01Approach to the Critical Patient/attcp40

Immediate stabilization

›Hemodynamic and rhythm priorities

›Continuous cardiac monitoring mandatory

›ST-segment trending in the distribution of the spasming artery

›Arrhythmia detection: polymorphic VT, VF, high-degree AV block

›IV access and pulse oximetry

›Two large-bore peripheral IVs

›SpO2 target >= 94%

›If hemodynamic instability present, escalate to resuscitation bay

›SBP < 90 mmHg as threshold

›MAP < 65 mmHg as threshold

Critical recognition

›Cannot-miss distinction: Prinzmetal angina vs STEMI

›Transient STE that resolves completely with NTG suggests vasospasm

›STEMI STE is persistent and evolves

›Activate cath lab until STEMI excluded

›Sublingual NTG 0.4 mg diagnostic and therapeutic

›Repeat every 5 minutes x 3 doses

›Dramatic rapid relief supports vasospastic etiology

›Serial 12-lead ECGs every 5-15 minutes during pain

›Capture transient STE before it resolves

›Normal ECG between episodes does not exclude diagnosis

Escalation triggers

›High-risk features requiring immediate action

›Syncope during or after episode

›Suggests malignant arrhythmia (VT, VF, high-degree AV block)

›42% risk of sudden death within 26 months if documented arrhythmias

›Lambda wave pattern on ECG

02History/hx81

Classic presentation

›Core symptom complex

›Chest pain at rest

›Substernal pressure or squeezing quality

›Similar to typical angina but without exertional pattern

›Circadian pattern: midnight to early morning predominance

›Vasomotor tone peaks in early morning hours

›Episodes may cluster in waves with symptom-free intervals

›Brief episodic duration

›Typically minutes

›Self-resolving or rapidly relieved by sublingual NTG

Alarm features

›High-risk symptoms

›Syncope

›Suggests life-threatening arrhythmia

›VT, VF, or high-degree AV block during spasm

›Prolonged pain > 15-20 minutes

›Risk of progression to MI

›5-10% of patients experience MI as complication

›Palpitations with lightheadedness

›Arrhythmia during ischemic episode

›Warrants continuous monitoring

Precipitating factors

›Known triggers

›Emotional stress

›Sympathetic activation pathway

›Panic attacks can trigger episodes

›Hyperventilation

›Respiratory alkalosis provokes vasospasm

›Useful as noninvasive provocative test

›Cold exposure

›Occupational cold exposure risk

›Reflex alpha-adrenergic stimulation

›Exercise

›Variable-threshold angina pattern

›One-third show STE on exercise stress testing

Substance and medication exposures

›Vasoconstrictive substances

›Cocaine and methamphetamine

›Direct coronary vasospasm

›Must be discontinued; critical risk factor

›Marijuana use

›Coronary vasospasm risk

›Tobacco smoking

›Most prominent coronary risk factor for vasospastic angina

›Smoking cessation is Class I intervention

›Medications causing vasospasm

›5-fluorouracil and paclitaxel (chemotherapy)

›Well-documented vasospasm risk

›Sumatriptan and pseudoephedrine

›Vasoconstrictive mechanism

›Inotropes and ergot derivatives

›Alpha-adrenergic stimulation

Risk factors

›Patient demographics and comorbidities

›East Asian ethnicity

›Up to 40% of angina patients in Japan have vasospastic angina

›RNF213 gene variants (p.R4810K) associated with vasospastic angina and fatal MI

›Female sex, younger age

›Variant angina more common in women

›Women < 50 with vasospastic angina have worse long-term prognosis

›History of MINOCA

›MI with nonobstructive coronary arteries

›Vasospasm accounts for ~20% of MINOCA cases

›History of migraines or Raynaud phenomenon

›Shared vasomotor dysregulation mechanism

›Migraine correlation reported in literature

Past medical history

›Relevant prior diagnoses

›Prior episodes of rest angina especially nocturnal

›Prior normal or nonobstructive coronary angiography

›Prior arrhythmias, syncope, or cardiac arrest

›Connective tissue disease or vasculitis

›Shared vasomotor dysregulation

›Myocardial bridging

›Independent predictor of LAD-specific vasospasm

›Family history

›Familial heritability of vasospastic angina demonstrated in Swedish nationwide study

›RNF213 variants in family members, especially East Asian populations

›First-degree relatives of affected individuals warrant counseling

Review of systems

›Associated symptoms

›Cardiovascular: palpitations, syncope/presyncope, dyspnea, diaphoresis

›Diaphoresis during acute episode common

›Neurologic: migraine history

›Vasospastic angina correlates with migraine disorders

›Pulmonary: hyperventilation episodes

›Known trigger for coronary vasospasm

03Physical Exam/exam44

Vitals and hemodynamics

›Assessment during acute episode

›Blood pressure

›Hypotension if severe spasm with hemodynamic compromise

›Hypertension from sympathetic activation

›Heart rate

›Tachycardia from pain and sympathetic response

›Bradycardia from high-degree AV block during ischemia

›Between episodes: vitals often entirely normal

›Normal exam does not exclude diagnosis

Cardiovascular exam

›Cardiac auscultation during acute episode

›Transient S3 or S4 gallop

›Ischemic diastolic dysfunction

›Resolves with termination of spasm

›New murmur during episode

›Transient mitral regurgitation from papillary muscle ischemia

›Resolves when spasm terminates

›Signs of heart failure if prolonged ischemia

›Pulmonary crackles

›Elevated JVP

General and systemic findings

›Signs of acute ischemia during episode

›Diaphoresis and pallor

›Sympathetic activation

›Distress and anxiety

›Visceral pain response

›Substance use stigmata

04Differential Diagnosis/ddx39

Life-threatening diagnoses

›Immediate cannot-miss conditions

›STEMI (ICD-10 I21.x)

›Persistent STE not resolving with NTG

›Biomarker rise with clinical evolution

›Aortic dissection (ICD-10 I71.0)

›Tearing pain, pulse deficits, widened mediastinum on CXR

›May involve coronary ostia causing true STEMI

›Malignant arrhythmia from vasospasm

›VT, VF, high-degree AV block

›Lambda wave pattern predicts lethal arrhythmias

Cardiac mimics

›Overlapping presentations

›Unstable angina / NSTEMI (ICD-10 I20.0 / I21.4)

›ST depression more common in NSTEMI

›Troponin elevation required for NSTEMI

›Takotsubo cardiomyopathy (ICD-10 I51.81)

›Stress-induced, apical ballooning pattern on echo

›STE predominantly V3-V6 with T wave inversion

›Myocarditis (ICD-10 I40.9)

›Diffuse STE with PR depression

›Troponin elevation disproportionate to symptoms

›Pericarditis (ICD-10 I30.9)

›Pleuritic positional pain

›Friction rub on auscultation

›Microvascular angina (ICD-10 I20.8)

›ST depression more common than STE

›No >90% epicardial constriction on provocation testing

05Laboratory Tests/lt34

Cardiac biomarkers

›Troponin (high-sensitivity preferred)

›Usually negative if spasm resolves quickly

›May be mildly elevated with prolonged spasm

›Elevation suggests MINOCA or true MI from sustained spasm

›Serial troponin at 0 and 3 hours

›Rising delta troponin mandates ACS pathway

›Negative serial troponin supports vasospastic etiology

Electrolytes and metabolic

›Basic metabolic panel

›Magnesium level

›Low magnesium predisposes to coronary vasospasm

›Replete if < 0.85 mmol/l

›Potassium

›Hypokalemia increases arrhythmia risk during ischemia

›Target > 4.0 mmol/l in high-risk patients

›Renal function

›Medication dosing adjustment (CCB metabolism)

›Creatinine baseline before contrast if angiography planned

Additional workup

›Lipid panel

›Fasting LDL, HDL, triglycerides

›Statin initiation threshold assessment

›LDL target < 1.8 mmol/l if concomitant atherosclerotic disease

›Urine drug screen

›Cocaine and amphetamine screening critical

›Cocaine-induced vasospasm changes prognosis and treatment

›Positive result mandates cessation counseling before CCB therapy

06Diagnostic Tests/dt69

Scoring Systems

›TIMI Risk Score for UA/NSTEMI

›Seven-variable risk stratification tool

›Score 0-2: low risk; score 3-4: intermediate; score 5-7: high risk

›Guides aggressiveness of anticoagulation and invasive strategy

›Limitations for Prinzmetal angina

›Designed for atherosclerotic ACS; may overestimate risk

›Clinical context (normal coronaries, NTG response) modifies interpretation

›HEART Score

›History, ECG, Age, Risk factors, Troponin

›Score 0-3: low risk (0.9-1.7% MACE)

›Score 4-6: moderate risk (12-16.6% MACE)

›Score >= 7: high risk (50-65% MACE)

›Application in vasospastic angina

›ECG component: transient STE scores highly

›Use in conjunction with clinical judgment about vasospastic pattern

›ACC/AHA Chest Pain Guideline Risk Stratification (2022)

›Incorporates high-sensitivity troponin pathways

›0/1-hour or 0/3-hour rapid rule-out/rule-in protocols

›Negative hs-troponin with low clinical probability supports discharge with outpatient workup

MRI

›Cardiac MRI (CMR) indications in Prinzmetal angina

›Assessment of LV function and wall motion abnormalities

›Identifies ischemic cardiomyopathy from recurrent spasm

›Detects myocardial fibrosis or infarction from prior events

›Late gadolinium enhancement (LGE)

›Subendocardial or transmural LGE suggests prior infarction

›Absence of LGE with preserved function supports pure vasospastic disease

›Stress perfusion CMR

›Not first-line for vasospastic angina

›Useful if microvascular disease co-suspected

›Adenosine or regadenoson protocol for perfusion imaging

CT

›CT coronary angiography (CTCA)

›Indications in Prinzmetal angina workup

›Rule out obstructive CAD in low-to-intermediate risk patients

›Sensitivity 95-99% and specificity 64-83% for obstructive CAD

›Myocardial bridging detection

›CTCA identifies bridging as independent predictor of LAD vasospasm

›Kawai et al. 2020: CTCA-verified bridging associated with invasive angiography-confirmed LAD vasospasm

›Calcium scoring adjunct

›Zero calcium score supports absence of obstructive atherosclerosis

›High calcium score shifts differential toward obstructive CAD

›CT aorta (CTA)

›If aortic dissection cannot be excluded clinically

›Widened mediastinum or discrepant pulses on exam

›Sensitivity and specificity approaching 100% for dissection

Ultrasound

›Transthoracic echocardiography (TTE)

›LV function assessment

›Regional wall motion abnormalities during acute spasm

›Abnormalities resolve when spasm terminates (differentiates from fixed infarct)

›LVEF and wall motion at rest between episodes

›Normal LVEF in pure vasospastic disease

›Reduced LVEF suggests recurrent spasm-related cardiomyopathy

›Valve assessment

›Transient MR during episode vs structural MR

›Repeat echo when pain-free to confirm resolution

›Point-of-care cardiac ultrasound (POCUS)

›Bedside LV function during acute episode

›Regional wall motion abnormality localizes culprit territory

›Pericardial effusion exclusion

›IVC assessment

›Volume status guidance

›Relevant if hypotension from severe spasm

›Coronary provocation testing (invasive)

›Intracoronary acetylcholine or ergonovine provocation

›Gold standard for definitive diagnosis

›>90% epicardial coronary constriction with symptoms and ECG changes is diagnostic

›Class I recommendation in appropriate candidates (AHA/ACC)

›Contraindicated in high-grade obstructive stenosis (Class III)

›Risk of refractory spasm on stenotic vessel

›Intracoronary NTG 0.3 mg reverses spasm during catheterization

07Disposition/dispo41

Admission indications

›Inpatient admission required

›New-onset transient STE with chest pain

›Must rule out STEMI with serial ECGs and troponins

›Cardiology consultation for angiography planning

›Troponin elevation

›MINOCA pathway activation

›ACS cannot be excluded until coronary anatomy known

›Arrhythmias during or after episode

›VT, VF, high-degree AV block

›Telemetry monitoring mandatory

›Syncope or hemodynamic instability

›ICU-level monitoring indicated

›Defibrillator and pacing access at bedside

›Refractory chest pain despite NTG

›IV NTG infusion initiation

›Cardiology urgent review

Observation unit

›Criteria for observation pathway

›Resolved symptoms with normal troponin and no arrhythmias

›Known vasospastic angina with typical breakthrough episode

›Rapid NTG response and hemodynamically stable

›Continuous telemetry during observation

›Minimum 6-12 hours of monitoring

›Serial ECG and troponin assessment

Discharge criteria

›Safe discharge parameters

›Known diagnosis with typical episode

08Treatment/t91

Acute episode management

›First-line acute therapy

›Sublingual nitroglycerin 0.4 mg

›Repeat every 5 minutes x 3 doses

›Exquisitely effective; rapid relief supports diagnosis

›If no relief after 3 doses, initiate IV NTG

›IV nitroglycerin infusion for refractory pain

›Start at 5-10 mcg/minute

›Titrate by 5-10 mcg/minute every 3-5 minutes

›Target: pain relief without hypotension (SBP > 90 mmHg)

›Intracoronary NTG 0.3 mg if spasm identified during catheterization

›Definitive acute reversal of documented spasm

›Used during diagnostic angiography

Calcium channel blockers (first-line chronic therapy)

›Dihydropyridine CCBs

›Amlodipine 5-10 mg once daily

›Class I recommendation (AHA/ACC)

›Long half-life; once-daily dosing improves compliance

›Nifedipine extended-release 60-120 mg/day

›Class I recommendation

›Avoid immediate-release (reflex tachycardia risk)

›Non-dihydropyridine CCBs

›Diltiazem 180-360 mg/day (divided or extended-release)

›Class I recommendation

›Additional rate-limiting effect

›Verapamil 240-480 mg/day

›Class I recommendation

›Constipation and AV conduction effects monitor

›Dual CCB therapy for refractory disease

›Combine dihydropyridine + non-dihydropyridine class

›Evidence supports superior spasm suppression over monotherapy

Nitrates (adjunctive therapy)

›Long-acting nitrates

›Isosorbide mononitrate as add-on when CCB alone insufficient

›Benefit debated due to tolerance concerns

›Mandatory nitrate-free interval 10-12 hours to prevent tolerance

›Apply asymmetric dosing schedule

›Morning and midday dosing for nocturnal spasm pattern

›Avoid continuous 24-hour coverage

Statins

›HMG-CoA reductase inhibitors

›Indicated for endothelial function improvement (Class I)

›Benefit independent of LDL-lowering effect

›Improve endothelium-dependent vasodilation

›Atorvastatin 10-40 mg nightly or rosuvastatin 5-20 mg nightly

›Higher intensity preferred if concomitant atherosclerotic risk

›LDL target < 1.8 mmol/l if coexisting atherosclerotic disease

Adjunctive and second-line agents

›Magnesium supplementation

›Oral magnesium glycinate or oxide 200-400 mg/day

›Low magnesium predisposes to vasospasm

›Replete IV if critically low (< 0.6 mmol/l)

›Alpha-receptor blockers

›For refractory cases with adrenergic trigger

›Prazosin or doxazosin as adjunct

›Limited evidence; specialist-directed

›Fasudil (Rho-kinase inhibitor)

›Available outside North America

›Inhibits Rho-kinase pathway mediating vasospasm

›Evidence for refractory cases

Lifestyle and substance cessation

›Smoking cessation

›Single most impactful lifestyle modification (Class I)

›Smoking is the most prominent risk factor for vasospastic angina

›NRT, varenicline, or bupropion as pharmacotherapy aids

›Substance cessation

›Cocaine and amphetamines must be discontinued

›Direct coronary vasospasm mechanism

›CCB therapy less effective with ongoing cocaine use

›Alcohol moderation

›Abstinence recommended

›Alcohol intake abatement per guidelines

›Stress reduction

›Emotional stress management

›Meditation, cognitive-behavioral techniques

›Emotional stress is a known spasm trigger

Contraindicated and cautioned therapies

›Beta-blockers

›Contraindicated in vasospastic angina

›Unopposed alpha-adrenergic activity worsens spasm

›Class III harm designation for pure vasospastic angina

›Exception: may be required if concomitant obstructive CAD

›Use with adequate CCB co-coverage

›Aspirin

›Caution in pure vasospastic angina without obstructive CAD

›Inhibits prostacyclin, a vasodilator

›DAPT associated with worse outcomes in vasospastic angina without significant CAD

›Use only if coexisting atherosclerotic disease mandates antiplatelet therapy

›Ergotamine derivatives

›Contraindicated

›Potent coronary vasoconstrictors

›Avoid in all patients with vasospastic angina

ICD consideration

›Implantable cardioverter-defibrillator

›Indicated for survivors of sudden cardiac death from vasospasm

›Refractory arrhythmias despite maximal medical therapy

›Electrophysiology consultation required

›Not routinely indicated for stable vasospastic angina

›Risk-benefit requires individual assessment

09Special Populations/sp66

Pregnancy

›Physiologic considerations

›Increased cardiac output and reduced SVR alter vasomotor tone

›Hormonal changes (estrogen/progesterone) may modify spasm frequency

›Hypercoagulability may worsen endothelial dysfunction

›Vasospastic angina in pregnancy is rare but high-risk

›Associated with adverse maternal and fetal outcomes

›Multidisciplinary obstetric cardiology management required

›Medication safety

›Nifedipine extended-release

›Relatively safe in pregnancy; used for hypertension

›First-line CCB choice in pregnancy

›Nitrates

›Sublingual NTG used for acute episodes

›Limited systemic safety data for chronic use in pregnancy

›Statins

›Contraindicated in pregnancy (Category X)

›Discontinue prior to conception or upon pregnancy recognition

›Verapamil and diltiazem

›Limited data; avoid unless no alternative

›Category C agents

›Beta-blockers contraindicated regardless of pregnancy status for vasospasm

›Monitoring in pregnancy

›Fetal growth monitoring if maternal cardiac compromise

›Uteroplacental insufficiency risk with severe spasm

›Cardiologist and MFM co-management

Geriatric

›Physiologic changes

10Background/b69

Epidemiology

›Prevalence and demographics

›Prevalence highly variable by ethnicity

›Up to 40% of angina patients in Japan have vasospastic angina

›Lower prevalence in Western populations (exact rates less well defined)

›Age distribution

›Typically younger patients than obstructive CAD

›Peak incidence in 4th-6th decade

›Sex distribution

›More common in women; younger women < 50 have worse prognosis

›Women with vasospastic angina have higher rates of cardiac events

›Familial heritability

›Swedish nationwide study demonstrates high familial clustering

›Genetic contribution via RNF213 variants, especially in East Asian populations

›Outcomes data

›Complications: MI in 5-10% of patients

›Fatal arrhythmias in 5-10%

›Sudden cardiac death risk highest in those with documented malignant arrhythmias

›Favorable prognosis with treatment adherence in absence of obstructive CAD

›Worst prognosis when superimposed on obstructive coronary disease

Pathophysiology

›Coronary vasospasm mechanism

›Focal or diffuse transient hyperconstriction of epicardial coronary artery

›Transmural ischemia results (full-thickness involvement)

›STE reflects transmural ischemia pattern

›Rho-kinase (ROCK) pathway upregulation

›Increased smooth muscle calcium sensitivity

›Sustained coronary smooth muscle contraction

›Endothelial dysfunction

›Reduced nitric oxide bioavailability

›Impaired endothelium-dependent vasodilation

›Autonomic nervous system dysregulation

›Enhanced alpha-adrenergic activity

›Circadian variation in sympathetic tone explains early-morning predominance

›Precipitating substrates

›Smoking-induced oxidative stress

›Impairs NO production; activates ROCK pathway

›Magnesium deficiency

›Magnesium is a physiologic calcium antagonist

›Low magnesium increases smooth muscle contractility

›Myocardial bridging

›Mechanical compression of LAD during systole

›Promotes vasospasm in overlying segment

›ECG changes explained

›Transmural ischemia produces STE (not ST depression)

›Reciprocal ST depression in non-ischemic territory

›ST depression if collateral flow limits transmural ischemia

›Lambda wave pattern: STE with distinctive morphology in inferior/anterolateral leads

›High-risk marker for lethal arrhythmias (JAMA Internal Medicine 2025)

Therapeutic Considerations

›Mechanism-targeted therapy rationale

›CCBs block L-type calcium channels in coronary smooth muscle

›Reduces intracellular calcium

›Directly inhibits smooth muscle contraction causing spasm

›Nitrates donate nitric oxide to vascular endothelium

›Activate guanylyl cyclase, increase cGMP

›Cause coronary vasodilation

›Statins improve endothelial NO production

›Pleiotropic anti-vasospastic effect beyond LDL lowering

›Class I recommendation for endothelial function

›Why beta-blockers are harmful

›Beta-blockade leaves alpha-adrenergic receptors unopposed

›Coronary vasoconstriction unopposed by vasodilatory beta-2 effect

›Worsens vasospasm frequency and severity

›Natural history and treatment response

›Most patients respond well to CCB therapy

›Disease activity may wax and wane over years

›Medication compliance is an independent determinant of cardiovascular events

›Absence of CCB therapy independently predicts cardiovascular events

›Per JACC 2022 review (Minissian et al.)

›Refractory cases require dual CCB therapy or adjunctive agents

›Fasudil (ROCK inhibitor) effective in refractory cases

11Patient Discharge Instructions/pdi50

copy discharge instructions

›What is Prinzmetal (vasospastic) angina?

›A type of chest pain caused by sudden temporary spasm of a coronary artery

›The artery squeezes shut briefly, cutting off blood flow to the heart

›The spasm usually resolves on its own or with nitroglycerin

›Your coronary arteries may look normal on testing

›This does not mean the condition is not serious

›The spasm can trigger dangerous heart rhythm problems

›Your medications

›Calcium channel blocker (amlodipine, diltiazem, nifedipine, or verapamil)

›Take every day even if you feel well; do not skip doses

›Missing doses can trigger chest pain episodes

›Sublingual nitroglycerin tablet or spray

›Use at the first sign of chest pain

›Place under the tongue; wait 5 minutes; repeat up to 3 times if pain persists

›If pain is not relieved after 3 doses, call 911 immediately

›Statin medication (if prescribed)

›Helps blood vessels work better; take nightly as directed

›Do NOT take beta-blockers for this condition unless specifically instructed

›They can make vasospastic angina worse

›Do NOT take aspirin or anti-inflammatory drugs unless specifically prescribed

›They can worsen coronary spasm in some patients

›Lifestyle changes

›Stop smoking immediately

›Smoking is the single most important risk factor for this condition

›Ask about nicotine replacement therapy or prescription cessation aids

›Avoid cocaine, amphetamines, and methamphetamine

›These substances directly cause coronary spasm and can be fatal

12References/r46

Guidelines and key sources

›ACC/AHA 2011 ACCF/AHA Focused Update: Management of UA/NSTEMI

›Wright RS et al. Journal of the American College of Cardiology. 2011

›PMID 21545940

›Class I recommendation for CCBs and nitrates in vasospastic angina

›AHA/ACC 2014 NSTE-ACS Guideline

›Amsterdam EA et al. Journal of the American College of Cardiology. 2014

›DOI 10.1016/j.jacc.2014.09.017

›Risk factor identification including substance use and medications

›2023 AHA/ACC Chronic Coronary Disease Guideline

›Virani SS et al. Journal of the American College of Cardiology. 2023

›Statin Class I recommendation for endothelial function

›2025 ACC/AHA/ACEP Acute Coronary Syndromes Guideline

›Rao SV et al. Journal of the American College of Cardiology. 2025

›Updated chest pain evaluation and disposition pathways

›2022 ACC Expert Consensus: Acute Chest Pain in the ED

›Kontos MC et al. Journal of the American College of Cardiology. 2022

›PMID available at PMC10691881

›High-sensitivity troponin rapid rule-out pathways

Landmark studies and reviews

›Geist M, Tarchitzky D. Coronary Spasm. NEJM 2002

›Arrhythmia risk: 42% sudden death risk within 26 months with documented malignant arrhythmias vs 6% without

›Lambda wave ECG pattern as high-risk marker

›Minissian MB et al. Ischemic Heart Disease in Young Women. JACC 2022

›PMID 36049799

›Women < 50 with vasospastic angina have worse long-term prognosis

›Medication compliance as independent outcome determinant

›Hikino K et al. RNF213 Variants, Vasospastic Angina, and Risk of Fatal MI. JAMA Cardiology 2024

Evidence & Review

Evidence & Review