent (1.4%), followed by PERD (1.0%) and CVA (0.6%). PERD was more likely to occur post-discharge than during the index CA (p < 0.05). CVA decreased by more than 50% in patients with recent compared with remote CA (p < 0.05). Compared with index CA, the incidence of PERD and hemorrhage/hematoma was greater at first repeat CA (p < 0.05 for both).
Conclusions CA is a relatively safe procedure with low incidence of major AEs. The incidence of procedure-related CVA appeared to decline significantly over time. Incidence of PERD remained relatively stable and was more likely to be diagnosed after discharge and following repeat CA.
Catheter ablation (CA) for atrial fibrillation (AF) is an established rhythm control strategy for patients with drug-refractory symptomatic AF (1,2). CA targets the triggers and substrate that initiate, perpetuate, and sustain AF (3). The therapeutic goal of the procedure is to restore and maintain sinus rhythm, thereby potentially reducing thromboembolic risk, enhancing cardiac performance, and improving survival (4,5). Randomized controlled trials have shown that CA decreases arrhythmia burden (4,6) and improves quality of life (4,7). Observational studies have suggested that CA is associated with reductions in ischemic stroke (8,9) and mortality (5,8).
However, CA has been associated with significant periprocedural adverse events (AEs), including cerebrovascular accident (CVA), pericardial effusion or tamponade, vascular AEs, pulmonary embolism, hemorrhage/hematoma, and all-cause mortality (10–12). The reported incidence of major AEs after CA has varied, ranging from <1% to 6% (11–13). Compared with other less complex ablations, left atrial ablations may be associated with specific types of AEs related to the use of trans-septal sheaths, the navigation time in the left atrium, and the amount of radiofrequency energy necessary to obtain pulmonary vein isolation (12). To date, published data regarding the safety of CA has been inconsistent among selected high-volume academic centers, nonacademic hospitals, and worldwide surveys (11–14).
As improvements in CA technology and operator experience broaden patient selection criteria for the procedure (1), the assessment of periprocedural AEs at the population level over time is essential. Our objective was to evaluate the safety and incidence of periprocedural AEs amongst patients who underwent CA for AF in the provinces of Quebec and Ontario, Canada.
A population-based cohort was constructed using administrative databases to assess the 30-day safety of CA among patients who underwent the CA at all 16 AF ablation centers in the provinces of Quebec (between April 2003 and March 2013) and Ontario (between April 1999 and March 2014), Canada. The study received institutional review board approval from the McGill University Faculty of Medicine (study number A05-M79-08B) and Sunnybrook Health Sciences Centre.
Data sources and population selection
Parallel cohorts were formed in Quebec and Ontario using physician claims files (Régie de l’assurance maladie du Québec [RAMQ] and Ontario Health Insurance Program [OHIP]) with billing codes for CA of AF (RAMQ code 291 excluding complex ablations for congenital heart disease and ventricular tachycardia, and OHIP codes G176, G178, Z423, Z424, and Z441) in conjunction with hospital discharge databases (Maintenance et Exploration de Données pour l’Étude de la Clintele Hospitalière [MED-ECHO] in Quebec and Discharge Abstract Database, Same Day Surgery, and National Ambulatory Care Reporting System from the Canadian Institute of Health Information [CIHI] in Ontario). Datasets were linked using unique encoded patient identifiers. MED-ECHO and CIHI databases provide data on admission diagnoses and list comorbidities using the International Classification of Disease-9th and 10th Revisions (ICD-9/10) system. Only patients with a primary or secondary diagnosis of AF (ICD-9/10 codes 427.3, 427.31, or 427.32/I48) at index CA hospitalization were included (15–17).
The incidence and predictors of AEs were assessed within 30 days of index CA. In patients with repeat CA, incidence of AEs was also assessed within 30 days post–first repeat CA. AEs were identified using ICD-9/10 codes in the MED-ECHO and CIHI databases. All discharge AEs listed were included as an AE. AEs after CA hospitalizations were determined from the primary diagnoses in the rehospitalization and emergency department visits records.
Major AEs included all-cause mortality, CVA (including transient ischemic attack [TIA]), pericardial effusion requiring drainage (PERD), vascular AEs, hemorrhage/hematoma, and pulmonary embolism (ICD-9/10 codes listed in the Online Appendix [Table A1]). PERD (including cardiac tamponade) was defined as effusion that required drainage (RAMQ code 0597 and 9334 OHIP code Z401). Vascular AEs were defined as any injury to blood vessels, accidental punctures, AV fistula, injury to retro-peritoneum, vascular complications requiring surgery, and vascular complications following a procedure (18).
Nonmajor AEs included any diagnosis that was not considered a major AE.
Covariates and statistical analysis
Patient age was calculated at the date of the CA, and comorbidities were identified from MED-ECHO and CIHI databases using the diagnostic codes linked to the CA hospitalization and within 12 months prior to CA. The baseline risk of stroke was assessed by CHA2DS2-VASc score (1 point for each: congestive heart failure, hypertension, age ≥65 years, diabetes mellitus, vascular disease, and female sex; and 2 points each for age ≥75 years and prior CVA or TIA). The CHA2DS2-VASc scores were stratified according to clinical risk: low (score = 0), intermediate (score = 1), and high (score ≥2).
Continuous variables were reported as mean ± SD where differences were compared by the Kruskal-Wallis test. Categorical variables were reported as percentages and differences were assessed by the McNemar chi-square test. Predictors of major AEs were put into multivariable logistic regression models, and models were reduced using log-likelihood tests to determine the predictors in the final model (p < 0.05). Predictor variables considered in the initial models included age, sex, hypertension, diabetes, coronary artery disease, prior myocardial infarction, heart failure, valvular disease, chronic obstructive pulmonary disease, prior stroke, prior bleeds, and number of AF hospitalizations during the month prior to index CA.
The cohort was divided in one-half by the date of index CA to compare the rates of a composite and specific major AEs in remote versus recent CAs.
SAS version 9.3 (SAS Institute, Cary, North Carolina) was employed for all statistical analyses. A 2-sided p value <0.05 was considered statistically significant.
Of the 488,755 patients in the AF cohort, a total of 6,388 individuals who underwent CA for AF were included in the study. Patients who had a major AE were older (age 61.1 ± 10.8 years), were more likely women (37.1%), and had a higher mean CHA2DS2-VASc score (1.7 ± 1.3) than patients without major AEs (age 57.1 ± 11.4 years, 27.3% women, CHA2DS2-VASc score 1.1 ± 1.2) (Table 1) (p < 0.05 for all comparisons). Patients with major AEs also had a higher proportion of hypertension (58.4%), diabetes mellitus (17.6%), coronary artery disease (14.0%), valvular disease (10.4%), and prior CVA (6.3%) compared with patients without major AEs (Table 1) (p < 0.05 for all comparisons).
Adverse events after index ablation
In the cohort of 6,388 patients, a total of 612 AEs developed within 30 days post–index CA (Table 2). Of these, 260 major AEs occurred in 221 (3.5%) patients within 30 days of index CA. Major AEs included hemorrhages/hematomas (1.4%), PERD (1.0%), CVA (0.6%), and all-cause mortality (0.1%) (Figure 1).
Timing of AEs revealed that 47.1% of major AEs occurred during the index hospitalization and 52.9% occurred post-discharge (Table 2). PERD and pulmonary embolism were more likely to occur post-discharge compared with during index hospitalization (Figure 1) (p < 0.05). PERD developed approximately 4.4 ± 15.4 days post–index CA and pulmonary embolism occurred 11.3 ± 3.8 days post–index CA (Quebec only data). There was no statistically significant difference between rates of other major AEs during index hospitalization and post-discharge.
Among nonmajor AEs with a plausible association to the procedure, other noncardiac AEs were the most common (1.6%) followed by respiratory AEs (0.8%).
Temporal trends in adverse events related to CA
Over time, major AEs tended to decline from 3.6% in the one-half of patients with a remote date of index CA, to 3.3% in the one-half of patients with a more recent date of index CA (p = 0.39). Specifically, post-procedure CVA decreased by more than 50% in patients with the contemporary CA compared with patients with more remotely performed CA (12 CVAs vs. 28 CVAs; p = 0.003). However, the overall rates of PERD (p = 0.47), hemorrhage and hematoma (p = 0.37), and vascular complications (p = 0.19) did not change over time (Figure 2). Although the rate of PERD was unchanged over the study period, the time to PERD diagnosis decreased (7.6 ± 27.0 days, remote CAs vs. 2.8 ± 6.1 days, recent CAs; p < 0.05). The CHA2DS2-VASc score of patients undergoing procedures did not increase significantly over time (from 0.97 ± 1.05 to 0.98 ± 1.09 for recent CA procedures; p = 0.24).
Predictors of major AEs
In multivariable analysis, advanced age was the only independent predictor for the composite outcome of any major AE (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01 to 1.04) while age and female sex were associated with a higher risk of hemorrhage/hematoma (age: OR: 1.05; 95% CI: 1.00 to 1.10; female sex: OR: 1.62; 95% CI: 1.04 to 2.80). There were no statistically significant clinical predictors for CVA, PERD, vascular AEs, and pulmonary embolism.
Major AEs after repeat CAs
Repeat CA was performed in 1,170 (18.3%) of the 6,388 patients, with a mean time to first repeat CA of 487.4 ± 517.6 days. Overall, patients who underwent repeat CA had an elevated incidence of major AEs at repeat CA (5.0%) compared with the incidence of major AEs at index CA (3.5%) (Figure 3) (p < 0.01). The incidence of hemorrhage and hematoma increased from index to first repeat CA (1.4% to. 2.3%; p = 0.02). Similarly, the proportion of CA patients with PERD increased from index to repeat CA (1.0% vs. 1.9%; p = 0.008), with a decrease in the mean number of days to PERD diagnosis compared with PERD at index CA (0.8 ± 2.9 days vs. 4.4 ± 15.4 days; p < 0.05). There was no statistically significant difference in the incidence of 30-day mortality, CVA, vascular AEs, or pulmonary embolism between the index CA and first repeat CA.
Our study demonstrates that in the 2 most densely populated provinces in Canada: 1) 3.5% of patients experienced AEs within 30 days of index-CA; 2) the rate of post-procedure CVA appeared to decrease in more recent CA procedures; 3) the overall rate of PERD remained relatively stable over time; however, there was an increased proportion of late PERD (detected after discharge vs. during admission); 4) female sex and age were independent predictors of hemorrhage/hematoma; and 5) repeat CA procedures were associated with an increased likelihood of PERD and hemorrhage/hematoma compared with index CA.
Overall AE rates
This study is first to assess periprocedural major AEs from CA in the Canadian population. Overall, our results are consistent with the 1% to 6% major complication rate in the current published data (11–13). The incidence of individual major AEs in our study was also comparable (2,3,13,18–20). Despite potential differences in patient selection and ablation strategies, the incidence of major AEs from CA is similar to other countries (Table 3) (11–13).
The trend of decreasing incidence of major AEs shown in our cohort mirrors a similar trend published in other longitudinal studies. A worldwide survey of CAs found a 6% major AE rate in 2005 (13), and a 4.5% major AE rate in 2010 (14). Further evidence of a declining incidence of AEs (21,22) in a large single-center series reported a decrease in complication rate from 11.1% in 2002 to 1.6% in 2010 (2). The results of the meta-analysis from Gupta et al. (3) support such observational data, demonstrating a significant decrease in the complication rate to 2.6% in the past 6 years (3). Although more complex procedures are being undertaken in higher-risk patients, and more new centers are offering intervention, CA is becoming a safer therapy (3,20). This is likely related to refinement in ablation technique, technology, optimized periprocedural therapy, and increased experience (3,20).
The only predictor for the composite outcome of any major periprocedural AE was age (10,11).
Comparing one-half of our cohort (3,169 patients) who had CA from 2003 to 2010 to patients with more recent CAs from 2010 to 2013 (Quebec) or 2014 (Ontario), patients more recently undergoing the procedure had less post-procedural CVA despite similar CHA2DS2-VASC score. Prior studies reporting AF ablation complications between 2000 and 2010 found CVA rates to remain stable over time, despite improvements in technology and operator experience (2,18). Our more recent data demonstrating a decline in CVA after 2010 may be a reflective of a trend toward more aggressive periprocedural anticoagulation with increasing intraprocedural activated clotting time targets over time (23,24) and greater use of continued OAC perioperatively (25,26).
Pericardial effusion requiring drainage
Delayed cardiac effusion or tamponade is a more recently recognized rare complication of CA (27,28). Current published data indicates that irrigated catheter use and paroxysmal AF are independent predictors of delayed cardiac tamponade (29). The mechanism of delayed PERD remains unclear. Goossens et al. (27) suggest delayed PERD results from a rupture of the sealed CA-induced left atrial wall or small pericardial hemorrhages due to the intense post-procedural anticoagulation (27). Another possible explanation is Dressler’s syndrome, where nonhemorrhagic pericardial effusion accumulation develops suddenly (28,30).
Despite the advances in technology, including irrigated catheters, intracardiac echocardiography, and advances in 3-dimensional electroanatomic mapping systems, the overall rate of PERD did not change over time. In Deshmukh et al. (18), the frequency of PERD increased over time. Possible reasons for the constant proportion of PERD post-procedure could be more aggressive ablation and anticoagulation strategies (18). Irrigated tip catheters have advantages compared with conventional catheters by avoiding char formation and creating of deeper lesions that may improve ablation efficacy (19,31); however, deeper lesions may be associated increased risk of delayed PERD. Aldhoon et al. (10) reported that the utilization of ICE during CA was associated with reduced PERD (10); however, while ICE may improve procedural safety and early detection of acute PERD, it would not be expected to have an effect on late PERD.
Patients in our cohort appear to have had more major AEs at first repeat CA due to increases in PERD and hemorrhage/hematoma. Prior CA for AF is an independent risk factor for pericardial effusion or tamponade (20). Studies have shown CA results in scarring and fibrosis of the atrial wall with subsequent thinning (32,33). Increases in acute PERD at time of first repeat may be due to extended cauterization of tissue in the same possibly thin-walled location in the atrium, which may be more likely to cause pericardial inflammation and subsequent pericardial effusion or tamponade. With the use of open-irrigation catheters capable of creating large transmural lesions, and with more extensive ablation particularly in patients with persistent AF, prior CA appears to be an important predictor for PERD (20).
Other major AEs
Both sex and age are established predictors of bleeding (11). Our study corroborates with current published data that suggest a higher incidence of post-procedural hemorrhage/hematoma in the elderly and females (2,10,11,20). Differences in bleeds between males and females may be due to differences in the vascular anatomy (20,34). Likewise, elderly age is an accepted predictor of hemorrhage/hematoma, as veins have been shown to become less elastic later in life (10,11).
The risk of developing symptomatic pulmonary embolism from electrophysiology procedures is 0% to 1.7% (35,36). Pulmonary embolism is a rare complication of CA (35,36), but it can be fatal (36). Our results corroborate that there is a minimal incidence of pulmonary embolism in a population-based cohort of CA patients, although the incidence of pulmonary embolism doubles post-discharge compared with during CA hospitalization. Prior published data suggest that pulmonary embolism develops within 8.5 h (37) to 14 days (36) after any radiofrequency CA, regardless of procedural anticoagulation. On average, patients observed within a 12- to 24-h period without a complication are deemed safe and discharged (38). Nevertheless, close follow-up for late occurring, albeit rare, AEs is warranted.
The administrative data used in this analysis lack the detail available in trials and registries. We were unable to assess clinical or procedural variables that may be associated with AE outcomes, including type of AF, radiofrequency time, procedural anticoagulation or medications, venous access sites, number and size of sheaths, sedation, laboratory variables (ACT, INR, and so on) or ablation and imaging technology used. Also, we could not accurately differentiate between PERD and cardiac tamponade or identify atrioesophageal fistulae from administrative hospital records. Information on causes of death are also not available in provincial administrative data.
The increased frequency and widening indications for CA to treat AF warrants ongoing evaluation of real-world periprocedural AEs. We found a relatively low major AE rate that has appeared to decrease over time, especially for CVA, which is reassuring and suggests increasing safety of CA. Increased attention to late PERD needs to be taken, as a majority of periprocedural PERD events were diagnosed post-discharge. There is an increased risk of acute PERD and hemorrhage/hematoma at repeat CA. Continued efforts to minimize AEs are required to further improve the safety of CA for AF.
COMPETENCY IN MEDICAL KNOWLEDGE: CA for AF has a relatively low rate of AEs, with decreasing rates of CVA in recent years. There should be increased awareness and monitoring for symptoms of PERD that may present post-discharge and after repeat CA.
TRANSLATIONAL OUTLOOK 1: Although the increased risk of delayed PERD has been identified in this population-level analysis, with the low rates of events, the results should be replicated in other large observational studies.
TRANSLATIONAL OUTLOOK 2: Large-scale studies with device and procedural information should be undertaken to evaluate the effect of different technologies on the rate of periprocedural AEs from CA.
This study was supported by an operating grant from the Canadian Institutes of Health Research, a Clinical Research Scholar Award from Fonds de recherché du Quebec-Santé (to Dr. Essebag), and the study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Jackevicius has received a coinvestigator CIHR grant for AF ablation. Dr. Verma has received grants from Biosense Webster, Medtronic, and Bayer. Dr. Pilote holds a James McGill chair. Dr. Essebag has received honoraria from Biosense Webster, St. Jude Medical, Medtronic, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. Parts of this material are based on data and information compiled and provided by Canadian Institute of Health Information. However, the analyses, conclusions, opinions, and statements expressed herein are those of the authors. Dr. Pilote and Dr. Essebag contributed equally to this work as cosenior authors. Gregory Feld, MD, served as Guest Editor for this paper.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- atrial fibrillation
- adverse event
- catheter ablation
- cerebrovascular accident
- pericardial effusion requiring drainage
- transient ischemic attack
- Received December 19, 2016.
- Revision received April 5, 2017.
- Accepted April 11, 2017.
- 2017 American College of Cardiology Foundation
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