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
 Myocardial infarction: myocardial cell death caused by prolonged ischemia [1][2]
 Acute coronary syndrome: suspicion or confirmed presence of acute myocardial ischemia and/or
myocardial infarction
 Further classified as unstable angina, NSTEMI, and STEMI
 Sudden cardiac death (SCD): sudden, unexpected death caused by loss of cardiac function (most
commonly due to lethal arrhythmia, e.g., ventricular fibrillation)
 Epidemiology
 Incidence
 ∼ 1.5 million cases of myocardial infarction per year in the US
 ♂ > ♀ (3:1)
 Risk factors: See atherosclerosis.
 Increasing age
 Male gender
 Personal history of angina and/or known coronary artery disease
 Family history of CAD
 Diabetes mellitus
 Systolic hypertension
 Tobacco use
 Hyperlipidemia

References:[6][7]
Epidemiological data refers to the US, unless otherwise specified.
 Etiology
 Most common cause: coronary artery atherosclerosis
 Less common
 Coronary artery dissection
 Coronary artery vasospasm (e.g., Prinzmetal angina, cocaine use)
 Takotsubo cardiomyopathy
 Myocarditis
 Thrombophilia (e.g., polycythemia vera)
 Coronary artery embolism (e.g., due to prosthetic heart valve, atrial
fibrillation)
 Vasculitis (e.g., polyarteritis nodosa, Kawasaki syndrome)
 Myocardial oxygen supply-demand mismatch
 Hypotension
 Severe anemia
 Hypertrophic cardiomyopathy
 Severe aortic stenosis

Pathophysiology
ACS is most commonly due to unstable plaque formation and subsequent rupture.
Plaque formation and rupture
 For plaque formation, see principles of coronary heart disease and atherosclerosis.
 Stable atherosclerotic plaque: manifests as stable angina (symptomatic during exertion)
 Unstable plaques are lipid-rich and covered by thin fibrous caps → high risk of rupture
 Inflammatory cells in the plaque (e.g., macrophages) secrete matrix metalloproteinases → breakdown
of extracellular matrix → weakening of the fibrous cap → minor stress → rupture of the fibrous cap →
exposure of highly thrombogenic lipid core → thrombus formation → coronary artery occlusion

Coronary artery occlusion

 Partial coronary artery occlusion

 Decreased myocardial blood flow → supply-demand mismatch → myocardial

ischemia

 Usually affects the inner layer of the myocardium (subendocardial infarction)

 Typically manifests clinically as unstable angina and/or NSTEMI

 Complete coronary artery occlusion

 Impaired myocardial blood flow → sudden death of myocardial cells (if no

reperfusion occurs)

 Usually affects the full thickness of the myocardium (transmural infarction)

 Typically manifests clinically as STEMI

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

 Tachycardia, arrhythmias

 Symptoms of CHF (e.g., orthopnea, pulmonary edema) or cardiogenic shock (e.g.,

hypotension, tachycardia, cold extremities)

 New heart murmur on auscultation (e.g., new S4)

 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.

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]

 Acute stage: myocardial damage ongoing

 Hyperacute T waves ("peaked T wave")

 ST elevations in two contiguous leads with reciprocal ST depressions

 Intermediate stage: myocardial necrosis present

 Absence of R wave

 T-wave inversions

 Pathological Q waves

 Chronic stage: permanent scarring

 Persistent, broad, and deep Q waves

 Often incomplete recovery of R waves

 Permanent T wave inversion is possible.

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.
 ST depression
 Inverted T wave
 Loss of R wave
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
 * 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]
 Elevated inflammatory markers: ↑ WBC, CRP
 Elevated BNP: especially in heart failure
 Elevated LDH
 Elevated AST (SGOT)

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
 Acute STEMI
 Other high-risk ACS (see TIMI score below)
 See also cardiac catheterization.

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

Additional studies
 Transthoracic echocardiogram
 Identification of any wall motion abnormalities and to assess LV function
 Important for risk assessment: In STEMI, the best predictor of survival is LVEF.
 Evaluation for complications: aneurysms, mitral valve regurgitation, pericardial effusion, free
wall rupture
 Cardiac CT
 May be considered as an alternative to invasive coronary angiography in patients with an
intermediate risk of ACS (based on TIMI score)
 Allows for noninvasive visualization of the coronary arteries
 Contraindication: arrhythmias, tachycardia [

TIMI score for unstable angina/NSTEMI [29]

 Method for calculating the risk of mortality in patients with unstable angina or NSTEMI
 Can be used to determine recommended therapeutic regimen and timing for revascularization
 Interpretation
 An increasing score is associated with a higher risk of mortality, new or recurrent myocardial
infarction, and need for urgent revascularization (e.g., progression of unstable angina to STEMI)
 Risk score ≥ 3
 Early angiography recommended
 Consider addition of glycoprotein IIb/IIIa inhibitor and treatment with enoxaparin
(rather than UFH)
 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

Differential diagnoses
See differential diagnoses of chest pain.

Differential diagnosis of increased troponin

 Cardiac causes
 Myocarditis
 Decompensated congestive heart failure
 Pulmonary embolism
 Cardiac arrhythmia, tachycardia
 Cardiac trauma
 Takotsubo cardiomyopathy
 Noncardiac causes
 Renal failure
 Stroke
 Critical illness (e.g., sepsis)

Differential diagnosis of ST-elevations on ECG [31]

 Early repolarization
 LBBB
 Brugada syndrome
  Myocarditis
 Pericarditis
 Pulmonary embolism
 Hyperkalemia
 Tricyclic antidepressant use
 Poor ECG lead placement

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

o Serial 12-lead ECG

o Continuous cardiac monitoring

o Serial serum troponin measurement

 Pharmacologic therapy

o Sublingual or intravenous nitrate (nitroglycerin or ISDN)

 For symptomatic relief of chest pain

 Does not improve prognosis

 Contraindications: inferior wall infarct (due to risk for hypotension),

hypotension, and/or PDE 5 inhibitor (e.g., sildenafil) taken within last 24
hours

o Morphine IV or SC (3–5 mg)

 Only if the patient has severe, persistent chest pain or severe anxiety related
to the myocardial event

 Administer with caution due to increased risk of complications (e.g.,

hypotension, respiratory depression) and adverse events

o Beta blocker

 Recommended within the first 24 hours of admission

 Avoid in patients with hypotension, features of heart failure, and/or risk of

cardiogenic shock (e.g., large LV infarct, low ejection fraction).
 o Statins: early initiation of high-intensity statin; (such as atorvastatin 80 mg; )
regardless of baseline cholesterol, LDL, and HDL levels

o Loop diuretic (e.g., furosemide) if the patient has flash pulmonary edema or features
of heart failure

 Supportive care

o Intravenous fluids (e.g., normal saline): in patients with an inferior MI that causes RV
dysfunction

o 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)

o Preferred method of revascularization

o Balloon dilatation with stent implantation (see cardiac catheterization)

o Ideally, door-to-PCI time should be < 90 minutes. It should not exceed 120 minutes.

 Thrombolytic therapy: tPA, reteplase, or streptokinase

o Indications:

 If PCI cannot be performed < 120 minutes after onset of STEMI

 If PCI was unsuccessful

 No contraindications to thrombolysis

o Contraindications

 Any prior intracranial bleeding

 Recent large GI bleeding

 Recent major trauma, head injury, and/or surgery

 Ischemic stroke within the past 3 months

 Hypertension (> 180/110 mm Hg)

  Known coagulopathy

o 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

o PCI should be performed even if lysis is successful.

 Coronary artery bypass grafting

o Not routinely recommended for acute STEMI

o 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

 Dual antiplatelet therapy: start as soon as possible

o Aspirin loading dose 162 mg–325 mg

o PLUS; ADP receptor inhibitor: prasugrel, ticagrelor, or clopidogrel

o Dual antiplatelet therapy should be continued for at least 12 months after PCI with
DES.

 GP IIb/IIIa receptor antagonist: (e.g., eptifibatide or tirofiban): should be considered in

precatheterization setting

 Anticoagulation

o Heparin or bivalirudin recommended

o Continue until PCI is performed or for 48 hours after a fibrinolytic is given.

"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

o Aspirin loading dose

o Plus; ADP receptor inhibitor: clopidogrel or ticagrelor

 o Dual antiplatelet therapy should be continued for at least 12 months if PCI with DES
was performed.

 Anticoagulation

o Heparin or enoxaparin

o Continue for the duration of hospitalization or until PCI is performed.

 Immediate vs. delayed revascularization

o The indication for and timing of revascularization depends on the mortality risk (e.g.,
TIMI score).

o 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

 See “Prevention” below.

 Secondary prophylaxis: See prevention of coronary heart disease, therapy of atherosclerotic

diseases; , and PTCA.

 See coronary artery surgery.

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

Acute management checklist

Acute management checklist for STEMI [31]

For patients < 120 min away from PCI-capable facility

 Immediate cardiology consult and evaluation for emergency revascularization (code

STEMI)

 Transfer patient to cardiac catheter suite for angiography.

 Start adjunctive medical therapy.

o ASA

o ADP receptor inhibitor

  Prasugrel

 Ticagrelor

 Clopidogrel

o Anticoagulation

 Unfractionated heparin

 If PCI and GPIIa/IIIa receptor antagonist are planned

 If PCI and GPIIa/IIIa receptor antagonist are not planned or

uncertain

 Bivalirudin

o Glycoprotein (GP) IIb/IIIa receptor antagonist: Consider at time of primary PCI in

conjunction with unfractionated heparin or bivalirudin.

 Abciximab

 Eptifibatide

 Tirofiban

For patients > 120 min away from PCI-capable facility and symptom onset < 12 hours

 Immediate cardiology consult (code STEMI), even if no PCI available

 Check for absolute and relative contraindications to fibrinolysis (see contraindications to

fibrinolysis).

 Consider relative contraindications to fibrinolysis

 If no absolute contraindications present: Administer a fibrinolytic.

o Tenecteplase

o Alteplase

o Reteplase

o Streptokinase

 Start adjunctive medical therapy

o ASA

o ADP receptor inhibitor: clopidogrel

 o Anticoagulation

 Unfractionated heparin

 Enoxaparin

 Fondaparinux

 Postfibrinolysis: Check TIMI coronary grade flow.

 Serial ECGs

 Transfer to PCI-capable facility

Streptokinase is nonfibrin-specific and highly antigenic. It is absolutely contraindicated within 6 months of

previous exposure to streptokinase

For all patients with STEMI

 Additional medical therapy

o Nitroglycerin

o High-intensity statin

o Beta blocker if no contraindications (e.g., metoprolol )

o Consider analgesia only for patients with very strong pain.

 Supplemental oxygen as needed: target SpO2 > 90%

 Order continuous telemetry, serial ECG, and serum troponins every 4–6 hours.

 Transfer to ICU/CCU.

Acute management checklist for NSTEMI/UA [5]

 Start medical therapy.

o ASA

o ADP receptor inhibitor [5]

 Clopidogrel

 Ticagrelor

o Anticoagulation
  Unfractionated heparin is preferred for ischemia-guided strategy.

 Enoxaparin

 Bivalirudin

 Fondaparinux

 Calculate the TIMI score for mortality risk stratification and to determine the urgency of
invasive investigation (e.g., angiography)

o High TIMI score (≥ 3), troponin dramatically increasing, persistent chest pain, and/or
evolving ECG changes

 Call cardiology consult immediately for consideration of early angiography

and initiation of GP IIa/IIIb antagonist.

 Eptifibatide

 Tirofiban

o Low (< 3) TIMI score, troponin stable/only mildly increasing, asymptomatic, no ECG
changes

 Call cardiology consult.

 Continue medical therapy and close monitoring.

 Additional medical therapy

o Nitroglycerin

o High-intensity statin

o Beta blocker (e.g., metoprolol ) within 24 hours if no contraindications

o Consider analgesia only for patients with severe pain.

 Supplemental oxygen as needed: target SpO2 > 90%

 Order continuous telemetry, serial ECG, and serum troponins every 4–6 hours.

 Transfer to cardiac telemetry floor or ICU/CCU.

Complications

0–24 hours post-infarction

 Sudden cardiac death

 o The most common underlying cause in elderly individuals is acute coronary
syndrome (∼ 70% of cases). [10]

o The most common cause is ventricular arrhythmia.

 Arrhythmias

o Ventricular tachyarrhythmias

o AV block

o Asystole

o Atrial fibrillation

 Acute left heart failure: : death of affected myocardium → absence of myocardial

contraction→ pulmonary edema

 Cardiogenic shock

1–3 days post-infarction

 Early infarct-associated pericarditis

o Typically occurs within the first week of a large infarct close to the pericardium

o Clinical features of acute pericarditis: pleuritic chest pain , dry cough , friction rub; ,
diffuse ST elevations on ECG

o Complications (rare): hemopericardium, pericardial tamponade

3–14 days post-infarction

 Papillary muscle rupture

o Usually occurs 2–7 days after myocardial infarction

o Can lead to acute mitral regurgitation

o Rupture of the posteromedial papillary muscle due to occlusion of the posterior

descending artery is most common.

o Clinical features

 New holosystolic, blowing murmur over the 5th ICS on the midclavicular line

 Signs of acute mitral regurgitation: dyspnea, cough, bilateral crackles,

hypotension

 Ventricular septal rupture

o Usually occurs 3–5 days after myocardial infarction

 o Due to structural degradation by macrophages

o Most commonly due to LAD infarction (septal arteries arise from LAD)

o Clinical features

 New holosystolic murmur over the left sternal border

 Acute-onset right heart failure (jugular venous distention, peripheral edema)

 Can progress to cardiogenic shock: tachycardia, hypotension, cool

extremities, altered mental status

o Treatment: emergency surgery and revascularization (often via CABG)

 Left ventricular free wall rupture

o Usually occurs 5–14 days after myocardial infarction

o Greatest risk during macrophage-mediated removal of necrotic tissue

o Clinical features: chest pain, dyspnea, signs of cardiac tamponade (e.g., Beck triad)

o Complications

 Cardiac tamponade

 LV pseudoaneurysm formation: rupture of LV wall that is contained by the

pericardium
2 weeks to months post-infarction

 Atrial and ventricular aneurysms

o Clinical features

 Persistent (> 3 weeks post-MI) ST elevation and T-wave inversions

 Systolic murmur, S3 and/or S4

o Diagnosis: echocardiography

o Complications

 Cardiac arrhythmias (risk of ventricular fibrillation)

 Rupture → cardiac tamponade

 Mural thrombus formation → thromboembolism (stroke, mesenteric

ischemia, renal infarction , acute obstruction of peripheral arteries)

o Treatment: anticoagulation, possibly surgery

 Postmyocardial infarction syndrome (Dressler syndrome): pericarditis occurring 2–10 weeks

post-MI without an infective cause

o Thought to be due to circulating antibodies against cardiac muscle cells

(autoimmune etiology)

o Clinical features

 Signs of acute pericarditis: pleuritic chest pain , dry cough , friction rub

 Fever

 Laboratory findings: leukocytosis, ↑ serum troponin levels

 ECG: diffuse ST elevations

o Treatment: aspirin, acetaminophen

o Complications (rare): hemopericardium, pericardial tamponade

 Arrhythmias (e.g., AV block)

 Congestive heart failure (e.g., ischemic cardiomyopathy)

o Can occur at any time after an ischemic event

o Treatment: for patients with LVEF < 40% or signs of heart failure, ACE inhibitor/ARB
and aldosterone antagonists have been shown to confer a mortality benefit.

 Reinfarction
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]

 Lifestyle modification and treatment of modifiable risk factors (see “Primary prevention”
above and treatment of diseases caused by atherosclerosis)

 Platelet-aggregation inhibitors

o Lifelong low-dose aspirin 75–100 mg/day

o DAPT with the addition of an ADP receptor inhibitor (e.g., prasugrel, ticagrelor, or
clopidogrel) is recommended for 12 months for all patients who have undergone
PCI.

o Glycoprotein IIb/IIIa antagonists (e.g., abciximab) may be considered but are not
used routinely.

 Beta blockers: Unless contraindicated, all patients should be started on a beta blocker, which
has been shown to confer a mortality benefit.

 Statin: All patients should be started on a high-intensity statin (e.g., atorvastatin).

 An aldosterone antagonist and ACE inhibitor/ARB are recommended for all patients with
ischemic cardiomyopathy and an LV ejection fraction < 40% or symptoms of heart failure.

Coronary artery disease (Coronary atherosclerosis…)

Summary
Coronary heart disease (CHD) refers to a mismatch between myocardial oxygen supply and
demand. Atherosclerosis is the most important cause. Atherosclerotic changes in coronary
vessel walls lead to a narrowing of the lumen and prevent vessels from dilating. As a result, an
increase in oxygen demand (e.g., during physical activity) can no longer be satisfied and/or
myocardial perfusion at rest is insufficient. Acute retrosternal chest pain (angina) is the cardinal
symptom of CHD. Other symptoms include dyspnea, dizziness, anxiety and nausea. If ischemia is
severe, myocardial infarction can occur. Coronary heart disease is diagnosed via a cardiac stress
test (possibly provoking symptoms and instrumental findings) and/or coronary catheterization
(e.g., measurement of coronary blood flow). Management of CHD involves primary and
secondary prevention of atherosclerosis (e.g., weight reduction), antianginal treatment (e.g.,
beta blockers) and, in some cases, revascularization (e.g., PCTA).

This learning card provides a basic overview of coronary heart disease and stable angina.
Atherosclerosis and acute coronary syndrome (including myocardial infarction) are discussed in
separate learning cards.

Epidemiology

 Lifetime risk of coronary heart disease

o Age 40: 49% in men and 32% in women

o Age 75: 35% in men and 24% in women

 Cardiovascular disease is the leading cause of death in the US and the world.

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

 Risk factors for atherosclerosis

References:[4]

Pathophysiology

Myocardial oxygen supply and demand

 Mismatch between the amount of oxygen the myocardium receives and the amount it needs

 Coronary flow reserve: the ability of the coronary capillaries to dilate and increase blood
flow to the myocardium

 Factors reducing oxygen supply

o Coronary atherosclerosis and sequelae

  Rupture of an unstable atherosclerotic plaque (most common cause)

 Stenosis

 Thromboembolisms

o Vasospasms

o ↑ HR

o Anemia

 Factors increasing oxygen demand

o ↑ HR

o ↑ Afterload

Increases in heart rate (e.g., during physical exertion) both reduce oxygen supply and increase
oxygen demand!

Myocardial ischemia in coronary atherosclerosis

 Depending on the extent of stenoses (and the corresponding ischemia), patients remain
asymptomatic or develop angina and other symptoms. Symptoms usually develop if stenosis
is ≥ 70%. If ischemia is severe enough, myocardial infarction can occur.

Effect of vascular stenosis on resistance to blood flow

 The greater the stenosis, the higher the resistance to blood flow through the blood vessel,
provided the length of the vessel and viscosity of blood remain constant.

 The degree of increased resistance is calculated using the Poiseuille equation: R = 8Lη/(πr 4);
where R = resistance to flow, L = length of the vessel, η = viscosity of blood, and r = radius of
the vessel.

 When the length of the vessel and viscosity of blood remain constant, the relationship
between resistance and the radius of the vessel can be simplified to R ∼ 1/r4.

References:[5][6][7][8]
Clinical features

Angina

 Typically retrosternal chest pain or pressure

o Pain can also radiate to left arm, neck, jaw, epigastric region, or back.

o Pain does not depend on body position or respiration

o No chest wall tenderness

o Angina may be absent, particularly in younger patients

o Often gradual progression

o Can also present as gastrointestinal discomfort

 Dyspnea

 Dizziness, palpitations

 Restlessness, anxiety

 Autonomic symptoms (e.g., diaphoresis, nausea, vomiting, syncope)

Stable angina

 Symptoms are reproducible/predictable

 Complaints often subside within minutes; , with rest or after administration of nitroglycerin

 Common triggers

o Mental or physical stress

o Exposure to cold

Unstable angina

 Symptoms are not reproducible/predictable

 Usually occurs at rest or with minimal exertion and is usually not relieved by rest or
nitroglycerin

 Every new-onset angina

 Severe, persistent, and/or worsening angina (crescendo angina)

 Increasing intensity, frequency, or duration in a patient with a known stable angina

Unstable angina is a form of acute coronary syndrome and may progress to myocardial
infarction. Most patients with CHD first become symptomatic with acute myocardial infarction
or sudden cardiac death!
References:[9][4][10][11][12][13]

Subtypes and variants

Vasospastic angina

 Description:

o Angina caused by transient coronary spasms (usually occurring close to areas of

coronary stenosis)

o Unrelated to exertion and may even occur at rest (classically at night)

 Etiology: e.g., cigarette smoking, use of stimulants (e.g., cocaine, amphetamines) or

sumatriptan, alcohol, stress, hyperventilation, exposure to cold

o There is an association with other disorders involving vasospasms (e.g., Raynaud

phenomenon, migraine headaches)

 Epidemiology: average onset around 50 years

 Diagnostics

o Reversible ST elevation on ECG

o No troponin I or T level elevations on serial measurements

o Coronary spasms on angiography confirm the diagnosis

 Treatment

o Risk factor modification

o Calcium channel blockers; and nitrates: first-line agent for acute attacks and
prophylaxis

o Avoid beta-blockers!

 Prognosis:

o The five-year survival rate is > 90% (with treatment).

 Persistence of symptoms is common.

References:[14][15][16]

Diagnostics

Patient history and physical exam

 History of recurrent angina episodes

 Signs of atherosclerotic vessel disease (e.g., absent foot pulses, carotid bruit) → see also
physical exam in cardiology

Resting ECG

 Best initial test for both types of angina (and other types of chest pain)

 Usually normal in stable angina

 Treat as unstable angina if abnormalities (of the ST segment or the T wave) occur during an
episode of chest pain

Cardiac stress test

Cardiac stress tests are generally most useful in patients with an intermediate pretest probability
of coronary artery disease.

Choosing the most appropriate provocation and detection methods

 Provocation

o Able to exercise (and no contraindications for exercise testing): exercise stress test

o Unable to exercise (and no contraindications to pharmacologic testing):

pharmacologic stress test

 Detection

o Resting ECG can be interpreted: ECG

o Resting ECG cannot be interpreted: imaging

 Example: In a 75-year-old patient with acute aortic dissection, exercise testing would be
contraindicated. If he also has atrial fibrillation, imaging would be indicated to monitor the
test. Therefore, a pharmacologic stress test with either echocardiography or scintigraphy
would be indicated.

Provocation methods

Both types of stress test can be used with ECG, echocardiography, and/or myocardial perfusion
imaging. Clinical features, blood pressure, and heart rate are evaluated/recorded
simultaneously.

 Cardiac exercise stress test

o The patient exercises until the target heart rate is achieved (e.g., on a treadmill).

 Maximum heart rate = 220 – age (in years)

 Target heart rate = 85% of the maximum heart rate

o Contraindications
  Acute myocardial infarction with elevated troponin levels and/or ST
elevations (in the past 2 days)

 Unstable angina pectoris or ST depressions at rest

 Decompensated heart failure or severe symptomatic stenosis of one or

more heart valves

 Acute endocarditis, myocarditis, or pericarditis

 Hemodynamically significant arrhythmias

 Acute thromboembolic disease

 Acute aortic dissection

 Mental or physical impairment to exercise

 Cardiac pharmacological stress test

o IV administration of positive inotropic/chronotropic substances (e.g., dobutamine)

or vasodilators (e.g., dipyridamole or adenosine) to simulate the effect of exercise
on the myocardium

o Contraindications

 Adenosine, dipyridamole:

 Active bronchospasm or reactive airway disease

 First-degree heart block

 Low systolic blood pressure (< 90 mm Hg)

 Methylxanthines

 Dobutamine

 Myocardial infarction within the last week

 Unstable angina

 Obstructive cardiomyopathy, aortic stenosis

 Tachyarrhythmias

 Left bundle branch block

 Untreated hypertension

 Thoracic aortic aneurysm

Preparation
 If cardiac stress test is done for primary diagnosis, withhold the following:

o Beta blockers, calcium channel blockers, nitrates (48 hours)

o Methylxanthines (especially if a pharmacological cardiac stress test is considered); :

caffeine (12 hours); , aminophylline; (24 hours), dipyridamole (48 hours)

 If cardiac stress test is done for treatment evaluation, medication can be continued.

Findings in stress-induced ischemia

 Clinical findings: If one of the following symptoms occurs, the exercise stress should be
stopped.

o New onset/intensification of chest pain

o Severe dyspnea, cyanosis, pallor, ataxia, or altered mental status

o Decrease in systolic BP below the resting BP

o Systolic BP > 250 mm Hg or diastolic BP > 120 mm Hg

 ECG

o Downsloping or horizontal ST depressions of ≥ 0.1 mV in the limb leads and ≥ 0.2 mV

in the precordial leads

o ST elevations ≥ 0.1 mV (requires immediate test termination!)

o Excessive or delayed increase in heart rate

o New onset ventricular arrhythmia

 Imaging

o The goal is to distinguish between:

 Irreversible ischemia: necrosis (myocardial scars)

 Reversible ischemia: tissue that is ischemic (but not yet irreversibly dead)
and therefore still potentially salvageable

 Myocardial stunning: acutely ischemic myocardial segments that

demonstrate transiently impaired contractility that is completely
reversible

 Hibernating myocardium: persistently impaired myocardial

contractility that is partially or completely reversible when adequate
oxygen supply is restored (e.g., after angioplasty or CABG)

 Caused by chronically reduced coronary blood flow

  Seen in angina pectoris, left ventricular dysfunction, and/or
heart failure

o Echocardiography

o Radionuclide myocardial perfusion imaging

Patients with new-onset chest pain, ST segment depression, hypotension or arrhythmias should
undergo cardiac catheterization!

Cardiac catheterization

 Indications

o Persistent symptoms of angina despite appropriate therapy or

o Pathological result of the non-invasive examination or

o Noninvasive procedure with ambiguous results and high clinical suspicion of CHD

 Gold standard of CHD diagnosis

o Information on several qualities; (e.g., coronary blood flow; , pressure within heart
chambers, cardiac output, oxygen saturation)

o Direct visualization of coronary arteries (coronary angiography)

o Opportunity for direct therapeutic intervention using percutaneous coronary

intervention (see "Treatment” below)

Additional tests

 Holter monitoring: can detect silent ischemia and arrhythmias and be used to evaluate heart
rate variability and pacemaker/ICD function

 Coronary magnetic resonance imaging (CMRI) or coronary computed tomography

angiography (CCTA)

References:[4][17][18][19][20][21][22][23][24][25]

Differential diagnoses
 See differential diagnosis of chest pain.

The differential diagnoses listed here are not exhaustive.

Treatment

Approach

 All patients: risk factor reduction and antiplatelet drugs; see “Prevention” below

 Mild CHD: pharmacologic therapy

 Moderate CHD; : consider coronary angiography and percutaneous transluminal coronary

angioplasty (PTCA)/percutaneous coronary intervention (PCI)

 Severe CHD: coronary angiography and revascularization or coronary artery bypass grafting

Antianginal treatment

 First-line

o Beta-blockers (except in vasospastic angina): can reduce the frequency of coronary

events

o Nitrates

 Can prevent exertional angina

 Suitable for relief of acute angina or for long-term treatment

 Second-line

o Calcium channel blockers (CCBs): indicated if there are contraindications to beta-

blockers or in addition to beta-blockers (if angina or hypertension persist)

o Ranolazine: indicated in stable angina that is refractory to first-line treatment

 Two mechanisms of action to reduce myocardial oxygen demand: 1) inhibit

late phase sodium influx into cardiac myocytes → reduced calcium flux (via
sodium-calcium channel pump) → reduced wall stress and oxygen demand;
and 2) decreased rate of fatty acid beta oxidation (aerobic process) with
simultaneous increase in glycolysis (anaerobic process).

 Combination therapy: indicated if angina persists with monotherapy

o Beta-blocker + nitrates

o Calcium channel blocker (nondihydropyridines) + nitrates

o Beta-blocker + calcium channel blockers (long-acting dihydropyridines, such as

nitrendipine)
Revascularization

 Indications

o In stable angina: activity-limiting symptoms despite optimal medical treatment,

contraindications to medical therapy, stenosis of critical (e.g., LCA) or multiple
coronary arteries

o Acute coronary syndrome

 Techniques

o Percutaneous coronary intervention

o Coronary artery bypass grafting

References:[26][27][28]

Prognosis

 Prognostic factors

o Left ventricular function: increased mortality if EF < 50%

o Involvement of left main coronary artery or involvement of more than one vessel is
associated with a worse prognosis.

 Stable angina

o Annual mortality rate: ∼ 5%

o 25% of patients will suffer an acute MI within the first 5 years.

o High-grade stenosis is associated with an unfavorable prognosis.

References:[4][29]

Prevention

Prevention of atherosclerosis

 Primary and secondary prevention of atherosclerosis

Special considerations in coronary heart disease

 Antiplatelet drugs indicated in all patients: aspirin; or clopidogrel (if aspirin/ASA is

contraindicated) → ↓ risk of infarction, ↓ morbidity

 Treating arterial hypertension

o Reduce blood pressure to < 140/90 mm Hg in cases of low/moderate risk and to <
130/80 mm Hg in high-risk patients
 o Beta-blockers are the first-line therapy for CHD combined with arterial hypertension.

o ACE-inhibitors patients post-MI, especially those with left ventricular systolic

dysfunction.

o Calcium channel blockers (for indications, see “Antianginal therapy” above)

 HbA1c of 6.5–7%

 Risk-adjusted LDL values: see Guidelines for lipid-lowering therapy (ATP III guidelines) for
details