New risk factor for lone atrial fibrillation

COPENHAGEN, DENMARK. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart’s electrical cycle. It is measured with a standard 12-lead electrocardiogram (ECG) and represents one ventricular “beat”, i.e. the time it takes for one complete cycle of electrical depolarization (contraction) and repolarization (recovery) of the right and left ventricles. The QT interval is obviously dependent on the heart rate (the faster the heart rate, the shorter the QT interval) and most studies report a corrected QT interval (QTc interval) rather than just the QT interval in order to provide more meaningful and comparable results. For more on this see Heart Rhythm 101. NOTE: In this study the authors used the Framingham formula to correct for heart rate. A prolonged QT interval is a risk factor for ventricular tachyarrhythmias and sudden cardiac death.

Now a group of Danish researchers reports that both an abnormally short and abnormally long QTc interval are significant risk factors for the development of atrial fibrillation (AF) and, in particular, for the development of lone atrial fibrillation (LAF). NOTE: In this study lone AF is defined as the occurrence of AF before the age of 65 years in the absence of hypertension, heart failure, heart attack, valvular heart disease, diabetes, and hyperthyroidism. The study involved 281,277 people living in Copenhagen who had one or more ECGs during the period 2001 to 2010. The average age of the study subjects was 54 years (41 to 65 years), 56% were women and only 16% had hypertension, while 3% had heart failure or had suffered a heart attack. Average heart rate was 69 bpm (62 to 78 bpm).

During the average follow-up of 5.7 years (1,614,832 person-years), 10,766 subjects developed AF corresponding to an annual incidence of 0.7%/year. The risk of being diagnosed with AF was 44% higher in subjects with a QTc interval at or above 464 ms when compared to the reference group (QTc interval between 411 and 419 ms). Similarly, subjects with an abnormally short QTc interval were found to have a 45% increased risk of AF when compared to the reference group.

A subgroup (LAF group) of 175,738 participants below the age of 65 years without hypertension, heart failure, previous heart attack, valvular heart disease, diabetes and hyperthyroidism was followed for a median of 4.7 years (816,322 person-years). During this time, 1467 persons (0.2%/year) were diagnosed with lone AF. The risk of being diagnosed with LAF was more than twice as high (Hazard Ratio = 2.32) among persons with a QTc interval of 464 ms or longer when compared to the reference group (384 to 397 ms).

The researchers conclude that there is a clear J-shaped association between QTc interval duration and development of AF. The risk associated with a prolonged QTc interval is significantly greater in the case of LAF.
Nielsen, JB, et al. J-shaped association between QTc interval duration and the risk of atrial fibrillation. Journal of the American College of Cardiology, Vol. 61, No. 25, June 25, 2013, pp. 2557-64

Editor’s comment: The incidence of new onset LAF was low at 0.18%/year or 27% of all new AF cases. It is interesting that the risk of AF associated with an elevated QTc interval (at or above 464 ms) was lower (36%) in a subgroup of patients with cardiovascular disease than in the subgroup without (LAF group). This could, according to the authors, indicate that LAF is not associated with undetected cardiovascular disease, but rather with some unknown inherent characteristics or remodelling of cardiac electrophysiology (fibrosis??). It is interesting that potassium and magnesium deficiencies are associated with long QT syndrome (inherited long QT interval). Thus, ensuring adequate potassium and magnesium status would seem to be an absolute must for anyone diagnosed with long QT interval on an ECG.