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OverviewAetiologyPathophysiologyClinical features and red flagsInvestigationsDifferential diagnosisManagementComplicationsMonitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Vasospastic and microvascular angina

Cardiology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

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Time-critical presentation

Treat new or prolonged rest pain with ECG change or troponin rise as possible ACS until excluded. Coronary spasm can cause infarction, syncope and ventricular arrhythmia and may require urgent monitored care.

Overview

Recognise angina with non-obstructive coronary arteries, identify vasospastic or microvascular endotypes and use mechanism-directed testing and treatment.

ANOCA describes angina with non-obstructive coronary arteries; INOCA additionally demonstrates ischaemia. Endotypes can overlap: epicardial vasospasm, microvascular spasm, impaired vasodilator reserve and increased microvascular resistance.

Diagnosis should be positive and mechanistic rather than a label of exclusion. Functional imaging can demonstrate ischaemia or impaired flow reserve, while invasive testing can reproduce symptoms and ECG change and measure coronary physiology.

Therapy is iterative: provide rescue medication and safety-netting, target the endotype, manage blood pressure and lipids, address smoking and triggers, and reassess symptom burden and treatment tolerance.

Key points

  • Non-obstructive coronary arteries do not make angina non-cardiac; consider epicardial spasm and coronary microvascular dysfunction.
  • Vasospastic angina often occurs at rest, particularly at night or early morning, with transient ST change and prompt nitrate response.
  • Microvascular angina may be exertional or occur at rest and can persist longer than classic obstructive angina.
  • Capture a 12-lead ECG during pain whenever possible and use serial troponin for prolonged or acute episodes.
  • If symptoms persist despite non-obstructive CTCA or angiography, ESC 2024 recommends invasive coronary functional testing to define endotypes and guide therapy.
  • Acetylcholine testing assesses epicardial and microvascular spasm; adenosine-based physiology assesses flow reserve and microvascular resistance.
  • Calcium-channel blockers are first-line for vasospasm; avoid unopposed beta-blockade in pure vasospastic disease.
  • Treat coexisting atherosclerotic risk and endothelial dysfunction even when no flow-limiting stenosis is present.

Aetiology

01

Epicardial smooth-muscle hyperreactivity

An abnormally reactive coronary segment can constrict transiently, sharply reducing flow despite no fixed severe obstruction. Tobacco and other vasoconstrictive triggers can increase susceptibility.

02

Endothelial dysfunction

Endothelial dysfunction impairs normal vasodilatation and may favour inappropriate epicardial or microvascular constriction. Hypertension, dyslipidaemia, diabetes and smoking can contribute even when angiography shows non-obstructive arteries.

03

Structural microvascular remodelling

Small-vessel wall thickening and reduced capillary density increase coronary resistance and limit flow reserve, particularly in people with hypertension, diabetes or cardiomyopathic remodelling.

04

Overlapping coronary mechanisms

Non-obstructive plaque, myocardial bridging, epicardial spasm and microvascular dysfunction may coexist. A single positive finding therefore may explain only part of the symptom burden.

Pathophysiology

  1. 1
    Vasomotor imbalance

    Endothelial dysfunction, heightened smooth-muscle reactivity or abnormal autonomic control disturbs the normal matching of coronary calibre to myocardial oxygen demand.

  2. 2
    Transient flow limitation

    Epicardial spasm markedly narrows a visible coronary segment, while microvascular spasm constricts resistance vessels without severe large-vessel narrowing. Both can occur at rest.

  3. 3
    Impaired flow reserve

    Structural or functional microvascular disease may prevent adequate arteriolar dilatation during increased demand, so myocardial perfusion can become insufficient despite non-obstructive epicardial anatomy.

  4. 4
    Reversible ischaemia

    The transient perfusion deficit may produce angina and ischaemic ST-segment change. Prolonged or intense spasm may cause myocardial injury rather than resolving without biomarker release.

  5. 5
    Recurrent endotype expression

    Circadian autonomic variation, smoking or other triggers can reactivate vasospasm, while persistent microvascular dysfunction may cause exertional or prolonged symptoms and continuing functional limitation.

Clinical features and red flags

Epicardial vasospasm

Rest pain with transient ST elevation or depression and at least 90% reversible epicardial constriction during provocation, accompanied by reproduced symptoms and ischaemic ECG change.

Microvascular spasm

Typical symptoms and ischaemic ECG change during provocation without severe epicardial constriction support a microvascular vasomotor mechanism.

Impaired microvascular reserve

Reduced coronary flow reserve or raised microvascular resistance with non-obstructive epicardial arteries supports structural or functional microvascular dysfunction.

High-risk spasmRed flag

Syncope, ventricular arrhythmia, infarction or prolonged ST elevation during an episode requires urgent monitored specialist management.

Overlapping disease

Non-obstructive plaque, myocardial bridging, hypertension, cardiomyopathy and spasm can coexist; one positive mechanism need not explain every symptom.

Investigations

  1. 01
    12-lead ECG during symptomsFirst step
    Why
    Document transient ischaemic change or arrhythmia.
    Interpretation and limitations
    A normal pain-free ECG is expected between episodes and does not exclude vasospasm.
  2. 02
    Serial high-sensitivity troponin
    Why
    Detect acute myocardial injury during prolonged or severe episodes.
    Interpretation and limitations
    Elevation triggers an ACS or MINOCA evaluation; normal troponin does not exclude angina.
  3. 03
    CTCA or invasive angiography
    Why
    Exclude or define obstructive epicardial CAD and identify non-obstructive plaque.
    Interpretation and limitations
    A non-obstructive result redirects rather than ends the coronary evaluation when symptoms persist.
  4. 04
    Invasive acetylcholine provocation
    Why
    Test epicardial and microvascular vasomotor responses in an expert laboratory.
    Interpretation and limitations
    Interpret angiographic constriction together with reproduced symptoms and ECG change; resuscitation and reversal capability are mandatory.
  5. 05
    CFR and microvascular resistance assessment
    Why
    Measure vasodilator reserve and resistance with guidewire physiology.

Differential diagnosis

01

Obstructive coronary disease

A flow-limiting epicardial stenosis produces demand-related ischaemia and is demonstrated by anatomical or physiological testing, whereas vasomotor disease may leave arteries unobstructed between episodes.

02

Acute coronary syndrome

Prolonged pain, persistent territorial ECG change or a dynamic troponin rise requires acute coronary assessment; a previous non-obstructive angiogram does not safely exclude a new event.

03

Gastro-oesophageal pain

Burning discomfort related to meals, recumbency or regurgitation without objective ischaemic change favours reflux, although symptomatic response to nitrates alone does not discriminate reliably.

04

Musculoskeletal chest pain

Pain reproducible by palpation, movement or a specific chest-wall action supports a musculoskeletal source, provided acute cardiac features and objective ischaemia are absent.

05

Pericarditis or myocarditis

Pleuritic positional pain, inflammatory features, diffuse ECG changes or non-ischaemic cardiac magnetic resonance findings point towards inflammatory cardiac disease rather than a coronary vasomotor endotype.

Management

01Preferred routeAcute rest painFirst stepPreferredCurrent severe or prolonged symptoms+
  1. 1Use the ACS pathway with ECG, serial troponin, monitoring and urgent assessment; give sublingual GTN when safe.
  2. 2Treat persistent ST elevation, arrhythmia or haemodynamic compromise as an emergency.
  3. 3Define obstructive, SCAD, embolic or other acute mechanisms with coronary imaging as indicated.
  4. 4Only settle on vasospasm after dangerous acute causes have been addressed.
02Preferred routePersistent ANOCA or INOCAPreferredAngina continues despite non-obstructive CTCA or angiography+
  1. 1Reassess the symptom pattern, adherence, anaemia, arrhythmia, valve disease and non-cardiac alternatives without dismissing the pain.

Complications

01

Myocardial infarction

Sustained severe coronary spasm can reduce perfusion long enough to cause myocardial necrosis, even when no fixed obstructive plaque is identified.

02

Ventricular arrhythmia and syncope

Severe transient ischaemia can destabilise ventricular conduction, allowing tachycardia or fibrillation. A resulting fall in cardiac output may cause syncope or cardiac arrest.

03

Persistent functional limitation

Recurrent pain and unpredictable episodes can reduce exercise, employment and quality of life, leading to repeated emergency presentations despite apparently reassuring coronary anatomy.

04

Ongoing cardiovascular risk

Endothelial dysfunction and non-obstructive atherosclerotic plaque may accompany vasomotor disease, so the absence of a flow-limiting stenosis does not remove future cardiovascular risk.

Monitoring and follow-up

  • Track weekly angina frequency, rest versus exertional pattern, GTN use and functional limitation.
  • Monitor blood pressure, heart rate, PR interval and oedema when titrating calcium-channel blockers or beta-blockers.
  • Review ECG QT interval, renal function and interacting medicines before and during ranolazine where indicated.
  • Reassess smoking, stimulant exposure, migraine medicines and other individual spasm triggers.
  • Escalate recurrent syncope, arrhythmia, prolonged rest pain or troponin-positive episodes urgently.

Special situations

ANOCA is not reassurance

Symptoms, impaired quality of life and cardiovascular risk persist even without a large-vessel obstruction.

Endotypes overlap

A patient may have both epicardial spasm and impaired microvascular reserve, so one drug may not control all symptoms.

Pain timing can help

Circadian rest pain points toward spasm, while exertional symptoms occur in both obstructive and microvascular disease.

Provocation is a specialist procedure

Acetylcholine testing intentionally challenges coronary tone and requires trained staff, continuous monitoring and rapid reversal or resuscitation capability.

Beta-blocker choice is mechanistic

It may help demand-related microvascular angina but aggravate pure vasospasm through unopposed vasoconstriction.

Measure function, not pain alone

Walking distance, work participation and GTN use show whether an endotype-directed plan is helping.

Common pitfalls

  1. 01

    Telling a patient that non-obstructive angiography proves symptoms are non-cardiac.

  2. 02

    Starting beta-blocker monotherapy in suspected pure vasospastic angina.

  3. 03

    Diagnosing vasospasm solely because pain responds to GTN.

  4. 04

    Ignoring prolonged rest pain or troponin elevation because prior angiography was normal.

  5. 05

    Escalating multiple antianginals without defining the endotype or monitoring blood pressure, conduction and interactions.

Practice

Two practice questions

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Question 1 of 2
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CardiologyOriginal SBA

Persistent angina with non-obstructive arteries

A patient has continuing angina despite non-obstructive coronary angiography and guideline-derived treatment. What does ESC 2024 recommend to define the mechanism?

Choose one answer, then submit
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Sources and review status8 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • ESC 2024 Guidelines for chronic coronary syndromes
  • NICE CG126: Stable angina management
  • Glyceryl trinitrate 400 micrograms spray SmPC
  • Amlodipine 5 mg tablets SmPC
  • Tildiem Retard 90 mg SmPC
  • Isosorbide mononitrate 30 mg prolonged-release tablets SmPC
  • Ranexa 375 mg SmPC
  • NHS: Common questions about glyceryl trinitrate

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom
Interpretation and limitations
In the ESC 2024 framework, CFR below 2.5 or IMR 25 or above supports dysfunction; the measurement method, hyperaemic agent, technical quality and clinical context still matter.
  • 06
    Stress PET, CMR or echocardiography
    Why
    Demonstrate ischaemia and, with PET or quantitative CMR, assess global flow reserve.
    Interpretation and limitations
    Diffuse reduction may occur without a focal territorial defect; a negative conventional relative test does not fully exclude microvascular disease.
    • 2
    Use functional imaging when ischaemia or flow reserve remains untested.
  • 3If symptoms persist despite guideline-derived therapy, refer for invasive coronary functional testing to identify endotypes.
  • 4Explain the positive diagnosis and agree measurable symptom and function goals.
    • 03Endotype therapyVasospastic anginaEpicardial or microvascular spasm is suspected or demonstrated+
    1. 1Start a calcium-channel blocker and provide short-acting GTN with emergency instructions.
    2. 2Titrate or combine specialist-selected calcium-channel blocker classes when symptoms persist and blood pressure or conduction permit.
    3. 3For persistent epicardial spasm, add a long-acting nitrate while preserving a daily low-nitrate interval; benefit in isolated microvascular spasm is uncertain, so individualise rather than adding it automatically.
    4. 4Stop smoking and avoid individual triggers such as cocaine or other sympathomimetics; avoid beta-blocker monotherapy in pure spasm.
    04Endotype therapyMicrovascular dysfunction without spasmImpaired flow reserve or increased microvascular resistance+
    1. 1Optimise blood pressure, lipids, exercise, weight, diabetes and smoking management.
    2. 2Use a beta-blocker, calcium-channel blocker or other antianginal matched to heart rate, blood pressure and comorbidity.
    3. 3First lineConsider ranolazine as add-on when first-line therapy is ineffective or not tolerated.
    4. 4EscalationReassess symptoms and function; revisit the endotype if treatment fails rather than escalating blindly.
    Key medicines and prescribing safety6 treatments · regimens, roles and cautions+
    Short-acting relief for vasospastic or other angina when haemodynamics permit.

    Glyceryl trinitrate sublingual spray

    400–800 micrograms under the tongue at symptom onset; repeat at 5-minute intervals if needed, to a maximum total of 3 sprays, then seek prompt medical help if unresolved.

    Avoid with hypotension, severe aortic stenosis or riociguat. Do not use within at least 24 hours of sildenafil or vardenafil or 48 hours of tadalafil; lack of response does not exclude ischaemia.

    First-line calcium-channel blockade for vasospastic angina and a useful antianginal when bradycardia limits non-dihydropyridines.

    Amlodipine

    5 mg orally once daily, increased to 10 mg once daily according to response and tolerance.

    Hypotension, ankle oedema and severe outflow obstruction; it does not provide acute relief.

    Rate-limiting calcium-channel blocker for vasospastic angina when ventricular function and conduction permit.

    Diltiazem modified release

    A product-specific typical start is 90 mg orally twice daily; titrate to response, with doses up to 480 mg/day used in some angina patients according to the SmPC.

    Contraindicated in sick-sinus syndrome or second- or third-degree AV block without a functioning pacemaker, severe bradycardia below 50 beats/min and LV failure with pulmonary stasis; formulations are not interchangeable and CYP3A interactions require review.

    Add-on prophylaxis for recurrent epicardial vasospastic angina; not for acute attacks.

    Isosorbide mononitrate prolonged release

    30 mg once daily for 2–4 days to reduce headache, then 60 mg each morning; may increase to 120 mg once daily.

    Avoid in marked hypotension or low-filling-pressure states and severe anaemia; never combine with a phosphodiesterase-5 inhibitor or riociguat, and preserve a daily low-nitrate interval.

    Add-on symptom treatment, especially for microvascular angina when first-line agents are inadequate or not tolerated.

    Ranolazine prolonged release

    375 mg orally twice daily, increasing after 2–4 weeks to 500 mg twice daily and, if needed and tolerated, up to 750 mg twice daily.

    Contraindicated with creatinine clearance below 30 ml/min, moderate or severe hepatic impairment, potent CYP3A4 inhibitors and class Ia or III antiarrhythmics other than amiodarone; review QT prolongation, P-glycoprotein interactions and interacting statins.

    Reduce demand in microvascular dysfunction without a vasospastic endotype.

    Bisoprolol

    For stable angina, start 5 mg orally once daily and increase to 10 mg once daily if needed; lower doses may be appropriate with bradycardia or comorbidity.

    Avoid beta-blocker monotherapy in pure vasospastic angina; bradycardia, AV block, hypotension, bronchospasm and decompensated heart failure.