Accelerated stenotic flow in the left anterior descending coronary artery explains the causes of impaired coronary flow reserve: an integrated transthoracic enhanced Doppler study

Abstract

Background: Accelerated stenotic flow (AsF) in the entire left anterior descending coronary artery (LAD), assessed by transthoracic enhanced color Doppler (E-Doppler TTE), can reveal coronary stenosis (CS) and its severity, enabling a distinction between the microcirculatory and epicardial causes of coronary flow reserve (CFR) impairment.

Methods: Eighty-four consecutive patients with a CFR <2.0 (1.5 ± 0.4), as assessed by E-Doppler TTE, scheduled for coronary angiography (CA) and eventually intracoronary ultrasounds (IVUS), were studied. CFR was calculated by the ratio of peak diastolic flow velocities: during i.v. adenosine (140 mcg/Kg/m) over resting; AsF was calculated as the percentage increase of localized maximal velocity in relation to a reference velocity.

Results: CA showed ≥50% lumen diameter narrowing of the LAD (critical CS) in 68% of patients (57/84) vs. non-critical CS in 32% (27/84). Based on the established CA/IVUS criteria, the non-critical CS subgroup was further subdivided into 2 groups: subcritical/diffuse [16/27 pts (57%)] and no atherosclerosis [11/27 pts (43%)]. CFR was similar in the three groups: 1.4 ± 0.3 in critical CS, 1.5 ± 0.4 in subcritical/diffuse CS, and 1.6 ± 0.4 in no atherosclerosis (p = ns). Overall, at least one segment of accelerated stenotic flow in the LAD was found in 73 patients (87%), while in 11 (13%) it was not. The AsF was very predictive of coronary segmental narrowing in both angio subgroups of atherosclerosis but as expected with the usage of different cutoffs. On the basis of the ROC curve, the optimal cutoff was 109% and 16% AsF % increment to successfully distinguish critical from non-critical CS (area under the curve [AUC] = 0.99, p < 0.001) and diffuse/subcritical from no CS (AUC = 0.91%, p < 0.001). Sensitivity and specificity were 96% and 100% and 82% and 100%, respectively.

Conclusion: E-Doppler TTE is highly feasible and reliable in detecting the CS of any grade of severity, distinguishing epicardial athero from microvascular causes of a severe CFR reduction.

Keywords: accelerated stenotic flow; coronary flow reserve (CFR); coronary physiology; critical coronary stenosis; diffuse coronary atherosclerosis; enhanced transthoracic Doppler echocardiography; subcritical coronary stenosis.

Figure 1

Example of how to perform color-guided PW Doppler sampling in the LAD. Plane orientation is shown on the top left. Color flow is recorded in the proximal LAD (coded in red) along with flow in the proximal LCx [blu signal as it is away from the transducer (arrowheads)]; an area of aliasing (accelerated flow) is shown in the proximal LAD (indicated by arrows); based on color guidance, PW wave Doppler recording is attained at the aliasing area first and then in a more proximal reference portion (reference site); the Doppler curves (on the right side) are then used to calculate %AsF and % CSA reduction. PW, pulsed wave Doppler; LAD, left anterior coronary artery; LCx, left circumflex coronary artery; AsF, accelerated stenotic flow; CSA, cross sectional area.

Figure 2

Flow chart indicating the different subgroups of coronary atherosclerosis based on angiography/IVUS and CFR results. CA, coronary angiography; CFR, coronary flow reserve; E-Doppler TTE, enhanced transthoracic Doppler; IVUS, intravascular ultrasounds; pts, patients.

Figure 3

Velocities and CFR as assessed by E-Doppler TTE. Left Panel: Scattergram of velocities in the distal LAD before and after adenosine (mean and SD are also shown) in the whole group; Right Panel: individual value bar graph of CFR overall and also broken down in the 3 subgroups of LAD athero (mean and SD are also reported in each subgroup). A one-way between-groups analysis of variance and Tukey HSD for post hoc comparison were used; PDV, peak diastolic velocity; LAD, left anterior descending coronary artery; CFR, coronary flow reserve; CAD, coronary artery disease.

Figure 4

Scattergram showing the relation between percentage CFR and AsF in the LAD for the whole 84 patient group. It shows a moderately strong negative correlation between the max accelerated stenotic flow expressed as the percentage increment of velocity (x-axis) and distal CFR (y-axis). Pearson product-moment correlation coefficient was used. Line of correlation (continuous line) is drawn. CFR, coronary flow reserve; AsF, accelerated stenotic flow; LAD, left anterior descending coronary artery.

Figure 5

CFR in the distal LAD by E-Doppler TTE in a patient with a critical LAD stenosis as assessed by angio. At the top, color flow in the distal LAD (in red); on the right, a cartoon of the tomographic plane orientation to obtain the LAD insonification. At the bottom, pulsed Doppler spectral tracing of the blood flow velocity in the distal LAD at baseline (left) and at maximal Adenosine-induced hyperemia (right); note the prevalent diastolic BF velocity at the baseline with a minimal predominance of the diastolic flow; during hyperemia the S/D ratio gets inverted and at the same time the diastolic flow gets reduced indicating a possible stealing phenomenon. The CFR (peak hyperemic diastolic velocity/peak resting diastolic velocity) is thus below 1 (0.9). S/D ratio, ratio of the systolic to diastolic waves of coronary flow velocity; CFR, coronary flow reserve; LAD, left anterior descending coronary artery.

Figure 6

E-Doppler TTE AsF tracking in the LAD in the same patient as that with CFR < 1. Left: long area of aliasing (>1 cm) in the LAD (indicated by arrows) almost 1 cm from the LMCA bifurcation. At the upper left a cartoon that explains the plane orientation to transect the left coronary fossa with its content. In the right area: pulsed-wave Doppler tracing at the aliasing (upper trace) shows much greater BFV than at the distal reference site (bottom trace) so detecting a very high AsF (670% increment of velocity). By applying the corrected continuity equation that utilizes the VTI (time velocity integral) of the 2 curves (first site and second site) the percentage reduction of the area at the stenosis site is 92% indicating a severe stenosis. A proximal LCx color flow is also visualized (the signal is blue because is away from the transducer) LCX, left circumflex coronary artery color flow; RVOT, right ventricular outflow tract; AO, aorta; PV, pulmonary valve; AsF, accelerated stenotic flow.

Figure 7

Coronary angiography in the same patient as in Figures 5, 6. In this right oblique view, the site of the stenosis (encircled in red) has been magnified (at the bottom) to measure the minimal and maximal diameters (QCA). Coronary angiography confirms a very tight stenosi almost occlusive of the proximal LAD (QCA = 98% area stenosis) confirming the E-Doppler TTE evaluation in terms of stenosis detection, location, and severity assessment. QCA, quantitative coronary angiography. LAD, left anterior descending coronary artery.

Figure 8

ROC curves in critical CAD. Left: individual value bar graph showing the maximum individual percentage increases in velocity in the LAD segments in patients with and without critical stenosis, and the cut-off value (dashed horizontal line). Right: plot of sensitivity against 1-specificity of the percentage increase in velocity (ROC curves) predicting critical stenosis in the left anterior descending coronary artery, as assessed by angiography. A, area under the curve; vel, velocity; CFR, coronary flow reserve; sen, sensitivity; spe, specificity.

Figure 9

Comparison of the severity assessment of the LAD stenoses: E-Doppler TTE vs QCA. Left panel: Scattergram showing the relation between percentage cross-sectional area reduction at the stenosis site (AS) obtained with two methods: enhanced transthoracic Doppler by the application of continuity equation (E-Doppler TTE, x-axis) and quantitative coronary angiography (QCA, y-axis). Lines of equality (dotted line) and correlation (continuous line) are drawn. Right panel: Plot of the average value against the difference of the QCA and E- Doppler TTE calculated %AS. The dotted lines represent the boundaries of the mean + 2 SD. Pearson product-moment correlation coefficient and Blandt Altmann plot were used. %AS, percent area stenosis; LAD, left anterior descending coronary artery; cont. eq., continuity equation.

Figure 10

CFR in the distal LAD by E-Doppler TTE in a patient with a subcritical/diffuse LAD athero as assessed by angio. Same layout as the other CFR example. The CFR (peak hyperemic diastolic velocity/peak resting diastolic velocity) is blunted (1.7). The S/D ratio is normal; S/D, ratio of the systolic to diastolic waves of coronary flow velocity.

Figure 11

E-Doppler TTE AsF tracking in the LAD in the same patient with the same layout of critical LAD stenosis. The cartoon indicates the plane orientation is different since this is a more caudal approach developed for the mid LAD and the terminal part of the proximal with the same cut. The color flow indicates a dysomogenous color signal with multiple areas of aliasing (encoded in blue) In the right area: pulsed-wave Doppler tracing at the more distal aliasing (upper trace) shows slightly greater BFV than at the reference site (bottom trace) so detecting a mild AsF (22%). By applying the continuity equation (not corrected) that utilizes the VTI (time velocity integral) of the 2 curves (first site and second site) the percentage reduction of the area at the stenosis site is 30% so indicating a mild but apparently diffuse athero as CFR was blunted. In addition, the reference shows high velocity (>50 cm/s), suspicious for diffuse athero. RVOT, right ventricular outflow tract; AO, aorta; PV, pulmonary valve; AsF, accelerated stenotic flow.

Figure 12

Coronary angiography in the same patient as in Figures 10, 11. Same layout as in the previous angiographic image. In this cranial right oblique view, the site of the mid LAD mild stenosis (encircled in green) is depicted and quantified (40% CSA stenosis) that confirms the E-Doppler TTE results in terms of location ad severity. In addition, angiography shows LAD luminal irregularities and subocclusive stenosis of the right coronary artery (not shown) so clearly pointing out a diffuse atherosclerosis. However, no deduction can be done of the real functional impact of this apparently mild athero. QCA, quantitative coronary angiography; LAD, left anterior descending coronary artery; CSA, cross sectional area.

Figure 13

ROC curves in sub-critical/diffuse CAD. Left: individual value bar graph showing the maximum individual percentage increases in velocity in the LAD segments in patients with and without subcritical/diffuse CAD, and the cut-off value (dashed horizontal line). Right: plot of sensitivity against 1-specificity of the percentage increase in velocity (ROC curves) predicting subcritical stenosis by angio in the left anterior descending coronary artery. AUC, area under the curve; vel, velocity; CFR, coronary flow reserve; IVUS, intracoronary ultrasounds.