T Peak – T End Interval Alteration as Parameter of Successful Fibrinolysis in Patients with ST Segment Elevation Acute Myocardial Infarction

Background: In STEMI patients, the duration of action potential dispersion occurs between normal and ischemic tissue due to the lengthening of the refractory period, causing transmural dispersion of repolarization, which could be detected with Tp-Te interval prolongation on the electrocardiogram (ECG). Benefits of fibrinolytic therapy in patients with STEMI has been demonstrated, with reduced mortality significantly and improve coronary patency in order to increase myocardial perfusion. The goal of this study was to determine Tp-Te interval alteration in STEMI patients before and after the fibrinolytic therapy between successful fibrinolysis compared to failed fibrinolysis. Method: Cross-sectional study was conducted to collect ECG from medical records at Dr. Sardjito General Hospital in January–September 2016. STEMI patients with onset less than 12 hours whom reperfused with fibrinolytic therapy were registered. Tp-Te interval was measured before, soon after (0 minute), and 30 minutes after fibrinolysis with successful and failed results. The unpaired t-test analysis was used to compare Tp-Te interval alteration after fibrinolysis. Then, ΔTp-Te cut-off value was determined to find sensitivity and specificity based on ROC. Result: Among 84 patients enrolled in this study, 46 patients with successful fibrinolysis and 38 patients with failed fibrinolysis. Both of groups had Tp-Te interval prolongation before fibrinolysis, with mean value of 120.30 ± 13.02 ms in successful fibrinolysis group and 118.57 ± 15.24 ms in failed fibrinolysis group. In successful fibrinolysis group, Tp-Te interval reduced significantly with ΔTp-Te value of 17.55 ± 13.35 ms on 0 minute and 20.85 ± 15.62 ms on 30 minutes after fibrinolysis, while in failed fibrinolysis group there was not a decrease of Tp-Te interval with ΔTp-Te value of -0.77 ± 11.00 ms on 0 minute (p <0.001) and -1.53 ± 14.35 ms on 30 minutes after fibrinolysis (p <0.001). Cut-off value ΔTp-Te 20 ms had sensitivity 52.2% and specificity 94.7% based on ROC, with strong discriminator value of AUC (0.888). Conclusion: There was a greater reduction of Tp-Te interval in STEMI patients with successful fibrinolysis compared to failed fibrinolysis, so it may be used as a alternative parameter of successful fibrinolysis.


INTRODUCTION
Coronary artery disease (CAD) is still the number one cause of mortality worldwide, with more than 7 million deaths due to CAD each year, which represented 12.8% of all causes of death. 1 ST elevation acute myocardial infarction (STEMI) is a clinical syndrome, which is a spectrum of acute coronary syndrome (ACS), which is defined by the characteristic symptoms of myocardial ischemia related with ST segment elevation in electrocardiography (ECG) and afterward followed with myocardial necrosis.
Myocardial ischemia causes metabolic changes and ion exchange.This cellular processes will lengthen repolarization and shorten the action potential in myocardium ischemic area. 2 Differences in the duration of action potentials between normal and ischemic tissue due to the lengthening of the refractory period raises electrophysiological inhomogenity in the ventricular myocardium and improves transmural dispersion of repolarization.This process may act as a predisposing factor reentry arrhythmias.This arrhythmia is the most common cause of death in STEMI patients. 3,4veral studies show a decrease in mortality due to STEMI, along with the increase use of reperfusion therapy, the availability of percutaneous coronary intervention (PCI) facilities, modernantithrombotic therapy and secondary prevention. 5Benefits of fibrinolytic therapy in patients with STEMI has been demonstrated, with significant reduction of mortality by administration of fibrinolytic therapy. 6aditional variables that had been used to assess response to fibrinolytic therapy was still less precision. 7spersion of repolarization increase can be detected by a peak interval prolongation Tpeak -Tend (Tp-Te) on 12 lead electrocardiogram examination.Tp-Te interval is a time interval measured from the top of the T wave to the end of the T wave In some studies, Tp-Te interval is proposed as a marker of increased risk of ventricular arrhythmias in patients with various conditions, including acute myocardial infarction. 8,9,10Another study said that STEMI patients who performed the reperfusion with primary PCI, rescue PCI and successful fibrinolysis, duration of repolarization is significantlydecreased as assessed by Tp-Te.

Tp-Te Interval Measurement
Tp-Te measurements performed on precordial leads.Measurements were done using standard ECG at V 5 , V 4 and V 6 lead.In previous study, V 5 lead is a measurement having high precision(Figure 1).If the calculation is not possible in V 5 , the alternative calculation of Tp-Te interval in a sequence can be calculated from V 4 and then V 6 . 13,14In the case of the T wave disturbed by waves U, Te is defined as nadir between the T wave with wave U. T wave with low voltage <0.1 mV is not analyzed. 15

Statistical Analysis
The data obtained will be analyzed using the software SPSS for Windows version 18.0.
The baseline characteristics are shown as mean or amount in figures and percentages.A comparative analysis was conducted between the 2 groups with paired t test in each group (pre and post-fibrinolysis) and unpaired t test to compare between the two groups of fibrinolysis success and failure or test Mann-Whitney and Wilcoxon two numeric variables when the data is not normal to see whether there is a significant difference between the two variables with a proficiency level of significance value of p < 0.05.Analysis of confounding variables will be performed by multivariate analysis with multiple linear regression analysis.Further changes in the value, expressed in delta, is used to find the limit value using receiver operator characteristics (ROC) curves then prepared a sensitivityspecificity curve to help determine the sensitivity and specificity of the limit value.

RESULT
In this study there were 84 patients enrolled and met the inclusion and exclusion criteria.It was then divided into two following groups, successful fibrinolysis with 46 patients (54.76%) and failed fibrinolysis in 38 patients (45.24%).Of the subjects of this study, there were a total of 77 male patients and 7 (8.33%)patients were female.The mean age at all subject was 56.63 ± 10.023 years.Average onset all the subjects were 4.36 ± 2.143 hours.Table 1 shows the baseline characteristics based on fibrinolysis results.
In this study, we obtained Tp-Te interval prolongation prior to the action of fibrinolysis in both groups of subjects, i.e. both in successful fibrinolysis group and failed fibrinolysis group, 120.30 ± 13.02 ms and 118.57± 15.24 ms, respectively.Table 2 shows the comparison of Tp-Te interval comparison before fibrinolysis, 0 minute, and 30 minutes after fibrinolysis in successful fibrinolysis group and failed fibrinolysis group.
In this study, Tp-Te interval evaluation was performed at 0 minutes (instantaneous) and 30 minutes after fibrinolysis.The Tp-Te interval value after successful fibrinolysis experienced significant reduction, both at 0 minute and at 30 minutes after fibrinolysis, 17.55 ± 13.35   special attention in cardiovascular disease prevention program.In addition, a high percentage of smokers subjects associated with increased mortality and arrhythmias. 14e mean onset of STEMI in each group was

DISCUSSION
The baseline characteristics of the subjects of this study showed that the percentage of

CONCLUSION
There was a greater reduction of Tp- parameter and marker of successful reperfusion.11However, until now there is no study evaluating the Tp-Te interval and the change in STEMI patients who performed fibrinolysis with successful and failed results and propose amendments Tp-Te interval as a parameter of successful fibrinolysis.The aim of this study was to determine Tp-Te interval alteration in STEMI patients before and after the fibrinolytic therapy between successful fibrinolysis compared to failed fibrinolysis.METHODS This is an analytic observational study with cross sectional method on two unpaired groups.Data were obtained retrospectively to see Tp-Te interval change in STEMI patients who received fibrinolysis with successful and failed results.The study took place in the Medical Record Installation Dr. Sardjito General Hospital in January-September 2016 for collection of secondary data.Subjects Inclusion criteria in this study were STEMI patient at first time with onset within 12 hours and receive reperfusion therapy with fibrinolysis, aged 18-80 years, with complete data on the patient's medical record.While exclusion criteria of this research is atrial fibrillation, atrial flutter, ECG with LBBB, total AV block, pacing rhythm, or pre-excitation, chronic heart failure, valvular heart disease, congenital heart disease, electrolyte disturbances, drug history amiodarone and digitalis, duration QRS more than 12 ms in the ECG, and T-wave in the ECG difficult to assess.ECG Recording ECG recording done by using a standard 12 lead ECG with a speed of 25 mm / sec and gain of 10 mm/mV by medical or paramedical personnel in the emergency department of Dr. Sardjito General Hospital accordance with the standard operating procedures of ECG collection.ECG data is used in STEMI patients with fibrinolysis action is ECG data when admission or pre-and post-fibrinolysis counted 90 minutes since the fibrinolysis started.ECG data is scanned in order to be processed digitally with a Canon brand scanner Canoscan Lide 110.

4.28 ± 2 .
126 hours on the successful fibrinolysis group and 4.45 ± 2.19 hours in the failed fibrinolysis group.There are significant differences in infarct location of the two groups, in which the percentage of anterior infarct location in the failed fibrinolysis group more than the successful fibrinolysis.This corresponds with the results of previous studies by Lopeset al. 16 that the anterior infarct location into one of the predictors of failed fibrinolysis.Nevertheless, infarct location does not affect the Tp-Te interval at baseline.This study showed an increase in ventricular repolarization dispersion in acute phase of STEMI, assessed with intervals Tp-Te.There is no consensus regarding the normal value Tp-Te interval, but on the setting of myocardial infarction, value Tp-Te interval of more than 100 ms are considered prolonged and associated with increased risk there was little Tp-Te interval prolongation, with the changes obtained was equal to -0.77 ± 11.00 ms at 0 min and -1.53 ± 14.35 ms at 30 minutes after fibrinolysis.Table 3 shows the comparison of Tp-Te interval changes (ΔTp-Te) based on the outcome of fibrinolysis.The ROC curve showed that Tp-Te interval changes (ΔTp-Te) had a strong discriminator value with area under the curve (AUC) of 0.888.In this study, the cut-off value proposed as a parameter of successful fibrinolysis based on the ROC curve is 20 ms.The value gave 52.2% sensitivity and 94.7% specificity, based on ROC curve analysis.

Figure 2
Figure 2 and 3 showed the ROC analysis.

Figure 3 .Figure 2 .
Figure 3. Sensitivity and specificity chart of ΔTp-Te interval at 30 minutes after fibrinolysis ms and 20.85 ± 15.62 ms respectively.Tp-Te interval reduction was not found in the failed fibrinolysis group, otherwise Table1.Baseline characteristics based on fibrinolysis results in STEMI patients

Table 2 .
Tp-Te interval comparison before fibrinolysis, 0 minute, and 30 minutes after fibrinolysis based on the success of fibrinolysis Comparison of Tp-Te interval changes (ΔTp-Te) based on the outcome of fibrinolysis *Unpaired T test, Tp-Te interval in units of milisecond (ms) Grupi C., Dina C.H., De Gois A.F., Hajjar L.A., Ayub B., et al. 2006.[QT interval