Long-term prognosis for lone afibbers

BELGRADE, SERBIA. In June 2007 cardiologists at the Mayo Clinic reported the results of a study carried out to determine the long-term prognosis of 76 patients with lone atrial fibrillation (AF). After an average follow-up of 30 years, 29% of paroxysmal and persistent afibbers had progressed to permanent AF. In most cases the progression to permanent AF occurred within the first 15 years after diagnosis. Survival in the study group at 92% at 15 years and 68% at 30 years was similar to or even slightly better than expected for an age- and sex-matched group of Minnesotans (86% and 57% at 15 and 30 years respectively). The development of congestive heart failure (19% of the group at 30 years follow-up) was not significantly higher than expected (15%).

During the follow-up, 5 strokes (0.2%/person-year) and 12 transient ischemic attacks (0.5%/person-year) occurred in the group – mostly among permanent afibbers. All strokes and TIAs (transient ischemic attacks) occurred in participants who had developed one or more risk factors for stroke during follow-up (hypertension in 12 patients, heart failure in 4, and diabetes in 3). Not a single stroke or TIA occurred among lone afibbers with no risk factors for stroke. This prompted the remark from the researchers – Our long-term data suggest that the increased risk of stroke in atrial fibrillation is due to “the company it keeps”. In other words, lone AF as such is not a risk factor for ischemic stroke. The overall conclusion of the study is highly reassuring to lone afibbers – After >30 years of follow-up of our rigorously defined cohort, findings confirm that overall survival is not affected adversely by lone atrial fibrillation.[1]

A group of Serbian cardiologists now report on a larger long-term study involving 346 patients with newly diagnosed lone atrial fibrillation (LAF). Their definition of LAF was AF in patients 60 years old or younger with no hypertension, underlying heart disease or other comorbid conditions that could explain the presence of AF. The average age of the study participants at baseline was 43 years (range of 18 to 60 years), 76% were male, and 12% had asymptomatic AF. The majority (70%) had paroxysmal (intermittent) AF at baseline with 22% having persistent and the remaining 8% having permanent AF. Permanent afibbers were significantly more likely to have an enlarged left atrium and asymptomatic AF when compared to paroxysmal afibbers. During the average 12-year follow-up, 35% of the group developed heart disease, 25% hypertension, and 10% diabetes.

During follow-up, 27% of paroxysmal afibbers and 55% of originally persistent afibbers progressed to permanent AF. The average time to progression was 10 years and the average age at which progression was documented was 55 years (range of 24 to 74 years). Older age at diagnosis and development of congestive heart failure were predictors of progression. Somewhat surprisingly, the development of hypertension was associated with a 30% decrease in the risk of progression from paroxysmal to persistent or permanent AF. It is likely that this is due to the fact that therapy with angiotensin II converting enzyme inhibitors was much more common among patients with hypertension (77%) than among those who retained normal blood pressure (5%). NOTE: Hypertension was defined as a blood pressure reading above 140/85 mm on 3 separate occasions.

A newly developed risk score, the so-called HATCH score (1 point each for hypertension, age of 75 years or older, and chronic obstructive pulmonary disease and 2 points each for heart failure and prior stroke or TIA) was found to accurately predict the risk of progressing from paroxysmal to permanent AF. A score of 0 was associated with a 20% risk of progression, a score of 1 with a 36% risk, and a score of 2 with a 63% risk of progressing to permanent AF.

Thromboembolism was documented in 14 patients (4%) over the 12-year follow-up period. Nine of the 14 patients suffered an ischemic stroke corresponding to an annual stroke incidence of 0.2%. This rate is identical to the one observed in the Mayo Clinic study and, once again, confirms that the risk of stroke associated with one AF is extremely low – actually lower than the rate observed in the general population. Furthermore, it should be noted that 6 of the 14 patients had developed one or more risk factors for thromboembolism (5 patients with hypertension, 1 with coronary artery disease, and 2 with diabetes) by the time they experienced their stroke or other thromboembolic event. It is also of interest to note, that of the 14 patients 8 were taking aspirin, while 6 had no antithrombotic therapy. In multivariate analysis only the development of hypertension and coronary artery disease was significantly associated with thromboembolism.

During follow-up, 14 patients (4%) developed congestive heart failure (CHF) at an average 10 years from diagnosis (range of 0 to 26 years). The only variable independently associated with an increased risk of CHF in multivariate analysis was progression from paroxysmal to permanent AF. The 10-year survival of study participants was 99.6%. It is not clear from the study whether permanent AF increases the risk of CHF, or CHF increases the risk of permanent AF. The former clearly makes more sense.

The Serbian researchers conclude that the prognosis of lone AF is favourable, but becomes less so with increasing age and the development of (new) underlying heart disease.
Potpara, TS, Lip, GYH, et al. A 12-year follow-up study of patients with newly diagnosed lone atrial fibrillation: Implications of arrhythmia progression on prognosis. Chest, Vol. 141, No. 2, 2012, pp. 339-47
Boriani, G, et al. Atrial fibrillation: It is better to be alone than in bad company! Chest, Vol. 141, No. 2, 2012, pp. 290-92

Editor’s comment: The Belgrade study clearly confirms the conclusions of the Mayo Clinic study that lone AF is a benign condition with excellent long-term prognosis. The risk of stroke is extremely low even without anticoagulation, and survival rate is excellent. There is a significant trend though for paroxysmal AF to progress to persistent or permanent AF. It is, however, likely that this trend would have been significantly less pronounced if 36% of paroxysmal and persistent afibbers had not been treated with digoxin. This “medicine from hell”, for lone afibbers at least, may not only prolong episode duration, but may actually convert paroxysmal AF to permanent.[2,3] NOTE: I personally do not agree that chronological age should enter into the definition of lone AF. This conviction is supported by the following statement by Dr. Lars Frost of the Aarhus University Hospital in Denmark, "Cardiologists with strong political influence have suggested that a diagnosis of lone atrial fibrillation should be restricted to patients <60 years of age, although there is no evidence of any threshold values by age regarding the risk of stroke in patients with atrial fibrillation – or in any other medical condition for that matter".[4]

References
1. Jahangir, A, et al. Long-term progression and outcomes with aging in patients with lone atrial fibrillation. Circulation, Vol. 115, June 19, 2007, pp. 3050-56
2. Sticherling, C, et al. Effects of digoxin on acute, atrial fibrillation: Induced changes in atrial refractoriness. Circulation, Vol. 102, November 14, 2000, pp. 2503-08
3. Falk, RH. Proarrhythmic responses to atrial antiarrhythmic therapy. In Atrial Fibrillation: Mechanism and Management, edited by Rodney H. Falk and Philip J. Podrid, Lippincott-Raven Publishers, Philadelphia, 2nd edition, 1997, p. 386
4. Frost, L. Lone atrial fibrillation: Good, bad or ugly? Circulation, Vol. 115, June 19, 2007, pp. 3040-41