Surgical Ablation for AF in Cardiac Surgery
Surgical Ablation for AF in Cardiac Surgery
Research efforts into the underlying pathophysiology and therapies for AF have empowered clinicians with the knowledge and tools to tackle this significant healthcare burden. For patients with AF and concurrent indications for CS, concomitant SA emerged as an effective treatment option. The efficacy and clinical outcomes of concomitant SA and CS are not well established. Thus, the present study aims to report the clinical outcomes of CS+SA versus CS alone via a cumulative meta-analysis of RCTs.
The restoration of SR in AF patients represents a crucial therapeutic strategy, given that SR is a profound, independent predictor of quality of life and survival.35–– The present meta-analysis demonstrated a higher SR prevalence in the CS+SA group at discharge, 3-month, 6-month, and beyond 12-month follow-up compared to the CS group, consistent with previous studies. Furthermore, the present cumulative meta-analyses demonstrates that both magnitude and precision of long-term >1 year SR point values have remained essentially unchanged since the RCTs published in 2004. There is consistent evidence that concomitant surgical ablation is superior to cardiac surgery only in terms of long-term SR restoration in AF patients.
In the present review, acceptable 30-day mortality rates (range: 0–15%) and all-cause mortality rates (range: 0–17%) were reported in the included RCTs. No significant difference was found between CS+SA and CS groups in terms of 30-day and all-cause mortality. Furthermore, cumulative meta-analysis showed that these trends have stabilised for the last decade, suggesting maturation of trials used to evaluate surgical ablation over time. This suggests that further small randomised trials will not substantially add to the evidence base, but rather emphasises the need for pragmatic, well-designed randomised studies with adequate power and sample sizes.
Previous meta-analyses by Khargi et al and Cheng et al have argued that permanent pacemaker implantations remained high following concomitant surgical AF ablation, suggesting that postoperative iatrogenically induced bradycardia and arrhythmias still warrant concern. However, there was significant heterogeneity in their analysis due to the inclusion of non-RCTs, and the need for permanent pacemakers have been reported anywhere from 6% to 56% in the literature, depending on lesion patterns and energy sources used. This was not reflected in the present meta-analysis, with no difference in permanent pacemaker implantations in the CS+SA group compared to the CS-only group.
AF is a major risk factor for strokes and thromboembolism, and thus elimination of AF via surgical ablation may have a protective effect against these risks. From 10 RCTs and 735 patients, no significant difference was found in terms of neurological events between the CS+SA and CS alone groups. However, the effect of anticoagulation therapy on stroke outcomes was difficult to ascertain, which varied among the included RCTs. This may account for underestimated stroke incidence, and therefore the meta-analysis results should be viewed with caution. Overall, the current study demonstrates that superior SR can be achieved with surgical ablation without additional risk of neurological events.
There are several limitations to this cumulative meta-analysis. Subgroup analysis based on the type of cardiac surgery, energy source or lesion set of surgical ablation was not feasible due to the low number of RCTs in each subgroup, the lack of comparative data for different lesion sets, as well as type of AF pathology. These outcomes will be crucial for resolving the current debate in the literature, propelled by conflicting results on the efficacy of surgical ablation in patients with paroxysmal and persistent AF. Furthermore, AF monitoring was mainly based on ECG and 24 h Holter methods at 3-month or 6-month intervals, which may not have detected paroxysmal or asymptomatic recurrent episodes. Small sample size and inadequate statistical power of the included studies are also significant limitations. Potential reporting and publication bias and the varying skill-sets and experiences of surgeons may further exaggerate the overall effect size of the endpoints studied in this meta-analysis. Additionally, the narrow range of clinical outcomes were reported by the RCTs, with only six out of the 16 included studies reporting outcomes at follow-up >1 year.
To overcome these key constraints and inadequate power of available RCTs in the evidence base, we propose a potential design for a large pragmatic randomised study. The study endpoints will be established in accordance with the recommendations of consensus statements from the American Heart Association, American College of Cardiology, and European Heart Rhythm Association. The primary endpoint hypothesis is that surgical ablation for atrial fibrillation would result in greater restoration of sinus rhythm at 1-year follow-up compared to cardiac surgery without ablation. Other endpoints studied should include mortality rates, neurological events, anticoagulation, antiarrhythmic therapies, and the need for implantable cardioverter defibrillator and pacemaker devices. These outcomes should be assessed at 1-year and 5-year follow-ups.
According to previous publications and the current meta-analysis, we assumed that the sinus rhythm restoration rate would be 70% in the ablation group and 30% in the non-ablation cardiac surgery group. The sample size required to detect this difference with 95% CI and 80% statistical power is 23 patients in each group, with effect size of 0.75. However, to facilitate subgroup analysis with regards to energy source (CS vs radiofrequency vs cryoablation vs microwave) and lesion sets (biatrial vs left atrial vs pulmonary vein isolation), the level of significance α should be adjusted to α* the overall type I error rate, resulting in α* value of 0.42%. Furthermore, the smallest primary endpoint proportion within the subgroup categories was 57.5% rather than 70%. To detect this, smaller effect size of 0.4 with the adjusted overall error rate requires a sample of 218 in each group. The expected attrition rates due to drop-out and failure to obtain endpoint information at 1-year and 5-year follow-up should also be compensated for, increasing the required sample size for each group to 251. As such, this proposed trial design will be adequately powered to detect any efficacy differences between various energy sources and lesion sets used in concomitant surgical ablation and cardiac surgery.
In summary, we conclude that surgical ablation is a viable treatment for AF during concomitant cardiac surgery without increased mortality or morbidity risks. Short-term, mid-term and long-term prevalence of SR are significantly improved in patients who undergo surgical ablation. However, limited sample sizes and inadequate power of available randomised evidence means that there is still uncertainty surrounding choice of technique and lesion sets, which should be addressed in large, multi-institutional and adequately powered randomised studies.
Discussion
Research efforts into the underlying pathophysiology and therapies for AF have empowered clinicians with the knowledge and tools to tackle this significant healthcare burden. For patients with AF and concurrent indications for CS, concomitant SA emerged as an effective treatment option. The efficacy and clinical outcomes of concomitant SA and CS are not well established. Thus, the present study aims to report the clinical outcomes of CS+SA versus CS alone via a cumulative meta-analysis of RCTs.
The restoration of SR in AF patients represents a crucial therapeutic strategy, given that SR is a profound, independent predictor of quality of life and survival.35–– The present meta-analysis demonstrated a higher SR prevalence in the CS+SA group at discharge, 3-month, 6-month, and beyond 12-month follow-up compared to the CS group, consistent with previous studies. Furthermore, the present cumulative meta-analyses demonstrates that both magnitude and precision of long-term >1 year SR point values have remained essentially unchanged since the RCTs published in 2004. There is consistent evidence that concomitant surgical ablation is superior to cardiac surgery only in terms of long-term SR restoration in AF patients.
In the present review, acceptable 30-day mortality rates (range: 0–15%) and all-cause mortality rates (range: 0–17%) were reported in the included RCTs. No significant difference was found between CS+SA and CS groups in terms of 30-day and all-cause mortality. Furthermore, cumulative meta-analysis showed that these trends have stabilised for the last decade, suggesting maturation of trials used to evaluate surgical ablation over time. This suggests that further small randomised trials will not substantially add to the evidence base, but rather emphasises the need for pragmatic, well-designed randomised studies with adequate power and sample sizes.
Previous meta-analyses by Khargi et al and Cheng et al have argued that permanent pacemaker implantations remained high following concomitant surgical AF ablation, suggesting that postoperative iatrogenically induced bradycardia and arrhythmias still warrant concern. However, there was significant heterogeneity in their analysis due to the inclusion of non-RCTs, and the need for permanent pacemakers have been reported anywhere from 6% to 56% in the literature, depending on lesion patterns and energy sources used. This was not reflected in the present meta-analysis, with no difference in permanent pacemaker implantations in the CS+SA group compared to the CS-only group.
AF is a major risk factor for strokes and thromboembolism, and thus elimination of AF via surgical ablation may have a protective effect against these risks. From 10 RCTs and 735 patients, no significant difference was found in terms of neurological events between the CS+SA and CS alone groups. However, the effect of anticoagulation therapy on stroke outcomes was difficult to ascertain, which varied among the included RCTs. This may account for underestimated stroke incidence, and therefore the meta-analysis results should be viewed with caution. Overall, the current study demonstrates that superior SR can be achieved with surgical ablation without additional risk of neurological events.
There are several limitations to this cumulative meta-analysis. Subgroup analysis based on the type of cardiac surgery, energy source or lesion set of surgical ablation was not feasible due to the low number of RCTs in each subgroup, the lack of comparative data for different lesion sets, as well as type of AF pathology. These outcomes will be crucial for resolving the current debate in the literature, propelled by conflicting results on the efficacy of surgical ablation in patients with paroxysmal and persistent AF. Furthermore, AF monitoring was mainly based on ECG and 24 h Holter methods at 3-month or 6-month intervals, which may not have detected paroxysmal or asymptomatic recurrent episodes. Small sample size and inadequate statistical power of the included studies are also significant limitations. Potential reporting and publication bias and the varying skill-sets and experiences of surgeons may further exaggerate the overall effect size of the endpoints studied in this meta-analysis. Additionally, the narrow range of clinical outcomes were reported by the RCTs, with only six out of the 16 included studies reporting outcomes at follow-up >1 year.
To overcome these key constraints and inadequate power of available RCTs in the evidence base, we propose a potential design for a large pragmatic randomised study. The study endpoints will be established in accordance with the recommendations of consensus statements from the American Heart Association, American College of Cardiology, and European Heart Rhythm Association. The primary endpoint hypothesis is that surgical ablation for atrial fibrillation would result in greater restoration of sinus rhythm at 1-year follow-up compared to cardiac surgery without ablation. Other endpoints studied should include mortality rates, neurological events, anticoagulation, antiarrhythmic therapies, and the need for implantable cardioverter defibrillator and pacemaker devices. These outcomes should be assessed at 1-year and 5-year follow-ups.
According to previous publications and the current meta-analysis, we assumed that the sinus rhythm restoration rate would be 70% in the ablation group and 30% in the non-ablation cardiac surgery group. The sample size required to detect this difference with 95% CI and 80% statistical power is 23 patients in each group, with effect size of 0.75. However, to facilitate subgroup analysis with regards to energy source (CS vs radiofrequency vs cryoablation vs microwave) and lesion sets (biatrial vs left atrial vs pulmonary vein isolation), the level of significance α should be adjusted to α* the overall type I error rate, resulting in α* value of 0.42%. Furthermore, the smallest primary endpoint proportion within the subgroup categories was 57.5% rather than 70%. To detect this, smaller effect size of 0.4 with the adjusted overall error rate requires a sample of 218 in each group. The expected attrition rates due to drop-out and failure to obtain endpoint information at 1-year and 5-year follow-up should also be compensated for, increasing the required sample size for each group to 251. As such, this proposed trial design will be adequately powered to detect any efficacy differences between various energy sources and lesion sets used in concomitant surgical ablation and cardiac surgery.
In summary, we conclude that surgical ablation is a viable treatment for AF during concomitant cardiac surgery without increased mortality or morbidity risks. Short-term, mid-term and long-term prevalence of SR are significantly improved in patients who undergo surgical ablation. However, limited sample sizes and inadequate power of available randomised evidence means that there is still uncertainty surrounding choice of technique and lesion sets, which should be addressed in large, multi-institutional and adequately powered randomised studies.
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