CORRESPONDENCE: RESEARCH CORRESPONDENCE
Short QT Interval and Atrial Fibrillation in Patients Without Structural Heart Disease
Gregor Poglajen, MD,
Misa Fister,
Branislav Radovancevic, MD and
Bojan Vrtovec, MD, PhD*
* Division of Cardiology, Ljubljana University Medical Center, MC SI-1000, Ljubljana, Slovenia (Email: bojan.vrtovec{at}mf.uni-lj.si).
To the Editor: The short QT syndrome is a newly described clinical entity characterized by the presence of a short QT interval associated with cardiac tachyarrhythmias in otherwise healthy individuals. A genetic basis has been identified linking the disease to mutations in KCNH2 in the familial forms and a mutation in KCNQ1 in a sporadic form of the disease (1). The description of a novel, de novo gain of function mutation in KCNQ1, responsible for atrial fibrillation (AF) and short QT syndrome in utero, indicates that gain of function mutations in KCNQ1 channels can shorten the duration of both ventricular and atrial action potentials (2), which could account for the high incidence of AF in patients with short QT syndrome (3). Atrial fibrillation can occur in the absence of detectable organic heart disease, so-called "lone AF," in about 30% of cases (4). Because the pathophysiology of lone AF remains poorly defined, we speculated that mechanisms underlying the high incidence of AF in short QT syndrome might also be responsible for the development of AF in the absence of structural heart disease. To test this hypothesis we examined QT interval duration in 165 consecutive healthy subjects presenting with an episode of AF (AF group). The control group included 165 age- and gender-matched subjects without any evidence of arrhythmia on a standard electrocardiogram (ECG).
Data on the AF group were collected at the hospital emergency department, and data on the control group were obtained in healthy individuals at the time of routine outpatient check-up as a part of national cardiovascular disease prevention program. Subjects treated with type I or type III antiarrhythmic drugs, anti-depressive drugs, antihistamines, or macrolide antibiotics were not included in the study.
In all subjects, we recorded resting 12-lead ECGs at a paper speed of 25 mm/s on a Marquette Resting ECG recorder (Marquette Electronics Inc., Milwaukee, Wisconsin). With calipers on printed ECGs, the QT interval of each lead was measured from the beginning of the QRS complex to the visual return of the T-wave to the isoelectric line. When the T-wave was interrupted by the U-wave, the end of the T-wave was defined as the nadir between the T-wave and the U-wave. When the nadir was not clearly visible or the maximal T-wave amplitude did not exceed 0.25 mV, the ECG lead was excluded. All the QT interval measurements were performed with patients in sinus rhythm. Heart rate correction was done with the Bazett formula, and QTc interval duration was defined as the mean duration of all QTc intervals measured.
Differences between the AF and control groups were analyzed with 1-factor analysis of variance (ANOVA). Comparisons of categorical variables were made with a chi-square test. Both forward and backward stepwise linear regression analyses were used to identify predictive multivariate models. A p value < 0.05 was considered significant.
The two groups did not differ significantly with regard to age (62 ± 10 years in AF group vs. 61 ± 9 years in control group, p = 0.67), gender (male: 67% in AF group vs. 66% in control group, p = 0.90), history of hypertension (72% in AF group vs. 71% in control group, p = 0.80), or diabetes (10% in AF group vs. 8% in control group, p = 0.76). Similarly, we found no inter-group differences in left ventricular ejection fraction (58.8 ± 7.9% in AF group vs. 61.1 ± 10.3% in control group, p = 0.80), dimensions of the left atrium (4.1 ± 1.2 cm in AF group vs. 4.0 ± 1.3 in control group, p = 0.69), resting heart rate (83 ± 23 beats/min in AF group vs. 78 ± 25 beats/min in control group, p = 0.62), or QRS complex duration (94 ± 15 ms in AF group vs. 91 ± 21 ms in control group, p = 0.54). No family history of premature sudden death was found in any of the groups; the history of syncope was present in 7% of patients from the AF group and in 4% of the control group (p = 0.24). The QTc interval of patients in the AF group, however, was significantly shorter compared with QTc interval in the control group (Fig. 1). Short QTc interval (<400 ms) was an independent predictor of AF occurrence in the multivariate analysis (p = 0.002), whereas hypertension, diabetes, decreased left ventricular ejection fraction (<60%), and increased left atrial size (>4 cm) were not.
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Figure 1 QTc interval duration in patients with atrial fibrillation and no structural heart disease (AF group) and in healthy subjects (control group).
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Our findings demonstrate that even in the absence of genetically identifiable chanellopathies, patients with AF and no structural heart disease have significantly shorter QT intervals than their age- and gender-matched healthy counterparts. We therefore speculate that pathophysiological mechanisms that lead to shortening of QT interval (even of mild degree) might also play an important role in genesis of AF in structurally normal hearts. Action potential duration of ventricular myocardium is largely determined by the activation of delayed rectifier potassium current (IKs): with the loss-of-function mutation of IKs, the ventricular action potential is prolonged (clinically long QT syndrome); and in the gain-of-function mutation of IKs, it is shortened (clinically short QT syndrome) (5). The resulting enhancement of transmural dispersion of myocardial repolarization together with heterogeneous reduction in action potential duration creates a vulnerable window for ventricular arrhythmias. Similarly, the potassium current in human atrium shows kinetically distinguishable rapid and slow components, which might be of principal importance in determining atrial repolarization and its regulation by the autonomic nervous system and antiarrhythmic drugs (6). Therefore, the association of AF and short QT interval in our study might be partially explained by the alterations in IKs in both atrial and ventricular myocytes. Further studies are needed to better define the underlying pathophysiology and to investigate whether atrial and ventricular arrhythmias are generated by similar electrophysiological mechanisms.
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References
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1. Hong K, Bjerregaard P, Gussak I, Brugada R. Short QT syndrome and atrial fibrillation caused by mutation in KCNH2 J Cardiovasc Electrophysiol 2005;16:394-396.[Web of Science][Medline]2. Hong K, Piper DR, Diaz-Valdecantos A, et al. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero Cardiovasc Res 2005;68:433-440.[Abstract/Free Full Text] 3. Schimpf R, Wolpert C, Gaita F, Giustetto C, Borggrefe M. Short QT syndrome Cardiovasc Res 2005;67:357-366.[Abstract/Free Full Text] 4. Levy S. Epidemiology and classification of atrial fibrillation J Cardiovasc Electrophysiol 1998;9(Suppl 8):S78-S82.[Web of Science][Medline] 5. Jost N, Virag L, Bitay M, et al. Restricting excessive cardiac action potential and QT prolongationa vital role for IKs in human ventricular muscle. Circulation 2005;112:1392-1399.[Abstract/Free Full Text] 6. Wang Z, Fermini B, Nattel S. Rapid and slow components of delayed rectifier current in human atrial myocytes Cardiovasc Res 1994;28:1540-1546.[Web of Science][Medline]
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References