This is because there were important limitations to these studies. Both studies primarily enrolled older patients (over 65 years of age) with persistent AF who were mildly symptomatic. Furthermore, in the AFFIRM study, fewer than two-thirds of those in the rhythm control arm were actually able to maintain normal sinus rhythm. Because of these limitations it is difficult to extrapolate the results to certain subgroups of patients. These include: younger patients; those with new, first-onset AF who may benefit from early conversion to sinus rhythm; patients with persistent AF who are highly symptomatic; and patients with poor left ventricular function or with significant heart failure.

The latest ACC/AHA/ESC guidelines also made two important changes to clinical recommendations. The guidelines now include the use of catheter ablation of AF as one of the therapeutic options for patients with more persistent AF. Furthermore, in the anticoagulation guidelines, the threshold for anticoagulation has actually been lowered and the guidelines now are quite specific about risk factors for stroke in various risk groups.¹

The Progression of Atrial Fibrillation

AF is a tachycardia-induced atrial cardiomyopathy. Atria beating at 3–400 to 600 beats per minute create an atrial cardiomyopathy that will subsequently transform the atria both structurally and functionally into a substrate that facilitates the maintenance of the AF. The experimental work of Wijffels and colleagues produced the theory known as ‘AF begets AF.^’12 The researchers, using rapid atrial pacing to provoke AF in goats, revealed that electrical, cellular, and metabolic changes in the atrium occur within 24 hours after AF is produced. Moreover, they observed electrical changes—such as shortening of the refractory period and action potential duration—within six hours of provoking AF. Nattel et al. have shown that these changes were associated with alterations in the function of cellular membrane channels that control the electrical and contractile function of cells. Application of this theory led to management strategies such as early cardioversion and atrial pacing to prevent AF, and treatment with atrial defibrillators that seek to avoid progression of paroxysmal and persistent AF to permanent AF by reducing the frequency and duration of episodes of AF.

A number of studies, including the Framingham Heart Study ^13,14 and the Cardiovascular Health Study5 have shown that factors such as the development of heart failure, coronary disease, and hypertension can also contribute to altering the atrial substrate and facilitate the development of AF. A recent study produced data complimentary to the Framingham Heart Study and the Cardiovascular Health Study (CARAF). The CARAF study investigated the natural history of paroxysmal AF after initial discovery. The study enrolled 757 patients at the time of first diagnosed paroxysmal AF, of whom 63% had electrocardiographically documented recurrence within five years. The investigators found that paroxysmal AF progressed to chronic AF in 8.6% of the study population by year one and in 25% by year five. The study defined risk factors similar to those reported by the Framingham and the CARAF studies. These include increased left atrial size, age, cardiomyopathy, aortic stenosis, and mitral regurgitation. Interestingly, the CARAF study showed that even a relatively mild degree of left atrial enlargement was associated with increased risk of developing permanent AF. Furthermore, higher ventricular response rates during AF were linked to a lower probability of progression to permanent AF.¹⁵ It is also important to emphasize that, from these data, progression to chronic AF is not inevitable.

Conclusion

AF has gained increasing importance and is currently the most common sustained cardiac arrhythmia in the US and Europe. The impact of AF is expected to grow significantly due to an increasing prevalence associated with an aging population and the growing problem of obesity. The heterogeneous nature of the AF population and a limited understanding of the disease has complicated management options. However, as our understanding of the pathogenesis and natural history of AF grows, this will hopefully lead to new approaches towards treatment and prevention. The non-invasive solutions have, in general, have been relatively insufficient and the non-pharmacological approaches have been better. The latest ACC/AHA/ESC guidelines have two important changes in clinical recommendations. The guidelines now include the use of catheter ablation of AF as one of the therapeutic options for patients with more persistent AF. Furthermore, in the anticoagulation guidelines, the threshold for anticoagulation has actually been lowered and the guidelines now are quite specific about risk factors for stroke in various risk groups. Pharmacological development needs to move its focus from finding the ‘son’ or ‘grandson’ of quinidine and search for new approaches.