ABSTRACT

Aim:

Myocardial bridge (MB) is generally known as an asymptomatic and benign anomaly, however, it can cause serious clinical conditions such as exercise-induced ventricular tachycardia and sudden death. Tp-e interval is the distance between the peak and the end of the T wave in electrocardiography. Tp-e/QT and Tp-e/QTc ratios are used as electrocardiographic indicators of ventricular arrhythmias. We have studied the effect of coronary angiographic features (the degree of stenosis and length of MB) of MB on myocardial repolarization parameters.

Methods:

The study group consisted of 53 patients with isolated MB and 58 patients with normal coronary arteries.

Results:

The QT interval and QTc were similar between the groups, however, Tp-e interval (92.72±14.72 and 79.59±12.12, respectively; p<0.001) and Tp-e/QT (0.24±0.041 and 0.21±0.025, respectively; p<0.001) and Tp-e/QTc (0.22±0.037 and 0.19±0.025, respectively; p<0.001) ratios were found to be significantly increased in MB group compared to the control group. In the comparison of the MB patients with critical and those with noncritical stenosis, Tp-e interval (100.69±10.79, 80.57±11.25, respectively; p<0.001) and Tp-e/QT (0.266±0.033, 0.219±0.037, respectively; p<0.001) and Tp-e/QTc (0.244±0.029, 0.196±0.027, respectively; p<0.001) ratios were higher in the MB with critical stenosis group.

Conclusion:

Our results indicate that these parameters can be practical ECG markers of ventricular arrhythmias in patients with MB.

Introduction

Myocardial bridge (MB) is an inborn coronary anomaly which is defined as an abnormal intramyocardial course of a segment of a major coronary artery (1). Although MB can be seen in any of the epicardial coronary arteries, it is mostly observed in the left anterior descending artery with an incidence of 67-98% (2,3). In autopsy series, angiographically detected MB was reported to have a prevalence between 0.5% and 16% The rate of angiographic bridging is <5%, attributable to thin bridges causing little compression. In subjects with angiographically normal coronary arteries, the use of provocation tests may enhance systolic myocardial compression and thereby reveal MBs in ≤40% of cases and the length was found to be between 4 to 80 mm (4). MB is generally known to be an asymptomatic and benign anomaly, however, it can cause serious clinical conditions, such as severe myocardial ischemia, acute myocardial infarction, syncope, exercise-induced ventricular tachycardia and atrioventricular block, acute left ventricular failure, and sudden death (5,6).

Myocardial repolarization is evaluated by QT interval (QT), corrected QT interval (QTc), QT dispersion (QTd) and transmular dispersion of repolarization (TDR). Tp-e interval is the distance between the peak and the end of the T wave in electrocardiography (ECG) and it is assumed as an index for TDR (7). Tp-e/QT and Tp-e/QTc ratios are used as electrocardiographic indicators of ventricular arrhythmias (8). We studied the effect of coronary angiographic features (the degree of stenosis and length of MB) of MB on myocardial repolarization parameters.

Methods

Study Population

A total of 165 consecutive patients, who were referred to our clinic for diagnostic coronary angiography (CAG) between January and November 2015, were prospectively enrolled in the study. The study group consisted of 53 patients with isolated MB and 58 patients with normal coronary arteries. Patients with coronary artery disease (CAD), left ventricular systolic dysfunction, pulmonary hypertension, chronic obstructive pulmonary disease, diabetes, valvular disease, cardiomyopathy, abnormal thyroid function test, electrolyte imbalance, renal failure, and abnormal ECG, as well as those who had a pacemaker and on antiarrhythmic drug therapy were excluded. Patients whose ECGs could not be analyzed clearly were also excluded.

Coronary Angiography

The femoral route was used in all patients. The images were recorded in digital angiography system (ACOM.PC; Siemens, Germany and Digital Radiography System, Toshiba DSR, Japan) with a speed of 15 frame per second. The contrast agent lopromide (Ultravist 370, Bayer Pharma AG, Berlin, Germany) was used. The conventional CAG images were evaluated by three independent cardiologists. MB was defined as an abnormal intramyocardial course of a segment of a major coronary artery. The length and degree of stenosis (%) of the bridged segment were calculated angiographically by quantitative coronary analysis. The patients were allocated into two groups according to the degree of stenosis including MB with critical (70% or greater stenosis) and noncritical stenosis (stenosis less than 70%) groups.

Electrocardiography

Twelve-lead ECG was performed in each patient in the supine position by a conventional ECG device (Nihon Kohden, Tokyo, Japan) with a speed and amplitude of 25 mm/s and 10 mm/mV, respectively. The ECG measurements were evaluated by two independent cardiologists who were blinded to the clinical data of the patients. In order to minimize the measurement errors, an electronic caliper was utilized. The mean value of the measurements was taken in order to increase accuracy. Heart rate and rhythm were determined and Tp-e interval and Tp-e/QT and Tp-e/QTc ratios were measured. QT interval was defined as the distance between the onset of QRS and the end of T wave where it intersects the isoelectric line. QTc was calculated by Bazett’s formula (9). The Tp-e interval was defined as the distance between the peak and the end of the T wave (Figure 1) (10). The measurement of Tp-e interval was performed using precordial leads as previously defined (11). The intraobserver and interobserver coefficients of variation [the standard deviation (SD) of differences between two observations divided by the mean value and expressed as a percentage] were found to be <5%.

Echocardiography

Transthorasic echocardiography was performed in all patients in the left lateral decubitus position by a Vivid 3 echocardiography device (GE Medical Systems, USA). The parasternal long and short axis, apical four- and two-chamber images were taken and evaluated according to the criteria of the American Society of Echocardiography (12).

Statistics Analysis

The normal distribution of data was tested by the 1-sample Kolmogorov-Smirnov test. Continuous variables are presented as mean ± SD. Categorical variables are presented as counts. All statistical comparisons were performed using the two-sided Student’s t-test. Categorical variables were compared using the chi-square test or Fisher’s exact test for small samples. Pearson’s correlation was used for numerical data. Spearman’s correlation was used for nominal data. A p value of less than 0.05 was considered statistically significant. Multivariate logistic regression model was performed to determine the effect of independent risk factors for prolonged Tp-e interval. Statistical analyses were performed using SPSS 22.0 software for Windows (SPSS Inc, Chicago, IL).

Results

A total of 165 patients were evaluated initially and after exclusion of 54 patients, 111 patients were included in the study. The number of patients with MB and controls was 53 and 58, respectively. The general characteristics of the study groups are shown in Table 1. 49 of the participants were female (44%) while 62 were male (56%) and the average age of the participants was 54.66±9.53 years in MB group and 60±9.15 years in the control group. Age and gender distribution did not differ between the groups. There were no significant differences between the groups in terms of baseline laboratory and clinical characteristics. The length of MB was found to be 15.1±3.7 mm in the MB patient group and the degree of diameter reduction in the bridged segments was found to be 69±15.4%. In MB group, the number of patients with critical (70% or greater stenosis) and non-critical stenosis (stenosis less than 70%) was found to be 32 (60.7%) and 21 (39.6%), respectively. No significant differences were observed in terms of conventional echocardiographic measurements between the groups (p>0.05) (Table 1). The QT interval and QTc were similar between the groups, however, Tp-e interval (92.72±14.72 and 79.59±12.12, respectively; p<0.001), Tp-e/QT (0.24±0.041 and 0.21±0.025,respectively; p<0.001) and Tp-e/QTc (0.22±0.037 and 0.19±0.025, respectively; p<0.001) ratio were found to be significantly increased in MB group compared to the control group (Table 1). In the comparison of the MB patients with critical and noncritical stenosis, Tp-e interval (100.69±10.79, 80.57±11.25, respectively; p<0.001) and Tp-e/QT (0.266±0.033, 0.219±0.037, respectively; p<0.001) and Tp-e/QTc (0.244±0.029, 0.196±0.027, respectively; p<0.001) ratios were higher in the MB with critical stenosis group compared to the ones with noncritical stenosis (Table 2). There was not any statistically significant difference between control and MB with noncritical stenosis groups in terms of ECG parameters. Multivariate analysis demonstrated that the degree of diameter reduction (standardized b coefficient=0.681; p<0.001) is an independent predictor of a prolonged Tp-e interval in the multivariate stepwise logistic regression model (Table 3).

Discussion

Our study is important as it showed significantly increased Tp-e interval and Tp-e/QT and Tp-e/QTc ratios in MB patients with angiographically detected critical stenosis, although there was not any significant relationship between these parameters and bridge length. These findings can be an evidence of relationship between ventricular repolarization change and MB. These results can also contribute to the explanation of pathophysiologic mechanisms of ventricular arrhythmias and the increase in the prevalence of sudden cardiac death among patients with MB.

In some studies, it was shown that increased repolarization dispersion alone can lead to ventricular arrhythmias (13,14). In a study by İlgenli et al. (15) the ventricular arrhythmias were reported to have a significant correlation with longer Tp-e intervals.

The duration of action potential (AP) is longer in midmyocardial M cells than in the other myocardial cells (16). The repolarization is completed first in epicardial cells. The end of epicardial AP indicates the peak of the T wave and the end of the midmyocardial AP indicates the end of the T wave. As a result, the Tp-e interval shows the transmural dispersion of repolarization (16). In previous studies, the relationship of increased Tp-e interval with Brugada syndrome, myocardial infarction treated by primary percutaneous coronary intervention (PCI), long QT syndrome, hypertrophic cardiomyopathy (HCM) (11-14), obstructive sleep apnea syndrome (17), mitral valve prolapsus (10), heavy smoking (15), and exercise in MB patients (18), was studied.

The characteristic angiographic finding of MB is systolic stenosis (milking effect). On the other hand, the intracoronary ultrasound and Doppler studies have shown that  coronary obstruction also involves the diastolic period. Additionally, these studies indicated that a decrease in systolic minimal lumen diameter (MLD) greater than 70% and a decrease in mid to late diastolic MLD more than 35% indicate a significant obstruction in the bridged segment (19,20). Exercise and emotional stress increase heart rate and contractility leading to increased oxygen demand. These conditions can trigger ischemia in patients with MB.

The data about the relationship between MB and atherosclerosis is scant. In contrast to the location of the MB, the proximal part of the bridged segment has been reported to be more prone to the atherosclerotic process (21). Two main reasons for atherosclerosis in the proximal part have been shown to be increased shear stress on the vessel wall and distribution of blood flow (22). Additionally, the vasoactive agents (endothelin-1, endothelial nitric oxide synthase, angiotensin-converting enzyme) were detected to be in higher concentrations in the proximal part than in the bridged segment (23).

Another probable mechanism of ischemia in patients with MB is coronary vasospasm (24). The coronary vasospasm has been shown to be present in the proximal part of the bridged segment (25). This may be due to vasoactive agents released from this part. The recent histopathologic studies indicated that myocardial fibrosis and interstitial edema can occur in the area of MB (26). Similarly, in a report by Hostiuc et al. (27), significant myocardial fibrosis and interstitial edema were demonstrated in the bridged segment in patients who had sudden cardiac death. Death in these patients was emphasized to be related to increased electrical instability due to myocardial fibrosis.

The relationship of Tp-e interval and Tp-e/QT and Tp-e/QTc ratios with myocardial ischemia was studied previously by some researchers. Xiao et al. (28) reported a significant decrease in Tp-e and QTc intervals, and Tp-e/QT ratio in patients with ST segment elevation myocardial infarction (STEMI) after successful thrombolytic therapy. In a study by Tatlisu et al. (29), Tp-e interval was shown to be a predictor of target vessel revascularization and death in patients with STEMI.

The shortening of Tp-e interval was demonstrated in STEMI patients with successful reperfusion who were treated by primary PCI (30). Aksan et al. (18) showed a significant increase in Tp-e interval and Tp-e/QT ratio after exercise in patients with MB. The findings of these two studies indicated that the percentage of MB stenosis and length of the bridged segment are the predictors of lengthening of Tp-e interval. In contrast, in our study, we did not see any significant relationship between the length of the bridged segment and the repolarization parameters. Here, we can speculate that the length of the bridged segment may not have a more important role in producing ischemia than the degree of stenosis.

Study Limitations

The number of study population is small. More accurate results can be achieved in a larger study group. Additionally, the relationship of Tp-e interval with ventricular arrhythmia incidence could not be evaluated. As a result, the prognostic role of increase in Tp-e interval and Tp-e/QT and Tp-e/QTc ratios in this patient group remained unclear.

Conclusion

In our study, we tried to figure out the relationship between angiographically detected MB and echocardiographic repolarization parameters. The Tp-e interval and Tp-e/QT and Tp-e/QTc ratios were found to be significantly increased in MB patients with 70% or greater stenosis. As a result, the presence of critical stenosis in the bridged segment should alert the physician about the deadly complications such as ventricular arrhythmias and sudden cardiac death.

Additionally, our results may indicate that these parameters can possibly be practical ECG markers of morbidity and mortality in patients with MB.

Ethics

Ethics Committee Approval: The study has been approved by Erzurum Region Training and Research Hospital Ethics Committee. Informed Consent: written informed consent was obtained from each participant.

Peer-review: Externally peer-reviwed.

Authorship Contributions

Surgical and Medical Practices: Erkan Yıldırım, Kamuran Kalkan. Concept: Erkan Yıldırım, Emrah İpek. Design: Erkan Yıldırım, Emrah İpek. Data Collection or Processing: Erkan Yıldırım, Emrah İpek, Kamuran Kalkan. Analysis or Interpretation: Erkan Yıldırım, Mustafa Öztürk, Hikmet Hamur. Literature Search: Mahir Cengiz, Erkan Yıldırım. Writing: Erkan Yıldırım, Emrah İpek.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.