Diagnostic Performance of PET vs. SPECT Myocardial Perfusion Imaging in Patients with Smaller Left Ventricles: a Substudy of the ¹⁸F-Flurpiridaz Phase-III Clinical Trial

Abstract

The performance of SPECT myocardial perfusion imaging (MPI) may deteriorate in smaller hearts, primarily due to the lower resolution of conventional Anger cameras. ¹⁸F-flurpiridaz is a novel PET MPI agent with superior image and defect resolution. We sought to determine the diagnostic performance of ^99mTc-labeled SPECT MPI compared to ¹⁸F-flurpiridaz PET MPI according to left ventricular (LV) size. Methods: We conducted a substudy of the phase-III clinical trial of flurpiridaz (n = 750) and stratified diagnostic performance according to the median PET LV end-diastolic volume (LVEDV), with smaller LV’s defined as LVEDV <113 mL (n = 369), and larger LV’s as LVEDV ≥113 mL (n = 381). Images were interpreted by the majority rule of three independent blinded readers. The reference standard was quantitative invasive angiography with ≥50% stenosis in ≥1 coronary artery considered significant. Results: SPECT performance decreased significantly from an area under the curve (AUC) =0.75 in larger LVs to 0.67 in smaller LVs (P = 0.03), whereas PET performance was similar in larger or smaller LVs (AUC=0.79 vs. 0.77, P = 0.49). Accordingly, in smaller LVs, PET had a higher AUC=0.77 than the SPECT AUC=0.67 (P<0.0001), a phenomenon driven by female patients (P<0.0001). There was a degradation of sensitivity of SPECT in smaller LVs that was highly significant (P<0.001), whereas there was no significant change in PET sensitivity according to LV size (P = 0.07). Overall, PET had significantly higher sensitivity than SPECT in both smaller (67% vs. 43%, P<0.001) and larger LVs (76% vs. 61%, P<0.001). The specificity of PET and SPECT was similar in larger LVs (76% vs. 83%, P = 0.11). While SPECT specificity improved in smaller compared to larger LVs (90% vs. 83%, P = 0.03), the PET specificity did not change with LV size (76% vs. 76%, P = 0.9). Conclusion: The diagnostic performance of ¹⁸F-flurpiridaz PET MPI is not affected by LV size and is superior to SPECT MPI in patients with smaller LVs, highlighting the importance of appropriate test selection in these patients.