Corrected QT-Interval and Dispersion After Revascularization by Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Chronic Ischemia

Abstract: Introduction. Electrocardiography parameters can predict cardiac events in ischemia. QT-interval parameters are potentially proposed as available non-invasive markers for assessing the ventricular homogeneity and electrical instability. Prolonged QT-interval (QTI) and QT dispersion (QTd) are predictors of poor prognosis and fatal arrhythmias. The improvement of cardiac perfusion may decrease QTI via percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. The aim of this study was to compare the effects of PCI and CABG on QT parameters in chronic ischemia. Methods. A total of 141 consecutive patients with coronary artery disease (70 who underwent PCI and 71 who underwent CABG) were entered into the study. Standard 12-lead electrocardiograms were recorded immediately before the procedure, immediately post procedure, 24 hours post procedure, and 7 days post procedure; corrected QTI (QTc) and corrected QTd (QTcd) and their changes were assessed and compared across the two therapeutic groups. Results. QTc and QTcd reduced significantly after 7 days of revascularization. After PCI, QTc reduced from 444.7 ± 46.9 msec to 427.4 ± 40.6 msec and QTcd reduced from 47.1 ± 23.3 msec to 38.1 ± 1.1 msec. QTc increased immediately after CABG from 443.2 ± 36.6 msec to 461.9 ± 38.1 msec, but reduced within 7 days of the procedure to 430.2 ± 28.2 msec. QTcd reduced from 49.6 ± 23.2 msec to 30.9 ± 3.9 msec. The trend of QTcd reduction were similar in the two therapeutic groups but the trend of QTc alteration was different in that QTc increased upwardly and then decreased after CABG. Conclusion. Revascularization in chronic ischemia can improve QTI parameters following both PCI and CABG.

J INVASIVE CARDIOL 2014;26(9):444-450

Key words: ischemic heart disease, electrocardiogram

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Ischemic heart disease is the leading cause of mortality worldwide.¹ Electrocardiogram (ECG) is one of the most readily available devices for estimating cardiac condition. QT-interval parameters are potentially proposed as available non-invasive markers for assessing the ventricular homogeneity as well as for predicting electrical instability.² QT interval (QTI) is defined as the longest interval from the beginning of the QRS complex to the end of the T-wave; QT dispersion (QTd) is defined as the difference between the longest and shortest QTI, and reflects electrical activity of the ventricles. The prolongation of the latter parameter is a main predictor for fatal arrhythmia in patients with long QT syndrome, hypertrophic cardiomyopathy, heart failure, and myocardial infarction (MI).³ The measurement of QTI and QTd parameters are dependent on heart rate and can be corrected by the QT correction formulas, which are termed the corrected QTI (QTc) and QTd (QTcd).^4,5 Acute and chronic ischemia can prolong QTc and QTcd.^6-10 Reperfusion occurring in acute MI led to decreasing QTc in some studies,^11-14 but the effect of revascularization on these parameters in chronic ischemia remains controversial.^15-26 Some researchers showed that QTI or QTd decreased after PCI in chronic ischemia.^6,14-17 Some others showed that these parameters were decreased after CABG,^17-20 while others revealed that QTI or QTd were increased after CABG.^23,24 No study has compared the effects of these two interventions on QTI and QTd. The aim of the current study was to compare the alterations of QTc and QTcd by reversing ischemia after PCI and CABG in patients with chronic ischemic heart disease.

Methods

The study was conducted on 141 consecutive patients with established coronary artery disease (CAD) by angiography. The participants were admitted to Heshmat Heart Hospital for elective stenting or CABG due to their coronary anatomy and guidelines of ischemia treatment. Therefore, the subjects included symptomatic patients with intermediate to high-risk exercise tolerance test (ETT) or moderate to severe inducible ischemia in single-photon emission computed tomography (SPECT). Exclusion criteria were existence of rhythm other than normal sinus, implanting pacemaker, electrolyte abnormalities, wide QRS complex, hereditary long QT syndrome, history of MI <3 months ago, and the use of drugs with known effects on QTI. All patients received chronic medical treatment including beta-blockers. Subsequent risk factors and characteristics were collected from recorded files or by interviewing, and included age, gender, hypertension (blood pressure >140/90 mm Hg or taking antihypertensive drugs), diabetes (fasting blood sugar >126 mg/dL, random blood sugar >200 mg/dL or taking drugs for diabetes), hyperlipidemia (low-density lipoprotein >130 mg/dL, triglycerides >200 mg/dL, high-density lipoprotein <35 mg/dL), left ventricular (LV) hypertrophy (LV mass >125 g/m² for males and >110 g/m² for females based on echocardiography), and MI (previous established admission for chest pain with troponin rise and ECG changes at least >3 months before the procedure). Left ventricular ejection fraction (LVEF) was measured using the Simpson method by two-dimensional echocardiography. All interventions were successful, with no serious complications. Complete revascularization was defined as revascularization by a stent or a graft in any vessel with >50% stenosis. Standard 12-lead ECGs at a paper speed of 25 mm/s and voltage of 10 mm/mV were recorded at 4 time points, including immediately before and after the procedure as well as 24 hours and 7 days post procedure, and were read by a cardiologist who was blind to baseline data of the patients. QTI was measured from the beginning of QRS to the end of the T-wave by a ruler. The end of T-wave was determined to be the point of the return to isoelectric line; if it could not be determined reliably, the measurement was not performed. The parameters of QT interval were also measured as: QTI max (maximal QT interval duration), QTc max (maximum Bazett’s formula heart rate corrected QT interval), QTd (difference between the maximum and minimum QTI), and QTcd (difference between the maximum and minimum QTc). QTc and QTcd and their changes were calculated in at least 8 leads, including 3 precordial leads, and were then compared between both therapeutic groups.  Because some data have shown Bazett’s formula may make errors in low or high heart rates,⁵ we also used another formula for correction of QTI named Hodges formula (QTc = QT + 1.75 [HR-60]), where HR = heart rate, and repeated the main analysis. The effect of patient characteristic data and times of revascularization were also assessed.

Statistical analysis was performed using SPSS version 19.0 (SPSS, Inc) and SAS version 9.1 for windows (SAS Institute, Inc). Continuous variables were reported as mean ± standard deviation (SD). QTI parameters after the procedure compared to baseline by paired t-test at any time and the alterations were calculated by subtracting new amounts from the baseline for each patient and are given as mean value with 95% confidence interval (CI). P-value <.05 was considered to be significant. The groups were compared using the Student’s t-test or one-way ANOVA test for the continuous variables and the chi-square test (or Fisher’s exact test if required) for the categorical variables. The trends of the changes in quantitative variables were assessed using the repeated measure ANOVA test. The multivariate analysis by Generalized Estimating Equations (GEE) was used to assess the effects of other variables on these alterations.

Results

One hundred and forty-one patients were included in the study, of which 70 patients underwent PCI and 71 patients underwent CABG. Baseline patient characteristics are summarized in Table 1. Distribution of sex and CAD risk factors such as history of MI and myocardial hypertrophy (LVH) were similar in the two groups; however, the patients who underwent PCI were younger than those in the CABG group (P=.01), and also had higher LVEF (P=.02). The CABG group had more severe CAD than the PCI group. Prevalence of single-vessel disease, double-vessel disease, and triple-vessel disease were 68.6%, 20.0%, and 11.4% in the PCI group and 2.8%, 19.7%, and 77.5% in CABG group, respectively. Also, 70% of patients in the PCI group and 93% in the CABG group underwent complete revascularization. 

The changes in QTI parameters are summarized in Tables 2 and 3. In the entire group, the patients had more tachycardia immediately and 24 hours post procedure compared with the baseline heart rates, but on day 7, it did not differ significantly. Mean heart rate did not change significantly in the PCI group at the different time points, but in the CABG group, patients had higher heart rates at each time point when compared to the baseline (Table 2). Moreover, 4% of patients before PCI and 2.7% immediately and also 24 hours after PCI had heart rates ranging from 100-110 bpm. Also, 2.7% of patients had heart rates ranging from 100-110 bpm before CABG and 13.3% and 9.3% had heart rates ranging from 100-130 bpm immediately and 24 hours after surgery. None of the patients had profound bradycardia.

Mean QTc was 443.9 ± 41.9 msec before revascularization in all patients and did not significantly change immediately and 24 hours after the procedure, but reduced on day 7 and reached 428.5 ± 35.3 msec. QTcd was initially 47.9 ± 22.7 msec, then reduced significantly after 24 hours and 7 days and reached 34.8 ± 16.1 msec.

In the PCI group, QTc and QTcd decreased significantly at 24 hours and 7 days after the procedure. QTc decreased from 444.7 ± 46.9 msec to 427.4 ± 40.6 msec and QTcd also decreased from 47.1 ± 23.3 msec to 38.1 ± 1.1 msec.

In the CABG group, QTc was 443.2 ± 36.6 msec at baseline, and significantly increased immediately after CABG to 461.9 ± 38.1 msec, then finally decreased after 7 days to 430.2 ± 28.2 msec. QTcd decreased after 24 hours and 7 days of CABG and went from 49.6 ± 23.2 msec to 30.9 ± 3.9 msec.  

Repeated measure ANOVA test revealed that the trend of QTc alteration was significantly different in the two groups (P=.01). As shown in Figure 1, QTc first increased after CABG and then decreased after that, but it had a descending pattern just after PCI. However, its changes did not differ finally on day 7 in either groups (P=.47) (Figure 1).There was no significant difference in patterns (P=.13) and times (P=.08) of QTcd alterations between the two procedures (Figure 2).

Using Hodges formula for correction of QTI, the only major different result was that QTc increment was not significant immediately after CABG. Other results were overall the same with Bazett’s formula (Table 5). 

In the PCI group, QTc and QTcd in patients with single-vessel disease decreased, but no significant changes were observed in the multivessel disease groups (P>.05). QTc in the CABG group increased significantly immediately after surgery in those with triple-vessel disease (P=.01) and also decreased after 7 days only in this subgroup. Changes in QTcd were only significant in triple-vessel disease. It was reduced 7 days post surgery (Table 4).

In multivariate analysis by GEE, in patients with myocardial hypertrophy, the reduction of QTcd was 4.3 msec less than the without myocardial hypertrophy (95% CI, 3.5-4.9; P=.01). In patients with history of MI, the reduction of QTc was 12.9 msec less than patients without MI (95% CI, 4.1-21.1; P=.01). Sex had no effect on QTc alteration, but QTcd was decreased 6.9 msec less in males than in females (95% CI, 4.7-8.9; P=.01). There was a positive correlation between LVEF and QTcd alteration that the reduction of QTcd was 0.9 msec more per each percent of ejection fraction (95% CI, 0.5-1.4; P=.01). The reduction of QTc and QTcd in complete revascularization was 18.9 msec (95% CI, 13.7-24.2; P=.01) and 8.6 msec (95% CI, 4.2-13.1; P=.01), respectively, more than partial revascularization. 

Discussion

Comparing the changes in different QT-interval parameters following CABG and PCI, we showed two important differential patterns. At first, we could show that although patterns of the changes in study parameters including QTI and QTc were different early after procedures, these changes are partially similar within 1 to 7 days after the procedures. Furthermore, some risk factors such as male gender, systolic hypertension, and history of MI as well as the number of diseased coronary vessels and myocardial hypertrophy were potential factors affecting the pattern of these changes following the procedures.

Impairment of autonomic regulation of the heart has been observed in patients with coronary artery disease.⁶ According to some reports, acute ischemia during balloon inflation in PCI and in the setting of acute MI increases QTI.^7-9 It has been suggested that transient ischemia during revascularization induces significant changes in ventricular repolarization, particularly during occlusion of the left anterior descending artery, resulting in significant changes in these parameters. Atemir et al found changes in the values of QTd during balloon angioplasty, compared to the values before the procedure.⁹ The results of other studies in patients undergoing PCI confirmed the ischemic mechanism of QT dispersion changes.⁸

Prolonged QTc in acute MI and after primary PCI was associated with adverse outcomes.^10,11 Reperfusion in MI could decrease QTc in some studies.^12-14

The results of chronic ischemia are controversial.^15-26 Finally, in our patients, both QTc and QTcd decreased significantly after revascularization by PCI and CABG. It is in line with the opinion of researchers who proposed that revision of ischemia could improve electrical stability of the heart.^6,15-21

In the PCI group, we observed a descending pattern of QTc and QTcd immediately after the procedure; however, significant reduction only occurred after 24 hours and 7 days. It’s possible that increased sympathetic activity during the first hours of PCI did not allow manifestation of the consequences of ischemia revision, but the final improvement was in agreement with the results of Yunus et al, who showed reduction of QTd 24 hours after PCI in 37 patients without history of MI¹⁵ and some other research that revealed QTI reduction after 7 days or more.^16,17,22 It has been proposed that the changes in QTI after successful PCI as independent risk factors would predict subsequent events and prognosis.²³

After CABG, there was an increase of QTc immediately after surgery, but then it decreased on day 7. In addition to underlying CAD, non-physiological procedures in CABG, including cardiopulmonary bypass, cross clumping, hypothermia, hemodilution, cardioplegia, and postoperative complications have detrimental effects on electrical and mechanical activity of the heart.²⁴ After the acute phase and removal of the influence of these factors, QTc could be decreased. Some studies have shown that Bazett’s formula does not have enough accuracy in very slow or fast heart rates, but linear models may be more useful in these conditions.⁵ We showed that QTc and QTcd overall reduced after revascularization even after corrected by Hodges formula; however, the only major difference was immediately after CABG, when patients had the highest heart rates, so that increment of QTc was not significant.

QTcd changes were not significant within the first hours, but reduced after 24 hours and 7 days. It conflicts with the results of Cagli et al, who showed the increase of QTd 24 hours after surgery.²³ Yavuz showed deterioration of QT parameters within 10 days post CABG.²⁴ However, our results had more similarity with the work done by Kaik et al and Kosar et al.^19,20,25 However, the pattern of QTc alteration was different in our two groups, whereas the pattern of the changes was similar at the end. It suggests different results that are more likely due to the procedure itself within the first hours, and it is obvious that CABG is much more invasive with more direct effects on the cardiovascular system, and that patients have faster heart rates during the 24 hours post CABG. After the acute phase, both revascularization methods had beneficial effects on these parameters; however, QTcd changes were similar in both groups.

Alteration of QTI parameters was more significant in single-vessel disease in the PCI group and in triple-vessel disease in the CABG group. As noted, most patients in the PCI group had single-vessel disease and most patients in the CABG group had triple-vessel disease. Because of the small numbers of patients in the subgroups, there was not enough power to show the significance of the changes.

The reduction in QTc was less in patients with a history of MI, which can be due to less viable myocardium and more scars. Viability studies by positron emission tomography scan in PCI patients  and dobutamine stress echo in CABG patients have suggested that changes in QTI have a direct relationship to the amount of viable myocardium.^6,27 It was also seen that higher LVEF was associated with more response rates in QTc and QTcd, which might have occurred for the same reason mentioned above. The reduction of QTcd was less in the myocardial hypertrophy subgroup, perhaps due to more scarring, and more endothelial and microvascular dysfunction that could not be resolved by revascularization of the epicardial vessels.

In all groups, complete revascularization caused more reduction in both parameters when compared with a partial procedure. This suggests that if the ischemia is revised more completely, more improvement of cardiac electrical activity will be achieved.

Study limitations. Although most characteristics were similar in our two groups, two important factors were different, ie, that LVEF was greater in the PCI group and revascularization was performed more completely in the CABG group. Patients had faster heart rates in the CABG group compared to the PCI group. It could have some effects beyond the specific method used. We could not determine exact ischemia burden before or after the procedures, which might be important in clarifying the cause of our results. Also, we did not evaluate the specific factors during the procedures that seem to have detrimental effects, especially within the first hours.

Conclusion

Revascularization improves electrical activity of the heart in any methods that is performed. If it is done more completely, more benefit can be achieved and it can be estimated by QTI parameters on ECG.

Acknowledgment. The authors wish to acknowledge the contributions of Sarvenaz Arami, PharmD, Tehran University of Medical Sciences, Tehran, Iran.

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From the Departments of 1Cardiology and 2Biostatistics, Dr Heshmat Heart Hospital, Guilan University of Medical Sciences, Rasht, Iran.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted April 2, 2012, provisional acceptance given April 23, 2012, final version accepted February 3, 2014.

Address for correspondence: Samira Arami, PharmD, Guilan University of Medical Sciences, Rasht, Iran. Email: samira_523@yahoo.com