What part of the FFR link don't we understand?

P hysiologists and physicians have long been interested in blood flow and pressure (i.e., hemodynamics). The importance of the circulatory system in regulating health and disease has been appreciated since the days of blood-letting and leaches. In 1738, Daniel Bernoulli (1) elegantly described the impact of narrowings on pressure and flow in his book Hydrodynamica. The principles he described then are still accurate today and underpin our current physiologic measurements. In the mid19th century, Volkmann (2) was recording arterial pressure waveforms in animals. The importance of translesional gradients was appreciated by Andreas Grünzig (3) from the first percutaneous coronary intervention (PCI). Even using crude measurement techniques, it was possible to show patient benefit when gradients were low post PCI (4). And, in the early 1990s, Nico Pijls et al. (5) validated a lesion specific, simple to use measure to determine the physiologic significance of individual coronary lesions: fractional flow reserve (FFR).