Editorials
Effect of Aging on Fractional Flow Reserve – Hyperemic Index Fractional Flow Reserve May Not Be Sufficient to Reveal the Whole Picture of Coronary Circulation –
2016 Volume 80 Issue 7 Pages 1527-1528
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2016 Volume 80 Issue 7 Pages 1527-1528
There is a growing body of evidence that increased thickening and stiffness of large arteries and endothelial dysfunction in apparently otherwise healthy older persons, along with the ensuing increase in systolic and pulse pressures that was formerly thought to be part of “normal” aging, precede clinical disease and predict a higher risk for developing clinical atherosclerosis, hypertension, and stroke.1 Structurally, left ventricular hypertrophy, heart failure and atrial fibrillation show dramatically increased incidences with age.2 However, the effect of age on physiological parameters is still not well clarified. Coronary physiology assessed by pressure wire and flow wire is a widely accepted method that enables separate evaluation of epicardial stenosis and microvascular resistance in the clinical setting (Figure).3–6 A previous report demonstrated an inverse relationship between age and fractional flow reserve (FFR) and found that FFR-guided percutaneous coronary intervention is beneficial regardless of age.7 However, older patients have fewer functionally significant lesions, despite a similar angiographic appearance.
Schematic representation of coronary flow with normal microvascular resistance at rest (A), during maximum hyperemia (B) and coronary flow with abnormally high microvascular resistance at rest (C), during maximum hyperemia (D). Physiologically, the pressure gradient (PG) across the stenosis is expressed as a quadrant equation of coronary flow velocity (PG=fv+Sv2). The PG at rest in an elderly patient is not different from that of a younger patient at rest if the severity of stenosis is identical, because the flow across the stenosis is maintained steadily by autoregulation. However, in elderly patients the flow cannot increase sufficiently during maximum hyperemia, causing a lower PG across the stenosis compared with younger patients. Lower delta-FFR observed in elderly patients means an inability to increase flow during hyperemia because of highly abnormal microvascular resistance.
Article p 1583
In this issue of the Journal, Jin et al8 uniquely demonstrate the effect of age on FFR by analyzing not only FFR itself, but also a relatively new index, delta-FFR defined as the difference between resting Pd/Pa and FFR. This new index includes very similar information as coronary flow reserve. Based on the relationship between the pressure gradient (PG) and blood flow velocity, which can be expressed as Bernoulli’s equation: PG=fv+Sv2, the coronary PG shows a quadratic relation to flow in the presence of stenosis. Each stenosis has a specific pressure–flow curve, which is determined by its morphological characteristics.9,10 By following this fundamental, big delta-FFR, meaning a big difference in the PG across the stenosis, implies a big flow increase during maximum hyperemia compared with resting state. Conversely, small delta-FFR means a small increase in flow despite induction of maximum hyperemia. Factors influencing delta-FFR are very similar to those affecting coronary flow reserve, including severity of epicardial stenosis, diffuseness of atherosclerosis, microvascular dysfunction, and reduced endothelial vascular dilatation capacity. Because judgement by FFR alone may dismiss some of these, an index adding pressure information in the resting state, such as Pd/Pa, iFR, or delta-FFR, may help to understand the whole picture of coronary circulation compared with judgement derived from FFR alone. Delta-FFR is reported to be closely related to the future risk of cardiac events, especially in patients with a positive FFR.7 This implication of delta FFR is very similar to that of CFR so simultaneous measurement of CFR and FFR should give the clinician a better insight of the respective contributions of the epicardial vessels and microvasculature.11 van de Hoef et al reported a relatively highly percentage of discordance (37% of all lesions) between CFR and FFR, which mainly originated from microvascular involvement.12 The prognosis in this type of lesions was retrospectively analyzed and proved to be poorest when the patients showed normal FFR with abnormal CFR. Prospective confirmation of prognostic value is now ongoing in the DEFINE-FLOW trial. From these theoretical considerations and clinical observations, age-related changes of microcirculation abnormality, endothelial dysfunction, diffuse atherosclerosis may decrease the contribution of epicardial stenosis to the total ischemic burden in elderly patients.
