Clinical and technical evidence

A literature search was carried out for this briefing in line with the interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.

Published evidence

Four studies involving 568 patients are summarised in this briefing.

Table 1 summarises the clinical evidence as well as its strengths and limitations.

Overall assessment of the evidence

Four studies are summarised in this briefing, but a larger body of evidence was identified mostly consisting of abstracts, technical reports, study protocols, presentations and experimental single-centre cohort studies on pilot devices. Early results from the China arm of the FAVOR II trial (Xu et al. 2017) are reported involving 5 sites and 306 patients, and those from the FAVOR trial (Tu et al. 2016): a pilot for FAVOR II. Rosendale et al. (2017) is presented, which examined the accuracy and reproducibility of 3 methods of quantitative flow ratio (QFR) calculation. Finally, Westra et al. (2018) is summarised, which reports results from the Wire-Free Functional Imaging II study. The reference standard in the reported studies is fractional flow reserve (FFR).

Table 1 Summary of selected studies

Tu et al. (2016)

Study size, design and location

73 patients (84 vessels).

Multicentre prospective observational study involving 8 sites in 7 countries (Belgium, Italy ×2, Netherlands, Germany, China, Japan and US).

Intervention and comparator(s)

QAngio XA 3D/QFR.

Reference standard (comparator): pressure-wire derived FFR measured during maximal stable hyperaemia, induced by intravenous adenosine/adenosine triphosphate infusion.

Key outcomes

Mean angiographic percent diameter stenosis (DS%) was 46.1±8.9%; 27 vessels (32%) had FFR ≤0.80. Good agreement with FFR was observed for fQFR, cQFR and aQFR, with mean differences of 0.003±0.068 (p=0.66), 0.001±0.059 (p=0.90) and −0.001±0.065 (p=0.90) respectively. The overall diagnostic accuracy for identifying an FFR of ≤0.80 was 80% (95% CI 71% to 89%), 86% (95% CI 78% to 93%) and 87% (95% CI 80% to 94%) respectively. The area under the ROC was higher for cQFR than fQFR (difference: 0.04; 95% CI 0.01 to 0.08; p<0.01), but did not differ significantly between cQFR and aQFR (difference: 0.01; 95% CI −0.04 to 0.06; p=0.65).

The PLR was 4.8, 8.4 and 8.9 for fQFR, cQFR and aQFR, with NLR of 0.4, 0.3 and 0.2 respectively.

Strengths and limitations

This is a pilot study with a relatively small study population. None of the centres were in the UK.

Van Rosendael et al. (2017)

Study size, design and location

17 patients, 20 vessels.

Single-centre prospective observational study (Netherlands).

Intervention and comparator(s)

QAngio XA 3D/QFR.

Reference standard (comparator): pressure-wire derived FFR measured during maximal stable hyperaemia, induced by continuous intravenous adenosine (0.14 mg/kg/min).

Key outcomes

Mean difference, standard deviation and 95% limits of agreement (LOA) between invasive FFR and aQFR, cQFR and fQFR for:

  • observer 1:

    • aQFR: mean difference ±SD: 0.01±0.04 (95% LOA: −0.07; 0.10)

    • cQFR: 0.01±0.05 (95% LOA: −0.08; 0.10)

    • fQFR: 0.01±0.04 (95% LOA: −0.06; 0.08)

  • observer 2:

    • aQFR: 0.00±0.03 (95% LOA: −0.06; 0.07)

    • cQFR: −0.01±0.03 (95% LOA: −0.07; 0.05)

    • fQFR: 0.00 ± 0.03 (95% LOA: −0.06; 0.05).

Between observer reproducibility for aQFR: 0.01±0.04 (95% LOA: −0.07; 0.09), for cQFR: 0.02±0.04 (95% LOA: −0.06; 0.09) and for fQFR: 0.01±0.05 (95% LOA: −0.07; 0.10).

Strengths and limitations

Supports other studies showing a high correlation between QFR and FFR. Additionally shows good agreement (reproducibility) between observers. Limited number of patients, 1 of the authors was the chief executive officer (CEO) of Medis and another an employee of Medis.

Xu et al. (2017)

Study size, design and location

306 patients (328 vessels).

Prospective multicentre observational study involving 5 sites in China.

Intervention and comparator(s)

QFR QCA.

Reference standard (comparator): wire-based FFR from QCA.

Key outcomes

Patient-level and vessel-level diagnostic accuracy (defined as accuracy of online QFR [≤0.8 or >0.8] to identify hemodynamically significant coronary stenosis with FFR [≤0.8 or >0.8]) of QFR were 92.4% (95% CI 88.9% to 95.1%) and 92.7% (95% CI 89.3% to 95.3%), that were both significantly higher than the pre‑specified target value of 75% (p<0.001). Sensitivity and specificity in identifying hemodynamically significant stenosis were significantly higher for QFR than QCA (sensitivity: 94.6% versus 62.5%, difference: 32.0%, p<0.001; specificity: 91.7% versus 58.1%, difference: 36.1%, p<0.001). Positive predictive value, negative predictive value, PLR and NLR for QFR was 85.5%, 97.1%, 11.4 and 0.06 respectively. Offline analysis showed vessel-level QFR had a high diagnostic accuracy of 93.3% (95% CI 90.0%, 95.7%).

Strengths and limitations

Multicentre partially blinded study (QFR, QCA and wire-based FFR were assessed online in blinded fashion during coronary angiography and re‑analysed offline at an independent core laboratory) with good patient numbers. Vessels with diameter stenosis below 30% or above 90% were not assessed; 15.6% patients had a previous myocardial infarction, which may have increased the possibility of inaccurate physiology measurements but is reflective of a standard clinical population.

Westra et al. (2018)

Study size, design and location

172 patients (225 lesions).

Prospective multicentre observational study involving 2 sites in Denmark.

Intervention and comparator(s)

QAngio XA 3D/QFR.

Reference standard (comparator): wire-based FFR.

Key outcomes

QFR and FFR ≤0.80 were used as the diagnostic cut‑off values.

Overall sensitivity, specificity, positive predictive value and negative predictive value were 77% (95% CI 66 to 85), 86% (95% CI 79 to 91), 75% (95% CI 65 to 84) and 87% (95% CI 80 to 92) respectively.

Mean difference between FFR and QFR was 0.01±0.08. QFR correctly classified 83% of the lesions using FFR. The area under the receiver operating characteristic curve was 0.86 (95% CI 0.81 to 0.91).

Strengths and limitations

Multicentre partially blinded study. QFR and FFR were assessed by blinded observers. Vessels with diameter stenosis below 30% or above 90% were not assessed. The study was part-funded by the company.

Abbreviations: aQFR, measured hyperaemic flow velocity derived from angiography during adenosine-induced hyperaemia; CI, confidence interval; cQFR, modelled hyperaemic flow velocity derived from angiography without drug-induced hyperaemia; FFR, fractional flow reserve; fQFR, fixed empiric hyperaemic flow velocity; LOA, limit of agreement; NLR, negative likelihood ratio; PLR, positive likelihood ratio; QCA, quantitative coronary angiography; QFR, quantitative flow ratio; ROC, receiver operating curve; SD, standard deviation.

Recent and ongoing studies