Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 15;20(2):e123-e134.
doi: 10.4244/EIJ-D-23-00448.

Coronary spasm and vasomotor dysfunction as a cause of MINOCA

Zachary S Yaker  1 , A Michael Lincoff  1 , Leslie Cho  1 , Stephen G Ellis  1 , Khaled M Ziada  1 , Joseph J Zieminski  2 , Rajiv Gulati  2 , Bernard J Gersh  2 , David Holmes Jr  2 , Claire E Raphael  2
Affiliations
Review

Coronary spasm and vasomotor dysfunction as a cause of MINOCA

Zachary S Yaker et al. EuroIntervention. .

Abstract

Increasing evidence has shown that coronary spasm and vasomotor dysfunction may be the underlying cause in more than half of myocardial infarctions with non-obstructive coronary arteries (MINOCA) as well as an important cause of chronic chest pain in the outpatient setting. We review the contemporary understanding of coronary spasm and related vasomotor dysfunction of the coronary arteries, the pathophysiology and prognosis, and current and emerging approaches to diagnosis and evidence-based treatment.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Cellular interplay between endothelial- and VSMC-mediated signalling pathways that promote relaxation and contraction.
AC: adenylyl cyclase; ACh: acetylcholine; ATP: adenosine triphosphate; CA2+: calcium; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; eNOS: endothelial nitric oxide synthase; GTP: guanosine triphosphate; iNOS: inducible nitric oxide synthase; L-Arg: L-arginine; K+: potassium; MLCK: myosin light chain kinase; MLCP: myosin light chain phosphate; NO: nitric oxide; PKA: protein kinase A; RhoA: Ras homolog family member A; RoK: Rho-kinase; sGC: soluble guanylate cyclase; VSMC: vascular smooth muscle cell
Figure 2
Figure 2. Acetylcholine (ACh) allows diagnosis of endothelium-dependent CMD and CS.
Endothelial function is assessed at lower doses of ACh, while patients with CS have VSMC-mediated vasoconstriction at higher doses of ACh. The overlap between the two doses makes it difficult to reliably differentiate endothelium-dependent CMD from isolated microvascular spasm. The x-axis includes common dosing patterns used in different protocols worldwide. CMD: coronary microvascular dysfunction; CS: coronary spasm; VSMC: vascular smooth muscle cell
Figure 3
Figure 3. Coronary angiography of the bridged segment of the LAD.
A) Coronary spasm is observed during ACh infusion. B) Resolution of spasm following nitroglycerine administration. ACh: acetylcholine; LAD: left anterior descending artery
Figure 4
Figure 4. Angiography of the mid- to distal LAD (white arrows).
A) After ACh administration and B) after intracoronary nitroglycerine. C) The RCA with obliteration of the PDA associated with inferior ST-elevation and chest pain. D) The same artery after nitroglycerine. ACh: acetylcholine; LAD: left anterior descending artery; PDA: posterior descending artery; RCA: right coronary artery
Figure 5
Figure 5. OCT of the same LAD artery.
A) After administration of 50 µg ACh and B) after nitroglycerine. Ninety percent spasm was induced with higher doses of ACh but would not have allowed high-quality OCT acquisition. During CS, the VSMC in the media (M) contract and the media is therefore thicker. A: adventitia; ACh: acetylcholine; CS: coronary spasm; I: intima; LAD: left anterior descending; OCT: optical coherence tomography; P: perivascular adventitial tissue; VSMC: vascular smooth muscle cell
Figure 6
Figure 6. Management algorithm for CS.
ACEi: angiotensin-converting enzyme inhibitors; ARB: angiotensin II receptor blockers; CCB: calcium channel blocker; CS: coronary spasm; DHP: dihydropyridine; ICD: implantable cardioverter defibrillator; SL: sublingual
Figure 7
Figure 7. Prognosis of CS patients.
Most studies of patients with obstructive CAD (non-black lines) demonstrated significantly worse prognoses than studies of patients without obstructive CAD (black lines). CAD: coronary artery disease; CS: coronary spasm
Central illustration
Central illustration. Coronary artery spasm.
ACh: acetylcholine; Ca2+: calcium; CCB: calcium channel blocker; CRP: C-reactive protein; CS: coronary spasm; ECG: electrocardiogram; ER: ergonovine; ICD: implantable cardioverter defibrillator; INOCA: ischaemia with non-obstructive coronary arteries; MINOCA: myocardial infarction with non-obstructive coronary arteries; SCD: sudden cardiac death
See this image and copyright information in PMC

References

    1. Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, Lerman A, Cushman M, Kumbhani DJ, Arslanian-Engoren C, Bolger AF, Beltrame JF American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Quality of Care and Outcomes Research. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019;139:e891–908. - PubMed
    1. Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN Coronary Vasomotion Disorders International Study Group (COVADIS) International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565–8. - PubMed
    1. Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med. 1959;27:375–88. - PubMed
    1. Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Cammà G, Lanza GA, Crea F. Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J. 2018;39:91–8. - PubMed
    1. Ong P, Athanasiadis A, Borgulya G, Mahrholdt H, Kaski JC, Sechtem U. High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries). J Am Coll Cardiol. 2012;59:655–62. - PubMed

LinkOut - more resources