Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis

Abstract

Objectives: To obtain more powerful assessment of the prognostic value of fractional flow reserve_CT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFR_CT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).

Methods: We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserve_CT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as 'all-cause mortality (ACM) or myocardial infarction (MI)' at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.

Results: Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFR_CT>0.80% and 1.4% (47/3334) with FFR_CT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFR_CT ≤0.80 versus patients with FFR_CT >0.80. Each 0.10-unit FFR_CT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001).

Conclusions: The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFR_CT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFR_CT numerical value was inversely associated with outcomes.

Keywords: angina pectoris; computed tomography angiography; diagnostic imaging.

Figure 1

Flowchart of search and selection of eligible studies.

Figure 2

Meta-analysis of the primary composite endpoint (death or any MI) and secondary endpoints at 12-month follow-up. FFR_CT>0.80: N=number of patients with adverse events; T=total number of patients. FFR_CT≤0.80: n and t=number of patients with adverse events and total number of patients. Strata with zero events were not included in the analysis. MACE (major adverse cardiac event) was defined as a composite of death, any MI or unplanned revascularisation. Unplanned revascularisation was defined as any revascularisation (percutaneous coronary intervention and/or coronary artery bypass grafting) occurring between 3-month and 12-month follow-up. ADVANCE, Assessing Diagnostic Value of Non-invasive FFR_CT in Coronary Care’ study; FFR_CT, CTA-derived fractional flow reserve; MI, myocardial infarction; NXT, Analysis of Coronary Blood Flow Using CT Angiography: Next Steps trial; PLATFORM, Prospective Longitudinal Trial of FFRCT: Outcome and Resource impacts trial; RR, risk ratio.

Figure 3

Relationship between the primary endpoint (death or MI) and the pooled numerical FFR_CT value. FFR_CT >0.90: N=number of patients with adverse events; T=total number of patients. FFR_CT 0.10-unit reduction strata: n and t=number of patients with adverse events and total number patients. Strata with zero events were not included in the analysis. Each 0.10-unit FFR_CT reduction was associated with a higher frequency of the primary endpoint, RR 1.67 (95% CI 1.47 to 1.87), p<0.001. FFR, fractional flow reserve; MI, myocardial infarction; RR, relative risk.