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European Journal of Heart Failure 2004 6(2):187-193; doi:10.1016/j.ejheart.2003.09.012
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© 2003 European Society of Cardiology

QT dispersion correlates to myocardial viability assessed by dobutamine stress echocardiography in patients with severely depressed left ventricular function due to coronary artery disease

Manolis Bountioukosa, Arend F.L. Schinkela, Don Poldermansa,*, Vittoria Rizzelloa, Eleni C. Vourvouria, Boudewijn J. Krenninga, Elena Biaginia, Jos R.T.C. Roelandta and Jeroen J. Baxb

a Thoraxcenter, Department of Cardiology Erasmus Medical Center, Rotterdam, The Netherlands
b Department of Cardiology Leiden University Medical Center, Leiden, The Netherlands

* Corresponding author. Tel.: +31-10-463-9222; fax: +31-10-463-4957. E-mail address: d.poldermans{at}erasmusmc.nl


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Background: T dispersion is prolonged in numerous cardiac diseases, representing a general repolarization abnormality.

Aim: To evaluate the influence of viable myocardium on QT dispersion in patients with severely depressed left ventricular (LV) function due to coronary artery disease.

Methods and results: 103 patients with ischemic cardiomyopathy (LV ejection fraction [EF]: 25±6%) were studied. Patients underwent 12-lead electrocardiography to assess QT dispersion, and two-dimensional echocardiography to identify segmental dysfunction. Dobutamine stress echocardiography (DSE) was then performed to detect residual viability. Resting echo demonstrated 1260 dysfunctional segments; of these, 476 (38%) were viable. Substantial viability (≥4 viable segments on DSE) was found in 62 (60%) patients. QT dispersion was lower in these patients, than in patients without viability (55±17 ms vs. 65±22 ms, P=0.012). Viable segments negatively correlated to QT dispersion (r=–0.333, P=0.001). In contrast, there was no correlation between LVEF and QT dispersion (r=–0.001, P=NS).

Conclusions: There is a negative correlation between QT dispersion and the number of viable segments assessed by DSE. Patients with severely depressed LV function and a low QT dispersion probably have a substantial amount of viable tissue. Conversely, when QT dispersion is high, the likelihood of substantial viability is reduced.

Key Words: QT dispersion • Ischemic cardiomyopathy • Dobutamine stress echocardiography

Received April 15, 2003; Revised May 29, 2003; Accepted September 15, 2003


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
A number of prospective studies have assessed the predictive value of QT dispersion for cardiac and all-cause mortality in the general population [1,2]. QT dispersion has been demonstrated to be prolonged in patients with various cardiac diseases; this is consistent with the concept that QT dispersion represents a general repolarization abnormality [3–7]. A limited number of studies have investigated the value of QT dispersion to predict myocardial viability in the setting of chronic coronary artery disease [8–10]. However, in most of these studies, patients had a relatively preserved left ventricular function. Current information on the relation of QT dispersion to the amount of viable myocardium in patients with ischemic cardiomyopathy is contradictory.

Accordingly, the aim of this study was to evaluate whether QT dispersion correlates to myocardial viability, assessed by dobutamine stress echocardiography, in a cohort of patients with severely depressed left ventricular (LV) function due to chronic coronary artery disease.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusions
 References
 
2.1. Eligibility
A total of 103 consecutive patients were referred for dobutamine stress echocardiography for the assessment of myocardial viability were included in the study. Patients had ischemic cardiomyopathy and a radionuclide LV ejection fraction (EF) ≤35%. In all patients, a resting 12-lead surface electrocardiogram (ECG) was performed. Exclusion criteria were: (1) recent (<3 months) myocardial infarction; (2) non-sinus rhythm or left bundle brunch block on ECG; (3) antiarrhythmic medication that could influence QT interval (class IA, IC, and III agents); and (4) suboptimal acoustic window. The Hospital Ethics Committee approved the protocol. All patients gave informed consent before the test.

2.2. Measurement of QT dispersion
Patients underwent surface electrocardiography with simultaneous 12-lead recordings, in order to avoid the effect of heart rate changes on QT dynamics. A single observer, who was blinded to the dobutamine stress echocardiography results, performed the analysis. A dedicated computer program (Mortara Instruments, Bilthoven, The Netherlands) was used for this purpose. On-screen measurement with electronic calipers and magnification, in order to obtain the maximal electrocardiographic detail, was used. The T wave offset was determined as an interception between a line characterizing the slope of the descending part of the T wave and the isoelectric line. The slope-characterizing line was a tangent to the point of steepest slope. When a U wave was also present, the nadir between the T and the U wave was considered the point of T wave offset [11]. QT dispersion was defined as the difference between the maximum and the minimum QT intervals on 12-lead ECG. Rate-corrected (QTc) interval was calculated by dividing QT interval by the square root of RR interval on ECG. Accordingly, QTc dispersion was the difference between the maximum and the minimum QTc interval. Measurements were repeated after a week in 60 randomly selected patients. Intraobserver variability for QT dispersion was 7.4±5.0 ms.

2.3. Resting 2D echocardiography, assessment of regional dysfunction
A commercially available imaging system (Hewlett Packard Sonos 5500, Andover, MA, USA) and a 1.8 MHz transducer using second harmonic imaging to optimize endocardial border visualization were used. Two-dimensional imaging was performed with the patient in the left lateral position; standard views were recorded on optical disk (cine loops) [12].

2.4. Dobutamine stress echocardiography
To assess myocardial viability in dysfunctional myocardium, dobutamine stress echocardiography was performed. After the resting echocardiographic study, dobutamine was administered intravenously, starting at a dose of 5 µg/kg per min for 5 min, followed by a 10 µg/kg per min dose for 5 min (low dose). Subsequently, the rate of dobutamine infusion was increased by 10 µg/kg per min every 3 min to a maximum dose of 40 µg/kg per min. Atropine (up to 2 mg) was added at the end of the last stage if the target heart rate had not been achieved. End points for interruption of the test were: (1) achievement of target heart rate; (2) maximal doses of both dobutamine and atropine; (3) extensive new wall motion abnormalities; (4) new horizontal or downsloping ST-segment depression ≥0.2 mV 80 ms after the J point; (5) severe angina; (6) symptomatic reduction in systolic blood pressure >40 mmHg from baseline; (7) hypertension (blood pressure >240/120 mmHg); (8) significant arrhythmia; or (9) any serious side effect regarded as being due to dobutamine infusion.

The baseline, low dose, peak stress and recovery images were displayed as a cineloop format. Two experienced observers, unaware of the clinical and electrocardiographic data, scored the digitized echocardiograms offline. In case of disagreement, a majority decision was achieved by considering the opinion of a third observer. For each study, the LV was divided into 16 segments, as described previously. Regional wall motion and systolic wall thickening were scored using a 5-point grading scale: 1=normal, 2=mildly hypokinetic, 3=severely hypokinetic, 4=akinetic, 5=dyskinetic. Only severely dysfunctional segments (severe hypokinesia, akinesia or dyskinesia at resting echocardiography) were evaluated for myocardial viability. Segments with improvement, worsening, or a biphasic wall motion response during stress echocardiography were considered viable. Segments with unchanged wall motion were considered non-viable [13]. A patient was classified as viable in the presence of ≥4 dysfunctional viable segments.

2.5. Assessment of LVEF
The LVEF was assessed by radionuclide ventriculography as follows: A small field-of-view gamma camera system (Orbiter, Siemens, Erlangen, Germany) was used, oriented in a 45° left anterior oblique position with a 5–10° caudal tilt. After injection of Tc-99m-pertechnate labeled autologous erythrocytes (550 MBq), radionuclide ventriculography was performed at rest with the patient in supine position. The LVEF was calculated by standard methods (Odyssey VP, Picker, Cleveland, OH, USA).

2.6. Statistical analysis
All continuous data are expressed as mean value±standard deviation. Percentages are rounded. Differences in continuous variables within groups were compared using the paired Student t-test, whereas differences between groups were assessed by Student's t-test for unpaired samples. The Pearson correlation coefficient was used to estimate correlation between variables. Receiver-operating characteristic (ROC) analysis was used to determine optimal cut-off values of QT dispersion and QTc dispersion to predict myocardial viability. The best cut-off value was defined as the point with the highest sum of sensitivity and specificity. All tests were two-sided, and a P-value<0.05 was considered statistically significant. Analyses were performed by an SPSS 10.0 software package (SPSS Inc., Chicago, IL, USA).


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusions
 References
 
3.1. Patient characteristics and hemodynamic data
Baseline characteristics of the study patients are presented in Table 1. Patients had a mean age of 59±9 years and a mean LVEF of 25±6% (range: 10–35%). Most of the patients were in New York Heart Association Class III or IV (78 patients, 76%). In total, 94 (91%) patients had a previous Q-wave myocardial infarction in at least one region (anterior in 72 patients, septal in 16, lateral in 18, and inferoposterior in 33).


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  		Table 1 Baseline patient characteristics

 
Dobutamine stress testing was completed without serious adverse events in all patients. The mean infusion rate of dobutamine was 35.7±7.6 µg/kg per min and atropine was added in 51 patients. Heart rate increased from 76.1±14.0 beats/min at baseline to 133.2 ±9.0 beats/min at peak (P<0.001). All but eight patients (92%) reached 85% of the maximal predicted for the age heart rate. Systolic and diastolic blood pressures had no significant changes between baseline and peak dobutamine infusion.

3.2. Echocardiographic results
From a total of 1648 segments that were evaluated by 2D echocardiography, 1260 (76%) were dysfunctional at rest; of these, 663 (52%) segments were severely hypokinetic, 588 (47%) akinetic, and nine (1%) dyskinetic. Of the 1260 dysfunctional segments, 476 (38%) were viable and 784 (62%) were non-viable according to dobutamine stress echocardiography. A total of 62 (60%) patients had a substantial amount of viable tissue, whereas the remaining 41 (40%) patients had no or limited (≤4 viable segments) viability. The distribution of patients with respect to the number of viable segments is shown in Fig. 1.


Figure 1
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  		Fig. 1 Distribution of study patients (n=103) according to the number of viable segments on dobutamine stress echocardiography.

 
3.3. QT dispersion vs. viability
Measurement of QT interval was feasible in ≥eight leads in all patients. The mean number of leads measured was 10.5±1.2. In total, eight leads were measurable in nine patients (9%), nine leads in 12 (12%), 10 leads in 23 (22%), 11 leads in 32 (31%), and 12 leads in 27 (26%) patients. Mean QT dispersion was 59±20 ms. Heart rate-adjusted QT dispersion (QTc dispersion) was 66±22 ms.

A significant negative correlation was found between QT dispersion and the number of viable myocardial segments on dobutamine stress echocardiography (r=–0.333, P=0.001). Similarly, QTc dispersion was negatively correlated to the number of viable segments (r=–0.303; P=0.002) (Fig. 2). Wall motion score index at rest did not correlate to QT dispersion (r=0.033; P=0.739) or QTc dispersion (r=0.126; P=0.204). In addition, there was no correlation between LVEF and QT dispersion (r=–0.060, P=0.545) or QTc dispersion (r=–0.132, P=0.184) (Fig. 3). Patients with ≥four viable segments on dobutamine stress echocardiography had a significantly lower QT dispersion, compared to patients with <four viable segments (55±17 ms vs. 65±22 ms, P=0.012). The difference in QTc dispersion between patients with and without a substantial amount of viable myocardium was also significant (62±21 ms vs. 72±22 ms, P=0.032). A value of QT dispersion ≤64 ms had 73% sensitivity and 46% specificity to predict the presence of viable myocardium (accuracy: 63%). The corresponding cut-off value for QTc dispersion was 72 ms (sensitivity: 71%, specificity: 46%, accuracy: 61%).


Figure 2
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  		Fig. 2 QT dispersion and QTc dispersion are significantly correlated to the number of viable segments on dobutamine stress echocardiography in patients with ischemic cardiomyopathy.

 


Figure 3
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  		Fig. 3 No correlation was found between QT/QTc dispersion and resting radionuclide left ventricular ejection fraction in patients with ischemic cardiomyopathy.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusions
 References
 
4.1. Main findings
According to the present study, QT dispersion was negatively correlated to the number of viable myocardial segments, assessed by dobutamine stress echocardiography. Patients with evidence of a substantial amount (≥four segments) of viable myocardium on dobutamine stress echocardiography had significantly lower QT dispersion than patients without viability.

4.2. QT dispersion in the setting of heart disease
An increased QT dispersion has been demonstrated in the setting of several cardiac diseases, such as during and after the acute phase of myocardial infarction, in hypertrophic cardiomyopathy, in left ventricular hypertrophy, in idiopathic dilated cardiomyopathy, and in long QT syndrome of various genotypes [3–7]. Prolonged QT dispersion may predict ventricular arrhythmias after myocardial infarction [14,15], as well as sudden death in patients with chronic heart failure [16]. In addition, patients with heart failure have a worse outcome when QT dispersion is prolonged [17], and it has been suggested that one of the mechanisms by which carvedilol improves survival in patients with heart failure may be shortening of QT dispersion [18].

4.3. Myocardial viability and QT dispersion
Detection of myocardial viability has become crucial for decision-making in patients with previous myocardial infarction and poor LV systolic function, since several studies have reported on the beneficial effects of revascularization in terms of survival and quality of life in the presence of viable tissue [19–21]. Moreover, coronary revascularization offers the maximum benefit when a substantial amount of viable myocardium has been detected during non-invasive testing [22–24].

The idea of extracting information on the presence of myocardial viability from a simple and inexpensive test, such as the resting surface ECG, is appealing from a clinical point of view. Three studies have reported on the value of QT dispersion to predict viability in patients with chronic coronary artery disease, however, the results are conflicting; Ikonomidis et al. studied 75 patients with a previous myocardial infarction and relatively preserved LV function (mean LVEF 34%). QT dispersion was measured at rest and during low dose dobutamine infusion. The authors concluded that the combination of a resting QT dispersion <65 ms and an increase in QT dispersion >30% during low dose dobutamine infusion had a sensitivity of 67% and a specificity of 96% to predict viability [8]. Schneider et al studied 44 patients with chronic Q-wave myocardial infarction using F-18 fluorodeoxyglucose positron emission tomography. As in the present study, patients with viability had low QT dispersion, whereas patients with predominantly nonviable scar tissue had a high QT dispersion. A QT dispersion value ≤70 ms had 85% sensitivity and 82% specificity to predict viability [9]. Notably, patients in that study had a mildly reduced or preserved LV function. The authors underlined the need for further research in order to establish the applicability of QT dispersion in patients with more severely depressed LV function. Al Mohammad et al. used a study with positron emission tomography and F18-fluorodeoxyglucose to evaluate 42 patients with prior myocardial infarction and poor LV function, and found no correlation between QT dispersion and the presence of viable myocardium [10]. This might be related to the relatively small number of patients enrolled, since there was a trend toward higher QT dispersion in patients without viability.

The present study is the first to report a correlation between QT dispersion and myocardial viability in patients with chronic coronary artery disease and severely depressed LV function. The optimal cut-off values of QT/QTc dispersions found in this study were quite similar to the cut-off values found in previous studies including patients with less severe LV dysfunction. Patients with ischemic cardiomyopathy and a low QT dispersion probably had a substantial amount of viable tissue, whereas in patients with a high QT dispersion the likelihood of substantial viability was low.

4.4. Mechanisms of prolongation of QT dispersion in ischemic cardiomyopathy
QT dispersion, when increased, indicates the presence of generalized myocardial electrical instability [16]. In patients with ischemic cardiomyopathy, a large proportion of scarred, fibrous tissue is likely to contribute to an abnormal and inhomogeneous LV repolarization, and thus to increased QT dispersion values [25]. Furthermore, ischemic cardiomyopathy is usually accompanied by LV dilatation and increased intracavitary pressures, which can cause load-induced changes in ventricular repolarization [26]. In the infarcted LV, dysfunctional segments consist of a combination of fibrotic and hibernating tissue. The infarcted area can be transmural, or localized to subendocardium, with more or less extensive involvement of the exterior myocardial layers. Although dobutamine stress echocardiography has a good accuracy to evaluate myocardial viability, this variation in the proportion of viable tissue in segments characterized as viable can be responsible for the overlapping QT dispersion values found in viable and nonviable segments in the present study.

4.5. Study limitations
Several limitations of this study have to be mentioned. First, measurement of QT intervals is occasionally not accurate, mainly due to the inability to assess precisely the offset of T waves. Nevertheless, by measuring only those leads with clear delineation of the end of the T wave, we minimized this limitation. Second, measurement of QT dispersion had a relatively low accuracy to predict viability; therefore QT dispersion currently is not an alternative for non-invasive tests to predict myocardial viability. Further studies are needed to define the clinical role of QT dispersion measurements in the assessment of viable myocardium.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
References
 
QT dispersion is negatively correlated to the amount of viable myocardium in patients with severely depressed LV function due to chronic coronary artery disease. A low QT dispersion increases the probability that a substantial amount of viable tissue may be found during non-invasive cardiac imaging. Conversely, patients with a high QT dispersion have a low likelihood of substantial viability.


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

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