Invasive minimal Microvascular Resistance Is a New Index to Assess Microcirculatory Function Independent of Obstructive Coronary Artery Disease

Figures

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  Figure 1. Example of the coronary hemodynamic data from a patient of cohort 1. Coronary angiography is shown in the left panel, with a 77% diameter stenosis in the mid‐LAD and no obstructions in the LCx. Invasive measurements of hyperemic pressure, Doppler flow velocity, and instantaneous microcirculatory resistance are shown in the right panels. HMR was sampled during the whole cardiac cycle (shaded in green), and mMR was sampled during the hyperemic wave‐free period (shaded in blue). Both HMR and mMR were calculated as the ratio of distal pressure and flow velocity. The LAD stenosis was hemodynamically severe with a FFR of 0.53, whereas FFR was 0.99 in the unobstructed LCx. HMR is numerically higher in the LAD than in the unobstructed LCx: 3.60 and 2.61 mm Hg·cm−1·s, respectively, attributable to higher systolic resistance. mMR was comparable in the LAD and LCx at 1.50 and 1.60 mm Hg·cm−1·s, respectively. FFR, fractional flow reserve; HMR, hyperemic microvascular resistance; LAD, left anterior descending coronary artery; LCx, left circumflex coronary artery; mMR, minimal microvascular resistance.

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  Figure 2. Flow chart. The flow of patients through the study.

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  Figure 3. Cohort 1: paired analysis. A, Parameters for quantification of MCD are shown for the paired analysis in cohort 1. CFR was significantly lower in arteries with a coronary stenosis than in unobstructed reference arteries (black bars), whereas HMR was significantly higher in stenoses (white bars). mMR did not differ between stenosed and reference arteries. B, The parameters stratified according to FFR values of ≥0.80, 0.60 to 0.80, and ≤0.60. Lower values of CFR were observed in stenoses with FFR 0.60 to 0.80 and ≤0.60, whereas higher values of HMR were observed in pairs with FFR ≤0.60. mMR remained equivalent in stenosed and reference arteries after stratification based on FFR. Bars represent mean with error bars as standard deviation. CFR, coronary flow reserve; FFR, fractional flow reserve; HMR, hyperemic microvascular resistance; MCD, microcirculatory dysfunction; mMR, minimal microvascular resistance.

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  Figure 4. Cohort 2: regression analysis. Stenosis severity defined by both fractional flow reserve (A through C) and diameter stenosis % (D through F) was plotted with the 3 parameters of MCD. A and D, There is a significant correlation between CFR and either FFR or DS%. The same is true for HMR in (B and E). For mMR, there is no correlation with either FFR (C) or DS% (F). Regression lines were calculated by standard linear regression, with P‐values estimated from generalized estimating equations. Measurements in reference vessels were graded as 0% DS. CFR, coronary flow reserve; DS%, diameter stenosis percentage; FFR, fractional flow reserve; HMR, hyperemic microvascular resistance; MCD, microcirculatory dysfunction; mMR, minimal microvascular resistance.

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  Figure 5. FFR and CFR relationship in all stenoses. A, The relationship between FFR and CFR for all stenoses in cohorts 1 and 2 is depicted. Dashed lines indicate the clinical cutoff values of FFR at 0.80 and CFR at 2.0, respectively, and divide the stenoses into 4 quadrants. In the right upper quadrant, CFR and FFR are concordantly negative (red circles), whereas in the left lower quadrant, CFR and FFR are concordantly positive (blue circles). In the left upper quadrant, CAD is predominantly located in the epicardial domain (orange circles). In the right lower quadrant, disease is predominantly located in the microcirculatory domain (yellow circles). B, HMR values are shown for the FFR‐CFR quadrants. HMR is only able to discriminate the right lower FFR‐CFR quadrant (yellow bar) from the right upper quadrant (red bar), but is unable to distinguish the right lower quadrant from the 2 quadrants with a positive FFR. C, mMR values for the quadrants are shown. mMR is able to clearly identify the involvement of primarily microcirculatory disease because mMR is significantly higher in the right lower quadrant (yellow bar) in comparison to the other quadrants. In contrast to HMR, mMR is able to…

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  Figure 6. Phasic APV, distal pressure, and microcirculatory resistance. Regression lines for the relationships between distal pressure (blue lines), APV (green lines), and microcirculatory resistance (red lines) for all measurements made in both reference vessels and coronary arteries with a stenosis in cohorts 1 and 2 are shown. Regression lines were estimated for 3 phases: whole cardiac cycle (A), systolic window (B), and wave‐free period window (C). Correlation coefficients (r) and P‐values (estimated by GEE) are shown for the microcirculatory resistance in each panel. APV, averaged peak Doppler flow velocity; GEE, generalized estimating equations.