Coronary Flow Reserve in Adults: Pathophysiology, Assessment Modalities, Clinical Applications, and Prognostic Significance

Figures

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  Figure 1. Physiological indices of coronary circulation. Schematic representation of the coronary circulation demonstrating the anatomical scope of physiological indices. The epicardial vessel (macrocirculation) contains a focal stenosis (yellow) and branches into the microvascular network (<400 μm diameter vessels). Epicardial indices (FFR, iFR, RFR) assess hemodynamic significance of epicardial stenoses. IMR specifically evaluates microvascular resistance. CFR provides integrated assessment across both compartments, quantifying overall coronary vasodilatory capacity. The gradient arrow for CFR illustrates its comprehensive evaluation from proximal epicardial to distal microvascular territories. FFR, fractional flow reserve; iFR, instantaneous wave-free ratio; RFR, resting full-cycle ratio; CFR, coronary flow reserve; IMR, index of microcirculatory resistance.

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  Figure 2. Invasive coronary physiological assessment demonstrating microvascular dysfunction in a symptomatic patient without obstructive coronary artery disease. A 69-year-old female with hypertension, active smoking, and CCS class II angina underwent comprehensive invasive physiological assessment of the left anterior descending artery. Coronary angiogram (upper-left panel) demonstrates diffuse atherosclerotic changes. Resting full-cycle ratio (RFR) was 0.90 and fractional flow reserve (FFR) during maximal hyperemia was 0.82 (lower panels). Both RFR and FFR values exceed ischemic thresholds (≤0.89 and ≤0.80, respectively), excluding hemodynamically significant epicardial stenosis. Thermodilution-derived indices (upper-right panel) reveal a coronary flow reserve (CFR) of 2.4 and index of microcirculatory resistance (IMR) of 44 U. The reduced CFR (<2.5) and elevated IMR (>25 U) indicate impaired coronary microvascular function, which likely accounts for the patient’s anginal symptoms despite non-obstructive epicardial disease.

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  Figure 3. (A) Anatomical diagram of the coronary arteries, highlighting the course of the right coronary artery (RCA) and its major branches, including the acute marginal and posterior descending arteries. The illustration provides anatomical context for the coronary territory assessed in the accompanying ultrasound images. (B) Color Doppler transthoracic echocardiography image demonstrating blood flow within the RCA territory. The color flow map visualizes direction and velocity of coronary perfusion during the cardiac cycle. (C) Spectral Doppler waveform of the RCA, showing coronary flow velocity patterns across multiple cardiac cycles. Distinct systolic and diastolic components are visible, allowing assessment of coronary flow dynamics.

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  Figure 4. Coronary Microvascular Assessment Using Transthoracic Doppler Echocardiography and Coronary Angiography. (Left panels): Transthoracic Doppler echocardiography of the left anterior descending artery (LAD) at rest (upper-left) and during hyperemia (lower-left), demonstrating diastolic-dominant coronary flow used for calculation of coronary flow reserve (CFR). (Right panels): Coronary angiography showing no obstructive epicardial coronary stenoses. The central polar strain map shows reduced global longitudinal strain (GLS = 13.3%). The combined Doppler recordings yield a CFR = 2, consistent with microvascular dysfunction despite angiographically normal coronary arteries.

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  Figure 5. Coronary microvascular assessment using transthoracic Doppler. Transthoracic Doppler echocardiography of the left anterior descending artery (LAD) at rest (upper-left) and during hyperemia (lower-left), demonstrating diastolic-dominant coronary flow velocity patterns. The combined Doppler recordings yield a CFR < 2, consistent with significant stenosis of the left anterior descending artery.

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  Figure 6. (A) Diastolic stress test—reduced coronary flow reserve. This panel illustrates Doppler-derived coronary flow velocities and tissue Doppler indices at rest and during stress. (A) Reduced coronary flow reserve (CFR = 2) indicating impaired vasodilatory response consistent with microvascular dysfunction. Tissue Doppler indices show limited augmentation of diastolic flow during stress. (B) Normal response (CFR = 3.4) demonstrating appropriate hyperemic augmentation. Tissue Doppler indices show preserved diastolic reserve (60% increase in septal e’ velocity, 20% increase in lateral e’ velocity).