• Clinical science

Acute coronary syndrome

Summary

Acute coronary syndrome (ACS) refers to acute myocardial ischemia and/or infarction due to partial or complete occlusion of a coronary artery. There are three clinical entities grouped under ACS: unstable angina pectoris, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). These conditions are often difficult to distinguish from one another based on clinical symptoms alone and require ECG and cardiac biomarker measurement to diagnose. Typical cardiac chest pain is substernal in nature, often described as a feeling of pressure, and is relieved with rest and/or nitrate use. The pain may radiate to the left jaw, neck, epigastrium, upper back, and/or left arm. Additionally, autonomic symptoms such as diaphoresis, nausea, and vomiting are common. ECG and laboratory tests are important diagnostic tools in the initial evaluation. In contrast to angina pectoris, NSTEMI and STEMI are characterized by the destruction of cardiac muscle tissue, which results in elevated cardiac enzymes in the blood (i.e., the elevation of troponin after 3–4 hours). Unlike unstable angina and NSTEMI, STEMI results in specific ECG changes (e.g., ST-segment elevation), which can help to determine the location and stage of the infarct. The need for revascularization with either fibrinolysis or cardiac catheterization should be evaluated immediately, as revascularization significantly affects the prognosis of patients with myocardial infarction. Cardiac catheterization should be performed as soon as possible in STEMI and electively within 2–72 hours in high-risk NSTEMI and/or unstable angina. Medical management of ACS includes anticoagulation, analgesics, and antiplatelet agents. Complications of ACS include congestive heart failure, papillary muscle rupture, arrhythmias, and sudden cardiac death. Subsequent management and secondary prevention of ACS depends on the presence of comorbidities, but most patients should be started on indefinite aspirin and statin therapy.

Definition

References:[3][4]

Overview

Unstable angina [5] Non-ST-segment elevation myocardial infarction (NSTEMI) [5] ST-segment elevation myocardial infarction (STEMI) [5]
Description
Clinical presentation
  • Angina at rest or with minimal exertion
  • New-onset angina
  • Severe, persistent, and/or worsening angina (crescendo angina)
  • Autonomic symptoms may be present: diaphoresis, syncope, palpitations, nausea, and/or vomiting
Pathophysiology
  • Partial occlusion of coronary vessel → decreased blood supply → ischemic symptoms (also during rest)
  • Classically due to partial occlusion of a coronary artery
  • Affects the inner layer of the heart (subendocardial infarction)
  • Classically due to complete occlusion of a coronary artery
  • Affects full thickness of the myocardium (transmural infarction)
Cardiac biomarkers
ECG findings
  • Normal
Treatment

Subtypes of ACS cannot be differentiated based on clinical presentation alone!

Epidemiology

References:[6][7]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathophysiology

ACS is most commonly due to unstable plaque formation and subsequent rupture.

Plaque formation and rupture

Coronary artery occlusion

References:[3][8][9]

Clinical features

  • Classic presentation
    • Acute retrosternal chest pain
      • Typically described as dull, squeezing pressure and/or tightness
      • Commonly radiates to left chest, arm, shoulder, neck, jaw, and/or epigastrium
      • Precipitated by exertion or stress
      • See also angina.
      • The peak time of occurrence is usually in the morning (8–11 a.m.). [10]
    • Dyspnea (especially with exertion)
    • Pallor
    • Nausea, vomiting
    • Diaphoresis, anxiety
    • Dizziness, lightheadedness, syncope
  • Other findings
  • Specific to inferior wall infarction
    • Epigastric pain
    • Bradycardia
    • Clear lung fields
  • Atypical presentation: minimal to no chest pain
    • More likely in elderly, diabetic individuals, and women
    • Autonomic symptoms (e.g., nausea, diaphoresis) are often the chief complaint.
    • In patients with diabetes, chest pain may be completely absent (e.g., silent MI) due to polyneuropathy. [11][12]

STEMI classically manifests acutely with more severe symptoms, while unstable angina/NSTEMI has a continuous course with milder symptoms.

References:[3][13][14][15]

Diagnostics

ECG should be performed immediately once ACS is suspected, followed by measurement of cardiac biomarkers. Further diagnostic workup (e.g., echocardiography) depends on the results of initial evaluation and further risk stratification (e.g., TIMI score).

ECG

  • 12-lead ECG is the best initial test if ACS is suspected.
  • Dynamic changes require serial ECG evaluation.
  • Compare to prior ECGs (if available).

ECG changes in STEMI [16]

The sequence of ECG changes over several hours to days: hyperacute T wave → ST elevation → pathological Q wave → T-wave inversion → ST normalization → T-wave normalization

An acute left bundle branch block accompanied by symptoms of acute coronary syndrome is also considered an ST-elevation myocardial infarction (STEMI) because ST elevations cannot be adequately assessed in the setting of an LBBB.

ECG changes in NSTEMI/unstable angina

  • No ST elevations present
  • Nonspecific changes may be present.

Localization of the myocardial infarct on ECG [16][11][17][18]

ECG leads affected Infarct location Vessel involved [17][18]
V1–V6
  • Extensive anterior (Leads aVL and I can also be affected.)
V1–V2
  • (Antero)septal
  • LAD
V3–V4
  • (Antero)apical
  • Distal LAD
V5–V6
  • (Antero)lateral
I, aVL
  • Lateral
II, III, aVF
  • Inferior
  • RCA (more common)
  • Distal LCX (less common)
V3R–V6R
V7-V9
  • Posterior/posterolateral

Infarction of the anterior wall is caused by obstruction of the LAD or its branches. Depending on the extent of anterior wall infarction, it results in ECG changes in the anterior wall leads (V1–6) and/or I and aVL. Infarction of the inferior wall is caused by obstruction of the LCX or RCA or their branches, and ECG changes are seen in leads II, III, and aVF.

To remember the ECG leads with maximal ST elevation in anterior MI, think “SAL”: “Septal (V1–2), Apical (V3–4), Lateral (V5–6).

In severe transmural posterior wall infarction, there may not be any ST elevation on a standard 12-lead ECG.

Laboratory findings

Cardiac biomarkers [19]

Biomarker/enzyme Rise* Maximum* Normalization* Characteristics
Troponin T/I

6-8 h

12–24 h

7–10 days
Myoglobin

∼ 1 h

4–12 h

24 h
  • Nonspecific marker that is no longer commonly used
CK-MB ∼ 4–9 h 12–24 h 2–3 days
  • CK-MB is more specific to cardiac tissue than total CK.
  • Can be helpful for evaluating reinfarction because of its short half-life but is no longer commonly used
  • The degree of elevation often correlates with the size of the infarct.
* The values rise, reach a certain maximum, and normalize in the span of hours or days following the onset of myocardial infarction or its symptoms. Values and time references may vary based on the precise laboratory methods employed.

Serum troponin T is the most important cardiac-specific marker and may be measured 3–4 hours after the onset of myocardial infarction. CK-MB values correlate with the size of the infarct, reach a maximum after approximately 12–24 hours, and normalize after only 2–3 days, making CK-MB a good marker for evaluating reinfarction.

Additional findings [21][22]

Coronary angiography

  • Best test for definitive diagnosis of acute coronary occlusion
  • Can be used for concurrent intervention (e.g., PCI; with stent placement)
  • Can identify site and degree of vessel occlusion
  • Indications include

The most commonly occluded coronary arteries (descending order): left anterior descending artery, right coronary artery, circumflex artery.

Additional studies

References:[3][3][13][24][25][26][27][28]

Risk stratification

TIMI score for unstable angina/NSTEMI [29]

Characteristics Points
Age ≥ 65 years 1

Three or more CAD risk factors (e.g., premature family history, DM, smoking, HTN, hyperlipidemia, PAD, abdominal aortic

aneurysm)

 1
Known CAD (prior stenosis > 50%) 1
Two or more episodes of severe angina in the last < 24 hours 1
ASA use in the last 7 days 1
ST deviation (≥ 0.5 mm) 1
Elevated cardiac biomarkers 1
Total points 0–7

References: [29]

Pathology

Histopathological findings of MI [30]

Time interval post-infarction Histopathological findings
Microscopic Macroscopic

0–24 hrs
  • 0–12 hours: no gross changes
  • 12–24 hours: dark mottling

1–3 days
  • Extensive coagulative necrosis (4–72 hours)
  • Neutrophilic infiltrate
  • Inflammation spreads to tissue surrounding infarct.
  • Hyperemia
  • Yellow pallor

3–14 days
  • Macrophage infiltration
  • Granulation tissue surrounds infarct margins (3–10 days)
  • Proliferation of blood vessels into granulation tissue (10–14 days)
  • Hyperemic border
  • Center: yellow-brown, soft

2 weeks to several months
  • Granulation tissue becomes more dense → collagenous scar formation
  • Grayish-white fibrosis

Obstruction of a coronary artery branch due to > 90% stenosis or embolization results in coagulation necrosis of the post-stenotic zone.

Cellular changes

  • See “Ischemia” in cellular changes and adaptive responses.
  • Reperfusion injury
    • Timing
      • Can occur spontaneously or after revascularization (e.g., fibrinolysis or PCI)
      • Typically occurs when reperfusion occurs > 3 hours after the acute coronary artery occlusion
    • Mechanism: blood flow restored → damaged myocytes release reactive oxygen species (ROS); → mitochondrial permeability transition pores are formed → cell swelling → cell death → Ca2+ entry into the cytosol → hypercontraction of myocytes → contraction band necrosis and increase in infarct size [9]
    • Microscopic findings: neutrophilic infiltration, capillary obstruction, and contraction band necrosis of the myocardium

References:[8]

Differential diagnoses

Differential diagnosis of chest pain

Differential diagnosis of increased troponin

Differential diagnosis of ST-elevations on ECG [31]

The differential diagnoses listed here are not exhaustive.

Treatment

Any patient with ST elevations on ECG requires immediate evaluation for urgent revascularization. The administration of other therapies should not delay care.

All patients [31][5]

  • Monitoring
    • Serial 12-lead ECG
    • Continuous cardiac monitoring
    • Serial serum troponin measurement
  • Pharmacologic therapy
  • Supportive care
    • Intravenous fluids (e.g., normal saline): in patients with an inferior MI that causes RV dysfunction
    • Oxygen; : only in case of cyanosis, severe dyspnea, or SpO2 < 90% (< 95% in STEMI)

Primary interventions of MI treatment include “MONA”: Morphine, Oxygen, Nitroglycerin, and Aspirin. But remember: Morphine, oxygen, and nitroglycerine are not necessarily indicated for every patient (see indications above).

STEMI [31]

Immediate revascularization

Revascularization is the most important step in the management of acute STEMI and initiation of further therapies (e.g., DAPT, anticoagulation) should not delay this step in management.

  • Emergent coronary angiography: with percutaneous coronary intervention (PCI)
    • Preferred method of revascularization
    • Balloon dilatation with stent implantation (see cardiac catheterization)
    • Ideally, door-to-PCI time should be < 90 minutes. It should not exceed 120 minutes.
  • Thrombolytic therapy: tPA, reteplase, or streptokinase
    • Indications:
      • If PCI cannot be performed < 120 minutes after onset of STEMI
      • If PCI was unsuccessful
      • No contraindications to thrombolysis
    • Contraindications
    • Timing
      • Symptom onset was within the past 3–12 hours
      • Should be administered within < 30 minutes of patient arrival to the hospital
      • Contraindicated if > 24 hours after symptom onset
    • PCI should be performed even if lysis is successful.
  • Coronary artery bypass grafting
    • Not routinely recommended for acute STEMI
    • Indications
      • If PCI is unsuccessful
      • If coronary anatomy is not amenable to PCI
      • If STEMI occurs at the time of surgical repair of a mechanical defect

Medical therapy

"Time is muscle": Revascularization should occur as soon as possible in patients with STEMI!

Unstable angina/NSTEMI [5]

  • Dual antiplatelet therapy: start as soon as possible
  • Anticoagulation
    • Heparin or enoxaparin
    • Continue for the duration of hospitalization or until PCI is performed.
  • Immediate vs. delayed revascularization
    • The indication for and timing of revascularization depends on the mortality risk (e.g., TIMI score).
    • In patients with therapy-resistant chest pain, a TIMI score ≥ 3, ↑ troponin, and/or ST changes > 1 mm
      • Consider the addition of a GPIIb/ IIIa inhibitor (e.g., tirofiban or eptifibatide)
      • Plan for revascularization within 72 hours (e.g., angiography with PCI or CABG)

Fibrinolytic treatment is not recommended in patients with unstable angina or NSTEMI.

Subsequent measures

References:[3][32][33][34][35][36]

Complications

0–24 hours post-infarction

1–3 days post-infarction

3–14 days post-infarction

2 weeks to months post-infarction

References:[3][32][37]

We list the most important complications. The selection is not exhaustive.

Prevention

Primary prevention [31]

  • Treatment/avoidance of modifiable risk factors for atherosclerosis (e.g., smoking cessation, treatment of hypertension, etc.)
  • Healthy, plant-based diet [38]
  • Regular physical activity and exercise
  • Low-dose aspirin is beneficial for certain high-risk groups. The choice to prescribe it should be made on an individual basis.

Secondary prevention [31]

References:[3][39][40][31]