Lenox Internal Medicine

Amidst the crowd of articles on medical therapeutics in the journals every week (it’s where the money is), I’m always pleased to find a good study on the pathophysiology of disease.

Here’s one from the American Heart Journal, Progression of paroxysmal atrial fibrillation to persistent atrial fibrillation in patients with bradyarrhythmias.

We know that some patients can have paroxysmal atrial fibrillation for decades, and others progress gradually to persistent atrial fibrillation.

The authors studied recordings from implantable devices for a bit over a year, looking at the “cumulative daily AT/AF burden.” The findings:

Seventy-eight patients (24%) progressed to persistent AT/AF during the follow-up period with a mean interval of 147 ± 149 days. Mean AT/AF burden increased progressively (slope 14 s/d, P < .001) over 500 days after implant, and median AT/AF burden also increased (P < .01) in this subgroup of patients. This increase was highly correlated with the presence of structural heart disease (P < .001).

In the discussion, the authors note that, first of all, implantable devices are useful for following the progression of atrial tachyarrhythmias. In terms of the pathophysiology of atrial fibrillation:

We observed that a proportion of patients progressed to persistent AF. In this population, this was 24% at a mean follow-up duration of 5 months. This is a more rapid transition than previously suspected and may be related to the more sensitive recording method. The mean AT/AF burden has remained relatively constant over time in the patients remaining in paroxysmal AF, whereas it steadily increased in those transitioning to persistent AF…

We were able to obtain unique insights into the period around transition from paroxysmal to persistent AF. Interestingly, this transition is rather sudden and discrete in most patients rather than gradual as previously hypothesized. There is no substantial AF burden surge immediately before the transition point, suggesting that the persistent AF event is triggered by a single or very low density triggering arrhythmia and may be maintained by a remodeled substrate.

The clinical implications? In patients with devices, we may be able to predict the likelihood of progression, with yet-to-be-defined algorithms. And, with regard to directions for therapeutic research:

The focus of many AF therapies has been to reduce trigger mechanisms. This new understanding from device data logs strongly promotes interventions directed at the substrate. Atrial-specific antiarrhythmic drugs, multisite atrial stimulation for electrical resynchronization, and linear ablation/isolation for ablative approaches are more likely to favorably affect the substrate. Drugs such as angiotensin converting enzyme inhibitors and other therapies such as dual-site atrial pacing may improve hemodynamics, potentially slowing the progress of substrate decay.

Finally, quantifying cumulative time and and out of fibrillation may help us to estimate thrombotic risk more precisely in individual patients and better direct anti-thrombotic therapy.