Cardiac troponin (I or T) has high myocardial tissue specificity as well as high clinical sensitivity because cTn T and I are essential contractile components of myocardial cells and are expressed almost exclusively in the myocardium. Release of cardiac troponin from the myocardium can result from normal turnover of myocardial cells, myocyte apoptosis, myocyte release of troponin degradation products, increased myocyte wall permeability and bleb formation, or myocyte necrosis [1]. 

Myocardial necrosis due to myocardial ischemia is defined as myocardial infarction [2]. Detection of a rise and a fall of troponin, expressed in ng/L or pg/mL, is essential to the diagnosis of acute MI [3,4],. Blood samples for the measurement of cTn should be drawn during the initial patient assessment and repeated 3-6 h later. Subsequent additional blood samples are required if further ischemic episodes occur, or when the timing of the initial symptoms onset is unclear [5]. The demonstration of a rise and fall in troponin measurements is extremely important in the differentiation of acute from chronic elevations in cTn concentrations that can be associated with structural heart disease such as patients with left ventricular hypertrophy (LVH), renal failure and heart failure (Table 1) [6]. 

The incidence of ST segment myocardial infarction (STEMI) has gradually declined over the past decade. However, it still accounts for 25%-40% of all acute coronary syndrome related hospitalizations in the United States [7]. Moreover, the incidence of acute myocardial infarction is increasing in the developing countries [8]. Heart disease is expected to be the leading cause of death in the developing world by the year 2020. With changing dietary and personal habits, the prevalence of smoking, hypertension, diabetes, obesity and metabolic syndrome are increasing in areas of the world with large populations such as India [9], China [10] and South America [11]. Advances made in the area of medical therapy and coronary interventions have resulted in a significant decrease in the mortality rates. Current in-hospital and one year mortality are in the order of 5%-6% and 7%-18% respectively [12,13]. During the course of last three decades, there have been significant advances in our understanding of the pathophysiology and treatment of STEMI. In addition to these scientific advances, substantial progress has been made in the areas of public awareness and guideline driven clinical practice [14]. This has led to a gradual decline in STEMI related mortality and improved patient related outcomes. However, there continues to be significant difference in the 30-d mortality rates based on the geographic region [15], age [16,17], gender [18] and race [19]. In addition, individuals with diabetes and chronic renal insufficiency continue to have high rates of mortality [20]. In the recent INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy During Primary PCI for Anterior STEMI) trial [21], diabetics compared to non-diabetics, had higher incidence of stent thrombosis at 30 d (4.3% vs 0.8%, p = 0.03) and higher rates of major cardiovascular and cerebrovascular events at 1 year (16.5% vs 8.0%, p = 0.04). It has been shown that patients with end-stage renal disease frequently do not receive guideline-based therapies. In one registry, it has been shown that only 45% of eligible patients on dialysis received coronary reperfusion therapy, and only 70% of patients received aspirin on admission for coronary syndromes. In-hospital mortality rate from myocardial infarction is 21.3% in those on dialysis and 11.7% in those with renal disease but not on dialysis [22]. 

Approximately 7% of the eligible patients with myocardial infarctions do not receive reperfusion therapy [23]. There is evidence suggesting that reperfusion therapy offers benefit in the elderly. However, age is the strongest predictor associated with an individual not receiving reperfusion therapy [24]. Programs that focus on patient education, systematic organization of STEMI programs and standardization of clinical practice result in improved care of all groups of patients and minimize disparities [25,26],. 

One of the most important components of STEMI management is getting the patients in a time efficient manner to a hospital that is capable of administering reperfusion therapies such as fibrinolytic therapy and primary percutaneous coronary intervention. Although approximately 98% of the United States population is within the reach of 911 based emergency medical service systems, patients with STEMI do not routinely utilize the system [27]. System based delays have been shown to increase STEMI related morbidity and mortality [28]. Hence increased community awareness and preparedness is important. In addition, regional STEMI centers with organized protocols, system based time-to-treatment goals and quality improvement programs must be established. Such efforts minimize delays and lower morbidity and mortality in STEMI patients [29,30]. In a study by Sørensenet al., [31], where 759 consecutive STEMI patients were divided into a group with pre-hospital diagnosis and direct referral to a primary PCI centervs a group without pre-hospital diagnosis. Pre-hospital diagnosis and direct referral resulted in shorter system delay (92 min vs 153 min, P <0.001).

Fibrinolytic therapy (FT) and Primary Percutaneous Coronary Intervention (P-PCI) are the two currently available modalities of reperfusion therapies. Both of these options are extensively studied. P-PCI, when performed in a timely manner at a high patient volume center is superior to FT. However, P-PCI is not universally available [32]. Delays in door-to-balloon times (D2B) are associated with increased mortality [33]. Adherence to D2B goal of < 90 min lowers mortality [34,35]. Although P-PCI is superior to FT, emphasis should be placed on timely administration of some form of reperfusion therapy rather than the mode of treatment [36]. 

For patients who present to a P-PCI capable hospital, the door to balloon time should not exceed 90 min. When patients present to a hospital that is not capable of P-PCI, factors such as time of onset of symptoms, risk of bleeding, presence of acute heart failure or shock, risk of mechanical complications, time- to-transfer to a P-PCI capable hospital should be taken into consideration. In patients who present within less than 1-2 h of onset of symptoms, immediate FT may be advantageous even if the transfer times are short [37].

When P-PCI is not available, FT is an alternative. It reduced mortality and morbidity when carefully administered within 12 h of symptom onset [38]. The usefulness of FT in patients presenting greater than 12 h from the onset of symptoms is not well established [39]. Fibrin specific agents such as tenecteplase, retaplase and alteplase are preferred. Tenecteplase is the most fibrin specific. None of the fibrin specific agents are antigenic. Patency rates of the infarct related artery [40] with fibrin specific agents are approximately 85%. Streptokinase is a non-fibrin-specific agent and can cause antigenic reactions. Infarct related artery patency rate with streptokinase is 60%-70% [41] When the delay from first medical contact to primary PCI is > 120 min, FT is indicated if the time of onset of symptoms is <12h. 

The role of Aspirin and Clopidogrel with fibrinolytic therapy is well established [42]. Aspirin and Clopidogrel should be given prior to the administration of fibrinolytic agent. Dual antiplatelelt therapy should be continued for at least one year [43]. The data on using newer antiplatelet agents like Prasugrel and Ticagrelor as an adjunct to thrombolytic therapy for fibrinolysis is not yet well established. In addition to antiplatelet therapy, the use of adjunctive anticoagulants is supported when fibrinolytic agents are used for STEMI [44]. Unfractionated heparin, Enoxaparin and Fondaparinux can be used. However, low molecular weight heparins (LMWH) should be avoided in patients with impaired renal function (Creatinine Clearance < 30 mL/min) [45]. 

Ongoing chest pain, lack of > 50% ST segment resolution and the absence of reperfusion arrhythmias at 60-90 min after the administration of fibrinolytics is considered failure of treatment. These parameters predict TIMI flow < 3 in the infarct artery [46]. In patients who don’t respond to (FT), “rescue” PCI has been shown to be beneficial. In the Rapid Early Action for Coronary Treatment Trail [47]. The primary components endpoint of death, reinfarction, stroke, or severe HF at 6 mo, was lower among patients randomized to rescue PCI compared to conservative care or repeat fibrinolysis (event-free survival rate: 84.6% vs 70.1% vs 68.7%, p = 0.004). This was due to reduction in reinfarction. There was no significant survival benefit. Minor bleeding was significantly higher among patients randomized to rescue PCI. However, there were no differences in major bleeding among the conservative therapy, repeat fibrinolysis or, rescue PCI groups. Similar findings of improved event free survival were reported in the Middlesbrough Early Revascularization to Limit Infarction trail. However, higher rates of stroke and periprocedural bleeding were associated with rescue PCI [48,49]. In patients with ongoing symptoms, lack of signs reperfusion, significant hypotension, severe CHF, cardiogenic shock, ECG evidence of large area of myocardium at risk, the benefit of early PCI justifies the risk of bleeding. Conservative treatment might be reasonable in a patient with improving symptoms and a limited inferior infarction despite the persistence of ST elevation.    

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