Prognostic value of CT-derived fractional flow reserve for major adverse cardiovascular events in patients with suspected or known coronary artery disease: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: p<0.0001

• Effect Size: HR 3.94 for FFR-CT ≤0.80 vs >0.80

• Primary Outcome: Major adverse cardiovascular events (MACE)

• Nnt Or Sensitivity: Hard endpoints (death/MI): HR 3.28 (95% CI 2.25-4.79) with I²=0%

• Confidence Interval: 95% CI 2.92 to 5.31

Clinical Application

FFR-CT is increasingly available in tertiary centres with appropriate CT technology and expertise Relevant to Australian cardiology practice where FFR-CT is emerging as alternative to invasive FFR. May inform risk stratification decisions and guide referral patterns to interventional cardiology services Patients with suspected or known coronary artery disease undergoing non-invasive cardiac assessment

Abstract

BACKGROUND: Fractional flow reserve derived from CT (FFR-CT) enables non-invasive functional assessment of coronary stenoses in patients with suspected or known coronary artery disease, but evidence regarding its prognostic value remains fragmented. We conducted a systematic review and meta-analysis to quantify the association between abnormal FFR-CT and major adverse cardiovascular events (MACE), updating the 2022 meta-analysis by Nørgaard et al METHODS: We searched PubMed, Embase and Scopus through December 2025 for studies comparing outcomes in patients with suspected or known coronary artery disease with FFR-CT ≤0.80 versus >0.80 (PROSPERO: CRD420261276897). Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was performed. Subgroup analyses examined FFR-CT technology, geography and follow-up duration. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. RESULTS: Twenty-two studies with 20 067 patients were included, representing a fourfold increase from the prior meta-analysis. Follow-up ranged from 12 to 120 months. Patients with FFR-CT ≤0.80 had significantly higher MACE risk (HR 3.94; 95% CI 2.92 to 5.31; p<0.0001) with substantial heterogeneity (I²=79.9%). However, restricting to hard endpoints (death/myocardial infarction; k=6) yielded HR 3.28 (95% CI 2.25 to 4.79) with zero heterogeneity (I²=0%). No significant differences emerged across FFR-CT technologies (p=0.812), including HeartFlow, machine learning and deep learning algorithms. Trim-and-fill analysis suggested possible publication bias, with adjusted HR 2.35. GRADE certainty was moderate. CONCLUSIONS: Abnormal FFR-CT is associated with nearly fourfold increased risk of MACE in patients with suspected or known coronary artery disease, with consistent prognostic value across technologies. The absence of heterogeneity for hard endpoints supports FFR-CT as a reliable prognostic marker. These findings address the evidence gap identified by current guidelines regarding FFR-CT prognostic utility. PROSPERO REGISTRATION NUMBER: CRD420261276897. CLINICAL TRIAL NUMBER: Not applicable (as this is a Systematic Review and Meta-Analysis and not a Clinical Trial).

References

1. 1.Biswas, S., Srivastava, Y., & Hamadttu, A. (2026). Prognostic value of CT-derived fractional flow reserve for major adverse cardiovascular events in patients with suspected or known coronary artery disease: a systematic review and meta-analysis. Open Heart, 13(1), e003979. https://doi.org/10.1136/openhrt-2026-003979