1 Introduction
2 Definitions, mechanisms, and rationale for AF ablation
AF episode | An AF episode is defined as AF that is documented by ECG monitoring or intracardiac electrogram monitoring and has a duration of at least 30 s, or if less than 30 s, is present throughout the ECG monitoring tracing. The presence of subsequent episodes of AF requires that sinus rhythm be documented by ECG monitoring between AF episodes. |
Chronic AF | Chronic AF has variable definitions and should not be used to describe populations of AF patients undergoing AF ablation. |
Early persistent AF | Early persistent AF is defined as AF that is sustained beyond 7 days but is less than 3 months in duration. |
Lone AF | Lone AF is a historical descriptor that is potentially confusing and should not be used to describe populations of patients with AF undergoing AF ablation. |
Long-standing persistent AF | Long-standing persistent AF is defined as continuous AF of greater than 12 months’ duration. |
Paroxysmal AF | Paroxysmal AF is defined as AF that terminates spontaneously or with intervention within 7 days of onset. |
Permanent AF | Permanent AF is defined as the presence of AF that is accepted by the patient and physician, and for which no further attempts to restore or maintain sinus rhythm will be undertaken. The term permanent AF represents a therapeutic attitude on the part of the patient and physician rather than an inherent pathophysiological attribute of AF. The term permanent AF should not be used within the context of a rhythm control strategy with antiarrhythmic drug therapy or AF ablation. |
Persistent AF | Persistent AF is defined as continuous AF that is sustained beyond 7 days. |
Silent AF | Silent AF is defined as asymptomatic AF diagnosed with an opportune ECG or rhythm strip. |
3 Modifiable risk factors for AF and impact on ablation
4 Indications
Recommendation | Class | LOE | References | |
---|---|---|---|---|
Indications for catheter ablation of atrial fibrillation | ||||
A. Indications for catheter ablation of atrial fibrillation | ||||
Symptomatic AF refractory or intolerant to at least one Class I or III antiarrhythmic medication | Paroxysmal: Catheter ablation is recommended. | I | A | |
Persistent: Catheter ablation is reasonable. | IIa | B-NR | ||
Long-standing persistent: Catheter ablation may be considered. | IIb | C-LD | ||
Symptomatic AF prior to initiation of antiarrhythmic therapy with a Class I or III antiarrhythmic medication | Paroxysmal: Catheter ablation is reasonable. | IIa | B-R | |
Persistent: Catheter ablation is reasonable. | IIa | C-EO | ||
Long-standing persistent: Catheter ablation may be considered. | IIb | C-EO | ||
B. Indications for catheter atrial fibrillation ablation in populations of patients not well represented in clinical trials | ||||
Congestive heart failure | It is reasonable to use similar indications for AF ablation in selected patients with heart failure as in patients without heart failure. | IIa | B-R | |
Older patients (>75 years of age) | It is reasonable to use similar indications for AF ablation in selected older patients with AF as in younger patients. | IIa | B-NR | |
Hypertrophic cardiomyopathy | It is reasonable to use similar indications for AF ablation in selected patients with HCM as in patients without HCM. | IIa | B-NR | |
Young patients (<45 years of age) | It is reasonable to use similar indications for AF ablation in young patients with AF (<45 years of age) as in older patients. | IIa | B-NR | |
Tachy-brady syndrome | It is reasonable to offer AF ablation as an alternative to pacemaker implantation in patients with tachy-brady syndrome. | IIa | B-NR | |
Athletes with AF | It is reasonable to offer high-level athletes AF as first-line therapy due to the negative effects of medications on athletic performance. | IIa | C-LD | |
Asymptomatic AF∗∗
| Paroxysmal: Catheter ablation may be considered in select patients.∗∗
| IIb | C-EO | |
Persistent: Catheter ablation may be considered in select patients. | IIb | C-EO | [68] | |
Indications for surgical ablation of atrial fibrillation | ||||
C. Indications for concomitant open (such as mitral valve) surgical ablation of atrial fibrillation | ||||
Symptomatic AF refractory or intolerant to at least one Class I or III antiarrhythmic medication | Paroxysmal: Surgical ablation is recommended. | I | B-NR | |
Persistent: Surgical ablation is recommended. | I | B-NR | ||
Long-standing persistent: Surgical ablation is recommended. | I | B-NR | ||
Symptomatic AF prior to initiation of antiarrhythmic therapy with a Class I or III antiarrhythmic medication | Paroxysmal: Surgical ablation is recommended. | I | B-NR | |
Persistent: Surgical ablation is recommended. | I | B-NR | ||
Long-standing persistent: Surgical ablation is recommended. | I | B-NR | ||
D. Indications for concomitant closed (such as CABG and AVR) surgical ablation of atrial fibrillation | ||||
Symptomatic AF refractory or intolerant to at least one Class I or III antiarrhythmic medication | Paroxysmal: Surgical ablation is recommended. | I | B-NR | |
Persistent: Surgical ablation is recommended. | I | B-NR | ||
Long-standing persistent: Surgical ablation is recommended. | I | B-NR | ||
Symptomatic AF prior to initiation of antiarrhythmic therapy with a Class I or III antiarrhythmic medication | Paroxysmal: Surgical ablation is reasonable. | IIa | B-NR | |
Persistent: Surgical ablation is reasonable. | IIa | B-NR | ||
Long-standing persistent: Surgical ablation is reasonable. | IIa | B-NR | ||
E. Indications for stand-alone and hybrid surgical ablation of atrial fibrillation | ||||
Symptomatic AF refractory or intolerant to at least one Class I or III antiarrhythmic medication | Paroxysmal: Stand-alone surgical ablation can be considered for patients who have failed one or more attempts at catheter ablation and also for those who are intolerant or refractory to antiarrhythmic drug therapy and prefer a surgical approach, after review of the relative safety and efficacy of catheter ablation versus a stand-alone surgical approach. | IIb | B-NR | |
Persistent: Stand-alone surgical ablation is reasonable for patients who have failed one or more attempts at catheter ablation and also for those patients who prefer a surgical approach after review of the relative safety and efficacy of catheter ablation versus a stand-alone surgical approach. | IIa | B-NR | ||
Long-standing persistent: Stand-alone surgical ablation is reasonable for patients who have failed one or more attempts at catheter ablation and also for those patients who prefer a surgical approach after review of the relative safety and efficacy of catheter ablation versus a stand-alone surgical approach. | IIa | B-NR | ||
It might be reasonable to apply the indications for stand-alone surgical ablation described above to patients being considered for hybrid surgical AF ablation. | IIb | C-EO |
5 Strategies, techniques, and endpoints
Recommendation | Class | LOE | References | |
---|---|---|---|---|
PV isolation by catheter ablation | Electrical isolation of the PVs is recommended during all AF ablation procedures. | I | A | |
Achievement of electrical isolation requires, at a minimum, assessment and demonstration of entrance block into the PV. | I | B-R | ||
Monitoring for PV reconnection for 20 min following initial PV isolation is reasonable. | IIa | B-R | ||
Administration of adenosine 20 min following initial PV isolation using RF energy with reablation if PV reconnection might be considered. | IIb | B-R | ||
Use of a pace-capture (pacing along the ablation line) ablation strategy may be considered. | IIb | B-R | ||
Demonstration of exit block may be considered. | IIb | B-NR | ||
Ablation strategies to be considered for use in conjunction with PV isolation | If a patient has a history of typical atrial flutter or typical atrial flutter is induced at the time of AF ablation, delivery of a cavotricuspid isthmus linear lesion is recommended. | I | B-R | |
If linear ablation lesions are applied, operators should use mapping and pacing maneuvers to assess for line completeness. | I | C-LD | ||
If a reproducible focal trigger that initiates AF is identified outside the PV ostia at the time of an AF ablation procedure, ablation of the focal trigger should be considered. | IIa | C-LD | ||
When performing AF ablation with a force-sensing RF ablation catheter, a minimal targeted contact force of 5 to 10 g is reasonable. | IIa | C-LD | ||
Posterior wall isolation might be considered for initial or repeat ablation of persistent or long-standing persistent AF. | IIb | C-LD | ||
Administration of high-dose isoproterenol to screen for and then ablate non-PV triggers may be considered during initial or repeat AF ablation procedures in patients with paroxysmal, persistent, or long-standing persistent AF. | IIb | C-LD | ||
DF-based ablation strategy is of unknown usefulness for AF ablation. | IIb | C-LD | ||
The usefulness of creating linear ablation lesions in the right or left atrium as an initial or repeat ablation strategy for persistent or long-standing persistent AF is not well established. | IIb | B-NR | ||
The usefulness of linear ablation lesions in the absence of macroreentrant atrial flutter is not well established. | IIb | C-LD | ||
The usefulness of mapping and ablation of areas of abnormal myocardial tissue identified with voltage mapping or MRI as an initial or repeat ablation strategy for persistent or long-standing persistent AF is not well established. | IIb | B-R | ||
The usefulness of ablation of complex fractionated atrial electrograms as an initial or repeat ablation strategy for persistent and long-standing persistent AF is not well established. | IIb | B-R | ||
The usefulness of ablation of rotational activity as an initial or repeat ablation strategy for persistent and long-standing persistent AF is not well established. | IIb | B-NR | ||
The usefulness of ablation of autonomic ganglia as an initial or repeat ablation strategy for paroxysmal, persistent, and long-standing persistent AF is not well established. | IIb | B-NR | ||
Nonablation strategies to improve outcomes | Weight loss can be useful for patients with AF, including those who are being evaluated to undergo an AF ablation procedure, as part of a comprehensive risk factor management strategy. | IIa | B-R | |
It is reasonable to consider a patient's BMI when discussing the risks, benefits, and outcomes of AF ablation with a patient being evaluated for an AF ablation procedure. | IIa | B-R | ||
It is reasonable to screen for signs and symptoms of sleep apnea when evaluating a patient for an AF ablation procedure and to recommend a sleep evaluation if sleep apnea is suspected. | IIa | B-R | ||
Treatment of sleep apnea can be useful for patients with AF, including those who are being evaluated to undergo an AF ablation procedure. | IIa | B-R | ||
The usefulness of discontinuation of antiarrhythmic drug therapy prior to AF ablation in an effort to improve long-term outcomes is unclear. | IIb | C-LD | ||
The usefulness of initiation or continuation of antiarrhythmic drug therapy during the postablation healing phase in an effort to improve long-term outcomes is unclear. | IIb | C-LD | ||
Strategies to reduce the risks of AF ablation | Careful identification of the PV ostia is mandatory to avoid ablation within the PVs. | I | B-NR | |
It is recommended that RF power be reduced when creating lesions along the posterior wall near the esophagus. | I | C-LD | ||
It is reasonable to use an esophageal temperature probe during AF ablation procedures to monitor esophageal temperature and help guide energy delivery. | IIa | C-EO |
6 Technology and tools
7 Technical aspects of ablation to maximize safety and anticoagulation
Recommendation | Class | LOE | References | |
---|---|---|---|---|
Preablation | For patients undergoing AF catheter ablation who have been therapeutically anticoagulated with warfarin or dabigatran, performance of the ablation procedure without interruption of warfarin or dabigatran is recommended. | I | A | |
For patients undergoing AF catheter ablation who have been therapeutically anticoagulated with rivaroxaban, performance of the ablation procedure without interruption of rivaroxaban is recommended. | I | B-R | [374] | |
For patients undergoing AF catheter ablation who have been therapeutically anticoagulated with a NOAC other than dabigatran or rivaroxaban, performance of the ablation procedure without withholding a NOAC dose is reasonable. | IIa | B-NR | [375] | |
Anticoagulation guidelines that pertain to cardioversion of AF should be adhered to in patients who present for an AF catheter ablation procedure. | I | B-NR | ||
For patients anticoagulated with a NOAC prior to AF catheter ablation, it is reasonable to hold one to two doses of the NOAC prior to AF ablation with reinitiation postablation. | IIa | B-NR | ||
Performance of a TEE in patients who are in AF on presentation for AF catheter ablation and who have been receiving anticoagulation therapeutically for 3 weeks or longer is reasonable. | IIa | C-EO | ||
Performance of a TEE in patients who present for ablation in sinus rhythm and who have not been anticoagulated prior to catheter ablation is reasonable. | IIa | C-EO | ||
Use of intracardiac echocardiography to screen for atrial thrombi in patients who cannot undergo TEE may be considered. | IIb | C-EO | ||
During ablation | Heparin should be administered prior to or immediately following transseptal puncture during AF catheter ablation procedures and adjusted to achieve and maintain an ACT of at least 300 s. | I | B-NR | |
Administration of protamine following AF catheter ablation to reverse heparin is reasonable. | IIa | B-NR | [394] | |
Postablation | In patients who are not therapeutically anticoagulated prior to catheter ablation of AF and in whom warfarin will be used for anticoagulation postablation, low molecular weight heparin or intravenous heparin should be used as a bridge for initiation of systemic anticoagulation with warfarin following AF ablation.∗
| I | C-EO | |
Systemic anticoagulation with warfarin∗or a NOAC is recommended for at least 2 months postcatheter ablation of AF. | I | C-EO | ||
Adherence to AF anticoagulation guidelines is recommended for patients who have undergone an AF ablation procedure, regardless of the apparent success or failure of the procedure. | I | C-EO | ||
Decisions regarding continuation of systemic anticoagulation more than 2 months post ablation should be based on the patient's stroke risk profile and not on the perceived success or failure of the ablation procedure. | I | C-EO | ||
In patients who have not been anticoagulated prior to catheter ablation of AF or in whom anticoagulation with a NOAC or warfarin has been interrupted prior to ablation, administration of a NOAC 3 to 5 h after achievement of hemostasis is reasonable postablation. | IIa | C-EO | ||
Patients in whom discontinuation of anticoagulation is being considered based on patient values and preferences should consider undergoing continuous or frequent ECG monitoring to screen for AF recurrence. | IIb | C-EO |
Differential | Suggested evaluation | |
---|---|---|
Signs and symptoms of complications within a month postablation | ||
Back pain | Musculoskeletal, retroperitoneal hematoma | Physical exam, CT imaging |
Chest pain | Pericarditis, pericardial effusion, coronary stenosis (ablation related), pulmonary vein stenosis, musculoskeletal (after cardioversion), worsening reflux | Physical exam, chest X-ray, ECG, echocardiogram, stress test, cardiac catheterization, chest CT |
Cough | Infectious process, bronchial irritation (mechanical, cryoballoon), pulmonary vein stenosis | Physical exam, chest X-ray, chest CT |
Dysphagia | Esophageal irritation (related to transesophageal echocardiography), atrioesophageal fistula | Physical exam, chest CT or MRI |
Early satiety, nausea | Gastric denervation | Physical exam, gastric emptying study |
Fever | Infectious process, pericarditis, atrioesophageal fistula | Physical exam, chest X-ray, chest CT, urinalysis, laboratory blood work |
Fever, dysphagia, neurological symptoms | Atrial esophageal fistula | Physical exam, laboratory blood work, chest CT or MRI; avoid endoscopy with air insufflation |
Groin pain at site of access | Pseudoaneurysm, AV fistula, hematoma | Ultrasound of the groin, laboratory blood work; consider CT scan if ultrasound negative |
Headache | Migraine (related to anesthesia or transseptal access, hemorrhagic stroke), effect of general anesthetic | Physical exam, brain imaging (MRI) |
Hypotension | Pericardial effusion/tamponade, bleeding, sepsis, persistent vagal reaction | Echocardiography, laboratory blood work |
Hemoptysis | PV stenosis or occlusion, pneumonia | Chest X-ray, chest CT or MR scan, VQ scan |
Neurological symptoms | Cerebral embolic event, atrial esophageal fistula | Physical exam, brain imaging, chest CT or MRI |
Shortness of breath | Volume overload, pneumonia, pulmonary vein stenosis, phrenic nerve injury | Physical exam, chest X-ray, chest CT, laboratory blood work |
Signs and symptoms of complications more than a month postablation | ||
Fever, dysphagia, neurological symptoms | Atrial esophageal fistula | Physical exam, laboratory blood work, chest CT or MRI; avoid endoscopy with air insufflation |
Persistent cough, atypical chest pain | Infectious process, pulmonary vein stenosis | Physical exam, laboratory blood work, chest X-ray, chest CT or MRI |
Neurological symptoms | Cerebral embolic event, atrial esophageal fistula | Physical exam, brain imaging, chest CT or MRI |
Hemoptysis | PV stenosis or occlusion, pneumonia | CT scan, VQ scan |
8 Follow-up considerations
Type of recorder | Typical monitoring duration | Continuous recording | Event recording | Auto trigger | Unique features |
---|---|---|---|---|---|
Holter monitor | 24–48 h, approximately 7–30 days | Yes | Yes | N/A | Short term, provides quantitative data on arrhythmia burden |
Patch monitor | 1–3 weeks | Yes | Yes | N/A | Intermediate term, can provide continuous data for up to several weeks; improved patient compliance without lead wires |
External loop recorder | 1 month | Yes | Yes | Variable | Good correlation between symptoms and even brief arrhythmias |
External nonloop recorder | Months | No | Yes | No | May be used long term and intermittently; will not capture very brief episodes |
Smartphone monitor | Indefinite | No | Yes | No | Provides inexpensive long-term intermittent monitoring; dependent on patient compliance; requires a smartphone |
Mobile cardiac telemetry | 30 days | Yes | Yes | Yes | Real time central monitoring and alarms; relatively expensive |
Implantable loop recorder | Up to 3 years | Yes | Yes | Yes | Improved patient compliance for long-term use; not able to detect 30-s episodes of AF due to detection algorithm; presence of AF needs to be confirmed by EGM review because specificity of detection algorithm is imperfect; expensive |
Pacemakers or ICDs with atrial leads | Indefinite | Yes | Yes | Yes | Excellent AF documentation of burden and trends; presence of AF needs to be confirmed by electrogram tracing review because specificity of detection algorithms is imperfect; expensive |
Wearable multisensor ECG monitors | Indefinite | Yes | Yes | Yes | ECG 3 leads, temp, heart rate, HRV, activity tracking, respiratory rate, galvanic skin response |
9 Outcomes and efficacy
Trial | Year | Type |
N
| AF type | Ablation strategy | Initial time frame | Effectiveness endpoint | Ablation success | Drug/ Control success |
P value for success | Ablation complications | Drug/Control complications | Comments |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Clinical Trials Performed for FDA Approval | |||||||||||||
JAMA 2010; 303: 333-340 (ThermoCool AF) [14] | 2010 | Randomized to RF ablation or AAD, multicenter | 167 | Paroxysmal | PVI, optional CFAEs and lines | 12 months | Freedom from symptomatic paroxysmal atrial fibrillation, acute procedural failure, or changes in specified drug regimen | 66% | 16% | <0.001 | 4.9% | 8.8% | FDA approval received |
JACC 2013; 61: 1713-1723 (STOP AF) [9] | 2013 | Randomized to cryoballoon ablation or AAD, multicenter | 245 | Paroxysmal | PVI | 12 months | Freedom from any detectable AF, use of nonstudy AAD, or nonprotocol intervention for AF | 70% | 7% | <0.001 | 3.1% | NA | FDA approval received |
Heart Rhythm 2014; 11: 202-209 (TTOP) [22] | 2014 | Randomized to phased RF ablation or AAD/cardioversion, multicenter | 210 | Persistent | PVI + CFAEs | 6 months | Acute procedural success, ≥90% reduction in AF burden, off AAD | 56% | 26% | <0.001 | 12.3% | NA | Not FDA approved |
JACC 2014; 64: 647-656 (SMART-AF) [13] | 2014 | Nonrandomzied multicenter study of contact force-sensing RF catheter, comparing to performance goals | 172 | Paroxysmal | PVI, optional CFAEs and lines | 12 months | Freedom from symptomatic AF, flutter, tachycardia, acute procedural failure, or changes in AAD | 72.5% | N/A | <0.0001 | 7.5% | NA | FDA approval received |
Circulation 2015; 132: 907-915 (TOCCASTAR) [12] | 2015 | Randomized to contact force sensing RF catheter or approved RF catheter, multicenter | 300 | Paroxysaml | PVI, optional triggers, CAFEs and lines in both arms | 12 months | Acute procedural success + Freedom from Symptomatic AF/Flutter/Tachycardia off AAD | 67.8% | 69.4% | 0.0073 for noninferiority | 7.2% | 9.1% | FDA approval received |
JACC 2015; 66: 1350-1360 (HeartLight) [11] | 2015 | Randomized to laserballoon or approved RF catheter, multicenter | 353 | Paroxysmal | PVI ± CTI ablation vs PVI, optional CFAEs, and Lines | 12 months | Freedom from Symptomatic AF/Flutter/Tachycardia, acute procedural failure, AAD, or non-prototocol intervention | 61.1% | 61.7% | 0.003 for noninferiority | 5.3% | 6.4% | FDA approval received |
First-Line Therapy Trials | |||||||||||||
JAMA 2005; 293: 2634-2640 (RAAFT) [29] | 2005 | Randomized to drug, multicenter | 70 | Paroxysmal (N=67), persistent (N= 3) | PVI | 12 months | Freedom from detectable AF | 84% | 37% | <0.01 | 9% | 11% | |
NEJM 2012; 367:1587-1595 (MANTRA-PAF) [30] | 2012 | Randomized to drug, multicenter | 294 | Paroxysmal AF | PVI, roof line, optional mitral and tricuspid line | 24 months | Cumulative AF burden | 13% AF burden | 19% AF burden | NS | 17% | 15% | |
JAMA 2014; 311: 692-700 (RAAFT-2) [31] | 2014 | Randomized to drug multicenter | 127 | Paroxysmal AF | PVI plus optional non-PVI targets | 24 months | Freedom from detectable AF, flutter, tachycardia | 45% | 28% | 0.02 | 9% | 4.9% | |
Other Paroxysmal AF Ablation Trials | |||||||||||||
JACC 2006; 48: 2340-2347 (APAF) [16] | 2006 | Randomized to drug single center | 198 | Paroxysmal AF | PVI, mitral line and tricuspid line | 12 months | Freedom from detectable AF, flutter, tachycardia | 86% | 22% | <0.001 | 1% | 23% | |
Circulation 2008; 118: 2498-2505 (A4) [7] | 2008 | Randomized to drug | 112 | Paroxysmal | PVI (optional LA lines, CTI, focal) | 12 months | Freedom from AF | 89% | 23% | <0.0001 | 5.7% | 1.7% | |
NEJM 2016; 374: 2235-2245 (FIRE AND ICE) [10] | 2016 | Randomized RF vs Cryo, multicenter | 762 | Paroxysmal AF | PVI | 12 months | Freedom from detectable AF, flutter, tachycardia | 64.1% (RF) | 65.4% (cryo) | NS | 12.8% | 10.2% | |
JACC 2016; 68: 2747-2757 [15] | 2016 | Randomized to hot balloon or drug, multicenter | 100 | Paroxysmal AF | PVI | 12 months | Freedom from AF | 59% | 5% | <0.001 | 10.4% | 4.7% | |
Other Persistent AF Ablation Trials | |||||||||||||
NEJM 2006; 354: 934-941 [25] | 2006 | Randomized to RF ablation or to CV and short term amio | 146 | Persistent | PVI, roof, mitral line | 12 months | No AF or flutter month 12 | 74% | 58% | 0.05 | 1.3% | 1.4% | |
EHJ 2014; 35: 501-507 (SARA) [26] | 2014 | Randomized to drug (2:1 ablation to drug), multicenter | 146 | Persistent | PVI (optional LA lines, CFAEs) | 12 months | Freedom from AF/flutter lasting >24h | 70% | 44% | 0.002 | 6.1% | 4.20% | |
NEJM 2015; 372: 1812-1822 [19] | 2015 | Randomized ablation strategies, multicenter | 589 | Persistent | PVI alone versus PVI & CFAEs or PVI & lines | 18 months | Freedom from afib with or without drugs | 59% (PVI alone) | 49% & 46% | NS | 6% | 4.3% & 7.6% | |
Other Mixed Paroxysmal and Persistent AF Ablation Trials | |||||||||||||
J Med Assoc Thai 2003; 86 (Suppl 1): S8-S16 [24] | 2003 | Randomized to RF ablation or amiodarone | 30 | Paroxysmal (70%), Persistent (30%) | PVI, mitral line, CTI, SVC to IVC | 12 months | Freedom from AF | 79% | 40% | 0.018 | 6.70% | 47% | |
EHJ 2006; 27: 216-221 [17] | 2006 | Randomized to RF ablation or drug, multicenter | 137 | Paroxysmal (67%), Persistent (33%) | PVI, mitral line, CTI | 12 months | Freedom from AF, flutter, tachycardia | 66% | 9% | <0.001 | 4.40% | 2.90% | |
JCVEP 2009, 20: 22-28 [18] | 2009 | Randomized to RF ablation or drug, multicenter | 70 | Paroxysmal (41%), Persistent (59%) & type 2 DM | PVI, CTI, optional mitral line and roof line | 12 months | Freedom from AF and atypical atrial flutter | 80% | 43% | 0.001 | 2.90% | 17% | |
Randomized Trials of AF Ablation in Patients with Heart Failure | |||||||||||||
NEJM 2008; 359: 1778-1785 (PABA-HF) [38] | 2008 | Randomized to RF ablation of AVJ abl and BiV pacing | 81 | Persistent (50%), Paroxysmal (50%), EF 27% abl, 29% AVJ | PVI, optional linear abl and CFAEs | 6 months | Composite EF, 6 min walk, MLWHF score; freedom from AF (secondary, mult proc, +/- AA drugs) | 88% AF free, EF 35% abl, 28% AVJ (P <.001), > QOL and 6 min walk increase with abl | <0.001 | 14.60% | 17.50% | ||
Heart 2011; 97: 740-747 [39] | 2011 | Randomized to RF ablation or pharmacological rate control | 41 | Persistent, EF 20% abl, 16% rate control | PVI, roof line, CFAEs | 6 months | Change in LVEF, sinus rhythm at 6 months (secondary) | 50% in NSR, LVEF increase 4.5% | 0% in NSR, LVEF increase 2.8% | 0.6 (for EF increase) | 15% | Not reported | |
JACC 2013; 61: 1894-1903 [46] | 2013 | Randomized to RF ablation or pharmacological rate control | 52 | Persistent AF (100%), EF 22% abl, 25% rate control | PVI, optional linear abl and CFAEs | 12 months | Change in peak O2 consumption (also reported single procedure off drug ablation success) | Peak O2 consumption increase greater with abl, 72% abl success | 0.018 | 15% | Not reported | ||
Circ A and E 2014; 7: 31-38 [40] | 2014 | Randomized to RF ablation or pharmacological rate control | 50 | Persistent AF (100%), EF 32% abl, 34% rate control | PVI, optional linear abl and CFAEs | 6 months | Change in LVEF at 6 months, multiple procedure freedom from AF also reported | LVEF 40% with abl, 31% rate control, 81% AF free with abl | 0.015 | 7.70% |
10 Complications
Asymptomatic cerebral embolism | Asymptomatic cerebral embolism is defined as an occlusion of a blood vessel in the brain due to an embolus that does not result in any acute clinical symptoms. Silent cerebral embolism is generally detected using a diffusion weighted MRI. |
Atrioesophageal fistula | An atrioesophageal fistula is defined as a connection between the atrium and the lumen of the esophagus. Evidence supporting this diagnosis includes documentation of esophageal erosion combined with evidence of a fistulous connection to the atrium, such as air emboli, an embolic event, or direct observation at the time of surgical repair. A CT scan or MRI scan is the most common method of documentation of an atrioesophageal fistula. |
Bleeding | Bleeding is defined as a major complication of AF ablation if it requires and/or is treated with transfusion or results in a 20% or greater fall in hematocrit. |
Bleeding following cardiac surgery | Excessive bleeding following a surgical AF ablation procedure is defined as bleeding requiring reoperation or ≥2 units of PRBC transfusion within any 24 h of the first 7 days following the index procedure. |
Cardiac perforation | We recommend that cardiac perforation be defined together with cardiac tamponade. See “Cardiac tamponade/perforation.” |
Cardiac tamponade | We recommend that cardiac tamponade be defined together with cardiac perforation. See “Cardiac tamponade/perforation.” |
Cardiac tamponade/perforation | Cardiac tamponade/perforation is defined as the development of a significant pericardial effusion during or within 30 days of undergoing an AF ablation procedure. A significant pericardial effusion is one that results in hemodynamic compromise, requires elective or urgent pericardiocentesis, or results in a 1-cm or more pericardial effusion as documented by echocardiography. Cardiac tamponade/perforation should also be classified as “early” or “late” depending on whether it is diagnosed during or following initial discharge from the hospital. |
Deep sternal wound infection/mediastinitis following cardiac surgery | Deep sternal wound infection/mediastinitis following cardiac surgery requires one of the following: (1) an organism isolated from culture of mediastinal tissue or fluid; (2) evidence of mediastinitis observed during surgery; (3) one of the following conditions: chest pain, sternal instability, or fever (>38°C), in combination with either purulent discharge from the mediastinum or an organism isolated from blood culture or culture of mediastinal drainage. |
Esophageal injury | Esophageal injury is defined as an erosion, ulceration, or perforation of the esophagus. The method of screening for esophageal injury should be specified. Esophageal injury can be a mild complication (erosion or ulceration) or a major complication (perforation). |
Gastric motility/pyloric spasm disorders | Gastric motility/pyloric spasm disorder should be considered a major complication of AF ablation when it prolongs or requires hospitalization, requires intervention, or results in late disability, such as weight loss, early satiety, diarrhea, or GI disturbance. |
Major complication | A major complication is a complication that results in permanent injury or death, requires intervention for treatment, or prolongs or requires hospitalization for more than 48 h. Because early recurrences of AF/AFL/AT are to be expected following AF ablation, recurrent AF/AFL/AT within 3 months that requires or prolongs a patient's hospitalization should not be considered to be a major complication of AF ablation. |
Mediastinitis | Mediastinitis is defined as inflammation of the mediastinum. Diagnosis requires one of the following: (1) an organism isolated from culture of mediastinal tissue or fluid; (2) evidence of mediastinitis observed during surgery; (3) one of the following conditions: chest pain, sternal instability, or fever (>38°C), in combination with either purulent discharge from the mediastinum or an organism isolated from blood culture or culture of mediastinal drainage. |
Myocardial infarction in the context of AF ablation | The universal definition of myocardial infarction [395] cannot be applied in the context of catheter or surgical AF ablation procedures because it relies heavily on cardiac biomarkers (troponin and CPK), which are anticipated to increase in all patients who undergo AF ablation as a result of the ablation of myocardial tissue. Similarly, chest pain and other cardiac symptoms are difficult to interpret in the context of AF ablation both because of the required sedation and anesthesia and also because most patients experience chest pain following the procedure as a result of the associated pericarditis that occurs following catheter ablation. We therefore propose that a myocardial infarction, in the context of catheter or surgical ablation, be defined as the presence of any one of the following criteria: (1) detection of ECG changes indicative of new ischemia (new ST-T wave changes or new LBBB) that persist for more than 1 h; (2) development of new pathological Q waves on an ECG; (3) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. |
Pericarditis | Pericarditis should be considered a major complication following ablation if it results in an effusion that leads to hemodynamic compromise or requires pericardiocentesis, prolongs hospitalization by more than 48 h, requires hospitalization, or persists for more than 30 days following the ablation procedure. |
Phrenic nerve paralysis | Phrenic nerve paralysis is defined as absent phrenic nerve function as assessed by a sniff test. A phrenic nerve paralysis is considered to be permanent when it is documented to be present 12 months or longer following ablation. |
Pulmonary vein stenosis | Pulmonary vein stenosis is defined as a reduction of the diameter of a PV or PV branch. PV stenosis can be categorized as mild <50%, moderate 50%–70%, and severe ≥70% reduction in the diameter of the PV or PV branch. A severe PV stenosis should be considered a major complication of AF ablation. |
Serious adverse device effect | A serious adverse device effect is defined as a serious adverse event that is attributed to use of a particular device. |
Stiff left atrial syndrome | Stiff left atrial syndrome is a clinical syndrome defined by the presence of signs of right heart failure in the presence of preserved LV function, pulmonary hypertension (mean PA pressure >25 mmHg or during exercise >30 mmHg), and large V waves ≥10 mmHg or higher) on PCWP or left atrial pressure tracings in the absence of significant mitral valve disease or PV stenosis. |
Stroke or TIA postablation | Stroke diagnostic criteria |
•Rapid onset of a focal or global neurological deficit with at least one of the following: change in level of consciousness, hemiplegia, hemiparesis, numbness or sensory loss affecting one side of the body, dysphasia or aphasia, hemianopia, amaurosis fugax, or other neurological signs or symptoms consistent with stroke | |
•Duration of a focal or global neurological deficit ≥24 h; OR <24 h if therapeutic intervention(s) were performed (e.g., thrombolytic therapy or intracranial angioplasty); OR available neuroimaging documents a new hemorrhage or infarct; OR the neurological deficit results in death. | |
•No other readily identifiable nonstroke cause for the clinical presentation (e.g., brain tumor, trauma, infection, hypoglycemia, peripheral lesion, pharmacological influences).∗
| |
•Confirmation of the diagnosis by at least one of the following: neurology or neurosurgical specialist; neuroimaging procedure (MRI or CT scan or cerebral angiography); lumbar puncture (i.e., spinal fluid analysis diagnostic of intracranial hemorrhage) | |
Stroke definitions | |
• Transient ischemic attack: new focal neurological deficit with rapid symptom resolution (usually 1 to 2 h), always within 24 h; neuroimaging without tissue injury | |
•Stroke: (diagnosis as above, preferably with positive neuroimaging study); | |
Minor—Modified Rankin score <2 at 30 and 90 days†
| |
Major—Modified Rankin score ≥2 at 30 and 90 days | |
Unanticipated adverse device effect | Unanticipated adverse device effect is defined as complication of an ablation procedure that has not been previously known to be associated with catheter or surgical ablation procedures. |
Vagal nerve injury | Vagal nerve injury is defined as injury to the vagal nerve that results in esophageal dysmotility or gastroparesis. Vagal nerve injury is considered to be a major complication if it prolongs hospitalization, requires hospitalization, or results in ongoing symptoms for more than 30 days following an ablation procedure. |
Vascular access complication | Vascular access complications include development of a hematoma, an AV fistula, or a pseudoaneurysm. A major vascular complication is defined as one that requires intervention, such as surgical repair or transfusion, prolongs the hospital stay, or requires hospital admission. |
Complication | Incidence | Selected prevention techniques | Diagnostic testing | Selected treatment options | References |
---|---|---|---|---|---|
Air embolism | <1% | Sheath management | Nothing or cardiac catheterization | Supportive care with fluid, oxygen, head down tilt, hyperbaric oxygen | |
Asymptomatic cerebral emboli (ACE) | 2% to 15% | Anticoagulation, catheter and sheath management, TEE | Brain MRI | None | |
Atrial esophageal fistula | 0.02% to 0.11% | Reduce power, force, and RF time on posterior wall, monitor esophageal temp, use proton pump inhibitors; avoid energy delivery over esophagus | CT scan of chest, MRI; avoid endoscopy with air insufflation | Surgical repair | |
Cardiac tamponade | 0.2% to 5% | Cather manipulation, transseptal technique, reduce power, force, and RF time | Echocardiography | Pericardiocentesis or surgical drainage | |
Coronary artery stenosis/occlusion | <0.1% | Avoid high-power energy delivery near coronary arteries | Cardiac catheterization | PTCA | |
Death | <0.1% to 0.4% | Meticulous performance of procedure, attentive postprocedure care | NA | NA | |
Gastric hypomotility | 0% to 17% | Reduce power, force, and RF time on posterior wall | Endoscopy, barium swallow, gastric emptying study | Metoclopramide, possibly intravenous erythromycin | |
Mitral valve entrapment | <0.1% | Avoid circular catheter placement near or across mitral valve; clockwise torque on catheter | Echocardiography | Gentle catheter manipulation, surgical extraction | |
Pericarditis | 0% to 50% | None proven | Clinical history, ECG, sedimentation rate, echocardiogram | NSAID, colchicine, steroids | |
Permanent phrenic nerve paralysis | 0% to 0.4% | Monitor diaphragm during phrenic pacing, CMAP monitoring, phrenic pacing to identify location and adjust lesion location | CXR, sniff test | Supportive care | |
Pulmonary vein stenosis | <1% | Avoid energy delivery within PV | CT or MRI, V/Q wave scan | Angioplasty, stent, surgery | |
Radiation injury | <0.1% | Minimize fluoroscopy exposure, especially in obese and repeat ablation patients, X-ray equipment | None | Supportive care, rarely skin graft | |
Stiff left atrial syndrome | <1.5% | Limit extent of left atrial ablation | Echocardiography, cardiac catheterization | Diuretics | |
Stroke and TIA | 0% to 2% | Pre-, post-, and intraprocedure anticoagulation, catheter and sheath management, TEE | Head CT or MRI, cerebral angiography | Thrombolytic therapy, angioplasty | |
Vascular complications | 0.2% to 1.5% | Vascular access techniques, ultrasound-guided access, anticoagulation management | Vascular ultrasound, CT scan | Conservative treatment, surgical repair, transfusion |
11 Training requirements
12 Surgical and hybrid AF ablation
13 Clinical trial design
Acute procedural success (pulmonary vein isolation) | Acute procedural success is defined as electrical isolation of all pulmonary veins. A minimal assessment of electrical isolation of the PVs should consist of an assessment of entrance block. If other methods are used to assess PVI, including exit block and/or the use of provocative agents such as adenosine or isoproterenol, they should be prespecified. Furthermore, it is recommended that the wait time used to screen for early recurrence of PV conduction once initial electrical isolation is documented be specified in all prospective clinical trials. |
Acute procedural success (not related by pulmonary vein isolation) | Typically, this would apply to substrate ablation performed in addition to PVI for persistent AF. Although some have proposed AF termination as a surrogate for acute procedural success, its relationship to long-term success is controversial. Complete elimination of the additional substrate (localized rotational activation, scar region, non-PV trigger, or other target) and/or demonstration of bidirectional conduction block across a linear ablation lesion would typically be considered the appropriate endpoint. |
One-year success∗
| One-year success is defined as freedom from AF/AFL/AT after removal from antiarrhythmic drug therapy as assessed from the end of the 3month blanking period to 12 months following the ablation procedure. Because cavotricuspid isthmus-dependent atrial flutter is easily treated with cavotricuspid isthmus ablation and is not an iatrogenic arrhythmia following a left atrial ablation procedure for AF, it is reasonable for clinical trials to choose to prespecify that occurrence of isthmus-dependent atrial flutter, if confirmed by entrainment maneuvers during electrophysiology testing, should not be considered an ablation failure or primary effectiveness endpoint. |
Alternative one-year success | Although the one-year success definition provided above remains the recommended end point that should be reported in all AF ablation trials, and the endpoint for which the objective performance criteria listed below were developed, the Task Force recognizes that alternative definitions for success can be used if the main goal of therapy in the study is to relieve AF-related symptoms and to improve patient QOL. In particular, it is appropriate for clinical trials to define success as freedom from only symptomatic AF/AFL/AT after removal from antiarrhythmic drug therapy as assessed from the end of the 3-month blanking period to 12 months following the ablation procedure if the main goal of therapy in the study is to relieve AF-related symptoms and to improve patient QOL. However, because symptoms of AF can resolve over time, and because studies have shown that asymptomatic AF represents a greater proportion of all AF postablation than prior to ablation, clinical trials need to continue to report freedom from both symptomatic and asymptomatic AF even if this alternative one year success definition is used as the primary trial endpoint. |
Clinical/partial success∗
| It is reasonable for clinical trials to define and incorporate one or more secondary definitions of success that can be referred to as “clinical success” or “partial success.” If these alternative definitions of success are included, they should be defined prospectively. In prior Consensus Documents the Task Force has proposed that clinical/partial success be defined as a “75% or greater reduction in the number of AF episodes, the duration of AF episodes, or the % time a patient is in AF as assessed with a device capable of measuring AF burden in the presence or absence of previously ineffective antiarrhythmic drug therapy.” Because there is no firm scientific basis for selecting the cutoff of 75% rather than a different cutoff, this prior recommendation is provided only as an example of what future clinical trials may choose to use as a definition of clinical/partial success. |
Long-term success∗
| Long-term success is defined as freedom from AF/AFL/AT recurrences following the 3-month blanking period through a minimum of 36-month follow-up from the date of the ablation procedure in the absence of Class I and III antiarrhythmic drug therapy. |
Recurrent AF/AFL/AT | Recurrent AF/AFL/AT is defined as AF/AFL/AT of at least 30 s' duration that is documented by an ECG or device recording system and occurs following catheter ablation. Recurrent AF/AFL/AT may occur within or following the post ablation blanking period. Recurrent AF/AFL/AT that occurs within the postablation blanking period is not considered a failure of AF ablation. |
Early recurrence of AF/AFL/AT | Early recurrence of AF/AFL/AT is defined as a recurrence of atrial fibrillation within three months of ablation. Episodes of atrial tachycardia or atrial flutter should also be classified as a “recurrence.” These are not counted toward the success rate if a blanking period is specified. |
Recurrence of AF/AFL/AT | Recurrence of AF/AFL/AT postablation is defined as a recurrence of atrial fibrillation more than 3 months following AF ablation. Episodes of atrial tachycardia or atrial flutter should also be classified as a “recurrence.” |
Late recurrence of AF/AFL/AT | Late recurrence of AF/AFL/AT is defined as a recurrence of atrial fibrillation 12 months or more after AF ablation. Episodes of atrial tachycardia or atrial flutter should also be classified as a “recurrence.” |
Blanking period | A blanking period of three months should be employed after ablation when reporting efficacy outcomes. Thus, early recurrences of AF/AFL/AT within the first 3 months should not be classified as treatment failure. If a blanking period of less than 3 months is chosen, it should be prespecified and included in the Methods section. |
Stroke screening | A risk-based approach to determine the level of postablation stroke screening in clinical trials is recommended by the Task Force. For ablation devices with a lower risk of stroke and for which a stroke signal has not been reported, a minimum standardized neurological assessment of stroke should be conducted by a physician at baseline and at hospital discharge or 24 h after the procedure, whichever is later. If this neurological assessment demonstrates new abnormal findings, the patient should have a formal neurological consult and examination with appropriate imaging (i.e., DW-MRI), used to confirm any suspected diagnosis of stroke. For devices in which a higher risk of stroke is suspected or revealed in prior trials, a formal neurological examination by a neurologist at discharge or 24 h after the procedure, whichever is later, is recommended. Appropriate imaging should be obtained if this evaluation reveals a new neurological finding. In some studies in which delayed stroke is a concern, repeat neurological screening at 30 days postablation might be appropriate. |
Detectable AF/AFL/AT | Detectable AF is defined as AF/AFL/AT of at least 30 s' duration when assessed with ECG monitoring. If other monitoring systems are used, including implantable pacemakers, implantable defibrillators, and subcutaneous ECG monitoring devices, the definition of detectable AF needs to be prespecified in the clinical trial based on the sensitivity and specificity of AF detection with the particular device. We recommend that episodes of atrial flutter and atrial tachycardia be included within the broader definition of a detectable AF/AFL/AT episode. |
AF/AFL/AT burden | It is reasonable for clinical trials to incorporate AF/AFL/AT burden as a secondary endpoint in a clinical trial of AF ablation. In stating this it is recognized that there are no conclusive data that have validated a rate of AF burden reduction as a predictor of patient benefit (i.e. reduction in mortality and major morbidities such as stroke, CHF, QOL, or hospitalization). If AF burden is included, it is important to predefine and standardize the monitoring technique that will be used to measure AF burden. Available monitoring techniques have been discussed in this document. Should AF burden be selected as an endpoint in a clinical trial, the chosen monitoring technique should be employed at least a month prior to ablation to establish a baseline burden of AF. |
Entrance block | Entrance block is defined as the absence, or if present, the dissociation, of electrical activity within the PV antrum. Entrance block is most commonly evaluated using a circular multielectrode mapping catheter positioned at the PV antrum. Entrance block can also be assessed using detailed point-by-point mapping of the PV antrum guided by an electroanatomical mapping system. The particular method used to assess entrance block should be specified in all clinical trials. Entrance block of the left PVs should be assessed during distal coronary sinus or left atrial appendage pacing in order to distinguish far-field atrial potentials from PV potentials. It is recommended that reassessment of entrance block be performed a minimum of 20 min after initial establishment of PV isolation. |
Procedural endpoints for AF ablation strategies not targeting the PVs | Procedural endpoints for AF ablation strategies not targeting the PVs: The acute procedural endpoints for ablation strategies not targeting the PVs vary depending on the specific ablation strategy and tool. It is important that they be prespecified in all clinical trials. For example, if a linear ablation strategy is used, documentation of bidirectional block across the ablation line must be shown. For ablation of CFAEs, rotational activity, or non-PV triggers, the acute endpoint should at a minimum be elimination of CFAEs, rotational activity, or non-PV triggers. Demonstration of AF slowing or termination is an appropriate procedural endpoint, but it is not required as a procedural endpoint for AF ablation strategies not targeting the PVs. |
Esophageal temperature monitoring | Esophageal temperature monitoring should be performed in all clinical trials of AF ablation. At a minimum, a single thermocouple should be used. The location of the probe should be adjusted during the procedure to reflect the location of energy delivery. Although this document does not provide formal recommendations regarding the specific temperature or temperature change at which energy delivery should be terminated, the Task Force does recommend that all trials prespecify temperature guidelines for termination of energy delivery. |
Enrolled subject | An enrolled subject is defined as a subject who has signed written informed consent to participate in the trial in question. |
Exit block | Exit block is defined as the inability to capture the atrium during pacing at multiple sites within the PV antrum. Local capture of musculature within the pulmonary veins and/or antrum must be documented to be present to make this assessment. Exit block is demonstrated by a dissociated spontaneous pulmonary vein rhythm. |
Nonablative strategies | The optimal nonablative therapy for patients with persistent and long-standing persistent AF who are randomized to the control arm of an AF ablation trial is a trial of a new Class I or III antiarrhythmic agent or a higher dose of a previously failed antiarrhythmic agent. For patients with persistent or long-standing persistent AF, performance of a direct-current cardioversion while taking the new or dose adjusted antiarrhythmic agent should be performed, if restoration of sinus rhythm is not achieved following initiation and/or dose adjustment of antiarrhythmic drug therapy. Failure of pharmacological cardioversion alone is not adequate to declare this pharmacological strategy unsuccessful. |
Noninducibility of atrial fibrillation | Noninducibility of atrial fibrillation is defined as the inability to induce atrial fibrillation with a standardized prespecified pharmacological or electrical stimulation protocol. The stimulation protocol should be prespecified in the specific clinical trial. Common stimulation approaches include a high-dose isoproterenol infusion protocol or repeated atrial burst pacing at progressively more rapid rates. |
Patient populations for inclusion in clinical trials | It is considered optimal for clinical trials to enroll patients with only one type of AF: paroxysmal, persistent, or long-standing persistent. If more than one type of AF patient is enrolled, the results of the trial should also be reported separately for each of the AF types. It is recognized that “early persistent” AF responds to AF ablation to a similar degree as patients with paroxysmal AF and that the response of patients with “late persistent AF” is more similar to that in those with long-standing persistent AF. |
Therapy consolidation period | Following a 3-month blanking period, it is reasonable for clinical trials to incorporate an additional 1- to 3-month therapy consolidation period. During this time, adjustment of antiarrhythmic medications and/or cardioversion can be performed. Should a consolidation period be incorporated into a clinical trial design, the minimum follow-up duration should be 9 months following the therapy consolidation period. Performance of a repeat ablation procedure during the blanking or therapy consolidation period would “reset” the endpoint of the study and trigger a new 3-month blanking period. Incorporation of a therapy consolidation period can be especially appropriate for clinical trials evaluating the efficacy of AF ablation for persistent or long-standing persistent AF. The challenge of this approach is that it prolongs the overall study duration. Because of this concern regarding overall study duration, we suggest that the therapy consolidation period be no more than 3 months in duration following the 3-month blanking period. |
Recommendations regarding repeat ablation procedures | It is recommended that all clinical trials report the single procedure efficacy of catheter ablation. Success is defined as freedom from symptomatic or asymptomatic AF/AFL/AT of 30 s or longer at 12 months postablation. Recurrences of AF/AFL/AT during the first 3-month blanking period post-AF ablation are not considered a failure. Performance of a repeat ablation procedure at any point after the initial ablation procedure should be considered a failure of a single procedure strategy. It is acceptable for a clinical trial to choose to prespecify and use a multiprocedure success rate as the primary endpoint of a clinical trial. When a multiprocedure success is selected as the primary endpoint, efficacy should be defined as freedom from AF/flutter or tachycardia at 12 months after the final ablation procedure. In the case of multiple procedures, repeat ablation procedures can be performed at any time following the initial ablation procedure. All ablation procedures are subject to a 3-month post blanking window, and all ablation trials should report efficacy at 12 months after the final ablation procedure. |
Cardioversion definitions | |
Failed electrical cardioversion | Failed electrical cardioversion is defined as the inability to restore sinus rhythm for 30 s or longer following electrical cardioversion. |
Successful electrical cardioversion | Successful electrical cardioversion is defined as the ability to restore sinus rhythm for at least 30 s following cardioversion. |
Immediate AF recurrence postcardioversion | Immediate AF recurrence postcardioversion is defined as a recurrence of AF within 24 h following cardioversion. The most common time for an immediate recurrence is within 30–60 min postcardioversion. |
Early AF recurrence postcardioversion | Early AF recurrence postcardioversion is defined as a recurrence of AF within 30 days of a successful cardioversion. |
Late AF recurrence postcardioversion | Late AF recurrence postcardioversion is defined as recurrence of AF more than 30 days following a successful cardioversion. |
Surgical ablation definitions | |
Hybrid AF surgical ablation procedure | Hybrid AF surgical ablation procedure is defined as a joint AF ablation procedure performed by electrophysiologists and cardiac surgeons either as part of a single “joint” procedure or performed as two preplanned separate ablation procedures separated by no more than 6 months. |
Surgical Maze ablation procedure | Surgical Maze ablation procedure is defined as a surgical ablation procedure for AF that includes, at a minimum, the following components: (1) line from SVC to IVC; (2) line from IVC to the tricuspid valve; (3) isolation of the PVs; (4) isolation of the posterior left atrium; (5) line from MV to the PVs; (6) management of the LA appendage. |
Stand-alone surgical AF ablation | A surgical AF ablation procedure during which other cardiac surgical procedures are not performed such as CABG, valve replacement, or valve repair. |
Nomenclature for types of surgical AF ablation procedures | We recommend that the term “Maze” procedure is appropriately used only to refer to the biatrial lesion set of the Cox-Maze operation. It requires ablation of the RA and LA isthmuses. Less extensive lesion sets should not be referred to as a “Maze” procedure, but rather as a surgical AF ablation procedure. In general, surgical ablation procedures for AF can be grouped into three different groups: (1) a full biatrial Cox-Maze procedure; (2) PVI alone; and (3) PVI combined with left atrial lesion sets. |
Hybrid epicardial and endocardial AF ablation | This term refers to a combined AF ablation procedure involving an off-pump minimally invasive surgical AF ablation as well as a catheter-based AF ablation procedure designed to complement the surgical lesion set. Hybrid ablation procedures may be performed in a single-procedure setting in a hybrid operating room or a cardiac catheterization laboratory environment, or it can be staged. When staged, it is most typical to have the patient undergo the minimally invasive surgical ablation procedure first following by a catheter ablation procedure 1 to 3 months later. This latter approach is referred to as a “staged Hybrid AF ablation procedure.” |
Minimum AF documentation, endpoints, TEE performance, and success rates in clinical trials | |
Minimum documentation for paroxysmal AF | The minimum AF documentation requirement for paroxysmal AF is (1) physician's note indicating recurrent self-terminating AF and (2) one electrocardiographically documented AF episode within 6 months prior to the ablation procedure. |
Minimum documentation for persistent AF | The minimum AF documentation requirement for persistent AF is (1) physician's note indicating continuous AF >7 days but no more than 1 year and (2) a 24-h Holter within 90 days of the ablation procedure showing continuous AF. |
Minimum documentation for early persistent AF | The minimum AF documentation requirement for persistent AF is (1) physician's note indicating continuous AF >7 days but no more than 3 months and (2) a 24-h Holter showing continuous AF within 90 days of the ablation procedure. |
Minimum documentation for long-standing persistent AF | The minimum AF documentation requirement for long-standing persistent AF is as follows: physician's note indicating at least 1 year of continuous AF plus a 24-h Holter within 90 days of the ablation procedure showing continuous AF. The performance of a successful cardioversion (sinus rhythm >30 s) within 12 months of an ablation procedure with documented early recurrence of AF within 30 days should not alter the classification of AF as long-standing persistent. |
Symptomatic AF/AFL/AT | AF/AFL/AT that results in symptoms that are experienced by the patient. These symptoms can include but are not limited to palpitations, presyncope, syncope, fatigue, and shortness of breath. For patients in continuous AF, reassessment of symptoms after restoration of sinus rhythm is recommended to establish the relationship between symptoms and AF. |
Documentation of AF-related symptoms | Documentation by a physician evaluating the patient that the patient experiences symptoms that could be attributable to AF. This does not require a time-stamped ECG, Holter, or event monitor at the precise time of symptoms. For patients with persistent AF who initially report no symptoms, it is reasonable to reassess symptom status after restoration of sinus rhythm with cardioversion. |
Minimum effectiveness endpoint for patients with symptomatic and asymptomatic AF | The minimum effectiveness endpoint is freedom from symptomatic and asymptomatic episodes of AF/AFL/AT recurrences at 12 months following ablation, free from antiarrhythmic drug therapy, and including a prespecified blanking period. |
Minimum chronic acceptable success rate: paroxysmal AF at 12-month follow-up | If a minimum chronic success rate is selected as an objective effectiveness endpoint for a clinical trial, we recommend that the minimum chronic acceptable success rate for paroxysmal AF at 12-month follow-up is 50%. |
Minimum chronic acceptable success rate: persistent AF at 12-month follow-up | If a minimum chronic success rate is selected as an objective effectiveness endpoint for a clinical trial, we recommend that the minimum chronic acceptable success rate for persistent AF at 12-month follow-up is 40%. |
Minimum chronic acceptable success rate: long-standing persistent AF at 12-month follow-up | If a minimum chronic success rate is selected as an objective effectiveness endpoint for a clinical trial, we recommend that the minimum chronic acceptable success rate for long-standing persistent AF at 12-month follow-up is 30%. |
Minimum follow-up screening for paroxysmal AF recurrence | For paroxysmal AF, the minimum follow-up screening should include (1) 12-lead ECG at each follow-up visit; (2) 24-h Holter at the end of the follow-up period (e.g., 12 months); and (3) event recording with an event monitor regularly and when symptoms occur from the end of the 3-month blanking period to the end of follow-up (e.g., 12 months). |
Minimum follow-up screening for persistent or long-standing AF recurrence | For persistent and long-standing persistent AF, the minimum follow-up screening should include (1) 12-lead ECG at each follow-up visit; (2) 24-h Holter every 6 months; and (3) symptom-driven event monitoring. |
Requirements for transesophageal echocardiogram | It is recommended that the minimum requirement for performance of a TEE in a clinical trial should be those requirements set forth in ACC/AHA/HRS 2014 Guidelines for AF Management pertaining to anticoagulation at the time of cardioversion. Prior to undergoing an AF ablation procedure a TEE should be performed in all patients with AF of >48 h' duration or of unknown duration if adequate systemic anticoagulation has not been maintained for at least 3 weeks prior to AF ablation. If a TEE is performed for this indication, it should be performed within 24 h of the ablation procedure. |
Scale | Definition/Details | Strengths/Weaknesses |
---|---|---|
Short Form (36) Health Survey (SF36)38(General) | Consists of 8 equally weighted, scaled scores in the following sections: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. Each section receives a scale score from 0 to 100.Physical component summary (PCS) and mental component summary (MCS) is an average of all the physically and mentally relevant questions, respectively.The Short Form (12) Health Survey (SF12) is a shorter version of the SF-36, which uses just 12 questions and still provides scores that can be compared with SF-36 norms, especially for summary physical and mental functioning.Gives more precision in measuring QOL than EQ-5D but can be harder to transform into cost utility analysis. | Advantages: extensively validated in a number of disease and health states. Might have more resolution than EQ-50 for AF QOL.Disadvantages: not specific for AF, so might not have resolution to detect AF-specific changes in QOL. |
EuroQol Five Dimensions Questionnaire (EQ-5D)39(General) | Two components: Health state description is measured in five dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Answers may be provided on a three-level (3L) or five-level (5L) scale. In the Evaluation section, respondents evaluate their overall health status using a visual analogue scale (EQ-VAS). Results can easily be converted to quality-adjusted life years for cost utility analysis. | Advantages: extensively validated in a number of disease and health states. Can easily be converted into quality-adjusted life years for cost-effectiveness analysis.Disadvantages: might not be specific enough to detect AF-specific changes in QOL. Might be less specific than SF-36. |
AF effect on Quality of Life Survey (AFEQT)40 (AF specific) | 20 questions: 4 targeting AF-related symptoms, 8 evaluating daily function, and 6 assessing AF treatment concerns. Each item scored on a 7-point Likert scale. | Advantages: brief, simple, very responsive to AF interventions. Good internal validity and well validated against a number of other global and AF-specific QOL scales. Used in CABANA.Disadvantages: validation in only two published studies (approximately 219 patients). |
Quality of Life Questionnaire for Patients with AF(AF-QoL)41(AF specific) | 18-item self-administered questionnaire with three domains: psychological, physical, and sexual activity. Each item scores on a 5-point Likert scale. | Advantages: brief, simple, responsive to AF interventions; good internal validity; used in SARA trial.Disadvantages: external validity compared only to SF-36; formal validation in 1 study (approximately 400 patients). |
Arrhythmia-Related Symptom Checklist (SCL)42 (AF specific) | 16 items covering AF symptom frequency and symptom severity. | Advantages: most extensively validated in a number of arrhythmia cohorts and clinical trials.Disadvantages: time-consuming and uncertain generalizability. |
Mayo AF Specific Symptom Inventory (MAFSI)43 (AF specific) | 10 items covering AF symptom frequency and severity. Combination of 5- point and 3-point Likert scale responses.Used in CABANA trial. | Advantages: validated in an AF ablation population and responsive to ablation outcome; used in CABANA trial.Disadvantages: external validity compared only to SF-36; 1 validation study (approximately 300 patients). |
University of Toronto Atrial Fibrillation Severity Scale (AFSS) (AF specific)44 | 10 items covering frequency, duration, and severity. 7-point Likert scale responses. | Advantages: validated and reproducible; used in CTAF trial.Disadvantages: time-consuming and uncertain generalizability. |
Arrhythmia Specific Questionnaire in Tachycardia and Arrhythmia (ASTA)45 (AF specific) | Records number of AF episodes and average episode duration during last 3 months. 8 symptoms and 2 disabling symptoms are recorded with scores from 1–4 for each. | Advantages: validated in various arrhythmia groups; external validity compared with SCL, EQ5D, and SF-36; used in MANTRA-PAF; brief; simple.Disadvantages: one validation study (approximately 300 patients). |
European Heart Rhythm Association (EHRA)46 (AF specific) | Like NYHA scale. I = no symptoms, II = mild symptoms not affecting daily activity, III = severe symptoms affecting daily activity, and IV = disabling symptoms terminating daily activities. | Advantage: very simple, like NYHA.Disadvantages: not used in studies and not well validated; not very specific; unknown generalizability. |
Canadian Cardiovascular Society Severity of Atrial Fibrillation Scale (CCS-SAF)47 (AF specific) | Like NYHA scale. O = asymptomatic, I = AF symptoms have minimal effect on patient's QOL, II = AF symptoms have minor effect on patient QOL, III = symptoms have moderate effect on patient QOL, IV= AF symptoms have severe effect on patient QOL. | Advantages: very simple, like NYHA; validated against SF-36 and University of Toronto AFSS.Disadvantages: poor correlation with subjectiveAF burden; not very specific. |
Stroke and bleeding endpoints | Definitions/Details |
---|---|
Stroke (2014 ACC/AHA Key Data Elements) | An acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction. Symptoms or signs must persist ≥24 h, or if documented by CT, MRI or autopsy, the duration of symptoms/signs may be less than 24 h. Stroke may be classified as ischemic (including hemorrhagic transformation of ischemic stroke), hemorrhagic, or undetermined. Stroke disability measurement is typically performed using the modified Rankin Scale (mRS). |
Transient ischemic attack (2014 ACC/AHA Key Data Elements) | Transient episode of focal neurological dysfunction caused by brain, spinal cord, or retinal ischemia without acute infarction and with signs and symptoms lasting less than 24 h. |
Major bleeding (ISTH definition) | Fatal bleeding AND/OR symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, or intramuscular with compartment syndrome AND/OR bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of blood. |
Clinically relevant nonmajor bleed (ISTH definition) | An acute or subacute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response such that it leads to one of the following: hospital admission for bleeding; physician-guided medical or surgical treatment for bleeding; change in antithrombotic therapy (including interruption or discontinuation). |
Minor bleeding (ISTH definition) | All nonmajor bleeds. Minor bleeds are further divided into clinically relevant and not. |
Incidence and discontinuation of oral anticoagulation | The number of patients receiving oral anticoagulation and the type of oral anticoagulation should be documented at the end of follow-up. If patients have their oral anticoagulation discontinued, the number of patients discontinuing, the timing of discontinuation, and the reasons for discontinuation of oral anticoagulation, as well as the clinical characteristics and stroke risk profile of the patients should be reported. |
Endpoint | Advantages | Disadvantages | Relevance and Comments |
---|---|---|---|
Freedom from AF/AFL/AT recurrence “gold standard” is 30 s | - Has been in use for many years | - Can systematically underestimate the efficacy of AF ablation, particularly for persistent AF, if 30-s cutoff is used | - Particularly well suited for paroxysmal AF outcomes |
- Can be used to compare results of new trials with historical trials | - Reporting of cutoffs other than 30 s encouraged as secondary endpoints to better contextualize results | ||
- Sets a high bar for AF elimination | - May be reported as proportion of patients free from arrhythmia or time to recurrence | ||
Freedom from stroke-relevant AF/AFL/AT-duration cutoff of 1 h | - Useful for trials in which interest is more for prognostic change conferred by ablation rather than elimination of all arrhythmias | - No consistent definition of what a stroke-relevant duration of AF is: ranges from 6 min to 24 h in literature | - More than 1 h could be a useful cutoff based on results of 505 trial |
- May be reported as proportion of patients free from arrhythmia or time to recurrence | |||
Freedom from AF/AFL/AT requiring intervention (emergency visits, cardioversion, urgent care visit, reablation, etc.) | - Can provide an endpoint more relevant to systemic costs of AF recurrence | - Will overestimate efficacy of ablation by ignoring shorter episodes not requiring intervention that still might be important to quality of life or stroke | - Determination of what is an “intervention” must be prespecified in protocol and biases mitigated to avoid over- or underintervention in the trial |
- Clinically relevant | |||
Freedom from persistent AF/AFL/AT-duration cutoff of 7 days | - Useful for trials assessing additional substrate modification in persistent AF | - Can systematically overestimate the efficacy of AF ablation, particularly for persistent AF | - Can require continuous monitoring to definitively assess if episode is >7 days |
Freedom from AF/AFL/AT on previously ineffective antiarrhythmic therapy | - If patient maintains sinus rhythm on previously ineffective drug therapy, this may be considered a clinically relevant, successful outcome | - Will increase the success rate compared with off-drug success | - Postablation drug and dosage of drug should be identical to preablation drug and dosage |
- May not be relevant to patients hoping to discontinue drug therapy | |||
Significant reduction in AF burden: >75% reduction from pre- to postablation and/or total postablation burden <12% | - Can be useful in persistent AF studies, but might not be suited for early, paroxysmal AF studies | - Ideally requires continuous monitoring using an implantable device | - AF burden can be estimated by intermittent monitoring and reporting of patient symptoms and recurrences like a “time in therapeutic range” report for oral anticoagulation; see text |
- No scientific basic exists showing that a 75% reduction in AF burden impacts hard endpoints, including heart failure, stroke, and mortality | |||
- Could also see 75% reduction in number and duration of AF episodes | |||
- Because there is no firm scientific basis for selecting the cutoff of 75%, this prior recommendation is provided only as an example of what future clinical trials may choose to use as a definition of clinical/partial success | |||
Prevention in AF progression: time to first episode of persistent AF (>7 days) | - Does not assume that total elimination of AF is required | - Prevention in progression might be irrelevant for stroke or thromboembolic outcomes | - Might be useful for specific populations such as heart failure or hypertrophic cardiomyopathy, in which progression to persistent AF can lead to increased hospitalization |
- Well suited for paroxysmal or “early” AF studies in which goal is to prevent progression to persistent AF | - Long follow-up time might be required unless population is “enriched” | ||
- Can ideally require continuous implantable monitoring | |||
Regression of AF: reduction in burden to a given threshold or conversion of persistent to paroxysmal AF | - Does not assume that total elimination of AF is required | - Regression endpoint will overestimate efficacy of AF ablation | - Could be particularly useful for long-standing persistent AF populations with structural heart disease, heart failure, etc. |
- Well suited for persistent “late” AF studies in which goal is to regress to paroxysmal AF, which might be easier to control with drug therapy | - Might ideally require continuous implantable monitoring | ||
- Patients will require ongoing drug therapy | |||
Acute AF termination during ablation procedure | - Could provide indication of successful modification of substrate responsible for maintaining AF, most relevant to persistent or long-standing persistent AF | - Relevance of acute AF termination has not consistently been shown to correlate to long-term success | - Intraprocedural administration of preprocedural oral antiarrhythmics or intraprocedural intravenous antiarrhythmics are discouraged |
- Limited studies have linked acute AF termination to long-term success | - Endpoint might not be relevant to paroxysmal AF patients in whom AF might terminate spontaneously | - If antiarrhythmics are used, their use and dosage before and during the ablation should be clearly documented | |
- Studies consider termination as reversion to sinus rhythm, whereas others consider reversion to any regular tachycardia as termination | - Some studies employ administration of intravenous or oral antiarrhythmics during ablation that could cause spontaneous termination | - Termination to sinus rhythm and termination to another regular tachycardia (AT or AFL) should be separately reported |