It was with great interest that we read the report by Rodés-Cabau et al titled “Importance of Diffuse Atherosclerosis in the Functional Evaluation of Coronary Stenosis in the Proximal-Mid Segment of a Coronary Artery by Myocardial Fractional Flow Reserve Measurements.” The investigators showed how fractional flow reserve (FFR) results can vary according to the location of the distal pressure sensor within the artery. Specifically, for the first time, it was shown that more distal measurements are more likely to be associated with lower FFR values. This finding strengthens the importance of the pressure wire as a functional assessment of disease severity. Its values not only reflect the significance of the visually obvious stenosis but represent the severity of the entire plaque burden across the vessel. By positioning the pressure wire more distally, the assessment was made over a longer segment of disease, therefore making it more likely for a significant pressure decrease to occur. Koo et al recently reported that anatomically similar coronary stenoses are 3 times more likely to produce abnormal FFR if they are located in proximal vessels. These findings could also be explained by the same principle that more proximal and longer stenoses are more likely to have bigger atheroma burdens even if they have similar cross-sectional areas, resulting in more significant pressure decrease and abnormal FFR readings.

This interesting finding highlights a few aspects of the pathophysiology of coronary disease and the way we assess it. From the physiologic perspective, it confirms that the limitation to blood flow inside a stenotic coronary artery is caused by a much longer segment of disease than we commonly think. We tend to focus our anatomic assessment on a relatively small part of the vessel that is macroscopically narrowed, forgetting the contribution of the remaining artery without “significant” epicardial disease. By choosing parameters such as percentage stenosis and minimal luminal area as our anatomic targets for disease severity, we are missing other important contributors to the pathophysiology of ischemia.

Rodés-Cabau et al’s results also bring to light the current lack of appropriate data on how to correctly measure FFR. There are no specific evidence-based recommendations on where to position the pressure wire during its acquisition, which may be particularly important when trying to assess for the presence of ischemia. We believe these findings will help raise awareness of the necessity of further studies designed to elucidate the precise mechanisms of why blood flow is reduced in coronary disease. Perhaps technologies such as optical coherence tomography will enable us to look beyond the macroscopic stenosis, yielding more detailed information about the microanatomy of the vessel (roughness and small irregularities of the arterial wall, etc.), which certainly play a major role in restricting blood flow.