About Electrograms and Their Structural Origin: Clues To More Effective Ablation Strategies for Atrial Fibrillation

The surgical “maze procedure,” which was the  rst nonpharmacologic curative technique for atrial  brillation (AF), was based on the insights that “multiple wavelets” around functionally refractory tissue perpetuate the arrhythmia.1 The procedure provided proof of the concept but was too draconical to become commonly applicable.2 Attempts to mimic the intervention via percutaneous access proved unpractical, unreliable, and prone to complication.3 ,4 Two new electrical concepts from the last decade markedly changed the clinical approach to AF. The  rst approach, introduced by Wijffels and Allessie, is that rapid atrial rates predispose the atria to ensuing atrial arrhythmias due to shortening and maladaptation to rate of the atrial effective refractory period (ERP). 5 The phenomenon is now known as “atrial electrical remodeling. ” Refractory period shortening leads to smaller wavelengths, so that the probability of persistence for multiple wavelets is increased. Similar remodeling changes occur in humans prone to AF, although most studies did not include direct left atrial (LA) measurements or those obtained only via the coronary sinus (CS). The concept of electrical remodeling inspired a more aggressive attitude to AF, with the hope of preventing its progressive domestication. The second concept is the recognition that some forms of AF are focal in nature or—more often—are focally induced. A majority of foci reside in the ori ces of the pulmonary veins. Ha ṏ ssaguerre’s group has shown that targeting these foci by ablation, or by isolation of the pulmonary veins from the atrium, can result in cure of the arrhythmia.6 However, a substantial proportion of patients still develop AF despite successful isolation of the pulmonary veins. More extensive ablation approaches may result in higher success rates.7 Therefore, the need for adjuvant (linear) atrial lesions, like in the maze procedure, is reemerging. A major issue will be which (minimal) set of lines is required and which patients will bene t. In this issue of the Journal, Ndrepepa et al.8 describe their recordings using a 64-pole basket catheter in the human LA, during both initiation of AF and sustained episodes. Their technique enabled whole LA mapping with reasonable spatial resolution. They compared recordings in 10 paroxysmal AF patients and 11 patients with persistent AF (at least 3 months). Their observations con rm the presence of atrial electrical remodeling in man. The average cycle length was 20% shorter in longer-standing AF, and the degree of electrical disorganization was clearly higher in chronic AF. Although CS electrograms showed a similar degree of shortening of the average cycle length between acute and chronic AF (21%), they were signi cantly longer than those of the adjacent posterior LA. Moreover, simultaneous registration in the CS and posterior LA wall showed uncoupling between the two areas (with disorganized vs organized patterns during some sequences). This also is in accordance with previous observations that the CS musculature is not fully contiguous with the LA. It implies a limited usefulness of CS recordings for LA mapping in patients with AF. Recordings during initiation of AF con rmed the high prevalence of (repetitive) atrial premature beats as the trigger. Ndrepepa et al. point to the presence of “intermediary rhythms” between the  rst atrial premature beat and the start of  brillation. These intermediary rhythms (with an organized atrial activation pattern) exhibit progressive shortening of the cycle length before leading to disorganized  brillatory activation. The authors denote the regions with earliest  brillatory activity as “generator regions. ” One or two such regions were identi ed in each patient, with secondary spreading of AF to other parts of the atrium. The majority of these generator regions were situated in the posterior (inferior) wall of the LA. Most interestingly, during consecutive initiations of AF (as observed in 14 of the 21 patients), the generator regions were the same, irrespective of whether AF was initiated by an atrial premature beat, right atrial  utter, or ventricular premature beat with retrograde conduction (in one patient). These  ndings may have important therapeutic implications. The authors speculate that targeting these generator regions as an adjunct to elimination of ectopic foci might enhance the success rate of ablative procedures. However tempting this suggestion may be, the available data must be seen as hypothesis generating rather than proven fact. The number of observations was relatively small and awaits de nitive con rmation. The authors do not provide any data on the immediate or long-term effect of radiofrequency lesions in their patients. There also is no obvious relationship between the location of the generator regions and the observations during AF. Only 2 of the 18 generator regions were located in the septal or superior LA region, which showed a similarly high degree of disorganization as the posterior wall during established AF. Therefore, identifying these regions is dependent on spontaneous initiation of AF and, hence, is cumbersome in clinical practice. It is not known whether the generator regions would be the same during induction of AF by programmed atrial stimulation or burst pacing and thus could be identi ed by provocative maneuvers. Finally, nothing is known about the effect of pharmacologic interventions. Drug treatment might be effective in suppressing some of these generator regions, obviating the need for ablative approaches. The concepts of “intermediary rhythms” and “generator region” both need further mechanistic clari cation. Although the authors point J Cardiovasc Electrophysiol, Vol. 13, pp. 533-534, June 2002.