In our study, we examined the correlation between QTd and the severity and extent of myocardial ischemia detected by myocardial perfusion imaging. Our findings suggest that QTd values both at rest and had a significant relationship with the extent and severity of myocardial ischemia and rises with the increase in the severity and extent of ischemia.
A significant increase in QTd value using dipyridamole upon the induction of abnormal ventricular wall motion was previously reported which means that ischemia could change QTd value [7].
Okishige et al. [8] demonstrated that QTd increases reversibly during ischemia in patients with CAD. This increase in dispersion should be presumed to result from a combination of a local repolarization abnormality and altered conduction within ischemic areas.
Some researchers have not considered QTd as a standard criterion for assessing the homogeneity of ventricular repolarization. They stated that not only the accuracy of the standards relating to the dispersion but also the existence of a direct correlation between homogeneity of ventricular repolarization and QTd is in question [9].
In contrast, other researchers believe that QTd is a reliable measure for investigating abnormalities of myocardial repolarization and is able to predict severe arrhythmias after myocardial infarction and also mortality because of cardiovascular diseases [10]. This could be explained that the increase in the heterogeneity of ventricular repolarization in myocardial ischemia results in an increase in QTd value [11].
We compared the QTd value in patients who suffered from ischemia with normal people based on myocardial scanning and found that this parameter was identical in both groups at rest but significantly increased with the induction of stress in the ischemic group compared with the normal one.
Intra-group difference also exists so that the QTd value rises significantly with the increase in the severity of ischemia.
It was previously shown that, in patients without chest pain or ST segment depression during stress induction, QTd calculation immediately after stress induction can be very useful for diagnosing CAD [12].
Moreover, QTd increases to more than 60 ms under stress, with 70% sensitivity and 95% specificity that can be useful in the diagnosis of CAD [13].
The patients with CAD have longer corrected QT (QTc) intervals at peak heart rates during exercise. This finding provides insufficient evidence to support routine incorporation of QTc at peak heart rates into exercise test interpretation [14].
Teragawa and his colleagues also observed that stress induction using ATP infusion was associated with increased QTd only in patients with ischemia (ischemia and ischemia with scar), whereas in normal patients or those who suffered from scars, ischemia as the result of ATP infusion caused reduced QTd. They stated that in the normal group, ATP infusion may simultaneously cause a significant reduction of the maximum and minimum QT segment duration. QTd at baseline and during ATP infusion correlated with the ATP-SPECT imaging pattern. Therefore, the induction of ischemia was associated with an increase in QTd in the group with ischemic injuries, and a decrease in QTd in the group without ischemic injuries [15].
Randomized clinical trials (RCTs) have shown that the addition of coronary CT angiography [16, 17] or functional imaging [18] to stress ECG clarifies the diagnosis, enables the targeting of preventive therapies and interventions, and potentially reduces the risk of myocardial infarction compared with an exercise ECG [19].
In recent ESC 2019 Guidelines for the diagnosis and management of chronic coronary syndromes (CCS), exercise ECG alone has been downgraded as an alternative to diagnose obstructive CAD if imaging tests are not available (class II b, level of evidence b) [20], keeping in mind the risk of false-negative and false-positive test results [21, 22].
Regarding diagnosis of IHD, our study shows that the sensitivity and specificity of stress ECG test for detecting ischemia are 61% and 90% respectively. We noticed that addition of QTd values to the results of stress ECG improves the sensitivity to 72% with an irrelevant effect on the specificity (91%).
We found a strong relation between the QTd difference and the defect size in MPS in the ischemic group. The increase in the defect size is associated with increase in QTd difference.
Takase and colleagues also observed that QTd at rest in patients with simultaneous reversible and irreversible injuries and those with only irreversible injury was significantly higher than the normal group and the group with reversible injury. However, QTd under stress increased in the group with reversible injury but decreased in other groups [23].
It should be noted that the correlation between QTd and ischemic parameters in the scan is much lower at rest than under stress. As mentioned, such QTd increase under stress might be because of the increase in the heterogeneity of ventricular repolarization caused by the incorrect reaction of the ischemic myocardium to catecholamine or the abnormal flow of calcium ions [24, 25].
The findings of Schmidt and his colleagues [26] are not consistent with ours. In their study, they investigated the QTd value in the diagnosis of myocardial ischemia compared with myocardial scan using thallium 201 (Tl-201 SPECT). They observed that there was no significant correlation between QTd at rest and under stress and scanning parameters such as the degree of myocardial ischemia, the number of ischemic segments, and summed ischemic stress score. They gave many explanations such as differences in QT duration of up to 60 ms have been reported in individuals without structural heart disease and a significant range of overlap exists between healthy volunteers with QT dispersion of 30 ± 10 ms and patients with heart disease with 56 ± 23 ms. Another explanation may come from potentially gross inter- and intraobserver variability of QT dispersion assessment as reported elsewhere [26].
Masaki and his colleagues also stated that not QTd, but QT peak dispersion (QTpd) can be useful in detecting stress-induced myocardial ischemia [25].
In our study, we tested an index called QTd difference that actually shows the difference between QTd at rest and under stress. The comparison of this index between the normal and ischemic groups indicates that its value increases significantly in patients with myocardial ischemia. Since QT difference gives a resultant of the two values of stress and rest QTd, this can possibly be a more appropriate index for diagnosis of myocardial ischemia and the homogeneity rate of repolarization of ventricular cells [27]. Schmidt and colleagues also examined this factor in their study [26].
We found also that the cut-off for QTd in the diagnosis and prediction of the ischemia equaled 9 ms. We could conclude that under exercise-induced stress, patients who had negative stress ECG test for exercise-induced myocardial ischemia but their QTd value was more than (9 ms), those patients most probably had abnormal perfusion scan results.
The most eminent results of our study are those concerning with QTd difference and stress. When adding QTd difference to its result, the sensitivity, specificity, and accuracy of exercise stress ECG test was improved.
Considering the different results obtained from our research regarding the QTd value and based on the findings of this study, we can conclude that QTd can be clinically useful in identifying ventricular ischemic myocardial events.
Further studies are needed to determine diagnostic capabilities of QT dispersion, including its sensitivity and specificity which are currently under investigation to detect the extent that the QTd could be clinically useful in identifying ventricular ischemic myocardial injuries.
