Fractional flow reserve-guided percutaneous coronary intervention: where to after FAME 2?

Fractional flow reserve (FFR) is a well-validated clinical coronary physiological parameter derived from the measurement of coronary pressures and has drastically changed revascularization decision-making in clinical practice. Nonetheless, it is important to realize that FFR is a coronary pressure-derived estimate of coronary blood flow impairment. It is thereby not the same as direct measures of coronary flow impairment that determine the occurrence of signs and symptoms of myocardial ischemia. This consideration is important, since the FAME 2 study documented a limited discriminatory power of FFR to identify stenoses that require revascularization to prevent adverse events. The physiological difference between FFR and direct measures of coronary flow impairment may well explain the findings in FAME 2. This review aims to address the physiological background of FFR, its ambiguities, and its consequences for the application of FFR in clinical practice, as well as to reinterpret the diagnostic and prognostic characteristics of FFR in the light of the recent FAME 2 trial outcomes.