Invasive “in the cath-lab” assessment of myocardial ischemia in patients with coronary artery disease: When does the gold standard not apply?

International guidelines recommend that revascularization for coronary artery disease (CAD) should be guided by evidence of myocardial ischemia. Fractional flow reserve (FFR) and instantaneous free wave ratio (iFR) are the main invasive indices for assessing the ischemic potential of angiographically intermediate coronary stenosis as a large body of evidence supports their routine application. Both indices have been tested and validated in patients with isolated stable CAD, but notably their application outside this specific context is a matter of debate and investigation. In the present review we aim to look into the available evidence about the reliability and feasibility of FFR and iFR in clinical contexts different from stable angina where these techniques have been validated. We aim to shed light on which technique can be used to invasively assess ischemia when an angiographic moderate coronary stenosis is observed in a clinical setting other than isolated stable CAD.