Recent reports suggest T peak to T end (Tpe) interval and Tpe/QT ratio as valuable indicators of increased arrhythmogenic risk in patients with coronary artery disease (CAD). We aimed to examine the exercise-induced changes in these indexes in patients with stable CAD, before and after percutaneous coronary intervention (PCI). Forty patients were consecutively included in the interventional group (n = 20), with significant lesions (≥75% luminal narrowing) suitable for PCI and in the control group (n = 20), with no significant coronary artery lesions (<50% luminal narrowing). One day before and 30 days after the coronarography, all patients performed treadmill exercise stress testing, and the electrocardiographic (ECG) indexes of repolarization were assessed during baseline and at peak exercise intensity. In the control group, the QT interval, QTc (QT-corrected) interval, Tpe interval, and Tpe/QT ratio measured at peak exercise significantly decreased from baseline values (p = 0.001, p = 0.004, p <0.001, and p = 0.017, respectively). Conversely, in interventional patients before the PCI, an increase in the Tpe interval and the Tpe/QT ratio was observed at exercise (p = 0.009, and p <0.001, respectively), with only the QT interval exhibiting a significant decrease from baseline (p <0.001). Thirty days after the PCI, all the ECG arrhythmogenic indexes measured at peak exercise significantly decreased from baseline values, thus assuming the same trend as detected in controls. In conclusion, restoration of blood supply normalized exercise-induced repolarization changes, suggesting that revascularization of previously ischemic myocardium lowers the cardiac arrhythmogenic potential in patients with stable CAD.
Two novel ECG indexes, T peak to T end interval (Tpe interval) and Tpe/QT ratio, have been proven as strong and reliable indicators of transmural dispersion of ventricular repolarization and, consequently, increased risk for malignant ventricular arrhythmias in various cardiac disorders. Observation that in patients with stable coronary artery disease (CAD), those parameters significantly increase at peak exercise, whereas in subjects without history of CAD, they decrease or remain unchanged suggests that exercise-induced myocardial ischemia causes spatial dispersion of ventricular repolarization, exposing patients with CAD to an increased arrhythmogenic risk. Previous studies investigating this phenomenon were limited by the lack of coronary angiography for confirming the existence of CAD and, also, by inclusion of heterogeneous patient population with conditions which alone have a strong arrhythmogenic potential. We aimed to investigate the impact of percutaneous coronary intervention (PCI) on the exercise-induced changes of these electrocardiographic (ECG) indexes in the stable patients with CAD.
Methods
The study enrolled consecutive patients who were scheduled to undergo coronary angiography according to guidelines for the diagnosis and management of patients with stable ischemic heart disease. Because of the impact of gender on arrhythmogenesis, all included subject were men. They were aged >18 years, exhibited sinus cardiac rhythm, and were able to perform treadmill exercise stress testing according to the Bruce protocol. The exclusion criteria were history of myocardial infarction, history of PCI or coronary artery bypass surgery, heart failure (New York Heart Association ≥II), presence of ECG disturbances (bundle branch block, preexcitation, second or third degree AV block, previous implantation of a pacemaker or an implantable cardioverter-defibrillator), administration of classes I and III of antiarrhythmic medications, administration of drugs that interfere with cardiac signal conduction (digitalis, verapamil, diltiazem), administration of drugs that prolong the QT interval (tricyclic antidepressants), thyroid dysfunction, acute or chronic infection, malignoma, renal failure, electrolyte disturbances, cardiomyopathy (dilated, hypertrophic), valvular disease, and echocardiographically established left ventricular (LV) hypertrophy (LV myocardial mass index >134 g/m 2 ) or LV systolic dysfunction (ejection fraction <50%). The study was conducted according to the principles of the Declaration of Helsinki and was approved by the local ethical committee, and all subjects gave written informed consent before entering the study.
On the first day of the study, patients who met the inclusion criteria underwent clinical and echocardiographic examination and treadmill exercise stress testing. The following day, they underwent coronary angiography and, based on the obtained findings, were consecutively included into either of 2 groups: control, consisting of patients with no significant coronary artery lesions (<50% luminal narrowing), and interventional, which included patients with a single-vessel disease suitable for PCI (≥75% luminal narrowing of the left anterior descending [LAD], right coronary artery [RCA], or circumflex artery [CxA]), and with no additional stenosis >50% either on the culprit or the other coronary arteries, including obtuse marginal and diagonal branches. In all patients, the treadmill exercise stress testing was repeated 30 days after the coronarography. Recruitment of patients was conducted until 2 groups with 20 patients in each were completed. Of 76 patients who met the initial entry criteria, 36 patients were excluded from further study, 16 patients with 50% to 75% stenosis in whom conservative treatment was recommended and/or additional functional testing (nuclear stress test, fractional flow reserve) was required to confirm ischemia before PCI, and 20 patients who were candidates for coronary artery bypass surgery according to current revascularization guidelines.
The ECG was recorded in standing position at baseline and at the peak exercise. To avoid diurnal variation, the stress tests were performed during the same time interval (between 9 and 11 a.m. ). Beta blockers were withdrawn 2 days before exercise stress testing. The QT and the QTpeak intervals were measured manually on ECG recordings obtained at a paper speed of 50 mm/s. The Tpe interval was calculated as QT–QT peak. The QT interval was measured in as many of the 12 leads as possible, whereas Tpe interval was assessed in the precordial leads. The Tpe/QT ratio was calculated using the corresponding values from each lead. The measurements were performed in 3 consecutive complexes of each lead, and the resulting average value was finally accepted. The QT interval corrected for heart rate (QTc) was calculated using Fridericia’s formula (QTc = QT/RR 0.33 ). The reported Tpe and QTc values were the maximum obtained values. All measurements were performed independently by 2 experienced investigators blinded to the treatment assignment.
Continuous variables are expressed as mean ± standard deviation or as median (twenty-fifth to seventy-fifth percentile), if their values were not normally distributed (tested by Kolmogorov–Smirnov test). Categorical variables are presented as absolute numbers and frequencies. Comparisons of continuous ECG variables were performed using the nonparametric Wilcoxon signed rank test. The chi-square test was used on comparison for discrete variables. A 2-tailed p value <0.05 was considered significant. For statistical significance of 0.05 and study power of 0.9, the required number of subjects per group was 20. Statistical analyses were performed using Statistical Package for Social Sciences 19.0 (SPSS Inc, Chicago, Illinois).
Results
The 2 groups did not differ significantly in demographic and clinical characteristics ( Table 1 ). In the interventional group, there were 9 patients (45%) with culprit stenosis on LAD, 7 (35%) with culprit stenosis on RCA, and 4 (20%) patients with culprit stenosis on CxA. The average percentage of culprit stenosis was 89 ± 5% (LAD 91 ± 3%; RCA 86 ± 5%; CxA 92 ± 4%). Syntax score in the interventional group was 7.2 ± 3.
| Variable | Control group (n=20) | Interventional group (n=20) | P |
|---|---|---|---|
| Age (year) | 57±8 | 56±8 | 0.399 |
| Body mass index (kg/m 2 ) | 27±3 | 26±3 | 0.510 |
| Diabetes mellitus | 3 (15%) | 3 (15%) | – |
| Hypertension | 14 (70%) | 12 (60%) | 0.507 |
| Hyperlipidaemia | 14 (70%) | 15 (75%) | 0.723 |
| Smoker | 6 (30%) | 7 (35%) | 0.736 |
| Left ventricular mass index (g/m 2 ) | 101±13 | 103±19 | 0.619 |
| Left ventricular ejection fraction (%) | 65±6 | 64±8 | 0.347 |
| Hemoglobin (g/L) | 146±11 | 146±9 | 0.755 |
| Sodium (mmol/L) | 140±3 | 141±2 | 0.552 |
| Potassium (mmol/L) | 4.4±0.5 | 4.4±0.5 | 0.648 |
| Magnesium (mmol/L) | 0.88±0.06 | 0.85±0.07 | 0.323 |
| Creatinine (μmol/L) | 68±13 | 72±13 | 0.139 |
| Glucose (mmol/L) | 5.6±1.4 | 5.9±2 | 0.792 |
| Total cholesterol (mmol/L) | 4.9±1 | 5.2±1.2 | 0.456 |
| (mg/dl) | 189±39 | 201±46 | |
| Triglycerides (mmol/L) | 1.8±1.1 | 1.5±0.6 | 0.323 |
| (mg/dl) | 162±93 | 133±53 | |
| Hs-CRP (mg/L) | 2.59±3.05 | 2.23±2.74 | 0.829 |
We found no differences in the exercise stress parameters (values of baseline and peak exercise heart rate, baseline and peak exercise systolic and diastolic blood pressure, recovery heart rate in third and sixth minute, metabolic equivalents [METs], and exercise duration) between the control and interventional groups, or within the interventional group alone, compared before and after the PCI ( Table 2 ). In 5 control patients, only marginal (1 mm) ST denivelation was observed. In the interventional group, significant ST changes detected before the PCI were completely normalized after the recanalization procedure in 10 of 18 patients, whereas in the remaining 8 patients, only 1-mm ST denivelation was recorded. In these patients, a potential restenosis or significant residual stenosis was excluded using dobutamine stress echocardiography.
| Variable | Control group | Interventional group | ||
|---|---|---|---|---|
| 1 st day | 30 th day | before PCI | after PCI | |
| Heart rate at baseline (beats/min) | 77 (65-87) | 75 (64-87) | 72 (63-81) | 74 (66-79) |
| Heart rate at peak exercise (beats/min) | 141 (128-153) | 139 (130-154) | 134 (120-147) | 141 (129-154) |
| Systolic arterial pressure at baseline (mm Hg) | 129 (117-140) | 130 (122-140) | 131 (118-140) | 133 (120-145) |
| Diastolic arterial pressure at baseline (mm Hg) | 81 (77-90) | 80 (79-85) | 79 (70-90) | 80 (70-89) |
| Systolic arterial pressure at peak exercise (mm Hg) | 169 (150-180) | 175 (167-180) | 161 (140-180) | 171 (157-182) |
| Diastolic arterial pressure at peak exercise (mm Hg) | 77 (70-90) | 80 (70-80) | 75 (70-82) | 75 (70-80) |
| METs | 9.5 (9-10) | 9.9 (9.1-10.2) | 9 (8-10) | 9.6 (8-10) |
| Exercise duration (min) | 7.9 (5-10) | 7.9 (7.3-8.8) | 7.7 (5.7-10) | 8.4 (5.7-10) |
| Heart rate recovery, third minute (beats/min) | 46 (35-42) | 47 (41-53) | 48 (44-53) | 48 (45-50) |
| Heart rate recovery, sixth minute (beats/min) | 50 (44-48) | 54 (50-64) | 55 (50-58) | 59 (58-60) |
| Positive ECG test | 5 (25%) | 5 (25%) | 18 (90%) | 8 (40%) |
| Chest discomfort | 5 (25%) | 3 (15%) | 18 (90%) | – |
| Maximal ST denivelation (mm, M±SD) | 1 | 1 | 1.7±0.45 | 0.42±0.49 |
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