European Journal of Cardiovascular Medicine

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, accounting for approximately 17.9 million deaths annually, representing nearly 32% of all global deaths.¹ Among these, ischemic heart disease constitutes the major burden, with acute myocardial infarction (AMI) being a critical and life-threatening manifestation.² ST-elevation myocardial infarction (STEMI) being a life-threatening form of acute coronary syndrome requiring prompt reperfusion therapy to reduce myocardial damage and mortality.^3,4

Although primary percutaneous coronary intervention (PCI) is the preferred strategy where available, fibrinolytic therapy remains a vital treatment modality, particularly in resource-limited settings including India, where timely PCI is not feasible Successful fibrinolysis, is traditionally assessed by ST-segment resolution, relief of chest pain, and

reperfusion arrhythmias; however, these markers have

limitations.^5,6 Therefore, newer non-invasive electrocardiographic markers such as the T peak–T end (Tp–Te) interval, which reflects ventricular repolarization dispersion, have emerged as promising indicators of successful myocardial reperfusion.^7,8

The Tpeak–Tend interval is defined as the time interval between the peak of the T wave and the end of the T wave on a surface electrocardiogram. It is considered an index of transmural dispersion of repolarization, representing differences in repolarization times among epicardial, mid-myocardial (M cells), and endocardial layers of the ventricular myocardium.⁹ In STEMI, myocardial ischemia increases repolarization heterogeneity, resulting in prolongation of the Tp–Te interval, whereas successful reperfusion restores electrical stability and shortens this interval.^10,11 Although ST-segment resolution remains the standard marker of successful fibrinolysis, it has important limitations.¹² Recent studies have shown that reduction in the Tp–Te interval after fibrinolytic therapy correlates with successful reperfusion, lower risk of ventricular arrhythmias, and better clinical outcomes.^13,14 However, evidence from the Indian population remains limited. Therefore, this study was undertaken to evaluate the reduction in the Tp–Te interval as a simple, non-invasive marker of successful fibrinolytic therapy in STEMI patients at a tertiary care centre in Central India.

After obtaining approval from the Institutional Ethics Committee and written informed consent was obtained from all participants or their legally authorized representatives, hospital-based, observational, cross-sectional study was carried out in the Department of General Medicine in collaboration with the Department of Cardiology at a tertiary care teaching hospital in Central India. A total of 119 consecutive adult patients (18–80 years) with STEMI who underwent fibrinolytic therapy within 12 hours of symptom onset and had both pre-fibrinolytic and post-fibrinolytic 12-lead ECGs available for analysis were enrolled. Patients with non-STEMI or unstable angina, prior PCI or CABG, significant baseline arrhythmias, severe comorbid conditions (including end-stage renal disease, liver failure, or terminal illness), incomplete or poor-quality ECG recordings precluding accurate measurement of the T peak–T end (Tp–Te) interval, pregnant or lactating women, and those unable to provide informed consent were excluded from the study.

Eligible STEMI patients underwent detailed clinical evaluation, baseline laboratory investigations, and a 12-lead ECG before fibrinolytic therapy. Standard thrombolytic treatment and guideline-directed medical therapy were administered as per institutional protocol. A repeat ECG was performed 90 minutes after fibrinolysis to assess ST-segment resolution and measure the T peak–T end (Tp–Te) interval. The reduction in Tp–Te interval (ΔTp–Te) was calculated by comparing pre- and post-fibrinolysis values, and patients were categorized into successful or failed fibrinolysis groups based on ≥50% ST-segment resolution. Clinical outcomes, laboratory findings, and ECG parameters were systematically recorded in a structured case record form for analysis.

Statistical Methods

Data were analyzed using SPSS version 25.0. Continuous variables were compared using the independent or paired t-test/Mann–Whitney U test/Wilcoxon signed-rank test, while categorical variables were analyzed using the Chi-square or Fisher's exact test. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal ΔTp–Te cutoff for predicting successful fibrinolysis. A p-value <0.05 was considered statistically significant.

Among the 119 STEMI patients, the majority were aged 51–60 years (32.8%), male (72.3%), from rural areas (56.3%), and belonged to the middle socioeconomic class (48.7%). Hypertension (51.3%) and diabetes mellitus (41.2%) were common comorbidities. Anterior wall myocardial infarction was the most common infarct location (43.7%), 63.9% of patients presented with Killip class I, and 39.5% reached the hospital within 3–6 hours of symptom onset. All patients had elevated cardiac biomarkers. Elevated random blood glucose (≥200 mg/dL) was observed in 38.6%, hypertriglyceridemia in 53.8%, and hypercholesterolemia in 48.7% of patients, (Table 1).

Streptokinase was the most commonly used fibrinolytic agent (65.5%), and most patients received fibrinolysis within 31–60 minutes (41.2%). All patients received dual antiplatelet therapy, while the majority also received anticoagulation (87.4%), statins (95.0%), beta-blockers (76.5%), and ACE inhibitors/ARBs (73.9%). Successful reperfusion (≥50% ST-segment resolution) was achieved in 63.9% of patients. Complete chest pain relief was observed in 59.7%, and reperfusion arrhythmias occurred in 31.9% of patients, with accelerated idioventricular rhythm (AIVR) being the most common arrhythmia, followed by ventricular premature complexes (VPCs) and non-sustained ventricular tachycardia (VT), (Table 2).

There were no significant differences in age (p=0.62), sex (p=0.69), hypertension (p=0.46), diabetes mellitus (p=0.37), smoking status (p=0.43), type of myocardial infarction (p=0.21), or Killip class at presentation (p=0.56). However, earlier presentation (≤3 hours) was significantly more frequent among patients with successful fibrinolysis (35.5% vs. 16.3%), whereas presentation after 6–12 hours was more common in the failed fibrinolysis group (46.5% vs. 23.7%; p=0.02).

The median baseline Tp–e interval of 95 ms (IQR: 82–110) decreased to 78 ms (IQR: 66–92) postfibrinolysis, with a median reduction (ΔTp–e) of 17 ms (IQR: 10–26). This reduction was found to be statistically highly significant (p < 0.001), indicating improvement in ventricular repolarization following reperfusion therapy. Patients with successful fibrinolysis had significantly lower baseline and post-fibrinolysis Tp–e intervals and a greater reduction in Tp–e (ΔTp–e) compared with those with failed fibrinolysis (all p ≤0.01). A ΔTp–e ≥15 ms was significantly more common in the successful reperfusion group, whereas ΔTp–e <15 ms predominated in the failed group (p <0.001). Moreover, patients with ΔTp–e ≥15 ms had 9.36-fold higher odds of achieving successful reperfusion, indicating that ΔTp–e is a strong predictor of successful fibrinolytic therapy, (Table 3).

Patients with successful reperfusion showed a significantly greater reduction in the Tp–e interval than those with failed reperfusion, with the highest ΔTp–e observed in patients achieving complete chest pain relief (p<0.001). Patients with reperfusion arrhythmias also demonstrated a significantly greater ΔTp–e than those without arrhythmias (p=0.002), supporting its association with successful myocardial reperfusion, (Table 4). Additionally, there was a strong positive correlation between ΔTp–e and percentage ST-segment resolution (r = 0.62, p < 0.001), (Figure 1).

The receiver operating characteristic (ROC) analysis demonstrated a good discriminative ability, with an area under the curve (AUC) of 0.84 (95% CI: 0.76–0.91, p < 0.001). An optimal cutoff value of ΔTp–e ≥15 ms yielded a sensitivity of 76.3% and specificity of 74.4%. The positive predictive value was 84.1%, while the negative predictive value was 64.0%, with an overall diagnostic accuracy of 75.6%, (Figure 2).

Ventricular arrhythmias occurred in 34 (28.6%) patients, with ventricular premature complexes (VPCs) being the most common type (15/34, 44.1%), followed by non-sustained ventricular tachycardia (NSVT) (32.4%), sustained ventricular tachycardia (VT) (14.7%), and ventricular fibrillation (VF) (8.8%). In-hospital complications included heart failure in 29 (24.4%), cardiogenic shock in 11 (9.2%), reinfarction in 6 (5.0%), and in-hospital mortality in 8 (6.7%) patients. Patients who developed ventricular arrhythmias had significantly higher baseline and post-fibrinolysis Tp–e intervals, along with a significantly lower reduction in the Tp–e interval compared to those without arrhythmias (all p<0.001). Baseline Tp–e >100 ms and ΔTp–e <15 ms were significantly more frequent among patients with ventricular arrhythmias (p<0.001), (Table 5). Furthermore, baseline Tp–e >100 ms was associated with a 7.8-fold increased risk of ventricular arrhythmias, while ΔTp–e <15 ms was associated with a 6.67-fold increased risk. These findings indicate that prolonged baseline Tp–e interval and inadequate reduction following fibrinolysis are strong predictors of ventricular arrhythmias, reflecting persistent electrical instability.

Patients who developed in-hospital MACE had significantly higher baseline and post-fibrinolysis Tp–e intervals, along with a significantly lower reduction in the Tp–e interval compared to those without MACE (all p<0.001). Baseline Tp–e >100 ms and ΔTp–e <15 ms were significantly more common among patients with MACE than those without (p<0.001), (Table 6). A baseline Tp–e interval >100 ms was associated with an 8.35-fold increased risk of MACE (95% CI: 3.52–19.80). Similarly, a reduction in Tp–e interval (ΔTp–e) <15 ms was associated with a 6.56-fold increased risk of MACE (95% CI: 2.86–15.02).

Table 1: Baseline characteristics of study participants (n = 119)

Table 2. Fibrinolytic therapy, and clinical and electrocardiographic markers of reperfusion after fibrinolytic therapy

Table 3: Comparison of Tp–e Interval Parameters and Association of ΔTp–e with Successful Fibrinolysis

Table 4: Correlation of Reduction in Tp–e Interval (ΔTp–e) with ST-Segment Resolution and Clinical Reperfusion Markers (n = 119)

Table 5: Association of Tp–e Interval Parameters with Ventricular Arrhythmias (n = 119)

Table 6: Association of Tp–e Interval Parameters with In-Hospital Major Adverse Cardiac Events (MACE) (n = 119)

In the present study, STEMI predominantly affected middle-aged males (72.3%), with most patients belonging to the 51–60-year age group (32.8%) and the majority originating from rural (56.3%), middle (48.7%), and lower (38.7%) socioeconomic backgrounds, findings comparable to those reported by De Luca et al⁴, Gupta et al¹⁵, and CREATE registry¹⁶. Hypertension, diabetes mellitus, smoking, dyslipidemia, obesity, and alcohol consumption were the major cardiovascular risk factors, consistent with previous Indian and international studies.^15,17 Most patients presented 3–6 hours after symptom onset, with anterior wall myocardial infarction and Killip class I being the most common presentations, similar to findings from the CREATE registry¹⁶ and the GUSTO trial.¹⁸ All patients had elevated cardiac biomarkers, while hyperglycemia, renal dysfunction, electrolyte abnormalities, and dyslipidemia were frequently observed, in agreement with earlier reports.^19,20 Baseline ECG findings showed moderate-to-severe ST-segment elevation, frequent reciprocal ST depression, QTc prolongation, and prolonged Tp–e intervals, indicating significant myocardial injury and repolarization abnormalities, consistent with observations by Birnbaum et al¹² and Schröder et al⁶.

Streptokinase was the most commonly used fibrinolytic agent (65.5%), while 30.3% of patients received fibrinolysis within the recommended door-to-needle time of ≤30 minutes. Guideline-directed medical therapy was well adhered to, with dual antiplatelet therapy administered to all patients (100%), heparin to 87.4%, statins to 95.0%, beta-blockers to 76.5%, and ACE inhibitors/ARBs to 73.9%. These findings are comparable with the CREATE registry by Xavier et al¹⁶ and Schwartz GG et al.²¹ Successful reperfusion was achieved in 63.9% of patients, complete chest pain relief was observed in 59.7%, and reperfusion arrhythmias occurred in 31.9%, with accelerated idioventricular rhythm (50.0%) being the most common. These observations are consistent with the GUSTO trial¹⁸ and the study by Schröder et al.⁶ Time to presentation was significantly associated with reperfusion success (p=0.02). Patients presenting within ≤3 hours were more likely to achieve successful fibrinolysis (35.5% vs 16.3%), whereas delayed presentation (6–12 hours) was more frequent in the failed fibrinolysis group (46.5% vs 23.7%). These findings are consistent with previous studies done by De Luca et al⁴, and Schröder et al⁶.

In the present study, the Tp–e interval decreased significantly after fibrinolytic therapy from a median of 95 ms to 78 ms, with a median ΔTp–e of 17 ms (p<0.001), this finding is consistent with the study done by Antzelevitch et al⁸, Gupta et al¹⁵, Zhao et al²², and Panikkath et al.²³ Patients with successful fibrinolysis had significantly lower baseline Tp–e intervals (92 ms vs. 101 ms; p=0.01), lower post-fibrinolysis Tp–e (70 ms vs. 92 ms; p<0.001), and a greater reduction in Tp–e (22 ms vs. 8 ms; p<0.001) than those with failed fibrinolysis. Similar observations have been reported by Antzelevitch et al⁸, Gupta et al¹⁵, Zhao et al²², and Wu et al²⁴, who found greater Tp–e reduction in patients achieving successful myocardial reperfusion. A ΔTp–e ≥15 ms was observed in 76.3% of patients with successful fibrinolysis compared with 25.6% in the failed group and was associated with a 9.36-fold higher likelihood of successful reperfusion (95% CI: 4.02–21.78; p<0.001). These findings are in agreement with studies by Gupta et al¹⁵, Zhao et al²², and Panikkath et al.²³ In the present study, ΔTp–e showed a strong association with established reperfusion markers. Patients with ≥50% ST-segment resolution had a significantly greater ΔTp–e (22 ms vs. 8 ms; p<0.001), with a strong positive correlation between ΔTp–e and ST-segment resolution (r=0.62; p<0.001). Greater ΔTp–e was also observed in patients with complete chest pain relief and reperfusion arrhythmias. The ROC analysis demonstrated good diagnostic performance of ΔTp–e for predicting successful fibrinolysis, with an AUC of 0.84, 76.3% sensitivity, 74.4% specificity, and 75.6% overall diagnostic accuracy. These findings are comparable with studies by Antzelevitch et al^8, Schröder et al⁶, Zhao et al²², and Panikkath et al²³.

In the present study, ventricular arrhythmias occurred in 28.6% of patients, with ventricular premature complexes (44.1%) being the most common, followed by non-sustained ventricular tachycardia (32.4%). Heart failure developed in 24.4%, cardiogenic shock in 9.2%, reinfarction in 5.0%, and in-hospital mortality was 6.7%. These findings are comparable with those reported by CREATE registry¹⁶, Eldar et al²⁵, and Goldberg et al²⁶. Patients who developed ventricular arrhythmias had significantly higher baseline Tp–e (108 vs. 91 ms), higher post-fibrinolysis Tp–e (94 vs. 73 ms), and lower ΔTp–e (9 vs. 20 ms) than those without arrhythmias (all p<0.001). Baseline Tp–e >100 ms and ΔTp–e <15 ms increased the risk of ventricular arrhythmias by 7.8-fold and 6.67-fold, respectively. These findings are consistent with studies by Antzelevitch et al⁸, Gupta et al¹⁵, and Panikkath et al²³, highlighting Tp–e as a marker of ventricular electrical instability. Similarly, patients with in-hospital MACE had significantly higher baseline Tp–e (106 vs. 90 ms), higher post-fibrinolysis Tp–e (92 vs. 72 ms), and lower ΔTp–e (10 vs. 21 ms) than those without MACE (all p<0.001). Baseline Tp–e >100 ms and ΔTp–e <15 ms were associated with an 8.35-fold and 6.56-fold increased risk of MACE, respectively. These observations are in agreement with the findings of Gupta et al¹⁵, Panikkath et al²³, and Wu et al.²⁴

Limitations

This was a single-center study with a relatively small sample size, which may limit the generalizability of the findings. The cross-sectional design did not permit long-term prognostic assessment. Reperfusion was evaluated using surrogate ECG markers rather than angiographic confirmation, and manual Tp–e interval measurement may have introduced observer bias. In addition, potential confounding factors such as infarct size, collateral circulation, and treatment variability were not fully controlled.

The present study demonstrates that the Tp–e interval is a simple, non-invasive, and reliable ECG marker for assessing myocardial reperfusion in STEMI patients undergoing fibrinolytic therapy. A greater reduction in the Tp–e interval was associated with successful reperfusion and favorable clinical outcomes, while prolonged baseline Tp–e and inadequate post-fibrinolysis reduction predicted ventricular arrhythmias and in-hospital major adverse cardiac events. As Tp–e interval can be readily measured from a standard 12-lead ECG, it represents a practical, cost-effective, and widely accessible bedside tool for early risk stratification and assessment of reperfusion, particularly in resource-limited settings.

Conflict of Interest: No conflict of interest.

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