• Clinical science

Acute coronary syndrome

Summary

Acute coronary syndrome (ACS) is characterized by acute chest pain due to partial or complete occlusion of a coronary artery that results from an unstable (often ruptured) plaque in the setting of advanced coronary heart disease. There are three clinical entities grouped under ACS: unstable angina pectoris (AP), 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. Chest pain typically radiates to the neck, epigastrium, upper back, and/or left arm. Additionally, autonomic symptoms such as diaphoresis, nausea, and vomiting are common. Myocardial infarction can also occur without prior angina pectoris and is often the first manifestation of coronary heart disease (see principles of coronary heart diseases and angina pectoris). ECG and laboratory tests are important diagnostic tools. 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., troponin T after 3–4 hours). Unlike unstable AP and NSTEMI, STEMI results in specific ECG changes (e.g., ST-segment elevation), which help to determine the location and acute stage of the infarct. ACS is initially managed with a standard algorithm consisting of blood thinners, analgesics, antiarrhythmic drugs, and O2 administration. Further management depends on diagnostic results, which should be quickly evaluated to ensure the best prognosis. Cardiac catheterization should be performed as soon as possible in STEMI and electively within (2–72 h) in NSTEMI. Other interventions should be carried out as soon as possible ("time is muscle"). Unstable AP may stabilize, in which case it can be understood as a temporary ischemic event, or may progress to myocardial infarction. Regardless, unstable AP should initially be managed in the same way as myocardial infarction, except for fibrinolysis. The decision to conduct early catheterization for unstable AP primarily depends on whether the patient's prognosis and whether he/she responds to medical therapy.

Definition

Acute coronary syndrome may manifest either as sudden cardiac death (SCD) or as one of the following conditions:

Unstable angina

Myocardial infarction

  • The sudden death of myocardial cells when they are critically undersupplied with blood due to obstruction of the coronary arteries

Non-ST-segment elevation myocardial infarction (NSTEMI)

ST-segment elevation myocardial infarction (STEMI)

References:[1][2]

Epidemiology

  • Myocardial infarction
    • ∼ 1.5 million cases of myocardial infarction in the US per year
    • Approximately 40% of all myocardial infarctions occur in the early morning hours.
    • ♂ > ♀ (3:1)
    • Only 70% of all patients with myocardial infarction reach the emergency room alive; around 50% of all infarct patients die within the first 4 weeks.
    • 5–10% of all infarct patients die within 2 years of being discharged from the hospital because of sudden cardiac death.

References:[3]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

Unstable plaque development

  • Coronary artery disease leads to plaque formation (see principles of coronary artery diseases and/or risk factors for atherosclerosis).
  • Both unstable and stable plaques normally increase in size in the outward direction (away from the lumen) and do not lead to stenosis.
  • Unstable plaques are lipid-rich and covered by thin fibrous caps → These plaques rupture easily.
    • Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap and exposes the highly thrombogenic lipid core of the atheroma

Development of coronary occlusion

  • Risk factors for coronary heart disease (CHD) → atherosclerosis → unstable plaque formation → plaque rupture → acts as a nidus for the formation of thrombus and/or thromboembolus → coronary occlusion → acute coronary syndrome → myocardial infarction and necrosis
    • Stable AP: A stable, stenosing plaque slowly develops → symptomatic only during exertion, when there is an increased demand for oxygen
    • Unstable AP: An unstable plaque ruptures, leading to thrombus formation that partially occludes the coronary vessel → A decrease in blood supply leads to symptoms regardless of demand (also during rest).
      • Constant interaction between thrombus formation ↔︎ endogenous thrombolysis (prevents complete vessel occlusion)
      • May progress to myocardial infarction (either by causing microemboli (→ NSTEMI) or cause an occluding thrombus (→ STEMI))
    • NSTEMI = inner wall infarction: : Small emboli form from the unstable plaque and are carried to smaller vessels before completely occluding small branches affecting the inner layer of the heart.
    • STEMI = transmural infarction: complete occlusion of a main coronary artery occurs due to thrombus formation directly at the ruptured plaque or thromboembolus directly after
  • Stenosis ≥ 90% (mostly due to thrombus formation) → infarction followed by coagulation necrosis (see "Pathology" below)

References:[1][4]

Clinical features

  • General symptoms: See also angina pectoris.
    • Retrosternal pain (often a squeezing type), acute in onset and continuous in nature
    • Location of pain (in decreasing order of frequency): retrosternal, left side of the chest, left arm, left shoulder, neck, lower jaw, back, epigastrium
    • Orthopnea, dyspnea
    • Cyanosis, pallor
    • Autonomic symptoms: diaphoresis, syncope, palpitations, nausea, and vomiting
    • If MI: Symptoms of CHF (pulmonary edema) or cardiogenic shock (↓ BP, ↑ HR, pallor) may occur.
    • Possibly a new murmur (typically systolic) and/or heart sound
  • Specific to inferior wall infarction
    • Epigastric pain
    • Often associated with bradycardia
  • Atypical presentation: little to no chest pain
    • More likely in elderly, diabetic individuals and women
    • Autonomic symptoms are often the chief complaint.
    • Sometimes retrosternal pressure as opposed to pain
    • In people with diabetes: silent MI due to polyneuropathy → Chest pain may be completely absent.

References:[1][5][6][7]

Diagnostics

ECG

ECG changes in STEMI

  • Acute stage
  • Intermediate stage
    • Absence of R wave
    • Terminal T-wave inversion
    • Pathological Q-wave formation
  • Chronic stage (lifelong)
    • Persistent, broad, and deep Q wave
    • Often incomplete recovery of the R wave
    • Permanent T-wave inversion may occur.

Localization of the infarct with the help of ECG changes

Coronary arteries

 Affected part - i.e., level of the stenosis Localization of the infarct ECG changes in myocardial infarction
Left coronary artery (LCA) Left anterior descending artery (LAD) Proximal LAD Large anterior wall infarction I, aVL, V1-6
Peripheral LAD + anterior interventricular branch Anteroseptal infarction I, aVL, V1-4
Peripheral LAD Apical infarction I, aVL, V3-5
Diagonal branch Lateral wall infarction (anterolateral wall infarction) I, aVL, V5-6/7
Left circumflex coronary artery (LCX) Proximal circumflex coronary artery Posterior wall infarction III, aVF, V7-9
Posterolateral artery Lateral wall infarction (posterolateral wall infarction) II, III, aVF, ∼ (sometimes I and aVL are also affected )
Right coronary artery (RCA) Proximal RCA Inferior wall infarction II, III, aVF
In approximately 20% of cases, inferior wall infarction is associated with infarction of the right ventricle. V1 and V3r-6r also
Posterior interventricular branch Posterior wall infarction V7-9, inverse in V1-2

An easy rule of thumb: "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 I, aVL, and/or anterior wall leads (V1-6). Infarction of the posterior wall is caused by obstruction of the LCX or RCA or their branches, and ECG changes are seen in leads II, III, and aVF."

Laboratory diagnostics (cardiac enzymes)

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

∼ 3 h

12–96 h

6–14 days
Myoglobin

∼ 2–4 h

6–12 h

24 h
  • Not a cardiac-specific marker
  • Cardiac muscle damage can be ruled out if enzyme levels return to normal within 6 h after the onset of chest pain.
Enzyme
Creatine kinase (creatine phosphokinase) Total CK ∼ 3–12 h 12–24 h 2–6 days
  • Nonspecific marker enzyme; levels rise due to cardiac as well as skeletal muscle damage
CK-MB ∼ 3–12 h 12–24 h

2–3 days
  • Total CK of 6–20% CK-MB indicates cardiac muscle damage.
  • Correlates with the size of the infarct
  • Important to evaluate reinfarction
SGOT (AST) ∼ 6–12 h 18–36 h 3–6 days
  • Not a cardiac-specific marker
LDH1 and LDH2 (HBDH )

∼ 6–12 h

 2–7 days

10–20 days
* 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.

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 h, and normalize after only 2–3 days, making CK-MB a good marker for evaluating reinfarction.

Instrumental diagnostic procedures

References:[1][1][5][8][9][10][11][12]

Pathology

Histopathological findings

  • Obstruction of a coronary artery branch with over 90% stenosis or embolization results in coagulation necrosis of the post-stenotic zone.
  • Microscopically, it proceeds according to the following phases:
Interval post-MI Histopathological findings
Microscopic Macroscopic
0–24 hrs

Early coagulative necrosis (> 4 hrs) → release of content from necrotic cells → release of inflammatory cytokines → recruitment of neutrophils (granulocytes). Hypercontraction of myofibrils and wavy fibers (1–4 hrs), coagulative necrosis (4–72 hrs).

 No gross changes (0–12 hrs), dark mottling (12–24 hrs)
1–3 days

Coagulative necrosis (4–72 hrs), neutrophilic infiltrate (1–3 days)

 Hyperemia, yellow pallor
3–14 days

Macrophages and granulation tissue around the margins (3–10 days), proliferation of blood vessels into the granulation tissue (10–14 days)

 Hyperemic border, central yellow pallor (yellowest at ∼ 10 days), softening
2 weeks to several months

Granulation tissue becomes denser and forms a collagenous scar.

 Grayish-white fibrosis

Cellular changes

  • Cellular swelling during the ischemia: secondary to more free water entering the cell to maintain osmotic balance in the setting of an increase in ion concentration (↑ intracellular Na+ + Ca2+)
    • Ischemic cardiac muscle depletes its ATP during anaerobic respiration, which leads to:
      • ↑ Lactate + intracellular ↓ pH → exchange of H+ ions for Na+ → ↑ intracellular Na+ → ↓ passive Ca2+ efflux (due to impaired Na+/K+-ATPase function)
      • ↓ ATP → ↓ active Ca2+ efflux through the cell membrane or by uptake into the endoplasmic reticulum
  • Cell death: ↑ intracellular Ca2+ → ↑ activation of cellular proteases → ↑ breakdown of cellular proteins → irreversible cell damage → cell death
  • Reperfusion injury: due to free radical formation after the introduction of oxygen into a previously ischemic environment.

References:[4]

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Initial management of suspected ACS

MONA: Morphine, Oxygen, Nitroglycerin, and Aspirin!

Intramuscular injections during the pre-hospital phase are contraindicated because they may lead to a nonspecific rise in CK.

Treatment algorithm based on ECG findings

  • STEMI: PTCA is performed as quickly as possible (balloon dilatation with stent implantation if necessary).
    • Alternative: thrombolytic therapy
      • Indication: if PTCA cannot be performed within 90–120 minutes, there are no contraindications (i.e., increased risk of bleeding), and symptom onset was within the past 12 hours
      • PTCA should be performed even if lysis is successful.
      • Monitor for bleeding as a potential complication
  • NSTEMI: PTCA is performed rapidly within 2–72 h
  • The appearance of typical symptoms without any ECG changes or elevation of cardiac enzymes in the blood
    • The patient should be admitted and observed
    • Continuing ECG monitoring
    • Remeasure cardiac enzymes (6 hours after admission)
    • Other investigations: echocardiogram and other noninvasive procedures to rule out/treat differentials or comorbidity

The expression "time is muscle" applies in ST-elevation myocardial infarction (STEMI)!

Other measures

References:[1][2][13][3][14][15]

Complications

Early complications (within 48 hours of MI)

Late complications (medium and long-term complications)

References:[1][2][16]

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

Prevention

Tertiary prevention for post-MI patients

References:[1][17][18][19]