WARREN, NEW JERSEY. Animal experiments have shown that continued pacing of the heart makes paroxysmal (intermittent, self-converting) atrial fibrillation (AF) progress to persistent (episodes lasting longer than 7 days needing cardioversion) and permanent AF. Hence the expression “afib begets afib”. The question is, “Do these findings apply to humans”? After all, patients with paroxysmal AF do not have their heart constantly paced and do spend often long periods in normal sinus rhythm. A group of electrophysiologists at the University of Florence, Italy, the Robert Wood Johnson School of Medicine, and Medtronic Inc. (a major manufacturer of pacemakers and implantable cardioverter/defibrillators) now provides at least a partial answer to this question.

Their study involved 330 patients with a history of paroxysmal AF and bradycardia (mean age of 70 years, 61% male). All suffered from heart failure to varying degrees and had had a pacemaker (Medtronic Model AT501) installed prior to the study. Most patients (79%) experienced some form of cardiovascular disease with 61% having hypertension; thus, the proportion of lone afibbers was insignificant and the results of the study may not apply to lone afibbers. After an average follow-up of one year and 3 months, 24% of the study participants had converted to persistent afib with the median time to conversion being 9 months (103 days). The researchers noted the following important differences between the patients who remained in paroxysmal AF (Group 1) and those who progressed to persistent AF (Group 2).

• Prior to conversion to persistent afib, patients in Group 2 were more likely to experience afib on any given day and had a higher average afib burden (no. of episodes x duration) than did those in Group 1.

• Prior to conversion to persistent afib, there was a significant linear increase in daily afib burden (mean increase of 14 sec/day) in Group 2, but no increase (on average) in Group 1.

• The transition from paroxysmal to persistent afib in Group 2 was quite abrupt and was preceded by a few days of normal sinus rhythm.

• The increase in afib burden over time was substantially higher among patients with cardiovascular disease (average 0.18 min/day) than among those with no cardiovascular disease (CVD) where the burden actually declined slightly over time (average –0.06 min/day). Patients with CVD were also more likely to progress to persistent AF.

• Atrial premature beats (PACs) were more frequent in patients without CVD, but decreased with time in all patients.

The researchers conclude that structural remodeling (substrate modification) is critical to the transition to persistent afib. The changes to the substrate may involve fibrosis, apoptosis (cell death), and altered cellular junction proteins. In an accompanying editorial, electrophysiologists at the Tufts-New England Medical Center suggest that the renin angiotensin aldosterone system (RAAS) may play a significant role in the substrate modification and that ACE inhibitors and/or angiotensin receptor blockers may help slow down the structural remodeling. They also suggest that targeting just the pulmonary veins during an ablation (pulmonary vein isolation) is unlikely to suffice in the case of persistent or permanent AF.

Saksena, S, et al. Progression of paroxysmal atrial fibrillation to persistent atrial fibrillation in patients with bradyarrhythmias. American Heart Journal, Vol. 154, No. 5, November 2007, pp.884-92
Homoud, MK and Estes, M. Shedding new light on the pathophysiology of conversion of paroxysmal atrial fibrillation into persistent atrial fibrillation. American Heart Journal, Vol. 154, No. 5, November 2007, pp.801-04

Editor’s comment: In considering the above findings it should be kept in mind that the study did not involve a significant proportion of lone afibbers. Nevertheless, the mechanism underlying the progression from paroxysmal to persistent AF (substrate modification) is likely to be similar. If increasing afib burden is indeed a universal sign of progression, then lone afibbers who experience such an increase may wish to consider medication with an ACE inhibitor (lisinopril, enalapril, ramipril) or an angiotensin receptor blocker (losartan, valsartan, irbesartan) in order to slow down structural remodeling. Although there is no published evidence to support this, it is also possible that proteolytic enzymes (Serrapeptase, Wobenzym, nattokinase) may be useful in slowing down, or perhaps even reversing, the fibrosis component of substrate modification and thereby help prevent progression to persistent AF.