Diagnostic performance of automated myocardial blood flow quantitation by flurpiridaz F18 positron emission tomography: a sub-study of the flurpiridaz F18 301 clinical trial

652 Objectives: Myocardial blood flow (MBF) quantitation by positron emission tomography (PET) provides an integrated assessment of epicardial and microvascular coronary artery disease (CAD). MBF quantitation with currently available PET radiopharmaceuticals is a powerful prognostic indicator, with potential utility in increasing diagnostic sensitivity for the detection of CAD and identification of 3-vessel CAD. We previously developed and validated a single-compartment model of MBF quantitation with flurpiridaz in humans over a wide range of flow conditions (J Nucl Med 2014;55:1438-44). In this study, we sought to develop an automated approach of flurpiridaz MBF quantitation, and to evaluate its diagnostic performance in a subgroup of 245 patients from a phase III multi-center flurpiridaz clinical trial. Methods: All patients from the phase III 301 clinical trial of flurpiridaz PET MPI who underwent rest-pharmacological stress and whose studies were suitable for flow quantitation were evaluated (n=245). Sixteen patients (8 males) were selected as reference normals (RN) based on having < 35% stenosis in any vessel, left ventricular ejection fraction ≥ 50%, and no history of hypertension, diabetes mellitus, myocardial infarction, coronary revascularization, or heart failure. The remaining n=229 were used for diagnostic assessment. The reference standard was blinded quantitative invasive coronary angiography. Results: To assess global flow, and flow in the combined (pooled) individual coronary territories, patients were subgrouped according to the maximal % narrowing of a given coronary artery as RN (n=16 and n=48), 0-29% (n=65 and n=371), 30-49% (n=56 and n=153), 50-69% (n=42 and n=77), and 70-100% (n=66 and n=86, respectively). Global stress MBF decreased significantly (P<0.001) in subgroups with increasing % stenosis; RN (2.22 ± 0.60), 0-29% (2.02 ± 0.56), 30-49% (1.90 ± 0.57), 50-69% (1.74 ± 0.52), and 70-100% (1.49 ± 0.46). Furthermore, global MFR (stress MBF / rest MBF) had a similar significant (P<0.001) trend; RN (3.10 ± 0.68), 0-29% (2.95 ± 0.97), 30-49% (2.90 ± 0.85), 50-69% (2.87 ± 1.08), and 70-100% (2.42 ± 0.84). An analogous significant (P<0.001) pattern was also observed for the pooled territories, with stress MBF’s; RN (2.22 ± 0.60), 0-29% (1.96 ± 0.59), 30-49% (1.74 ± 0.54), 50-69% (1.55 ± 0.50), and 70-100% (1.31 ± 0.50), and with MFR’s; RN (3.10 ± 0.68), 0-29% (2.93 ± 0.99), 30-49% (2.81 ± 0.89), 50-69% (2.64 ± 0.96), and 70-100% (2.11 ± 0.83). We further determined receiver operating characteristic (ROC) areas under the curve (AUC) of stress MBF and MFR. In global flow, the stress MBF AUC was significantly greater than the MFR AUC (0.70 vs. 0.63, P=0.007) defining CAD as ≥ 50%, with similar results for CAD ≥ 70% (0.72 vs. 0.66, P=0.033). In pooled territories, the stress MBF AUC was significantly greater than the MFR AUC (0.73 vs. 0.67, P=0.002) defining CAD as ≥ 50%, but not for CAD ≥ 70% (0.75 vs. 0.74, P=0.31). Using CAD ≥ 50% and ≥ 70% as the reference, the optimal cutoff points for the highest sensitivity and specificity were 1.8 and 1.7 for global stress MBF, 2.8 and 2.7 for global MFR, 1.7 and 1.6 for pooled territories stress MBF, and 2.6 and 2.5 for pooled territories MFR, respectively. Conclusions: We have developed an automated method for quantitation of global and regional myocardial blood flow (MBF) by flurpiridaz PET MPI which demonstrates discrimination between subgroups with different degrees of angiographic stenosis. The diagnostic accuracy of stress MBF was superior to myocardial flow reserve (MFR) when assessing global flow with CAD ≥ 50% and ≥ 70% as the reference, whereas in pooled territories, stress MBF was superior to MFR only in CAD ≥ 50%. Finally, we established reference values for determination of significant CAD both for stress MBF and for MFR.