Chronic coronary disease

Chronic coronary disease (CCD) is characterized by chronic myocardial ischemia due to atherosclerosis, endothelial dysfunction, and/or microvascular disease. CCD encompasses all stable manifestations of ischemic heart disease, including coronary artery disease (CAD) and ischemia with nonobstructive coronary arteries (INOCA). Symptoms include stable angina or anginal equivalents (e.g., dyspnea). Some patients remain asymptomatic or have atypical symptoms. The diagnostic approach should begin with evaluation for CAD, the most common and severe cause of CCD, and it can involve ECG, cardiac imaging (e.g., CAC score, CTA), cardiac stress testing, and invasive coronary angiography. Management of CCD includes optimizing cardiovascular risk factors through lifestyle modifications (e.g., smoking cessation, exercise), treating comorbidities (e.g., diabetes, hypertension, dyslipidemia), antiplatelet therapy, and symptomatic treatment with antianginal medication (e.g., beta blockers, calcium channel blockers, nitrates). For some patients with CAD, coronary revascularization is necessary to reduce the risk of major adverse cardiovascular events (MACE).

For approaches to acute chest pain, see “Acute coronary syndrome” and “Chest pain.” See “Atherosclerotic cardiovascular disease” for further details on risk factors and risk calculation for CAD.

Causes of CCD ^[1]

• Atherosclerosis
• Coronary spasm
• Coronary microvascular dysfunction
• Other nonatherosclerotic causes in younger adults ^[2]
  • Kawasaki disease
  • Structural coronary abnormalities
    • Coronary artery anomalies
    • Myocardial bridging

General risk factors ^[3][4]

• Traditional ASCVD risk factors (e.g., smoking, diabetes mellitus, dyslipidemia)
• ASCVD risk-enhancing factors (e.g., family history of premature ASCVD, chronic kidney disease, chronic inflammatory diseases)
• Additional risk factors
  • History of chest radiation
  • History of cardiotoxic chemotherapy
  • Evidence of coronary calcifications on prior imaging (e.g., chest x-ray, chest CT)

Risk factors for CCD in young adults ^[2]

• Traditional risk factors
  • Hypertension
  • Obesity and metabolic syndrome
  • Diabetes mellitus
  • Hyperlipidemia
  • Smoking
  • Family history of premature CAD
  • Unhealthy diet
  • Lack of physical activity
• Nontraditional risk factors
  • Familial hypercholesterolemia
  • Chronic inflammatory disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis)
  • Vasculitides
  • HIV infection and antiretroviral HIV therapy
  • History of chest radiation
  • Complications related to pregnancy (e.g., gestational diabetes, hypertensive disorders of pregnancy)
  • Use of cocaine or marijuana

Cardiotoxic chemotherapy agents or targeted therapies used in cancer treatment increase ASCVD risk and, in patients with CCD, increase the risk of cardiovascular adverse events. ^[2]

• Ischemic heart disease (IHD): a condition of inadequate myocardial perfusion (myocardial oxygen supply-demand mismatch and ischemia) ^[5]
• Chronic coronary disease (CCD): an umbrella term for all stable forms of IHD; applies to patients diagnosed with: ^[2][3]
  • Stable CAD
    • Obstructive CAD
    • Nonobstructive CAD
    • History of acute coronary syndrome and/or coronary artery revascularization
    • Ischemic cardiomyopathy with or without reduced LVEF
  • Ischemia with nonobstructive coronary arteries (INOCA): a type of IHD without obstruction of coronary arteries
    • Vasospastic angina: episodic obstruction of epicardial coronary arteries due to vasomotor disorders
    • Microvascular angina: ischemia due to microvascular dysfunction
  • Presumed IHD based on symptoms or screening
    • Medically controlled stable angina (regardless of imaging studies)
    • Positive screening test (e.g., cardiac stress testing or CTA)
    • Reduced LVEF of suspected ischemic origin

• Prevalence: ∼ 7% (∼ 20 million individuals) ^[2]
• Sex: ♂ > ♀ ^[2]

Epidemiological data refers to the US, unless otherwise specified.

Screening for CCD in patients without symptoms of ischemia may be considered for the following: ^[3]

• ASCVD risk assessment ^[3][4]
  • Borderline or intermediate 10-year ASCVD risk: CAC scoring (preferred initial test) or ECG stress test (alternative). ^[3][7][8]
  • High 10-year ASCVD risk: CAC scoring, cardiac stress testing, or CCTA. ^[3]
• Evaluation of new cardiac signs or symptoms, e.g. : ^[3]
  • Newly diagnosed heart failure ^[9]
  • Arrhythmias (e.g., frequent PVCs, VTs) ^[10]
  • Syncope (if initial evaluation suggests CCD)
• Chest radiation ≥ 5 years ago (increases risk of radiation-induced heart disease) ^[3]
• Pretreatment evaluation
  • Before starting antiarrhythmic medication (in patients with a high risk for CAD) ^[3]
  • Before unsupervised exercise programs
  • May be considered as part of preoperative cardiac assessment

Screening is not recommended for asymptomatic patients with a low 10-year ASCVD risk. ^[3][7]

Approach ^[6]

• Consider CCD in patients with:
  • Symptoms of ischemia
  • Positive screening results (e.g., signs of CAD on ECG)
• Evaluate for CAD.
  • Comprehensive clinical evaluation
  • Resting ECG
  • Consider further testing depending on risk assessment.
• Consider INOCA in patients with stable chest pain and no obstructive CAD.

Evaluation for CAD ^[6]

• Assess pretest probability (PTP) of obstructive CAD.
• Obtain initial testing based on PTP.
  • Low PTP: Consider CAC scoring or exercise ECG testing to rule out myocardial ischemia.
  • Intermediate to high PTP: either coronary CT angiography (CCTA) or cardiac stress testing
• See “Diagnostics for coronary artery disease” for details.

Evaluation for INOCA ^[6]

• Suspect INOCA in patients with stable chest pain and no obstructive or nonobstructive CAD.
• Assess for evidence of myocardial ischemia.
• Consider either:
  • Invasive coronary function testing
  • Stress MPI (PET) or stress CMR with myocardial blood reserve measurement
• Confirm diagnosis using:
  • Diagnostic criteria for vasospastic angina
  • Diagnostic criteria for microvascular angina

General principles ^[2]

• Patients should be managed by a multidisciplinary team.
• Provide patient education and emphasize shared decision-making.
• Assess social determinants of health.
• Follow up at least once per year.
  • Evaluate for new or worsening symptoms, functional status, and adequacy of current management. ^[11]
  • Assess for complications.

Treatment ^[2]

• Start nonpharmacological management for all patients with CCD (e.g., lifestyle modifications for ASCVD prevention).
• Manage comorbidities.
• Measures to prevent cardiovascular events, including:
  • Antiplatelet therapy
  • Lipid-lowering therapy
  • Consider colchicine therapy
• Offer selected patients cardiac rehabilitation (e.g., after PCI or CABG).
• Symptomatic treatment: Offer antianginal treatment depending on the underlying disease.
• For details on management (including dosages), see:
  • “Management of CAD”
  • “Management of vasospastic angina”
  • “Management of microvascular angina”

Management for CCD is also indicated for patients with medically controlled stable angina (regardless of imaging studies) and those with a diagnosis of CCD based on a positive screening test (e.g., cardiac stress testing or CTA). ^[2]

Vasospastic angina ^[2]

Vasospastic angina is caused by ; coronary vasomotor dysfunction that leads to transient coronary spasms and myocardial ischemia.

Epidemiology ^[12]

• Highest prevalence: Japanese population (especially women)
• Average age of onset: 40–70 years ^[12]

Etiology ^[13]

• Cigarette smoking; use of stimulants (e.g., cocaine, amphetamines), alcohol, or triptans ^[13][14][15]
• Associated with other vasospastic disorders (e.g., Raynaud phenomenon, migraine headaches) ^[16][17]
• Triggers (e.g., stress, hyperventilation, exposure to cold)

ASCVD risk factors (except smoking) do not apply to vasospastic angina.

Clinical features ^[13]

• Angina not affected by exertion (may also occur at rest)
• Typically occurs early in the morning

Diagnosis ^[17][18]

The goal of diagnostic testing is to detect transient ischemic changes and/or coronary artery spasm during anginal episodes as well as concomitant coronary artery stenosis. Specialist consultation is advised. ^[13]

• Initial testing ^[17][19]
  • Resting ECG: Obtain during an acute anginal attack.
  • Consider Holter monitor in patients with : ^[19]
    • No ischemic changes on resting ECG
    • Syncope or bradyarrhythmias ^[17][19]
  • Exercise stress test
    • Consider if ischemic changes have not been identified using other methods.
    • Approx. one-third of patients with vasospastic angina do not have ST segment changes during an exercise stress test. ^[17]
• Cardiac biomarkers
  • Measure serial troponin I and/or troponin T levels during periods of acute chest pain (i.e., at arrival and 1–6 hours later) if acute coronary syndrome is suspected (see also “Complications”).
  • Serial troponin levels are unlikely to be elevated in patients with transient ischemic changes. ^[13][20]
• Advanced testing ^[17][18]
  • Coronary angiography: commonly indicated in vasospastic angina with ST-segment elevation to rule out underlying coronary artery stenosis
  • Coronary artery spasm provocation testing ^[17][18]
    • Usually only performed to aid diagnosis or treatment decisions when further information is required following other tests
    • Not recommended for patients with severe coronary artery stenosis or advanced heart failure ^[13]
    • Spasms are usually induced pharmacologically.
    • Nitrates and calcium channel blockers (CCBs) should be held before testing.
    • Noninvasive coronary artery spasm provocation testing is not advised. ^[18]

Noninvasive bedside coronary artery spasm provocation testing can lead to significant adverse effects and even death. Provocation testing to diagnose vasospastic angina should only be attempted by a specialist, and usually only during coronary angiography. ^[18]

Treatment of vasospastic angina ^{[2][13][17][21]}

• General recommendations
  • Smoking cessation
  • Avoidance of beta blockers (particularly nonselective beta blockers) and other agents that induce vasoconstriction, e.g.: ^[19][21]
    • Triptans
    • High-dose aspirin (> 325 mg) ^[19][21]
    • Certain chemotherapeutic agents
    • Alcohol and recreational use of drugs
  • Atherosclerotic risk factor modification, as appropriate (see “Management of ASCVD”) ^[2][13]
• Pharmacological treatment ^[17][19]
  • First-line: calcium channel blockers (e.g., verapamil ) ^[2]
  • Second-line
    • Long-acting nitrates (e.g., isosorbide dinitrate ) ^[2]
    • Combination therapy for symptom control: nitrates with up to two CCBs from different classes ^[13][17]
• Additional therapy
  • Short-acting nitrates (e.g., nitroglycerin ) ^[2]
    • May be used during acute attacks
    • Patients should seek medical attention if pain persists after three doses of nitroglycerin taken over 15 minutes.
  • Statins (e.g., fluvastatin ) can further prevent coronary artery spasm when added to CCB treatment. ^[13][22]
  • Alpha blockers: The addition of prazosin to CCBs or long-acting nitrates may reduce episodes of spasm. ^[13][21]
  • Magnesium supplementation may help prevent spasms. ^[13][19][23]

Complications ^[17][19]

• Myocardial infarction
  • May occur with prolonged spasms or in patients with concomitant coronary artery stenosis
  • See “Acute coronary syndrome.”
• Arrhythmias ^[17]
  • AV block: A pacemaker may be required (see “Management approach to patients with AV block”).
  • Ventricular arrhythmia and sudden cardiac death: An implantable cardioverter defibrillator may be required.

Prolonged coronary artery spasms can lead to MI or fatal arrhythmias. ^[17]

Prognosis

• The 5-year survival rate is > 90% with treatment. ^[24]
• The persistence of symptoms is common.

Coronary artery stenosis, which is caused by obstructive atherosclerotic plaques, can coexist with vasospastic angina and is associated with a worse prognosis than vasospastic angina alone. ^[13]

Microvascular angina ^[2][25]

Microvascular angina is caused by coronary microvascular dysfunction (CMD). ^[2]

Epidemiology ^[25]

• Prevalence in individuals with chest pain but nonobstructive CAD: 30–50% ^[25]
• ♀ > ♂ ^[25]

Etiology ^[26][27]

• The etiology is not fully understood.
• Chronic inflammatory response to risk factors for CAD (e.g., smoking, hypertension) is a significant factor.

Pathophysiology ^[2]

• Multifactorial
• Mechanisms include:
  • Endothelial dysfunction: ↓ coronary vasorelaxation, ↓ microvasodilator capacity
  • Nonendothelial dysfunction: ↑ microvascular resistance, microvascular spasm
  • Structural factors

Clinical features ^[25][27]

• Patients may be asymptomatic or present with angina or anginal equivalents.
• Symptoms can occur at rest or during or after exertion.
• Less pronounced response to nitrates than patients with obstructive CAD

Diagnosis ^[6][25][26]

• Refer to a specialist.
• Rule out flow-limiting coronary stenosis using CCTA or invasive coronary angiography. ^[26]
• Confirm signs of cardiac ischemia on noninvasive testing (resting ECG and/or cardiac stress testing).
• Obtain coronary function testing to confirm impaired coronary microvascular function.

Obstructive CAD can coexist with CMD. ^[27]

Treatment of microvascular angina ^[2]

• General recommendations (all patients)
  • Lifestyle modifications for ASCVD prevention
  • Consider indications for aspirin, statin, and ACE-inhibitor therapy.
• Antianginal pharmacological treatment
  • First-line: beta blockers (e.g., carvedilol)
  • Second line : nondihydropyridine CCBs (e.g., verapamil)
  • Third-line: additional therapy
    • Sublingual nitroglycerin as needed for angina symptoms
    • Dihydropyridine CCBs, e.g., amlodipine (only for patients on beta blockers)
    • Ranolazine

Complications ^[26]

• HFpEF
• Myocardial infarction with nonobstructive coronary arteries (MINOCA) is rare.

Prognosis

• CMD increases the risk of MACE in patients with nonobstructive CAD. ^[28]
• Women are more likely than men to have persistent symptoms. ^[29]