Diagnosing and Treating Coronary Microvascular Dysfunction






Angiography Doesn't Tell You the Whole Story

Approximately 112 million people globally are affected by angina and undergo coronary angiography, the primary diagnostic test for angina.1 Unfortunately, angiography is limited to assessing the epicardial arteries and cannot assess the microcirculation, which is largely responsible for the regulation and distribution of blood flow to the myocardium.2

Additionally, too often patients with ischemia with non-obstructive coronary arteries (INOCA) on angiography—remain undiagnosed.3 About 40-60% of chronic coronary syndrome (CCS) patients undergoing angiography have INOCA, and a large proportion of these patients may have coronary microvascular dysfunction (CMD).4,5

Proper diagnosis of CMD and treatment is the only way to improve outcomes in these patients at high risk for major adverse cardiac events (MACE).4


How Patients Benefit From a Microvascular Dysfunction Diagnosis

The recent Coronary Microvascular Angina (CorMicA) trial revealed that patients may benefit when coronary microvascular dysfunction is accurately diagnosed and appropriately treated:6


Sustained Angina Improvement with CMD Treatment6,†
† According to the Seattle Angina Questionnaire score.

The CorMicA study data6 reveals that adequate evaluation and optimal treatment of patients who have ischemia with non-obstructive coronary arteries (INOCA) can:

  • Relieve patient symptoms
  • Improve patient quality of life (QOL)
  • Reduce healthcare resource consumption

When patients are diagnosed and treated in fewer cath lab visits, overall healthcare costs may be reduced accordingly.

Challenges of Diagnosing Underlying Causes of Chest Pain


Ischemic heart disease continues to be the leading cause of death globally.7  Yet chest pain—while often ischemic in nature—could have many etiologies, as illustrated.8 When chest pain is caused by ischemia (angina), proper management depends on accurately identifying and treating the underlying cause of angina.

Here are some of the structural and functional causes of recurrent or persistent angina despite non-obstructive coronary artery disease.9

Structural Causes9
  • In-stent restenosis
  • Stent thrombosis
  • Progression of atherosclerotic disease in other segments
  • Incomplete revascularization
  • Diffuse atherosclerotic disease without focal stenosis
  • Presence of myocardial bridges
Functional Causes9
  • Coronary microvascular dysfunction
  • Epicardial vasospasm
  • Stent-related mechanical stretch of the arterial wall

The Common Diagnosis of Ischemia with Non-Obstructive Coronary Arteries (INOCA)

Only 41% of patients assessed for angina are found to have obstructive chronic coronary artery disease.4 The majority (59%) have no angiographic abnormalities,4 but still have symptoms of a coronary disorder.10

20-30% of patients experience recurrent angina in 1 year after percutaneous coronary intervention (PCI).11



INOCA patients with persistent angina frequently remain underdiagnosed. Without a clear diagnosis and treatment, this may result in recurrent hospitalizations, poor functional health, and adverse cardiovascular outcomes.12

Up to 50-65% of patients who have angina but non-obstructive CAD are believed to have coronary microvascular dysfunction (CMD).8

How to Diagnose INOCA



The recently published European Association of Percutaneous Cardiovascular Interventions (EAPCI) Expert Consensus Document defines INOCA and guidance to its diagnosis and management.1

ESC guidelines recommend measuring coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) using a guidewire-based approach.2


EAPCI Consensus Document on INOCA


Kunadian et al. European Heart Journal. 2020; 0:1-21.


An updated standardisation of CMD criteria is provided by the COVADIS group including the cut-off values of CFR<2.0 and IMR≥25 that characterise CMD.1

Kunadian et al. European Heart Journal. 2020; 0:1-21.

The Microvasculature can have a Major Impact: Clinical and Economic Outcomes

The microcirculation carries far more myocardial blood volume compared to the epicardial arteries. CMD can be defined as impaired CFR in the absence of epicardial obstructive CAD—i.e., downstream vasomotor dysfunction.3

INOCA Is Not Benign: The Impact on Clinical Outcomes

Patients with INOCA, including those diagnosed with CMD, have an increase in major adverse cardiac events (MACE) including:

  • Myocardial infarction4
  • Stroke4
  • Diastolic dysfunction3 and heart failure3,4
  • Cardiovascular death4
  • Cardiac death3
  • All-cause mortality4

Coronary Flow Reserve Associated with MACE Risks3

Image adapted from Taqueti et al, J Am Coll Cardiol 20183

The clinical spectrum of CMD may be characterised by three factors:3

  • The severity of CMD
  • The degree of atherosclerosis
  • Any associated clinical risks

Coronary Flow Reserve Associated with MACE Risks3

Image adapted from Taqueti et al, J Am Coll Cardiol 20183



The Impact on Healthcare Costs, Cath Labs, and Patients

INOCA frequently impacts patient quality of life (QOL) and consumes significant health care expenditures.5,6 With multiple evaluations and frequent hospitalization5,6, each additional hospitalization can add $2,100 (the Netherlands) to $7,300 (the U.S.) in healthcare costs.7

Nevertheless, it is possible to accurately diagnose patients on their first visit to the cath lab and to provide effective treatment.

How to Diagnose CMD with the PRESSUREWIRE™ X Guidewire

Pressure and temperature sensors

Image adapted from Lee et al, J Am Coll Cardiol 20155

Having a comprehensive physiology testing of both the epicardial arteries and microcirculation can provide clear diagnosis to guide treatment and outcomes.5

How to Diagnose CMD with the PRESSUREWIRE™ X Guidewire

Microvascular angina and vasospastic angina are the two most common causes of INOCA, and both types of angina can be identified with diagnostic testing. The randomised CorMicA trial provides a diagnostic and treatment approach.9

The trial protocol assessed patients to determine:

CorMicA Trial: 1-Year RCT Outcomes9

The CorMicA results indicate a role for a more thorough investigation of coronary microvascular dysfunction among patients with INOCA, as well as an opportunity to better tailor patient treatment.9

INOCA Patient Management

INOCA is not benign and associated with under-diagnosis, under-treatment and poor prognosis. The EAPCI Expert Consensus Document defines INOCA and provides guidance to the clinical community on the diagnostic approach and management of INOCA based on existing evidence and best current practices.1

Kunadian et al. European Heart Journal. 2020; 0:1-21.
angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB)

Introduction and Relevance of INOCA
Tom Ford, AU

Complete Advanced Diagnosis of INOCA Patient Illustrating OCT Imaging and Vasopasm Testing with Acetylcholine
Thomas Engstrom, DK

Diagnosing an INOCA Patient - Procedure (Part 1)
Martin Ng MD, PHD, NSW, Australia

Diagnosing an INOCA Patient - Procedure (Part 2)
Martin Ng MD, PHD, NSW, Australia

Explore Our Physiology Digilab


  1. Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemic 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. European Heart Journal. 2020; 0:1-21.
  2. Knuuti J, Wijns W, Saraste A, et al., for the Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407-477. doi:10.1093/eurheartj/ehz425.
  3. Taqueti VR, Di Carli MF. Coronary microvascular disease pathogenic mechanisms and therapeutic options: JACC state-of-the-art review. J Am Coll Cardiol. 2018;72:2625–2641. doi:10.1016/j.jacc.2018.09.042.
  4. Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734-744. doi:10.1093/eurheartj/ehr331.
  5. Lee B, Lim H, Fearon WF, et al. Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease. Circulation. 2015;131:1054–1060.
  6. Reriani M, Flammer AJ, Duhé J, et al. Coronary endothelial function testing may improve long-term quality of life in subjects with microvascular coronary endothelial dysfunction. Open Heart. 2019;6:e000870. doi: 10.1136/openhrt-2018-000870.
  7. Omerovic E. FFR-Guided Complete Revascularization During Primary Angioplasty: Effects on Societal Costs. EuroPCR 2017.
  8. PressureWire X guidewire IFU. Coroventis CoroFlow Cardiovascular System IFU.
  9. Ford TJ, Stanley B, Sidik N, et al. 1-year outcomes of angina management guided by invasive coronary function testing (CorMicA). J Am Coll Cardiol Intv. 2020;13:33-45.
  10. Ford TJ, Stanley B, Good R, et al. Stratified medical therapy using invasive coronary function testing in angina: the CorMicA trial. J Am Coll Cardiol. 2018;72:2841-2855.


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