1. A patient presents with one episode of chest pain that lasted 10 minutes. He does not have any pain currently. He reports a prior history of a large MI 2 years previously. His ECG shows 1.5 mm ST elevation in the anterior leads with Q waves and T-wave inversion. Should he undergo emergent reperfusion?

Emergent reperfusion is probably not warranted. It is important to seek old ECGs and urgently obtain an echocardiogram. In fact, ST elevation may represent an old STEMI with a chronic dyskinetic myocardium and a chronic, persistent ST elevation with Q waves; T waves may be inverted or upright, but not ample. A history of an old MI, an old ECG (if available), or a quick bedside echocardiogram may allow the diagnosis. Echocardiography shows a myocardium that is thin, not just in systole but in diastole, bright (scarred) and possibly aneurysmal in case of an old infarct, whereas in acute STEMI the myocardium is neither thin nor scarred yet. If the patient does not report a history of MI, if T wave is ample, or if he had a typical angina within the last 24 hours, ST elevation is generally considered acute STEMI.

2. A patient presents with ongoing chest pain for the last 8 hours. His ECG shows inferior ST elevation of 1 mm with deep Q waves. Should he undergo emergent reperfusion?

Q waves often develop at 1–14 hours after STEMI onset, while the ST segment is still elevated. While Q waves are associated with a more delayed presentation, larger MI, less myocardial salvage, and worse short-term prognosis, they are not synonymous with irreversible myocardial damage and do not preclude reperfusion therapy; significant myocardial salvage is achieved in the overwhelming majority of those patients (>70%).^5–7 Persistent Q waves at >1 month have a stronger prognostic value than acute Q waves.

3. A patient presents with intermittent chest pain for the last 3 days. He had an episode of pain 2 hours previously but is currently free of any pain. His ECG shows anterolateral ST elevation. Should he undergo emergent reperfusion?

Some patients have episodes of unstable angina for hours or days before STEMI. Presume that the onset of STEMI is the onset of the last episode of prolonged chest pain. Thus, this patient qualifies for emergent reperfusion.

4. A patient presents with chest pain that started 4 hours previously and inferior ST elevation. His pain has just resolved with aspirin and nitroglycerin, but ST elevation is persistent. Should he undergo emergent reperfusion?

Some patients have resolution of chest pain with nitroglycerin or antithrombotic therapies but ST elevation persists. These patients should still undergo emergent reperfusion therapy, as long as they present within 24 hours of pain onset.

5. A patient presents with chest pain that started 4 hours previously and inferior ST elevation. Both his pain and ST elevation resolve after aspirin and nitroglycerin administration. Should he undergo emergent reperfusion?

Chest pain and ST elevation may both resolve spontaneously or with the acute therapies. This often indicates spontaneous thrombolysis and occurs in ~15% of STEMIs, leading to a much lower mortality and a smaller infarct size.^8,9 Occasionally, this may represent resolution

of a coronary spasm. Coronary angiography may be performed emergently, but this is not mandatory: delayed angiography (mean 23 hours) was associated with a similarly low event rate and infarct size in TRANSIENT-STEMI trial.⁹ Full ACS therapy and early coronary angiography, within the next day, are indicated.

6. A patient presents with chest pain that lasted 2–3 hours earlier today and has now resolved. His ECG shows subtle ST elevation (<1 mm) in leads II, aVF, V₅, and V₆ (Figure 2.2). Should he undergo emergent reperfusion?

Yes, he should. This patient has mild ST elevation (<1 mm) with a morphology that is, nonetheless, consistent with STEMI. Q waves are

also present. STEMI may be over 12–24 hours old, at a stage where ST elevation is resolving but has not fully resolved yet (close to phase 3). Alternatively, STEMI may be more recent with ongoing or resolving ischemia. This patient does not qualify for fibrinolytics, as ST elevation is <1 mm and the occlusion duration is questionable, but qualifies for emergent PCI if the discomfort is ongoing or if the discomfort occurred within the last 24 hours, even if it is not ongoing.

7. A patient presents with chest pain that has lasted 2–3 hours earlier today and has now resolved. His ECG shows inferior Q waves and T-wave inversion, without any significant ST elevation. Should he undergo emergent reperfusion?

PCI is preferably, but not necessarily, performed emergently. Resolution of ST elevation with appearance of Q waves (phase 3) often implies a late presentation, >12–24 hours, but may also occur after a brief ischemia, e.g., 1–2 hours, as in this case. This patient does not qualify for fibrinolysis (no residual ST elevation). He still qualifies for PCI, not necessarily on an emergent basis.

A. Fibrinolytics (also called thrombolytics): mortality benefit

In the GISSI-1 and ISIS-2 trials and a large meta-analysis, fibrinolytics (mainly streptokinase) have shown:^10,17–19

• A striking 6.5% absolute mortality reduction and 50% relative mortality reduction in the first hour after STEMI onset, called the golden hour
  
• A 4% absolute mortality reduction in the second hour
  
• A plateau 3% mortality reduction between 3 and 6 hours (relative mortality reduction ~25%)
  
• Absolute mortality reduction of ~2% between 6 and 12 hours. Beyond that, between 12 and 24 hours, the benefit is marginal and questionable.

This time-dependent benefit is due to the fact that very early reperfusion of the occluded coronary artery may lead to full recovery of the ischemic tissue and thus prevent necrosis. In addition, fibrinolytic therapy in the first 2–3 hours is highly efficacious in lysing a fresh thrombus.

The benefit is more striking in high-risk subgroups, such as anterior STEMI, STEMI with bundle branch block, or high STEMI risk score (tachycardia, hypotension). The elderly subgroup is the only high-risk subgroup that, paradoxically, only derives a marginal benefit from fibrinolysis; this is partly because of the high bleeding risk but also because of the more extensive CAD that makes it less likely for fibrinolysis to re-establish perfusion; a half-dose TNK is recommended in patients ≥75 (ESC class IIa).

The mortality benefit is also more striking with the fibrin-specific fibrinolytics (~1% additional mortality reduction).

B. Fibrinolytics: limitations, contraindications, definition of successful response, and definition of TIMI flow (Table 2.1)^1,10,20,21

In addition to the classic contraindications, fibrinolysis is contraindicated in a patient with an expected intracranial bleeding risk of >4% (e.g., an elderly [>75] small woman with HTN).²⁰

Consider fibrinolytic therapy successful if: chest pain resolves and initial ST-segment elevation decreases by more than 50% (preferably 70%) at 60–90 minutes after therapy initiation, in the lead showing the worst ST-segment elevation. Also, the occurrence of an accelerated idioventricular rhythm (AIVR) in conjunction with the preceding features is highly specific for reperfusion. In the absence of a response (persistent ischemic symptoms, ST elevation, or both), plan for emergent rescue PCI. It is best to start transferring the patient to a PCI-capable hospital as soon as fibrinolytic therapy is started, so that, if no response is seen at 60 minutes, cardiac catheterization is readily available.

A successful fibrinolysis correlates with TIMI 3 flow on coronary angiography. TIMI grade 0 flow implies the absence of any flow. TIMI 1 flow implies the presence of some flow beyond the obstruction but without full distal perfusion. TIMI 2 flow means that the vessel is fully perfused but the flow is slow compared with a normal artery and/or the contrast material clears more slowly than in a normal artery; TIMI 2 flow is related to a residual mechanical obstruction or to microvascular obstruction from microvascular emboli. TIMI 3 flow means full perfusion of the vessel with normal flow. In fibrinolytic trials, TIMI 3 flow has been shown to be associated with the lowest mortality. TIMI 2 flow is associated with an intermediate mortality, while TIMI 0–1 flow is associated with the highest mortality.^22,23 The outcome is improved in patients whose TIMI 2 flow eventually improves to TIMI 3 flow within a few days (this happens two-thirds of the times).²⁴ In a patent artery, TIMI 2 and 3 flow patterns are associated with divergent outcomes and should not be grouped together.

Following PCI and in the absence of any residual mechanical obstruction, the flow may still be TIMI 0–2 flow because of microvascular embolization, spasm, or edema; this is called no reflow, i.e., TIMI 0–2 flow without any residual epicardial stenosis. The term “no reflow” is used only with PCI, not with fibrinolysis.

C. Fibrinolytics: various agents

Fibrinolytics bind to the clot-bound plasminogen and convert it to plasmin, which promotes the degradation of fibrin (Figure 2.3). The old fibrinolytic streptokinase also binds to free plasminogen; thus, in addition to lysing fibrin, it depletes systemic, free fibrinogen and affects systemic coagulation for 12–24 hours.

Alteplase (recombinant tissue plasminogen activator [r-tPA]) binds to the plasminogen entrapped in a thrombus and thus mainly degrades fibrin of a thrombus, rather than systemic fibrinogen (fibrin-specific fibrinolytic). Being more concentrated at the thrombus level, it is a more effective lytic than streptokinase. It generally does not affect the systemic fibrinogen and has a short half-life of only 6 minutes; thus, after the infusion is discontinued and the drug eliminated (~30 min), there is no significant residual effect on systemic coagulation. Therefore, the performance of PCI soon after r-tPA administration is not necessarily associated with a significant increase in bleeding. On the other hand, this short half-life and the lack of residual effect on the systemic coagulation explain the high risk of recurrent thrombosis and the need to start heparin infusion immediately at the end of r-tPA infusion in MI.

In the GUSTO trial of r-tPA vs. streptokinase, r-tPA further reduced mortality by 1% and reduced major bleeding in general, but increased intracranial hemorrhage by 0.25% in comparison with streptokinase.²¹

Reteplase (r-PA) is a mutation variant of r-tPA. It is slightly less fibrin-specific than r-tPA and has a longer half-life (~15 min), allowing its administration in two boluses rather than an infusion. It has the same mortality benefit and bleeding risk as r-tPA.

Tenecteplase (TNK) is also a mutation variant of r-tPA that is 14 times more fibrin-specific than r-tPA and less likely to be degraded by tPA inhibitors. Thus, TNK is slightly more effective, which explains the higher TIMI 3 flow rate achieved with TNK vs. r-tPA (~65% vs. 60%). It also has a longer half-life than r-tPA, with a duration of effect of ~120 minutes. In the ASSENT-2 trial, TNK was associated with the same overall mortality as r-tPA, but a reduction in major non-cerebral bleeding and a reduction in mortality of patients presenting >4 hours after symptom onset.²⁵

D. Primary PCI is superior to fibrinolytic therapy; importance of time of presentation, door-to-balloon time, and PCI delay

In comparison with fibrinolytic therapy, primary PCI is more effective in re-establishing TIMI 3 flow (95%), and thus reduces 30-day mortality by 2% (7% vs. 9%), recurrent MI by 4% (3% vs. 7%), and stroke by 1%.^26–28 However, this superiority of PCI depends on a DTB <120 minutes and PCI-related delay <60 minutes (delay between the expected time of fibrinolytic therapy and the expected time of balloon inflation). In fact, the “90-minute” and “120-minute” cutoffs of DTB have been established in terms of PCI delays beyond which PCI loses its advantage over fibrinolysis (120-min DTB corresponds to equipoise between PCI and fibrinolysis).

DTB is particularly important if the patient presents early, <3 hours after symptom onset, or if the patient is high-risk (anterior MI, tachycardia, SBP <100 mmHg, Killip class ≥II, age ≥65), as those patients derive the greatest benefit from fibrinolytics and are most harmed by reperfusion delays. In CAPTIM, PRAGUE-2, and the modern STREAM trial, fibrinolytic therapy resulted in the same mortality reduction as primary PCI in patients presenting <2–3 hours after symptom onset (granted that rescue PCI is done if needed, and routine early PCI<24 hours is carried in all patients, as in STREAM).^29–31 Conversely, in low-risk patients presenting late, DTB is less important and, in a large MI registry, PCI-related delays of 100 minutes did not negate the survival advantage of primary PCI over fibrinolytic therapy in those patients.³² In fact, the superiority of PCI over fibrinolysis widens as the presentation is more delayed; while the benefit from fibrinolysis strikingly drops beyond 3 hours, PCI has a less pronounced drop in benefit.³³ In two retrospective analyses that only assessed PCI patients, DTB >90–120 minutes did not impair outcomes vs. DTB<120 min in low-risk patients presenting late.^34,35 Yet in all patients, systems should strive for as small a DTB as possible.

In high-risk patients presenting early, any DTB delay, even within the 90-minute window, is associated with increased mortality compared to a shorter DTB (mortality difference of 0.5–1% for every 30 min DTB delay, e.g., between DTB of 30 min and 60 min).³⁶ This is the rationale behind the ESC recommendations, which go beyond DTB <90 min. ESC recommends a STEMI diagnosis-to-wire crossing time <60 min in patients self-presenting to PCI centers and <90 min in patients transported by paramedics or from non-PCI centers. While this is valuable in early presenters with definite STEMI, keep in mind that aggressive reduction of DTB in all comers on a system level has not been consistently associated with improvement of outcomes,^34,35,37,38 particularly in registries comparing the modern DTB era with a previous era of longer DTB. Overzealous reduction of DTB should not preclude proper clinical and ECG assessment and should not lead to a rushed procedure in a patient whose clinical and ECG picture is not definite for STEMI.

Elderly patients (age >75) – In fibrinolytic trials, the benefit from fibrinolytic therapy was much less striking in the elderly than in the young.^10,39 Conversely, primary PCI remains effective in the elderly, with more absolute mortality reduction in the elderly than in young patients. This makes fibrinolytic therapy, whether standalone or combined with PCI, a less attractive alternative to primary PCI in the elderly. Studies of combined fibrinolytic therapy and PCI included very few patients over the age 75.⁴⁰ In the modern STREAM trial of fibrinolysis vs. PCI, the dose of TNK was reduced by 50% in the elderly midway through the trial, which attenuated intracranial hemorrhage without reducing TNK efficacy.41 Hence, ESC guidelines suggest a half-dose of TNK in the elderly ≥ 75 (class IIa).²

E. Combination of PCI and fibrinolytic therapy

Three different combinations of PCI and fibrinolytics have been studied in STEMI (Figure 2.4):⁴⁰

• Facilitated PCI is a strategy of emergent PCI with a planned door-to-balloon time of <120 minutes. Fibrinolytic therapy is administered “on the way” to a timely PCI.^42,43
  
• Pharmacoinvasive therapy means that fibrinolytic therapy is administered at a non-PCI facility, then the patient is promptly and sys- tematically transferred to a PCI facility, where PCI is performed 2–3 to 24 hours after the start of fibrinolytic therapy, regardless of whether fibrinolysis results in successful reperfusion. Thus, the time to PCI is longer than with facilitated PCI. Facilitated PCI addresses patients primarily treated with a timely PCI, and looks at the value of pre-treatment with fibrinolytics or glycoprotein IIb/IIIa inhibitors (GPI), whereas pharmacoinvasive therapy addresses patients who are primarily treated with fibrinolytics, as they cannot undergo a timely PCI, and looks at the value of routine early PCI after fibrinolysis.^44–46
  
• Rescue PCI refers to PCI that is performed urgently if fibrinolysis fails, failure being defined as persistent hemodynamic or electrical instability, persistent ischemic symptoms, or failure to achieve at least a 50–70% resolution of the maximal ST-segment elevation 90 minutes after fibrinolysis is started.⁴⁷ Approximately 35% of patients treated with fibrinolysis require rescue PCI.^30,44,45

Facilitated PCI has been associated with worse outcomes than primary PCI, probably because the administration of fibrinolytics before a timely PCI cannot offer any ischemic advantage yet increases the bleeding risk. Also, fibrinoytics expose clot-bound thrombin, a potent platelet activator, which heightens platelet activation and aggregation. PCI facilitated with fibrinolytics is associated with increased mortal- ity, ischemic complications, HF, and bleeding (ASSENT-4 trial). Even PCI facilitation with a brief upstream GPI therapy leads to increased bleeding without any ischemic benefit (FINESSE trial).^42,43 Conversely, pharmacoinvasive therapy, also called routine early PCI 2–24 hours after fibrinolytics, has been shown to improve outcomes, mainly recurrent MI and recurrent ischemia in high-risk STEMI, without increasing the bleeding risk (despite the use of femoral access in the trials). Patients who achieve successful reperfusion with fibrinolytics are actually left with severe residual disease in ~85% of the cases, and benefit from early PCI.

A. PCI: microvascular and cellular reperfusion

Approximately 15% of occluded arteries acutely recanalize before the PCI procedure, in the first 4 hours, and achieve TIMI 2 or 3 flow (from spontaneous or antithrombotic-induced lysis). This STEMI is called “transient STEMI”, and may also be called “aborted STEMI” if cardiac biomarkers only rise minimally (CK-MB <2× normal).⁹ Residual stenosis usually persists.^60–62

During PCI, the lesion is dilated with balloon angioplasty then stented. In comparison with standalone balloon angioplasty, stenting reduces the early risk of reocclusion/reinfarction by 50% (to <2%) and the late risk of restenosis, without affecting mortality.⁶¹ Drug-eluting stents are used, as they do not increase late stent thrombosis and significantly reduce restenosis.⁶² A routine initial use of aspiration thrombectomy has not shown superiority to balloon angioplasty in two large trials.⁶³

Following primary PCI, ~95% of patients achieve TIMI 3 flow, while 5% achieve TIMI 0–2 flow despite wide macrovascular patency, also called “no reflow.” The term “no reflow” implies poor microvascular flow and is only used after treating all significant epicardial stenoses. TIMI flow <3 is a predictor of poor outcomes, but TIMI 3 flow does not necessarily imply appropriate microvascular flow. In fact, only ~60% of patients with TIMI 3 flow achieve significant ST-segment resolution (= cellular reperfusion), and only 70% achieve appropriate myocardial blush (= microvascular reperfusion).^63,64 “Appropriate myocardial blush,” also called “myocardial blush grade 2 or 3,” is used to describe brisk contrast staining of the myocardium followed by contrast clearance and no residual myocardial stain by the next injection. Impaired coronary flow, impaired myocardial blush, or the lack of ST resolution implies: (i) distal microembolization, (ii) microvascular spasm, or (iii) myocyte injury and swelling from ischemia or reperfusion injury, especially late reperfusion, sometimes irreversible. The best long-term outcomes (survival and LV function) are seen in patients with ST-segment resolution and good myocardial blush, while intermediate outcomes are seen in patients with discordant findings.⁶⁵

When angiography is performed in patients who have been successfully reperfused with fibrinolytics, data from the pharmacoinva- sive trials suggests that ~15–20% of the infarct-related arteries have a residual stenosis <50% that does not require PCI.^30,43,66,67 While most plaques that lead to MI are <50% at baseline, fibrinolytics often partially dissolve the thrombus, not fully, hence the frequent residual obstruction.

B. Multivessel disease in STEMI

Approximately 50–60% of patients presenting with STEMI have multivessel CAD, and up to 40% have multiple complex plaques.^45,61,68

Outside cardiogenic shock, complete revascularization of non-culprit arteries with stenoses >70%, regardless of the presence of residual symptoms or ischemia, was beneficial and reduced the 3-year risk of future MI, mainly NSTEMI, in comparison to culprit-only PCI, according to the large COMPLETE trial (5.4% vs. 7.9%); of note, mortality was not reduced. Non-culprit PCI was performed during a procedure separate from culprit PCI, within the same hospitalization or up to 45 days after discharge.⁷⁰ Other trials have suggested the safety of non-culprit PCI in the same setting as culprit PCI (PRAMI, Compare-acute) or separately during the same hospitalization (DANAMI-3 PRIMULTI).^71,72 Only COMPLETE has shown a reduction in MI, and thus, non-culprit PCI at a separate setting may be favored, during the same hospitalization (especially if critical stenosis >90%) or soon after it, as long as non-culprit PCI is feasible and the patient is not too sick to tolerate it. Immediate non-culprit PCI may be performed, while accounting for the complexity of PCIs and the total contrast load.

CABG is rarely required acutely in STEMI (~0.2-1%),^62,63 but may be more frequently required in patients with cardiogenic shock and severe left main or three-vessel disease. In fact, in the SHOCK trial, 37% of invasively managed patients were emergently revascularized with CABG (a median of 2.7 hours after randomization, 19 hours after MI).⁷³ Acute CABG may also be required after a failed PCI.

If staged CABG is judged necessary for full revascularization of non-culprit arteries after culprit PCI, it is preferred to wait at least 24 hours, and preferably 3–7 days. CABG mortality is increased in the first 3 days after a large MI.⁷⁴ In patients who developed RV infarct and were not successfully reperfused in the first 6 hours, it is better to delay CABG 4 weeks to let the RV heal (otherwise, there may be severe, intractable RV dilatation upon opening the pericardium during CABG). In a patient with left main or three-vessel disease and RCA-related MI, the RCA is stented and CABG performed 1 month later. If CAD is critical (e.g., > 75% left main stenosis), one may recanalize the RCA with balloon angioplasty and perform CABG sooner, a few days later.

A. Antithrombotic therapies in conjunction with primary PCI

1. Aspirin 325 mg upon presentation.
   
2. ADP-receptor antagonist is loaded at the time of PCI, or in the emergency room before catheterization if STEMI diagnosis is certain.⁷⁵ Even prasugrel may be loaded before catheterization in STEMI. Yet, ATLANTIC trial failed to show a benefit of pre-cath loading vs. loading during PCI.⁷⁶
   

   Ticagrelor and prasugrel are preferred as they further reduce ischemic events compared to clopidogrel, particularly in STEMI.

   
   
3. Upstream unfractionated heparin (UFH) in the ED (60 units/kg, up to a maximum dose of 4000 units).
   
4. During PCI:
   
   
   
   • UFH
     
   • Bivalirudin vs. UFH: initial studies suggested lower bleeding with bivalirudin, but these studies were flawed by an unbalanced GPI use with UFH. A radial-access study with balanced and limited GPI use (SWEDEHEART) showed an ischemic and bleeding risk identical to UFH.⁷⁷ Also, bivalirudin may be associated with a higher risk of acute stent thrombosis than UFH, which is reduced by 1-4 hours of high-dose bivalirudin post-PCI.
     

     Except for this optional brief infusion of bivalirudin, anticoagulants are stopped after PCI.

     
     
   • GPI, in conjunction with either UFH or bivalirudin, is reserved for bailout use during PCI (large thrombus burden, thrombotic complications, or no reflow) (class IIa).⁷⁸ In contemporary trials, ~15% of STEMI patients require the use of GPI.

B. Antithrombotic therapies in patients treated with fibrinolytics (started upon presentation)

1. Aspirin 325 mg.
   
2. Clopidogrel 300 mg load if patient is <75 years old, or 75 mg if >75 years old (300 mg rather than 600 mg is the dose studied with fibrinolytics, even in pharmacoinvasive trials; 75 mg is the only dose studied with fibrinolytics in elderly patients).^79,80
   
3. UFH IV bolus 60 units/kg (not more than 4000 units), followed immediately by heparin drip 12 units/kg/h, adjusted Q6h to keep the PTT 1.5–2.0× the control.

If the patient is going to have fibrinolytic reperfusion rather than PCI reperfusion, and if PCI is not expected in the next 24 hours, enoxaparin SQ or fondaparinux SQ may be used instead of UFH. In the patient receiving primary fibrinolytic reperfusion, enoxaparin or fondaparinux has a more favorable effect on reinfarction risk than UFH, with less major bleeding with fondaparinux, vs. more major bleeding with enoxaparin.^81,82 Patients undergoing standalone fibrinolytic therapy should receive anticoagulants for at least 48 hours and preferably for the duration of the hospitalization. Regimens other than UFH are preferred for anticoagulation >48 hours, because UFH is of no proven benefit beyond 48 hours.

• Dosage of enoxaparin: initial 30 mg IV dose, followed 15 minutes later by 1 mg/kg SQ Q12h
  
  
  
  • For patients >75 years old, avoid IV dose and administer 0.75 mg/kg Q12h
    
  • If GFR <30 ml/min, administer 1 mg/kg SQ Q24h
  
  
• Dosage of fondaparinux: 2.5 mg IV initially, then 2.5 mg SQ Qday. Avoid if GFR <30 ml/min.

A. Killip classification uses clinical features upon presentation to assess STEMI prognosis.

• Class I: no HF (30-day mortality = 3%)⁹⁶
  
• Class II: crackles up to one-third of the lung fields or S3 (= HF, mortality = 13%)
  
• Class III: pulmonary edema (mortality = 27%)
  
• Class IV: cardiogenic shock (mortality = 50–60%)

Note that Killip classification is only applied at presentation. It also has a prognostic value in NSTE-ACS.

B. TIMI risk score for STEMI

Depending on the STEMI TIMI risk score (Table 2.3), the 30-day mortality of fibrinolytic-treated STEMI patients ranges from 1% to 35%.⁹⁷ The benefit of reperfusion is highest in the higher risk groups.

C.Troponin I peaks at a level of 50–300 ng/ml (at ~24 h), CK typically peaks at 2500–5000 units/l (at 18–24 h). Reperfusion therapy makes these biomarkers peak earlier and often at higher levels; however, the total volume of CK or troponin released is smaller, i.e., the distribution curves over time are narrower and the decline is faster (3–4 days for troponin I). The CK or troponin mass, rather than the CK or troponin peak, correlates with the infarct size and the prognosis. Aborted STEMI, whether aborted spontaneously or with very early reperfusion, is characterized by a biomarker rise that is usually mild (CK-MB <2× normal).

A. Discharge medications

See Chapter 1, Section VI.

B.EF improves 1–3 months after discharge and justifies follow-up echocardiography for risk assessment. There are two explanations for EF improvement:

• LV dysfunction that occurs immediately after MI is partly due to post-ischemic stunning rather than necrosis. When an artery occludes transiently, necrosis occurs in part of the myocardium, while dysfunction without necrosis, called stunning, occurs in other parts. The stunned myocardium recovers over the course of days to weeks after arterial recanalization.
  
• ACE-Is, β-blockers, and aldosterone antagonists reduce LV remodeling and LV size, allowing an increase in EF for the same amount of necrotic myocardium (Figure 2.5). Each one of these drugs allows an EF improvement of up to 5%.

C. ICD

The risk of sudden death is highest in the first 30 days after MI (1.2%) and increases with HF and severe LV dysfunction (~3%).⁹⁸ However, placing an ICD in the first 40 days after MI has not been shown to reduce the overall mortality; it reduces sudden-death mortality by 50%, but the patients prone to early sudden death are typically high-risk patients also prone to dying from pump failure or recurrent MI.^99,100 Early ICD placement only changes the mode of death of these patients, from sudden death to pump-failure death (conversion hypothesis). Also, early LV dysfunction/stunning may improve and some patients may turn out to be at a lower long-term risk than expected, and thus would not require an ICD. Therefore, ICD is indicated for primary prevention of VT/VF if EF is ≤35% at 40 days post-MI.

On the other hand, ICD is indicated early on, before hospital discharge, for the patient who develops sustained VT or VF anytime beyond the first 2 days after MI.