Cardiac troponins (cTnI and cTnT) are regulatory proteins unique to cardiac myocytes and are considered the gold standard biomarkers for the detection of myocardial injury. Their high sensitivity and specificity have revolutionized the diagnosis of acute myocardial infarction (AMI) and the differentiation between ischemic and non-ischemic myocardial injury. According to the Fourth Universal Definition of Myocardial Infarction, a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit, together with evidence of myocardial ischemia, confirms the diagnosis of MI (1).

Myocardial infarction can occur due to either thrombotic (Type 1 MI) or non-thrombotic (Type 2 MI) mechanisms. Thrombotic MI results from atherosclerotic plaque rupture or erosion leading to intraluminal thrombus formation and subsequent coronary artery occlusion (2). This process initiates acute myocardial ischemia, culminating in myocyte necrosis and troponin release into the circulation. Elevated troponin levels in this setting are directly related to the extent of ischemic necrosis and thrombus burden (3). These patients typically benefit from urgent reperfusion therapy and antithrombotic treatment, including antiplatelet and anticoagulant agents (4).

In contrast, non-thrombotic or antithrombotic-related troponin elevation occurs in conditions where myocardial oxygen supply–demand imbalance is the primary mechanism, such as tachyarrhythmia, severe anemia, hypotension, or coronary vasospasm (5). Such elevations may also be observed in patients on antithrombotic therapy due to microvascular injury, bleeding-induced anemia, or hypotension-related ischemia without evidence of coronary thrombosis (6). This entity is frequently classified as Type 2 MI or myocardial injury rather than infarction caused by plaque rupture.

Distinguishing thrombotic from non-thrombotic troponin elevation is of major clinical importance, as the therapeutic implications differ markedly. Thrombotic MI mandates aggressive antithrombotic and reperfusion strategies, while non-thrombotic causes require correction of the underlying precipitating factors rather than intensification of antithrombotic therapy, which may increase bleeding risk without improving outcomes (7,8). Serial measurement of troponin, coupled with clinical assessment, electrocardiographic changes, and imaging modalities, assists in accurate diagnosis and appropriate management (9).

A deeper understanding of the mechanisms underlying thrombotic and antithrombotic troponin elevations can improve diagnostic precision and guide individualized therapy in patients presenting with elevated troponin levels.

Aim and Objective

Aim: - To study and compare the patterns, mechanisms, and clinical significance of thrombotic and antithrombotic (non-thrombotic) troponin elevation in patients with myocardial infarction.

Objectives: - To evaluate the incidence and pattern of troponin elevation in patients presenting with myocardial infarction.

To differentiate between thrombotic (Type 1 MI) and antithrombotic/non-thrombotic (Type 2 MI) causes of troponin elevation based on clinical, biochemical, and angiographic findings.

To assess the correlation between the degree of troponin elevation and severity of coronary artery involvement.

To analyze the impact of thrombotic versus non-thrombotic mechanisms on patient management strategies and short-term outcomes.

To emphasize the diagnostic and therapeutic importance of distinguishing between thrombotic and non-thrombotic myocardial injury for better risk stratification and individualized treatment planning.

Study Design and Setting

This was a prospective observational study conducted in the Department of Cardiology Department of Medicine and Cardiology at Konaseema institute of medical sciences Amalapuram AP India a tertiary care teaching hospital, between January 2018 and December 2018 over a period of 12 months. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants before enrollment.

Study Population

Patients aged ≥18 years who presented to the emergency or cardiology department with clinical suspicion of acute myocardial infarction (AMI) and elevated cardiac troponin levels were included. Diagnosis of myocardial infarction was made according to the Fourth Universal Definition of MI (2018) criteria (1), which require a rise and/or fall in cardiac troponin with at least one value above the 99th percentile upper reference limit and evidence of myocardial ischemia.

Exclusion Criteria

Patients with chronic kidney disease, myocarditis, sepsis, pulmonary embolism, or recent cardiac surgery were excluded to minimize confounding causes of troponin elevation. Those with incomplete medical records or who declined participation were also excluded.

Classification of Study Groups

Based on clinical, biochemical, and angiographic evaluation, patients were categorized into two groups:

Group A (Thrombotic MI): Patients with evidence of plaque rupture or intraluminal thrombus on coronary angiography consistent with Type 1 MI.

Group B (Antithrombotic/Non-thrombotic MI): Patients without angiographic evidence of acute thrombosis, where troponin elevation resulted from oxygen supply–demand mismatch or secondary ischemic injury consistent with Type 2 MI.

Data Collection

Detailed demographic, clinical, and laboratory data were collected, including:

Clinical parameters: Age, gender, cardiovascular risk factors, symptom onset, hemodynamic status, and associated comorbidities.

Biochemical parameters: Serial high-sensitivity cardiac troponin (hs-cTnI or hs-cTnT) measurements at admission, 3 hours, and 6 hours; lipid profile; renal function tests; and inflammatory markers (CRP, ESR).

Electrocardiography (ECG) and echocardiography findings were recorded for all patients.

Coronary angiography was performed in eligible cases to confirm the presence or absence of thrombotic lesions.

Treatment details including antithrombotic therapy, reperfusion strategy, and clinical outcome at discharge were documented.

Outcome Measures

The primary outcome was the pattern and magnitude of troponin elevation in thrombotic versus non-thrombotic MI patients. Secondary outcomes included in-hospital mortality, major adverse cardiac events (MACE), and duration of hospital stay.

Statistical Analysis

Data were analyzed using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) and compared using the Student’s t-test or Mann–Whitney U test as appropriate. Categorical variables were presented as frequencies and percentages, and comparisons were made using the Chi-square test or Fisher’s exact test. Correlation between troponin levels and angiographic severity of coronary artery disease was assessed using Pearson’s correlation coefficient. A p-value <0.05 was considered statistically significant.

A total of 100 patients diagnosed with myocardial infarction and elevated troponin levels were included in the study. Of these, 64 patients (64%) were classified as thrombotic MI (Group A) and 36 patients (36%) as antithrombotic/non-thrombotic MI (Group B) based on angiographic and clinical criteria.

Demographic and Clinical Characteristics

The mean age of patients in the thrombotic group was 58.6 ± 9.4 years, while that in the antithrombotic group was 61.2 ± 10.1 years (p = 0.18). Males constituted 72% of the thrombotic group and 67% of the antithrombotic group. Hypertension (62%) and diabetes mellitus (56%) were the most common comorbidities observed in both groups.

Chest pain was the predominant symptom in the thrombotic group (92%), whereas dyspnea and generalized weakness were more frequent in the antithrombotic group (68%).

Table 1. Baseline Demographic and Clinical Characteristics

*Statistically significant

Troponin Elevation Pattern

The mean peak troponin-I level was significantly higher in the thrombotic group (12.8 ± 6.4 ng/mL) compared to the antithrombotic group (3.9 ± 2.1 ng/mL, p < 0.001). The rise-and-fall pattern of troponin was more pronounced in thrombotic MI, while sustained mild elevation was typical in non-thrombotic MI.

Table 2. Comparison of Troponin Levels and ECG Findings

Angiographic Findings

Among thrombotic MI patients, single-vessel disease was present in 41%, double-vessel disease in 33%, and triple-vessel disease in 26%. In contrast, normal or non-obstructive coronaries were seen in 58% of the antithrombotic group.

A significant positive correlation was observed between peak troponin levels and angiographic severity of coronary artery disease (r = 0.62, p < 0.001).

Table 3. Coronary Angiography Findings

Treatment and Outcomes

All thrombotic MI patients received dual antiplatelet therapy, anticoagulation, and statins, with 78% undergoing primary PCI. In contrast, the antithrombotic MI group was managed conservatively with optimization of underlying causes (e.g., anemia correction, rate control, or oxygen therapy).

In-hospital mortality was higher in the thrombotic group (9.3%) compared to the antithrombotic group (5.6%, p = 0.48), though the difference was not statistically significant.

Major adverse cardiac events (MACE) occurred in 14% and 8% of the thrombotic and antithrombotic groups respectively.

Table 4. Treatment and In-hospital Outcomes

*Statistically significant

In the present study, patients with elevated cardiac troponin levels were categorized into thrombotic myocardial infarction (Type 1 MI) and non-thrombotic myocardial infarction/myocardial injury (Type 2 MI) based on clinical presentation, electrocardiographic findings, biochemical profile, and angiographic assessment. The results demonstrated clear differences between the two groups in terms of troponin magnitude, ECG patterns, coronary anatomy, and therapeutic approach, highlighting the importance of distinguishing the underlying mechanism of myocardial injury.

The mean troponin-I concentration was significantly higher in the thrombotic MI group than in the non-thrombotic group. This finding is in agreement with previous evidence showing that acute atherothrombotic plaque disruption typically produces greater myocardial necrosis and higher biomarker release, whereas Type 2 MI and myocardial injury are often associated with relatively lower troponin elevations due to oxygen supply–demand imbalance or secondary ischemic stress rather than acute coronary thrombosis [11],[13],[14]. High-sensitivity troponin assays have further strengthened the recognition that troponin elevation is highly sensitive for myocardial injury, but its interpretation must always be contextual rather than isolated [9],[14].

Electrocardiographic findings in our study also supported this distinction. ST-segment elevation was predominantly observed in the thrombotic group, whereas non-ST-segment elevation patterns were more common among non-thrombotic cases. This pattern is consistent with prior reports indicating that Type 2 MI more frequently presents with non-ST elevation changes and lower peak troponin concentrations compared with classical Type 1 MI [11],[13],[14]. These observations reflect the differing pathophysiological basis of the two entities, with complete or near-complete coronary occlusion being more typical of thrombotic infarction.

Coronary angiography revealed obstructive coronary artery disease or angiographic evidence suggestive of thrombosis in the thrombotic MI group, while a substantial proportion of patients in the non-thrombotic group had normal or non-obstructive coronary arteries. This observation is concordant with studies demonstrating that patients with Type 2 MI frequently lack acute plaque rupture or occlusive coronary thrombosis and instead develop myocardial injury in the setting of systemic illness, hemodynamic instability, anemia, arrhythmia, or hypoxemia [11],[13]. The positive correlation observed between troponin level and angiographic severity in our study further suggests that higher biomarker release may reflect greater ischemic burden and myocardial damage.

The treatment strategies adopted in both groups were also notably different. Patients with thrombotic MI were more likely to undergo reperfusion therapy and receive antithrombotic treatment, whereas management in the non-thrombotic group was directed primarily toward correction of the underlying precipitating factor. This approach is supported by available literature showing that outcomes in Type 2 MI depend largely on recognition and treatment of the causal condition rather than routine use of invasive coronary intervention or aggressive antithrombotic therapy [12],[13]. Prior studies have emphasized that indiscriminate treatment of all troponin-positive patients as classical acute coronary syndrome may not be appropriate, particularly in those with secondary myocardial injury [11],[12].

Although in-hospital mortality was numerically higher in the thrombotic MI group, the difference was not statistically significant. This may be explained by timely recognition and prompt revascularization in thrombotic MI, while patients with non-thrombotic MI often have substantial comorbid illness that independently contributes to adverse outcomes. Earlier studies have similarly shown that Type 2 MI and myocardial injury are associated with poor long-term prognosis, largely because of the severity of the underlying systemic disease burden [12],[13].

Overall, the present study reinforces that elevated cardiac troponin should not be interpreted as synonymous with thrombotic myocardial infarction. Troponin is a highly sensitive marker of myocardial injury, but it lacks etiological specificity when used in isolation [9],[14]. A careful integrated assessment of symptoms, ECG findings, serial troponin changes, and coronary anatomy is essential to distinguish thrombotic from non-thrombotic causes. Such differentiation has important clinical implications, as it guides appropriate therapy, prevents unnecessary exposure to antithrombotic agents, and supports more individualized patient management [11]-[14].

Limitations

The present study was conducted at a single tertiary center with a relatively small sample size, which may limit generalizability. Follow-up data beyond hospital discharge were not included. Larger, multicentric studies are warranted to validate these findings and to establish standardized criteria for differentiating between thrombotic and non-thrombotic troponin elevations.

Troponin elevation in myocardial infarction patients arises from both thrombotic and non-thrombotic mechanisms. Thrombotic MI is characterized by higher troponin levels, ST-segment elevation, and angiographic evidence of plaque rupture or thrombosis, requiring urgent reperfusion and antithrombotic therapy. Antithrombotic/non-thrombotic MI, on the other hand, shows modest troponin elevation, non-obstructive coronaries, and benefits primarily from correction of precipitating factors rather than aggressive anticoagulation. Accurate differentiation between these entities is vital for appropriate management and improved patient outcomes.

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