PET-measured longitudinal flow gradient correlates with invasive fractional flow reserve in CAD patients

Abstract

Aims: We aimed to evaluate whether a PET-determined longitudinal decrease in myocardial blood flow (MBF) or gradient, assumed as a more specific flow parameter for epicardial resistance, correlates with invasively measured fractional flow reserve (FFR) in coronary artery disease (CAD) patients.

Methods and results: In 29 patients with suspected or known CAD, myocardial perfusion and MBF in mL/g/min was determined with 13N-ammonia PET/CT during regadenoson stimulation and at rest, and corresponding myocardial flow reserve (MFR = MBF stress/MBF rest) was calculated. MBF parameters were assessed in the myocardial region with stress-related perfusion defect and with stenosis ≥50% (Region 1), without defect but with stenosis ≥50% (Region 2), or without stenosis ≥50% (Region 3). Hyperaemic MBFs were significantly lower in the mid-distal than in the mid-left ventricular myocardium in Regions 1-3 [median and IQ range: 1.57 (1.24, 1.84) vs. 1.87 (1.61, 2.00), and 1.23 (1.11, 1.86) vs. 1.89 (1.80, 1.97), and 1.78 (1.48, 2.00) vs. 1.94 (1.84, 2.05) mL/g/min, P < 0.0001]. Resulting longitudinal MBF gradient during hyperaemic flows was more pronounced in Region 2 than in Regions 1 and 3, respectively [-0.46 (-0.70, -0.10) vs. -0.17 (-0.29, -0.11) and -0.15 (-0.25, -0.09) mL/g/min, respectively, P < 0.01]. There was a significant correlation between the hyperaemic longitudinal MBF gradient and FFR (r = 0.95; P < 0.0001), while this association was less pronounced for corresponding MFR (r = 0.50; P = 0.006).

Conclusion: The observed close correlation between a longitudinal MBF gradient during hyperaemic flows and invasively measured FFR suggests the longitudinal flow gradient as an emerging non-invasive index of flow-limiting CAD.

Keywords: CAD; PET; circulation; coronary stenosis; flow gradient; microvascular function; myocardial blood flow; myocardial flow reserve; myocardial perfusion.

Figure 1

Normal myocardial perfusion and MBF study with ¹³N-ammonia PET/CT in a 45-year-old women with atypical chest pain and borderline arterial hypertension. (A) Regadenoson-stress and rest ¹³N-ammonia PET/CT images in corresponding short-axis (top), vertical long-axis (middle), and horizontal long-axis (bottom) slices. As can be appreciated, there is normal and homogeneous radiotracer uptake of the left ventricular wall on stress and rest ¹³N-ammonia PET/CT, indicative of normal perfusion. (B) Regional MBF quantification signifies normal hyperaemic MBFs and MFR in all three major coronary artery territories of the LAD, LCx, and RCA with hyperaemic MBFs ≥1.8 mL/g/min (upper-middle panel). Calculated MFR is widely normal (≥2.0) except for a borderline reduction in the RCA distribution (upper-right panel). Notably, there is no decrease but rather a mild increase in segmental MBF from the mid- to distal segments and, thus, no abnormal MBF gradient during hyperaemic MBFs is noted (lower-middle panel).

Figure 2

Abnormal stress-rest myocardial perfusion and MBF study with ¹³N-ammonia PET/CT in a 58-year-old man with typical, effort-induced chest pain. (A) Regadenoson-stress and rest ¹³N-ammonia PET/CT images in corresponding short-axis (top), vertical long-axis (middle), and horizontal long-axis (bottom) slices. On stress images, a moderate-to-severe decrease in myocardial perfusion, involving the antero-septo-apical and apical wall, is realized that becomes reversible on rest images and thus signifies ischaemia in the LAD distribution. (B) Regional MBF quantification demonstrates abnormally reduced hyperaemic MBFs and MFR in all three major coronary artery territories of the LAD, LCx, and RCA, respectively (upper panel). Segment MBF analysis unravels a decrease in MBF from the mid- to distal segments with a mean longitudinal MBF gradient during hyperaemic flow in the LAD (0.12 mL/g/min), LCx (0.19 mL/G/min), and RCA (0.30 mL/g/min) (lower-middle panel). (C) Invasive coronary angiography of the left coronary artery in this patient demonstrated a long 99% stenosis in the mid-LAD that accounted for the observed stress-induced perfusion defect antero-apical and apical on ¹³N-ammonia PET/CT perfusion images. In addition, large calibre diagonal branches of the LAD present a ≈70–80% and ≈80–90% stenosis, respectively. The proximal LCx has a proximal ≈80–90% stenosis. Invasively measured FFR of the proximal LCx lesion was abnormally reduced with 0.68 signifying also downstream flow-limiting effects of this lesion. (D) Invasive coronary angiography of the right coronary artery demonstrates serial epicardial lesion from the proximal to mid-segments of ≈70–90%, respectively.

Figure 3

Abnormal stress-rest myocardial perfusion and MBF study with ¹³N-ammonia PET/CT in a 64-year-old man with atypical chest pain and previous percutaneous intervention of a LAD lesions. (A) Regadenoson-stress and rest ¹³N-ammonia PET/CT images in corresponding short-axis (top), vertical long-axis (middle), and horizontal long-axis (bottom) slices. On rest images, there is a mild decrease of myocardial perfusion of the inferior and inferolateral wall to suggest mild necrosis that, however, markedly worsens during vasomotor stress signifying large size and severe ischaemia in the LCx distribution. (B) Regional MBF quantification demonstrates abnormally reduced hyperaemic MBFs and MFR in all three major coronary artery territories of the LAD, LCx, and RCA, respectively (upper panel). Segment MBF analysis outlines a decrease in MBF from the mid- to distal segments with a mean longitudinal MBF gradient during hyperaemic flow in the LAD (0.18 mL/g/min), LCx (0.56 mL/G/min), and RCA (0.09 mL/g/min) (lower-middle panel). (C) Invasive coronary angiography of the left coronary artery in this patient demonstrated a complete occlusion of the mid LCx, which is responsible for the stress-induced ischaemia in the inferior and inferolateral wall, and a ≈50% stenosis in the mid-LAD just after a patent stent (left panel). (D) An additional left-anterior-oblique projection, however, unmasks a ≈95% stenosis of the proximal diagonal branch in addition to the described LAD lesion (right panel). Invasively measured FFR of the LAD lesions proved to be normal with 0.84. (E) Invasive coronary angiography of the right coronary artery demonstrates two serial lesions of ≈50% in the mid- and distal RCA, respectively.

Figure 4

Relationship among hyperaemic longitudinal MBF gradient, Δlongitudinal MBF gradient, hyperaemic MBF, MFR, and severity of invasively determined FFR. Correlation between hyperaemic longitudinal MBF gradient (A) and Δlongitudinal MBF gradient (B) with corresponding FFR, respectively (negative values on the y-axis indicate an increase in longitudinal MBF gradient). In addition, C and D display the correlation between hyperaemic MBF and MFR with the FFR, respectively. SEE, standard error of the estimate.