Abstract
Since Agatston et al. first reported quantification of the coronary artery calcification score (CACS) in 1990, discussion of its clinical significance and use in diagnostic management has continued. Recent papers have reported the relationship between CACS and myocardial perfusion single photon emission computed tomography (SPECT: MPS) and its combined diagnostic value. When interpreting CACS results, it should be noted that the frequency of significant ischemia detected by MPS, likelihood of coronary artery disease (CAD), and event rate gradually increased from mild to moderate CACS (1-400). At present, high CACS is considered to be moderately consistent with abnormal MPS, and abnormal CACS in normal MPS may contribute to CAD risk stratification. However, it should be noted that CACS = 0 does not completely exclude CAD, which is particularly important when using CACS as a gatekeeper for MPS. Both stand-alone computed tomography (CT) scanner and hybrid SPECT-CT scanner are available for combined risk stratification of CACS and MPS in addition to improvement of image quality with attenuation correction.
Since Agatston et al. first reported quantification of the coronary artery calcification score (CACS) in 1990, discussion of its clinical significance and use in diagnostic management has continued (1–4). CACS can be easily measured by electrocardiogram (ECG)-gated computed tomography (CT) without contrast, and in addition to being useful alone for event risk stratification in coronary artery disease (CAD), it is also known to have additional prognostic ability for other noninvasive physiologic tests, including treadmill exercise ECG test (5). In addition, previous reports have shown that CACS is an independent predictor of dementia (6). Recent papers have reported the relationship between CACS and myocardial perfusion single photon emission computed tomography (SPECT: MPS) and its combined diagnostic value. This review article summarizes the findings to date, focusing on the relationship between CACS and MPS, and also describes the clinical implications of using CACS in combination with MPS for risk stratification of CAD.
Clinical significance of CACS for asymptomatic patients
In 2017, an expert consensus statement on the society of cardiovascular CT (SCCT) suggested that CACS is useful in accurately predicting CAD risk, even in asymptomatic patients, and helps guide treatment decisions (7). In addition, Dudum et al. reported that CACS is a reliable predictor of all-cause death, cardiovascular death, and CAD for asymptomatic populations in the United States with a family history of CAD (8).
Relationship between CACS and MPS results
In order to understand the relationship between CACS value and MPS result, it is important to organize significant cut-off values for CACS. In several previous reports, a CACS cut-off value of 400 was used for the validation of the assessment of significant ischemia or CAD events (9–11). In addition, the 2013 European Society of Cardiology (ESC) guidelines on the management of stable CAD and the Japanese Circulation Society (JCS) 2018 guidelines on the diagnosis of chronic coronary heart disease describes a CACS cut-off value 400 as a criterion for the recommendation of myocardial perfusion imaging in asymptomatic patients (12, 13). Although a CACS cutoff value of 400 has been used symbolically in several previous studies, the Society of Cardiovascular CT and Society of Thoracic Radiology guidelines in 2016 classified CACS ≥300 as moderate to severely increased risk (14). When interpreting CACS results, it should be noted that the frequency of significant ischemia detected by MPS, likelihood of CAD, and event rate gradually increased from mild to moderate CACS (1-400) (5, 15–19). In addition, previous study from Hecht et al reported that detection rate of abnormal MPS in the patients with CACS ≥400 was approximately 35% (17). Furthermore, Blumenthal et al previously reported that there was only modest agreement between abnormal exercise stress MPS results and high CACS (20). According to their report, an abnormal exercise stress MPS result occurred in >50% of subjects with a CACS >100, but also in 12% with CACS =0, 9% of with CACS 1 to 10, and 20% with CACS 11 to 100 (20). Interestingly, even when patients with normal MPS have a very high CACS, such as CACS > 1000, the association with severe coronary artery disease has been reported to be only moderate (21). Another significant cut-off value is CACS = 0. It should also be noted that although CACS = 0 has been reported to be associated with a low incidence of significant ischemia in MPS and a risk of CAD events, they cannot be completely ruled out (15, 20, 22).
Clinically useful setting for combination of CACS and MPS
Understanding the variability in the frequency of abnormalities relative to each other’s results of MPS and CACS, we should be aware that there are reports that the combination of CACS and MPS is useful in several conditions. There were several reports suggesting the additive value of CACS to normal or mild to moderate abnormal MPS for detection of cardiac event risk. Chang et al reported that severe CACS >400 added incremental prognostic information in subjects with normal MPS with a 3.55-fold relative increase for any cardiac event in comparison to the subjects with minimal CACS (≤10) (23). In addition, Barros et al reported CACS ≥400 was significant predictor of major adverse cardiac event in patients with mild to moderate abnormality in MPS (24). Furthermore, previous reports by Suzuki et al and Sharma et al suggested that combination of CACS and MPS results significantly stratify the risk of coronary revascularization, mortality and myocardial infarction in patients with normal MPS using moderate range of CACS cut-off value (200-300) (22, 25). Figure 1 shows an example of a male patient in his 80s with atypical chest pain and normal MPS. The patient’s CACS was 901. Coronary angiography revealed significant stenosis in right coronary artery (Figure 2). CACS obtained from attenuation scan in perfusion scan is highly predictive of risk, including in patients for whom there is no evidence of ischemia.
CACS as a gatekeeper to MPS
In addition to a combination of CACS and MPS to determine risk stratification, the use of CACS as a gatekeeper for MPS has also been reported. Previous studies reported that CACS = 0 was associated with a low prevalence of obstructive CAD (<5%) and a low risk of death or nonfatal myocardial infarction (<1% annual risk) (26, 27). According to the 2019 ESC guidelines, CACS measurement for the purpose of reclassifying CAD risk in the management of chronic coronary syndrome is a test that can be considered (2). Harmark et al previously reported that the combination of CACS (cut-off value <10) and N-terminal pro - B type natriuretic peptide (NT-pro BNP: cut-off value <26) could tentatively avoid 8% of MPS scan (28).
Modality selection for combination of CACS and MPS
The SPECT-CT hybrid machine not only improves the image quality of MPS with attenuation correction, but also enables risk assessment using a combination of CACS and MPS by one-stop shop (25). In addition, previous study by Schepis et al reported that attenuation maps from stand-alone CT scanner for CACS allows accurate attenuation correction of MPS images (29). Therefore, both types of imaging modalities are considered to be useful for risk stratification combining CACS and MPS and for improving the image quality of MPS using attenuation correction.
Conclusion
In this article, the relationship between CACS and MPS has been summarized, in addition to the clinical implication of the combination of CACS and MPS for risk stratification of CAD. Previous reports to date suggest that abnormalities in CACS and MPS are in moderate agreement, and CACS may stratify CAD risk in normal MPS.
Acknowledgments
None.
Sources of funding
None.
Conflicts of interest
None.
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