Impact of previous cardiac surgery on long-term outcome of cavotricuspid isthmus-dependent atrial flutter ablation

Abstract

Aims

The aim of this study was to determine the acute and long-term outcome of radiofrequency catheter ablation (RFCA) for cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) in adults with and without previous cardiac surgery (PCS), and predictors of these outcomes. Structural alterations of the anatomical substrate of the CTI-AFL are observed in post-operative patients, and these may have an impact on the acute success of the ablation and in the long-term.

Methods and results

Clinical records of consecutive adults undergoing RFCA of CTI-AFL were analysed. Two main groups were considered: No PCS and PCS patients, who were further subdivided into acquired heart disease (AHD: ischaemic heart disease and valvular/mixed heart disease) and congenital heart disease [CHD: ostium secundum atrial septal defect (OS-ASD) and complex CHD]. Multivariate analysis identified clinical and procedural factors that predicted acute and long-term outcomes. A total of 666 patients (73% men, age 65 ± 12 years) were included: 307 of them with PCS. Ablation was successful in 647 patients (97%), 96% in the PCS group and 98% in the No PCS group (P = 0.13). Regression analysis showed that surgically corrected complex CHD was related to failure of the procedure [odds ratio 5.6; 95% confidence interval (CI) 1.6–18, P = 0.008]. After a follow-up of 45 ± 15 months, recurrences were observed in 90 patients (14%), more frequently in the PCS group: absolute risk of recurrence 18 vs. 10.5%, relative risk 1.71, 95% CI: 1.2–2.5, P = 0.006. Multivariate analysis indicated that the types of PCS [OS-ASD vs. No PCS: hazard ratio (HR) 2.57; 95% CI: 1.1–6.2, P = 0.03 and complex CHD vs. No PCS: HR 2.75; 95% CI: 1.41–5.48, P = 0.004], female gender (HR 1.55; 95% CI: 1.04–2.4, P = 0.048), and severe LV dysfunction (HR 1.36; 95% CI: 1.06–1.67, P = 0.04) were independent predictors of long-term recurrence.

Conclusion

Radiofrequency catheter ablation of CTI-AFL after surgical correction of AHD and CHD is associated with high acute success rates. The severity of the structural alterations of the underlying heart disease and consequently the type of surgical correction correlates with higher risk for recurrence.

Introduction

Cavotricuspid isthmus-dependent atrial flutter (CTI-AFL), an arrhythmia frequently seen in clinical practice, is the consequence of a macro-re-entrant circuit located in the right atrium (RA) between the tricuspid annulus on one side and the crista terminalis and the Eustachian ridge on the other side.¹ The functional block offered by these two barriers along with the slow conduction zone in the cavotricuspid isthmus enables the development and maintenance of this arrhythmia. Knowledge of this anatomical substrate, coupled with the low efficacy of antiarrhythmic drugs (AADs) have led to radiofrequency catheter ablation (RFCA) of the cavotricuspid isthmus becoming the first line treatment of CTI-AFL.²

Previous studies have shown that the structures involved in the CTI-AFL may have considerable variation, which affect the effectiveness of ablation.^3–7 Specifically, it has been found that patients with structural heart disease show marked morphological alterations of the isthmus area and correspondingly greater difficulty in obtaining isthmus block.^8,9 Among patients with structural heart disease those who have undergone cardiac surgery for correction of congenital or acquired heart disease (CHD and AHD, respectively) merit special interest; this is a population particularly at risk for development of atrial arrhythmias, because of the presence of suture lines, scars, and structural heart disease previous to surgery.^10,11 In this group of patients, the most common macro-re-entrant arrhythmia is CTI-AFL.^12–14

High success rates of CTI-AFL ablation have been reported in this population, but data on long-term recurrence are lacking or not definitive, since many studies have not differentiated CTI-AFL from other macro-re-entrant right atrial tachycardias, left atrial (LA) flutter, or focal tachycardias, which are characterized by different anatomical and electrophysiological substrates.¹²

Therefore, the aims of the present investigation were (i) to evaluate the effectiveness of the ablation procedure of CTI-AFL in patients with and without previous cardiac surgery (PCS) and (ii) to analyse the long-term outcome of such patients for potential predictors of recurrences and adverse events during follow-up.

Methods

Patient selection and data collection

In this retrospective multicentre study, we identified 307 patients from nine centres in Spain who had been referred for ablation of drug-refractory post-operative CTI-AFL. Only patients with final diagnosis of CTI-AFL were included. This group was compared with 359 patients referred for ablation of non-post-operative CTI-AFL.

Data regarding congenital and acquired defects and surgical history were obtained from hospital records. Information was collected about the clinical and electrophysiological features of the tachycardia, presenting symptoms, electrocardiographic findings, and number and characteristics of macro-re-entrant circuits induced during the electrophysiological study (EPS) prior to the ablation procedure. Uses of non-fluoroscopic electroanatomic mapping systems, targeted circuits, technical characteristics of the procedures in terms of duration, radioscopy times, type of catheters used, procedural success, and complications were all noted.

For the analysis of baseline characteristics, EPS, and ablation procedure, the group of patients undergoing cardiac surgery was considered as a whole. Subsequently, an analysis of predictors of acute success and long-term recurrences considering the type of underlying heart disease and surgery prior to ablation was performed. Patients with CHD were divided into two groups: those with isolated ostium secundum atrial septal defect (OS-ASD) who underwent right atriotomy without other incisions and those with complex CHD, with more extensive structural alterations and more complex surgical approach. Regarding the group of patients with AHD we considered separately those with isolated coronary artery disease in whom a coronary artery bypass graft surgery was performed from those with valvular or mixed valvular and ischaemic heart disease. Both groups of patients underwent cardiac surgery without RA atriotomy but were considered separately to emphasize the underlying heart disease.

Mapping and ablation technique

Under light sedation multipolar electrode catheters were inserted percutaneously into the femoral vein and, using single-plane fluoroscopy, were guided into the coronary sinus and His bundle recording positions. In the RA, a multipolar HALO catheter was placed in the vast majority of patients, if not possible (due to anatomical reasons or the presence of pacemaker leads), a quadripolar catheter was placed in the lateral RA. If AFL was not present at the onset of the procedure, it was induced using programmed electrical stimulation.

To delineate the tachycardia circuit, RA activation sequence and entrainment mapping protocols were used. Cavotricuspid isthmus-dependent atrial flutter was defined as a macro-re-entry circuit located in the RA between the endocardial barriers described above with short (<30 ms) post-pacing interval when pacing from the tricuspid annulus and concealed fusion plus short post-pacing interval when pacing from the CTI, confirming the CTI to be the protected zone of slow conduction. Three-dimensional (3D) electroanatomic mapping systems were also available in all centres and used at the operator's discretion. Bipolar activation and voltage maps were constructed using electroanatomic mapping systems during AFL to (i) identify the underlying mechanism and (ii) select target sites for ablation. If during the EPS, other circuits apart from the CTI-dependent AFL were induced they were targeted for ablation at the discretion of the operator.

Linear ablation in the CTI was performed until termination of the tachycardia was achieved, and bidirectional conduction block from the tricuspid annulus to the inferior vena cava was established. Bidirectional block across the line of ablation was assessed by using all the available manoeuvres at the time of ablation (activation sequence, differential pacing, transisthmus conduction time, double potentials separation, and polarity^15–17). If bidirectional block could not be achieved, the procedure was considered to have failed.

Follow-up

Following completion of the ablation procedure, all patients were followed by the electrophysiology team at each hospital. All centres carried out a thorough monitoring of adverse events, including AFL recurrence, onset of heart failure (HF), requirement for a pacemaker or implantable defibrillator, development of atrial fibrillation (AF), and death. All data relating to the clinical and electrophysiological characteristics of recurrences and re-ablation procedures were collected. For the purposes of this study, only CTI-AFL episodes were considered as true recurrences, and data regarding incidence and predictors of recurrences refer only to CTI-AFL episodes after a successful CTI ablation. Other types of arrhythmia recurrences in patients with ablation of more than one circuit other than CTI were also recorded.

Statistical analysis

Quantitative variables are given as mean ± SD and were compared using t-tests. Variables that did not follow normal distributions were compared using the Mann–Whitney test. Binary categorical variables were compared using χ² test. The analysis of factors related to recurrences was performed using the Cox proportional hazards model through a backward stepwise regression. Possible confounders were analysed testing three accepted confusion criteria: first we studied the relationship between potential confounders and the exposure (surgically corrected heart disease), and those variables that showed odds ratio (OR) < 0.67 or OR > 1.5 were further analysed. Variables that were not an intermediate cause between the exposure and the disease (recurrence, third criteria) and that were predictors of recurrence at univariate analysis [hazard ratio (HR) < 0.67 or HR > 1.5 or P < 0.2, second criteria] plus variables considered clinically relevant in previously published studies were included in the multivariate analysis. For all tests, a value of statistical significance of P < 0.05, two-sided was used. The data analysis was performed with SPSS 18.3 (SPSS Inc., Chicago, IL, USA).

Results

Patient population

The study population consisted of 666 patients, 307 of whom had undergone with PCS (PCS group) for correction of either AHD or CHD. Surgical correction of AHD was performed in 244 patients while 63 had undergone surgery for CHD. The most common CHDs were isolated OS-ASD (n = 22, 35% of CHD patients), tetralogy of Fallot (n = 11, 18% of CHD patients), valvular atresia (n = 8, 12.7% of CHD patients), and transposition of the great arteries (n = 4, 6.3% of CHD patients). Patients with AHD showed mostly ischaemic (41%) or valvular (57%) disease (Table 1).

The baseline characteristics of the sample are presented in Table 2. The majority of patients was male and the mean age at referral for ablation was 65 ± 12 years. Previous cardiac surgery patients showed significantly higher prevalence of pulmonary hypertension (PAH) and right chambers dilatation. The most common symptom during tachyarrhythmia was palpitations (52.1%).

Among patients with PCS mean age at surgery (27 vs. 60 years, P = 0.001) and mean age at ablation (48 vs. 67 years, P = 0.001) were lower in patients operated on for CHD compared with patients operated on for AHD. In contrast, the mean time from surgery to ablation was longer in patients operated on for CHD compared with patients operated for AHD (254 vs. 90 months, P < 0.001). No patients underwent concomitant MAZE ablation during surgery.

Electrophysiology study

Results of EPS are presented in Table 3. At the time of ablation, 50.5% (n = 336) of patients had used and failed at least one AAD, more frequently in patients with no PCS than in patients with PCS (55.7 vs. 44.4%, P = 0.004). From the electrocardiographic point of view, a typical flutter appearance was seen in 639 (95.9%) patients, and was more frequent in no PCS patients as compared with PCS patients (98.6 vs. 92.8%, P < 0.001). The mean tachycardia cycle length (CL) was 253 ± 32 ms, and it was longer in patients with PCS when compared with patients with no PCS. This resulted in higher 1:1 conduction and higher heart rate in patients with PCS when compared with no PCS patients (7.5 vs. 3.3%, P = 0.02 and 115 vs. 107 b.p.m., P < 0.001, respectively). Additional tachycardia circuits were identified in 31 (4.7%) patients. Overall, 718 circuits were mapped in 666 patients. In the PCS group, the presence of more than one circuit responsible for the tachycardia was observed more frequently than in patients with no PCS (6.8 vs. 2.8%, P = 0.01), and therefore a greater number of circuits were targeted during the ablation procedure (mean 1.1 vs. 1, P = 0.001).

Ablation procedure

The characteristics of the ablation procedure are presented in Table 3. The mean procedure duration was 90 ± 60 min and was longer in patients with PCS than in no PCS patients (117 vs. 65 min, P < 0.001). Electroanatomic mapping systems were used more frequently in patients with PCS (27%) than in patients with no PCS (2.8%, P < 0.001); similarly, fluoroscopy times were longer in PCS patients when compared with no PCS group (26 vs. 14 min, P < 0.001).). Eight-millimetre-tip catheter was used in the majority of patients (66.8%), followed by irrigated catheters (27.8% of patients).

The mean success rate for the overall population of patients was 97.3%. The success rate was only slightly higher in patients with no PCS compared with the PCS group (98.1 vs. 96.1%, P = 0.1). Successful ablation of CTI-AFL was achieved in 97% of patients with ischaemic heart disease, 97.2% of patients with valvular heart disease, 95.5% of patients with OS-ASD, and 90% of patients with complex CHD (RR for failure of the procedure complex CHD vs. No PCS: 5, 95% confidence interval (CI): 1.6–12, P = 0.01; CHD vs. AHD: 2.8, 95% CI: 0.97–8.5, P = 0.06, CHD vs. No PCS: 4.1, 95% CI: 1.4–12.1. P = 0.02; P-value for trend 0.015). On the univariate logistic regression analysis, the presence of surgically corrected complex CHD was associated with failure of the ablation procedure compared with no PCS group (OR 5.6; 95% CI: 1.6–18, P = 0.008).

The presence of more pronounced structural disease of the right heart, as indicated by PAH or RA enlargement, showed a trend towards a less successful ablation (95% for patients with PAH or RA enlargement vs. 97.8% for patients without, P = 0.08). Patients with LA dilatation or moderate to severe depression of left ventricular ejection fraction (LVEF) also showed a moderate trend towards lower success rates of the ablation procedure. The mean procedure length and fluoroscopy time were significantly longer in failed procedures.

The type of catheter used did not affect the efficacy of the ablation procedure; we observed high rates of success with both 8-mm-tip and irrigated-tip catheter (97.3 and 97.5%, respectively).

Complications were reported in 11 patients (1.7%). There was one case of complete heart block suffered by a patient with PCS that required pacemaker implantation. No other major complications were described.

Recurrences of atrial flutter

After a mean follow-up of 45 ± 15 months, recurrences were observed in 101 patients (15.2%) (Table 4). Among all recurrences, 73.3% (n = 74) occurred during the first 2 years post-ablation, mostly during the first 12 months (70.3% of 2-year recurrences, n = 52). Recurrences were more frequent in patients with PCS compared with no PCS (20.2 vs. 10.9%, P = 0.001). Recurrences after a successful index procedure (n = 647) were more likely to occur in patients with PCS (n = 53) than with no PCS (n = 37): the absolute risk of recurrence 18 vs. 10.5%, relative risk 1.71, 95% CI: 1.2–2.5, P = 0.006. The mean time to recurrence was 20 ± 17 months. The majority of patients with recurrences underwent re-ablation. Re-ablation was acutely successful in 94.5% of cases.

Acute procedural success and cumulative freedom from recurrence after a successful ablation (12 months, 24 months, and end of follow-up) are shown in Figure 1 according to surgical status. There is a trend towards more recurrences with increasing structural heart involvement and the complexity of the surgical repair.

In patients with a successful index procedure, univariate variables significantly related to recurrences were female gender, age at ablation, type of previous surgery, 1:1 AV conduction, right chambers dilatation, LA dilatation, CL longer than 253 ms, lower LVEF, and longer procedure time. Table 5 shows multivariate analysis of predictors of recurrence after RFCA. Three variables were identified as independent predictors of recurrences: type of PCS (valvular heart disease vs. No PCS: HR 1.66; 95% CI: 1.01–2.7, P = 0.05, OS-ASD vs. No PCS: HR 2.57; 95% CI: 1.1–6.2, P = 0.03 and complex CHD vs. No PCS: HR 2.75; 95% CI: 1.41–5.48, P = 0.004), female gender (HR 1.55; 95% CI: 1.04–2.4, P = 0.048), severe LV disfunction (HR 1.36; 95% CI: 1.06–1.67, P = 0.04). Figure 2 shows survival free of recurrences according to the presence and type of PCS.

Events during long-term follow-up

During the long-term follow-up, AF was observed in 234 patients (35.1%) (Table 4). Atrial fibrillation was more frequent, although not significant, in the no PCS group compared with patients with PCS (36.8 vs. 33.2%, P = 0.3) and it was more frequently persistent or permanent in PCS patients.

Table 4 shows the observed non-arrhythmic events during follow-up. A permanent pacemaker was implanted in 80 patients (12%) and in-hospital admission for HF was required in 129 patients (19.4%). At the end of follow-up, 469 patients (70.4%) maintained sinus rhythm, and the remaining patients were in AF (22.1%) or had a paced rhythm (4.3%). There was a trend towards less sinus rhythm and more AF in PCS compared with no PCS patients (73 vs. 67% and 25 vs. 20%, both not significant). A total of 80 patients (12%) died during the follow-up period, 37 (5.6%) for cardiac cause and 43 (6.5%) for non-cardiac cause. Among cardiac deaths 24 (65%) were due to progressive HF and 10 (27%) were due to sudden death.

Discussion

Main findings

The aim of this retrospective analysis involving a large number of patients was to describe the success rates of CTI-AFL ablation and long-term outcome in different clinical settings. It found that the effectiveness of the ablation was high in all types of patients, but patients with CHD, specifically those with surgically corrected complex CHD, showed significantly lower rates of success. The rate of recurrences during follow-up differed among groups, being intimately related to the type and severity of the underlying heart disease and the extent of the surgical repair. In particular, post-operative patients showed significantly higher recurrence rates, especially those operated on for CHD

Acute ablation success

The present study found that rates of successful ablation of CTI-AFL were high in the study population and not far from previously published studies.^12,18 While this overall result shows that it is possible to achieve high rates of isthmus block, not all subgroups were found to behave the same way. Patients operated on for AHD showed success rates similar to no-PCS patients, although with longer fluoroscopy time and longer procedures.¹² Patients with CHD, despite the higher use of irrigated catheters and fluoroscopic navigation systems showed lower rates of success. So, despite sharing the same tachycardia circuit and electrophysiological substrate, the differences in the anatomical characteristics could account for the acute results of the ablation. The difference in acute CTI-AFL ablation success between patients post-operative from CHD and no-PCS patients has not been addressed previously although some studies have reported comparable data.¹³ Several factors could account for the difficulty in obtaining effective ablation in patients with post-operative CTI-AFL: ability to easily access the tachycardia circuit with the ablation catheter can be complicated by anatomical barriers caused by surgical repair. In some cases, catheter stability can be compromised by severe tricuspid regurgitation. Finally, the presence of hypertrophy and/or fibrosis, markedly enlarged RA or PAH may have a negative impact on the transmurality of the ablation lesions.

Recurrences

The overall recurrence rate in our population (15.2%) is moderately higher than previously reported. The meta-analysis of Perez et al.,¹⁸ which has collected the highest number of patients with CTI-AFL ablation so far, reported a recurrence rate of 10% but it should be noted that the prevalence of patients with CHD was minimal and that follow-up was just about 14 months. We observed a clear difference in recurrence rate between patients without PCS and those operated for AHD or CHD, the latter being those with the highest recurrence rate.¹⁹ In our study, the presence of PCS was found to be an independent predictor of recurrence after ablation of CTI-AFL; even after having demonstrated bidirectional isthmus block this group of patients shows high rates of recurrences. Cabrera et al.^7,8 observed that patients with structural heart disease have longer CTI, more fibrotic component in the CTI area, and tissue hypertrophy. Furthermore, there is evidence that these anatomical abnormalities are associated with an increased number of RF pulses, increased need to rely on irrigated catheters, and longer ablation procedures.^8,9 This is consistent with the observation of a trend towards increased recurrence in case of more serious underlying structural alteration. Patients with complex CHD and OS-ASD are characterized by a higher involvement of the right heart which is also affected by surgical atriotomies, this occurs to a lesser extent in patients with AHD. These factors may account partially for these high recurrence rates after an effective ablation. Anatomic abnormalities related to surgery in addition to structural and haemodynamic impairment such as atrial dilatation or PAH could promote fibre reconnection of the CTI area and restore the flutter circuit. In this setting, a careful check of the isthmus block is advisable, using all available techniques. In some cases, evaluation of CTI block with adenosine could be considered, which has recently been shown to be useful in assessing the degree of recovery of post-ablation transisthmus conduction.^20,21 Furthermore, a positive response to the adenosine test has been related to higher long-term recurrence.^20,21

Study limitations

This is a retrospective study with the intrinsic limitations related to this type of study model. An attempt was made to collect all the variables of interest but we cannot rule out the possibility that some variables were not considered. The baseline characteristics of the two groups analysed were not homogeneous, by virtue of the underlying heart disease, but this weakness is to some extent compensated for by the use of multivariate analysis. Given the retrospective nature of the study, the techniques used to evaluate the complete bidirectional block of the CTI may have changed over the inclusion period. As a result, recently described techniques showing high predictive value of complete CTI block²² could not be used in a number of the study patients, and these may have impacted on outcomes. Finally, only clinically symptomatic recurrences were recorded and monitoring to detect non-symptomatic episodes was not conducted, so the real incidence of recurrences may have been underestimated.

Conclusions

Radiofrequency catheter ablation of CTI-AFL after surgical correction of AHD and CHD is associated with high acute success rates, nevertheless patients operated on for CHD have success rates significantly lower than the non-operated patients. The presence of PCS is an independent risk factor for CTI-AFL recurrence, specifically in patients operated on for complex CHD and OS-ASD. These findings could be in relation to the anatomical changes in the pathophysiological substrate of CTI-AFL, typical of patients with PCS.

Conflict of interest: none declared.

References

Author notes