QT Dispersion Is Determined by the Extent of Viable Myocardium in Patients With Chronic Q-Wave Myocardial Infarction
Background QT dispersion is lower in patients with successful thrombolysis after acute myocardial infarction, suggesting that QT dispersion may be determined by the extent of viable and scarred myocardium.
Methods and Results To test this hypothesis, QT dispersion was measured in a 12-lead resting ECG in 44 patients with chronic Q-wave myocardial infarction. To assess the extent of viable and scarred myocardium, all patients underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). In addition, all patients had revascularization of the infarct-related artery and repeated angiography 4 months later. QT dispersion was lower (53±20 versus 94±24 ms, P<.0001) in patients with evidence of a substantial amount of viable myocardium in the infarct region as demonstrated by PET (average FDG uptake ≥50% of normalized, maximum FDG uptake) than in patients with only minimal residual viability. Average FDG uptake of the infarct region and FDG defect size were significantly related to QT dispersion (r=.64, P<.0001; r=.67, P<.0001), whereas ejection fraction was not (r<.1, P=NS). QT dispersion of ≤70 ms had a sensitivity of 85% and a specificity of 82% to predict viable myocardium in the infarct region. QT dispersion was also lower in patients with improvement of left ventricular function 4 months after revascularization (54±21 versus 88±30 ms, P=.0003). QT dispersion of ≤70 ms had a sensitivity of 83% and a specificity of 71% to predict improvement of left ventricular function.
Conclusions QT dispersion is determined by the amount of viable myocardium in the infarct region and may serve as a novel, rapidly available marker of substantial viability in the infarct region of patients with chronic Q-wave myocardial infarction.
A significant reduction of postinfarct QT dispersion was shown in patients with acute myocardial infarction and successful thrombolysis.1 These data suggest that QT dispersion may be influenced by the extent of myocardial damage after myocardial infarction, because successful thrombolysis and a patent infarct artery are associated with smaller infarct sizes and improved left ventricular function.2 However, the exact relationship between the extent of myocardial scar, persisting viability in the infarct region, recovery of function, and QT dispersion after myocardial infarction is unknown. To test the hypothesis that QT dispersion is related to the extent of scarred and viable myocardium, patients with chronic Q-wave myocardial infarction were examined by PET with FDG and [99mTc]-methoxy-isobutyl-isonitril (99mTc-Sestamibi) SPECT. All patients underwent revascularization of the infarct-related coronary artery. Left ventricular function was assessed by angiography at baseline and 4 months after revascularization, and QT dispersion values were analyzed in patients with and without improvement in function. Thus, the value of QT dispersion could be assessed both for detection of viable myocardium as defined by FDG PET and for prediction of functional recovery after revascularization.
After giving informed consent, 44 consecutive patients (34 men; mean age of all patients, 56 years; 95% CI, 53 to 59 years) with chronic Q-wave myocardial infarction, angiographically documented high-grade stenosis (>75% diameter reduction) of the infarct-related coronary artery, and regional severe hypokinesia, akinesia or dyskinesia by left ventriculography were included in the study between February 1995 and April 1996. Indications for coronary angiography included angina or a pathological exercise test in 38 patients, severe dyspnea judged to be of cardiac origin in 4 patients, and prognostic reasons (young age) in 2 patients. Patients with evidence of atrial fibrillation, bundle-branch block, or diabetes mellitus were excluded. The index myocardial infarction was at least 4 months old (mean infarct age, 34 months; 95% CI, 14 to 55 months) to make sure that the dynamic changes of the QT dispersion occurring in the early postinfarct period would not interfere with the measurements.3,4 The site of myocardial infarction was inferior in 20 patients and anterior in 24 patients. Mean ejection fraction was 50% (SD=14). Most patients (35 of 44) had angina class II or III (Table 1⇓) according to the classification system of the Canadian Cardiovascular Society.5
QT dispersion was calculated from a standard 12-lead ECG on the day of admission. To assess myocardial viability in regions with severe wall motion abnormalities, all patients underwent FDG PET and 99mTc-Sestamibi SPECT on 2 separate days within 4 days before revascularization of the infarct-related vessel. Independent of the results of the viability study, the infarct-related vessel was revascularized in all patients according to the study protocol. Twenty-four patients underwent PTCA of the infarct-related vessel, and 20 patients underwent CABG. Indication for revascularization was based on the angiographic and clinical status of the patients (see above). Four months after revascularization, all patients had repeated angiography and ventriculography. At this second angiography, 3 patients had an occlusion of the bypass graft of the infarct-related vessel, and 3 patients had a significant restenosis (>75% diameter reduction) and were excluded from the postrevascularization analysis of QT dispersion, because persisting ischemia could have precluded an improvement of function. In the remaining 38 patients, no cardiac event (myocardial infarction, unstable angina, repeated revascularization) was noted during the 4 months of follow-up as judged from history, ECG, and repeated angiography.
The characteristics of the 38 patients with successful PTCA or CABG are shown in Table 2⇓. Infarct location was similarly distributed in both groups: In the CABG group, 10 patients had anterior and 7 patients had inferior infarcts; in the PTCA group, 11 patients had anterior and 10 patients had inferior infarcts (P=.77). In addition, the severity of angina was similar in both groups: 13 of 17 patients in the CABG group and 17 of 21 patients undergoing PTCA had angina class II or III (P=.66). The incidence of multivessel disease was higher in patients undergoing bypass surgery: All patients undergoing CABG had multivessel disease (17 patients), while only 7 of 21 patients in the PTCA group had multivessel disease (P=.001). All study parameters used in this study (all parameters of QT dispersion, degree of wall motion abnormality, left ventricular ejection fraction, FDG defect size, and average FDG uptake in the infarct region; Table 2⇓) were comparable at baseline in patients undergoing PTCA or CABG. In addition, the differences in wall motion abnormality of the infarct region from baseline to repeated angiography were similar in PTCA patients and in CABG patients with improvement of function (1.3 standard deviation [standard deviation=0.5]) versus 1.3 standard deviation (standard deviation=0.4, P=NS) as were the changes in wall motion abnormality in patients without improvement of function (0.08 standard deviation [standard deviation=0.54] for PTCA patients versus 0.01 standard deviation [standard deviation=0.37; P=NS] for CABG patients). The data of patients with PTCA and CABG were therefore pooled for analysis of the predictive value of QT dispersion for recovery of function.
The study was approved by the Hospital Human Rights Committee (Institutional Review Board).
QT interval analysis was done on a surface 12-lead ECG (50-mm/s paper speed) by a single observer who was not aware of the PET or angiographic findings. In all patients, QT intervals in at least 8 leads could be measured from the onset of QRS to the end of T wave (ie, return to the TP baseline). If U waves were present, the QT interval was measured to the nadir of the curve between the T waves and the U waves6 (Fig 1⇓). All ECGs were analyzed on 2 separate days with a time interval of at least 2 weeks, and the mean of both measurements was used for further analysis. Intraobserver variability for QT dispersion was 8 ms (95% CI, 7.4 to 8.6 ms), and the correlation of the measurements on separate days was significant (r=.91, P<.001).
QT intervals are presented without (QT) and with (QTc) adjustment for RR intervals using Bazett’s formula (QTc=QT/RR1/2).6 QT dispersion was defined as the difference between maximum and minimum QT interval, and QTc dispersion was calculated accordingly. Adjusted QTc dispersion takes into account the numbers of leads measured and is the QTc dispersion divided by the square root of number of leads measured.6 In addition, the QT SD was calculated as the SD of QT intervals measured in a single resting ECG.6
Ten or more leads in 39 patients (88%), 9 leads in 2 patients, and 8 leads in 3 patients could be analyzed. Thus, 42 leads (8%) were excluded from analysis because of difficulties in defining the end of the T wave reliably. Of these 42 leads, 26 (62%) were located in the limb leads, and 16 (38%) were in the precordial leads.
Selective coronary angiography was performed by the Judkins technique, and arteries were viewed in multiple projections. Biplane left ventriculography was performed in the right and left anterior oblique positions. Analysis of wall motion abnormalities was performed in the right anterior oblique view because in 42 of the 44 patients the right coronary artery or left anterior descending coronary artery was the infarct artery. In 2 patients, a dominant left circumflex artery was the infarct artery in the presence of a hypoplastic right coronary arterty, leading to akinesia of the diaphragmatic and posterobasal wall. The left ventriculographies of these 2 patients were also analyzed in the right anterior oblique view.7
Regional left ventricular wall motion was quantified and expressed as SD per chord of a normal control population by use of the centerline method7 in the right anterior oblique projection. Chords 1 through 9 and 81 through 100 were excluded from analysis because they reflect movement of the aortic root and mitral valve, respectively.7 The remaining chords of the left ventricle in right anterior oblique projection were divided into five segments (anterobasal, chords 10 through 26; anterolateral, chords 27 through 43; apical, chords 44 through 60; diaphragmatic; chords 61 through 70; and posterobasal, chords 71 through 807). Wall motion abnormality was quantified from the chords belonging to each segment and expressed as mean SD. Infarct segments were defined as segments with an average wall motion >2 SD below that of a normal population and constituted the infarct region.7 An increase in SD of the infarct region at control angiography by >0.8 SD in patients with anterior infarcts and >0.6 SD in patients with inferior infarcts was defined as significant improvement of left ventricular wall motion indicative of recovery of viable myocardium.8 Global left ventricular ejection fraction was calculated from end-diastolic and end-systolic contours by use of the area-length method.9
Perfusion of the infarct-related artery was assessed according to the criteria of the Thrombolysis in Myocardial Infarction trial.10 A grade of 0 indicates no flow of contrast beyond the point of occlusion; 1, penetration with minimal perfusion; 2, penetration with partial perfusion; and 3, penetration with complete perfusion. Coronary artery narrowing was measured in the projection showing the most severe stenosis by use of electronic calipers. A diameter reduction of >50% was considered significant.
FDG PET Studies
PET was performed with a whole-body scanner (Siemens CTI ECAT Exact 921) as described previously.11 To improve myocardial glucose uptake, each patient received a solution of 50 g of glucose 1 hour before the administration of FDG. Images were corrected for attenuation by use of coefficients measured by a transmission scan of 30-minute duration. Emission scans (six for 5 minutes) were started 30 minutes after injection of 370 MBq of FDG.
Patients fasted except for their standard antianginal medication, and 370 MBq 99mTc-Sestamibi (Cardiolite, Dupont) was injected in the patients at rest. This injection was followed by a standard meal (Biloptin) 1 hour after 99mTc-Sestamibi injection to improve 99mTc-Sestamibi clearance from the hepatobiliary tract. SPECT was performed 2 hours after 99mTc-Sestamibi injection.12 99mTc-Sestamibi SPECT data were used as a normalization reference for the PET data.
For analysis of the relationship of QT dispersion and the extent of viability in the infarct region, the angiographic extent of wall motion abnormality (see above), the average FDG uptake in the infarct area, and the FDG defect size were assessed.
PET and SPECT images were analyzed side by side by use of computer-generated polar maps on a Sun SPARC 20 workstation.11,12 The apical and basal limits of the ventricle in the PET images were visually defined from the horizontal and vertical long-axis slices. The images of the left ventricle were reconstructed as short-axis slices and normalized to the region with maximum 99mTc-Sestamibi uptake in the heart (normalized, maximum FDG uptake). The left ventricle was individually divided into six contiguous short-axis slices with the most basal slice just below the mitral valve level. An automatic circumferential profile analysis program was then applied to each of the six short-axis slices to generate polar maps. Quantitative analysis was performed by use of the polar map of the heart and a continuous color-graded scale.
We have previously shown that a threshold of 50% of normalized, maximum FDG uptake discriminates myocardium with minimal residual viability from myocardium with larger amounts of viable myocardium with high sensitivity and specificity.11 Accordingly, FDG defect size was calculated as the percent of the FDG polar map with <50% of normalized, maximum FDG uptake. In addition, average FDG uptake of the infarct region as defined by angiography (eg, segments with a wall motion abnormality of more than −2 SD; see above) was quantified by use of the polar map. To facilitate the comparison with the right anterior oblique angiogram, the polar map was divided into five segments (anterobasal, anterolateral, apical, diaphragmatic, and posterobasal, Fig 2⇓), and the average FDG uptake in the infarct region was quantified. Infarct regions with an average FDG uptake of <50% of normalized, maximum FDG uptake were defined as myocardium with only minimal residual viability, and regions with an average FDG uptake of ≥50% of normalized, maximum FDG uptake were defined as myocardium with larger amounts of viable myocardium.11
The relationship between QT dispersion and viability was analyzed in two ways. First, patients were divided into those with and without larger amounts of viable myocardium in the infarct region on the basis of the average FDG uptake (44 patients). Second, patients were divided according to the presence or absence of improvement of left ventricular wall motion 4 months after successful revascularization (38 patients).
All data are presented as mean (SD). The median and the 95% CIs are also reported in the tables. Student’s t test was used to compare group means; the null hypothesis was rejected at the 95% confidence level, considering a probability value of P<.05 as significant. Differences in the SD were tested by use of the F test with a significance level of P<.05. If significant differences were detected between SDs, an appropriate nonparametric test was used. The Pearson correlation coefficient was calculated to estimate correlation between variables. Categorical variables were compared by use of contingency table analysis and Fisher’s exact test. Sensitivity and specificity of QT dispersion for prediction of viability and improvement of left ventricular function were calculated with standard formulas.
QT Dispersion and FDG Uptake in the Infarct Region
Clinical and angiographic data of the patients grouped according to the average FDG uptake in the infarct region are shown in Table 1⇑. The patients were well matched. The mean global left ventricular ejection fraction at baseline angiography was 55% (SD=16) in patients with an average FDG uptake ≥50% of normalized, maximum FDG uptake and was similar to the ejection fraction of patients with an average FDG uptake <50% (mean left ventricular ejection fraction, 48%; SD=10; P=.15). Similarly, mean wall motion abnormality at baseline was −2.9 standard deviations (SD=0.45) in patients with an average FDG uptake ≥50% in the infarct region and −3.0 standard deviation (SD=0.4) in patients with an average FDG uptake <50% in the infarct region (P=.46). Patients with an average FDG uptake of ≥50% in the infarct region had more severe angina symptoms than patients with an average FDG uptake <50% (Table 1⇑).
QT dispersion was significantly lower in patients with evidence of a substantial amount of viability in the infarct region (eg, average FDG uptake ≥50%) compared with patients without such evidence (Table 3⇓, Fig 3⇓). Lower values for QT SD, QTc dispersion, and adjusted QTc dispersion were also found in patients with evidence of a substantial amount of viability in the infarct region, whereas longer QT dispersion values were found in the presence of larger FDG defects (Table 3⇓).
No significant correlation was found between ejection fraction and QT dispersion (Fig 4⇓). In contrast, QT dispersion was significantly correlated to FDG defect size and average FDG uptake (Figs 5⇓ and 6⇓). QT dispersion of ≤70 ms had the best sensitivity (23 of 27 patients; 85%) and specificity (14 of 17 patients; 82%) to predict viable myocardium in the infarct region as demonstrated by FDG PET (Fig 7⇓). QT dispersion of ≤70 ms had a positive predictive value of 88% (23 of 26 patients), a negative predictive value of 78% (14 of 18 patients), and a diagnostic accuracy of 84% (37 of 44 patients).
QT Dispersion and Improvement of Function
The baseline clinical data of the patients grouped according to improvement of left ventricular function are shown in Table 4⇓. There were no significant differences between the two groups at baseline. The mean time between first and second angiographies was 3.9 months (SD=0.5) in patients with improved left ventricular function and 4.1 months (SD=0.6) in patients without improvement of function (P=.28). Mean left ventricular ejection fraction assessed in the baseline angiogram before revascularization was 51% (SD=15) in patients with improvement of function and 52% in patients without improvement of function at the 4-month follow-up (SD=8, P=.34). Mean wall motion abnormality of the infarct region assessed at baseline before revascularization was −3.0 standard deviations (SD=0.4) in patients with improvement of function and −2.8 standard deviations (SD=0.4) in patients without improvement of function (P=.15).
Left ventricular ejection fraction increased significantly in patients with significant improvement of wall motion abnormality (51% [SD=15] versus 62% [SD=11], P<.0002) but was essentially unchanged in the remaining patients (52% [SD=8] versus 51% [SD=8]; P=.49; Table 5⇓). All parameters of QT dispersion, assessed in the baseline ECG, were significantly lower in patients with improvement of function compared with patients with unchanged left ventricular function (Table 5⇓). Average FDG uptake in the infarct region was significantly higher and FDG defect size was significantly smaller in patients with improvement of wall motion (Table 5⇓). Sensitivity and specificity of QT dispersion of ≤70 ms to predict improvement of left ventricular function was 83% (20 of 24 patients) and 71% (10 of 14 patients), respectively. The positive predictive value was 87% (20 of 24 patients), the negative predictive value was 71% (10 of 14 patients), and the diagnostic accuracy was 79% (30 of 38 patients).
Sensitivity and specificity of an average FDG uptake of ≥50% of normalized, maximum FDG uptake to predict improvement of left ventricular function were 95% (23 of 24 patients) and 79% (11 of 14 patients), respectively. The positive predictive value was 89% (23 of 26 patients), the negative predictive value was 92% (11 of 12 patients), and the diagnostic accuracy was 89% (34 of 38 patients).
This study shows that the duration of QT dispersion is influenced by the presence of a substantial amount of viable myocardium in the infarct region: First, in patients with a larger extent of viable myocardium in the infarct region, as proven by FDG PET, QT dispersion was significantly lower than in patients with minimal residual myocardial viability. Second, patients with improvement of left ventricular function after successful revascularization, which is a generally accepted proof of viability, also showed significantly smaller QT dispersion values in the baseline ECG before revascularization.
Identification of viable myocardium in the infarct region is important for clinical decisions with respect to the future therapy for an individual patient. Scintigraphic techniques using FDG11 or thallium-20113 and echocardiographic techniques14 are widely accepted methods for the identification of viable myocardium after infarction. However, these techniques are time consuming, expensive, and usually available only at specialized medical centers. Thus, a simple and inexpensive method to estimate the extent of viable myocardium after myocardial infarction would be advantageous. Although the resting ECG is such a method, the use of the resting ECG for evaluation of residual viability has not attracted much attention over the last years. The presence and extent of pathological Q waves have been used to characterize an infarct as transmural, suggesting a low probability of a substantial amount of viable myocardium.15 However, in a significant percentage of patients with Q-wave infarcts, a significant amount of viable myocardium can be detected in the infarct region, thus bringing into question the value of the analysis of pathological Q waves for the reliable estimation of scarred myocardium.16
The data presented in this paper demonstrate that QT dispersion assessed in the resting ECG is related to the presence of a substantial amount of viable myocardium in the infarct region. Indirect evidence for the relationship between QT dispersion and viability is provided by data of Moreno et al.1 They showed that successful thrombolysis after acute infarction leads to lower QT dispersion values (52 versus 81 ms, P<.0001). Although they did not provide measures of infarct size, it is reasonable to assume that successful thrombolysis was associated with smaller infarcts.2 The present work strongly supports this view by demonstrating that even in patients with chronic Q-wave infarcts, lower QT dispersion values were associated with smaller infarcts.
In addition, QT dispersion of ≤70 ms had a good sensitivity and specificity to predict substantial amounts of viable myocardium in the infarct region and compares well with other techniques routinely used to assess viable myocardium. Thallium-201 scintigraphy has been extensively used to predict viable myocardium after myocardial infarction, yielding sensitivity values of ≈74% and specificity values of ≈75%.13,14,17 More recently, dobutamine echocardiography has been used to identify viable myocardium after myocardial infarction. The sensitivity of this technique ranges between 74% and 92%, and the specificity ranges between 77% and 95%.14,17 The highest sensitivity and specificity values for the identification of viable myocardium are found in patients assessed by PET. The sensitivity values are between 78% and 96%, and the specificity values are between 69% and 92%.17,18 Considering the simplicity, availability, and low cost of a resting ECG and the good diagnostic accuracy of QT dispersion in the detection of viable myocardium, the calculation of QT dispersion is a reasonable initial approach to estimate the probability of a substantial amount of viable myocardium in patients with chronic infarcts and left ventricular dysfunction. In patients with QT dispersion values of <60 ms (10 of 44 patients), the probability of a larger extent of viable myocardium in the infarct region was 100%. In patients with a QT dispersion of >90 ms (8 of 44 patients), the probability of a larger extent of viable myocardium in the infarct region was 0%. Thus, further viability tests may not be indicated in these patients.
In patients with QT dispersion values between 60 and 90 ms (26 of 44 patients in our study), the diagnostic accuracy was between 80% and 84% (Fig 7⇑). When a QT dispersion threshold of ≤70 ms was used, 7 patients were not correctly categorized with respect to viability. Three patients below the threshold had only minimal viable myocardium in the infarct region, and 4 patients above the threshold showed evidence of a substantial amount of viable myocardium in the infarct region. In this patient population, further viability tests with higher diagnostic accuracies may therefore be necessary.
Increased QT dispersion values have been associated with an increased risk of fatal arrhythmia19–21 and sudden cardiac death22 after myocardial infarction. The underlying mechanisms for the increased QT dispersion in these conditions are not well defined. The degree of left ventricular dysfunction has been proposed as a potential mechanism leading to an increased QT dispersion. Pye et al19 have previously shown a significant correlation of left ventricular ejection fraction as a parameter of damage and QT dispersion in a mixed population of patients with coronary artery disease and dilated cardiomyopathy and without evidence of heart disease. In contrast, in this study and in a previous article,20 no significant correlation between ejection fraction and QT dispersion could be found in a homogeneous study population of patients with coronary artery disease and myocardial infarction. This lack of correlation can be explained by our observation that only a larger extent of scarred myocardium is associated with prolonged QT dispersion values, whereas dysfunctional but viable myocardium is not. However, both conditions lead to a reduction in left ventricular ejection fraction, precluding a correlation between ejection fraction and QT dispersion.
An explanation for the observation of increased QT dispersion values in patients with larger infarcts could be the presence of larger amounts of fibrous tissue, which may influence the duration and homogeneity of repolarization.23 In addition, larger infarcts may be accompanied by an enhanced mechanical stretch to the myocardial wall or dilation of the infarcted ventricle, which potentially increase repolarization inhomogeniety24,25 and may contribute to longer QT dispersion values. These mechanisms may also be operative in patients with fatal arrhythmias or sudden cardiac death after myocardial infarction, conditions known to be associated with increased QT dispersion values and with larger infarcts.19–22,26 In contrast, smaller infarcts and successful thrombolysis may decrease the repolarization inhomogeneity that is reflected by smaller QT dispersion values1 and improved electrical stability.27
There are some limitations of our study that must be considered. First, we studied only a small group of patients. However, the differences in QT dispersion are large, regardless of the mode that QT dispersion was analyzed, and are consistent independently of the mode by which viability was defined (FDG uptake and recovery of function). Second, QT dispersion was assessed in a selected group of patients with chronic Q-wave myocardial infarction. The applicability of our results to other patient populations (eg, patients with non–Q-wave myocardial infarctions, patients with more severely depressed left ventricular function) has to be established. Third, the analysis of QT dispersion is sometimes difficult because in some cases the end of the T wave cannot be reliably determined and may lead to spurious calculation of QT dispersion. To avoid this problem, only leads in which the end of the T wave could be clearly delineated were used. In addition, four different parameters of QT dispersion were used, all of which gave highly significant differences between the groups tested. Methodological problems are therefore unlikely to account for our findings.
In summary, QT dispersion after myocardial infarction is determined by the extent of scarred and viable tissue. Increased values of QT dispersion indicate larger amounts of scarred tissue, whereas shorter QT dispersion values (eg, ≤70 ms) indicate the presence of a substantial amount of viable myocardium in the infarct region. Thus, the analysis of QT dispersion may provide information not only about the individual risk of a patient for fatal arrhythmia but also about the presence and the extent of viable myocardium in the infarct region and the probability of recovery of function after revascularization in patients with chronic Q-wave myocardial infarction.
Selected Abbreviations and Acronyms
|CABG||=||coronary artery bypass graft surgery|
|PET||=||positron emission tomography|
|PTCA||=||percutaneous transluminal coronary angioplasty|
|SPECT||=||single-photon emission tomography|
- Received January 13, 1997.
- Revision received July 28, 1997.
- Accepted August 14, 1997.
- Copyright © 1997 by American Heart Association
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