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European Journal of Echocardiography Advance Access originally published online on July 8, 2008
European Journal of Echocardiography 2009 10(1):139-143; doi:10.1093/ejechocard/jen199
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.

Echocardiographic evaluation of patients with undocumented arrhythmias occurring in adults late after repair of tetralogy of Fallot

S. Rosianu, D. Paprika, I. Osztheimer, A. Temesvari and T. Szili-Torok*

Gottsegen Gyorgy, Hungarian Institute of Cardiology, Haller u. 29, H-1096 Budapest, Hungary

Received 29 January 2008; accepted after revision 22 June 2008; online publish-ahead-of-print 8 July 2008.

* Corresponding author. Tel: +36 30 2 187637; fax: +36 1 2151220. E-mail address: szili.torok{at}kardio.hu or t.szilitorok{at}erasmusmc.nl


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Aims: Arrhythmias occurring late after repair of tetralogy of Fallot (ToF) are common. Due to the risk of sudden cardiac death, attention is focused towards ventricular tachycardias (VT). The aims of this study were to determine the clinical profile of patients with known benign and malignant arrhythmias and to assess patients with palpitations without documented arrhythmias.

Methods and results: Fifty-two patients with prior ToF repair were included in this study (mean follow-up: 18 ± 7.3 years). Echocardiographic measurements such as left ventricular ejection fraction, left and right atrial (LA and RA) diameters, left and right ventricular diameters (LVEDD and RVEDD), pulmonary and tricuspid regurgitation (TI and PI) and electrocardiographic parameters such as QRS duration, P-wave duration, P-wave dispersion were obtained and compared in patients with and without a history of palpitations. The same comparisons were performed between patients with documented supraventricular tachycardias (SVT) and VT. Twenty-seven of 52 patients had a clinical history of palpitations. The remaining 25 patients served as controls. Eleven patients had documented SVT and 6 patients had documented VT. In patients with documented SVT, the RA size and the QRS durations were significantly higher than in the controls (RA: 55.3 ± 5.6 vs. 47.4 ± 4.8 mm, P = 0.03, QRS: 160.0 ± 25.9 vs. 131.8 ± 26.1 ms, P = 0.01). In patients with VT, the LVEDD, LA, and QRS durations showed significantly higher values compared with the control patients (LVEDD: 53.5 ± 4.7 vs. 45.6 ± 6.8 mm; LA: 56.0 ± 3.4 vs. 48.5 ± 4.8 mm, P = 0.01; QRS: 169.5 ± 29.7 ms vs. 131.8 ± 26.1 ms; P = 0.001). The only significant differences between patients with and without palpitations were the RA size (58.2 ± 3.9 vs. 50.5 ± 5.2 mm, P = 0.02) and the P-wave dispersion (26.8 ± 15.2 vs. 16.6 ± 4.3 ms, P = 0.04).

Conclusion: Our present data suggest that undocumented arrhythmias are most likely SVTs and are associated with increased RA size.

Keywords: Tetralogy of Fallot; Arrhythmias; Echocardiography


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The overall incidence of tetralogy of Fallot (ToF) accounts for ~10% of all forms of congenital heart disease (CHD) and it is the most common cardiac malformation responsible for cyanosis after 1 year of age.1 Early definitive repair of ToF is now advocated with a survival rate of almost 90% at 30 years.2–5 Indeed, improvement in surgical techniques has created a new population of young adults with heart diseases. This patient population might develop right ventricular dysfunction and/or arrhythmias.6–9 Sudden cardiac death (SCD) is the most devastating late complication of ToF.2,6,7,10,11 The main cause of SCD (35–45%) is the development of malignant ventricular tachyarrhythmias.2,10 On the other hand, atrial incisions and secondary atrial scars create pathological substrate for atrial re-entrant tachyarrhythmias.12 Furthermore, atrial tachyarrhythmias have been postulated as a possible cause of SCD as these relatively young and fragile patients have the ability for one-to-one atrioventricular conduction. This overlap between sustained atrial and ventricular arrhythmias, particularly with underlying haemodynamic substrate, raises the issue of better identification of these rhythm disturbances and most importantly improved identification of patients who are at higher risk for developing SCD. Our primary aim was to determine the clinical profile of patients with known benign and malignant arrhythmias and to assess patients with palpitations without documented arrhythmias. Although multiple studies evaluated patients with documented ventricular and supraventricular tachycardias (SVT), this is the first report focusing on a group of patients with palpitation symptoms without documented arrhythmias. We hypothesized that this approach can clarify whether these symptomatic arrhythmias are benign or malignant.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Patient population
In total, 52 patients (14 females and 38 males) with prior ToF operated with total correction, late after surgery, were included in this study using an ongoing CHD registry. Patients who had all relevant ECG and echocardiographic data (see below) available for this retrospective analysis were included. The mean age was 41.0 ± 10.1 years with a mean follow-up period of 18 ± 7.3 years after surgery. The patients were divided into subgroups and were analysed according to the presence of history of palpitations, documented SVT, and documented VT. Patients without arrhythmia complaints (no history of palpitations and no documentation of any arrhythmias) were considered control group. Palpitation was defined as a main symptom presented by the patient at two follow-up visits.

Data collection
Non-invasive measurements were scheduled regularly during each follow-up. Only patients with a regular follow-up visits and with a set of non-invasive screening tests including standard 12-lead ECG, Holter ECG, and transthoracic echocardiography measurements were included in this study.

ECG measurements
The following electrocardiographic parameters were collected: QRS duration, P-wave duration, and P-wave dispersion.

Echocardiographic measurements
From echocardiographic measurements LV ejection fraction, left and right atrial (LA and RA) diameters, left and right ventricular end-diastolic diameters (LVEDD and RVEDD), and pulmonary and tricuspid regurgitation (PI and TI) were collected. All measurements were performed in accordance with the recommendations of the American Society of Echocardiography.13 Echocardiography was performed using an Acuson Sequoia (Acuson, Mountain View, CA, USA), or a Hewlett Packard Sonos 5500 system (Agilent, Andover, MA, USA) with images recorded on videotape. Echocardiographic examinations were done with the participants in supine position with a pillow under the right shoulder. The heart was imaged with 2D echocardiography in the parasternal long-axis view, parasternal short-axis view, apical view, subxiphoid views, and suprasternal notch image. M-mode echocardiography, 2D, and 2D directed pulsed-wave Doppler recordings were obtained by standard methods as the core measurements in the institutionally approved standard follow-up protocol.13,14

Data analysis
The above-mentioned parameters were compared between patients with and without the history of palpitations and between patients with documented SVT or VT (control group).

Prospective arm
Patients with palpitations, but without documented arrhythmias, were further evaluated by means of 24 h Holter monitoring. They were scheduled for a monthly Holter ECG monitoring for an extended 6-month follow-up period.

Statistical analysis
Values were expressed as mean ± SD. Independent samples t-test for parametric and Kologmorov–Smirnov test for non-parametric data were performed to compare echocardiographic and electrocardiographic data. A P-value <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Patient population
Among the 52 patients, 27 patients had the history of palpitations, 11 had documented SVT (40.74%), 6 had documented VT (22.22%), and 10 had palpitations without documentation. The remaining 25 patients were free of arrhythmias and served as controls. In patients with documented SVT, the RA size and the QRS duration were significantly higher than in the control group (Table 1). In patients with VT, the LVEDD, LA size, QRS duration, and P-wave duration showed significantly higher values compared with the control group (Table 1). All six patients with documented VT had electrophysiologic evaluation. Two of these patients had easily inducible monomorphic VT. In another two patients, VT and ventricular fibrillation was also induced. The remaining two patients were non-inducible. In all VT patients, an implantable cardioverter defibrillator (ICD) was implanted. In one patient, successful radiofrequency catheter ablation was performed 2 years after the ICD implantation because of frequent monomorphic VTs. The only significant differences between patients with and without history of palpitations were the RA size and the P-wave dispersion (Table 1).


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  		Table 1 Comparison of electrocardiographic and echocardiographic data between patients with documented arrhythmias and palpitations

 
Extended Holter monitoring in patients with palpitations
In patients with the history of palpitations, Holter monitoring revealed short runs of monomorphic VT (longest duration 12 bpm) in one patient. In two patients, short runs of atrial tachycardias were present with a maximum duration of 1.5 h. One patient was in incessant atrial flutter at the time of the monitoring. He was then admitted and treated with radiofrequency catheter ablation after electrophysiology study confirmed the presence of cavo-tricuspid isthmus-dependent atrial flutter. Three patients had short runs of atrial fibrillation. No sustained malignant ventricular arrhythmias were observed in this group.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
The major finding of this study is that a high percent (>50%) of the patients late after total repair of ToF have palpitations. The majority of documented arrhythmias are SVTs and less VTs are documented. Our data suggest that undocumented arrhythmias are most likely SVTs based on the extended follow-up of the patients. Right atrial diameter is the most important prognostic factor for the development of SVTs. Other abnormalities detected by non-invasive test are not different between patients with arrhythmias on the ventricular and supraventricular level.

The significance of arrhythmias in ToF
Tetralogy of Fallot is the most common cyanotic CHD with a good outcome after total surgical correction.2 Today, in centres with a good experience, the perioperative mortality is low, <1%, and a survival rate 30 years after the surgery is very close to 90% with a good quality of live. However, late sudden death remains a significant clinical problem, mainly related to episodes of VT.2,15 Several pathophysiological mechanisms responsible for cardiac arrhythmias can be presented in patients after repair of ToF. Electrical instability results mainly from anatomical modifications following surgery or mechanical events such as ventricular dilatation and stretching.2,16 Echocardiographic examination provides relevant information that can also be used in risk stratification. The presence of structural abnormalities of the right ventricle, such as outflow tract aneurysm, tricuspid, and pulmonary regurgitation, was found more frequently in patients with sustained VT.17 The analysis of right ventricular volume represents a prognostic factor for episodes of sustained VT or ventricular fibrillation.18 Moreover, higher ratio of right to left ventricular systolic pressure after surgery was shown as an independent predictor of long-term survival.19

Patient selection: patients with palpitations—clinical significance
The most unique feature of this study is that we focused on a difficult subgroup of patients suffering from arrhythmia-like symptoms; however, they had no ECG or Holter ECG monitoring documentation about any arrhythmias. This is an important issue since this is the disease which increases the risk for SVT as well as for VT. In this respect, these patients are quite different from most of the patients with repaired congenital defects where the aetiology highly determines the type of arrhythmia during the follow-up.20–22 Even more difficult to characterize patients with palpitations if we take into consideration some early studies showing fairly high level of palpitation symptoms even in a healthy young population.22,23 Obviously, this uncertainty is an important issue not only for the correct scientific interpretation, but also for the appropriate management of this fragile patient population. Since we appreciated this problem, we designed a prospective arm of this investigation, which actually consisted of a rather vigorous monitoring phase. This, together with the non-invasive tests, confirmed our hypothesis, that the arrhythmias behind the palpitation symptoms are most likely supraventricular ones.

Novel concept: profiling patients with non-invasive test
This study was initiated by the known fact that many of the patients late after complete repair of CHD experience palpitations. Moreover, palpitation as a symptom associated with atrial flutter can significantly diminish the so-called ability index,24,25 which represents their ability to conduct normal life. Therefore, it seems to be crucial to identify patients with palpitations and determine the underlying pathology, especially the one having high risk for malignant arrhythmias. Our study showed a good correlation between higher RA size and presence of palpitations or SVT, whereas LVEDD and LA size were significantly higher in patients with VT. This finding is consistent with data showing fibro-fatty substitution around infundibular resection, intraventricular septal scar, and patchy myocardial fibrosis, since it can serve as a pathological substrate of abnormal depolarization and repolarization. This may result in the development of re-entrant ventricular arrhythmias.2,26 The incidence of atrial arrhythmias after ToF repair is relatively high, ~30%, including atrial fibrillation, atrial flutter, and focal or re-entrant atrial tachycardia.27 Patients suffering from such arrhythmias are characterized by the presence of increased right atrial volumes, pulmonary regurgitation, and older age at surgical repair.2 The anatomical substrates for atrial tachycardias are more frequently represented by re-entrant circuits that are often multiple and unstable, and in some patients the presence of macrore-entrant circuits are localized around the atriotomy scar. Roos-Hesselink et al.27 described a series of 53 patients, mean age 23.2 years, who had undergone surgical repair of ToF and were followed up for a mean interval of 17.5 years. Nineteen patients (36%) had sinus node dysfunction. Atrial fibrillation or atrial flutter developed 12 patients, while 6 had other types of SVT. In all, 34% of the patients suffered from SVT. In comparison, non-sustained VT occurred in 10 patients (19%). These data are similar to the findings of our study.

Prognostic value of non-invasive measurements
Intraventricular conduction is typically prolonged in patients after ToF repair, and it is characterized by the presence of a right bundle branch block. QRS duration was the first non-invasive parameter showing a significant correlation with the occurrence of malignant ventricular arrhythmias and SCD. Particularly, it is generally accepted that the patients with a QRS longer than 180 ms are at higher risk, associated with VT, and sudden death several years after surgical repair.6,18 On the other hand, Daliento28 suggested a low significance of such a wide QRS in the presence of complete right bundle branch block. In fact, it is almost impossible to distinguish the increased duration of the QRS complex secondary to surgical damage of the conduction tissue from that due to right ventricle dilation. Rather than the absolute value of the QRS duration, simultaneously occurring modifications in the duration of the QRS complex and in the end-diastolic volume of the right ventricle during post-surgical follow-up assume a more predictive significance. Our patients with documented VT had these two parameters significantly higher compared with control group. In this regard, our data are confirmatory. The fact that RA size was associated with arrhythmias is more interesting. First, it suggests that in contrast to the normal population corrected Fallot patients more likely develop right-sided arrhythmias and these rhythms disturbances can be predicted by the increased RA size and QRS width.

Limitations of the study
This study is retrospective and indeed rather speculative. On the other hand, attempt was made to clarify the issue raised by the data of the retrospective analysis. This attempt (extended follow-up) suggests that these arrhythmias are benign. However, larger series of patients are needed to clearly prove this issue. Another limitation is that some non-invasive tests were underutilized in this patient group and, therefore, were not included into this analysis. For example, signal averaged ECG (SAECG) was not available for all of the study patients. Although SAECG was reported to be a possibly useful tool for predicting ventricular arrhythmias, its value is still controversial, and its role in SVT prediction does not seem to be realistic.29 Moreover, the mean age of the patients was 41 ± 10 years, with a follow-up of 18 ± 7 years. This means that most patients are operated upon at adult age. Knowing the natural history of unoperated Fallot's itetrology, with only 5% surviving until adult age, the patient group is a highly selected one. This is explained by the fact that complex congenital surgery was started relatively late in the region where this study was conducted. On the other hand, this has some potential advantages from the scientific point of view as well. This is indeed the group with the most optimal anatomy and haemodynamics; however, they have been operated very late. A similar population will be very difficult to find; the results should be interpreted with caution.

In conclusion, our present data suggest that undocumented arrhythmias associated with increased RA size are most likely SVTs.


   Acknowledgement
 
The authors express their personal appreciation of the valuable assistance given them by Richard Alloway (Erasmus MC, Thoraxcentre) in reading and correcting our paper.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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This Article
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