Incremental value of dedicated [201Tl] cadmium-zinc-telluride thallium SPECT over rest/stress [99mTc] technetium sestamibi SPECT MPI: a comparative analysis of fixed perfusion defects

Background Rest/stress [ 99m Tc]technetium sestamibi single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) is a mainstay for evaluating coronary artery disease. However, fixed defects on standard MPI present a well-documented clinical challenge, as they can represent either non-viable scars or viable hibernating myocardium. We aimed to examine the incremental value and rate of diagnostic reclassification provided by performing subsequent dedicated cadmium-zinc-telluride (CZT) [ 201 Tl]thallium myocardial SPECT in patients presenting with fixed defects on standard sestamibi MPI. Methods In this retrospective study, we analyzed 174 patients—totaling 2,958 myocardial segments—who underwent both protocols. Intermodality correlation was assessed, and the rates of segmental and patient-level reclassification (segments converting from <50% maximum uptake on sestamibi to ≥50% maximum uptake on thallium) were quantified. Results While a moderately high correlation was observed between the baseline uptake scores of the two modalities (Spearman's r = 0.817 for rest sestamibi vs. thallium), thallium imaging provided substantial additional information, with 48.0% of segments classified as fixed defects on sestamibi SPECT demonstrating improved uptake on thallium SPECT. At the patient level, 78.9% of individuals who had fixed defects on the initial sestamibi SPECT had at least one segment reclassified. Receiver operating characteristic analysis showed that a rest sestamibi uptake score of <20% predicted a lack of reclassification with 99% specificity, although with low sensitivity (12%). Conclusion In a selected cohort of patients presenting with fixed defects on standard rest/stress sestamibi SPECT MPI, supplementary imaging with thallium myocardial CZT SPECT provided incremental data, altering the clinical interpretation in nearly 80% of patients. However, in the absence of an independent viability reference standard, this finding represents intertracer diagnostic reclassification rather than proven functional recovery. A rest sestamibi uptake of <20% demonstrated high specificity for non-reclassification; however, this cutoff should be interpreted cautiously as a potential gatekeeping finding when considering downstream testing rather than a rigid rule for omitting further myocardial viability evaluation.