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European Journal of Heart Failure 2005 7(2):277-282; doi:10.1016/j.ejheart.2004.07.009
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© 2005 European Society of Cardiology

QT dispersion in nonischemic dilated cardiomyopathy. A long-term evaluation

Laurent Fauchier*, Julien Douglas, Dominique Babuty, Pierre Cosnay and Jean Paul Fauchier

Service de Cardiologie B et Laboratoire d'électrophysiologie cardiaque, Centre Hospitalier Universitaire Trousseau Tours, France

* Corresponding author. Cardiologie B, Centre Hospitalier Universitaire Trousseau, 37044 Tours, Cedex, France. Tel.: +33 2 47 47 46 50; fax: +33 2 47 47 59 19. E-mail address: lfau{at}med.univ-tours.fr


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Background: In idiopathic dilated cardiomyopathy (IDC), the predictive value of QT dispersion is still under debate.

Aims: This study assessed the role of QT dispersion for the long-term risk of cardiac death and of major arrhythmic events in IDC.

Methods and results: In 162 patients with IDC (age 52±12 years), the QT interval on a 12-lead ECG was measured manually. QT dispersion was evaluated with QT range and QT standard deviation, for both QT and QTc (Bazett formula). With a follow-up of 53±41 months, QT dispersion was not a predictor of cardiac death in univariate or in multivariate analysis, and was of similar value for patients with or without bundle branch block. Using multivariate analysis, increased pulmonary capillary wedge pressure (p=0.003), decreased heart rate variability (Standard deviation of all NN intervals, p=0.01) and non-sustained ventricular tachycardia (NSVT) (p=0.03) were predictors of cardiac death. Sudden death and/or major arrhythmic events were independently predicted by NSVT (p=0.005), decreased heart rate variability (p=0.01) and late ventricular potentials on signal averaged ECG (p=0.02).

Conclusion: This study confirms the poor prognostic value of QT dispersion in patients with IDC. Other methods to assess repolarization abnormalities need to be evaluated in such patients.

Key Words: QT dispersion • Idiopathic dilated cardiomyopathy • Prognosis

Received February 9, 2004; Revised June 21, 2004; Accepted July 15, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Idiopathic dilated cardiomyopathy (IDC) is associated with a high incidence of ventricular arrhythmias and cardiac death. Identification of patients at high risk for cardiac sudden or non-sudden death remains a challenge since protective techniques such as implantable cardioverter defibrillator (ICD) are available [1,2]. The negative results of the AMIOVIRT and CAT pilot studies suggest that the selection of patients for prophylactic therapy with implantable cardiac defibrillator, using non-sustained ventricular tachycardia (VT) and decreased left ventricular ejection fraction, was not sufficient [3,4]. In IDC, the predictive value of QT dispersion was recently debated [5]. We investigated the prognostic value of QT dispersion for cardiac death and for major arrhythmic events in patients with IDC with a long-term follow-up of more than 4 years on average.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusion
 References
 
2.1. Patients
One hundred and ninety four patients with IDC as defined by the World Health Organization were consecutively and continuously studied between February 1987 and October 2001. Diagnosis was established by normal coronary angiography in all patients, echocardiography and radionuclide-gated blood pool ventriculography. Patients with chronic renal failure, diabetes mellitus, atrial arrhythmias, sinus node dysfunction, atrioventricular block or with a permanent pace-maker were excluded for analysis of QT interval dispersion and heart rate variability. As the aim of the study was to identify patients with IDC who could benefit from prophylactic therapy with ICD, patients with a history of documented sustained ventricular tachyarrhythmia were also excluded. QT interval dispersion was analysed in 169 patients. At the time of the evaluation, patients were treated with angiotensin-converting enzyme (ACE) inhibitors (53%), diuretics (49%), digoxin (49%) and/or nitrates (15%). Because they were seen at the time of the diagnosis of IDC, 32% of the patients were not receiving medical treatment for heart failure. None of the patients was receiving Beta blockers or antiarrhythmic agents. The patients were treated during follow-up over the long-term with ACE inhibition (86%), and/or diuretics (60%) or digoxin (58%) where necessary. Beta-blockers were prescribed (since 1997) in 25% of the patients and amiodarone in 22%.

2.2. Electrocardiography and investigations at baseline
The QRS duration was measured on a surface 12-lead electrocardiogram with a simultaneous recording of 6 leads at 25 mm/s. Mean QRS duration was 113±33 ms in the whole population and left bundle branch block (LBBB) was present in 28% of the patients. The QT interval on the 12-lead ECG was measured manually by a single observer, without any computer assistance or electronic calipers. As recommended, in some difficult cases (relatively flat T wave with possible U wave), the U wave was included in the measurement of the T wave [6]. However, none of the patients had clearly pathologic U waves. Biphasic T waves were measured from the beginning of the Q wave to the end of the T wave. QT dispersion was evaluated with QT range (QT max–QT min) and QT standard deviation (QT SD), both for QT and QTc (Bazett formula). Evaluation of the intra-observer variability with two measurements of QT dispersion on the first 35 patients found a high correlation (R>0.9, p<0.001) and no significant differences between the two measurements. Other investigations included a complete hemodynamic investigation and an evaluation of the risk of ventricular arrhythmia. Twenty-four-hour ambulatory ECG recordings were performed in all patients with grading of ventricular arrhythmias. All recordings were analysed using the ELATEC Holter analysis software (Ela Medical, Montrouge, France) with manual edition and correction of RR intervals and QRS. Non-sustained ventricular tachycardia (NSVT) was defined as three or more ventricular premature complexes, <30 s, at a rate >100/min. Time domain analysis of heart rate variability included Mean RR (mean duration [ms] of all normal-to-normal [NN] intervals) and SDNN (standard deviation [ms] of all NN intervals). A recording of signal averaged ECG (Arrhythmia Research Technology model 101, Austin, TX, USA) was performed using the methods and thresholds values for late potentials as described in a previous study from our group, with specific criteria in patients with bundle branch block [7]. The high-pass filter was set at 25 Hz, the low-pass filter at 250 Hz and the sampling frequency was 2000 Hz. Analysis followed standards of measurement [8]. Results were considered positive if the filtered QRS complex was >120 ms, root-mean-square voltage was <25 µV during the last 40 ms of the filtered QRS complex, and duration of the filtered QRS complex was >35 ms after the voltage decreased to <40 µV. In cases of bundle branch block, results were considered positive if the filtered QRS complex was >145 ms, root-mean-square voltage was <17 µV during the last 40 ms of the filtered QRS complex, and duration of the filtered QRS complex was >45 ms after the voltage decreased to <40 µV [9].

2.3. Statistical analysis
Statistical analysis was performed in the 162 patients who had a major cardiac event (death due to heart failure, sudden death, heart transplantation, sustained ventricular tachycardia or ventricular fibrillation) or who were followed for more than 6 months and were free of events. Comparisons between groups were made by using the Student's t-test for continuous variables. Survival curves were estimated by the Kaplan–Meier method and curves were compared using the log rank test. Sudden death was defined as instantaneous death or death occurring within 1 h of the onset of symptoms in a patient with no evidence of progressive heart failure, or death during sleep. The effects of variables during follow-up were studied with univariate and multivariate analysis (proportional hazards model). A forward stepwise model with a p value for entry of 0.05 was used. All values are given as mean±standard deviation. LV ejection fraction and heart rate variability were used as continuous rather than dichotomy variables. Statview 4.5 software (Abacus Concepts, Berkeley CA, USA) was used for statistical analysis.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusion
 References
 
The mean age of the patients on hospital admission was 51±12 years (range 21–70). Clinical data and results of ECG, radionuclide ventriculography, hemodynamic investigations and 24-h ambulatory ECG are summarised in Table 1. No differences were found for any parameters of QT dispersion between patients with or without non-sustained VT or late ventricular potentials on signal averaged ECG. Mean follow-up was 53±41 months. Thirty patients died during follow-up: 12 with progressive CHF, 14 sudden deaths and 4 non-cardiac deaths (cancer). Four patients were resuscitated from documented ventricular fibrillation (VF) and five other patients had sustained VT. Of these nine patients, six were treated with an implantable cardioverter-defibrillator, one was treated with sotalol and had no recurrence, one underwent heart transplantation and the last one was treated with amiodarone but had poor therapy compliance and suffered a sudden death. Sixteen patients underwent heart transplantation and were censored at the time of the transplantation for the survival analysis. Table 2 compares the characteristics of event-free patients, of patients with cardiac death and of patients with major arrhythmic events (sudden death, sustained ventricular tachycardia or ventricular fibrillation) during follow-up. No difference was found for any parameters of QT dispersion between patients with and without events. Figs. 1 and 2 show the similar survival curve of cardiac death and of major arrhythmic events, respectively, according to QT range and QT SD using median values as cutoffs (40 ms for QT range and 20 ms for QT SD). There were also no differences between patients with QT range <100 or >100 ms, considered to be a very abnormal value, that may in some cases have practical value [6]. These results were similar when patients with bundle branch block were excluded. In the 117 remaining patients, there were 15 cardiac deaths and 13 major arrhythmic events ; the relative risk of cardiac death was 0.88 (95% CI 0.18–3.70, p=NS) for patients with QT range >40 ms and 0.98 (95% CI 0.34–2.86, p=NS) for patients with QT SD >20 ms ; the relative risk of major arrhythmic events was 0.43 (95% CI 0.06–3.33, p=NS) for patients with QT range >40 ms and 0.96 (95% CI 0.30–3.03, p=NS) for patients with QT SD >20 ms.


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  		Table 1 Clinical characteristics and results of investigations in patients with IDC (n=162)

 


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  		Table 2 Characteristics of event-free patients, of patients with cardiac death and of patients with major arrhythmic events (sudden death, sustained ventricular tachycardia or ventricular fibrillation) during follow-up

 


Figure 1
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  		Fig. 1 Survival curves of cardiac death according to QT dispersion in patients with IDC (comparison by log rank test).

 


Figure 2
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  		Fig. 2 Survival curves of major arrhythmic events (sudden death, sustained ventricular tachycardia or ventricular fibrillation) according to QT dispersion in patients with IDC (comparison by log rank test).

 
Univariate and multivariate predictors for cardiac death and for major arrhythmic events (sudden death, sustained ventricular tachycardia or ventricular fibrillation) are shown in Table 3. Using multivariate analysis, increased pulmonary capillary wedge pressure (PCWP) (p=0.003), decreased heart rate variability (p=0.01) and non-sustained ventricular tachycardia (NSVT) (p=0.03) were predictors of cardiac death. Sudden death and/or arrhythmic event (sustained VT or VF) were independently predicted by NSVT (p=0.005), decreased heart rate variability (p=0.01) and late ventricular potentials on signal averaged ECG (p=0.02).


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  		Table 3 Univariate and multivariate predictors (proportional hazards model) of cardiac death and of major arrhythmic events (sudden death, sustained ventricular tachycardia or ventricular fibrillation) in patients with IDC

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusion
 References
 
It has been reported that an increased QT dispersion is associated with arrhythmic events in various clinical settings, such as long QT syndrome, heart failure, coronary artery disease, post myocardial infarction or hypertrophic cardiomyopathy [6]. However, the ability of QT dispersion to identify cardiac patients at high risk of sudden death remains uncertain due to conflicting findings [6,10]. This study assessed the role of QT interval dispersion for risk stratification in IDC. The patients in this study were well characterized as all had normal coronary angiography and the observed incidence of cardiac death observed was in agreement with recent studies on mortality in CHF due to IDC. A main interest of our study is the long duration of the follow-up (the longest to our knowledge for a series of patients with IDC) with 8957 patients-months of follow-up, markedly higher than that of other studies (4590 in the study of Fei et al. [11], about 2850 in the study of Galinier et al. [12], 1391 in the study of Grimm et al. [13]) with follow-ups in these series of between 12 and 36 months. A long follow-up seems mandatory in IDC patients as we found in our series that the mean delay for a major arrhythmic event was 41 months and was 46 months for cardiac death. Our results suggest that QT dispersion is not useful for the stratification of cardiac risk in IDC even with a long follow-up. It is therefore unlikely to be useful for a cost-effective management strategy in these patients.

Fei et al. [11] have already found, in 60 patients with heart failure secondary to IDC, that there was no significant difference in QTd between survivors and those who died or were transplanted during follow-up. Furthermore, no significant difference in QTd was observed between patients with and without ventricular tachycardia detected on ambulatory ECG. Grimm et al. [12] have evaluated QTd in 107 patients with IDC compared with 100 healthy matched controls. The usefulness of QTd for risk stratification was limited due to the large overlap of QTd among patients with and without arrhythmic events during a follow-up of 13±7 months. The same authors have recently found negative results with QTc dispersion with a longer follow-up in 343 patients with IDC in the recently published Marburg Cardiomyopathy Study [14].

The results published by Galinier et al. [13] were the most encouraging. In 205 heart failure patients, 119 had dilated cardiomyopathy (101 IDC, 18 hypertensive dilated cardiomyopathy). In these latter patients, QTd was significantly higher in those with sudden death. In multivariate analysis, only a QTd >80 ms was an independent predictor of sudden death and arrhythmic events (Relative Risk of 4.9 and 4.5) in dilated cardiomyopathy, but not in ischaemic heart disease. Although the authors concluded that abnormal QTd can identify patients with dilated cardiomyopathy who are at high risk of arrhythmic events and sudden death, more data were needed to make firm conclusions about the clinical utility of QTd for identification of patients at risk of sudden death in IDC. There has been no other study to confirm the results obtained in the study of Galinier. Our study in which the results of QT measurements were made blindly by a single physician who was not aware of any other clinical characteristic or risk factor of patients provides further data.

In addition to QT dispersion, we report the results obtained with QTc dispersion. This is not an appropriate measure of the dispersion of ventricular repolarization because QT dispersion on a 12-lead ECG does not depend (and should not be corrected) for heart rate in the same way as the QT interval [6]. Our wish to be exhaustive is the only justification for the presentation of these negative supplementary results.

It has been suggested that JT interval dispersion was a better predictor of sudden death than QT dispersion in patients with myocardial infarction. This test may at least have a practical value for a large population group or in the particular situation of bundle branch block [5,6], a relatively common finding in patients with dilated cardiomyopathy. However, it is not sure that JT dispersion offers further information than QT dispersion, and we found that our results were similar when patients with bundle branch block were excluded from the statistical analysis.

It should be noted that left ventricular ejection fraction (LVEF) was an univariate predictor but it was not found to be an independent predictor of cardiac death or of major arrhythmic events in contrast to other studies in IDC. The independent prognostic value of an increased PCWP and of a decreased heart rate variability may explain these findings. It is possible that PCWP and heart rate variability have been included in the regression model instead of LVEF at the time of the multivariate analysis considering the positive or negative correlations that are usually found for these two variables with LVEF in heart failure. Moreover, some patients may have a decreased LVEF but may have a relatively good prognosis if the medical treatment is associated with a decrease in filling pressures. Furthermore, in some other patients, the low ejection fraction of a very large LV end-diastolic volume may result in a relatively preserved cardiac output and this may also explain the lack of independent prognostic value of a decreased LVEF in our study.

Other methods of exploration of repolarization abnormalities are currently being evaluated [15]. QT dynamicity, an evaluation of the rate dependence of QT duration on 24-h ambulatory ECG, might be of interest for risk stratification in IDC, and is currently evaluated in our institution. Changes have been observed in heart failure at a molecular or a cellular level and may explain a particular pattern of QT dynamicity [16]. This technique should be of interest to define a strategy of prophylactic ICD therapy in nonischemic dilated cardiomyopathy.

4.1. Study limitations
The number of patients may seem small compared to some studies on QT dispersion performed in populations with heart failure or coronary artery disease. However, this series is one of the largest with well-characterized IDC and has the longest average follow-up. The percentage of patients treated with beta-blockers (25%) is lower than in current practice in therapeutic studies of heart failure but it also reflects the "real life" practice in the last 5 years in patients with IDC with mild heart failure (only 39% of the patients were in functional class NYHA III or IV). Moreover, beta-blockers improve prognosis in such patients but it has not been demonstrated than beta blockers modify the prognostic value of an electrocardiographic measurement such as QT dispersion.


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
References
 
This study confirms the poor prognostic value of QT dispersion in patients with IDC. Other methods to assess repolarization abnormalities need to be evaluated to determine the risk of cardiac death or of major arrhythmic events in patients with IDC.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 

  1. Borggrefe M., Block M., Breithardt G. Identification and management of the high risk patient with dilated cardiomyopathy. Br. Heart J. (1994) 72:S42–S45. [Suppl.].[Free Full Text]
  2. Brachmann J., Hilbel T., Grünig E., et al. Ventricular arrhythmias in dilated cardiomyopathy. Pacing Clin. Electrophysiol. (1997) 20(II):2714–2718.[CrossRef][Medline]
  3. Strickberger SA. Multicenter Randomized Trial Comparing Amiodarone to Implantable Defibrillator in Patients With Nonischemic Cardiomyopathy and Asymptomatic Nonsustained Ventricular Tachycardia: AMIOVIRT Trial. Circulation. 102:2794.
  4. Bansch D., Antz M., Boczor S., et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the Cardiomyopathy Trial (CAT). Circulation (2002) 105(12):1453–1458.[Abstract/Free Full Text]
  5. Yi G., Malik M. Can the ECG data help to identify IDC patients at risk of sudden cardiac death? In: Progress in clinical pacing—Santini M., ed. (1998) Armonk, NY, USA: Futura Media Sciences Inc. 257–262.
  6. Malik M., Batchvarov V.N. Measurement, interpretation and clinical potential of QT dispersion. J. Am. Coll. Cardiol. (2000) 36(6):1749–1766.[Abstract/Free Full Text]
  7. Fauchier L., Babuty D., Cosnay P., et al. Long-term prognostic value of time domain analysis of signal-averaged electrocardiography in idiopathic dilated cardiomyopathy. Am. J. Cardiol. (2000) 85(5):618–623.[CrossRef][Web of Science][Medline]
  8. Breithardt G., Cain M.E., el-Sherif N., et al. Standards for analysis of ventricular late potentials using high resolution or signal-averaged electrocardiography. A statement by a task force committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology. Circulation (1991) 83:1481–1488.[Abstract/Free Full Text]
  9. Buckingam T.A., Thessen C.C., Stevens L., Red R.M., Kennedy H.L. Effects of conduction defects on the signal-averaged electrocardiographic determination of late potentials. Am. J. Cardiol. (1988) 61:1265–1271.[CrossRef][Web of Science][Medline]
  10. Brendorp B., Elming H., Jun L., et al. QT dispersion has no prognostic information for patients with advanced congestive heart failure and reduced left ventricular systolic function. Circulation (2001) 103:831–835.[Abstract/Free Full Text]
  11. Fei L., Goldman J.H., Prasad K., et al. QT dispersion and RR variations on 12-lead ECGs in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy. Eur. Heart J. (1996) 17:258–263.[Abstract/Free Full Text]
  12. Grimm W., Steder U., Menz V., et al. Clinical significance of increased QT dispersion in the 12-lead standard ECG for arrhythmia risk prediction in dilated cardiomyopathy. Pacing Clin. Electrophysiol. (1996) 19(11 Pt. 2):1886–1889.[CrossRef][Medline]
  13. Galinier M., Vialette J.C., Fourcade J., et al. QT interval dispersion as a predictor of arrhythmic events in congestive heart failure. Importance of aetiology. Eur. Heart J. (1998) 19:1054–1062.[Abstract/Free Full Text]
  14. Grimm W., Christ M., Bach J., Muller H.H., Maisch B. Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Circulation (2003) 108:2883–2891.[Abstract/Free Full Text]
  15. Coumel P., Maison-Blanche P., Badilini F. Dispersion of ventricular repolarization: reality? Illusion? Significance? Circulation (1998) 97:2491–2493.[Free Full Text]
  16. Coumel P., Maison-Blanche P. Physiology of QT interval dynamicity. Card. Electrophysiol. Rev. (1997) 3:364–367.

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