Diagnostic accuracy

The diagnostic accuracy of QFR has been widely studied, with 39 studies in this review, including 5940 patients (over 7043 vessels or lesions). QFR, as measured using QAngio, is highly correlated with FFR measured with an invasive pressure wire. The average difference between FFR and QFR measurements is almost zero, and they rarely differ by more than 0.1, with about 50% of measurements differing by less than 0.04.

QAngio XA 3D/QFR at a cut-off point of 0.8 has good diagnostic accuracy to predict FFR (also at a cut-off point of 0.8), cQFR mode had a sensitivity of 85% (95% CI 78% to 90%) and a specificity of 91% (95% CI 85% to 95%) and fQFR mode had a sensitivity of 82% (95% CI 68% to 91%) and a specificity of 89% (95% CI 77% to 95%). Although there is some discordance between QFR and FFR, most FPs or FNs arise near the boundary (e.g. where one is 0.81 and the other 0.79), and the discordance may not be clinically meaningful. Data on how this accuracy may vary by key patient characteristics was very limited, and no conclusive variation could be found.

The use of a ‘grey-zone’ strategy, where patients with a QFR between 0.78 and 0.84 receive confirmatory FFR, improves diagnostic accuracy, compared with using QFR alone, to a sensitivity of 93.1% and a specificity of 92.1%. However, this improvement is dependent on assuming that the exact FFR cut-off point of 0.8 is clinically meaningful. Most FFR and QFR values differ by 0.05 or less; therefore, the grey-zone approach is mainly identifying discordant FFR and QFR results very close to the 0.8 boundary; 30.4% of patients with QFR results in the grey zone have results that are discordant with their FFR.

Data on the diagnostic accuracy of CAAS vFFR were limited to only three studies. Owing to variable reporting of results and apparent substantial heterogeneity in results across studies, a full meta-analysis was not feasible.

Although assessing the diagnostic accuracy of using standard ICA alone was not the focus of this report, studies that reported data on ICA, and targeted searches for additional data, found that ICA alone had poor diagnostic accuracy when compared with FFR. All studies that compared QFR with ICA found QFR to be superior in diagnostic accuracy.

Clinical value and implementation

This review found limited evidence on the clinical impact of using QFR. The use of a grey zone could significantly reduce the proportion of adenosine and pressure-wire-free procedures compared with universal use of FFR, without significantly affecting diagnostic accuracy. Evidence on the applicability of QAngio XA 3D/QFR suggests that the technology is applicable in a clinical context.

Given the limitations in the evidence, a simulation study was performed to investigate the impact of using QFR, with or without a grey zone, on future coronary events. The simulation found that using QFR slightly increased the revascularisation rate compared with using FFR for all, from 40.2% to 42%. Using a grey-zone strategy increased it further to 43.2%. However, all three strategies had similar numbers of resulting coronary events, suggesting that all have a broadly similar benefit when making decisions as to who should receive revascularisation.

Although CAAS vFFR appears promising, its clinical value is currently uncertain because of limited evidence and a lack of on-site prospective studies.

Cost-effectiveness

The base-case cost-effectiveness results showed that the test strategy with the highest net benefit (most cost-effective strategy) was ICA followed by confirmatory FFR/iFR (strategy 2) at a cost-effectiveness threshold of £20,000 per QALY gained. However, the difference in net benefit between this strategy and the next best strategies was relatively small at 0.007 QALYs (or equivalently £140) per patient diagnosed for ICA with QFR (strategy 3), 0.012 QALYs (or equivalently £240) per patient diagnosed for ICA with QFR followed by confirmatory FFR/iFR when QFR is inconclusive (strategy 4) and 0.011 QALYs (or equivalently £220) per patient diagnosed for ICA with vFFR (strategy 5).

A number of alternative scenarios were considered in which the assumptions used as part of the base-case results were varied. These alternative scenarios showed that the cost-effectiveness results were robust to the mode of QFR measurement (contrast-flow QFR or fixed-flow QFR), the use of an alternative diagnostic threshold of 0.75 for FFR and QFR, the use of a wider definition of the grey-zone region for confirmatory FFR/iFR when QFR is inconclusive, throughput assumptions for QFR and vFFR, alternative estimates of procedural complication rates for FFR/iFR, and dependency of MACE risk on FFR. The scenarios were also used to identify the main drivers of cost-effectiveness. The key drivers identified were (1) the sensitivity (rather than specificity) of test results because TP test results translated into higher QALY gains than mismanagement of FN test results, (2) the procedural QALY loss associated with FFR/iFR, (3) the magnitude and duration of the QALY gains associated with revascularisation and (4) the additional costs associated with confirmatory testing with FFR/iFR in strategy 4. Strategy 1 of ICA alone, without additional testing, appeared cost-effective relative to the other strategies only when it was assumed that there were no benefits of revascularisation.

Overall, the differences in net benefit at a cost-effectiveness threshold of £20,000 per QALY between ICA followed by confirmatory FFR/iFR (strategy 2), and ICA with QFR (strategy 3) are small in an interventional setting. When considering a diagnostic-only setting, ICA with QFR may result in higher net benefit at a cost-effectiveness threshold of £20,000 per QALY than strategy 1, assuming QAngio XA 3D/QFR has similar diagnostic accuracy across settings.

Strengths

This review includes a comprehensive systematic review of all the published literature on QFR as assessed by QAngio XA 3D/QFR and CAASS vFFR technologies, and has been conducted following recognised guidelines to ensure high quality.

The review identified a substantial literature on the diagnostic accuracy of QAngio XA 3D/QFR (37 studies and > 5000 patients) and, despite evidence of heterogeneity and variable quality in the evidence, future research is unlikely to significantly change the overall diagnostic accuracy review findings. Study authors were contacted to provide additional data, and the review includes additional data from published studies and data from as yet unpublished studies.

This review has made best use of all available data, including extracting data from published figures, to maximise the range of analyses, including analysing the diagnostic impact of using a grey zone with QFR, and performing a simulation study to assess the clinical impact of QFR on future coronary events. To our knowledge, this goes beyond any previous review or meta-analysis in the field.

This is the first study, to our knowledge, to assess the cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR. The decision model comprehensively assessed both the short-term costs and consequences associated with diagnostic testing and the longer-term impact of treatment on both costs and consequences to ensure that lifetime differences (e.g. the risk of major adverse cardiovascular events and HRQoL benefits associated with revascularisations) were appropriately quantified.

Limitations

Evidence on the CAAS vFFR technology was limited to four studies, which varied in their reporting, and appeared to have heterogeneous results. This prevented any full meta-analyses of diagnostic accuracy for CAAS vFFR or any assessment of its clinical effectiveness.

There were insufficient data allowing exploration of the impact of key patient characteristics (such as multivessel disease or diabetes) on diagnostic accuracy or clinical effectiveness, so these could not be fully investigated.

As is common in reviews of diagnostic tests, data beyond basic diagnostic accuracy, such data on the clinical impact of QAngio XA 3D/QFR, or its practical implementation, were extremely limited and could not be fully reviewed. Although a simulation study was performed to address this, it was innately limited by having to make strong assumptions about the relevant population, and the risk of events, in that population.

The cost-effectiveness results for strategy 5 with vFFR must be interpreted with caution because of very limited data available from diagnostic accuracy studies of vFFR. The use of alternative diagnostic accuracy estimates for vFFR highlighted the substantial uncertainty surrounding the cost-effectiveness of vFFR. The cost-effectiveness results were very sensitive to the procedural disutility assumed in the model for FFR/iFR and the duration of HRQoL benefits associated with revascularisation.