The Power of Zero, Revisited: Should a Zero Coronary Calcium Score Still Reassure Symptomatic Patients?

New PROMISE trial data presented at SCCT 2026 show that noncalcified plaque on CCTA reclassifies risk in a meaningful minority of CAC-zero patients with chest pain, reigniting a debate over how far quantitative plaque assessment should extend into everyday practice.

Cardiology & Investing Insights · Preventive Cardiology / Cardiac Imaging

For a generation of cardiologists, a coronary artery calcium (CAC) score of zero has functioned as a reassuring off-ramp for symptomatic patients undergoing chest pain evaluation.

New data presented at the 2026 Society of Cardiovascular Computed Tomography (SCCT) meeting complicate that reassurance for a meaningful subset of patients.

Investigators analyzing the PROMISE trial found that 12% of symptomatic, CAC-zero patients had noncalcified plaque on coronary computed tomography angiography (CCTA), and that this group carried a nearly sixfold higher risk of major adverse cardiac events (MACE).

The findings arrive as AHA guidance on nonobstructive coronary artery disease has already pushed clinicians toward more individualized, plaque-informed decision-making rather than calcium-score shortcuts.

What the PROMISE Reanalysis Showed

The analysis included 3,722 PROMISE participants who underwent CCTA with quantitative plaque assessment (QPA), of whom 40% had a CAC score of zero.

Among CAC-zero patients, those with noncalcified plaque were slightly older, less often female, and had a stenosis rate of 50% or greater that was roughly double that of CAC-zero patients without plaque.

Overall MACE was far higher with CAC present than absent (3.9% vs 1.2%), but once noncalcified plaque was factored in, event rates converged regardless of whether calcium was present (4.5% vs 3.9%).

Critically, the MACE rate fell to just 0.8% in patients with neither CAC nor noncalcified plaque, the group the presenting investigator termed the true "power of zero plaque."

On adjusted analysis, CAC-zero patients with noncalcified plaque had almost six times the hazard of MACE compared with CAC-zero patients without plaque, a signal that was attenuated but not eliminated after accounting for stenosis severity, ASCVD risk, and baseline statin or aspirin use.

MACE Rates Across CAC and Plaque Strata

Median follow-up 25 months, PROMISE trial reanalysis

Two Views From the Podium

The presenting investigator argued for extending plaque assessment specifically to the CAC-zero subgroup, reasoning that most of these patients can be confidently downgraded while a minority are unmasked as truly high-risk.

A discussant offered a more skeptical counterpoint, noting that "zero CAC does not guarantee zero risk" is already well established, and that the more relevant questions are how often the signal appears, how strong it is, and what it costs to chase.

That discussant highlighted that more than half of all MACE events in the CAC-zero group occurred in patients without any noncalcified plaque, undercutting the idea that a negative QPA result offers airtight reassurance.

Using data from a separate national imaging cohort, he estimated that finding one additional true-positive patient via CCTA rather than CAC scoring costs roughly $24,500 more, and that adding QPA on top pushes the cost of detecting one event-bound, noncalcified-plaque-positive patient to about $280,000.

Incremental Cost to Detect One Event-Bound Patient

Illustrative figures cited in SCCT 2026 cost-effectiveness debate

PROMISE-Derived Risk Snapshot

Table 1. MACE and stenosis rates by CAC and plaque status (PROMISE reanalysis, median follow-up 25 months)

Group	Proportion of CAC-zero cohort	≥50% stenosis	MACE rate
CAC zero, no noncalcified plaque	88%	9%	0.8%
CAC zero, noncalcified plaque present	12%	22%	4.5%
CAC present (any plaque)	—	—	3.9%
All CAC-zero patients (composite)	100%	1.1%	1.2%

Where This Leaves Practice Today

No professional society currently recommends routine QPA for patients who already have a CAC score of zero, so today's decision remains a judgment call rather than a guideline mandate.

For a symptomatic patient whose pretest risk is otherwise low, a zero CAC score plus normal symptoms and risk factors still supports conservative management and rescanning in 5 to 7 years, per existing chest pain guidance.

For patients with amplified risk-factor burden, atypical or escalating symptoms, or a strong family history despite a zero CAC score, added CCTA with plaque quantification is a reasonable discussion point rather than a reflexive order.

Two AI-enabled quantitative plaque analysis platforms, Cleerly and HeartFlow, have driven much of the recent expansion in reimbursed, automated plaque quantification and are the software layer underlying most QPA discussed in this debate.

Both platforms run on CT hardware from major imaging manufacturers, including GE HealthCare, whose installed base of cardiac CT scanners is a key channel for QPA adoption.

Relevant Public Companies

Table 2. Selected companies in the CCTA / quantitative plaque assessment ecosystem

Company	Role	Ticker	Analyst consensus	12-month price target
HeartFlow, Inc.	AI-based FFR-CT and plaque analysis software	NASDAQ: HTFL	Strong Buy	~$37
Cleerly	AI-driven quantitative coronary CT plaque platform	no ticker (private)	N/A	N/A
GE HealthCare Technologies	Cardiac CT imaging hardware	NASDAQ: GEHC	Buy	~$79

Cleerly remains privately held with no public ticker; figures for publicly traded companies reflect analyst consensus at the time of writing and will move with the market.

Clinical Vignette

A 54-year-old active patient with hypertension and a family history of premature coronary disease presents with several months of exertional chest tightness.

A CAC scan returns a score of zero, and the referring clinician is prepared to reassure the patient and stop the workup.

Given the atypical but progressive symptom pattern and multiple risk factors, the cardiologist instead proceeds to CCTA, which reveals a moderate segment of noncalcified plaque without flow-limiting stenosis.

Rather than reflexively escalating to invasive angiography, the patient is started on high-intensity statin therapy and scheduled for close clinical follow-up, illustrating how plaque data—not the calcium score alone—can recalibrate a preventive care plan.

Bottom Line

A CAC score of zero still identifies a large majority of symptomatic patients as truly low risk, but roughly one in eight will harbor noncalcified plaque that meaningfully raises MACE risk.

Quantitative plaque assessment adds real discriminatory value in this subgroup, yet its added cost, currently estimated near $1,000 beyond the CCTA itself, means it is not yet ready for indiscriminate use in all CAC-zero patients.

The most defensible approach today reserves added CCTA and plaque quantification for CAC-zero patients whose symptom pattern or risk-factor burden raises independent concern, rather than applying it universally.

Downstream Practice Note

Clinicians should expect QPA costs to fall as competing AI vendors expand and as reimbursement pathways mature, which may shift this cost-benefit calculation within a few years.

Larger, prospective outcome trials with longer follow-up are still needed before quantitative plaque assessment can be formally incorporated into chest pain guidelines for CAC-zero patients.

Physician education disclaimer: This article is intended for healthcare professional education and summarizes recently presented and published data; it does not constitute clinical practice guidance for any individual patient and should not replace independent clinical judgment or current society guidelines.

Financial disclaimer: Stock tickers, analyst ratings, and price targets referenced above are for informational purposes only, reflect data available at the time of writing, and are not investment advice; consult a licensed financial advisor before making investment decisions.

References

1. TCTMD. Zero CAC Questionable for Ruling Out Obstructive CAD in Young Adults.
2. American Heart Association. State of the Art: Evaluation and Medical Management of Nonobstructive Coronary Artery Disease in Patients With Chest Pain. Circulation.
3. JACC: Cardiovascular Imaging. The Fallacy of the Power of Zero.
4. Cleerly. Personalized Analysis and Treatment of Heart Disease.
5. HeartFlow, Inc. Announces Pricing of Upsized Initial Public Offering.
6. StockAnalysis.com. GE HealthCare Technologies (GEHC) Stock Overview.

Want this adapted into a short video script, a social media summary, or a plain-language patient handout on what a "zero calcium score" does and doesn't mean? Just say the word.