Vasospastic and microvascular angina

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

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.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

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.

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.

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.

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.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

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
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
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
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
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.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

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.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

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.
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.
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.
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.
05
CFR and microvascular resistance assessment
Why
Measure vasodilator reserve and resistance with guidewire physiology.
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.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

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.

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.

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.

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.

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.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Preferred routeAcute rest painFirst stepPreferredCurrent severe or prolonged symptoms

1Use the ACS pathway with ECG, serial troponin, monitoring and urgent assessment; give sublingual GTN when safe.
2Treat persistent ST elevation, arrhythmia or haemodynamic compromise as an emergency.
3Define obstructive, SCAD, embolic or other acute mechanisms with coronary imaging as indicated.
4Only settle on vasospasm after dangerous acute causes have been addressed.

02Preferred routePersistent ANOCA or INOCAPreferredAngina continues despite non-obstructive CTCA or angiography

1Reassess the symptom pattern, adherence, anaemia, arrhythmia, valve disease and non-cardiac alternatives without dismissing the pain.
2Use 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

1Start a calcium-channel blocker and provide short-acting GTN with emergency instructions.
2Titrate or combine specialist-selected calcium-channel blocker classes when symptoms persist and blood pressure or conduction permit.
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.
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

1Optimise blood pressure, lipids, exercise, weight, diabetes and smoking management.
2Use a beta-blocker, calcium-channel blocker or other antianginal matched to heart rate, blood pressure and comorbidity.
3First lineConsider ranolazine as add-on when first-line therapy is ineffective or not tolerated.
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.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Myocardial infarction

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

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.

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.

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.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

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.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

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.

11Common pitfallsFrequent interpretation and management errors.

01
Telling a patient that non-obstructive angiography proves symptoms are non-cardiac.
02
Starting beta-blocker monotherapy in suspected pure vasospastic angina.
03
Diagnosing vasospasm solely because pain responds to GTN.
04
Ignoring prolonged rest pain or troponin elevation because prior angiography was normal.
05
Escalating multiple antianginals without defining the endotype or monitoring blood pressure, conduction and interactions.