Is there an age limitation for lone AF?

MAASTRICHT, THE NETHERLANDS. Most definitions of lone atrial fibrillation (LAF) use the age of 60 years as a cutoff point beyond which the condition is no longer lone. I have always felt that, while it may make some sense to use biological age as a cutoff, it makes no sense at all to use chronological age for this purpose. This opinion is echoed by Lars Frost, MD of Aarhus University Hospital in Denmark who expressed it thus. Cardiologists with strong political influence have suggested that a diagnosis of lone atrial fibrillation should be restricted to patients less than 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.[1]

A group of international researchers from Canada, France, Germany, Greece and the Netherlands now confirms that the cardiovascular outcome in patients with idiopathic (no known cause) atrial fibrillation (AF) may be closer related to the “biological age” of the cardiovascular system (primarily expressed as left atrial enlargement) than to one’s “calendar age”.

CLASSIFICATION OF ATRIAL FIBRILLATION

Heart disease related AF
The vast majority of cases of AF are associated with underlying heart disease, in particular:

  • Heart valve disease
  • Coronary artery disease
  • Ventricular hypertrophy (thickening of left ventricle walls)
  • Cardiomyopathy (weakening of heart muscle leading to heart failure)
  • Hypertension (elevated blood pressure)
  • Sick sinus syndrome
  • Pericarditis (inflammation of the sac surrounding the heart)
  • Myocarditis (inflammation of the heart muscle).

Most episodes associated with heart disease are adrenergic in nature thus explaining the tendency of cardiologists to prescribe beta-blockers as a first line treatment for AF.

Non-valvular AF
Non-valvular AF is AF occurring in the absence of rheumatic mitral valve disease, mitral valve repair, or the presence of a prosthetic heart valve. About 70% of all cases of AF are non-valvular.

Lone AF
Lone AF is AF occurring in the absence of clinical or echocardiographic findings of cardiovascular disease (including hypertension), related pulmonary disease, or cardiac abnormalities such as valve problems or gross enlargement (> 50 mm) of the left atrium. A cutoff point of 60 to 65 years of age is usually specified as well.

Idiopathic AF
Idiopathic means “of no known cause”, so idiopathic AF is essentially lone AF not associated with any known cause. The most important known causes of LAF (heart disease has already been ruled out) are thyroid disorders, hypoglycemia, pheochromocytoma, chromosomal abnormalities (genetic connection), serious electrolyte imbalances, Conn’s syndrome (hyperaldosteronism), binge drinking, recreational drug use (especially cocaine), and treatment with pharmaceutical drugs including digoxin and certain drugs used in the treatment of asthma, emphysema and bronchitis. I suspect most members of afibbers.org would be classified as having idiopathic rather than lone AF.

The researchers involved in the study used the following definition for idiopathic AF:

  • Absence of cardiovascular disease (including coronary and valvular disease)
  • Absence of hypertension defined as a systolic blood pressure greater than or equal to 140 mmHg, a diastolic pressure greater than or equal to 90 mmHg, or the use of antihypertensive drugs.
  • Absence of left ventricular hypertrophy
  • No history of diabetes
  • Total fasting cholesterol less than 6.4 mmol/L (248 mg/dL)
  • No history of coronary artery disease or angina
  • No previous heart attack, stroke, heart surgery, evidence of heart failure, or a left ventricular ejection fraction of less than 50%
  • No present or past evidence of thyroid or pulmonary disease
  • No cancer or significant renal dysfunction.

NOTE: Age was not included in this definition of idiopathic AF.

A total of 3978 AF patients taking part in the Euro Heart Survey were screened and 119 (3%) were found to meet the above strict criteria for idiopathic AF. The average (mean) age of the 119 study participants was 58 years (48% were older than 60 years) and 72% were male. Persistent and permanent AF, not unexpectedly, were more common among older patients (66%) than in the younger group (age under 60 years) where 34% had non-paroxysmal AF. There was no statistically significant difference in the time since diagnosis or in the left atrium size between the older and younger groups. However, left atrial size was significantly higher among persistent and permanent afibbers (average of 42 mm) than among paroxysmal ones (average of 38 mm). Despite the fact that all patients had a low stroke risk, 44% in the younger group and 65% in the older group had been prescribed warfarin or other vitamin K antagonists. No strokes or other cardiovascular events occurred in the groups during the 1-year follow-up.

The characteristics of the 119 patients were compared to a group of 152 matched AF patients fulfilling the criteria for idiopathic AF except for the presence of hypertension (treated or untreated). There were no significant differences in baseline characteristics between the two groups. However, 5 patients (6%) in the hypertension group suffered a stroke during follow-up indicating that hypertension on its own confers a substantial stroke risk. NOTE: None of the 5 stroke victims were anticoagulated.

The researchers conclude that idiopathic AF, even if diagnosed at an advanced age, is not associated with significant atrial enlargement, AF progression (from paroxysmal to persistent/permanent), or an adverse short-term prognosis. In contrast, elevated blood pressure seems to imply a worse prognosis even if not associated with atrial enlargement. Therefore, a yet to be defined cutoff for blood pressure rather than age should be used when defining idiopathic AF.
Weijs, B, et al. Idiopathic atrial fibrillation revisited in a large longitudinal clinical cohort. Europace, Vol. 14, 2012, pp. 184-90
Wyse, DG. Idiopathic atrial fibrillation: a rose by any other name? Europace, Vol. 14, 2012, pp. 151-52

Editor’s comment: Most members of afibbers.org probably have idiopathic rather than lone AF. Thus it is reassuring to see that chronological age as such is not related to prognosis or risk of stroke. However, hypertension (treated or untreated) clearly increases the risk of stroke even in otherwise idiopathic afibbers, so it would be prudent for such patients to take appropriate measures for stroke prevention.
[1] Frost, L. Lone atrial fibrillation – good, bad, or ugly? Circulation, Vol. 115, 2007, pp. 3040-41