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Department of Cardiology, Prince of Wales Hospital, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, AustraliaHeart Research Institute, Sydney, NSW, Australia
Atrial fibrillation (AF) often coexists with congestive cardiac failure (CCF), with multiple treatment options available.
Methods
Systematic review and meta-analysis of randomised control trials (RCT) comparing pulmonary vein isolation (PVI), pharmacological rate control, and atrioventricular junction ablation with pacemaker insertion (AVJAP) for AF, with a subgroup analysis in patients with CCF. We analysed changes in left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, six-minute walk distance (6MWD), treadmill exercise time, and treatment complications. Results were expressed as weighted mean differences (WMD) with 95% Confidence-Intervals (95%CI).
Results
We included seven RCT (425 participants). PVI was associated with a greater increase in LVEF (WMD+6.5%, 95%CI:+0.6to+12.5) and decrease in MLHFQ score (WMD-11.0, 95%CI:-2.6to-19.4) than pharmacological rate control in patients with CCF. PVI was also associated with a greater increase in LVEF (WMD+9.0%, 95%CI:+6.3to+11.7) and 6MWD (WMD+55.0metres, 95%CI:+34.9to+75.1), and decrease in MLHFQ score (WMD-22.0, 95%CI:-17.0to-27.0), compared to AVJAP in patients with CCF. Irrespective of cardiac function, pharmacological rate control had similar effects to AVJAP on LVEF (WMD+0.6%, 95%CI:-8.3to+9.4) and treadmill exercise time (WMD+0.5 minutes, 95%CI:-0.4to+1.3).
Conclusions
Our results support the clinical implementation of PVI over AVJAP or pharmacological rate control in AF patients with CCF, who may or may not have already trialled pharmacological rhythm control.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation – An update of the 2010 ESC Guidelines for the management of atrial fibrillation.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation – An update of the 2010 ESC Guidelines for the management of atrial fibrillation.
] recommending whether to use pharmacological rate or rhythm control depend on age, symptoms, haemodynamic instability, the presence of a reversible cause, the duration of AF and concurrent cardiovascular disease. However, several large multi-centre randomised control trials (RCT) have failed to demonstrate a clear superiority of either approach [
] compared pharmacological rate and rhythm control specifically in a group of 1376 patients with AF and co-existing CCF (left ventricular ejection fraction (LVEF) ≤ 35%), and did not demonstrate a statistically significant difference between the two strategies.
Non-pharmacological treatments include percutaneous pulmonary vein isolation (PVI) and atrioventricular junction ablation with pacemaker insertion (AVJAP). Current guidelines [
2012 focused update of the ESC Guidelines for the management of atrial fibrillation – An update of the 2010 ESC Guidelines for the management of atrial fibrillation.
], based on multi-centre RCT comparing PVI to pharmacological rhythm control, recommend PVI in patients with paroxysmal or persistent symptomatic AF refractory to antiarrhythmic medications. PVI is also recommended as first-line therapy in patients with symptomatic paroxysmal AF who have a low risk of stroke, no structural heart disease, and state a preference for interventional treatment. AVJAP is recommended [
2012 focused update of the ESC Guidelines for the management of atrial fibrillation – An update of the 2010 ESC Guidelines for the management of atrial fibrillation.
] in patients where pharmacological rate control has been unsuccessful and in patients with symptomatic AF recurrences despite pharmacological rhythm control or prior PVI attempts.
Despite evidence in the literature comparing pharmacological rhythm control to the three alternative treatments (pharmacological rate control, PVI or AVJAP), there are few RCT comparing these three options to each other. Furthermore, patients who have already unsuccessfully trialled or are unsuitable for pharmacological rhythm control will commonly be offered these treatment options. We therefore aimed to compare pharmacological rate control, PVI, and AVJAP, in patients with AF, and determine their effects on LVEF, symptoms, and functional capacity. Specifically, we aimed to determine treatment effects in patients with AF and concomitant CCF or left ventricular (LV) dysfunction.
Methods
Eligibility Criteria and Study Selection
We included RCT where our interventions of interest were compared in patients with atrial fibrillation with a minimum follow-up period of six months. We excluded studies where patients had atrial flutter or other forms of supraventricular tachycardia. Pharmacological rate control was defined based on the medication classes listed in the European Heart Journal's 2010 guidelines for AF management [
2012 focused update of the ESC Guidelines for the management of atrial fibrillation – An update of the 2010 ESC Guidelines for the management of atrial fibrillation.
], and pharmacological rhythm control was excluded. PVI was defined as application of radiofrequency energy or cryotherapy via a percutaneously-inserted catheter to ablate tissue surrounding the pulmonary veins in the left atrium [
]. AVJAP was defined as catheter-mediated radiofrequency ablation of the atrioventricular junction or His bundle, followed by insertion of a permanent implantable pacing device [
Prospective randomized study of ablation and pacing versus medical therapy for paroxysmal atrial fibrillation: effects of pacing mode and mode-switch algorithm.
Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction.
Three independent researchers searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (1946 to April 2014), and Embase (1966 to April 2014) using the Medical Subject Headings (MeSH) and free text terms: ‘atrial fibrillation’, ‘catheter ablation’, ‘radiofrequency ablation’, ‘pulmonary vein isolation’, ‘atrioventricular junction ablation’, ‘atrioventricular node ablation’, and ‘His bundle ablation’. Ongoing trials were reviewed through the US National Institutes of Health Clinical Trials registry, the Current Controlled Trials database, and grey literature through the Open Grey database. There were no search restrictions based on date of publication or language. Reference lists of relevant trials, systematic reviews, and review articles were subsequently manually searched in an attempt to identify any RCT not identified by electronic searches.
Data Collection and Items
Data were extracted independently and in duplicate from eligible publications [
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
] using a standardised data extraction template. We recorded: author(s), year of publication, RCT inclusion and exclusion criteria, RCT size and duration, and completeness of follow-up. Specifically, we recorded data for the following outcome measures: percentage change in left ventricular ejection fraction (LVEF), change in symptoms of CCF as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score (points), change in the distance (metres) a participant could walk in six minutes (6MWD), change in the time (minutes) a participant could exercise on a treadmill, and the number and type of complications. A meta-analysis was conducted for all outcome measures listed except complications.
Risk of Bias in Individual Studies
We assessed methodological quality within studies (Data supplement A) using the Cochrane risk of bias tool [
Higgins J, Green S. (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from http://handbook.cochrane.org.
] which objectively assesses risk of bias in six specific domains. Specifically, sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective outcome reporting are considered.
Summary Measures and Statistical Synthesis of Results
Continuous outcomes were synthesised as weighted mean differences (WMD) with their 95% confidence intervals (CI). For all analyses, a p-value of ≤ 0.05 was considered to represent a statistically significant result. The random effects model of analysis was used, as there was expected clinical and methodological heterogeneity between studies and hence this should be accounted for when computing the summary effect estimate. Revman version 5.2 [
] was used for meta-analyses. We performed a pre-specified subgroup analysis to determine whether the effects of treatment differed in patients with CCF.
Results
Study Selection, Characteristics and Outcomes
We identified 7878 articles and reviewed 622 RCT in full (Figure 1). We included seven RCT [
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
] of the six RCT with a pharmacological rate control group administered beta-blockers, non-dihydropyridine calcium channel antagonists, and/or digitalis glycosides only. In one [
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
] RCT, three participants were treated with either amiodarone or sotalol as an interim rate-controlling agent for rapid ventricular response rate. Duration of follow-up ranged from six months to 12 months. Outcomes reported varied amongst studies (Table 2). Change in LVEF was the most commonly reported outcome, followed by change in MLHFQ score.
The first number corresponds to the number of patients in the first comparison group, and the second number corresponds to the number of patients in the second comparison group.
A positive WMD represents an incremental change in the outcome measure, favouring treatment with the first comparison group. A negative WMD represents a decremental change in the outcome measure, favouring treatment with the first comparison group.
The first number corresponds to the number of patients in the first comparison group, and the second number corresponds to the number of patients in the second comparison group.
A positive WMD represents an incremental change in the outcome measure, favouring treatment with the first comparison group. A negative WMD represents a decremental change in the outcome measure, favouring treatment with the first comparison group.
The first number corresponds to the number of patients in the first comparison group, and the second number corresponds to the number of patients in the second comparison group.
A positive WMD represents an incremental change in the outcome measure, favouring treatment with the first comparison group. A negative WMD represents a decremental change in the outcome measure, favouring treatment with the first comparison group.
The first number corresponds to the number of patients in the first comparison group, and the second number corresponds to the number of patients in the second comparison group.
A positive WMD represents an incremental change in the outcome measure, favouring treatment with the first comparison group. A negative WMD represents a decremental change in the outcome measure, favouring treatment with the first comparison group.
Results reaching statistical significance are in bold font. LEGEND AVJAP=atrioventricular junction ablation with pacemaker insertion; CI=confidence intervals; LVEF=left ventricular ejection fraction; MLHFQ=Minnesota Living with Heart Failure Questionnaire; PRC=pharmacological rate control; PVI=pulmonary vein isolation; WMD=weighted mean difference; 6MWD=6-minute walk distance
PVI vs PRC
3 (70/67)
+6.5 (+0.6 to +12.5)
0.03
3 (71/67)
−11.0 (−19.4 to −2.6)
0.01
2 (43/41)
+15.4 (−21.7 to +52.5)
0.41
-
-
-
PVI vs AVJAP
1 (41/40)
+9.0 (+6.3 to +11.7)
<0.00001
1 (41/40)
−22.0 (−27.0 to −17.0)
<0.00001
1 (41/40)
+55.0 (+34.9 to +75.1)
<0.00001
-
-
-
PRC vs AVJAP
2 (71/60)
+0.6 (−8.3 to +9.4)
0.90
1 (26/28)
−4.0 (−13.6 to +5.6)
0.41
-
-
-
3 (84/74)
+0.5 (−0.4 to +1.3)
0.27
Percutaneous intervention (PVI or AVJAP) vs PRC
5 (130/138)
+3.9 (−1.7 to +9.4)
0.17
4 (99/93)
−8.8 (−15.5 to −2.0)
0.01
-
-
-
-
-
-
Rhythm (PVI) vs rate (PRC or AVJAP) control
4 (111/107)
+7.5 (+3.7 to +11.2)
<0.0001
4 (112/107)
−14.8 (−23.5 to −6.0)
0.0009
3 (84/81)
+35.6 (+2.4 to +68.7)
0.04
-
-
-
a The first number corresponds to the number of patients in the first comparison group, and the second number corresponds to the number of patients in the second comparison group.
b A positive WMD represents an incremental change in the outcome measure, favouring treatment with the first comparison group. A negative WMD represents a decremental change in the outcome measure, favouring treatment with the first comparison group.
c Results reaching statistical significance are in bold font.LEGENDAVJAP = atrioventricular junction ablation with pacemaker insertion; CI = confidence intervals; LVEF = left ventricular ejection fraction; MLHFQ = Minnesota Living with Heart Failure Questionnaire; PRC = pharmacological rate control; PVI = pulmonary vein isolation; WMD = weighted mean difference; 6MWD = 6-minute walk distance
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Comparing PVI (n=70 patients) to pharmacological rate control (n=67), we observed a 6.5% higher increase in LVEF favouring PVI (3 RCT, WMD+6.5, 95%CI +0.6 to +12.5, p=0.03) (Figure 2). When PVI (n=41) was compared to AVJAP (n=40), PVI resulted in an increase in LVEF which was 9.0% higher than AVJAP (1 RCT, WMD+9.0, 95%CI +6.3 to +11.7, p<0.01). Notably, these RCTs comparing PVI to pharmacological rate control or AVJAP included patients with CCF only. Also, PVI (n=111) was superior to any rate control strategy (pharmacological or AVJAP, n=107) in patients with CCF, with a 7.5% higher increase in LVEF (4 RCT, WMD+7.5, 95%CI +3.7 to +11.2, p<0.01).
Figure 2Change in LVEF (%) in pharmacological rate control versus percutaneous intervention (PVI or AVJAP) groups across 5 studies.
Overall, there was no significant difference in LVEF when pharmacological rate control (n=71) was compared to AVJAP (n=60) in patients irrespective of cardiac function (2 RCT, WMD+0.6, 95%CI −8.3 to +9.4) (Figure 2). When only CCF patients were examined, pharmacological rate control (n=24) and AVJAP (n=26) still had similar effects on LVEF (1 RCT, WMD-4.0, 95%CI −11.0 to +3.0). Finally, when percutaneous intervention (either PVI or AVJAP, n=130) was compared to pharmacological rate control (n=138), there was no significant difference in change in LVEF (5 RCT, WMD+3.9, 95%CI −1.7 to +9.4) (Figure 2). However, when only patients with CCF were examined (n=91 pharmacological rate control, n=96 percutaneous intervention), a significant 6.1% higher increase in LVEF was observed in patients treated percutaneously (4 RCT, WMD+6.1, 95%CI +1.4 to +10.7, p=0.01).
Change in MLHFQ Score
Change in MLHFQ score was assessed by RCTs which exclusively recruited patients with CCF. PVI (n=71) was superior to pharmacological rate control (n=67), with a decrease in MLHFQ score which was 11.0 points greater in patients treated with PVI than medication (3 RCT, WMD-11.0, 95%CI −19.4 to −2.6, p=0.01) (Figure 3). When PVI (n=41) was compared to AVJAP (n=40), the decrease in MLHFQ score was 22.0 points greater in the PVI group (1 RCT, WMD −22.0, 95%CI −27.0 to −17.0, p<0.01). Furthermore, the decrease in MLHFQ score was 14.8 points greater in patients treated with PVI (n=112) versus any rate control (pharmacological or AVJAP, n=107) (4 RCT, WMD −14.8, 95%CI −23.5 to −6.0, p<0.01).
Figure 3Change in MLHFQ score (points) in pharmacological rate control versus percutaneous intervention (PVI or AVJAP) across 4 studies.
There was no difference in change in MLHFQ score when pharmacological rate control (n=26) was compared to AVJAP (n=28) (1 RCT, WMD −4.0, 95%CI −13.6 to +5.6) (Figure 3). Finally, comparing percutaneous intervention (n=99) to pharmacological rate control (n=93), we observed a decrease in MLHFQ score which was 8.8 points greater in the percutaneous group (4 RCT, WMD −8.8, 95%CI −15.5 to −2.0, p=0.01) (Figure 3).
Change in 6MWD
Change in 6MWD was assessed by RCTs which exclusively recruited patients with CCF. There was no difference in change in 6MWD when PVI (n=43) was compared to pharmacological rate control (n=41) (2 RCT, WMD +15.4, 95%CI −21.7 to +52.5) (Figure 4). When PVI (n=41) was compared to AVJAP (n=40), PVI was associated with a 55 metre higher increase in 6MWD (1 RCT, WMD +55.0, 95%CI +34.9 to +75.1, p<0.01) (Figure 4). Finally, increase in 6MWD was 35.6 metres greater in patients treated with PVI (n=84) than any rate control (pharmacological or AVJAP, n=81) (3 RCT, WMD +35.6, 95%CI +2.4 to +68.7, p=0.04).
Figure 4Change in 6MWD (metres) in rhythm control (PVI) versus rate control (AVJAP or pharmacological) groups across 3 studies.
Overall, there was no difference in change in treadmill exercise time when pharmacological rate control (n=84) was compared to AVJAP (n=74) (3 RCT, WMD +0.5, 95%CI −0.4 to 1.3) (Figure 5). Specifically in patients with CCF (pharmacological rate control n=21; AVJAP n=24), there remained no difference (1 RCT, WMD +0.4, 95%CI −1.6 to 2.4).
Figure 5Change in treadmill exercise time (minutes) in pharmacological rate control versus AVJAP groups across 3 studies.
Complications reported in the seven RCT are summarised in Data Supplement B. Due to the small number of RCT which met our eligibility criteria, and the low incidences of complications across the seven RCT, there was no opportunity to synthesise data in meta-analysis.
Discussion
In this systematic review of seven RCT including data on 425 participants, we compared the effects of PVI, AVJAP and pharmacological rate control on left ventricular function, symptoms of heart failure, and functional capacity in patients with AF. Using a subgroup analysis, we further investigated the important clinical question of optimum AF management in setting of concomitant CCF or LV dysfunction.
We found that CCF patients treated with PVI had a greater improvement in LVEF and MLHFQ score versus pharmacological rate control, and a greater improvement in LVEF, MLHFQ score, and 6MWD versus AVJAP. When we compared PVI to rate control (pharmacological and AVJAP) as a single group, rhythm control was superior to rate control for all outcomes. These findings suggest that in AF patients with CCF, PVI is significantly superior to any form of rate control (AVJAP or pharmacological) for improvement in LV function, symptoms of heart failure, and functional capacity.
Comparing percutaneous intervention (PVI or AVJAP) to pharmacological rate control irrespective of cardiac function, the percutaneous approach was superior for improvement in the MLHFQ score only. In patients with CCF, however, the percutaneous approach led to a significant improvement in LVEF (presumably driven by PVI over AVJAP). Finally, there was no difference between AVJAP and pharmacological rate control in either the whole cohort, or the CCF subgroup, with respect to the study outcomes.
A decision to focus on the heart failure subgroup was made as AF commonly co-exists with CCF and can complicate its management. AF contributes to the onset and progression of CCF via loss of atrial systole, rapid ventricular rate, and irregular ventricular filling time [
]. However, altered cardiac haemodynamics (elevated cardiac filling pressures), dysregulation of intracellular calcium, and neuroendocrine dysfunction in CCF also predisposes to the onset of AF [
]. Several studies have shown that the co-existence of AF and CCF yields a poorer prognosis and worse outcomes than either of the conditions in isolation [
2012 focused update of the ESC Guidelines for the management of atrial fibrillation – An update of the 2010 ESC Guidelines for the management of atrial fibrillation.
]. Thus, a targeted, evidence-based approach to management must be implemented.
A key limitation of this review was the relatively small number of RCT suitable for inclusion in the meta-analysis, and subsequently small cohort sizes. Therefore, although this review was able to yield statistically significant results regarding the relative merits of PVI, AVJAP and pharmacological rate control, it was likely underpowered to detect subtle differences in outcome between treatment groups. We included only RCT in our meta-analysis, as they provide the most robust evidence of the efficacy of therapeutic options and yield the best possible estimates of true effect by minimising spurious causality and bias. We did not include observational studies as they would introduce significant inconsistency in terms of study protocols and designs, and therefore reduce the strength of our conclusions. As a result of the small number of suitable RCT funnel plots were not included in the results to assess for publication bias. Data on PVI was also limited to radiofrequency ablation as no RCT with a cryotherapy PVI intervention satisfied the inclusion criteria.
This review was further limited by a lack of data on harms and risks, and hard clinical endpoints. A meta-analysis of morbidity and mortality event rates was not conducted as the number of reported complications were too few to yield any clinically relevant differences in outcome between treatment groups (Data Supplement B). Additionally, although surrogate endpoints such as LV function, symptoms of heart failure, and functional capacity are useful in their own right, there is a need for further large multi-centre RCT to evaluate the relative merits of PVI, AVJAP, and pharmacological rate control in terms of prognostic endpoints such as survival and rates of hospitalisation. Two such studies are currently underway and will seek to address this gap in the literature [
Moreover, there were several sources of clinical and methodological heterogeneity between the seven studies. Statistical heterogeneity was not evaluated, as Cochran's Q statistic and the I2 test have low power for meta-analyses with a small number of studies, as was the case for this review. Clinical heterogeneity stemmed from differences in study participants (Table 1) such as differing age groups for recruitment and different forms of AF. Furthermore, various RCT employed differing definitions of CCF (Table 1), and hence patients who were recruited in some RCT [
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
]. Other differences in the inclusion criteria of patients with CCF may also have impacted on our results, as certain comorbidities can independently exacerbate LV function, symptoms of heart failure, and diminished functional capacity. For example, only three RCT [
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
Methodological heterogeneity was also evident between the study protocols implemented (Table 1), such as differences in follow-up intervals after treatment, and different methods of assessing LVEF employed. All PVI and AVJAP procedures were performed at well-established centres with experienced ablationists. Therefore, our results may not be reproducible in all centres. Furthermore, amongst the four RCT evaluating AVJAP in our meta-analysis, only one [
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
] implemented conventional right ventricular (RV) pacing. Chronic RV pacing can cause electricomechanical dyssynchrony which contributes to progressive LV dysfunction and worsening heart failure. A recent multi-centre RCT [
] confirmed that biventricular pacing is preferable to RV pacing in patients with atrioventricular block (such as our AVJAP cohort) and LV systolic dysfunction (LVEF≤50%) with New York Heart Association Class I, II, or III heart failure. One could extrapolate that the benefits of biventricular pacing would be even greater in patients with more severe CCF, although this has not been formally evaluated. Regardless, the inclusion in our meta-analysis of three [
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
] RCT (all of which compared AVJAP to pharmacological rate control) utilising RV pacing instead of the preferred biventricular modality, would bias results in favour of pharmacological rate control. Finally, we identified limitations in the methodological quality of five of the seven RCT included (Data supplement A), in particular selective outcome reporting bias and lack of random sequence generation [
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
To the authors’ knowledge, this is the first meta-analysis that directly compares the relative merits of PVI, AVJAP and pharmacological rate control. Patients who have already unsuccessfully trialled or are unsuitable for pharmacological rhythm control will commonly be offered these treatment options. Whilst there is an abundance of literature comparing pharmacological rhythm control to rate control, PVI, or AVJAP; a formal systematic review excluding patients being treated with pharmacological antiarrhythmic agents has not yet been published. Importantly, the results of this systematic review support the clinical implementation of PVI over AVJAP or pharmacological rate control in AF patients with CCF, who may or may not have already trialled pharmacological rhythm control. The prior use of antiarrhythmic medications should have no bearing on recommending PVI to these patients, as multiple multi-centre RCT [
] have failed to demonstrate a clinical benefit of pharmacological rhythm control over rate control, but our systematic review did demonstrate a significant benefit of PVI over both pharmacologic and percutaneous rate control. A possible explanation for this difference is the difficulty in maintaining sinus rhythm using medication alone [
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
] in our review demonstrated that older patients with more severe LV systolic dysfunction and longer-standing persistent AF, all of which promote atrial dilatation and fibrosis, had lower procedural success and higher complication rates with PVI. Therefore, there remains a need to clearly define the ideal patient cohort to derive clinical benefit from PVI compared to rate control. Finally, in patients (irrespective of cardiac function) with symptomatic AF recurrences despite attempts at pharmacological rhythm control and/or PVI, the results of this systematic review failed to identify any clinical benefit of AVJAP over pharmacological rate control or vice versa.
Conclusion
PVI confers a statistically significant benefit over both AVJAP and pharmacologic rate control in terms of improving LV function and symptoms, in patients with AF and CCF. Furthermore, this systematic review found that there was no demonstrable benefit between AVJAP and pharmacological rate control for any of the outcomes assessed, in patients with AF irrespective of cardiac function.
2012 focused update of the ESC Guidelines for the management of atrial fibrillation – An update of the 2010 ESC Guidelines for the management of atrial fibrillation.
Prospective randomized study of ablation and pacing versus medical therapy for paroxysmal atrial fibrillation: effects of pacing mode and mode-switch algorithm.
Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction.
Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.
Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.
Assessment of Atrioventricular Junction Ablation and VVIR Pacemaker Versus Pharmacological Treatment in Patients with Heart Failure and Chronic Atrial Fibrillation: A Randomized, Controlled Study.
Higgins J, Green S. (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from http://handbook.cochrane.org.
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