Atrial fibrillation in heart failure: Prime time for ablation!

Among heart failure (HF) patients, the onset of atrial fibrillation (AF) is often associated with a marked worsening of HF symptoms and increased morbidity and mortality. Among AF patients, 30%–40% experience at least 1 HF episode. New data suggest that, in HF patients, AF rhythm control is superior to rate control and that rhythm control by catheter ablation is superior to antiarrhythmic drugs. In recent years, several trials that addressed the impact of AF ablation on morbidity and mortality included HF patients; however, studies also have specifically investigated the growing cohort of patients suffering from both HF and AF. Although the majority of these trials showed a marked benefit of AF ablation, there are hints that not all HF patients benefit equally from AF ablation. AF treatment in HF is challenging because the same cardiac morbidities that lead to HF can also act as risk factors for the development of the arrhythmogenic substrate that causes AF. In many patients, this arrhythmogenic substrate can be successfully treated by antral pulmonary vein isolation pulmonary vein isolation (PVI). However, due to advanced atrial disease, some patients also might require multiple procedures and/or “PVI plus” ablation strategies. In this review, we summarize current data on the effect of AF ablation in HF patients, with a special focus on the beneficial effect of AF ablation in different clinical HF subgroups. Among heart failure (HF) patients, the onset of atrial fibrillation (AF) is often associated with a marked worsening of HF symptoms and increased morbidity and mortality. Among AF patients, 30%–40% experience at least 1 HF episode. New data suggest that, in HF patients, AF rhythm control is superior to rate control and that rhythm control by catheter ablation is superior to antiarrhythmic drugs. In recent years, several trials that addressed the impact of AF ablation on morbidity and mortality included HF patients; however, studies also have specifically investigated the growing cohort of patients suffering from both HF and AF. Although the majority of these trials showed a marked benefit of AF ablation, there are hints that not all HF patients benefit equally from AF ablation. AF treatment in HF is challenging because the same cardiac morbidities that lead to HF can also act as risk factors for the development of the arrhythmogenic substrate that causes AF. In many patients, this arrhythmogenic substrate can be successfully treated by antral pulmonary vein isolation pulmonary vein isolation (PVI). However, due to advanced atrial disease, some patients also might require multiple procedures and/or “PVI plus” ablation strategies. In this review, we summarize current data on the effect of AF ablation in HF patients, with a special focus on the beneficial effect of AF ablation in different clinical HF subgroups. Key Findings▪Heart failure (HF) and atrial fibrillation (AF) share common risk factors, and both have a negative impact on morbidity and mortality of cardiovascular patients.▪HF and AF form a vicious circle, promoting by multiple pathways the occurrence of each other and increasing exponentially cardiovascular morbidity and mortality in patients with both conditions.▪In HF patients, rhythm control of AF has been shown to be superior to rate control with regard to hard endpoints such as mortality, morbidity, and worsening of HF symptoms.▪For AF rhythm control, catheter ablation has been proven to be superior to antiarrhythmic medication.▪In HF patients, AF ablation should be regarded as the primary therapeutic option. ▪Heart failure (HF) and atrial fibrillation (AF) share common risk factors, and both have a negative impact on morbidity and mortality of cardiovascular patients.▪HF and AF form a vicious circle, promoting by multiple pathways the occurrence of each other and increasing exponentially cardiovascular morbidity and mortality in patients with both conditions.▪In HF patients, rhythm control of AF has been shown to be superior to rate control with regard to hard endpoints such as mortality, morbidity, and worsening of HF symptoms.▪For AF rhythm control, catheter ablation has been proven to be superior to antiarrhythmic medication.▪In HF patients, AF ablation should be regarded as the primary therapeutic option. Heart failure (HF) and atrial fibrillation (AF) both have a wide impact on mortality, hospitalization, stroke risk, and quality of life (QoL) in patients with one of these conditions. If both HF and AF coexist, the risk of developing one of them not only is the summation of each individual disease but increases exponentially, with a major increase in hospitalizations and a 2–3 times higher mortality.1Hindricks G, Potpara T, Dagres N, et al; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021;42:373–498. Erratum in Eur Heart J 2021;42:546–547.Google Scholar, 2Javed S. Koniari I. Fox D. Skene C. Lip G.Y. Gupta D. Catheter ablation for atrial fibrillation in heart failure: untying the Gordian knot.J Geriatr Cardiol. 2021; 18: 297-306PubMed Google Scholar, 3Wang T.J. Larson M.G. Levy D. et al.Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study.Circulation. 2003; 107: 2920-2925Crossref PubMed Scopus (1393) Google Scholar The Framingham study demonstrated that patients with one of the conditions are prone to experience the other, with an estimated 40% of HF patients developing AF and almost 35% of AF patients experiencing at least 1 episode of HF.3Wang T.J. Larson M.G. Levy D. et al.Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study.Circulation. 2003; 107: 2920-2925Crossref PubMed Scopus (1393) Google Scholar The most important reason for this interlacing of diseases is that—from a pathophysiological standpoint—“AF begets HF” and vice versa. HF is often associated with congestion of the heart chambers with consecutive dilation (of atria), stretch, and fibrosis, but it also causes changes on the neurohumoral as well as cellular levels, which ultimately result in electrical instability (Figure 1). AF can promote HF as a result of the rapid and irregular heart rate and the lack of atrial systole (and thus only passive ventricular filling), which in turn might lead to congestion, heart chamber dilation, fibrosis, and similar neurohumoral changes.4Anselmino M. Matta M. D'Ascenzo F. et al.Catheter ablation of atrial fibrillation in patients with left ventricular systolic dysfunction: a systematic review and meta-analysis.Circ Arrhythm Electrophysiol. 2014; 7: 1011-1018Crossref PubMed Scopus (127) Google Scholar The AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial showed that if only antiarrhythmic drugs (AADs) were used, rate control equaled rhythm control in longer-term follow-up (FU) with regard to hard outcomes such as mortality and stroke. However, it soon became clear that the outcomes in the rhythm control arm were significantly negatively impacted by AAD side effects. Moreover, in the rhythm control arm the sinus rhythm (SR) rate (provided by AAD) was quite low and the stroke rate was excessively high, mostly due to (inadequate) termination of oral anticoagulation.5Corley S.D. Epstein A.E. DiMarco J.P. et al.Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study.Circulation. 2004; 109: 1509-1513Crossref PubMed Scopus (992) Google Scholar These results triggered an interest in rhythm control by AF ablation, analyzing the safety and feasibility of AF ablation in HF patients. The first observational report published in 2006 showed in patients with concomitant AF and heart failure with reduced ejection fraction (HFrEF) a benefit of (successful) AF ablation with regard to left ventricular ejection fraction (LVEF), peak O2 consumption, and occurrence of decompensated HF, but also improvement of QoL.6Hsu L.F. Jaïs P. Sanders P. et al.Catheter ablation for atrial fibrillation in congestive heart failure.N Engl J Med. 2004; 351: 2373-2383Crossref PubMed Scopus (725) Google Scholar After this first encouraging report, several (smaller) randomized controlled trials (RCTs) compared rhythm control provided by catheter ablation to medical treatment (mostly with rate control) in patients with AF and HF (Table 1).4Anselmino M. Matta M. D'Ascenzo F. et al.Catheter ablation of atrial fibrillation in patients with left ventricular systolic dysfunction: a systematic review and meta-analysis.Circ Arrhythm Electrophysiol. 2014; 7: 1011-1018Crossref PubMed Scopus (127) Google Scholar,7Jones D.G. Haldar S.K. Hussain W. et al.A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure.J Am Coll Cardiol. 2013; 61: 1894-1903Crossref PubMed Scopus (276) Google Scholar, 8Hunter R.J. Berriman T.J. Diab I. et al.A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial).Circ Arrhythm Electrophysiol. 2014; 7: 31-38Crossref PubMed Scopus (274) Google Scholar, 9Prabhu S. Taylor A.J. Costello B.T. et al.Catheter ablation versus medical rate control in atrial fibrillation and systolic dysfunction: the CAMERA-MRI Study.J Am Coll Cardiol. 2017; 70: 1949-1961Crossref PubMed Scopus (261) Google ScholarTable 1Randomized trials comparing AF ablation in HFrEF to BMTNo. and characteristics of patientsEndpointsResults with regard to SREndpoints (major results)RemarksMacDonald et alPersistent AF; 22 vs 19 rhythm vs rate controlLVEF in MRISecondary: LVEF in MIBI; BNP50% in SR after ablationPrimary: FailureSecondary: Yes15% complications in ablation armAATAC 2016All Pers AF, LVEF <35%; 102 vs 100 ablation vs amiodaroneFreedom from AF recurrenceSecondary: Unplanned hospitalization and mortality70% vs 40% with 1.4 ablation proceduresPrimary and secondary: Positive1.4 procedures per patientCAMTAF (Hunter et Pers AF; LVEF and vs ablation vs medical rate controlLVEF at peak in SR and secondary: procedures per as AF Pers AF; vs ablation vs medical due to should have been of LVEF at in SR after vs AF in vs and secondary: only in 40% and on AF and Pers AF; vs with vs LVEF and AAD) in SR after of primary in with of AF to et AF LVEF <35%; randomized vs rhythm vs rate peak O2 after 1 ablation, after to and LVEF and improvement with AF, LVEF for vs LVEF in LVEF at secondary: improvement at AF heart chamber with AAD on only isolation in in AAD antiarrhythmic AF atrial medical atrial cardiac HFrEF heart failure with reduced ejection LVEF left ventricular ejection New Heart Pers pulmonary vein quality of sinus in a AAD antiarrhythmic AF atrial medical atrial cardiac HFrEF heart failure with reduced ejection LVEF left ventricular ejection New Heart Pers pulmonary vein quality of sinus These trials included mostly patients with persistent AF and and the ablation such as left atrial atrial ablation in to antral pulmonary vein isolation (PVI). The most common endpoints were from AF LVEF peak consumption, and and/or was and were and common of These (mostly with the and of AF ablation showed a effect of ablation, with LVEF increase of and improvement of and D.G. Haldar S.K. Hussain W. et al.A randomized trial to assess catheter ablation versus rate control in the management of persistent atrial fibrillation in heart failure.J Am Coll Cardiol. 2013; 61: 1894-1903Crossref PubMed Scopus (276) Google Scholar, 8Hunter R.J. Berriman T.J. Diab I. et al.A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial).Circ Arrhythm Electrophysiol. 2014; 7: 31-38Crossref PubMed Scopus (274) Google Scholar, 9Prabhu S. Taylor A.J. Costello B.T. et al.Catheter ablation versus medical rate control in atrial fibrillation and systolic dysfunction: the CAMERA-MRI Study.J Am Coll Cardiol. 2017; 70: 1949-1961Crossref PubMed Scopus (261) Google Scholar However, negative randomized trials compared AF ablation to medical study by et et ablation for persistent atrial fibrillation in patients with advanced heart failure and left ventricular systolic dysfunction: a controlled PubMed Scopus Google Scholar that included only persistent AF patients with concomitant HFrEF showed improvement of LVEF as by because only of the patients were in SR at the of In as many as of the patients from ablation et ablation for persistent atrial fibrillation in patients with advanced heart failure and left ventricular systolic dysfunction: a controlled PubMed Scopus Google Scholar In the (Atrial Fibrillation Management in Heart et al.Catheter ablation versus medical in patients with persistent atrial fibrillation and congestive heart failure: the randomized Arrhythm Electrophysiol. PubMed Scopus Google Scholar which also LVEF improvement in as a primary there was a similar with a but not increase in LVEF provided by ablation. However, due to a rate and with the LVEF it challenging to In the versus with for of Atrial Fibrillation in with Heart which compared rate by ablation and cardiac with AF ablation by the of Jaïs P. et isolation for atrial fibrillation in patients with heart failure.N Engl J Med. PubMed Scopus Google Scholar with this rate control, AF ablation provided a significantly with regard to and peak O2 in patients with persistent AF and Jaïs P. et isolation for atrial fibrillation in patients with heart failure.N Engl J Med. PubMed Scopus Google Scholar In we have multiple of that AF ablation in the of HFrEF peak consumption, and/or compared to a medical in to In with this et M. Matta M. D'Ascenzo F. et al.Catheter ablation of atrial fibrillation in patients with left ventricular systolic dysfunction: a systematic review and meta-analysis.Circ Arrhythm Electrophysiol. 2014; 7: 1011-1018Crossref PubMed Scopus (127) Google Scholar included not only randomized but also observational data in their in showed a clear benefit of AF ablation in HF patients, with a improvement in that the benefit of AF ablation was if it was in the of AF and M. Matta M. D'Ascenzo F. et al.Catheter ablation of atrial fibrillation in patients with left ventricular systolic dysfunction: a systematic review and meta-analysis.Circ Arrhythm Electrophysiol. 2014; 7: 1011-1018Crossref PubMed Scopus (127) Google Scholar In the for of Atrial Fibrillation in with Heart and an 1 compared rhythm control vs catheter patients with reduced LVEF and persistent AF. In this patients were randomized to ablation treatment to rhythm P. S. et versus for treatment of persistent atrial fibrillation in patients with congestive heart failure and an results from the randomized PubMed Scopus Google Scholar The primary was from after endpoints HF hospitalizations and mortality. of the patients in the ablation were in the of the to ablation. The trial demonstrated that in to the of by ablation from after ablation vs with there was a in risk of HF hospitalization in the ablation vs in the and in the ablation vs in the provided by AF ablation. to this rate of SR in a cohort of persistent AF patients, a of 1.4 ablation procedures per was an advanced ablation with ablation and ablation of In AF ablation for rhythm control was superior to for rhythm control with regard to of AF, but also for HF hospitalization and mortality. These results were mostly by the higher rate of ablation in AF. Although the vicious of HF promoting AF and vice is in both of HF, the mortality by concomitant AF to be significantly in HFrEF in heart failure with ejection fraction D. P. Lip G.Y. Atrial fibrillation and heart failure due to reduced versus ejection a systematic review and of and J Cardiol. PubMed Scopus Google Scholar data on the of AF ablation in are and there are observational studies the benefit of AF ablation (Table trials on AF ablation in and characteristics of patientsEndpointsResults SREndpoints (major et with AF; Pers rhythm in on and AAD after multiple AAD and SR after of increases to with multiple on AAD and after multiple of Pers AF and all in in ablation et AF, Pers AF, Pers AF; on of rhythm in on and AAD after multiple in AAD and SR after of increases to with of of at Pers significantly if in SR vs in Pers AF included multiple on with heart Pers in symptoms and heart 1 after in SR at 1 provided significantly all SR at of in AF of that SR in these et with AF; with 35% with Pers at 1 and changes in AAD after ablation with multiple procedures on AAD rate SR in HF and HFrEF in LVEF increased and in both HF on ablation with with heart failure with ejection left superior wide antral other as in in a heart failure with ejection left superior wide antral other as in In as in the effect of AF ablation on New Heart Association and to be to the to successfully AF in these patients. However, there are data the rate of AF ablation in recent observational study in patients that in a multiple procedures and AAD treatment were to from in of D. P. I. et ablation for atrial fibrillation in patients with results and clinical Electrophysiol. 2021; PubMed Scopus Google Scholar et et and outcomes of catheter ablation of atrial fibrillation in patients with heart failure with ejection Am Coll Cardiol. 2013; PubMed Scopus Google Scholar in an observational study with that SR be in only of patients, and only by multiple procedures and AAD In in a recent observational study almost patients with et I. et al.Catheter ablation for atrial fibrillation by heart failure with ejection feasibility and in and 2021; PubMed Scopus Google Scholar that similar ablation compared to HFrEF patients and patients HF, a majority of patients from recent AF. In with a recent showed that AF ablation in patients results in similar with regard to and in and symptoms in compared to in HFrEF F. D. et of the of catheter ablation of atrial fibrillation in patients with heart failure with ejection J Cardiol. 2021; PubMed Scopus Google Scholar reason for the results of AF ablation in patients is that was often a clinical diagnosis an and is a common in AF and it can be to the of and the of in AF patients is et M. of heart failure with ejection fraction patients with atrial fibrillation and PubMed Scopus Google Scholar that patients with heart to from the effect of AF ablation in these patients, catheter ablation for AF and investigated patients for AF ablation and patients heart and were as if pulmonary S. D. et al.A catheter ablation for AF and J Heart 2021; PubMed Scopus Google Scholar patients, in the by et M. of heart failure with ejection fraction patients with atrial fibrillation and PubMed Scopus Google and ablation. patients the for all of were in After patients been successfully showed improvement in pulmonary and there is a rate of in AF patients, and AF ablation significantly the trials mostly such as from AF, peak consumption, improvement as primary mostly to recent randomized trials have been to endpoints such as mortality, hospitalizations and risk of in longer-term In these not all of which on HF patients but in some provided of HF patients, AF ablation was compared to medical rate control and a of rhythm control and rate The first of these studies was versus in with and Atrial in which patients with LVEF and AF were randomized to catheter ablation medical treatment D. et ablation for atrial fibrillation with heart failure.N Engl J Med. PubMed Scopus Google Scholar The primary was the of and worsening HF endpoints were the of the primary cardiovascular hospitalization, and The primary and which showed a benefit from AF ablation for all endpoints and a marked increase in LVEF of in the patients in the medical were published in In the important were addressed et C. et of left ventricular and heart failure symptoms on outcomes ablation of atrial fibrillation in heart failure: Arrhythm Electrophysiol. PubMed Scopus Google Scholar investigated the between and the primary study and that both patients with as well as with ejection fraction between and 35% significantly from ablation with regard to the primary with the experiencing often the primary patients with HF from ablation with advanced ablation should be as as the of HF and AF et C. D. et fibrillation and clinical outcomes in heart failure: The Electrophysiol. 2021; 7: PubMed Scopus Google Scholar the between AF and clinical outcomes in in the of patients for AF was that ablation patients AF as by a of hard clinical outcomes such as and AAD patients with a AF not benefit from the low AF is in with the AF ablation has to be in AF in a of patients to be and only rhythm control by ablation hard clinical endpoints rhythm control only AF to but not AF was associated with thus challenging the most AF ablation trial The ablation trial with hard clinical vs for Atrial which compared catheter ablation to AAD treatment in AF patients with and HF, not a benefit from ablation with regard to the primary of cardiac and et of catheter ablation vs antiarrhythmic on mortality, and cardiac patients with atrial the randomized clinical PubMed Scopus Google Scholar In et J.P. et versus for atrial fibrillation in heart failure: results from the 2021; PubMed Scopus Google Scholar were to in the HF which included patients with HF in that the ablation patients vs patients in the medical significantly from ablation with regard to the primary was a risk in the primary and a risk in mortality in the ablation compared to the medical treatment In the of the which most and least from ablation. patients, patients with AF of the and patients with risk factors for AF and were the and the of AF patients was the only that with by only of patients included in LVEF and between 40% and the majority of patients some form of the with and between 40% and benefit but not significantly as a result of ablation with regard to hard clinical in HF, the patients most from AF ablation with regard to hard clinical mortality, were with persistent AF and patients with can be that the reason for this is that these patients have with higher AF ablation In to and the atrial fibrillation rhythm control versus rate control trial in patients with heart failure and atrial not of rhythm control by AF ablation rate control by in HFrEF and patients with a primary of and HF et al.A randomized atrial fibrillation rhythm control versus rate control trial in patients with heart failure and atrial the trial and Heart 2021; PubMed Scopus Google randomized atrial fibrillation rhythm control versus rate control trial in patients with heart failure and atrial at the of Cardiology Scientific Scholar in the trial was of because of a rate and and a effect of AF ablation on the primary which was not the trial is not for this negative result has not been In the published European Society of Cardiology on HF which mostly on and of AF catheter ablation is M. M. et Scientific Document ESC Guidelines for the diagnosis and treatment of and heart Heart 2021; PubMed Scopus Google Scholar However, the on patients with regard to for AF ablation. comparing AF ablation vs medical in HF patients have been published (Table In with the AF ablation in significantly reduced mortality and HF hospitalization and and/or S. C. et control for patients with atrial fibrillation with heart failure in the of catheter a of randomized Heart PubMed Scopus Google Scholar, et al.Catheter ablation versus medical for atrial a systematic review and of randomized controlled Arrhythm Electrophysiol. PubMed Scopus Google Scholar, M. Catheter ablation compared with medical for atrial fibrillation with heart failure: a systematic review and of randomized controlled J 2021; 18: PubMed Scopus Google Scholar In these there are hints that AF ablation might not be beneficial in all of HF data on AF ablation and of AF et trials with HFrEF and AF ablation included safety and of AF ablation in of impact on in by AF diagnosis and advanced HF with with ablation should be in AF and HF effect of AF ablation is et AF ablation vs with of HFrEF and of with AF ablation equally in with and of mortality, hospitalization with ablation, by HFrEF of AF ablation in HF from et of AAD rhythm control rate AF ablation rhythm control in vs rhythm control by ablation significantly mortality, of increase in LVEF after AF rhythm control) benefit from rhythm control control by studies with and mostly multiple ablation et comparing AF ablation to in HFrEF hospitalization, of in ablation compared to of mortality and all endpoints significantly with ablation is because of SR heart randomized controlled heart other as in 1 and in a HF heart randomized controlled heart other as in 1 and the effect of AF ablation in HF is to a on the to significantly AF with AF ablation are to benefit from AF ablation in patients patients with persistent AF, and with risk factors for AF In a et D. et of mortality by catheter ablation in atrial fibrillation patients with heart 2021; PubMed Scopus Google Scholar that, AF ablation in a in mortality, cardiovascular HF and the of patients not benefit from AF ablation with regard to cardiovascular the of AF, et M. et of left ventricular after catheter ablation of atrial fibrillation in patients with left ventricular systolic Cardiol. 2021; PubMed Scopus Google Scholar that the of on is on the of AF after ablation, with a in the of from AF with to AF and persistent AF the of AF was associated with the of AF, persistent AF patients a patients with AF. in the hard there are hints from the as well as HF trials that patients with advanced HF not benefit from AF ablation, if SR is In with et et of improvement of left ventricular systolic after catheter ablation of persistent atrial fibrillation in patients with heart failure with reduced ejection 2021; PubMed Scopus Google Scholar in an observational study for LVEF improvement after AF ablation. of patients with HFrEF showed LVEF after Although in the of ablation, and from AF were significantly associated with LVEF only a for LVEF improvement after catheter ablation. reduced effect of AF ablation in patients with and with advanced HF might be by the ventricular in these patients. However, in these the outcomes of ablation are with and because the of ablation are AF ablation is a treatment with a of ablation for Catheter ablation of AF in the of HF is associated with a clear benefit medical not only with regard to symptoms and but also hard clinical endpoints such as mortality, and benefit is but not by the rhythm control from ablation. rhythm control AF ablation is associated with clinical compared to rhythm control, due to the side effect of AF ablation in HF should be and by AF risk