Table 1

Feature	ANOCA	INOCA
Primary definition	Presence of angina symptoms without obstructive epicardial coronary artery disease	Presence of objective myocardial ischemia without obstructive epicardial coronary artery disease
Symptom profile	Angina-like chest pain, exertional or rest-related, may be atypical	Typically angina associated with demonstrable ischemia
Objective evidence of ischemia	May be present or absent	Mandatory for diagnosis
Main underlying mechanisms	Coronary microvascular dysfunction, vasospastic disorders, endothelial dysfunction, altered pain processing	Predominantly coronary microvascular dysfunction and/or coronary vasospasm
Pathophysiological spectrum	Broad clinical syndrome encompassing ischemic and non-ischemic mechanisms	Subset within ANOCA focused on ischemia-driven mechanisms
Diagnostic emphasis	Mechanism-based evaluation beyond anatomy	Confirmation of ischemia plus functional coronary assessment
Clinical implications	Heterogeneous presentation, high symptom burden, requires individualized assessment	Higher prognostic risk when associated with microvascular dysfunction
Relationship between entities	Encompasses INOCA as a subgroup	Considered a specific phenotype within ANOCA

Table 1: Comparative Overview of ANOCA and INOCA

Abbreviations: ANOCA: angina with non-obstructive coronary arteries; INOCA: ischemia with non-obstructive coronary arteries.

Table 2

ANOCA Endotype	Pathophysiology	Key Diagnostic Findings	Preferred Diagnostic Test	First-Line Treatment
CMD (Functional)	Impaired vasodilation	↓ CFR, normal IMR	CFR, IMR	β-blocker, ACEi
CMD (Structural)	Microvascular remodeling	↓ CFR, ↑ IMR	IMR	ACEi, statin
Vasospastic Angina	Epicardial spasm	Acetylcholine-induced spasm	Provocation testing	CCB, nitrates
Overlap Phenotype	CMD + spasm	Mixed abnormalities	Full functional testing	Combination therapy

Table 2: Mechanism-Based Phenotypes in ANOCA

Table 3

Feature	CMD	Vasospastic Angina
Typical symptoms	Effort-related	Rest/night
Ischemia	Often diffuse	Transient
CFR	Reduced	Often normal
Provocation test	Usually negative	Positive
Treatment	β-blocker, ACEi	CCB, nitrates

Table 3: CMD vs Vasospastic Angina in ANOCA

Abbreviations: ANOCA: Angina with Non-Obstructive Coronary Arteries CMD: Coronary Microvascular Dysfunction CFR: Coronary Flow Reserve ACEi: Angiotensin-Converting Enzyme Inhibitor CCB: Calcium Channel Blocker

Table 4

Diagnostic Method	Assesses	Strengths	Limitations in ANOCA
Exercise ECG	Epicardial ischemia	Widely available	Low sensitivity for CMD
Stress Echocardiography	Wall motion	Functional info	Misses microvascular ischemia
SPECT/PET	Perfusion	PET: quantitative CFR	Limited access, radiation
CMR Perfusion	Microvascular perfusion	No radiation	Availability, expertise
Coronary Angiography	Epicardial anatomy	Gold standard for stenosis	No microvascular info
CFR / IMR	Microvascular function	Mechanism-based	Invasive
Acetylcholine Test	Vasomotor function	Diagnoses spasm	Requires expertise

Table 4: Diagnostic Modalities in ANOCA

Abbreviations: ANOCA: Angina with Non-Obstructive Coronary Arteries, ECG: Electrocardiography, CMD: Coronary Microvascular Dysfunction, SPECT: Single-Photon Emission Computed Tomography, PET: Positron Emission Tomography, CFR: Coronary Flow Reserve, CMR: Cardiac Magnetic Resonance, IMR: Index of Microvascular Resistance

Table 5

ANOCA Mechanism	Pathophysiological Target	Preferred Therapy	Avoid
CMD (functional)	↓ Oxygen demand	β-blocker	Short-acting nitrates
CMD (structural)	Endothelial dysfunction	ACEi, statin	—
Vasospastic angina	Coronary spasm	CCB, nitrates	Non-selective β-blockers
Overlap phenotype	Mixed mechanisms	Combination therapy	Monotherapy

Table 5: Mechanism-Oriented Treatment Strategies in ANOCA

Abbreviations: ANOCA: Angina with Non-Obstructive Coronary Arteries, CMD: Coronary Microvascular Dysfunction, ACEi: Angiotensin-Converting Enzyme Inhibitor, CCB: Calcium Channel Blocker

Tables at a glance

Table 1

Table 2

Table 3

Table 4

Table 5

Figures at a glance

Figure 1

FIGURE 1

Figure 1: Angina with non-obstructive coronary arteries (ANOCA) is a heterogeneous clinical syndrome predominantly driven by coronary microvascular dysfunction (CMD) and coronary vasomotor disorders. CMD may result from functional impairment, characterized by reduced coronary flow reserve (CFR) with normal microvascular resistance, or from structural remodeling associated with increased index of microvascular resistance (IMR) and endothelial dysfunction. Coronary vasomotor disorders include epicardial and microvascular vasospasm, which may be provoked by acetylcholine testing. Endothelial dysfunction, autonomic imbalance, and inflammatory processes contribute to the development and progression of these abnormalities. These mechanisms lead to angina symptoms and impaired quality of life despite the absence of obstructive epicardial coronary artery disease. Diagnostic evaluation begins with coronary angiography demonstrating no significant stenosis and is complemented by invasive functional testing, including assessment of CFR, IMR, and vasoreactivity, as well as exclusion of non-cardiac causes of chest pain. Management should be mechanism-based, with beta-blockers, angiotensin-converting enzyme inhibitors, and statins commonly used in CMD, calcium channel blockers and nitrates as first-line therapy in vasospastic angina, and comprehensive cardiovascular risk factor control as part of an individualized treatment strategy.