How often should we monitor for reliable detection of atrial fibrillation recurrence? Efficiency considerations and implications for study design

Abstract

Objective: Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns.

Methods: The rhythm histories of 647 patients (mean AF burden: 12 ± 22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations.

Results: The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM frequencies will under-detect AF recurrence and introduce significant bias in the evaluation of therapeutic interventions. More frequent but of shorter duration, IRMs (24-hour) are significantly more time effective (sensitivity per monitored time) than a fewer number of longer IRM durations (p<0.0001).

Conclusions: Reliable AF recurrence detection requires higher IRM frequencies than currently recommended. Current IRM frequency recommendations will fail to diagnose a significant proportion of patients. Shorter duration but more frequent IRM strategies are significantly more efficient than longer IRM durations.

Clinical trial registration url: Unique identifier: NCT00806689.

Conflict of interest statement

Competing Interests: Drs Charitos, Stierle, Graf, Robinson, and Sievers have no conflict of interest to disclose. Dr. Hanke has received modest lecture honoraria from Medtronic (<10.000 USD). Mr. Ziegler is an employee and stockholder of Medtronic (>10.000 USD). This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Four examples of different temporal aggregation for the same AF burden (0.173).

After reconstruction of the rhythm history (upper panels), the minimum time required for the development of each proportion of the patient's total observed AF burden throughout the monitored period is evaluated (lower panels, dotted lines). AF density is defined as the ratio of the cumulative deviation of the patient's actual burden development (blue or red area) from the uniform burden development (black diagonal line, lower panels and Uniform Burden), to that of the maximum possible burden aggregation for that level of burden (the complete burden as one continuous episode, green area). The black diagonal (lower panels) represents a hypothetical uniform burden aggregation (Uniform Burden). Adapted from .

Figure 2. Illustration of the simulation procedure: Initially, the “first day” of the first monitoring period (IRM) was chosen at random, and then the subsequent k-1 days were counted to make a k day monitoring period (IRM).

In this example the 7-day IRM would be on days 179–185. Any future sampling that includes days 173–191 will be rejected (any 7 day IRM starting on these days would intersect with the sampled IRM on days 179–185). Second, the simulation procedure scans the total observation period of the patient and at even intervals (based on the pre-specified IRM frequency) attaches weights at the following days: first sampled day±k*(365/sampling strategy frequency), where k = {1,2,3,4, …, sampling strategy frequency}. In this example, the algorithm attaches higher sampling weights at days 9, 99, 279, 370. Gaussian smoothing was used to construct a smoothed sampling weight curve such that the zeniths have about 3 times higher probability to be sampled than the nadirs. Attaching higher sampling probability weights at even intervals mimics the follow-up strategy of clinical trials, while also simultaneously allowing some randomness (just as in real life follow-up examinations, patients often are seen slightly before or after their nominal follow-update). Thereafter the simulation proceeds with sampling from the weighted sample space.

Figure 3. The effect of AF burden and AF density on the probability of AF detection with a single 24-hour IRM (left panel) for the AF recurrence pattern of two example patients (right panel).

For any given AF burden b, observed during any time frame, the probability of successful identification using a given IRM duration ranges between ≅b and 1. The range [≅b,1] depends on the temporal aggregation of the AF recurrences (AF density). If the AF occurs as one episode, the probability of AF detection is ≅b (Patient B), whereas if the AF recurrence is uniformly spread throughout the observation time the probability of AF recurrence detection is 1 (Patient A). IRM: intermittent rhythm monitor, AF: atrial fibrillation.

Figure 4. Required 24-hour IRM frequency to achieve 80% (left) and 95% (right) probability of AF detection.

The black dots represent our patient population. IRM: intermittent rhythm monitor, AF: atrial fibrillation.

Figure 5. Required 7-day IRM frequency to achieve 80% (left) and 95% (right) probability of AF detection.

The black dots represent our patient population. IRM: intermittent rhythm monitor, AF: atrial fibrillation.

Figure 6. Required 14-day IRM frequency to achieve 80% (left) and 95% (right) probability of AF detection.

The black dots represent our patient population. IRM: intermittent rhythm monitor, AF: atrial fibrillation.

Figure 7. Required 30-day IRM frequency to achieve 80% (left) and 95% (right) probability of AF detection.

The black dots represent our patient population. IRM: intermittent rhythm monitor, AF: atrial fibrillation.

Figure 8. Time efficiency (sensitivity obtained per monitored day) of IRM strategies.

For the same amount of total monitored time, shorter IRM durations result in higher sensitivities. The dotted and solid horizontal line represents sensitivities of 0.5 and 0.95 respectively. IRM: intermittent rhythm monitor, AF: atrial fibrillation.