Added value of coronary artery calcium score to myocardial perfusion 15O-water PET scans to identify patients at high risk of cardiac events
Authors: Dobrolinska M , Jukema R A J , Van Diemen P A A , Greuter M J W , Prakken N H J , Van Der Werf N R , Raijmakers P G , Slart R H J , Knaapen P , Danad I I 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Coronary artery calcium (CAC) is a marker of atherosclerosis and a well-known cardiovascular risk predictor for both asymptomatic and symptomatic patients. In patients at intermediate risk of coronary artery disease, myocardial perfusion imaging (MPI) is performed. Within MPI methods, 15O-water PET is considered a gold standard. However, MPI provides information only about perfusion lacking information about the atherosclerotic process within coronary arteries. Nevertheless, calcium scoring CT (CSCT) scans are not routinely performed in combination with MPI scans.

Purpose
The aim of this study was to assess the added value of CSCT to myocardial perfusion 15O-water PET scan in prediction of long-term major adverse cardiac events (MACE).

Methods
We included 572 patients who underwent subsequent myocardial perfusion 15O-water – PET scan and a dedicated CSCT scan between 2008 and 2014. The endpoint was a MACE defines as a composite of all-cause death, myocardial infarction, late and urgent revascularisation (PCI or CABG), and unstable angina. The follow-up data were tracked from the date of PET scan until 1st February 2019. A hyperaemic MBF ≤ 2.3 ml/min/g in 2 adjacent segments was considered indicative of myocardial ischemia. This cut-off value was predefined in a comparable population and published previously. Manual scoring of CSCT scans was performed according to the Agatston method. We employed a previously described 6-point scale reflecting patient risk groups (0; 1–10; 11–100; 101–400; 401–1000; &gt;1000 Agatston score (AS)).

Results
During the median follow up of 6.6 (interquartile range 4.5–7.8) years, 16.6% of patients experienced an end-point event. Event-free survival curves stratified by CAC risk groups are presented in Figure 1. Patients with CAC 0 were at lowest risk compared with all other groups (for all risk groups log-rank P &lt; 0.001, and for CAC 1-100 log rank P = 0.004). Patients with CAC&gt;1000 were at the highest risk of MACE compared with all groups except from patients with CAC 401–1000 (log-rank P=0.394). Based on multivariable Cox regression analysis of associations with MACE between CAC and myocardial perfusion defects, increasing CAC was associated with an increased risk of MACE, which was significant for patients with CAC 1-10 (adjusted hazard ratio (HR) 3.75, 95% CI 1.35–10.4, P = 0.11), CAC 11–100 (adjusted HR 4.12, 95% CI 1.71–9.93 P = 0.002), CAC 101–400 (adjusted HR 4.74, 95% CI 1.98– 11.3, P &lt; 0.001), CAC 401–1000 (adjusted HR 8.43, 95% CI 3.38–20.98, P &lt; 0.001), CAC &gt;1000 (adjusted HR 11.17, 95% CI 4.55–27.43, P &lt; 0.001) compared with patients with CAC 0 (Figure 2).

Conclusions
CAC scoring improved identification of patients at higher risk of long-term MACE, independently from ischemic information acquired with a 15O-water PET scan. Therefore, we suggest routinely performing CSCT scans in addition to results of MPI scan to determine patients of higher cardiovascular risk.