What Have We Learned From Randomized Controlled Trials of Catheter Ablation for Atrial Fibrillation in Patients With Chronic Heart Failure?
2019; Lippincott Williams & Wilkins; Volume: 12; Issue: 4 Linguagem: Inglês
10.1161/circep.119.007222
ISSN1941-3149
Autores Tópico(s)Cardiac pacing and defibrillation studies
ResumoHomeCirculation: Arrhythmia and ElectrophysiologyVol. 12, No. 4What Have We Learned From Randomized Controlled Trials of Catheter Ablation for Atrial Fibrillation in Patients With Chronic Heart Failure? Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBWhat Have We Learned From Randomized Controlled Trials of Catheter Ablation for Atrial Fibrillation in Patients With Chronic Heart Failure? Milton Packer, MD Milton PackerMilton Packer Milton Packer, MD, Baylor Heart and Vascular Institute, 621 N. Hall St, Dallas, TX 75226. Email E-mail Address: [email protected] Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX. Imperial College, London, United Kingdom. Originally published22 Mar 2019https://doi.org/10.1161/CIRCEP.119.007222Circulation: Arrhythmia and Electrophysiology. 2019;12:e007222Catheter ablation can be used to treat atrial fibrillation (AF) in patients with chronic heart failure (HF). The procedure is predicated on the belief that restoration of atrial kick enhances systolic function; however, it is not clear why additional blood transport at end-diastole would be beneficial once the left ventricle is dilated and filling pressures are elevated. Although inadequately treated atrial tachyarrhythmias can lead to cardiomyopathy, irregularity of the ventricular rate has not been shown to be disadvantageous if the rate is well controlled.1Patients with HF, left ventricular systolic dysfunction, and AF have exertional dyspnea. Although they may experience symptomatic paroxysms, it is difficult in most patients to discern whether long-standing rate-controlled AF contributes to breathlessness or exercise intolerance. Many cardiologists try to assess the contribution of AF by evaluating the short-term symptomatic response to electrical cardioversion. However, any patient-reported benefits may be related to the psychological impact of the procedure, to the physiological benefits of restoring sinus rhythm, or to concomitant changes in medical therapy for HF.Catheter ablation is an invasive procedure that is performed differently by different electrophysiologists, and it carries risks of major complications. In patients with mild HF, ablation is generally successful in achieving sinus rhythm, but often a second or third procedure is required. Yet, each ablation procedure causes necrosis and replacement fibrosis of a meaningful proportion of the atrial myocardium.2 Scarring may impair atrial capacitance, which can have serious clinical consequences.Six trials have evaluated the effects of catheter ablation for AF in chronic HF (Table).3–8 Four compared catheter ablation to medical therapy directed at rate-control.3–6 These studies primarily enrolled patients with long-standing AF, and the control groups received atrioventricular nodal blocking drugs. In contrast, 2 trials compared catheter ablation to medical therapy primarily directed at rhythm control.7,8 These studies generally enrolled patients with paroxysmal or nonpermanent AF, and the control groups received membrane-active antiarrhythmic drugs.Table. Characteristics of Randomized Controlled Clinical Trials of Catheter Ablation for Atrial Fibrillation in Patients With Chronic Heart FailureStudy DesignPrimary End pointMajor FindingsLimitationsShort-term trials with medical rate control as the comparatorMacDonald et al3n=41, EF ≈18%, N-terminal proBNP ≈2200 pg/mL, most with long-standing AF, trial duration 6 moEF by CMRNo benefit on CMR EF, exercise tolerance, or quality-of-life; high rate of procedural complicationsLack of blinding; baseline imbalances (medical group had less severe disease)ARC-HF4n=52, EF ≈24%, BNP ≈350 pg/mL, most with long-standing AF, trial duration 12 moPeak oxygen consumption↑Exercise tolerance, quality-of-life; trend for ↑ EF by radionuclide ventriculography, but P>0.05; procedural complicationsLack of blindingCAMTAF5n=55, EF ≈32%, BNP ≈500 pg/mL, most with long-standing AF, trial duration 6 moEF by echocardiography↑Exercise tolerance, quality-of-life, and EF; many repeat ablationsLack of blinding; EF assessed by echocardiographyCAMERA-MRI6n=66, EF ≈33%, BNP ≈260 pg/mL, 6MWD ≈490 m, most with long-standing AF, trial duration 6 moEF by CMR↑EF, no between-group differences in exercise tolerance or quality-of-lifeBNP and 6MWD inconsistent with meaningful heart failure; lack of blindingLong-term trials with medical rhythm control as the comparatorAATAC7n=203, EF ≈30%, BNP not reported, 6MWD ≈350 m, mean AF duration < 1 y, trial duration 24 moLong-term freedom from AFNumerically fewer deaths in ablation group; no data on hospitalization for heart failure; ↑EF, exercise tolerance, and quality-of-lifeLack of blinding; EF assessed by echocardiographyCASTLE-AF8n=397, EF ≈30%, baseline BNP and 6MWD not reported, long-standing AF in 30%, trial duration 38 moAll-cause mortality or hospitalization for heart failureReduced risk of death and of hospitalization for heart failure; ↑EF; ↑exercise tolerance at 1 y but not thereafter; no measures of quality-of-lifeLack of blinding; 34 randomized patients not in primary analysis; 20% lost to follow-up (more in ablation group); baseline imbalances (medical group had more severe disease); concerns about adjudication of cause-specific hospitalizations; EF assessed by echocardiography6MWD indicates 6-minute walk distance; AATAC, Ablation Versus Amiodarone for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted ICD/CRTD; AF, atrial fibrillation; ARC-HF, A Randomized Trial to Assess Catheter Ablation Versus Rate Control in the Management of Persistent Atrial Fibrillation in Chronic Heart Failure; BNP, B-type natriuretic peptide; CAMERA-MRI, Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction; CAMTAF, Catheter Ablation Versus Medical Treatment of Atrial Fibrillation; CASTLE-AF, Catheter Ablation Versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation; CMR, cardiac magnetic resonance; and EF, ejection fraction.All 6 trials reported the effects of catheter ablation on ejection fraction (EF). The measurement of EF by echocardiography is unreliable in patients with AF, particularly in the absence of blinding; yet, the 2 largest trials7,8 evaluated EF by this method. Because of the limitations of echocardiography, 2 trials assessed EF using cardiac magnetic resonance imaging. The CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction) investigators6 reported an increase in EF, but the patients in the trial did not have meaningful HF; their exercise tolerance was preserved, and their natriuretic peptide levels were consistent with those seen in AF in the absence of HF. In contrast, MacDonald et al3 reported no significant increase in EF in patients with well-established HF (NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≈2200 pg/mL and baseline EF of 18%).All trials reported the effects of catheter ablation on effort tolerance and quality-of-life (Table). Although often assessed by different methods, several trials noted improved exercise performance and measures of health and comfort. However, these findings are difficult to interpret because the trials were unblinded, and knowledge of the treatment assignment is known to bias these assessments. In the trial that enrolled patients with the most advanced disease,3 catheter ablation did not have favorable effects on symptoms and exercise capacity.Two trials7,8 contributed information on the effects of catheter ablation on morbidity and mortality. The trials each enrolled <400 patients, and most did not have long-standing AF. Both trials reported that catheter ablation reduced the risk of death or hospitalization for HF, but the supporting data were sparse; there were <100 deaths in the trials combined. In CASTLE-AF (Catheter Ablation Versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation),8 there were significant imbalances across the treatment groups at randomization; 20% of all randomized patients were not included in the primary analysis; follow-up was twice as likely to be missing in the ablation than in the control group; and the trial was stopped for futility and achieved only 70% of the planned number of primary end point events.9 An unexplained increase in noncardiovascular hospitalizations in the ablation group also raises concerns about the lack of blinding in the reporting of cause-specific hospital admissions. In both trials,7,8 the comparator groups received membrane-active agents, which have been linked to an increased mortality risk when used to treat AF in patients with HF.10The totality of evidence suggests that catheter ablation for AF may have benefits on EF and functional capacity in chronic HF. However, the trials have been small and largely focused on patients with minimal or mild HF and only modest impairment of left ventricle function. In patients with meaningful degrees of HF and low EF, little efficacy has been observed, and the complication rate has been high.3 Because of the sparse number of events, the large number of patients with excluded or missing data, the lack of balance at randomization, and the use of comparator groups who were treated with cardiotoxic antiarrhythmic drugs to achieve rhythm control,9 it is not possible to suggest that a benefit of catheter ablation on morbidity and mortality has been demonstrated.Although the results of the 6 randomized trials of catheter ablation have been combined in numerous meta-analyses, summary estimates cannot overcome the inherent limitations of the component trials. Importantly, the available evidence from the 6 trials was not persuasive to the writers of the most recent guideline,11 which provided its weakest possible positive recommendation for the use of catheter ablation in patients with AF and chronic HF.Therefore, additional randomized controlled trials are needed to understand the range of potential responses to this procedure. Such trials should focus on patients with meaningful degrees of HF and long-standing AF and include individuals with preserved as well as decreased EF (especially <30%). Participants would be randomized to pharmacological rate control (target rate <110/minute) or to catheter ablation; patients would not need or receive cardiotoxic drugs to achieve rhythm control. If the trials are powered to detect a reduction in the primary end point of death, no blinding is needed. If the benefit of catheter ablation on mortality is as striking as is currently claimed, future trials in high-risk patients will not need to be large or follow patients for long periods of time.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Milton Packer, MD, Baylor Heart and Vascular Institute, 621 N. Hall St, Dallas, TX 75226. Email milton.[email protected]eduReferences1. Melenovsky V, Hay I, Fetics BJ, Borlaug BA, Kramer A, Pastore JM, Berger R, Kass DA. Functional impact of rate irregularity in patients with heart failure and atrial fibrillation receiving cardiac resynchronization therapy.Eur Heart J. 2005; 26:705–711. doi: 10.1093/eurheartj/ehi066CrossrefMedlineGoogle Scholar2. Cochet H, Scherr D, Zellerhoff S, Sacher F, Derval N, Denis A, Knecht S, Komatsu Y, Montaudon M, Laurent F, Pieske BM, Hocini M, Haïssaguerre M, Jaïs P. Atrial structure and function 5 years after successful ablation for persistent atrial fibrillation: an MRI study.J Cardiovasc Electrophysiol. 2014; 25:671–679. doi: 10.1111/jce.12449CrossrefMedlineGoogle Scholar3. MacDonald MR, Connelly DT, Hawkins NM, Steedman T, Payne J, Shaw M, Denvir M, Bhagra S, Small S, Martin W, McMurray JJ, Petrie MC. Radiofrequency ablation for persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic dysfunction: a randomised controlled trial.Heart. 2011; 97:740–747. doi: 10.1136/hrt.2010.207340CrossrefMedlineGoogle Scholar4. Jones DG, Haldar SK, Hussain W, Sharma R, Francis DP, Rahman-Haley SL, McDonagh TA, Underwood SR, Markides V, Wong T. 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; 61:1894–1903. doi: 10.1016/j.jacc.2013.01.069CrossrefMedlineGoogle Scholar5. Hunter RJ, Berriman TJ, Diab I, Kamdar R, Richmond L, Baker V, Goromonzi F, Sawhney V, Duncan E, Page SP, Ullah W, Unsworth B, Mayet J, Dhinoja M, Earley MJ, Sporton S, Schilling RJ. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial).Circ Arrhythm Electrophysiol. 2014; 7:31–38. doi: 10.1161/CIRCEP.113.000806LinkGoogle Scholar6. Prabhu S, Taylor AJ, Costello BT, Kaye DM, McLellan AJA, Voskoboinik A, Sugumar H, Lockwood SM, Stokes MB, Pathik B, Nalliah CJ, Wong GR, Azzopardi SM, Gutman SJ, Lee G, Layland J, Mariani JA, Ling LH, Kalman JM, Kistler PM. Catheter ablation versus medical rate control in atrial fibrillation and systolic dysfunction: the CAMERA-MRI Study.J Am Coll Cardiol. 2017; 70:1949–1961. doi: 10.1016/j.jacc.2017.08.041CrossrefMedlineGoogle Scholar7. Di Biase L, Mohanty P, Mohanty S, Santangeli P, Trivedi C, Lakkireddy D, Reddy M, Jais P, Themistoclakis S, Dello Russo A, Casella M, Pelargonio G, Narducci ML, Schweikert R, Neuzil P, Sanchez J, Horton R, Beheiry S, Hongo R, Hao S, Rossillo A, Forleo G, Tondo C, Burkhardt JD, Haissaguerre M, Natale A. Ablation versus amiodarone for treatment of persistent atrial fibrillation in patients with congestive heart failure and an implanted device: results from the AATAC Multicenter Randomized Trial.Circulation. 2016; 133:1637–1644. doi: 10.1161/CIRCULATIONAHA.115.019406LinkGoogle Scholar8. Marrouche NF, Brachmann J, Andresen D, Siebels J, Boersma L, Jordaens L, Merkely B, Pokushalov E, Sanders P, Proff J, Schunkert H, Christ H, Vogt J, Bänsch D; CASTLE-AF Investigators. Catheter ablation for atrial fibrillation with heart failure.N Engl J Med. 2018; 378:417–427. doi: 10.1056/NEJMoa1707855CrossrefMedlineGoogle Scholar9. Packer M, Kowey PR. Building castles in the sky. Catheter ablation in patients with atrial fibrillation and chronic heart failure.Circulation. 2018; 138:751–753.LinkGoogle Scholar10. Connolly SJ, Camm AJ, Halperin JL, Joyner C, Alings M, Amerena J, Atar D, Avezum Á, Blomström P, Borggrefe M, Budaj A, Chen SA, Ching CK, Commerford P, Dans A, Davy JM, Delacrétaz E, Di Pasquale G, Diaz R, Dorian P, Flaker G, Golitsyn S, Gonzalez-Hermosillo A, Granger CB, Heidbüchel H, Kautzner J, Kim JS, Lanas F, Lewis BS, Merino JL, Morillo C, Murin J, Narasimhan C, Paolasso E, Parkhomenko A, Peters NS, Sim KH, Stiles MK, Tanomsup S, Toivonen L, Tomcsányi J, Torp-Pedersen C, Tse HF, Vardas P, Vinereanu D, Xavier D, Zhu J, Zhu JR, Baret-Cormel L, Weinling E, Staiger C, Yusuf S, Chrolavicius S, Afzal R, Hohnloser SH; PALLAS Investigators. Dronedarone in high-risk permanent atrial fibrillation.N Engl J Med. 2011; 365:2268–2276. doi: 10.1056/NEJMoa1109867CrossrefMedlineGoogle Scholar11. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society [published online January 28, 2019].Circulation. doi: 10.1161/CIR.0000000000000665Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByWaldmann V, Jouven X, Narayanan K, Piot O, Chugh S, Albert C and Marijon E (2020) Association Between Atrial Fibrillation and Sudden Cardiac Death, Circulation Research, 127:2, (301-309), Online publication date: 3-Jul-2020. Packer M (2020) A Compelling Case for Less Aggressive Arrhythmia Management in Patients With Chronic Heart Failure and Long-Standing Atrial Fibrillation, Journal of Cardiac Failure, 10.1016/j.cardfail.2019.08.011, 26:1, (85-92), Online publication date: 1-Jan-2020. Packer M (2020) Is Long-Standing Atrial Fibrillation a Biomarker of or Contributor to the Symptoms or Progression of Chronic Heart Failure?, The American Journal of Medicine, 10.1016/j.amjmed.2019.05.026, 133:1, (17-18), Online publication date: 1-Jan-2020. Packer M (2019) Risks of Intensive Treatment of Long-Standing Atrial Fibrillation in Patients With Chronic Heart Failure With a Reduced or Preserved Ejection Fraction, Circulation: Cardiovascular Quality and Outcomes, 12:8, Online publication date: 1-Aug-2019. April 2019Vol 12, Issue 4 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.119.007222PMID: 30897965 Originally publishedMarch 22, 2019 Keywordsantiarrhythmic drugsclinical trialscatheter ablationatrial fibrillationheart failurePDF download Advertisement SubjectsAtrial FibrillationCatheter Ablation and Implantable Cardioverter-DefibrillatorHeart Failure
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