If the Coronary Artery Calcium (CAC) score is zero, is a Coronary Computed Tomography Angiography (CCTA) necessary?

Should You Get CCTA if CAC Score is Zero?

In most cases, CCTA is not necessary after a zero CAC score, but the decision depends critically on whether the patient is symptomatic or asymptomatic.

Asymptomatic Patients with CAC = 0

For asymptomatic individuals, CCTA is not recommended after a zero CAC score. 1

• A zero CAC score in asymptomatic patients indicates excellent prognosis with annual cardiovascular event rates <0.5% and can safely defer further cardiac testing 2
• The 2024 ESC guidelines explicitly state that individuals with very low likelihood of obstructive CAD (which includes those with CAC=0) do not require further diagnostic testing 1
• The "power of zero" is well-established in asymptomatic populations, with event rates of only 0.8 per 1,000 person-years in the MESA cohort 1
• CCTA is not recommended as a screening tool in asymptomatic individuals, even with the knowledge that some non-calcified plaque may be present 3

Symptomatic Patients with CAC = 0

For symptomatic patients, CCTA should be strongly considered despite a zero CAC score, as non-calcified plaque causing obstructive disease cannot be excluded. 1

Evidence Supporting CCTA in Symptomatic Patients:

• A zero CAC score does not exclude obstructive CAD in symptomatic patients because noncontrast CT cannot detect non-calcified atherosclerotic plaque 1, 2
• In the CORE64 substudy, 19% of symptomatic patients with CAC=0 had at least one vessel with ≥50% stenosis, and 20% of occluded vessels had no calcium 1
• The CONFIRM registry found that among symptomatic patients with zero CAC, 13% had non-obstructive disease, 3.5% had ≥50% arterial stenosis, and 1.4% had ≥70% stenosis 2
• Obstructive disease is present in 7-38% of symptomatic patients with CAC=0 1

The 2021 ACC/AHA Guidelines Approach:

The ACC/AHA guidelines recommend a selective strategy using CAC to guide CCTA in symptomatic patients 1:

• In the CRESCENT trial, symptomatic patients were randomized to CAC scanning versus exercise ECG 1
• Only patients with detectable CAC or high pretest risk underwent follow-up CCTA 1
• This CAC-guided approach was associated with a reduction in cardiovascular events at 1 year compared to exercise testing alone (p=0.011) 1
• However, this strategy still performed CCTA in high-risk patients even with CAC=0 1

Age-Specific Considerations

Age significantly impacts the reliability of zero CAC for excluding obstructive CAD:

• In younger patients (<40 years), obstructive CAD when present is more likely to be non-calcified: 58% of those younger than 40 years with obstructive CAD have CAC=0, compared to only 9% among those aged 60-69 years 1
• In symptomatic patients under 40 years, CAC=0 does not reliably exclude obstructive CAD, and CCTA should be strongly considered 4
• The "power of zero" is strongest in older patients whose CAD burden predominantly involves calcified plaque 4

Clinical Algorithm

For Asymptomatic Patients with CAC = 0:

1. Provide reassurance about low cardiovascular risk 2
2. Continue standard preventive measures based on other risk factors 2
3. Do not proceed with CCTA 1, 3

For Symptomatic Patients with CAC = 0:

1. Assess symptom characteristics (typical angina, atypical chest pain, or non-cardiac) 1
2. Calculate pretest probability using contemporary models (RF-CL model preferred over older Diamond-Forrester) 1
3. If intermediate-high pretest probability OR age <40 years with concerning symptoms: proceed with CCTA 1, 4
4. If low pretest probability in older patients: consider exercise ECG testing as alternative 1
5. Exclude non-cardiac causes if symptoms persist despite negative testing 1

Common Pitfalls to Avoid

• Do not assume CAC=0 excludes all coronary disease in symptomatic patients - up to 25.9% may have some CAD, and 5.1% may have >50% stenosis 5
• Do not rely on CAC=0 alone in young symptomatic patients (<40 years) - they have higher rates of non-calcified obstructive disease 1, 4
• Do not confuse "ultralow" CAC (0.1-0.9 AU) with true zero CAC - ultralow CAC patients have 87.7% prevalence of CAD and should not be downgraded to zero CAC status 5
• Do not use CCTA as routine screening in asymptomatic patients regardless of risk factors - this is explicitly not recommended 3

Nuances in the Evidence

While the 2024 ESC guidelines emphasize that CAC=0 has >95% negative predictive value for obstructive CAD 1, this applies primarily to the general population. The ACC/AHA guidelines take a more nuanced approach, acknowledging that in symptomatic patients, particularly those with intermediate-high risk or younger age, CCTA provides valuable diagnostic information beyond CAC scoring alone 1. The CRESCENT trial demonstrated that a CAC-guided selective CCTA strategy is superior to exercise testing alone, but this still included performing CCTA in high-risk patients even with zero calcium 1.