Table 13.

Advantages and disadvantages of AF-related endpoints in AF ablation trials

Endpoint	Advantages	Disadvantages	Relevance and Comments
Freedom from AF/AFL/AT recurrence "gold standard" is 30 seconds	-Has been in use for many years -Can be used to compare results of new trials with historical trials -Sets a high bar for AF elimination	-Can systematically underestimate the efficacy of AF ablation, particularly for persistent AF, if 30-second cutoff is used	-Particularly well suited for paroxysmal AF outcomes -Reporting of cutoffs other than 30 seconds encouraged as secondary endpoints to better contextualize results -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 hour	-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 minutes to 24 hours in literature	-More than 1 hour 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 -Clinically relevant	-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
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 -May not be relevant to patients hoping to discontinue drug therapy	-Postablation drug and dosage of drug should be identical to preablation drug and dosage
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 -No scientific basic exists showing that a 75% reduction in AF burden impacts hard endpoints, including heart failure, stroke, and mortality	-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 -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 -Well suited for paroxysmal or "early" AF studies in which goal is to prevent progression to persistent AF	-Prevention in progression might be irrelevant for stroke or thromboembolic outcomes -Long follow-up time might be required unless population is "enriched" -Can ideally require continuous implantable monitoring	-Might be useful for specific populations such as heart failure or hypertrophic cardiomyopathy, in which progression to persistent AF can lead to increased hospitalization
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 -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	-Regression endpoint will overestimate efficacy of AF ablation -Might ideally require continuous implantable monitoring -Patients will require ongoing drug therapy	-Could be particularly useful for long-standing persistent AF populations with structural heart disease, heart failure, etc.
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 -Limited studies have linked acute AF termination to long-term success	-Relevance of acute AF termination has not consistently been shown to correlate to long-term success -Endpoint might not be relevant to paroxysmal AF patients in whom AF might terminate spontaneously -Some studies employ administration of intravenous or oral antiarrhythmics during ablation that could cause spontaneous termination -Studies consider termination as reversion to sinus rhythm, whereas others consider reversion to any regular tachycardia as termination	-Intraprocedural administration of preprocedural oral antiarrhythmics or intraprocedural intravenous antiarrhythmics are discouraged -If antiarrhythmics are used, their use and dosage before and during the ablation should be clearly documented -Termination to sinus rhythm and termination to another regular tachycardia (AT or AFL) should be separately reported

AF = atrial fibrillation; AFL = atrial flutter; AT = atrial tachycardia.