A Bridge to the Future

Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation

Eric N. Prystowsky MD


J Cardiovasc Electrophysiol. 2019;29(12):1604-1606. 

In This Article


Since the primary goal in treating patients with AF other than minimizing stroke and heart failure is to treat symptoms, is it appropriate to allow this patient to have permanent AF for the rest of his life? I would not be in favor of this approach and suggest it is important to re-evaluate previous major rate vs rhythm controlled trials in AF. Probably the most influential of such trials was Atrial Fibrillation mean Follow-up Investigation of Rhythm Management (AFFIRM).[1] In AFFIRM, 4060 patients were randomized to either rate or rhythm control strategy, and the mean age was approximately 69.7 years. Importantly, the mean follow-up time was only 3.5 years. The primary endpoint of mortality was not different between patient groups. A smaller but still important randomized trial comparing rate control vs rhythm control strategies was Rate Control vs Electrical Cardioversion for Persistent Atrial Fibrillation (RACE).[2] In RACE, there were 522 patients who were randomized to rate control or maintenance of sinus rhythm. The mean age was 68 years and the mean follow-up was 2.3 years. The primary endpoint was a composite of death and morbidity from cardiovascular causes and did not differ between treatment strategies.

In my experience, after these trial results were reported many physicians opted for a rate control strategy in their patients, which is certainly easier to accomplish than dealing with the complexities of rhythm control. What may not be known by many nonelectrophysiologists is that persistence of AF over time typically leads to fibrosis of the atria and atrial enlargement, and in many patients a point of no return is reached.[3,4] In such situations, it may be impossible to restore and maintain sinus rhythm, even though the patient may need it several years after the initial diagnosis for either new symptoms or a change in their underlying cardiovascular status. It is for these reasons that a cautionary note was stated in the 2006 Atrial Fibrillation Management Guidelines: "…this makes it important to ensure that a window of opportunity to maintain sinus rhythm is not overlooked early in the course of management of a patient with AF."[3] It is also important to note that AFFIRM and RACE enrolled patients in their late 60s and the follow-up was a few years in a disease that is present for decades. As with any randomized clinical trial, it is key not to have "trial creep" and extend the observations to groups not tested in the trial. My patient is only 47 years old, and the safety of allowing such an individual to persist in AF for decades is unknown.

In fact, a population-based study from Canada suggests otherwise.[5] This study from Quebec, Canada was a retrospective evaluation of patients 65 years and older that evaluated patients taking rhythm control vs rate control drugs over a period of time. The study demonstrated little difference in mortality during 4 years of treatment, but mortality decreased in the rhythm control group after year 5. These data need to be viewed cautiously for the kind of study this is, but they are thought-provoking regarding potential results of rate vs rhythm control extended for longer periods of time. More recent data on the possible effects of AF on cognitive function are troubling. Bunch et al.[6] evaluated the association between AF and dementia in a prospective database of approximately 37 000 patients. Their conclusion was that AF was independently associated with senile, vascular, and Alzheimer's dementia. In a subsequent study, Bunch et al.[7] evaluated long-term outcomes in patients with AF, with and without ablation, and those with no history of AF. Patients with AF again had a significant risk of all three types of dementia, but those who had ablation demonstrated a reduction in such risk.

Cognitive function and the prevalence of silent cerebral ischemia was evaluated in patients with paroxysmal and persistent AF as well as control subjects.[8] The final study population of 270 subjects included 180 patients (90 paroxysmal and 90 persistent) who had AF and 90 controls in sinus rhythm. Standardized screening tests were used to evaluate cognitive function, and patients also underwent magnetic resonance imaging of the brain. Silent cerebral ischemia was detected in 92 patients with persistent AF and 89% with paroxysmal AF but in only 46 patients without AF. Further, cognitive performance was significantly worse in persistent and paroxysmal AF patients than in controls. A recent meta-analysis of 14 studies[9] concluded that AF was significantly associated with the risk of developing cognitive impairment.

Another area of concern are patients who have heart failure. In the AF and Congestive Heart Failure trial,[10] the results suggested that rate control compared with rhythm control using antiarrhythmic drugs were similar regarding death from cardiovascular causes. Unfortunately, these results have led many physicians to allow patients with heart failure to remain in AF without attempting the restoration and maintenance of sinus rhythm. I feel this approach needs to be individualized for each patient, and there are more recent trials showing the benefits of sinus rhythm in patients with heart failure. For example, significant improvement in left ventricular ejection fraction was demonstrated by Hsu et al[11] after catheter ablation of AF in patients who were reported to have good rate control. Many had thought that reduction in ejection fraction was primarily related to inappropriate rate control, which certainly can result in a reduced LV ejection fraction, but these data clearly showed the importance of restoring sinus rhythm in many such patients. A similar finding was noted by Gentlesk et al[12] and Prabhu et al.[13] A recent major trial, "Catheter Ablation versus Standard Conventional Treatment in patients with Left ventricular dysfunction and Atrial Fibrillation (Castle-AF)," evaluated catheter ablation in patients with AF and heart failure and showed a benefit of ablation on death from any cause and heart failure hospitalizations.[14] This was a relatively small prospective trial, but the results support the important role of sinus rhythm obtained by catheter ablation in at least some patients with AF and heart failure. Of course, whether similar results would be obtained with medications only is not clear.

Now, back to my patient. After a full discussion of risks and benefits of both approaches, he opted for sinus rhythm; and after receiving an appropriate antiarrhythmic drug before cardioversion, he has been successfully maintained in sinus rhythm after cardioversion. It is not uncommon for patients who thought they had no symptoms when in AF to suddenly feel more energy when in sinus rhythm. However, my patient felt the same after maintenance of sinus rhythm.

I feel it is very important for any healthcare providers managing patients with AF to have a detailed discussion with their patient about the rhythm and rate control strategies. If a patient is in an age group consistent with the AFFIRM and RACE Studies, one at least has some data over a short period of time on the safety of a rate control strategy. However, the patient should know that years of persistent AF has not been studied for safety. When a patient is younger than the entry criteria of RACE and AFFIRM, the healthcare provider should explain to that individual that persistence of AF for years will likely cause progressive scarring and dilatation of the atria to the point where restoration and maintenance of sinus rhythm may no longer be possible. Only after knowing all these possibilities can patients make informed decisions about their future care.