Correlation between Tp-Te Interval and Myocardial Blush Grade Value in Anterior ST Elevation Myocardial Infarction Patient

Background: Clinical manifestations of coronary herat disease (CHD) may be an ST-Elevation Myocardial Infarction (STEMI). In STEMI condition, there is a metabolic disorder and ion exchange disturbance which causes dispersion of transmural repolarization, as well as micro coronary circulation disturbance involving mechanism of microvascular dysfunction. The Tp-Te interval is an electrocardiogram paramener that could be described as the transmural dispersion of repolarization. Assessment of Myocardial Blush Grade (MBG) is a coronary angiography densitometry method that can be used to assess microvascular dysfunction. This study aims to examine the correlation between Tp-Te interval and MBG in anterior STEMI. Methods: The research desgin is cross sectional. Data were taken consecutive from August to November 2017. The Tp-Te interval assessment was performed on the basis of an electrocardiogram record from the subjects. The MBG value assessment was performed using a Quantitative Blush Evaluator (QuBE) computer program based on coronary angiography. The Tp-Te interval is divided into 2 groups: Tp-Te interval > 94 ms and Tp-Te interval ≤ 94 ms. The MBG values are divided into 3 groups: MBG QuBE 1, MBG QuBE 2 and MBG QuBE 3. The assessment of Tp-Te interval and MBG value was performed by observer in intra-observer which were acknowledged based on Kappa and blindness conformity test results against patient clinical data. Pearson correlation test was used to analyze the correlation between Tp-Te interval and MBG value, while logistic regression test was used for multivariate test. Results: Of the total 32 study subjects, there were 23 subjects with Tp-Te interval >94 ms and 9 subjects with Tp-Te interval ≤94 ms. There was a negative correlationwith moderate strength between the Tp-Te interval and the MBG value in the anterior STEMI patients (r =-0.501, p =0.004). There was a prevalence ratio of 4.304 between Tp-Te interval >94 milliseconds against MBG QuBE 1 (95%CI: 1.264-14.658, p <0.001). Multivariate tests showed Tp-Te intervals consistently as independent risk factors for MBG values in subjects with anterior STEMI. Conclusion: There is a negative correlation with moderate strength between the Tp-Te interval and the MBG value in the anterior STEMI patients.


INTRODUCTION
Coronary Heart Disease (CHD) is one of the leading causes of death in the world. 1 Atherosclerosis is one of the most common causes of CHD.
2 Clinical presentation of CHD may be an ST Segment Elevation Myocardial Infarction (STEMI).A STEMI condition is an emergency condition based on patomechanism of intra coronary thrombus formation.The formation of an intra coronary thrombus will cause regional perfusion disorders in the myocardium and may cause a myocardial infarction condition.3   In STEMI condition there is a metabolic change and ion exchange disturbance.The process of change occurring at the cellular level causes a change in the repolarization period and the action potential in the infarcted myocardium.4 These repolarization differences will lead to electrophysiological heterogeneity in the myocardium and increase transmural repolarization dispersion.

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The transmural dispersion of repolarization due to myocardial infarction can be assessed through the Tpeak-Tend interval (Tp-Te interval) on the electrocardiogram (ECG).The Tp-Te interval is the time interval measured from the peak of the T wave to the end of the T wave on the ECG. 6,7In STEMI there is also a micro-circulatory disorder involving the process of microvascular dysfunction.Microvascular dysfunction can be assessed using both invasive and noninvasive assessments.In the invasive assessment, the assessment of microvascular dysfunction can utilize Myocardial Blush Grade (MBG) assessment that provides a direct description and evidence of microcirculation coronary and assesses the occurrence of microvascular dysfunction.Coronary angiography video capture was performed at the start of a 5-10 mL contrast medium injection, in which the video was taken using a speed cinefilm of 12.5-25 frames per second, with RAO coronary angiography projection 20° -Caudal 20° and using unzoom technique.Coronary angiography retrieval and recording time is performed more elongated, starting from charging contrast media in epicardial coronary artery vessels to phases where the flow of contrast media fills the coronary sinus.The coronary angiography results was analyzed by calculating the MBG value using the QuBE program by a cardiologist-interventionist consultant who had competence in MBG value assessment and have done intraobserver consistency test.
The data will be analyzed using SPSS for Windows software version 22.0.The correlation test was performed to find the correlation between Tp-Te interval and MBG value using Pearson correlation test and multivariate analysis using logistic regression test.

RESULTS
There are 32 research subjects that met the inclusion and exclusion criteria of the study.The study period was from August 2017 to November 2017.During the study period, there were 44 subjects who met the inclusion criteria, but as many as 12 subjects were excluded because of previous history of coronary heart disease, previous STEMI history, chronic heart failure and has a picture of ECG in the form of atrial fibrillation and flat T wave.
From the 32 subjects of the study, consisted of male gender as many as 27 people (84%) and women as many as 5 people (16%).The subjects with hypertension were 24 subjects, diabetes mellitus were 18 subjects, dyslipidemia were 13 subjects and smoker were 16 subjects.The median BMI value in this study was 25.92 kg / m2 (19.75 -29.75)  and the median value of ischemic time was 6.00 (3.00-96.00)hours.In this study, there were 6 subjects who were undergone previous fibrinolysis, with successful fibrinolysis results of 5 subjects and fibrinolysis failed by 1 subject.The infarct area was found to be ≥ 4 EKGs on 23 subjects and ≤ 3 EKGs on 9 subjects.
The mean value of the Tp-Te interval was 107.15 ± 19.66 ms and the mean value of MBG in this study was 7.84 ± 2.94 AU.In this study, we found the involvement of coronary artery of LAD segment in 22 subjects, as well as blood vessel involvement in coronary segment of LAD and LCX in 10 subjects.Sub analysis was performed to know about Tp-Te interval is an independent variable to MBG value.A univariate analysis of the Tp-Te interval group was performed, with the Tp-Te interval group divided into 2 groups, those with the Tp-Te ≤ 94 millisecond interval and the Tp-Te interval group> 94 milliseconds based on the cut-off interval Tp-Te by previous research.
12 Description of the characteristics of both groups in the form of hypertension, diebetes, smoking, body mass index, previous fibrinolysis, extent of infarction and involvement of coronary artery lesions was shown in table 2

Multivariate
analysis was performed on variables that could potentially be a confounding factor with a value of p <0.25 in univariate analysis.Multivariate analysis in this study included age, diabetes mellitus, dyslipidemia, smoking, body mass index and previous fibrinolysis (Table 5).Based on the result of multivariate analysis found that Tp-Te interval variable was independent predictor to MBG value with prevalence ratio 2.471 (95%CI: 1.283-12.725,p =0.035).

DISCUSSION
The variables that differed significantly between the Tp-Te ≤94 ms and the Tp-Te interval >94 ms groups included diabetes mellitus, smoking and previous fibrinolysis.The variables that had statistically significant differences between the MBG QuBE groups were the smoking and fibrinolysis.In this study we found 15 subjects with smoking in the MBG QuBE 1 group, compared with 1 study subjects with smoking in the MBG QuBE 2 group (p =0.014).This is in accordance with the previous study which showed smoking may cause a decrease in coronary microvascular function, which is associated with the inflammatory response and anatomical changes in the microvascular due to various substances within tobacco.

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In the MBG QuBE 1 group, there were only 2 subjects who underwent fibrinolysis, while in the MBG QuBE 2 group, 4 subjects were subjected to fibrinolysis (p = 0.023).In IMA-EST patients, fibrinolysis may improve myocardial condition by a decreased in the area of infarction in the myocardium.14,15   In the correlation test between the Tp-Te interval and the MBG value using the Pearson correlation test, there was a moderate-strength negative correlation between the Tp-Te interval and the MBG value (r = -0.501,p = 0.004).It shows the longer Tp-Te interval the lower the MBG value.Acute myocardial infarction causes changes in action potential through interference of intracellulare K + , Na + and intra-cellular Ca 2 + ions.The ion exchange disturbance will cause a change in the heterogeneity of myocardial repolarization, which increases the repolarization difference between epicardium cells, endocardium and myocardium M cells.Such increased repolarization will lead to an increase in the dispersion of myocardial transmural repolarization.The transmural repolarization dispersion can be represented in the ECG record of the Tp-Te interval increasingly elongated. 16This is in accordance with previous research that showed an extension of Tp-Te interval in STEMI patients compared with healthy control group. 16 In this study, the factors of age, diabetes mellitus, dyslipidemia, smoking, body mass index and previous fibrinolysis were calculated as confounding factors of Tp-Te interval and MBG value.Acute hyperglycaemia and diabetes mellitus did not affect the vasodilatory response of the coronary microcirculatory, thus causing no coronary artery micro-disturbance and microvascular dysfunction. 20An increase in BMI >30 and obesity are associated with a decrease in coronary microvascular density, which contributes to microvascular dysfunction, decreased myocardial blood flow, myocardial metabolic disorders, diastolic dysfunction and increased risk of heart failure. 21Smoking can also cause a decrease in coronary blood flow through decreased rates of hyperemic coronary blood flow. 22Research by Mikelsone et al. (2011) showed that in the group of adult patients who smoked chronically with mean duration of smoking >20 years associated with higher degree of microvascular dysfunction.

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The fibrinolysis is the administration of a medical agent to lyse or dissolve blood clots that acutely obstruct the coronary arteries in the STEMI, thus providing an improvement in myocardia.Its improvement decreased myocardial and microcirculation disturbance and improved microvascular dysfunction.
In this study there is a limited time research, so the number of research subjects recruited in this study has not met the number of subjects according to the calculation of estimated number research subjects.Another limitation of this study is the coronary angiography performed for MBG assessment, contrast media injection in this study has not used contrast media injector tool, performed manually, due to unavailability of contrast media injector device in coronary vein, so the pressure and speed of injection contrast media at the time of coronary angiography does not meet the standard.

CONCLUSION
There was a negative correlation with moderate strength between the Tp-Te interval and the MBG value in the anterior STEMI patients and the Tp-Te interval was an independent variable against the MBG value.

Figure 1 .
Figure 1.Scatter-plot graphic the correlation between Tp-Te interval and MBG value in anterior STEMI patients showed negative correlation with moderate strength (r =-0.501, p =0.004).

Table 2 . Univariate analysis of variables that affect the Tp-Te interval on the anterior
** Abnormal data distribution, shown in median and percentile.Data were analyzed with Mann Whitney Test.

Table 4 . Univariate analysis between Tp-Te interval and MBG value in the anterior STEMI patients
Then a univariate analysis was performed between the Tp-Te interval and the MBG value and the result was shown in Table4.

Multivariate analysis of factors affecting MBG values in anterior STEMI subjects
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