(Circulation. 1997;95:562-564.)
© 1997 American Heart Association, Inc.
Articles |
Atrial Fibrillation
A Tachycardia-Induced Atrial Cardiomyopathy
the Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, and the Roudebush Veterans Administration Medical Center, Indianapolis, Ind.
Correspondence to Douglas P. Zipes, MD, Krannert Institute of Cardiology, 1111 W 10th St, Indianapolis, IN 46202-4800.
Key Words: Editorials • fibrillation • arrhythmia • atrium • cardiomyopathy
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Introduction |
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 Top Introduction References |
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Atrial fibrillation and ventricular tachyarrhythmias occurring in patients with structurally abnormal hearts are the most important arrhythmias in contemporary cardiology. They represent the most frequently encountered tachycardias, account for the most morbidity and mortality, and, despite much progress, remain therapeutic challenges. Virtually all other supraventricular arrhythmias and most monomorphic ventricular tachycardias in patients with structurally normal hearts can be cured by RFCA.
Atrial fibrillation affects a larger population than ventricular tachyarrhythmias, with a prevalence of 
0.5% in patients 50 to 59 years old, incrementing to 8.8% in patients in their 80s. Indeed, Framingham data indicate that the age-adjusted prevalence, particularly in men, has increased substantially over the last 30 years.1 Atrial fibrillation usually accompanies disorders such as rheumatic and coronary heart disease, heart failure, mitral valve prolapse, hypertension, cardiomyopathies, hyperthyroidism, and the postoperative state but can occur in the absence of any recognized abnormality (lone atrial fibrillation) in at least 10% of cases. Although it may not carry the inherent lethality of a ventricular tachyarrhythmia, it does have a mortality twice that of control subjects,1 and the palpitations, hemodynamic consequences, side effects of drugs, and, most importantly, brain involvement due to thromboembolic complications make atrial fibrillation a formidable problem. It is a frontier to be challenged, as clinicians wrestle with its three most important clinical issues: control of the ventricular rate, maintenance of sinus rhythm, and prevention of thromboembolism.
Recently, we have begun to understand some of the electrophysiological issues surrounding atrial fibrillation, and in the context of this editorial, two aspects will be addressed because they translate into therapeutic advances. The first is what we have learned about the electrophysiological mechanisms responsible for the onset of atrial fibrillation, and the second is what we know about its maintenance. It is important to remember, however, that there are probably different types of atrial fibrillation, even though they can have similar ECG appearances, so that this new information may not necessarily apply to all forms of atrial fibrillation.
The report by Jais et al2 in this issue of Circulation, which represents a continuation of their initial observation published in the Journal of Cardiovascular Electrophysiology,3 sheds light on the first question. They have found that atrial fibrillation in nine patients from a cohort (number not specified) referred for treatment of resistant paroxysmal atrial fibrillation was not due to the multiple reentrant wavelet hypothesis of Moe but rather to a single, rapidly discharging focus, similar to a pacemaker or a generator, that created an ECG pattern of atrial fibrillation. Elimination of the focus by RFCA also eliminated the apparent fibrillation.
This observation is important for two reasons. First, from an electrophysiological standpoint, it provides one mechanism to explain how atrial fibrillation can start. Second, it identifies a population of patients, the size of which has yet to be established, for whom RFCA can provide a cure. It is probable that in some of these patients, the atria remodel over a period of time (see below), owing to the frequent recurrence of fast atrial rates, and develop sustained atrial fibrillation, which is then much more difficult to cure with RFCA. Thus, it becomes important for the cardiologist to recognize the patient who may have a focal source of atrial fibrillation: relatively young of either sex; no structural heart disease; frequent episodes of intermittent atrial fibrillation, along with episodes of an atrial tachycardia; monomorphic premature atrial systoles that have contours similar to the P waves during tachycardia; and a rate of atrial tachycardia, which is often irregular, >400/min and creating the ECG pattern of atrial fibrillation.
Electrophysiologically, the focal origin of the tachycardia in most patients created a centrifugal endocardial activation, moving away from the focus. Because of the marked irregularity of the focal discharge, Jais et al2 postulated an abnormal automatic or triggered mechanism. While this may or may not be true, at the present time it is of secondary importance because RFCA was effective, regardless of the mechanism. The foci were located at sites where atrial tachycardias have been noted in other studies, ie, near the sinus node and venae ostia, the coronary sinus in the right atrium and pulmonary veins in the left. Importantly for the electrophysiologist, foci located near the ostia of the right pulmonary veins, because they are located behind the right atrium, can create a positive P wave in leads I, II, and III that appears to originate in the right atrium.
No complications are mentioned from the RFCA, and one patient required a second ablation procedure. Follow-up at 10 months showed no recurrence of the atrial tachycardia or fibrillation. It is important to stress that application of extensive RFCA lesions in the left atrium, not so much to ablate focal atrial fibrillation but to replicate the principle of the maze surgical procedure (see below), is not without risk of potential thrombus formation and systemic embolization. After the RFCA procedure, patients received subcutaneous low-molecular-weight heparinate daily for an unspecified time. No mention is made of long-term aspirin or warfarin treatment.
A second type of atrial fibrillation onset occurs in patients who have other forms of SVTs, specifically AVNRT and AVRT. Because elimination of the AVNRT or AVRT by RFCA also eliminates atrial fibrillation in the majority of these patients, a logical conclusion is that the SVT in some manner initiates the atrial fibrillation, an example of a tachycardia-induced tachycardia. The following hypothesis can explain the connection. During AVRT and AVNRT, atrial systole occurs simultaneously with or shortly after ventricular systole, and therefore the AV valves are closed or at least not fully open when the atria contract. This then increases atrial pressure and produces atrial stretch, which in turn prolongs atrial refractoriness, an example of excitation-contraction feedback.4 5 Recently, it was shown in dogs that acute atrial stretch in response to a volume load that increased atrial pressure occurred heterogeneously, with thin areas of the atria stretching more than thick areas. Refractoriness followed suit, also being prolonged heterogeneously, and this dispersion of excitability made the atria vulnerable to induction of fibrillation.6 Thus, an excitation-contraction feedback loop in the atria creating electrical heterogeneity may be a second, stretch-induced mechanism responsible for the onset of atrial fibrillation.
Other mechanisms, including autonomic influences,7 are probably operative in some of the disease states noted above, but the two just mentioned generate interest if for no other reason than the atrial fibrillation with which they are associated is easily cured by RFCA.
Advances in understanding electrophysiological mechanisms responsible for the maintenance of atrial fibrillation have brought with them the recognition that the arrhythmia causes a tachycardia-induced atrial cardiomyopathy that results in electrophysiological and anatomic remodeling of the atria. These changes in turn facilitate the induction and perpetuation of the arrhythmia.
In most instances, atrial fibrillation is maintained by multiple wavelets of reentry. Recently, Wijffels et al8 showed that induction of atrial fibrillation by intermittent rapid atrial pacing in goats led to a shortening of atrial refractoriness with loss of rate adaptation and caused an increase in the rate, inducibility, and stability of the atrial fibrillation. These electrophysiological changes facilitated the generation of multiple reentrant wavelets and thus caused atrial fibrillation to beget atrial fibrillation. Morillo et al9 made similar observations in dogs subjected to sustained rapid atrial pacing and also showed that dogs developed biatrial enlargement, an increase in mitochondrial size and number with disruption of the sarcoplasmic reticulum, and that cryoablation of the posterior left atrium could eliminate the atrial fibrillation. Most recently, Elvan and Zipes10 confirmed the findings of Wijffels et al8 and found that rapid pacing–induced atrial fibrillation in dogs prolonged intra-atrial conduction time and also depressed sinus node function. This latter observation raises the possibility that the tachycardia-induced atrial myopathy also causes sinus node remodeling and may contribute to clinical presentations such as the bradycardia-tachycardia syndrome. Because the changes shown by these groups of investigators appear to be reversible, at least to a degree, the therapeutic corollary is naturally whether attempts to restore sinus rhythm are warranted under the premise that sinus rhythm begets sinus rhythm. These concepts are being tested.
It is often difficult to maintain sinus rhythm, particularly when atrial fibrillation has been present for long durations and presumably the atria have undergone extensive remodeling. Drug therapy can reduce the number of recurrences of atrial fibrillation and lengthen the interval between episodes,1 but breakthrough arrhythmia does occur, and drug side effects often limit patient compliance. A recent study in dogs11 showed that the pericardial sac can be used as a drug dispenser to target a drug such as amiodarone at the heart and minimize systemic effects while still having an impact on atrial fibrillation.
Nonpharmacological approaches to treating patients with atrial fibrillation are proliferating. Control of the ventricular rate is easily achieved with RFCA modification of AV conduction,12 and studies with an implantable atrial defibrillator are under way.13 At least three different surgical techniques have been used to eliminate atrial fibrillation, the most well known being the maze operation developed by Cox.14 This is based on the principle that if the amount of excitable atrial myocardium at any one time could be reduced by surgically creating lines of block that form an obligatory path of depolarization in the atria, the number of reentrant wavelets of fibrillation would also be reduced and atrial fibrillation could not be maintained. Once again the arrhythmia surgeon has pioneered a new approach to eliminate cardiac arrhythmias by altering structure to improve function, and once again the electrophysiologist is fast on his heels. RFCA, by replicating the principle of the maze operation by introducing linear lesions in the atria, has now been shown capable of eliminating atrial fibrillation in animals (Reference 15 and A. Elvan, MD, et al, unpublished data, 1996) and patients,16 17 although the procedure must be regarded as investigative with many issues still to be worked out. Nevertheless, it offers the possibility of eradicating atrial fibrillation without surgery.
Atrial RFCA also vagally denervates the atria, which may contribute to its effectiveness15 ; this may be true of the maze operation also. Complete and selective vagal denervation of the atria in dogs has now been accomplished and experimentally can prevent induction of atrial fibrillation.18 If this approach is effective clinically, it should be easily completed by thoracoscopy. Finally, combined therapies may be useful, eg, drug-delivery devices and/or atrial RFCA to lower atrial defibrillation thresholds and make shocks from the implantable atrial defibrillator more tolerable, biatrial pacing to prevent recurrences, and so forth.
In summary, it is clear that atrial fibrillation no longer takes a back seat to other SVTs such as AVNRT and AVRT. In fact, as the potential pool of patients with these arrhythmias diminishes,19 RFCA of atrial fibrillation may become the mainstay of the clinical cardiac electrophysiologist. Considering the number of patients with this arrhythmia, clinical cardiac electrophysiologists should expect job security into the 21st century.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported in part by the Herman C. Krannert Fund and by grant HL-52323 from the National Heart, Lung, and Blood Institute of the National Institutes of Health.
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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References |
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TopIntroductionReferences |
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1. Prystowsky EN, Benson DW Jr, Fuster V, Hart RG, Kay GN, Myerburg RJ, Naccarelli GV, Wyse DG. Management of patients with atrial fibrillation: a statement for healthcare professionals from the Committee on Electrocardiography and Electrophysiology, American Heart Association. Circulation. 1996;93:1262-1277.
2.
Jais P, Haissaguerre M, Shah DC, Chouairi S, Gencel L, Hocini M, Clementy J. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation.. 1997;95:572-576.
3. Haissaguerre M, Marcus FI, Fischer B, Clementy J. Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation: report of three cases. J Cardiovasc Electrophysiol. 1994;5:743-751.[Medline] [Order article via Infotrieve]
4. Kaseda S, Zipes DP. Contraction-excitation feedback in the atria: a cause of changes in refractoriness. J Am Coll Cardiol. 1988;11:1327-1336.[Abstract]
5.
Klein LS, Miles WM, Zipes DP. Effect of atrioventricular interval during pacing or reciprocating tachycardia on atrial size, pressure and refractory period: contraction-excitation feedback in human atrium. Circulation. 1990;82:60-68.
6. Satoh T, Zipes DP. Unequal atrial stretch in dogs increases dispersion of refractoriness conducive to developing atrial fibrillation. J Cardiovasc Electrophysiol. 1996;7:833-842.[Medline] [Order article via Infotrieve]
7. Coumel P. Cardiac arrhythmias and the autonomic nervous system. J Cardiovasc Electrophysiol. 1993;4:338-355.[Medline] [Order article via Infotrieve]
8.
Wijffels MCEF, Kirchof CJHJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation: a study in awake, chronically instrumented goats. Circulation. 1995;92:1954-1968.
9.
Morillo CA, Klein GJ, Jones DL, Guiradon CM. Chronic rapid atrial pacing: structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation. 1995;91:1588-1595.
10. Elvan A, Zipes DP. Pacing induced chronic atrial fibrillation impairs sinus node function in dogs. Circulation. In press.
11. Ayers GM, Rho TH, Ben-David J, Besch HR Jr, Zipes DP. Amiodarone instilled into the canine pericardial sac migrates transmurally to produce electrophysiologic effects and suppress atrial fibrillation. J Cardiovasc Electrophysiol. 1996;7:713-721.[Medline] [Order article via Infotrieve]
12.
Williamson BD, Man KC, Daoud E, Niebauer M, Strickberger SA, Morady F. Radiofrequency catheter modification of atrioventricular conduction to control the ventricular rate during atrial fibrillation. N Engl J Med. 1994;331:910-917.
13. Hillsley RE, Wharton JM. Implantable atrial defibrillators. J Cardiovasc Electrophysiol. 1995;6:634-648.[Medline] [Order article via Infotrieve]
14.
Cox JL, Jaquiss RD, Schuessler RB, Boineau JP. Modification of the maze procedure for atrial flutter and fibrillation, II: surgical technique of the maze II procedure. J Thorac Cardiovasc Surg. 1995;110:485-495.
15.
Elvan A, Pride HP, Eble JN, Zipes DP. Radiofrequency catheter ablation of the atria reduces the inducibility and duration of atrial fibrillation in dogs. Circulation. 1995;91:2235-2244.
16. Swartz JF, Pellersels G, Silvers J, Patten L, Cervantes D. Catheter based curative approach to atrial fibrillation in humans. Circulation. 1994;90(suppl I):I-335. Abstract.
17. Haissaguerre M. Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 1996;7:1132-1144.[Medline] [Order article via Infotrieve]
18. Chiou CW, Eble JN, Zipes DP. Efferent vagal innervation of the canine atria, sinus and atrioventricular nodes: the third fat pad. Circulation. In press.
19. Zipes DP. Arrhythmias on the endangered list. J Am Coll Cardiol. 1993;21:918-919.[Medline] [Order article via Infotrieve]
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