Table I.

Endotypes: definitions and guidance therapy for attending cardiologists

Diagnostic group/endotype		Outcome definitions	Linked therapy
Microvascular angina	Increased microvascular resistance	IMR >25 IMR is a quantitative method for specifically assessing microvascular function independent resting hemodynamics.	Baseline therapy: consider aspirin, statin, and ACE-i therapy in all patients. Sublingual GTN as required. Antianginal therapy (except microvascular spasm): 1st line β-Blocker (eg, carvedilol 6.25 mg twice daily, to be uptitrated) 2nd line Non-DHP CCBs substituted (eg, verapamil 120 mg slow release) where β-blockers are not tolerated or ineffective. 3rd line (add in therapy) DHP CCB (eg, amlodipine) for those on β-blockers Nicorandil (5 mg twice daily, to be uptitrated) Ranolazine (375 mg twice daily, to be uptitrated) Antianginal therapy (microvascular spasm only): treat like vasospastic angina (see below) Refer for cardiac rehabilitation
	Reduced coronary vasorelaxation	CFR <2 This reflects the inability to increase coronary flow above 2× the resting flow.
	Reduced microvasodilator capacity	RRR <2 This reflects the vasodilator capacity of the microcirculation to change from baseline to hyperemia
	Microvascular spasm	Angina with typical ischemic ECG changes and epicardial coronary constriction <90% reduction in epicardial coronary artery diameter during ACh infusion. This represents increased microvascular constriction.
Vasospastic angina	Epicardial spasm	Epicardial coronary artery spasm (>90% reduction in coronary diameter) with symptoms and ST-segment changes following IC ACh in comparison with baseline resting condition following IC GTN administration in any epicardial coronary artery segment.	Baseline therapy: Aspirin and statin should be considered. PRN sublingual GTN Antianginal therapy: 1st line Non-DHP CCB (eg, verapamil 120 mg slow release, to be uptitrated) 2nd line (add in therapy) Add nitrate, eg, isosorbide mononitrate 10 mg BD 3rd line Change nitrate to nicorandil (5 mg twice daily, to be uptitrated) Refer for cardiac rehabilitation
Obstructive epicardial stenosis		FFR ≤ 0.80	Baseline therapy: Aspirin and statin should be considered. Sublingual GTN as required. Consideration of revascularization, antianginal therapy as per ESC guidelines. Refer for cardiac rehabilitation
Noncardiac chest pain		FFR >0.80 CFR ≥2 RRR ≥2 IMR ≤25 No functional angina/spasm during ACh infusion	Cessation of antianginal therapy. Stop antiplatelet and statin unless other indication present. Consider noncardiac investigation or referral where appropriate.

RRR, resistance reserve ratio; ACh, acetylcholine; ACE-I, angiotensin-converting enzyme inhibitor; DHP, dihydropyridine; CCB, calcium channel blocker; IC, intracoronary; ESC, European Society of Cardiology.