© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Establishing the link between a specific pathology and atrial fibrillation
Cardiothoracic Surgery Research Laboratories, 660 South Euclid, St. Louis, MO 63110, USA
schuesslerr{at}msnotes.wustl.edu
* Tel.: +1-314-362-8300; fax: +1-314-361-8706
Received 24 August 2001; accepted 30 August 2001
See article by Shi et al. [5] (pages 217–225) in this issue.
Atrial fibrillation (AF) is associated with numerous pathologies, as well as the normal aging process. The most common pathologies are valvular and ischemic heart disease, hyperthyroidism, hypertension, and cardiomyopathies. Less common etiologies, but still clearly associated with AF, include cardiac tumors, various inflammatory diseases, abnormal autonomic tone, and substance abuse [1]. What has become clear over the last 100 years of AF research is that at the electrophysiological level there are four interacting substrates that contribute to AF. These include: (1) premature impulse formation; (2) the magnitude and distribution of repolarization and refractory period; (3) the magnitude, distribution, and anisotropy of propagation velocity; and (4) the microscopic and macroscopic anatomy of the atria. The interaction of these factors determines whether or not AF will be initiated and maintained. Yet despite our knowledge of the underlying pathologies and the mechanisms of AF, pharmacological treatments for AF have met with limited success. In part, this failure is due to a lack of understanding of how various pathologies interact with the electrophysiological substrates. In 1995, two important studies appeared by Wijffels et al. and Morillo et al. that changed how we thought about AF [2,3]. They demonstrated that these substrates were dynamic, and in particular they showed that rapid atrial rate altered refractoriness and atrial size. These changes increased the atrial vulnerability to fibrillation and lead Wijffels et al. to propose that ‘atrial fibrillation begets atrial fibrillation’. Subsequently, numerous studies have now elucidated the cellular ion channel changes that are responsible for remodeling the electrophysiological substrates [4].
In this issue, Shi et al. examine how heart failure, caused by rapid ventricular pacing, affects the vulnerability to AF [5]. Just as important, they compare the changes that occur in a heart failure model with those that occur in a model of rapid atrial pacing. This paper extends an earlier excellent study out of the laboratory of Dr. Stanley Nattel by Li et al. using rapid ventricular pacing to produce heart failure [6]. They showed in that study that vulnerability to AF increased with ventricular pacing without changing the magnitude or dispersion of refractoriness. However, there was an increased heterogeneity of propagation velocity due to increased interstitial fibrosis. In the present study, they examine the time course of left and right atrial diastolic and systolic areas as well as the fractional area shortening during rapid atrial pacing and pacing induced heart failure. They correlated these data along with the refractory period with the duration of induced AF. They showed that the duration of AF in the heart failure model was dependent on the atrial size and not refractory period. In the rapid atrial pacing animals, they showed exactly the opposite effect, with little dependence of duration on atrial size, but with a correlation with refractory period. This study demonstrates why it is important to understand how specific pathologies affect the underlying substrates for AF. Implications for therapy are clear. As an example, if a treatment strategy were designed for preventing or reversing the remodeling of refractory period in a patient with lone atrial fibrillation, then you could anticipate a positive outcome. However, if it were applied to a patient with heart failure, the same approach may have limited success. What is lacking are animal models for different clinical pathologies. It is only in these models that we can follow the evolution of the changes that occur with each substrate and test therapeutic options. Caution should be used in extrapolating rapid ventricular pacing data to patients with various diseases. Chronic heart failure due to ischemic heart disease may modify the underlying substrates differently. Still despite the limitation of the rapid pacing models, the study by Shi et al. adds to our understanding of different underlying mechanisms of AF. Future success in treatment of AF will require this understanding.
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Acknowledgements |
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Supported in part by HL RO1-08894 and HL RO1-33722.
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References |
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 Top References |
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- Bharati S., Lev M. Atrial Fibrillation: Mechanisms and Management. Falk R.H Podrid P.J., ed. (1992) New York: Raven Press. 15–39.
- Wijffels M.C.E.F., Kirchhof C.J.H.J., Dorland R., Allessie M.A. Atrial fibrillation begets atrial fibrillation. Circulation (1995) 92:1954–1968.
[Abstract/Free Full Text] - Morillo C.A., Klein G.J., Jones D.L., Guiraudon C.M. Chronic rapid atrial pacing: structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation (1995) 91:1588–1595.
[Abstract/Free Full Text] - Nattel S., Li D. Ionic remodeling in the heart: pathophysiological significance and new therapeutic opportunities for atrial fibrillation. Circ Res (2000) 87(6):440–447.
[Abstract/Free Full Text] - Shi Y., Ducharme A., Li D., Gaspo R., Nattel S., Tardif J. Remodeling of atrial dimensions and emptying function in canine models of atrial fibrillation. Cardiovasc Res (2001) 52:217–225.
[Abstract/Free Full Text] - Li D., Fareh S., Leung T.K., Nattel S. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. Circulation (1999) 100:87–95.
[Abstract/Free Full Text]
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