By Timir K. Paul, MD, PhD, FSCAI; Jimmy Kerrigan, MD, FSCAI; Nadia R. Sutton, MD, FSCAI

Introduction

Coronary microvascular dysfunction (CMD) refers to the subset of disorders affecting the structure and function of the coronary microcirculation and is associated with increased major adverse cardiovascular events (MACE).¹ Approximately 3-4 million Americans suffer from ischemia/angina with nonobstructive coronary artery disease (ischemia with nonobstructive coronary arteries [INOCA]/angina with nonobstructive coronary arteries [ANOCA]). Up to half of patients undergoing angiography have no obstructive coronary artery disease (CAD), and this occurs more commonly in women (65%) than men (32%).² Patients with INOCA have increased hospitalization rates and higher likelihood of undergoing repeat noninvasive testing or angiography.² The 2021 American Heart Association (AHA)/American College of Cardiology (ACC) Guideline for the Evaluation and Diagnosis of Chest Pain provide a Class 2a recommendation to consider invasive coronary function testing for patients with persistent stable chest pain and INOCA.³ In this Tip of the Month, we focus on the invasive diagnosis of coronary function disorders, along with a framework of endotype-guided management.

Diagnosis

Coronary flow reserve (CFR) measures the reserve capacity of the myocardial microvasculature in response to a vasodilator, while the index of microcirculatory resistance (IMR) and hyperemic myocardial velocity resistance (HMR) measure microvascular resistance.^4,5 There are historically two methods available for assessing CMD invasively, using either an assessment based on Doppler flow velocity (FloWire or ComboWire, Philips) or thermodilution (PressureWire X, Abbott), but only thermodilution is available commercially at the time of this publication. Assessment of endothelium-dependent function is usually done with intracoronary administration of acetylcholine; this may be performed before or after measurement of CFR. Finally, assessment of the significance of myocardial bridging is completed with intravascular imaging (usually ultrasound) and administration of dobutamine with measurement of a diastolic fractional flow reserve (dFFR), instantaneous wave-free ratio (iFR), or resting full-cycle ratio (RFR). Protocols for performing these tests has been discussed elsewhere, and best practices for assessing microvascular function by the thermodilution method may be recalled using a mnemonic: CATH CMD.⁶ Studies have described that the use of intracoronary acetylcholine for the diagnosis of epicardial and microvascular spasm is associated with a low rate of complications.⁷

• Endothelial-Independent CMD Diagnosis (Adenosine)^6,8
  • Doppler: CFR <2.0 and HMR ≥ 2.5
  • Thermodilution: CFR < 2.5, and IMR ≥25
• Endothelial-Dependent Assessment (Acetylcholine)^6,8
  •  Epicardial Vasospasm
    • >90% diameter reduction of epicardial coronary with acetylcholine
    • With angina and
    • Ischemic electrocardiogram (ECG) changes
  • Endothelial Dysfunction^6,8
    • A 0%-89% diameter reduction and/or < 50% increase in coronary blood flow with acetylcholine
  • Microvascular Vasospasm^6,8
    • No epicardial diameter reduction
    • With angina and
    • Ischemic ECG changes
• Myocardial Bridge Assessment^6,7,8
  • Intravascular Imaging
    • Half-moon sign
    • ≥ 10% systolic compression by intravascular ultrasound (IVUS)
    • Dobutamine dFFR/iFR/RFR ≤ 0.76

Table 1: INOCA Endotypes and Diagnostic Criteria^6,8

*Ach: Acetylcholine challenge

Table 2: Treatments^8,9,10,11

Conclusion

Patients with INOCA have an increased risk of MACE and have historically been underdiagnosed and undertreated. Increasing recognition of coronary function disorders have led to clinical trials demonstrating improvement in outcomes for patients who receive a definitive diagnosis. As such, we recommend pursuing invasive testing for CMD, spasm/endothelial dysfunction, and myocardial bridging — especially in patients who have INOCA and persistent symptoms — to inform a treatment strategy considering each patient's specific endotype. Ongoing research efforts will help inform future options to improve outcomes for this often-overlooked patient population.

References

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