Raising Questions on the Prognostic Value of Fractional Flow Reserve from CCTA

A new Circulation study provides one of the largest real-world evaluations of the prognostic value of fractional flow reserve from computed tomography (FFR-CT).¹

In 7,836 patients from 27 centers who were followed for about three years, progressively lower FFR-CT values were associated with increasing risk of myocardial infarction (MI), cardiovascular death and revascularization.¹

After adjustment for risk factors and CAD-RADS, stenosis-specific FFR-CT ≤ 0.70 was associated with approximately threefold higher MI risk while the optimal threshold for MI or cardiovascular death was 0.67, substantially lower than the conventional 0.80 ischemic threshold.¹

These are interesting findings but there is another question one should consider: How much prognostic information did FFR-CT actually add?

Clinical risk factors alone produced a C-index of 0.758.
Adding anatomical stenosis severity increased it to 0.771.
Adding FFR-CT increased it further to 0.783.
So the incremental improvement attributable to FFR-CT was ΔC-index = 0.012.¹
Is this statistically significant? Yes.
Is it transformative prognostic information? Meh. Maybe? That is a very different question.

What is My Take on This Study and FFR-CT?

I firmly believe FFR-CT is going to become an integral part of coronary computed tomography angiography (CCTA) evaluation when needed.

This is a strong study supporting FFR-CT as a marker of prognosis, particularly when values become markedly abnormal.
However, association should not be confused with mechanism.
Lower FFR-CT inevitably reflects, at least partly, the underlying atherosclerotic burden, stenosis severity and diffuse coronary disease.

We should also consider the most important limitation of the study: Plaque burden was not available.

Does FFR-CT Offer Prognostic Value Beyond Quantitative Total Plaque Burden?

The study authors acknowledge that it remains unknown whether FFR-CT provides incremental prognostic value over quantitative total plaque burden.

This distinction matters.

FFR-CT describes the physiological consequence of coronary disease. Plaque imaging measures the disease itself.With quantitative CCTA, AI-based plaque analysis and increasingly photon-counting CT (PCCT), the next comparison should therefore not simply be: “stenosis + FFR-CT” but rather “plaque burden + plaque phenotype + stenosis + physiology.”

Only then will we understand how much independent prognostic information physiology really adds.

Dr. Cademartiri is the director of advanced cardiovascular imaging and photon-counting CT at the Scientific Institute for Research, Hospitalization, and Healthcare Synlab Diagnostic Network in Naples, Italy. He is also a consultant in advanced cardiovascular imaging at CDI/Centro Diagnostico Italiano in Milan, Italy.

(Editor’s note: This blog is adapted with permission from Dr. Cademartiri’s original LinkedIn post available at: https://www.linkedin.com/feed/update/urn:li:activity:7509196634615070720/ ).