Table 10.
Definitions for use when reporting outcomes of AF ablation and in designing clinical trials of catheter or surgical ablation of AF
| 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. |
AF atrial fibrillation, DW-MRI diffusion-weighted magnetic resonance imaging, CHF congestive heart failure, QOL quality of life, ECG electrocardiogram, CABG coronary artery bypass grafting, PV pulmonary vein, SVC superior vena cava, IVC inferior vena cava, CFAE complex fractionated atrial electrogram, PVI pulmonary vein isolation, AFL atrial flutter, AT atrial tachycardia, ACC American College of Cardiology, AHA American Heart Association, HRS Heart Rhythm Society
∗When reporting outcomes of AF ablation, the development of atrial tachycardia or atrial flutter should be included in the broad definition of recurrence following AF ablation. All studies should report freedom from AF, atrial tachycardia, and atrial flutter. These endpoints can also be reported separately. All studies should also clearly specify the type and frequency of ECG monitoring as well as the degree of compliance with the prespecified monitoring protocol