August 1, 2026Journal of the American College of Cardiology
Addition of Computed Tomography-derived Fractional Flow Reserve in the diagnostic pathway of patients with stable coronary artery disease: the FUSION randomized controlled trial
Simran P. SharmaRicardo P.J. BuddeP. Marc van der ZeeCihal GürlekCasper MihlAttila DirkaliChristiane A GelukWilco TanisEdwin O F van GorselenThomas OosterhofRichard L. BraamGabija Pundziute - do PradoJ.E. van VelzenWisam YassiSander L. WoltersJudit FehérCaroline H. C. JanssenCornelis J. van RoodenRalph P.G.J. CarisJan‐Willem GratamaRozemarijn VliegenthartJacob M. van WerkhovenTjebbe W. GalemaThomas S. KorthalsKarim D. MahmoudMartijn W. SmuldersAlexander Hirsch
Why the study?
The impact of adding computed tomography-derived fractional flow reserve (FFRct) to the diagnostic pathway in stable CAD patients with 50% to 90% stenosis on CCTA was investigated.
Does adding FFRct to the diagnostic pathway reduce the rate of invasive coronary angiography without obstructive CAD in patients with stable CAD and 50-90% stenosis on CCTA?
Key Points
- To evaluate the clinical utility of adding computed tomography-derived fractional flow reserve (FFRct) to the diagnostic pathway of stable coronary artery disease patients with intermediate-to-high stenosis on coronary computed tomography angiography.
- Multicenter, investigator-initiated randomized controlled trial (FUSION) enrolling 528 patients (median age 63 years; 59% male) with 50% to 90% stenosis in ≥1 coronary artery on coronary computed tomography angiography.
- Participants were randomly assigned to an FFRct-guided diagnostic strategy (n = 263) or standard usual care (n = 265), with assessments at 90 days and 1 year.
- At 90 days, invasive coronary angiography (ICA) without obstructive disease occurred in 18% (48 of 263) of the FFRct-guided group versus 33% (87 of 265) of the usual care group (OR: 0.46; 95% CI: 0.31-0.69; P < 0.001).
- Overall ICA utilization at 90 days was significantly lower with FFRct guidance than usual care (39% [102 of 263] vs 51% [136 of 265]; P = 0.004), a difference that persisted at 1 year.
- At 1 year, coronary revascularization rates were 20% (52 of 263) with FFRct versus 20% (53 of 265) with usual care (P = 0.948), with no significant differences in major adverse cardiac events, costs, or quality of life.
Study Design
Type
RCT (n=528)
Randomization
randomized
Multicenter
Yes
Structured PICO
Does adding FFRct to the diagnostic pathway reduce the rate of invasive coronary angiography without obstructive CAD in patients with stable CAD and 50-90% stenosis on CCTA?
P
Population
528 patients (median age 63, 41% female) with stable coronary artery disease and 50% to 90% stenosis on CCTA, randomized to FFRct-guided or usual care and followed for up to 1 year.
I
Intervention
Computed tomography-derived fractional flow reserve (FFRct)-guided diagnostic pathway
C
Comparator
Usual care diagnostic pathway
O
Outcome
Invasive coronary angiography (ICA) without obstructive CAD at 90 days
Main Result
Odds Ratio: 0.46 (95% CI 0.31–0.69)
Absolute Event Rate: 18% vs 33%
p-value: p=< 0.001
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“When a CCTA shows intermediate stenosis, physicians face a critical decision point: is this blockage significant enough to warrant an invasive procedure in case of persistent symptoms or high-risk anatomy? Sending every one of these patients to the cath lab means unnecessary risk, recovery time and anxiety. Furthermore, cath labs lose capacity that could be directed to patients needing urgent care. The FUSION data show that diagnostic efficiency can be significantly improved with Heartflow FFRCT Analysis, which can cut unnecessary catheterizations nearly in half without compromising safety, easing pressure on the system while ensuring the right patients still get timely, appropriate care.”
“One of the persistent challenges in cardiology has been accurately identifying, prior to catheterization, which patients have disease severe enough to warrant an invasive procedure. The FUSION data demonstrate that our technology can meaningfully address this challenge, providing physicians with more precise insight into a patient's disease burden after CCTA has documented stenosis over 50%.”
“Patients with a 50-90% stenosis on CCTA represent a clinically challenging population, as anatomical stenosis severity alone does not reliably identify flow-limiting lesions and often warrants further functional assessment. FUSION addresses whether FFRct-guided care offers incremental value in patient selection for ICA in an era in which guideline-directed first-line testing has increasingly shifted toward CCTA, alongside greater emphasis on initial medical therapy in the management of patients with CAD.”
Implication
Adding FFRct to the diagnostic pathway for patients with intermediate stenosis on CCTA significantly reduces unnecessary invasive coronary angiography without increasing adverse events.
Abstract
BACKGROUND: Computed tomography-derived fractional flow reserve (FFRct) integrates anatomical and functional information, which is particularly useful for stable coronary artery disease (CAD) patients with at least intermediate stenosis. OBJECTIVES: We investigated the impact of adding FFRct to the diagnostic pathway of CAD patients with a 50% to 90% stenosis on coronary computed tomography angiography (CCTA). METHODS: FUSION is an investigator-initiated, multicenter, randomized controlled trial involving patients with 50% to 90% stenosis in ≥1 coronary artery on CCTA. Patients were randomized to FFRct-guided or usual care. The primary endpoint was invasive coronary angiography (ICA) without obstructive CAD at 90 days. Secondary endpoints included ICA without obstructive CAD, major adverse cardiac events, and costs at 1 year, as well as revascularizations, and quality of life at 90 days and 1 year. ICA use was assessed as a post hoc exploratory endpoint. RESULTS: Overall, 528 patients (median age: 63 years [25th-75th: 57-69 years]; 59% male) were randomized to FFRct-guided (n = 263) or usual care (n = 265). At 90 days, the rate of ICA without obstructive CAD was significantly lower in the FFRct group than in the usual care group (18% [48 of 263] vs 33% [87 of 265]; OR: 0.46; 95% CI: 0.31-0.69; P < 0.001). ICA rate was 39% (102 of 263) vs 51% (136 of 265), respectively (P = 0.004). Both differences persisted at 1 year. Revascularization rates were similar: 20% (52 of 263) vs 20% (53 of 265) at 1 year, respectively (P = 0.948). Quality of life, costs, and major adverse cardiac events did not differ between groups, although the clinical event rates were low. CONCLUSIONS: Adding FFRct to the diagnostic pathway of patients with a 50% to 90% stenosis on CCTA reduced the rate of ICA without obstructive CAD at 90 days and 1 year, without differences in revascularizations, quality of life, and costs compared with usual care. Clinical event rates were similar, although low. The rate of overall ICA use, a post hoc exploratory outcome, was also reduced at 90 days and 1 year.
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Cite This Study
Sharma et al. (2026) conducted an RCT in stable coronary artery disease (n=528). Computed tomography-derived fractional flow reserve (FFRct) vs. Usual care was evaluated on Invasive coronary angiography (ICA) without obstructive CAD at 90 days (OR 0.46, 95% CI 0.31-0.69, p=< 0.001).