Core Reading Materials

The following articles were compiled by members of the MVN physician education subcommittee as a suggested starting point for those interested in diagnosing and/or treating patients with ANOCA due to CMD, coronary vasospasm, or myocardial bridging:

1. Samuels BA, Shah SM, Widmer RJ, Kobayashi Y, Miner SES, Taqueti VR, Jeremias A, Albadri A, Blair JA, Kearney KE, Wei J, Park K, Barseghian El-Farra A, Holoshitz N, Janaszek KB, Kesarwani M, Lerman A, Prasad M, Quesada O, Reynolds HR, Savage MP, Smilowitz NR, Sutton NR, Sweeny JM, Toleva O, Henry TD, Moses JW, Fearon WF, Tremmel JA; Microvascular Network (MVN). Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Sep 19;82(12):1245-1263. doi: 10.1016/j.jacc.2023.06.043. PMID: 37704315.

Description: This publication from the MVN defines angina with nonobstructive coronary arteries (ANOCA) as encompassing coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. The publication covers diagnostic testing, noninvasively and in the cardiac catheterization laboratory and includes details on how to perform coronary function testing (CFT). 

2. Smilowitz NR, Prasad M, Widmer RJ, Toleva O, Quesada O, Sutton NR, Lerman A, Reynolds HR, Kesarwani M, Savage MP, Sweeny JM, Janaszek KB, Barseghian El-Farra A, Holoshitz N, Park K, Albadri A, Blair JA, Jeremias A, Kearney KE, Kobayashi Y, Miner SES, Samuels BA, Shah SM, Taqueti VR, Wei J, Fearon WF, Moses JW, Henry TD, Tremmel JA; Microvascular Network (MVN). Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Sep 19;82(12):1264-1279. doi: 10.1016/j.jacc.2023.06.044. PMID: 37704316.

Description: This publication from the MVN covers the development of multidisciplinary teams for the care of patients with ANOCA and their clinical management. Therapeutic options for ANOCA are covered, including lifestyle, pharmacology, and device-based interventions to reduce angina burden and quality of life in affected patients. 

3. Takahashi T, Samuels BA, Li W, Parikh MA, Wei J, Moses JW, Fearon WF, Henry TD, Tremmel JA, Kobayashi Y; Microvascular Network. Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols. J Am Coll Cardiol. 2022 Jun 21;79(24):2367-2378. doi: 10.1016/j.jacc.2022.03.385. PMID: 35710187; PMCID: PMC8972358.

Description: This meta-analysis performed by MVN members examined the estimate of complications of performing coronary provocation testing for the diagnosis of vasospastic angina. The study reports that even when different protocols were considered, the procedure is safe, with an incidence of major complications of 0.5% (95% CI: 0.0%-1.3%), without any reports of death.

4. Collet C, Yong A, Munhoz D, Akasaka T, Berry C, Blair JEA, Collison D, Engstrøm T, Escaned J, Fearon WF, Ford T, Gori T, Koo BK, Low AF, Miner S, Ng MKC, Mizukami T, Shimokawa H, Smilowitz NR, Sutton NR, Svanerud J, Tremmel JA, Warisawa T, West NEJ, Ali ZA. A Systematic Approach to the Evaluation of the Coronary Microcirculation Using Bolus Thermodilution: CATH CMD. J Soc Cardiovasc Angiogr Interv. 2024 Apr 3;3(7):101934. doi: 10.1016/j.jscai.2024.101934. PMID: 39131992; PMCID: PMC11308200.

Description: This article reviews the bolus thermodilution method of measuring coronary function, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. 

5. Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N, McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM, Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25. PMID: 30266608.

Description: This study tested whether coronary function testing results linked to a study-protocol recommended pharmacological strategy would improve health status in patients with ischemia and nonobstructive coronary arteries (INOCA). The study found that, after 6 months of follow up, the strategy improved angina in patients with no obstructive CAD.

6. Ford TJ, Stanley B, Sidik N, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, McCartney P, Corcoran D, Collison D, Rush C, Sattar N, McConnachie A, Touyz RM, Oldroyd KG, Berry C. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020 Jan 13;13(1):33-45. doi: 10.1016/j.jcin.2019.11.001. Epub 2019 Nov 11. PMID: 31709984; PMCID: PMC8310942.

Description: This CorMicA study tested whether coronary function testing results linked to a study-protocol recommended pharmacological strategy would improve health status in patients with ischemia and nonobstructive coronary arteries (INOCA). The study found that, after 6 months of follow up, the strategy improved angina in patients with no obstructive CAD. In this follow up analysis, after 1 year, patients who underwent invasive coronary function testing with a stratified medical therapy approach had sustained improvement in their angina symptoms and better quality of life.

7. Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020 Oct 1;41(37):3504-3520. doi: 10.1093/eurheartj/ehaa503. PMID: 32626906; PMCID: PMC7577516.

Description: This consensus document, organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), provides a definition of INOCA and guidance on the diagnostic approach and management of INOCA based on existing evidence from research and best available clinical practice; noting gaps in knowledge and potential areas for further investigation.

8. Taqueti VR, Di Carli MF. Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Nov 27;72(21):2625-2641. doi: 10.1016/j.jacc.2018.09.042. PMID: 30466521; PMCID: PMC6296779.

Description:  In this state-of-the-art review, the authors summarize the pathophysiology of coronary microvascular disease (CMD), provide an update of diagnostic testing strategies, and classify CMD into phenotypes according to severity and coexistence with atherosclerosis. They examine emerging data highlighting the significance of CMD in specific populations, discussing the role of CMD as a potential target for novel interventions beyond conventional approaches.

9. Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010 Jun 22;55(25):2825-32. doi: 10.1016/j.jacc.2010.01.054. PMID: 20579539; PMCID: PMC2898523.

Description: The WISE (Women's Ischemia Syndrome Evaluation) study investigated whether coronary microvascular dysfunction predicts major adverse outcomes during follow-up among women with signs and symptoms of ischemia. The publication reported the risk of a low coronary flow reserve was associated with an increased risk for major adverse outcomes (hazard ratio 1.16, (95% CI: 1.04 to 1.30)). 

10. Candreva A, Gallinoro E, van 't Veer M, Sonck J, Collet C, Di Gioia G, Kodeboina M, Mizukami T, Nagumo S, Keulards D, Fournier S, Pijls NHJ, De Bruyne B. Basics of Coronary Thermodilution. JACC Cardiovasc Interv. 2021 Mar 22;14(6):595-605. doi: 10.1016/j.jcin.2020.12.037. PMID: 33736767.

Description: This review article provides an overview on bolus and continuous thermodilution for the measurement of coronary flow and microvascular resistance. The authors describe the basic principles of indicator-dilution theory and of coronary thermodilution and detail the practicalities of their application in the catheterization laboratory. The authors discuss contemporary clinical applications of coronary thermodilution-based microvascular assessment in humans and future perspectives.

11. Widmer RJ, Samuels B, Samady H, Price MJ, Jeremias A, Anderson RD, Jaffer FA, Escaned J, Davies J, Prasad M, Grines C, Lerman A. The functional assessment of patients with non-obstructive coronary artery disease: expert review from an international microcirculation working group. EuroIntervention. 2019 Mar 20;14(16):1694-1702. doi: 10.4244/EIJ-D-18-00982. PMID: 30561368.

Description: In this 2019 consensus document, the authors detail steps for the interventional cardiologist to evaluate the patient with ANOCA in the cardiac catheterization laboratory, first with the assessment of coronary flow reserve (CFR), and then with delineation of deficiencies in non-endothelium-dependent CFR (CFRne) versus endothelium-dependent CFR (CFRe) using provocative agents such as adenosine and acetylcholine. Use of Doppler wire technology is covered. 

12. Tapp DN, Ashokprabhu ND, Hamstra MS, Losekamp M, Schmidt C, Palmer C, Julie Gallatin NP, Tierney D, Trenaman T, Canoniero M, Frizzell J, Henry TD, Quesada O. Developing a Women's Heart Center With a Specialization in Coronary Microvascular and Vasomotor Dysfunction: If You Build It, They Will Come.Catheter Cardiovasc Interv. 2024 Dec;104(7):1337-1343. doi: 10.1002/ccd.31281. Epub 2024 Nov 6. PMID: 39506505.

Description: The goal of this review is to provide an overview of a Women’s Heart Center structure that allows for the establishment and growth of a Coronary Microvascular Disease program and to outline core activities supporting the approach.