Article

PDF
Access to the PDF text
Advertising


Free Article !

Archives of cardiovascular diseases
Volume 106, n° 1
pages 12-18 (janvier 2013)
Doi : 10.1016/j.acvd.2012.10.001
Received : 28 July 2012 ;  accepted : 2 October 2012
Slower heart rate and altered rate dependence of ventricular repolarization in patients with lone atrial fibrillation
Fréquence cardiaque plus lente et altération de la fréquence-dépendance de la repolarisation ventriculaire chez les sujets avec fibrillation atriale idiopathique
 

Philippe Maury a, , Guillaume Caudron a, Frédéric Bouisset a, Joëlle Fourcade a, Alexandre Duparc a, Pierre Mondoly a, Anne Rollin a, Sébastien Hascoët a, Nicolas Detis a, Christelle Cardin a, Marc Delay a, Olivier Lairez a, Jérome Roncalli a, Michel Galinier a, Didier Carrié a, Meyer Elbaz a, Jean Ferrières a, Jean-Marie Fauvel a, Marc Zimmermann b
a Federation of Cardiology, University Hospital Rangueil, 1, avenue Jean-Poulhès, 31059 Toulouse cedex 09, France 
b Clinique de la Tour, Meyrin, Switzerland 

Corresponding author. Fax: +33 5 61 32 22 46.
Summary
Background

Electrophysiological alterations in atrial fibrillation (AF) may be genetically based and may lead to changes in ventricular repolarization. Short QT syndrome is a rare channelopathy with abbreviated ventricular repolarization and a propensity for AF.

Aims

To determine if minor unrecognized forms of short QT syndrome can explain some cases of lone AF.

Methods

We prospectively compared QT intervals in 66 patients with idiopathic lone AF and 132 age- and sex-matched controls. QT intervals were measured during sinus rhythm in each of the 12 surface electrocardiogram leads and corrected using Bazett’s formula (QTc). QT intervals were also corrected using other formulae. Uncorrected QT and heart rate regression lines were compared between AF patients and controls.

Results

AF patients presented with a slower resting heart rate (64±10 beats per minute [bpm] vs 69±9 bpm; P =0.0006). QTc intervals were shorter in AF patients in 11/12 electrocardiogram leads (significant in 7/12, borderline in 2/12; mean QTc 381±21ms vs 388±22ms; P =0.02). QTc intervals were also shorter in AF patients, significantly or not, using other correction formulae. For similar heart rates, uncorrected QT intervals were shorter in patients when heart rates were greater than 70 bpm and longer when heart rates were less than 60 bpm. AF patients displayed steeper QT/heart rate regression line slopes than controls (P =0.009).

Conclusion

Heart rate is significantly slower and the rate dependence of ventricular repolarization is significantly altered in patients with lone AF compared with controls. Further study is warranted to determine if AF induces subsequent ventricular repolarization changes or if these modifications are caused by an underlying primary electrical disease.

The full text of this article is available in PDF format.
Résumé
Hypothèse

Les modifications électrophysiologiques dans la fibrillation atriale sont parfois d’origine génétique et pourraient donc conduire à des modifications de la repolarisation ventriculaire. Le syndrome du QT court est une canalopathie rare caractérisée par une repolarisation ventriculaire raccourcie et une propension pour les arythmies ventriculaires et la fibrillation atriale. Les deux pourraient être liés.

Objectifs

Rechercher une anomalie de la repolarisation chez les patients avec fibrillation atriale idiopathique à la recherche d’un syndrome du QT court fruste sous-jacent.

Méthodes

Les intervalles QT de 66 patients avec fibrillation atriale idiopathique ont été comparés de manière prospective à ceux de 132 témoins appariés en âge et en sexe. Les intervalles QT étaient mesurés en rythme sinusal dans chacune des 12 dérivations de surface et corrigés avec la formule de Bazett (QTc). Les intervalles QT étaient aussi corrigés selon d’autres formules et les pentes des droites de régression entre QT et fréquence étaient comparées entre patients et témoins.

Résultats

Les patients avec fibrillation atriale avaient une fréquence cardiaque plus basse (64±10 bpm vs 69±9 bpm ; p =0,0006). Les QTc étaient plus courts chez les patients avec fibrillation atriale dans 11/12 dérivations (significatif dans 7/12, limite dans 2/12 ; QTc moyen 381±21ms vs 388±22ms ; p =0,02). Les QTc étaient aussi plus courts chez les patients avec fibrillation atriale, de manière significative ou non, quand d’autres formules de correction étaient utilisées. À fréquence comparable, les QT non corrigés étaient plus courts chez les patients avec fibrillation atriale pour les fréquences supérieures à 70 bpm et plus longs pour les fréquences inférieures à 60 bpm. La pente de la droite de regression QT–fréquence était plus grande chez les patients que chez les témoins (p =0,009).

Conclusion

La fréquence cardiaque est significativement plus lente et la fréquence-dépendence de la repolarisation ventriculaire est significativement altérée chez les patients avec fibrillation atriale idiopathique comparées aux témoins. Il reste à déterminer si la fibrillation atriale induit secondairement des changements dans la repolarisation ventriculaire ou si ces modifications sont le témoin d’une atteinte primitive électrique sous-jacente.

The full text of this article is available in PDF format.

Keywords : Lone atrial fibrillation, Short QT syndrome, QT interval

Mots clés : Fibrillation atriale idiopathique, Syndrome du QT court, Intervalle QT

Abbreviations : AF, bpm, ECG, ICC, QTc, SQTS


Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia, reaching a prevalence of 1% in the general population [1]. In 2 to 30% of cases, AF occurs without any cardiac alteration or facilitating extracardiac abnormality and is called lone AF [2, 3, 4, 5]. Most of the time, AF is a consequence of a multifactorial process involving various acquired structural alterations, while primitive electrical disease can be suspected in lone AF, where no structural heart disease is present. A genetic background is suspected in familial cases, which account for 15% of lone AF cases [6]. Several mutations or variants have been discovered during the past decade [7, 8], mainly on genes encoding various membrane ion channels involved in atrial but also ventricular action potentials.

Short QT syndrome (SQTS) is a recently recognized channelopathy associating abbreviated atrial and ventricular repolarizations and a propensity for atrial and ventricular arrhythmias [9, 10, 11]. In particular, AF is frequently observed in SQTS patients [10]. To date, discovered mutations in SQTS mainly involve potassium channels, leading to a gain of function [12, 13, 14, 15], similar to that observed in some familial cases of AF [7, 8], although QT intervals are apparently normal in these patients.

The aim of this study was to compare QT interval durations in patients with lone AF and matched controls, based on the hypothesis that minor unrecognized forms of SQTS may explain some cases of lone AF.

Methods

We performed a case-control study at two centres, comparing QT interval durations during sinus rhythm in patients with lone AF and matched controls.

Patients with lone AF were prospectively recruited over the past 2 years at our two institutions (University Hospital Rangueil, Toulouse, France and Hôpital de la Tour, Meyrin, Switzerland). To be included, patients had to be aged less than 75 years and present with a history of documented paroxysmal AF without any detectable underlying heart disease and without diabetes, hypertension or any precipitating condition, such as a history of renal, hormonal or pulmonary disease [3, 5]. Transthoracic echocardiography was available in each case and had to be compatible with the diagnosis of lone AF [2] (no ventricular hypertrophy or dilatation, normal ventricular systolic function, no valvular or pericardial abnormality, no increased left ventricular diastolic filling pressure). An isolated left atrial dilatation was not an exclusion criterion [16]. Patients with a recent episode of AF occurring during the previous 48h – either documented or suspected by suggestive symptoms – were excluded, as well as patients under antiarrhythmic drugs, digoxin, beta-blockers, calcium channel blockers or, more generally, under any cardioactive drug or medication with some electrophysiological action or known to alter cardiac repolarization or to perturb ionic homeostasis. Patients aged<16 years and those with a familial history of AF were excluded, as were professional sportsmen or patients practising intensive physical activity (>7h a week).

Once this population was selected, we prospectively recruited age- and sex-matched controls over the following months. Controls were matched with a 2:1 ratio according to sex and age (patients and controls were grouped in sections of 10 years of age). Control patients were recruited during preoperative consultations before non-cardiac surgery or by means of consultations for non-organic cardiovascular symptoms or from the medical or paramedical staff. These recruits were men or women without any personal or familial cardiovascular history, with unremarkable physical examination and without any cardioactive medication. Exclusion criteria for patients with AF also applied for controls. Patients or controls with a resting sinus node heart rate that was too high (>85 beats per minute [bpm]) or too low (<45 bpm) were excluded because of the inaccuracy of most QT correction formulae at these rates [17].

One standard 12-lead surface electrocardiogram (ECG) was used for analysis for each patient or control. The ECG was recorded at rest during the same standard clinical conditions in patients and controls (i.e. common conditions for ECG recording as performed during usual medical consultation, at a paper speed of 25mm/s with a standard ECG recorder [1kHz sampling rate, 0.1–250Hz filters]). For each tracing, sinus node heart rate, PR interval and QRS duration were measured in lead II. The QT interval duration was then measured in each of the 12 ECG leads, from the QRS onset to the end of the T wave, as defined by the intersection of the tangent of the steepest slope of the last part of the T wave and the isoelectric line, according to the technique described by Surawicz [18]. QT was not measured in case of flat T wave (less than 0.1mV) or when the end of the T wave was difficult to determine. Measurements were averaged over five successive beats in case of sinus node arrhythmia (defined by instantaneous heart rate variations10% of the mean heart rate). ECG analysis was independently performed by two cardiologists blinded to the groups in a subset of 20 cases, for evaluation of interobserver variability.

To allow determination of corrected QT (QTc), QT durations were then corrected according to Bazett’s formula (QTc=QT/√RR) [19]. For each ECG, the mean QTc was determined over the 12 leads. QT durations were additionally corrected according to the formulae by Hodges (QTc=QT+1.75 [heart rate60]) [20], Fridericia (QTc=QT/√3RR) [21], Rautaharju (QTc=QT+[410656/(1+heart rate/100)]) [22] and Sagie Framingham (QTc=QT+154 [1RR]) [23].

Statistical analysis

Statistical analysis was performed using StatView 5 (version 4.57; Abacus Concepts, Inc., Berkeley, CA, USA; 1992–1996) and StatA (version 11.1; StataCorp LP, College Station, TX, USA). Numerical values are presented as means±standard deviations (ranges) and categorical data as proportions. Normal distribution was expected, given the significant number of patients in each group, so unpaired t tests were used to compare numerical data between groups. Proportions were compared using the Chi2 test. The intraclass correlation coefficient (ICC) was calculated to determine the reliability of QT measurements; interobserver variability was assessed by comparing the results from observers 1 and 2. Furthermore, due to the imperfection of correction formulae, especially in case of different heart rates between groups, uncorrected QT interval durations were compared in subgroups sharing a similar heart rate. In addition, significant interaction between uncorrected QT/heart rate regression lines for patients and controls was determined. A P value<0.05 was considered significant for each analysis.

Results

Sixty-six successive patients with paroxysmal lone AF were prospectively included and compared with 132 matched controls. Two controls – but no patients – were excluded before enrolment because of intensive sporting activity. There were no differences in sex (72% men) or age (mean, 49±13 years) between groups due to the matching. All patients or controls were Caucasian. ECGs were always recorded during the daytime (12:00±3h without difference between groups). Mean heart rate was 67±10 bpm (45–85 bpm). Mean PR interval was 156±26ms (100–220ms) and mean QRS duration was 82±4ms (80–100ms).

Heart rate was significantly slower in patients with lone AF than in controls (64±10 bpm vs 69±9 bpm; P =0.0006). Prevalence of sinus node arrhythmia was similar between groups (17% in both groups; P =0,8). The PR interval was longer in patients with lone AF (160±29ms) than in controls (154±24ms), although the difference was not significant (P =0.15). No complete bundle branch block or pre-excitation was observed in any ECG. There was no difference in QRS width between groups (82±4ms for both groups).

Repolarization was found to be unremarkable on every ECG (positiveT wave in each lead except V1, V2, VR and sometimes III). There was good agreement between observers for the determination of QT intervals (ICC 0.83). Differences in QTc intervals are shown in Table 1. In each ECG lead (except V2), Bazett-corrected QT intervals were found to be shorter in patients with lone AF than in controls. Differences were significant for 7/12 ECG leads and borderline in two other leads (Figure 1): in V5, for example, QTc was 384±22ms vs 393±24ms in controls (P =0.01). Mean QTc was 381±21ms in AF patients and 388±22ms in controls (P =0.02) (a difference of 7ms).



Figure 1


Figure 1. 

Graphic representation of the differences in corrected QT (QTc) in each electrocardiogram lead and in mean QTc between atrial fibrillation patients (grey) and controls (white). * indicates a significant difference (P <0.05); b indicates a borderline difference (P <0.1).

Zoom

These results were also globally observed when QT corrections were made according to the Hodges formula (significantly shorter QTc in the lone AF group in every lead except V1 and V2), or the Sagie-Framingham and Rautaharju formulae (shorter QTc in most leads in AF patients with significant differences in VL, V1 and V6 and borderline in lead III). QTc intervals were also shorter in patients with lone AF but without any significant difference when the Fridericia formula was used.

A short QT (defined by mean QTc<340ms and/or mean QT<320ms) was found in two AF patients and none of the controls. No QTc cutoff value could be found due to the overlap between groups.

Significant differences in QTc between AF patients and controls were also found in the subgroup of men but the differences were no more significant in the subgroup of women. Men with lone AF had a significantly lower heart rate than controls (63±11 bpm vs 69±10 bpm; P =0.0005) while the difference was not significant for women (66±9 bpm vs 68±8 bpm). Similar differences in QTc and heart rate were also present in each age subgroup, but were often borderline or not significant due to the low number of patients and controls in each subgroup.

Due to the imperfection of correction formulae, especially in case of different heart rates between groups, as documented here, we performed additional analyses using uncorrected QT interval durations in subgroups of patients sharing similar heart rates (see statistical analysis section). In the subgroup of patients/controls with a resting heart rate greater than 75 bpm, the QT intervals in most leads as well as mean QT were significantly shorter in AF patients than in controls. Similar but non-significant differences were observed in most ECG leads for patients and controls with heart rates between 70 and 75 bpm. QT intervals were often quite similar in patients and controls in most leads between 60 and 70 bpm, while the reverse situation was observed in most leads between 50 and 60 bpm (longer QT intervals in AF patients), although the difference was not significant.

Uncorrected QT/heart rate regression lines for patients and controls displayed significant interaction (P =0.01) (Figure 2): the slope of the regression line in AF patients was significantly steeper than that in controls.



Figure 2


Figure 2. 

Uncorrected QT heart rate regression lines for patients and controls, displaying significant interaction. The slope of the regression line for atrial fibrillation (AF) patients is significantly steeper than that for controls (P =0.01). bpm: beats per minute.

Zoom

Discussion

In this study, we compared resting heart rate and QT interval duration in patients with lone AF without any condition or therapy leading to alteration in ventricular repolarization and matched controls. We found that the resting heart rate was significantly slower and QTc intervals were significantly shorter in patients with paroxysmal lone AF compared with the control group. QTc interval durations were shorter in most leads in patients with lone AF, the differences being significant (Bazett, Hodges, Rautaharju and Framingham) or not (Fridericia) according to the formula used, with a difference of 7ms between the mean QTc intervals in each group using Bazett’s formula. Both findings were also observed in the subgroups of men or women and in each age-related subgroup, even if the differences were sometimes not significant because of the low number of cases in some subgroups. No cutoff value could be found due to the overlap in QTc durations between both groups and a short QT interval was diagnosed in two patients with lone AF but in none of the controls.

As heart rates were different between AF patients and controls, and because of the imperfection of most correction formulae, we performed additional analyses of uncorrected QT intervals in subgroups of patients and controls sharing similar heart rates: QT intervals were shorter in AF patients compared with controls when the heart rate was greater than 70 bpm and longer when the heart rate was less than 60 bpm. We also demonstrated that QT/heart rate regression lines had different slopes; patients with lone AF displayed steeper slopes than controls. Both these results mean that QT intervals were longer in AF patients than in controls when the heart rate was low and that the reverse was true for faster heart rates. Even if no firm conclusions about differences in corrected QT intervals could be drawn here because of the non-similar heart rates, it appears, however, that the rate dependence of ventricular repolarization is significantly different in patients with lone AF.

A previous study had already found shorter QTc intervals in patients with AF compared with matched controls [24] but the patients and controls were older, most presented with hypertension and some presented with diabetes; their results could not, therefore, be compared with ours, as hypertension, age and diabetes are known to modify repolarization, which means that such patients cannot be considered as having lone AF. Moreover, heart rate was faster in this study than in our population and did not differ between patients and controls.

The population in our study was quite representative of lone AF patients, with a male predominance, which is known to be present in lone AF [25, 26]. Due to the low number of female patients, some results were non-significant in this subgroup, although a trend for lower heart rate and shorter QTc was also present in women.

The relationships between AF and ventricular repolarization are poorly known. AF may induce subsequent ventricular repolarization changes but primary electrical disease may also facilitate the development of AF. The interpretation of these results remains difficult and beyond the scope of this study, although some hypotheses may be postulated.

The main hypothesis relates to the existence of underlying genetic mutations or variants leading to electrophysiological alterations in both atrial and ventricular myocardial cells. To date, discovered mutations in patients with lone AF involve different genes [7, 8] but frequently lead to gains of function of potassium channels. Some of these mutations are associated with a reduction in duration of atrial action potentials [27, 28]. Mutations with gain of function of potassium channels have also been described in patients with SQTS [12, 13, 14, 15] and the prevalence of AF in patients with SQTS is high (around 25%), occurring at every age, even during childhood [10]. In view of our results, it is tempting to postulate that patients with lone AF may be considered as presenting with minor subclinical forms of SQTS, at least in some cases. The different behaviour of ventricular repolarization according to the heart rate present in patients with lone AF in this study is, however, the reverse to what is observed in SQTS patients, where QT adaptation to heart rate is poor [29].

A decrease in the QT interval because of previous fast AF terminated in the last minutes before the ECG recording and due to restitution or QT hysteresis is less likely. The QT interval is known, rather, to increase immediately after spontaneous or electrical restoration of sinus rhythm, remaining 5–10ms longer than baseline over the following weeks to months [30], which rather reinforces our findings of shorter QT intervals in patients with paroxysmal AF.

The QT interval is modulated by parasympathetic agents [31]. A more marked basal vagal tone in patients with lone AF would therefore explain the lower heart rate, the higher risk of AF (i.e. vagally mediated AF), together with shorter QT intervals. However, PR intervals were not significantly longer in patients with AF, ECG recordings were always performed under the same conditions, there was no apparent difference in sporting activity between the populations due to age and sex matching and competitive or high-intensity sportsmen or women had been excluded.

The slower heart rate observed in patients with paroxysmal lone AF could also be explained on a different basis. Sinus node remodelling with transient or prolonged sinus node bradycardia is known to occur after AF episodes of various durations [32, 33, 34].

Limitations

Comparisons of corrected QT intervals were biased by the fact that most correction formulae are highly dependent on heart rate, which was different between patients and controls. Bazett’s formula is known to overcorrect QT duration for fast heart rates [17] and therefore may have led to artificially longer QTc intervals in controls, as the heart rate was faster in this group. However, even if they were different, the mean heart rates were close to 60 bpm in both groups, a rate at which correction formulae are more reliable. Furthermore, this difference was found again using most other correction formulae. For these reasons, we performed additional analyses on uncorrected QT intervals and demonstrated a significantly different rate dependence behaviour between patients and controls (see results section), validating the significant difference in the ventricular repolarization process in AF patients found in this study, even if no firm conclusions about QTc should be made.

Echocardiography was performed for the control group. It is, however, highly probable that left atrial size was larger in patients than in controls [16]. It is unclear if changes in left atrial size only, without underlying heart disease, would have an action on ventricular repolarization, but this deserves further study.

Genetic analysis was not performed. These results would be confirmed, therefore, if correlated to mutations in candidate genes.

Conclusion

Heart rate and rate dependence of ventricular repolarization are significantly altered in patients with lone AF. Underlying variants or mutations in various genes encoding for cardiac ionic currents leading to altered ventricular repolarization and slower sinus node heart rate may be suspected as an explanation for these results, although other alternative mechanisms cannot be ruled out. Further studies are mandatory for validating these findings and subsequent mechanistic hypotheses. If confirmed, the existence of a common genetic background may help in targeting adapted antiarrhythmic therapies in patients with lone AF.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

References

Feinberg W.M., Blackshear J.L., Laupacis A., and al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications Arch Intern Med 1995 ;  155 : 469-473 [cross-ref]
Chugh S.S., Blackshear J.L., Shen W.K., and al. Epidemiology and natural history of atrial fibrillation: clinical implications J Am Coll Cardiol 2001 ;  37 : 371-378 [cross-ref]
Kopecky S.L., Gersh B.J., McGoon M.D., and al. The natural history of lone atrial fibrillation. A population-based study over three decades N Engl J Med 1987 ;  317 : 669-674 [cross-ref]
Levy S. Epidemiology and classification of atrial fibrillation J Cardiovasc Electrophysiol 1998 ;  9 : S78-S82
Potpara T.S., Lip G.Y. Lone atrial fibrillation: what is known and what is to come Int J Clin Pract 2011 ;  65 : 446-457 [cross-ref]
Darbar D., Herron K.J., Ballew J.D., and al. Familial atrial fibrillation is a genetically heterogeneous disorder J Am Coll Cardiol 2003 ;  41 : 2185-2192 [cross-ref]
Mann S.A., Otway R., Guo G., and al. Epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk J Am Coll Cardiol 2012 ;  59 : 1017-1025 [cross-ref]
Roberts J.D., Gollob M.H. Impact of genetic discoveries on the classification of lone atrial fibrillation J Am Coll Cardiol 2010 ;  55 : 705-712 [cross-ref]
Gaita F., Giustetto C., Bianchi F., , and al. Short QT Syndrome: a familial cause of sudden death Circulation 2003 ;  108 : 965-970 [cross-ref]
Giustetto C., Di Monte F., Wolpert C., and al. Short QT syndrome: clinical findings and diagnostic-therapeutic implications Eur Heart J 2006 ;  27 : 2440-2447 [cross-ref]
Gussak I., Brugada P., Brugada J., and al. Idiopathic short QT interval: a new clinical syndrome? Cardiology 2000 ;  94 : 99-102 [cross-ref]
Bellocq C., van Ginneken A.C., Bezzina C.R., and al. Mutation in the KCNQ1 gene leading to the short QT-interval syndrome Circulation 2004 ;  109 : 2394-2397 [cross-ref]
Brugada R., Hong K., Dumaine R., and al. Sudden death associated with short-QT syndrome linked to mutations in HERG Circulation 2004 ;  109 : 30-35
Hong K., Piper D.R., Diaz-Valdecantos A., and al. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero Cardiovasc Res 2005 ;  68 : 433-440 [cross-ref]
Priori S.G., Pandit S.V., Rivolta I., and al. A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene Circ Res 2005 ;  96 : 800-807 [cross-ref]
Sitges M., Teijeira V.A., Scalise A., and al. Is there an anatomical substrate for idiopathic paroxysmal atrial fibrillation? A case-control echocardiographic study Europace 2007 ;  9 : 294-298 [cross-ref]
Karjalainen J., Viitasalo M., Manttari M., and al. Relation between QT intervals and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval values J Am Coll Cardiol 1994 ;  23 : 1547-1553 [cross-ref]
Moss A.J. Measurement of the QT interval and the risk associated with QTc interval prolongation: a review Am J Cardiol 1993 ;  72 : 23B-25B
Bazett H.C. An analysis of the time-relations of the electrocardiogram Heart 1920 ;  7 : 353-370
Hodges M. Rate correction of the QT interval Card Electrophysiol Rev 1997 ;  1 : 360-363 [cross-ref]
Fridericia L.S. Die Systolendauer in Elektrokardiogramm bei normalen Menschen und bei Herzkranken Acta Med Scand 1920 ;  53 : 469-486
Rautaharju P.M., Warren J.W., Calhoun H.P. Estimation of QT prolongation. A persistent, avoidable error in computer electrocardiography J Electrocardiol 1990 ;  23 : 111-117 [cross-ref]
Sagie A., Larson M.G., Goldberg R.J., and al. An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study) Am J Cardiol 1992 ;  70 : 797-801 [cross-ref]
Poglajen G., Fister M., Radovancevic B., and al. Short QT interval and atrial fibrillation in patients without structural heart disease J Am Coll Cardiol 2006 ;  47 : 1905-1907 [cross-ref]
Brand F.N., Abbott R.D., Kannel W.B., and al. Characteristics and prognosis of lone atrial fibrillation. 30-year follow-up in the Framingham Study JAMA 1985 ;  254 : 3449-3453 [cross-ref]
Chen L.Y., Herron K.J., Tai B.C., and al. Lone atrial fibrillation: influence of familial disease on gender predilection J Cardiovasc Electrophysiol 2008 ;  19 : 802-806 [cross-ref]
Chen Y.H., Xu S.J., Bendahhou S., and al. KCNQ1 gain-of-function mutation in familial atrial fibrillation Science 2003 ;  299 : 251-254 [cross-ref]
Yang Y., Xia M., Jin Q., and al. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation Am J Hum Genet 2004 ;  75 : 899-905 [cross-ref]
Wolpert C., Schimpf R., Giustetto C., and al. Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG J Cardiovasc Electrophysiol 2005 ;  16 : 54-58 [cross-ref]
Tan H.L., Smits J.P., Loef A., and al. Electrocardiographic evidence of ventricular repolarization remodelling during atrial fibrillation Europace 2008 ;  10 : 99-104
Diedrich A., Jordan J., Shannon J.R., and al. Modulation of QT interval during autonomic nervous system blockade in humans Circulation 2002 ;  106 : 2238-2243 [cross-ref]
Hocini M., Sanders P., Deisenhofer I., and al. Reverse remodeling of sinus node function after catheter ablation of atrial fibrillation in patients with prolonged sinus pauses Circulation 2003 ;  108 : 1172-1175 [cross-ref]
Manios E.G., Kanoupakis E.M., Mavrakis H.E., and al. Sinus pacemaker function after cardioversion of chronic atrial fibrillation: is sinus node remodeling related with recurrence? J Cardiovasc Electrophysiol 2001 ;  12 : 800-806
Zupan I., Kozelj M., Butinar J., and al. Impaired sinus node function and global atrial conduction time after high rate atrial pacing in dogs Cell Mol Biol Lett 2002 ;  7 : 383-384



© 2012  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Close
Article Outline