“Lone” Atrial Fibrillation: Finding Optimal Treatment Strategies

atrial fibrillation
atrial fibrillation
Optimal treatment strategies for lone atrial fibrillation have been unclear, but more technological advances and understanding of disease are propelling researchers forward.

Part 1

Introduction to “Lone” Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia globally, with an estimated prevalence of 9% among Americans older than 65 years of age and 2% of individuals younger than 65 years of age. These rates are expected to increase as the elderly population continues to grow.1 Although the precise mechanisms of AF etiology have yet to be fully elucidated, there have been significant advances in clarifying its pathophysiology in recent decades.

For example, it is now established that male sex, European ancestry, and older age are risk factors for AF, as well as modifiable risk factors such as hypertension, smoking, obesity, sedentary lifestyle, diabetes, and obstructive sleep apnea.1 According to a recent review, each of these factors “has been shown to induce structural and electric remodeling of the atria,” which aligns with the current understanding that “AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending on comorbid conditions, genetics, sex, and other factors.”2

Although patients with AF often have comorbid heart disease or other serious comorbidities or cardiovascular abnormalities, a portion of patients have structurally normal hearts and no apparent major comorbidities.2 Historically, these patients were said to have “lone AF,” although this term is starting to decline among some practitioners.3

“I think many cardiologists are now uncomfortable with the term, as it does not really have much clinical basis — it has not been defined consistently, and thus this is a heterogeneous group,” according to Erin D. Michos, MD, MHS, FACC, FAHA, associate professor of medicine and epidemiology and associate director of preventive cardiology at the Ciccarone Center for the Prevention of Heart Disease at Johns Hopkins School of Medicine in Baltimore, Maryland.3

“Even in someone who may appear to be healthy, the presence of AF can be a marker of abnormal underlying substrate, such as genetic risk or abnormalities in cellular or molecular signaling, or more subtle cardiac or pulmonary disease that was overlooked,” Dr Michos noted.

As imaging and diagnostic techniques have improved, prevalence estimates of lone AF have decreased, from 30% by some observations, to 11% in the Framingham Heart Study, to 3% in the Euro Heart Survey.4 It has been noted that because of the lack of a consistent definition and guidance regarding appropriate imaging or management in these cases, the term is confusing and not clinically useful.

Regardless of terminology, this is a patient group for whom optimal strategies are often unclear. For updates on treatment options, Cardiology Advisor checked in with Dr Michos and 2 other experts, Randall K. Wolf, MD, FACCS, FACC, a cardiothoracic surgeon who invented the Wolf Mini-Maze procedure for AF, and professor of surgery at University of Texas Health Science Center at Houston; and Phillip S. Cuculich, MD, an associate professor of medicine in the Cardiovascular Division at Washington University School of Medicine in St. Louis, Missouri.

Cardiology Advisor: What are the reasons that AF recurs frequently in some patients?

Dr Wolf: The reasons are not clear, but a few possible mechanisms have been proposed. Recurrent AF is more common as patients age, [al]though it affects people of all ages. This suggests that there may be a hereditary predisposition in some patients that is complicated by an environmental component that amplifies it. [In addition], the incidence of AF is very high after heart surgery, which suggests that inflammatory processes in the heart sac may represent another mechanism for recurrent AF. There could also be an autonomic nervous system imbalance — as in vagally mediated AF — that may be triggered when atrial ganglionic plexi are stimulated.

Treatment Options

Cardiology Advisor: What are the current treatment options for patients with AF who have structurally normal hearts and no major comorbidities like diabetes?

Dr Wolf: Traditionally, the first-line approach has been medication to control the heart rate when the patient is out of rhythm or to control the rhythm with an antiarrhythmic drug like amiodarone along with a blood thinner when indicated. Amiodarone was never actually approved for an AF indication. It received [US Food and Drug Administration] approval for life-threatening ventricular arrhythmias, [al]though it is most frequently prescribed for AF. Because it is associated with many side effects, patients [who take] amiodarone for more than a year must be checked for toxicity in organs such as the thyroid gland, lungs, and skin.

If medical approaches fail, catheter ablation is often the next option, although success rates have not been that high. [Editor’s note: For example, a 2013 meta-analysis showed that 3-5 years after a single catheter ablation, 53.1% of all patients remained free of AF (95% CI, 46.2%-60.0%), while the success rate was 54.1% (95% CI, 44.4%-63.4%) for paroxysmal AF and 41.8% (95% CI, 25.2%-60.5%) for nonparoxysmal AF.5 Higher success rates were found in patients who had undergone multiple catheter ablations (79.8%; 95% CI, 75.0%-83.8%), although substantial heterogeneity was observed for both single-procedure and multiple-procedure outcomes (I2 >50%).5]

Dr Michos: As with all [patients with AF], we use the CHADS2-VASc score to determine stroke risk and make recommendations about anticoagulation. For a CHADS2-VASc score of 0, anticoagulation may be deferred, as risks of bleeding might outweigh benefits of stroke prevention. Of note, there may be a tendency to think that a [patient with] low-risk AF should be treated with aspirin, but a recent study by Dr Jared Bunch presented at the 2017 Heart Rhythm Society meeting showed that aspirin increased the risk [for gastrointestinal] bleeding [and] was ineffective for stroke prevention.6

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I think we would manage recurrent AF in a similar fashion [in] patients with and without apparent risk factors, which is to say that if an individual is symptomatic and has failed antiarrhythmic drugs for symptom control, then catheter ablation is a good option. Of course, this decision would be made in the context of a shared discussion with the patient. Catheter ablation has an even better chance for success when performed in conjunction with an aggressive lifestyle management program. I do not think patients should ever consider themselves “cured” after a successful catheter ablation, as attention to prevention and healthy lifestyle warrants lifelong vigilance. I have had patients with AF [who had recurrence] many years after an initially successful ablation.

Dr Cuculich: There is some good and bad news about AF. The bad news first: Historically, it can be one of the most challenging heart rhythm disorders to control. But there is good news too: We now have more tools, tricks, and treatments for AF than ever before. We are making great strides toward treating and even preventing AF, especially as we combine traditional therapies like medicines or procedures with more holistic approaches, like sustained weight loss and treatment of other linked diseases. For patients who are generally healthy with a structurally normal heart, a patient-tailored treatment plan stands a very high chance of controlling AF. In my career, I now come to expect that we can control AF in our healthy patients with normal hearts, particularly with aggressive risk factor modification and meticulous catheter ablation techniques.

For some patients, however, it may be reasonable to simply stay in AF, especially if they are not bothered by it. In a large randomized trial of over 4000 patients with asymptomatic AF, where half received rhythm control strategies and half received rate control strategies, there was no survival advantage to either intervention.7 In fact, there were potential advantages to the simplicity of a rate-control strategy, such as fewer adverse drug effects. What became clear, however, was that minimizing stroke risk with anticoagulation was effective and important in both groups.7

If a patient remains symptomatic with AF, referral to a large-volume medical center would be an appropriate choice. Treatment options and expertise may exist there which are not available elsewhere. A second opinion is never a bad option.

Read Part II, in which the experts will discuss lifestyle management, alternative therapies, and future research.


  1. US Centers for Disease Control and Prevention. Arial Fibrillation Fact Sheet. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillation.htm. Updated August 22, 2017. Accessed October 9, 2017.
  2. Staerk L, Sherer JA, Ko D, Benjamin EJ, Helm RH. Atrial fibrillation: epidemiology, pathophysiology, and clinical outcomes. Circ Res. 2017;120(9):1501-1517.
  3. Pison L, Hocini M, Potpara TS, et al; Scientific Initiative Committee, EHRA. Work-up and management of lone atrial fibrillation: results of the European Heart Rhythm Association Survey. Europace. 2014;16(10):1521-1523.
  4. Wyse DG, Van Gelder IC, Ellinor PT, et al. Lone atrial fibrillation: does it exist? A “white paper” of the Journal of the American College of Cardiology. J Am Coll Cardiol. 2014;63(17):1715-1723.
  5. Ganesan AN, Shipp NJ, Brooks AG, et al. Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis. J Am Heart Assoc. 2013;2(2):e004549. 
  6. Jacobs V, May HT, Bair TL, et al. Long-term aspirin does not lower risk of stroke and increases bleeding risk in low-risk atrial fibrillation ablation patients [published online September 26, 2017]. J Cardiovasc Electrophysiol. doi:10.1111/jce.13327
  7. Wyse DG, Waldo AL, DiMarco JP, et al; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-1833.
  8. Pathak RK, Middeldorp ME, Meredith M, et al. Long-term effect of goal-directed weight management in an atrial fibrillation cohort: a long-term follow-up study (LEGACY). J Am Coll Cardiol. 2015;65(20):2159-2169.
  9. Mozaffarian D, Furberg CD, Psaty BM, Siscovick D. Physical activity and incidence of atrial fibrillation in older adults: the Cardiovascular Health Study. Circulation. 2008;118(8):800-807.
  10. Wolf RK. Treatment of lone atrial fibrillation: minimally invasive pulmonary vein isolation, partial cardiac denervation and excision of the left atrial appendage. Ann Cardiothorac Surg. 2014;3(1):98-104.
  11. Diener H-C, Weber R, Lip GYH, Hohnloser SH. Stroke prevention in atrial fibrillation: do we still need warfarin? Curr Opin Neurol. 2012;25(1):27-35.