Diagnostic and Prognostic Value of Myocardial Flow Reserve Quantification with Single Photon Emission Computed Tomography – a Systematic Review and Meta-Analysis

Background : Myocardial flow reserve (MFR), derived from dynamic single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), offers quantitative insight into coronary physiology and may overcome limitations of conventional semi-quantitative SPECT. We aimed to systematically review and meta-analyse the diagnostic accuracy and prognostic value of SPECT-derived MFR in comparison with invasive coronary angiography (ICA), PET-MPI, and long-term patient outcomes. Results: A comprehensive literature search was done in scientific databases for studies comparing SPECT-derived MFR in patients with known or suspected coronary artery disease to ICA, PET-MPI, or ≥12-month follow-up for major adverse cardiac events. A meta-analysis was conducted using random-effects models for studies comparing SPECT-MFR with PET-MPI, and reporting diagnostic performance metrics including sensitivity and specificity. Thirty-two studies were included (n = 19 for ICA; n = 8 for PET-MPI; 1 for both ICA and PET-MPI and n = 4 for follow-up). Thirty studies showed a significant correlation between SPECT-derived MFR and reference standards with excellent area under the curve values (AUC>0.7) reported. Six PET-MPI comparator studies (with a total number of participants, n = 180) were included in the meta-analysis, yielding a pooled sensitivity of 78.5% (95% CI: 71.7-84.1%) and specificity of 89.3% (95% CI: 70.4-96.7%) (diagnostic odds ratio = 15.7 (95% CI: 6.270-39.269)). MFR consistently predicted major adverse cardiac events in prognostic studies, independent of obstructive coronary status. Conclusions: Quantitative MFR derived from dynamic SPECT-MPI correlates well with established diagnostic reference tests and independently predicts adverse outcomes. While PET remains the reference standard, SPECT-MPI offers a viable and more accessible alternative. Standardised protocols and large-scale prospective validation are needed to optimise its clinical implementation. PROSPERO Registration: CRD42024507703