D S Echt, P R Liebson, L B Mitchell, R W Peters, D Obias-Manno, A H Barker, D Arensberg, A Baker, L Friedman, H L Greene
Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.
N Engl J Med. 1991 Mar 21;324(12):781-8. doi: 10.1056/NEJM199103213241201.
Abstract/Text
BACKGROUND AND METHODS: In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo.
RESULTS: Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty.
CONCLUSIONS: There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.
Meiso Hayashi, Wataru Shimizu, Christine M Albert
The spectrum of epidemiology underlying sudden cardiac death.
Circ Res. 2015 Jun 5;116(12):1887-906. doi: 10.1161/CIRCRESAHA.116.304521.
Abstract/Text
Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15%-20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who experience a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly because of inherited disorders. Coronary heart disease is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. During the past 3 decades, declines in SCD rates have not been as steep as for other causes of coronary heart disease deaths, and there is a growing fraction of SCDs not due to coronary heart disease and ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms underlying SCD present major challenges for SCD prevention, which are magnified further by a frequent lack of recognition of the underlying cardiac condition before death. Multifaceted preventative approaches, which address risk factors in seemingly low-risk and known high-risk populations, will be required to decrease the burden of SCD. In this Compendium, we review the wide-ranging spectrum of epidemiology underlying SCD within both the general population and in high-risk subsets with established cardiac disease placing an emphasis on recent global trends, remaining uncertainties, and potential targeted preventive strategies.
© 2015 American Heart Association, Inc.
Task Force members, Michele Brignole, Panos Vardas, Ellen Hoffman, Heikki Huikuri, Angel Moya, Renato Ricci, Neil Sulke, Wouter Wieling, EHRA Scientific Documents Committee, Angelo Auricchio, Gregory Y H Lip, Jesus Almendral, Paulus Kirchhof, Etienne Aliot, Maurizio Gasparini, Frieder Braunschweig, Document Reviewers, Gregory Y H Lip, Jesus Almendral, Paulus Kirchhof, Gian Luca Botto, EHRA Scientific Documents Committee
Indications for the use of diagnostic implantable and external ECG loop recorders.
Europace. 2009 May;11(5):671-87. doi: 10.1093/europace/eup097.
Abstract/Text
D G Wyse, A L Waldo, J P DiMarco, M J Domanski, Y Rosenberg, E B Schron, J C Kellen, H L Greene, M C Mickel, J E Dalquist, S D Corley, Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators
A comparison of rate control and rhythm control in patients with atrial fibrillation.
N Engl J Med. 2002 Dec 5;347(23):1825-33. doi: 10.1056/NEJMoa021328.
Abstract/Text
BACKGROUND: There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended.
METHODS: We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality.
RESULTS: A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic.
CONCLUSIONS: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.
Copyright 2002 Massachusetts Medical Society
Oussama M Wazni, Nassir F Marrouche, David O Martin, Atul Verma, Mandeep Bhargava, Walid Saliba, Dianna Bash, Robert Schweikert, Johannes Brachmann, Jens Gunther, Klaus Gutleben, Ennio Pisano, Dominico Potenza, Raffaele Fanelli, Antonio Raviele, Sakis Themistoclakis, Antonio Rossillo, Aldo Bonso, Andrea Natale
Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial.
JAMA. 2005 Jun 1;293(21):2634-40. doi: 10.1001/jama.293.21.2634.
Abstract/Text
CONTEXT: Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation (AF). Pulmonary vein isolation (PVI) with radiofrequency ablation may cure AF, obviating the need for antiarrhythmic drugs and anticoagulation.
OBJECTIVE: To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter prospective randomized study conducted from December 31, 2001, to July 1, 2002, of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs.
INTERVENTION: Patients were randomized to receive either PVI using radiofrequency ablation (n=33) or antiarrhythmic drug treatment (n=37), with a 1-year follow-up.
MAIN OUTCOME MEASURES: Recurrence of AF, hospitalization, and quality of life assessment.
RESULTS: Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up. At the end of 1-year follow-up, 22 (63%) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 (13%) of 32 patients who received PVI (P<.001). Hospitalization during 1-year follow-up occurred in 19 (54%) of 35 patients in the antiarrhythmic drug group compared with 3 (9%) of 32 in the PVI group (P<.001). In the antiarrhythmic drug group, the mean (SD) number of AF episodes decreased from 12 (7) to 6 (4), after initiating therapy (P = .01). At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey. There were no thromboembolic events in either group. Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 (6%) of 32 patients in the PVI group.
CONCLUSION: Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF. Larger studies are needed to confirm its safety and efficacy.
Jens Cosedis Nielsen, Arne Johannessen, Pekka Raatikainen, Gerhard Hindricks, Håkan Walfridsson, Ole Kongstad, Steen Pehrson, Anders Englund, Juha Hartikainen, Leif Spange Mortensen, Peter Steen Hansen
Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.
N Engl J Med. 2012 Oct 25;367(17):1587-95. doi: 10.1056/NEJMoa1113566.
Abstract/Text
BACKGROUND: There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation.
METHODS: We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis.
RESULTS: There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation.
CONCLUSIONS: In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).
Carlos A Morillo, Atul Verma, Stuart J Connolly, Karl H Kuck, Girish M Nair, Jean Champagne, Laurence D Sterns, Heather Beresh, Jeffrey S Healey, Andrea Natale, RAAFT-2 Investigators
Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial.
JAMA. 2014 Feb 19;311(7):692-700. doi: 10.1001/jama.2014.467.
Abstract/Text
IMPORTANCE: Atrial fibrillation (AF) is the most common rhythm disorder seen in clinical practice. Antiarrhythmic drugs are effective for reduction of recurrence in patients with symptomatic paroxysmal AF. Radiofrequency ablation is an accepted therapy in patients for whom antiarrhythmic drugs have failed; however, its role as a first-line therapy needs further investigation.
OBJECTIVE: To compare radiofrequency ablation with antiarrhythmic drugs (standard therapy) in treating patients with paroxysmal AF as a first-line therapy.
DESIGN, SETTING, AND PATIENTS: A randomized clinical trial involving 127 treatment-naive patients with paroxysmal AF were randomized at 16 centers in Europe and North America to received either antiarrhythmic therapy or ablation. The first patient was enrolled July 27, 2006; the last patient, January 29, 2010. The last follow-up was February 16, 2012.
INTERVENTIONS: Sixty-one patients in the antiarrhythmic drug group and 66 in the radiofrequency ablation group were followed up for 24 months.
MAIN OUTCOMES AND MEASURES: The time to the first documented atrial tachyarrhythmia of more than 30 seconds (symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia), detected by either scheduled or unscheduled electrocardiogram, Holter, transtelephonic monitor, or rhythm strip, was the primary outcome. Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool.
RESULTS: Forty-four patients (72.1%) in the antiarrhythmic group and in 36 patients (54.5%) in the ablation group experienced the primary efficacy outcome (hazard ratio [HR], 0.56 [95% CI, 0.35-0.90]; P = .02). For the secondary outcomes, 59% in the drug group and 47% in the ablation group experienced the first recurrence of symptomatic AF, atrial flutter, atrial tachycardia (HR, 0.56 [95% CI, 0.33-0.95]; P = .03). No deaths or strokes were reported in either group; 4 cases of cardiac tamponade were reported in the ablation group. In the standard treatment group, 26 patients (43%) underwent ablation after 1-year. Quality of life was moderately impaired at baseline in both groups and improved at the 1 year follow-up. However, improvement was not significantly different among groups.
CONCLUSIONS AND RELEVANCE: Among patients with paroxysmal AF without previous antiarrhythmic drug treatment, radiofrequency ablation compared with antiarrhythmic drugs resulted in a lower rate of recurrent atrial tachyarrhythmias at 2 years. However, recurrence was frequent in both groups.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00392054.
Antti Hakalahti, Fausto Biancari, Jens Cosedis Nielsen, M J Pekka Raatikainen
Radiofrequency ablation vs. antiarrhythmic drug therapy as first line treatment of symptomatic atrial fibrillation: systematic review and meta-analysis.
Europace. 2015 Mar;17(3):370-8. doi: 10.1093/europace/euu376. Epub 2015 Feb 1.
Abstract/Text
AIMS: New evidence about first-line radiofrequency catheter ablation (RFA) in symptomatic atrial fibrillation (AF) has emerged. In a single study the comparative treatment effect is potentially diminished by the high rate of cross-over to the alternative therapy. Therefore, we conducted a systematic review and meta-analysis of the available data to further evaluate the efficacy and safety of RFA vs. antiarrhythmic drugs (AADs).
METHODS AND RESULTS: Five databases were searched for randomized controlled trials comparing RFA and AAD therapy as first-line treatment of AF in August 2014. Three studies with 491 patients with recurrent symptomatic AF were included. The patients were relatively young and the majority of them had paroxysmal AF (98.7%) and no major comorbidity. Radiofrequency catheter ablation was associated with significantly higher freedom from AF recurrence compared with AAD therapy [risk ratio (RR) 0.63, 95% confidence interval (CI) 0.44-0.92, P = 0.02]. The difference in the rate of symptomatic AF recurrences was not statistically significant (RR 0.57, 95% CI 0.30-1.08, P = 0.09). There was one procedure-related death and seven tamponades with RFA, whereas symptomatic bradycardia was more frequent with AAD therapy.
CONCLUSION: Radiofrequency catheter ablation seems to be more effective than medical therapy as first-line treatment of paroxysmal AF in relatively young and otherwise healthy patients, but may also cause more severe adverse effects. These findings support the use of RFA as first-line therapy in selected patients, who understand the benefits and risks of the procedure.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
Oussama M Wazni, Gopi Dandamudi, Nitesh Sood, Robert Hoyt, Jaret Tyler, Sarfraz Durrani, Mark Niebauer, Kevin Makati, Blair Halperin, Andre Gauri, Gustavo Morales, Mingyuan Shao, Jeffrey Cerkvenik, Rachelle E Kaplon, Steven E Nissen, STOP AF First Trial Investigators
Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.
N Engl J Med. 2021 Jan 28;384(4):316-324. doi: 10.1056/NEJMoa2029554. Epub 2020 Nov 16.
Abstract/Text
BACKGROUND: In patients with symptomatic paroxysmal atrial fibrillation that has not responded to medication, catheter ablation is more effective than antiarrhythmic drug therapy for maintaining sinus rhythm. However, the safety and efficacy of cryoballoon ablation as initial first-line therapy have not been established.
METHODS: We performed a multicenter trial in which patients 18 to 80 years of age who had paroxysmal atrial fibrillation for which they had not previously received rhythm-control therapy were randomly assigned (1:1) to receive treatment with antiarrhythmic drugs (class I or III agents) or pulmonary vein isolation with a cryoballoon. Arrhythmia monitoring included 12-lead electrocardiography conducted at baseline and at 1, 3, 6, and 12 months; patient-activated telephone monitoring conducted weekly and when symptoms were present during months 3 through 12; and 24-hour ambulatory monitoring conducted at 6 and 12 months. The primary efficacy end point was treatment success (defined as freedom from initial failure of the procedure or atrial arrhythmia recurrence after a 90-day blanking period to allow recovery from the procedure or drug dose adjustment, evaluated in a Kaplan-Meier analysis). The primary safety end point was assessed in the ablation group only and was a composite of several procedure-related and cryoballoon system-related serious adverse events.
RESULTS: Of the 203 participants who underwent randomization and received treatment, 104 underwent ablation, and 99 initially received drug therapy. In the ablation group, initial success of the procedure was achieved in 97% of patients. The Kaplan-Meier estimate of the percentage of patients with treatment success at 12 months was 74.6% (95% confidence interval [CI], 65.0 to 82.0) in the ablation group and 45.0% (95% CI, 34.6 to 54.7) in the drug-therapy group (P<0.001 by log-rank test). Two primary safety end-point events occurred in the ablation group (Kaplan-Meier estimate of the percentage of patients with an event within 12 months, 1.9%; 95% CI, 0.5 to 7.5).
CONCLUSIONS: Cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation. Serious procedure-related adverse events were uncommon. (Supported by Medtronic; STOP AF First ClinicalTrials.gov number, NCT03118518.).
Copyright © 2020 Massachusetts Medical Society.
Jason G Andrade, George A Wells, Marc W Deyell, Matthew Bennett, Vidal Essebag, Jean Champagne, Jean-Francois Roux, Derek Yung, Allan Skanes, Yaariv Khaykin, Carlos Morillo, Umjeet Jolly, Paul Novak, Evan Lockwood, Guy Amit, Paul Angaran, John Sapp, Stephan Wardell, Sandra Lauck, Laurent Macle, Atul Verma, EARLY-AF Investigators
Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation.
N Engl J Med. 2021 Jan 28;384(4):305-315. doi: 10.1056/NEJMoa2029980. Epub 2020 Nov 16.
Abstract/Text
BACKGROUND: Guidelines recommend a trial of one or more antiarrhythmic drugs before catheter ablation is considered in patients with atrial fibrillation. However, first-line ablation may be more effective in maintaining sinus rhythm.
METHODS: We randomly assigned 303 patients with symptomatic, paroxysmal, untreated atrial fibrillation to undergo catheter ablation with a cryothermy balloon or to receive antiarrhythmic drug therapy for initial rhythm control. All the patients received an implantable cardiac monitoring device to detect atrial tachyarrhythmia. The follow-up period was 12 months. The primary end point was the first documented recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) between 91 and 365 days after catheter ablation or the initiation of an antiarrhythmic drug. The secondary end points included freedom from symptomatic arrhythmia, the atrial fibrillation burden, and quality of life.
RESULTS: At 1 year, a recurrence of atrial tachyarrhythmia had occurred in 66 of 154 patients (42.9%) assigned to undergo ablation and in 101 of 149 patients (67.8%) assigned to receive antiarrhythmic drugs (hazard ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66; P<0.001). Symptomatic atrial tachyarrhythmia had recurred in 11.0% of the patients who underwent ablation and in 26.2% of those who received antiarrhythmic drugs (hazard ratio, 0.39; 95% CI, 0.22 to 0.68). The median percentage of time in atrial fibrillation was 0% (interquartile range, 0 to 0.08) with ablation and 0.13% (interquartile range, 0 to 1.60) with antiarrhythmic drugs. Serious adverse events occurred in 5 patients (3.2%) who underwent ablation and in 6 patients (4.0%) who received antiarrhythmic drugs.
CONCLUSIONS: Among patients receiving initial treatment for symptomatic, paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy, as assessed by continuous cardiac rhythm monitoring. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).
Copyright © 2020 Massachusetts Medical Society.
Wilber W Su, Vivek Y Reddy, Kabir Bhasin, Jean Champagne, Robert M Sangrigoli, Kendra M Braegelmann, Fred J Kueffer, Paul Novak, Sanjaya K Gupta, Teiichi Yamane, Hugh Calkins, STOP Persistent AF Investigators
Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: Results from the multicenter STOP Persistent AF trial.
Heart Rhythm. 2020 Nov;17(11):1841-1847. doi: 10.1016/j.hrthm.2020.06.020. Epub 2020 Jun 24.
Abstract/Text
BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation to treat patients with symptomatic drug-refractory atrial fibrillation (AF).
OBJECTIVE: The purpose of this study was to assess the safety and efficacy of PVI using the cryoballoon catheter to treat patients with persistent AF.
METHODS: STOP Persistent AF (ClinicalTrials.gov Identifier: NCT03012841) was a prospective, multicenter, single-arm, Food and Drug Administration-regulated trial designed to evaluate the safety and efficacy of PVI-only cryoballoon ablation for drug-refractory persistent AF (continuous episodes <6 months). The primary efficacy endpoint was 12-month freedom from ≥30 seconds of AF, atrial flutter (AFL), or atrial tachycardia (AT) after a 90-day blanking period. The prespecified performance goals were set at >40% and <13% for the primary efficacy and safety endpoints, respectively. Secondary endpoints assessed quality of life using the AFEQT (Atrial Fibrillation Effect on Quality of Life) and SF (Short Form)-12 questionnaires.
RESULTS: Of 186 total enrollments, 165 subjects (70% male; age 65 ± 9 years; left atrial diameter 4.2 ± 0.6 cm; body mass index 31 ± 6) were treated at 25 sites in the United States, Canada, and Japan. Total procedural, left atrial dwell, and fluoroscopy times were 121 ± 46 minutes, 102 ± 41 minutes, and 19 ± 16 minutes, respectively. At 12 months, the primary efficacy endpoint was 54.8% (95% confidence [CI] 46.7%-62.1%) freedom from AF, AFL, or AT. There was 1 primary safety event, translating to a rate of 0.6% (95% CI 0.1%-4.4%). AFEQT and SF-12 assessments demonstrated significant improvements from baseline to 12 months postablation (P <.001).
CONCLUSION: The STOP Persistent AF trial demonstrated cryoballoon ablation to be safe and effective in treating patients with drug-refractory persistent AF characterized by continuous AF episodes <6 months.
Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Nassir F Marrouche, Johannes Brachmann, Dietrich Andresen, Jürgen Siebels, Lucas Boersma, Luc Jordaens, Béla Merkely, Evgeny Pokushalov, Prashanthan Sanders, Jochen Proff, Heribert Schunkert, Hildegard Christ, Jürgen Vogt, Dietmar Bänsch, CASTLE-AF Investigators
Catheter Ablation for Atrial Fibrillation with Heart Failure.
N Engl J Med. 2018 Feb 1;378(5):417-427. doi: 10.1056/NEJMoa1707855.
Abstract/Text
BACKGROUND: Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment.
METHODS: We randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure.
RESULTS: After a median follow-up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical-therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009).
CONCLUSIONS: Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188 .).
M Haïssaguerre, P Jaïs, D C Shah, A Takahashi, M Hocini, G Quiniou, S Garrigue, A Le Mouroux, P Le Métayer, J Clémenty
Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins.
N Engl J Med. 1998 Sep 3;339(10):659-66. doi: 10.1056/NEJM199809033391003.
Abstract/Text
BACKGROUND: Atrial fibrillation, the most common sustained cardiac arrhythmia and a major cause of stroke, results from simultaneous reentrant wavelets. Its spontaneous initiation has not been studied.
METHODS: We studied 45 patients with frequent episodes of atrial fibrillation (mean [+/-SD] duration, 344+/-326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of atrial fibrillation was mapped with the use of multielectrode catheters designed to record the earliest electrical activity preceding the onset of atrial fibrillation and associated atrial ectopic beats. The accuracy of the mapping was confirmed by the abrupt disappearance of triggering atrial ectopic beats after ablation with local radio-frequency energy.
RESULTS: A single point of origin of atrial ectopic beats was identified in 29 patients, two points of origin were identified in 9 patients, and three or four points of origin were identified in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium, 1 in the posterior left atrium, and 65 (94 percent) in the pulmonary veins (31 in the left superior, 17 in the right superior, 11 in the left inferior, and 6 in the right inferior pulmonary vein). The earliest activation was found to have occurred 2 to 4 cm inside the veins, marked by a local depolarization preceding the atrial ectopic beats on the surface electrocardiogram by 106+/-24 msec. Atrial fibrillation was initiated by a sudden burst of rapid depolarizations (340 per minute). A local depolarization could also be recognized during sinus rhythm and abolished by radiofrequency ablation. During a follow-up period of 8+/-6 months after ablation, 28 patients (62 percent) had no recurrence of atrial fibrillation.
CONCLUSIONS: The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation. These foci respond to treatment with radio-frequency ablation.
Carlo Pappone, Salvatore Rosanio, Giuseppe Augello, Giuseppe Gallus, Gabriele Vicedomini, Patrizio Mazzone, Simone Gulletta, Filippo Gugliotta, Alessia Pappone, Vincenzo Santinelli, Valter Tortoriello, Simone Sala, Alberto Zangrillo, Giuseppe Crescenzi, Stefano Benussi, Ottavio Alfieri
Mortality, morbidity, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled nonrandomized long-term study.
J Am Coll Cardiol. 2003 Jul 16;42(2):185-97.
Abstract/Text
OBJECTIVES: This study was designed to investigate the potential of circumferential pulmonary vein (PV) ablation for atrial fibrillation (AF) to maintain sinus rhythm (SR) over time, thus reducing mortality and morbidity while enhancing quality of life (QoL).
BACKGROUND: Circumferential PV ablation is safe and effective, but the long-term outcomes and its impact on QoL have not been assessed or compared with those for medical therapy.
METHODS: We examined the clinical course of 1,171 consecutive patients with symptomatic AF who were referred to us between January 1998 and March 2001. The 589 ablated patients were compared with the 582 who received antiarrhythmic medications for SR control. The QoL of 109 ablated and 102 medically treated patients was measured with the SF-36 survey.
RESULTS: Median follow-up was 900 days (range 161 to 1,508 days). Kaplan-Meier analysis showed observed survival for ablated patients was longer than among patients treated medically (p < 0.001), and not different from that expected for healthy persons of the same gender and calendar year of birth (p = 0.55). Cox proportional-hazards model revealed in the ablation group hazard ratios of 0.46 (95% confidence interval [CI], 0.31 to 0.68; p < 0.001) for all-cause mortality, of 0.45 (95% CI, 0.31 to 0.64; p < 0.001) for morbidities mainly due to heart failure and ischemic cerebrovascular events, and of 0.30 (95% CI, 0.24 to 0.37; p < 0.001) for AF recurrence. Ablated patients' QoL, different from patients treated medically, reached normative levels at six months and remained unchanged at one year.
CONCLUSIONS: Pulmonary vein ablation improves mortality, morbidity, and QoL as compared with medical therapy. Our findings pave the way for randomized trials to prospect a wider application of ablation therapy for AF.
Christian T Ruff, Robert P Giugliano, Eugene Braunwald, Elaine B Hoffman, Naveen Deenadayalu, Michael D Ezekowitz, A John Camm, Jeffrey I Weitz, Basil S Lewis, Alexander Parkhomenko, Takeshi Yamashita, Elliott M Antman
Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.
Lancet. 2014 Mar 15;383(9921):955-62. doi: 10.1016/S0140-6736(13)62343-0. Epub 2013 Dec 4.
Abstract/Text
BACKGROUND: Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes.
METHODS: We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity.
FINDINGS: 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045).
INTERPRETATION: This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.
FUNDING: None.
Copyright © 2014 Elsevier Ltd. All rights reserved.
J Campbell Cowan, Jianhua Wu, Marlous Hall, Andi Orlowski, Robert M West, Chris P Gale
A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation.
Eur Heart J. 2018 Aug 21;39(32):2975-2983. doi: 10.1093/eurheartj/ehy411.
Abstract/Text
Aims: To determine whether changing patterns of anticoagulant use in atrial fibrillation (AF) have impacted on stroke rates in England.
Methods and results: English national databases, 2006-2016, were interrogated to assess stroke admissions and oral anticoagulant use. The number of patients with known AF increased linearly from 692 054 to 983 254 (prevalence 1.29% vs. 1.71%). Hospital episodes of AF-related stroke/100 000 AF patients increased from 80/week in 2006 to 98/week in 2011 and declined to 86/week in 2016 (2006-2011 difference 18.0, 95% confidence interval (CI) 17.9-18.1, 2011-2016 difference -12.0, 95% CI -12.1 to -11.9). Anticoagulant use amongst patients with CHA2DS2-VASc ≥2 increased from 48.0% to 78.6% and anti-platelet use declined from 42.9% to 16.1%; the greatest rate of change occurred in the second 5 year period (for anticoagulants 2006-2011 difference 4.8%, 95% CI 4.5-5.1%, 2011-2016 difference 25.8%, 95% CI 25.5-26.1%). After adjustment for AF prevalence, a 1% increase in anticoagulant use was associated with a 0.8% decrease in the weekly rate of AF-related stroke (incidence rate ratio 0.992, 95% CI 0.989-0.994). Had the use of anticoagulants remained at 2009 levels, 4068 (95% CI 4046-4089) more strokes would have been predicted in 2015/2016.
Conclusion: Between 2006 and 2016, AF prevalence and anticoagulant use in England increased. From 2011, hospitalized AF-related stroke rates declined and were significantly associated with increased anticoagulant uptake.
T Jared Bunch, Heidi T May, Tami L Bair, J Peter Weiss, Brian G Crandall, Jeffrey S Osborn, Charles Mallender, Jeffrey L Anderson, Brent J Muhlestein, Donald L Lappe, John D Day
Atrial fibrillation ablation patients have long-term stroke rates similar to patients without atrial fibrillation regardless of CHADS2 score.
Heart Rhythm. 2013 Sep;10(9):1272-7. doi: 10.1016/j.hrthm.2013.07.002. Epub 2013 Jul 5.
Abstract/Text
BACKGROUND: Atrial fibrillation (AF) is a leading cause of total and fatal ischemic stroke. Stroke risk after AF ablation appears to be favorably affected; however, it is largely unknown whether the benefit extends to all stroke CHADS2 risk profiles of AF patients.
OBJECTIVE: To determine if ablation of atrial fibrillation reduces stroke rates in all risk groups.
METHODS: A total of 4212 consecutive patients who underwent AF ablation were compared (1:4) with 16,848 age-/sex-matched controls with AF (no ablation) and to 16,848 age-/sex-matched controls without AF. Patients were enrolled from the large ongoing prospective Intermountain Atrial Fibrillation Study and were followed for at least 3 years.
RESULTS: Of the 37,908 patients, the mean age was 65.0 ± 13 years and 4.4% (no AF), 6.3% (AF, no ablation), and 4.5% (AF ablation) patients had a prior stroke (P < .0001). The profile of CHADS2 scores between comparative groups was similar: 0-1 (69.3%, no AF; 62.3%, AF, no ablation; 63.6%, AF ablation), 2-3 (26.5%, no AF; 29.7%, AF, no ablation; 28.7%, AF ablation), and ≥4 (4.3%, no AF; 8.0%, AF, no ablation; 7.7%, AF ablation). A total of 1296 (3.4%) patients had a stroke over the follow-up period. Across all CHADS2 profiles and ages, AF patients with ablation had a lower long-term risk of stroke compared to patients without ablation. Furthermore, AF ablation patients had similar long-term risks of stroke across all CHADS2 profiles and ages compared to patients with no history of AF.
CONCLUSIONS: In our study populations, AF ablation patients have a significantly lower risk of stroke compared to AF patients who do not undergo ablation independent of baseline stroke risk score.
Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Hirofumi Tomita, Joji Hagii, Norifumi Metoki, Shin Saito, Hiroshi Shiroto, Hiroyasu Hitomi, Takaatsu Kamada, Satoshi Seino, Koki Takahashi, Satoko Sasaki, Minoru Yasujima, Ken Okumura
Severity and Functional Outcome of Patients with Cardioembolic Stroke Occurring during Non-vitamin K Antagonist Oral Anticoagulant Treatment.
J Stroke Cerebrovasc Dis. 2015 Jun;24(6):1430-7. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.004. Epub 2015 Apr 2.
Abstract/Text
BACKGROUND: Severity and functional outcome of patients with cardioembolic stroke (CE) occurring during non-vitamin K antagonist oral anticoagulant (NOAC) treatment remain uncertain.
METHODS: The consecutive 355 CE patients within 48 hours after onset and with modified Rankin Scale (mRS) score of 1 or less before onset were studied. Of all, 262 patients were treated with no anticoagulants (non-AC), 63 with warfarin below therapeutic range of prothrombin time-international normalized ratio (PT-INR) on admission (PT-INR <1.6 [WF-Lo]), 16 with warfarin within therapeutic range (PT-INR ≥1.6 [WF-Tp]), and 14 with NOACs (9 dabigatran and 5 rivaroxaban [NOAC-DR]). We compared severity and functional outcome of CE patients among these 4 groups, especially focusing on patients during NOAC treatment.
RESULTS: Stroke severity on admission, assessed by the National Institutes of Health Stroke Scale, was lower in WF-Tp (median, 5 [1-15]) and NOAC-DR (5 [3-6]) than in non-AC (11 [5-19]) and WF-Lo (12 [5-19]; P = .006). Functional outcome at discharge, assessed by mRS, was favorable in WF-Tp (median, 1 [0-4]) and NOAC-DR (1 [1-2]) compared with that in non-AC (2 [1-4]) and WF-Lo (3 [1-5]; P = .02), and ratios of the patients with mRS score of 1 or less were 63% and 64% versus 31% and 33%, respectively (P = .005). Multivariate analysis also showed a favorable functional outcome at discharge in WF-Tp and NOAC-DR groups. Drug management was likely associated with NOAC-associated CE.
CONCLUSIONS: Stroke severity and functional outcome of CE patients treated with warfarin within therapeutic range and with NOACs are similar to each other, and are more favorable than those with no anticoagulants and with warfarin below therapeutic range.
Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Ayman A Hussein, Walid I Saliba, Amr Barakat, Mohammed Bassiouny, Mohammed Chamsi-Pasha, Rasha Al-Bawardy, Ali Hakim, Khaldoun Tarakji, Bryan Baranowski, Daniel Cantillon, Thomas Dresing, Patrick Tchou, David O Martin, Niraj Varma, Mandeep Bhargava, Thomas Callahan, Mark Niebauer, Mohamed Kanj, Mina Chung, Andrea Natale, Bruce D Lindsay, Oussama M Wazni
Radiofrequency Ablation of Persistent Atrial Fibrillation: Diagnosis-to-Ablation Time, Markers of Pathways of Atrial Remodeling, and Outcomes.
Circ Arrhythm Electrophysiol. 2016 Jan;9(1):e003669. doi: 10.1161/CIRCEP.115.003669.
Abstract/Text
BACKGROUND: Various ablation strategies of persistent atrial fibrillation (PersAF) have had disappointing outcomes, despite concerted clinical and research efforts, which could reflect progressive atrial fibrillation-related atrial remodeling.
METHODS AND RESULTS: Two-year outcomes were assessed in 1241 consecutive patients undergoing first-time ablation of PersAF (2005-2012). The time intervals between the first diagnosis of PersAF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide and C-reactive protein before the procedures. The median diagnosis-to-ablation time was 3 years (25th-75th percentiles 1-6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in recurrence rates in addition to an increase in B-type natriuretic peptide levels (P=0.01), C-reactive protein levels (P<0.0001), and left atrial size (P=0.03). The arrhythmia recurrence rates over 2 years were 33.6%, 52.6%, 57.1%, and 54.6% in the first, second, third, and fourth quartiles, respectively (P(categorical)<0.0001). In Cox Proportional Hazard analyses, B-type natriuretic peptide levels, C-reactive protein levels, and left atrial size were associated with arrhythmia recurrence. The diagnosis-to-ablation time had the strongest association with the ablation outcomes which persisted in multivariable Cox analyzes (hazard ratio for recurrence per +1Log diagnosis-to-ablation time 1.27, 95% confidence interval 1.14-1.43; P<0.0001; hazard ratio fourth versus first quartile 2.44, 95% confidence interval 1.68-3.65; P(categorical)<0.0001).
CONCLUSIONS: In patients with PersAF undergoing ablation, the time interval between the first diagnosis of PersAF and the catheter ablation procedure had a strong association with the ablation outcomes, such as shorter diagnosis-to-ablation times were associated with better outcomes and in direct association with markers of atrial remodeling.
© 2016 American Heart Association, Inc.
