Interplay between myocardial Ischemia and extensive coronary artery disease - insights from a Hybrid CCTA -13N-NH3-PET MPI study

Abstract Background/Introduction Anatomically extensive (high-risk) coronary artery disease (CAD), jeopardizing more than half of the myocardium, as well as myocardial ischemia and impaired myocardial blood flow have significant diagnostic, therapeutic, and prognostic implications. We aimed to assess the interplay between high-risk CAD, non-invasively identified by CCTA, and myocardial ischemia/myocardial blood flow (MBF) as assessed using PET-MPI. Methods Retrospectively, 264 patients with known or suspected CAD referred for hybrid CCTA and 13N-NH3-PET-MPI between 2015 and 2021 were included. The CT-BCIS-Jeopardy score, a simple angiographic scoring system, enabling quantification of the extent of jeopardized myocardium related to clinically significant CAD, was estimated for all patients using an online calculator, with a score of ≥6 indicating extensive CAD. Abnormal PET-MPI was defined as (1) the presence of visually detectable myocardial ischemia, (2) reduced total stress myocardial blood flow (sMBF ≤1.86ml/min/gr) or (3) reduced total myocardial blood flow reserve (MFR ≤2) evaluated in three separate readouts. Logistic regression analysis with adjustment for clinical variables (age, sex, cardiovascular risk factors) was used to determine i) the risk of extensive CAD at CCTA in patients with abnormal PET-MPI and ii) the risk of ischemia and pathological myocardial blood flow in patients with extensive CAD. Results Mean patients’ age was 62±11 years and 194 (73%) were male. Median delta time between CCTA and PET-MPI was 0 days (IQR: 0-14.5; range -55 to 95). Extensive CAD at CCTA was detected in 50 (19%) patients, while PET-MPI revealed ischemia in 33 patients (13%), reduced sMBF in 82 patients (31%) and reduced MFR in 36 (14%) patients. Compared to non-extensive CAD, patients with extensive CAD had an 11-fold higher risk of myocardial ischemia (odds ratio OR: 11.19 4.38-28.6; p0.001), 3-fold higher risk of abnormal sMBF (OR: 3.17 1.45-6.96; p=0.004), and 3-fold higher risk of abnormal MFR (OR: 3.39 1.36-8.42, p=0.009). Compared to patients with no ischemia, presence of ischemia was associated with 11-fold increased risk of extensive CAD (OR: 11.25 4.39-28.8; p0.001). Patient with impaired sMBF had 2.9-fold higher risk of extensive CAD (OR: 2.89 1.36-6.16; p=0.006) and patients with impaired MFR hat 3.7-fold higher risk (OR: 3.71 1.53-8.99; p=0.004) of extensive CAD. Conclusions CCTA and PET-MPI can independently, and with similar performance, identify and risk-stratify patients with abnormal myocardial perfusion/myocardial blood flow and extensive CAD, respectively.