Prognostic value of coronary flow reserve in patients with suspected or known coronary artery disease referred to PET myocardial perfusion imaging: A meta-analysis

We performed a meta-meta-analysis to evaluate the prognostic value of coronary flow reserve (CFR) assessed by cardiac positron emission tomography (PET) imaging in patients with suspected or known coronary artery disease (CAD). Studies published until April 2019 were identified by database search. We included studies if they evaluated CFR by PET providing data on adjusted hazard ratio (HR) for the occurrence of adverse events. Annualized event rates were calculated and the incidence rate ratios with 95% confidence interval (CI) were estimated to compare patients with impaired and preserved CFR. We identified 13 eligible articles including 11,867 patients with a follow-up ranging from 0.6 to 7.1 years. The HR for the occurrence of major adverse cardiac events (MACE) was reported in 11 studies and pooled HR was 1.93 (95% CI 1.65-2.27). The HR for the occurrence of hard events was reported in 5 studies and pooled HR was 3.11 (95% CI 1.88-5.14). Six studies reported data useful to calculate separately the incidence rate of MACE in patients with preserved and impaired CFR and pooled IRR was 2.26 (CI 95% 1.79-2.85). Three studies reported data useful to calculate separately the incidence rate of hard events in patients with preserved and impaired CFR and pooled IRR was 4.12 (CI 95% 3.08-5.51). At meta-regression analysis, we found an association between HR for MACE and gender, diabetes and hypertension, while no significant association was found between HR for hard events and demographic and clinical variables. In patients with suspected or known CAD, an impaired CFR is associated with adverse cardiovascular events. However, the large heterogeneity in study population underlines the need for further investigations to maximize the prognostic role of CFR.