Aims

We determined the feasibility and diagnostic performance of segmental 18F-flurpiridaz myocardial blood flow (MBF) measurement by positron emission tomography (PET) compared with the standard territory method, and assessed whether flow metrics provide incremental diagnostic value beyond relative perfusion quantitation (PQ).

Methods and results

All evaluable pharmacological stress patients from the Phase III trial of 18F-flurpiridaz were included (n = 245) and blinded flow metrics obtained. For each coronary territory, the segmental flow metric was defined as the lowest 17-segment stress MBF (SMBF), myocardial flow reserve (MFR), or relative flow reserve (RFR) value. Diagnostic performances of segmental and territory MBF metrics were compared by receiver operating characteristic (ROC) areas under the curve (AUC). A multiple logistic model was used to evaluate whether flow metrics provided incremental diagnostic value beyond PQ alone. The diagnostic performances of segmental flow metrics were higher than their territory counterparts; SMBF AUC = 0.761 vs. 0.737; MFR AUC = 0.699 vs. 0.676; and RFR AUC = 0.716 vs. 0.635, respectively (P < 0.001 for all). Similar results were obtained for per-vessel coronary artery disease (CAD) ≥70% stenosis categorization and per-patient analyses. Combinatorial analyses revealed that only SMBF significantly improved the diagnostic performance of PQ in CAD ≥50% stenoses, with PQ AUC = 0.730, PQ + segmental SMBF AUC = 0.782 (P < 0.01), and PQ + territory SMBF AUC = 0.771 (P < 0.05). No flow metric improved diagnostic performance when combined with PQ in CAD ≥70% stenoses.

Conclusion

Assessment of segmental MBF metrics with 18F-flurpiridaz is feasible and improves flow-based epicardial CAD detection. When combined with PQ, only SMBF provides additive diagnostic performance in moderate CAD.

Background

Computerized methodologies standardize the myocardial perfusion imaging (MPI) interpretation process.

Methods

To develop an automated relative perfusion quantitation approach for ¹⁸F-flurpiridaz, PET MPI studies from all phase III trial participants of ¹⁸F-flurpiridaz were divided into 3 groups. Count distributions were obtained in N = 40 normal patients undergoing pharmacological or exercise stress. Then, N = 90 additional studies were selected in a derivation group. Following receiver operating characteristic curve analysis, various standard deviations below the mean normal were used as cutoffs for significant CAD, and interobserver variability determined. Finally, diagnostic performance was compared between blinded visual readers and blinded derivations of automated relative quantitation in the remaining N = 548 validation patients.

Results

Both approaches yielded comparable accuracies for the detection of global CAD, reaching 71% and 72% by visual reads, and 72% and 68% by automated relative quantitation, when using CAD ≥ 70% or ≥ 50% stenosis for significance, respectively. Similar results were observed when analyzing individual coronary territories. In both pharmacological and exercise stress, automated relative quantitation demonstrated significantly more interobserver agreement than visual reads.

Conclusions

Our automated method of ¹⁸F-flurpiridaz relative perfusion analysis provides a quantitative, objective, and highly reproducible assessment of PET MPI in normal and CAD subjects undergoing either pharmacological or exercise stress.