ST-Segment Elevation Myocardial Infarction

ST-Segment Elevation Myocardial Infarction


I. Definition

STEMI is a clinical syndrome of angina or angina equivalent along with:13

  • ST-segment elevation ≥2 mm in men or ≥1.5 mm in women in leads V2–V3, or ≥1 mm in two other contiguous chest or limb leads, with a shape consistent with ischemic ST elevation. The shape must be distinguished from early repolarization, pericarditis, or ST-segment elevation secondary to LVH or LBBB; emergent echo or coronary angiography may be performed in case of doubt.


  • Isolated or most prominent ST-segment depression in leads V1–V3 ≥ 0.5 mm, which is reciprocal to posterior ST elevation in leads V7-V9 (true posterior STEMI). In leads V7–V9, the ST-segment elevation cutoff is only 0.5 mm, as the distant location of these leads behind the heart minimizes ST-segment elevation.

ST-segment elevation below these cut-points may still imply myocardial injury when the clinical setting or the ST-segment morphology suggests ischemia. Emergent reperfusion may still be indicated in these patients, generally with PCI (thrombolysis is not an established therapy for mild degrees of ST elevation, <1 mm).

Conversely, ST-segment elevation that exceeds these cut-points may not represent STEMI. Careful attention to the morphology of the ST segment and the associated features (Q wave, inverted or ample T wave) is critical.

STEMI usually evolves into electrocardiographic Q waves (Q-wave MI) and is usually a transmural and large MI. NSTEMI usually evolves into a non-Q-wave MI and is usually a subendocardial, smaller MI. However, there is some overlap: STEMI may not generate Q waves while NSTEMI may generate Q waves.

Since it takes up to 3 hours for troponin to rise after the onset of infarction, it should not be relied upon for the diagnosis or initiation of emergent therapies.

Approximately 12.5% of MIs are totally silent and ~12.5% have a mild, atypical presentation (e.g., dyspnea, malaise, nausea).4 These cases go unrecognized, and patients may present with HF days or months after acute MI. This presentation is more common in diabetic and elderly patients.

II. Timing of reperfusion

  1. Emergent reperfusion with PCI or fibrinolytics is indicated in patients who present within 12 (24) hours of symptom onset and who have persistent ST elevation in two or more contiguous leads or ST depression that is isolated or most prominent in V1–V3 (class I recommendation for PCI or fibrinolytics at ≤12 h, class IIa for PCI at 12–24 h).1 This applies even if ischemic symptoms have resolved, as long as ST elevation is persistent and the onset of ischemic symptoms is ≤24 hours.

    PCI is the preferred strategy, and it should be performed with a door-to-balloon time (DTB) of ≤90 min in patients presenting to PCI- capable hospitals, and ≤120 min in patients transferred from non-PCI-capable to PCI-capable hospitals. If PCI cannot be performed with a DTB of ≤120 min, fibrinolytics should be given to patients presenting within 12 hours of symptom onset (initiated ≤ 10 min from diagnosis).* Regardless of the setting, the DTB that mitigates PCI’s benefit over fibrinolysis is 120 min (ESC).

  2. Patients presenting >24 hours after symptom onset generally do not have an indication for emergent PCI. Emergent PCI (not fibrinolysis) is selectively indicated in some of these patients, such as patients with persistent ischemic symptoms, cardiogenic shock, acute severe HF with massive pulmonary edema, or when the onset of STEMI is not clearly >24 hours.

    Otherwise, non-urgent coronary angiography and PCI are indicated in patients with recurrent chest pain at rest or mild exertion or severe ischemia on stress testing.

III. ECG phases of STEMI (Figure 2.1)

Schematic illustration of phases of STEMI.

Figure 2.1 Phases of STEMI.

Phase 3 does not imply that MI has already been too prolonged to benefit from PCI; some patients with phase 3 morphology have had only a brief period of ischemia.

ST elevation may persist for days, weeks, or chronically >3 weeks in patients with a dyskinetic or aneurysmal myocardium. In this case, the age of the infarct is implied clinically. Let’s take the case of a patient who had chest discomfort several days previously and currently has HF without angina; if his ECG shows Q waves and ST elevation, his STEMI is likely >24 hours old and the persistent ST elevation likely reflects dyskinesia. An echocardiogram showing a dilated LV with a truly thin wall in diastole confirms this suspicion.

The inverted T waves may persist for days, weeks, months, or even years. Patients with LV dyskinesia and persistent ST-segment elevation may have chronic T-wave inversion as well.

IV. STEMI diagnostic tips and clinical vignettes

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%).57 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?

Schematic illustration of a patient presents with chest discomfort that has lasted 3 hours and resolved 2 hours ago.

Figure 2.2 The patient presents with chest discomfort that has lasted 3 hours and resolved 2 hours ago. Subtle ST elevation is seen in leads II and aVF, and in leads V5 and V6, with subtle ST depression in V1–V2. Three features suggest that this mild ST elevation is actually STEMI: (i) Q waves; (ii) ST depression in reciprocal leads (V1–V2); (iii) wide T-wave morphology and fused ST-T segments in leads I, II, V5, and V6 (arrows). This patient qualifies for emergent catheterization since his discomfort occurred in the last 24 hours. He is found to have an acutely occluded large obtuse marginal branch.

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.

V. Specific case of new or presumably new LBBB

Normally, LBBB is associated with ST-segment deviation that is discordant to QRS, i.e., directed opposite to QRS. If a patient has an ischemic presentation and LBBB on the ECG, one cannot tell whether ST elevation is purely secondary to LBBB, if an ischemic injury is partially contributing to the ST elevation, or if there is ischemic ST depression masked by the ST elevation. STEMI is definite if ST abnormality is concordant to QRS, but STEMI or non-ST elevation ischemia is still possible if ST changes are discordant to QRS. This would be the case of a patient with a true anterior injury in V1–V4 or inferior injury, where LBBB’s QRS is negative and where ischemic ST elevation would inherently appear discordant. RBBB, on the other hand, is not associated with significant ST abnormality, and thus ST changes in a patient with RBBB are diagnostic of ischemia. Early thrombolytic trials and their meta-analysis have shown a striking benefit from thrombolytic therapy in patients with any bundle branch block, particularly that a new bundle branch block in STEMI indicates a high-risk STEMI.10 Both types of bundle branch blocks, if secondary to STEMI, represent high-risk categories, but since only LBBB poses a diagnostic challenge, a new or presumably new LBBB has been considered a STEMI equivalent in old ACC guidelines, in order not to miss a high-risk STEMI.

However, STEMI rarely causes left bundle branch infarction, because the left bundle is supplied by both the LAD and RCA and is only affected in extensive infarction. In the GUSTO-1 trial, only ~1% of STEMIs had LBBB on presentation. In fact, a new LBBB often results from a chronic cardiomyopathy, ischemic or non-ischemic, with a dilated or hypertrophied myocardium, rather than an exten- sive acute infarction, and may be first diagnosed in the setting of HF presentation or uncontrolled HTN. 11 A new LBBB may also be rate-related and may have been unveiled by an increase in heart rate.

Evidence has shown that only ~10% of patients with an ischemic presentation and a new LBBB have a STEMI-equivalent (acute coro- nary occlusion on angiography), and <40% have any MI, most commonly NSTEMI.1215 STEMI is even far less likely when all comers with new LBBB, both atypical or typical presentations, are included (<5%).14 Therefore, in order to make the diagnosis of STEMI, an ischemic presentation is required (ongoing angina, flash pulmonary edema) along with additional ECG features:

  • Concordant ST-segment depression or elevation of ≥1 mm is >95% specific for the diagnosis of STEMI, but has a limited sensitivity of 20% (Sgarbossa’s concordance). If present, STEMI diagnosis is definite, and emergent reperfusion with fibrinolytics or PCI should be achieved.
  • Concordant negative T wave or biphasic T wave in multiple leads increases the likelihood of STEMI.
  • Extreme discordance increases the likelihood of STEMI but has a reduced specificity: discordant ST elevation that exceeds 25% of the QRS height; or upright T wave that exceeds 50% of the QRS height. This discordance ratio is more sensitive and specific than an absolute ST discordance >5 mm, initially suggested by Sgarbossa, but may still be seen in 9% of control patients without MI.16

In the absence of these features, particularly Sgarbossa’s concordance, and in the absence of ongoing typical angina, it is reasonable to urgently perform bedside echocardiography. The presence of a segmental wall motion abnormality without severe thinning, aneurysm, or severe LV dilatation suggests acute ischemia and warrants early angiography; fibrinolytics are preferably avoided since many of these patients have NSTEMI rather than STEMI, and transfer for angiography is preferred even if delays are expected to exceed 120 minutes.12 Abnormal septal motion is universal with LBBB but the anterior and apical contraction is preserved; therefore, anterior and apical akinesis implies ischemia. Global hypokinesis often implies ischemic or non-ischemic cardiomyopathy, such as hypertensive cardiomyopathy, rather than acute ischemia;11 angiography may be needed eventually but is not urgent.

Thus, the 2013 STEMI guidelines state that “new or presumably new LBBB should not be considered diagnostic of acute myo- cardial infarction (MI) in isolation.” 1 The 2020 ESC ACS guidelines state: “hemodynamically stable patients presenting with chest pain and LBBB only have a slightly higher risk of having MI compared to patients without LBBB.”

VI. Reperfusion strategies: fibrinolytics, primary PCI, and combined fibrinolytics–PCI

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:10,1719

  • 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.

Table 2.1 Limitations and contraindications of fibrinolysis.


  • Patency of the infarct-related artery (TIMI 2 or 3 flow) is achieved in ~75–80%. TIMI 3 flow is achieved in 55–60% a
  • Intracranial hemorrhage: 0.5–1.5%
  • Major bleeding: ~5%
  • Early recurrent ischemia or MI: 10–20% (within hours or days)

Most important absolute contraindications

  • Any prior intracranial hemorrhage
  • Ischemic stroke <3 months. Ischemic stroke >3 months is a relative contraindication
  • Severe acute hypertension unresponsive to acute therapy
  • Active bleeding (except menses)
  • Cranial or spinal surgery <2 months
  • Closed head or facial trauma <1 month, even without a documented bleed (e.g., recent fall with head trauma)

Most important relative contraindications

  • Ischemic stroke >3 months
  • Severe acute HTN (SBP >180 or DBP >110) responsive to acute therapy
  • Chronic severe hypertension
  • Recent major surgery or internal bleed <2–4 weeks. Proliferative retinopathy is not a contraindication
  • Oral anticoagulant therapy, including warfarin with INR >2 (strong relative contraindication)

a Full patency with <50% residual disease is achieved in only 15–20%.

Schematic illustration of fibrinolysis cascade and mechanism of action of fibrinolytics.

Figure 2.3 Fibrinolysis cascade and mechanism of action of fibrinolytics. Fibrinolytics activate plasminogen into plasmin, which degrades fibrin. PAI-1, plasminogen activator inhibitor (~ tPA inhibitor); r-PA, reteplase; r-tPA, alteplase; TNK, tenecteplase; tPA, tissue plasminogen activator.

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%.2628 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).2931 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.4446
  • 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.

Schematic illustration of the timing of PCI in relation to thrombolysis in the pharmacoinvasive strategy, rescue PCI strategy, and facilitated PCI strategy, with the clinical trials that addressed and defined these strategies.

Figure 2.4 The timing of PCI in relation to thrombolysis in the pharmacoinvasive strategy, rescue PCI strategy, and facilitated PCI strategy, with the clinical trials that addressed and defined these strategies.

F. Putting it all together: management of patients presenting to non-PCI-capable hospitals

  1. If there is a pre-established transfer system with a predicted DTB <120 minutes, a transfer for primary PCI is the best strategy and is superior to fibrinolysis (DANAMI-2 and PRAGUE trials).27 This usually implies a distance <60 miles, often with a helicopter transfer, a door-in door-out time <30 minutes, direct activation of the outside PCI team through a central pager, and direct transfer to the outside cath lab.48
  2. When DTB is expected to be >120 minutes, administer primary fibrinolytic therapy and immediately transfer the patient to allow the performance of routine early PCI 2–24 hours later, or to allow immediate rescue PCI if no response to fibrinolysis. Several registries suggest that timely fibrinolysis followed by semiurgent transfer for PCI offers a benefit similar to that seen in patients presenting to a PCI hospital and undergoing a timely primary PCI.48,49

    Beside fibrinolytics, the patient should receive aspirin, heparin bolus and infusion, and 300 mg of clopidogrel. Prasugrel, ticagrelor, or 600 mg of clopidogrel have not been studied in the first 24 hours of fibrinolytic therapy and may only be used if PCI is performed >24 hours later. Subcutaneous enoxaparin is not appropriate in patients undergoing early PCI. Glycoprotein IIb/IIa inhibitors may be used during PCI (rather than upstream of PCI).44

  3. When DTB is expected to be >120 minutes but the patient is presenting >3–4 hours after symptom onset and has a non-anterior MI with low-risk clinical features (Killip class I, heart rate <100 bpm, SBP >100 mmHg), a transfer for primary PCI without preceding fibrinolytic therapy may be reasonable in individual cases, although not clearly expressed in the guidelines.
  4. If fibrinolytic therapy is contraindicated, immediately transfer for primary PCI regardless of the expected DTB.
  5. For cardiogenic shock or acute severe HF (Killip class III or IV), administer fibrinolytic therapy if DTB is expected to be >120 minutes, and immediately transfer for PCI.
  6. In patients presenting early, prehospital fibrinolytic therapy delivered by paramedics and followed by early transfer to a PCI facility has been associated with further reduction in mortality compared with in-hospital fibrinolytic therapy according to a meta-analysis of randomized trials, and a mortality comparable to that of primary PCI (STREAM, CAPTIM trial).30,50 This is the preferred strategy in patients unable to undergo timely PCI, in regions where such a system can be implemented, as per ESC guidelines.49

VII. Coronary angiography and PCI later than 24 hours after presentation-role of stress testing

In the OAT trial, patients with MI older than 24 hours (1–28 days old specifically, mainly STEMI/Q-wave MI), who were selected based on the following features did not benefit from PCI and had a trend towards more frequent reinfarctions:53

  • Totally occluded infarct-related artery (TIMI 0 or 1 flow)
  • Akinetic or dyskinetic infarcted wall
  • One- or two-vessel CAD
  • No recurrent rest or low-threshold angina
  • No severe ischemia on stress testing
  • No shock and no persistent functional class III–IV HF

Further analysis showed that PCI was not beneficial even among patients enrolled 1–3 days after MI onset.54 Thus, late PCI of an occluded infarct artery is only indicated in patients with persistent ischemic symptoms, persistent HF, or severe ischemia on stress testing.

On the other hand, data suggest that an infarct artery that is not totally occluded (TIMI 2–3 flow) may benefit from late revasculariza- tion (>24 h) to the same extent that it may benefit from early revascularization, as a patent infarct artery with good collaterals is associated with a more limited MI size and a significant amount of viable myocardium that can be salvaged with revascularization.5557 Approximately 35% of totally occluded infarct-related arteries spontaneously recanalize in the first 24 hours and may qualify for late revascularization.

Therefore, patients who did not receive emergent reperfusion (late presenters >24 hours) or patients who received fibrinolytics, with or without response, but did not undergo angiography in the first 24 hours after symptom onset may still undergo angiography later than 24 hours (class II):

  • A non-occluded infarct-related artery may be treated with PCI (class IIb).
  • Left main disease or three-vessel CAD that largely extends beyond the occluded artery should receive revascularization, typically surgical revascularization, after a post-MI waiting period of at least 3–7 days.
  • A totally occluded artery should not be treated with PCI unless the patient has a low-threshold angina, severe ischemia on stress testing (class I), or persistent HF after initial therapy (high-risk case with stress test contraindication). If not performed before angiography, the stress test may be performed afterwards, and the patient brought back for PCI once severe ischemia is documented.
  • If one is unsure that the MI is >24 hours old, PCI may still be performed. While not beneficial, late PCI in the OAT trial was not significantly harmful either, which may justify its use when timing is unclear. Not that ESC uses 48 hours cutoff for avoidance of routine PCI.

Table 2.2 summarizes the PCI timelines. Questions 2, 9,10, and 14 at the end of this chapter illustrate these concepts.

Table 2.2 Revascularization timelines in STEMI.

<12 h after STEMI onset: Emergent primary PCI or fibrinolytic therapy (class I, level of evidence A)
12–24 h: Emergent primary PCI (class IIa). ESC uses 48-h cutoff
>24 h: Delayed, non-emergent PCI for: (i) recurrent angina, (ii) severe ischemia on stress testing (class I), (iii) persistent HF.
After fibrinolytic therapy

  • Delayed routine PCI 3–24 h later (2-24 h per ESC) (class IIa ACC, class I ESC)
  • Rescue PCI for fibrinolytic failure (class I ESC)

If PCI was not performed in the first 24 h, whether the patient received fibrinolytic therapy, with or without success, or did not receive fibrinolytic therapy
In the absence of angina recurrence, stress testing is an alternative to coronary angiography. Coronary angiography and late revascularization have the following recommendations:

  • Coronary angiography >24 h after STEMI onset: class IIa
  • PCI of a stenotic but not totally occluded artery: class IIb
  • Avoid PCI of a totally occluded artery >24 h (OAT trial, class III), except in cases of recurrent angina, high-risk stress test (class I), persistent HF with severe functional limitation, or uncertain timing. ESC uses 48-h cutoff
  • CABG if left main or three-vessel CAD extending largely beyond the infarct artery

Cardiogenic shock or acute severe HF (massive pulmonary edema = Killip III): emergent PCI regardless of time (class I)

The OAT trial does not apply to a coronary chronic total occlusion (CTO) that has not led to a large transmural infarct, in which case the myocardial contractility is fairly preserved because of the collateral network. A progressive occlusion that allows for an adequate collateral network to develop may not present as MI. It typically presents as chronic angina or a small NSTEMI, not STEMI. Opening a CTO has a beneficial effect on symptoms and, possibly, LV function.

VIII. Angiographic findings, PCI, and cellular reperfusion; multivessel disease in STEMI

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.6062

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.

IX. Antithrombotic therapies in STEMI

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.

X. Other acute therapies

  1. β -Blockers (e.g., metoprolol orally 25 mg Q8–12h, titrated to 50 mg Q8–12h). A meta-analysis of old trials addressing β-blockers in acute MI has shown that β-blockers reduce mortality after MI, whether HF is present or not.83 In the COMMIT-CCS trial, the use of β-blockers beyond the first 24–48 hours after MI was beneficial and significantly reduced the risk of recurrent MI and VF at 15 days.84 However, the earlier administration of β-blockers, especially IV β-blockers, increased the risk of cardiogenic shock, particularly in high-risk subgroups, where a net adverse effect was seen. Thus, β-blockers should be acutely avoided in these subgroups:

  • Killip class ≥ II (any degree of HF); age >70 years.
  • Sinus tachycardia >110 bpm: The more tachycardic the patient, the less likely he is to acutely benefit from β-blockers. In general, tachycardia reflects a large MI and compensates for a low stroke volume (pre-shock state). Slowing the heart rate precipitates shock.
  • SBP <120 mmHg or 30 mmHg lower than baseline, or evidence of low output. However, beyond the first 24–48 hours, SBP <90–100 mmHg, rather than 120 mmHg, is the contraindication to β-blocker use.
  • Also, avoid β-blockers in other classic contraindications: Sinus bradycardia <60 bpm, PR >0.24 s, any second- or third-degree AV block, history of severe asthma, or active bronchospasm.

    β-Blockers are generally titrated to the maximal tolerated dose before hospital discharge and are expected to have a short- and long-term benefit, for up to one year in patients with normal EF.85-87 In patients with LVEF <40% or patients who developed HF but are now stable, β-blockers are started slowly, later than 24 hours, then titrated in the outpatient setting (e.g., carvedilol is started as 6.25 mg BID in the hospital, 3 days after MI, and uptitrated every 3–10 days, as in the CAPRICORN trial; this regimen reduced late mortality in patients with low EF, with or without HF).88

  • Oral ACE-Is (or ARBs if cough or angioedema occurs with ACE-I). Wait a few hours before starting an ACE-I to ensure the patient is stable and not evolving into cardiogenic shock. Try to start an ACE-I early, in the first 24 hours. In landmark trials of ACE-inhibition in acute MI, ACE-I was initiated in the first 24 hours of all types of MI, whether anterior or inferior, accompanied by HF or not, and improved early mortality (survival curves start to diverge at day 1 and become significant at 1 week and 6 weeks).89,90 ACE-I therapy is particularly beneficial in LV dysfunction, anterior MI or HF (SAVE trial).91 The benefit is less marked when ACE-I is used unselectively in all MI patients, including those with inferior MI and without HF, but ACE-I is still reasonable for a duration of 6 weeks, as in those trials. ACE-I is avoided in acute renal failure or when SBP <100 mmHg or 30 mmHg below baseline; intravenous ACE-I is avoided in all patients because of the risk of hypotension. A low-dose, short-acting ACE-I may be used in the acute setting in order to verify tolerability. Sacubitril-valsartan did not prove superior to ACE-I in acute MI with low EF (PARADISE-MI trial). Examples of ACE-I dosing:

    • Captopril 6.25 mg TID, to be doubled with each subsequent dosage, until 50 mg TID
    • or Lisinopril 5 mg Qday, to be increased to 20–40 mg Qday

  • Nitroglycerin. Administer 0.4 mg of sublingual NTG up to three times during active angina, then start IV drip if tolerated hemodynamically. NTG is useful for chest pain, HTN, or HF concomitant to MI. It may lead to hypotension or vagal shock and should be avoided if SBP

    <100 mmHg, bradycardia <50 bpm, tachycardia >100 bpm, or if RV infarct is suspected with inferior MI (even if RV infarct is clinically silent).

  • Morphine. Administer morphine if the pain is severe and uncontrolled despite NTG, provided that reperfusion therapy is underway.
  • High statin dose (atorvastatin 80 mg, rosuvastatin 20 mg)
  • Glucose control. In hyperglycemia, with or without prior diabetes, insulin (IV or SQ) is administered to maintain blood glucose

    ≤180 mg/dl during acute MI/ACS. Afterwards, when the patient is less ill, try to achieve normoglycemia.92

  • Monitoring. The patient is monitored in a coronary care unit for 12–24 hours, then transferred to a step-down unit in the absence of complications. In general, an uncomplicated STEMI is safely discharged after 72 hours of hospitalization (PAMI-II trial), or even 48 hours according to modern data.93-95 Patients qualify for early discharge if they undergo a successful reperfusion with primary PCI, have one- or two-vessel CAD, are younger than 70 years of age without major comorbidities, and have no arrhyth- mias or pump failure.
  • Echo. Echo should be performed before hospital discharge in all patients, and should be performed or repeated urgently in a patient with shock or suspected mechanical complication.

XI. Risk stratification

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).

XII. LV remodeling and infarct expansion after MI (see Figure 2.5)

XIII. Discharge, EF improvement, ICD

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%.


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.

Table 2.3 STEMI TIMI risk score.

Variable Score
Age ≥65 yr / ≥75 yr 2 for ≥65; 3 for ≥75
SBP <100 mmHg 3
Sinus tachycardia >100 bpm 2
Killip class ≥ II 2
Anterior location of MI or LBBB 1
Prior history of diabetes, HTN, or angina 1
Time to treatment >4 h after symptom onset 1
Weight <67 kg (higher bleeding with fibrinolytics) 1

30-day mortality according to the score: score ≤2 → <2.2%; score 3–4 → 4–7%; score ≥5→ >12%.

Schematic illustration of stages of negative LV remodeling post-MI, also called infarct expansion.

Figure 2.5, Stages of negative LV remodeling post-MI, also called infarct expansion.

For the same amount of necrosis, the dashed infarcted area thins and stretches out (from 1 to 2). Then, this stretched infarcted area increases tension at its edges (arrows), which eventually leads to progressive dilatation of the normal, non-necrotic myocardium (from 2 to 3). The dilatation occurs as a compensatory attempt to increase stroke volume, albeit counterproductive and maladaptive. The LV loses its normal elliptical shape and becomes a sphere, which further increases wall stress and reduces the efficiency of the non-infarcted myocardium.

Thus, for the same amount of tissue necrosis the infarcted area and the EF vary largely, depending on:

  1. Loading conditions.
  2. Opening of the occluded artery, even at a time when necrosis has already occurred (e.g., 3–24 h). Reperfusion accelerates myocardial scar formation and turgor and reduces the thinning of the necrotic area, even if it does not salvage myocardium beyond 3–6 hours.
  3. Medical therapy: ACE-Is reduce afterload and exert a direct myocardial effect that reduces LV dilatation and reduces fibrosis in peri-infarct areas. Aldosterone antagonists also exert a direct myocardial effect that reduces LV dilatation and fibrosis. β-Blockers reduce the high wall stress induced by the sympathetic tone. Diuretics reduce preload and afterload.


I. Cardiogenic shock

A. Differential diagnosis (see Table 2.4)

B. Pathophysiology of LV-related cardiogenic shock and failure in acute MI

In the SHOCK trial, LVEF was ~30 ± 12%, implying that at least half the patients only had a moderate LV insult and a moderate reduction of LV systolic function.73 Also, ~40% of patients had non-anterior MI, mainly inferior MI.73,102 Thus, an EF that is well tolerated in chronic HF may be associated with cardiogenic shock in acute MI. In a way, this is similar to tolerating chronic MR or AI vs. developing shock with acute MR or AI. Beside systolic dysfunction, several mechanisms explain cardiogenic shock in acute MI:

  • While the progressive LV dilatation that occurs chronically raises afterload and is maladaptive, some early degree of LV dilatation is adaptive and increases stroke volume at a given LV contractility. Also, some degree of LA dilatation is adaptive and lessens the rise in backward pressure. This is similar to the chronic LV adaptation to MR or AI. In fact, half of patients with cardiogenic shock have a small or normal-size LV, which represents failure of the mechanism of acute LV dilatation.103,104

Table 2.4 Differential diagnosis of shock in MI.

  1. LV-related cardiogenic shock: anterior MI, MI with a prior history of MI or LV dysfunction, or MI in a patient with multivessel CAD. Cardiogenic shock occurs in 4–7% of STEMI (vs. 2.5% of NSTEMI). It is occasionally present on admission, and more typically develops soon after admission, at a median of 5.5 hours after MI onset (vs. a later shock development, at ~3 days, in NSTEMI with three-vessel disease).
  2. RV infarct: RV-related shock should be considered whenever hypotension occurs in inferior MI. RV infarct occurs in 30% of inferior MIs, mainly with proximal RCA occlusion. Only one-half of RV infarcts produce clinical RV failure.
  3. Mechanical complications (mitral regurgitation, ventricular septal rupture, free wall rupture) or tamponade.
  4. Arrhythmias (inappropriate bradycardia, advanced AV block, VT).
  5. Vagal stimulation and vagal shock in inferior MI. It manifests as bradycardia with clear lungs and low JVP. It is treated with atropine and fluid administration.
  6. Hypovolemic hypotension: hypotension with clear lungs, low JVP, and no bradycardia. May attempt small fluid challenge in this situation.

During or after PCI, shock may develop from the use of sedative and vasodilatory drugs in a patient with limited cardiac output reserve, or from myocardial reperfusion injury that aggravates myocardial depression. Coronary reocclusion, coronary perforation with tamponade, and bleeding complications are also considered.

  • For a given LV contractility, the more severe impairment of LV compliance in acute MI leads to a more severe rise of LV filling pressure, which further reduces coronary perfusion pressure.

  • Transient hypotension (drugs, arrhythmia, sedation) in an initially stable patient may transiently reduce coronary blood flow and thus initiate a vicious circle of progressive myocardial ischemia that sustains the hypotension. Furthermore, since the pulmonary edema of MI results from volume redistribution rather than florid volume overload, aggressive diuresis may precipitate shock in MI. Also, β-blockers, ACE-Is, and other vasodilators, including sedatives administered during PCI or during intubation, may precipitate shock in a pre-shock patient who depends on the compensatory vasoconstriction and tachycardia. This partly explains why cardiogenic shock often develops after hospital admission.
  • In over 25% of MI-associated cardiogenic shock, SVR is inappropriately low or normal rather than elevated, despite the use of vasopres-sors (SVR ≤1000–5).105 This mismatch between myocardial depression and inappropriate vasodilatation (or lack of compensa- tory vasoconstriction) may result in cardiogenic shock. Also, 18% of patients, mainly those with a low initial SVR, go on to develop a clinical picture of sepsis with fever or leukocytosis 2–4 days later, mostly with positive bacterial cultures. Thus, inappropriate vasodilata- tion is initiated by a systemic inflammatory response syndrome (SIRS) secondary to MI early on, then a septic process later on, and contributes to shock in a substantial proportion of patients. This implies a role for vasopressors in this subset of patients. High levels of cytokines and inducible nitric oxide synthase, beyond the healthy levels of endothelial nitric oxide synthase, precipitate vasodilatation and further myocardial depression. The initial vasodilatation, per se, is associated with an increased risk of later sepsis (bacterial translocation?).105

Some patients with a pre-shock state before PCI develop a full-blown shock after PCI. PCI may initiate a reperfusion injury with further activation of inducible nitric oxide synthase, and thus vasodilatation and myocardial depression. This is a temporary phenomenon, as the benefit from PCI eventually takes over. Also, the use of sedatives and supine positioning may precipitate shock during PCI.

C. Management of LV-related cardiogenic shock

A shock is defined as sustained SBP <90 mmHg for at least 30 minutes, with signs of low perfusion (oliguria <30 ml/h, cold/clammy extremi- ties, impaired mentation, increased lactate >2 mmol/l).73 LV-related cardiogenic shock is characterized by additional features suggestive of increased left-sided filling pressure, such as clinical or radiographic pulmonary edema. Supportive hemodynamic features consist of a car- diac index ≤2.2 l/min and PCWP ≥15 mmHg, but right heart catheterization was not absolutely required in the SHOCK trial when pulmo- nary congestion was evident in a patient with anterior MI. Echo may be used to assess left-sided filling pressures and confirm the diagnosis, in addition to ruling out mechanical complications.

In the SHOCK trial, patients with cardiogenic shock and STEMI or Q-wave MI of less than 36 hours’ duration were randomized to emergent revascularization vs. medical therapy. The median time from the onset of MI to shock was 5.6 hours, from MI to PCI 11 hours, and from MI to CABG 19 hours. Approximately 65% of patients had three-vessel disease and ~20% had left main disease. Revascularization with PCI or CABG, as appropriate, reduced the absolute 6-month mortality by a drastic 13% (30-day mortality 46% vs. 56%, with a lower mortality of 38% if successful PCI was performed; 6-month mortality 50% vs. 63%). Patients who survive the acute phase of cardiogenic shock have a good long-term survival, two-thirds being alive at 6 years.106,107

Notably, fibrinolytics were administered to 63% of the SHOCK trial patients managed medically and were associated with a marked and significant 40% mortality reduction in comparison to no fibrinolytic therapy.108 In addition, fibrinolytics were administered to ~50% of patients managed with revascularization, as half of SHOCK trial patients presented to non-PCI-capable hospitals; the mortality benefit of fibrinolytics in this subgroup was less clear. In the SHOCK registry, fibrinolytic therapy was associated with a mortality reduction even in those who eventually underwent revascularization.109 The impaired systemic perfusion may impede the lytic delivery to its target; fibrinolysis remains, nonetheless, effective, particularly if IABP is used.

In the SHOCK trial, 37% of patients received emergent CABG rather than PCI, and CABG was performed briskly, at a median of 2.7 hours after randomization. CABG was associated with the same survival as PCI, despite the higher prevalence of extensive CAD.110 However, this quick CABG is not feasible at many institutions and the CABG rate in the community is lower.

IABP was recommended in all SHOCK trial patients, including medically treated patients and those initially presenting to a non-PCI hospital, and was used in 86% of patients. In the SHOCK registry, IABP was associated with a reduced mortality.109 However, randomized trials such as CRISP-AMI failed to show a benefit of IABP in STEMI patients with LV failure,111 and the IABP-SHOCK II trial failed to show a benefit of IABP even in MI patients with cardiogenic shock.112 The failure of the IABP-SHOCK II trial may be due to the heterogeneity of cardiogenic shock and the inclusion of patients whose shock was not purely related to LV dysfunction (median EF was 35%, 33% of patients had NSTEMI), or whose organ failure was advanced (45% had post-cardiac arrest shock); also, IABP was mostly placed after rather than before PCI. In patients with true LV shock, it is reasonable to place the IABP before PCI as an early measure to stabilize the patient, unload the LV and reduce O2 demands, and perform a safer PCI with potentially less reperfusion injury. Also, outside shock, IABP is useful in patients with a large STEMI who have persistent ischemia/slow coronary flow after primary PCI.

In sum, the following strategy is recommended in cardiogenic shock:

  1. Emergent revascularization of the infarct-related artery only, irrespective of the time of presentation (even >24 hours after MI onset). Ongoing ischemia and necrosis are typical of the vicious cycle that characterizes shock, even late shock. Non-culprit artery PCI is preferably avoided as it adds contrast load and procedural time and therefore worsens LV volume overload and possibly myocardial injury (CULPRIT-SHOCK trial, STEMI [62%] or NSTEMI).69 Even patients with RCA culprit and severe LAD non-culprit do not appear to benefit from non-culprit PCI. This does not apply to cases without a clearly identifiable culprit, especially NSTEMI, where multivessel PCI may be required. Also, non-culprit PCI may be required in the patient with severe and refractory cardiogenic shock requiring multiple vasopressors despite culprit PCI, although a ventricular assist device is probably more useful in this case.
  2. In patients presenting to non-PCI-capable hospitals within 12 hours of MI onset, administer fibrinolytics whenever transfer delays are expected. Also, IABP may be placed before transfer. Augmentation of blood pressure with IABP or vasopressors may increase coronary flow and facilitate fibrinolysis.
  3. In patients with multivessel CAD on angiography:

    • Severe three-vessel CAD (>90%) or critical left main disease dictates immediate CABG if possible. Alternatively, PCI of only the infarct-related artery is performed. Balloon angioplasty of the culprit artery followed by early CABG is another alternative.

  4. IABP may be placed during or before the revascularization procedure and may be tailored to patients who continue to decline and require higher inopressor doses, yet are not in extremis and are not post-cardiac arrest.
  5. Mechanical ventilation is often necessary to reduce the respiratory work, improve oxygenation, and reduce LV preload and afterload.
  6. Inotropic support: dobutamine is used in patients whose SBP is >80 mmHg, while norepinephrine is required in patients with SBP <80 mmHg or inappropriately low or normal SVR. While vasoconstriction may be harmful, the maintenance of an appropriate systemic perfusion pressure, including coronary perfusion pressure, is a priority and justifies the use of norepinephrine in severely hypotensive patients; in fact, afterload remains low in hypotensive patients, even if vasopressors are used. Also, norepinephrine stimulates the myocardial release of local coronary vasodilators which counteract its direct α1-constrictive effect. Patients whose shock has been precipitated by vasodilators or sedation may also be temporarily treated with vasopressors, until the effect of the drugs wears off.
  7. Temporary pacing, usually at a rate over 80–100 bpm, is required if the heart rate is inappropriately low or even “normal” (60–70 bpm).
  8. PA catheter is generally placed to support the diagnosis and guide management, unless the patient quickly improves with revascularization; the finding of a low SVR may dictate the use of vasopressors.

    Echo should be done to rule out mechanical complications and to assess left-sided filling pressures.

    Alternatively, LV pressure measurement and LV angiography are performed during the emergent cardiac catheterization.

  9. LV assist device, such as percutaneous Impella or TandemHeart, may be considered in patients with refractory shock as it provides better hemodynamic support than IABP. The survival benefit in patients with irreversible stage of shock and multiple organ failure is, however, uncertain, and is compounded by these devices’ high complication rates. In 3 large retrospective analyses, including two analyses of shock patients, Impella was associated with worse outcomes vs IABP, worse outcomes compared to the pre-Impella era, and worse outcomes vs matched patients from IABP-SHOCK II trial: more major bleeding (absolute risk >20%), death (1.25 times higher), vascular complications, hemolysis and stroke.113115

D. Management of severe acute left heart failure without shock

In acute MI, pulmonary edema results from volume redistribution to the lungs without overt volume overload and sometimes without LV dilatation. Treatment consists of small doses of furosemide (e.g., 20–40 mg IV), along with a low dose of intravenous NTG to reduce preload. Excessive preload or afterload reduction may, however, precipitate shock.

Severe HF (Killip class III), i.e., massive pulmonary edema that frequently requires mechanical ventilation, is an indication for primary PCI of the culprit artery irrespective of the delay to presentation (approach similar to cardiogenic shock).1,2

Nov 27, 2022 | Posted by in CARDIOLOGY | Comments Off on ST-Segment Elevation Myocardial Infarction

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