Repolarization Alternans Reveals Vulnerability to Human Atrial Fibrillation

Abstract

Background The substrates for human atrial fibrillation (AF) are poorly understood but involve abnormal repolarization (action potential duration, APD). We hypothesized that beat-to-beat oscillations in APD may explain AF substrates and why vulnerability to AF forms a spectrum from control subjects without AF to patients with paroxysmal then persistent AF. Methods and Results In 33 subjects (12 persistent AF, 13 paroxysmal AF, 8 controls without AF), we recorded left (n=33) and right (n=6) atrial APD on pacing from cycle lengths (CL) 600–500 ms (100–120 beats/min) to AF. APD alternans required progressively faster rates for patients with persistent AF, paroxysmal AF and controls (CL 411±94 vs 372±72 vs 218±33 ms; p<0.01). In AF patients, APD alternans occurred at rates as slow as 100–120 beats/min, unrelated to APD restitution (p=NS). In this milieu, spontaneous ectopy initiated AF. At fast rates, APD alternans disorganized to complex oscillations en route to AF. Complex oscillations also arose at progressively faster rates for persistent AF, paroxysmal AF and controls (CL: 316±99 vs 266±19 vs 177±16 ms; p=0.02). In paroxysmal AF, APD oscillations amplified prior to AF (p<0.001). In controls, APD alternans arose only at very fast rates (CL < 250 ms; p<0.001 vs AF groups) just prior to AF. In n=4 AF patients in whom rapid pacing did not initiate AF, APD alternans arose transiently then extinguished. Conclusions Atrial APD alternans reveals dynamic substrates for AF, arising most readily (at lower rates and higher magnitudes) in persistent AF then paroxysmal AF, and least readily in controls. APD alternans preceded all AF episodes, and was absent when AF did not initiate. The cellular mechanisms for APD alternans near resting heart rates require definition.

Theoretical considerations for mapping activation in human cardiac fibrillation

“…29 Although this imposes a potential mapping limit, re-entry on this small scale may be uncommon in human atria since wavelength considerations suggest a minimum wavelength of %4-5 cm. [31][32][33][34] Moreover, the inability to precisely resolve the spiral tip path may be of less clinical relevance if the approximate center of rotation can be identified, since a single ablation lesion typically covers a region of diameter 5-7 mm. 20 Finally, we note that although we have focused on atrial wave propagation, our theoretical and computational estimates should also be valid for spiral waves in the ventricles, provided that we use parameters applicable to ventricular tissue and that our analyses would be restricted to the mapping plane(s).…”

Response to Letter Regarding Article, “Repolarization Alternans Reveals Vulnerability to Human Atrial Fibrillation”

“…1 Dr Madias hypothesizes that prolongation of the P wave on the surface ECG, which has been epidemiologically linked with atrial fibrillation (AF), 2 may complement our report 1 that oscillations of atrial repolarization indicate a spectrum of AF vulnerability from control subjects without AF, through patients with paroxysmal AF to those with persistent AF.…”

“…3 The interaction between dynamic conduction slowing and repolarization oscillations is likely complex, and under certain conditions may enable functional conduction block, reentry, and AF initiation. 1,3,4 In the future, these indices may offer more pathophysiologically specific and clinically accurate predictors of AF risk than baseline ECG measurements of P-wave duration or potentially of atrial repolarization (T a waves). 5 We fully agree with Dr Madias that there is an urgent need to translate pathophysiologic observations to clinical practice, and thank him for these important comments.…”

Atrial Fibrillation and Heart Failure: Approaches to Antithrombotic Therapy

“…РААС также вносит прямой вклад в проаритмическое ремо-делирование, при этом ангиотензин II вызывает фиброз предсердий и анизотропное проведение [16]. У пациентов с СН также имеет место нарушенный обмен кальция и перегрузка кальцием, которые могут привести к постдеполяризациям и аритмии [17].…”