Invasive pressure wire–based assessment remains the gold standard for guiding percutaneous coronary intervention (PCI), yet its real-world use lags despite strong guideline recommendations, largely due to procedural complexity and workflow burden. We spoke to Dr William F Fearon (Stanford University School of Medicine, Stanford, CA, USA) and Dr Ajay J Kirtane (Columbia University Department of Medicine, New York, NY, USA) following their presentation at the American College of Cardiology (ACC) Annual Scientific Session 2026 on their large-scale global randomized trial of coronary physiology derived from conventional angiography compared with an invasive pressure wire-based approach to guide PCI, and their recent results. As clinicians seek more efficient yet evidence-based approaches, this study positions angiography-derived physiology as a promising tool to expand adoption while maintaining clinical rigor.
What clinical gap were you aiming to address with this trial comparing angiography-derived coronary physiology with traditional pressure wire–based physiological assessment to guide PCI?
William F Fearon: Pressure wire-based physiologic assessment of coronary disease has a Class Ia recommendation in the US and European guidelines. Yet, it remains underutilized, in part because of the “hassle factor”. Angiography-derived physiology (FFRangio) streamlines the assessment and has been shown to correlate well with simultaneous pressure wire-based assessment. However, to date there had not been a large, multicenter, randomized clinical outcomes study comparing the two approaches.
What were the key design features of the trial, including inclusion/exclusion criteria, primary and secondary endpoints and so on?
William F Fearon: Some key features of this study are that we designed it to be as “real world” as possible. Investigators could include most patients/lesions in whom we currently use pressure wire-based physiology. There were few exclusion criteria. Operators could use any pressure wire-based technique, either FFR [fractional flow reserve] or a NHPR [non-hyperemic pressure ratio]. The primary endpoint was a meaningful one, including the important events of death, MI [myocardial infarction], or clinically indicated revascularization. There were also some very important secondary endpoints, namely, procedure time, fluoroscopy time and contrast media utilization.
Could you outline the results of the trial? Which technique proved to be superior?
William F Fearon: The goal of the study was to test whether FFRangio is noninferior to pressure wire-based physiology when evaluating the composite of death, MI, or revascularization at one year. We found a 6.9% rate in the FFRangio arm and a 7.1%, allowing FFRangio to easily meet the criterion for noninferiority (p=0.0008). Moreover, patients in the FFRangio arm had shorter procedures, were exposed to less fluoroscopy and received less contrast media as compared with the pressure wire-based strategy.
From a clinical perspective, how do you think these results might change routine practice?
Ajay J Kirtane: We hope that – by choosing clinical endpoints for this study – this will allow clinicians to feel more comfortable using this technology to manage their patients in the cath lab. As a result, we hope that this study can improve the overall utilization of coronary physiologic testing with the clear clinical validation of FFRAngio in this trial. Finally, we hope that these positive results will lead to further iterations of the technology, allowing even greater integration of this tool into daily clinical workflow.
What do you see as the key remaining questions for angiography-derived physiology, particularly regarding broader implementation, operator training and long-term clinical outcomes?
Ajay J Kirtane: What degree of training is needed is an open question, especially as the AI [artificial intelligence]-based tools get better and better. To me, one of the key additional questions is further validation of these results among non-culprit lesions in patients with AMI [acute myocardial infarction] (because the majority of patients were not biomarker-positive).
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References
- Fearon WF, Jeremias A, Witberg G, et al. Angiography-Derived Fractional Flow Reserve to Guide PCI. N Engl J Med. 2026. DOI: 10.1056/NEJMoa2600949 Available at: www.nejm.org/doi/full/10.1056/NEJMoa2600949 (accessed 1 April 2026).
Cite: Fearon WF and Kirtane AJ. Angiography-Derived Physiology Matches Pressure Wire Guidance. touchCARDIO. 1 April 2026.
Editor: Heather Hall, Managing Editor
Advisory Editors: Sven Awege
Disclosures: William F Fearon wishes to disclose consultancy for Edwards Lifesciences and grant/research support from Abbott Vascular, CathWorks and Medtronic. Ajay J Kirtane wishes to disclose consultancy and grant/research support from Cathworks/Medtronic and was part of the ALL-RISE trial, which was funded by Cathworks/Medtronic. This interview was conducted as part of our coverage of the American College of Cardiology (ACC) 2026 conference and does not constitute endorsement from the ACC. This article was edited by the touchCARDIO team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. Views expressed are the author’s own and do not necessarily reflect the views of Touch Medical Media. No funding was received in the publication of this article.
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