Diagnostic yield of second-line functional imaging after an abnormal coronary computed tomography angiography: an individual patient-data meta-analysis

Aims: Second-line functional imaging is recommended following an abnormal coronary computed tomography angiography (CCTA). However, evidence guiding the choice of imaging modality is limited. We assessed the diagnostic performance of second-line functional imaging using different invasive reference standards. Methods and results: We conducted an individual patient-data meta-analysis of seven prospective diagnostic studies including 1410 patients (mean age 62 ± 8.1 years, 67% male) with abnormal CCTA [≥50% diameter stenosis (DS)], who underwent second-line functional imaging tests (dobutamine stress ECHO, SPECT, CMR, and/or PET) followed by invasive angiography with fractional flow reserve (FFR) and quantitative coronary angiography (QCA). Haemodynamically obstructive coronary artery disease (CAD) was defined as invasive FFR ≤0.80 or >90% visual DS; anatomically severe CAD as ≥70% DS by QCA. Pooled and per test, 904/1906 (47.2%) functional imaging tests had haemodynamically obstructive CAD, and 504/1906 (26.3%) functional imaging tests had anatomically severe CAD. In total, 730/1906 (38.3%) functional imaging tests were abnormal. Pooled sensitivity and specificity were 63% and 84% for haemodynamically obstructive CAD, and 81% and 77% for anatomically severe CAD. Findings were generally stable across sex and age. More advanced second-line functional imaging tests showed higher sensitivities, but lower specificities compared to less advanced techniques. Conclusion: Second-line functional imaging after an abnormal CCTA enables identification of patients with anatomically severe CAD. In contrast, moderate stenoses (<70% DS) with FFR ≤0.80 do not consistently result in myocardial ischaemia detectable by functional imaging tests. Substantial diagnostic accuracy differences were found between non-invasive diagnostic test which need further investigation.