Physiological Basis and Long-Term Clinical Outcome of Discordance Between Fractional Flow Reserve and Coronary Flow Velocity Reserve in Coronary Stenoses of Intermediate Severity

Abstract

Background-Discordance between fractional flow reserve (FFR) and coronary flow velocity reserve (CFVR) may reflect important coronary pathophysiology but usually remains unnoticed in clinical practice. We evaluated the physiological basis and clinical outcome associated with FFR/CFVR discordance. Methods and Results-We studied 157 intermediate coronary stenoses in 157 patients, evaluated by FFR and CFVR between April 1997 and September 2006 in which revascularization was deferred. Long-term follow-up was performed to document the occurrence of major adverse cardiac events: cardiac death, myocardial infarction, or target vessel revascularization. Discordance between FFR and CFVR occurred in 31% and 37% of stenoses at the 0.75, and 0.80 FFR cut-off value, respectively, and was characterized by microvascular resistances during basal and hyperemic conditions. Follow-up duration amounted to 11.7 years (Q1-Q3, 9.9-13.3 years). Compared with concordant normal results of FFR and CFVR, a normal FFR with an abnormal CFVR was associated with significantly increased major adverse cardiac events rate throughout 10 years of follow-up, regardless of the FFR cut-off applied. In contrast, an abnormal FFR with a normal CFVR was associated with equivalent clinical outcome compared with concordant normal results: ≤3 years when FFR <0.75 was depicted abnormal and throughout 10 years of follow-up when FFR ≤0.80 was depicted abnormal. Conclusions-Discordance of CFVR with FFR originates from the involvement of the coronary microvasculature. Importantly, the risk for major adverse cardiac events associated with FFR/CFVR discordance is mainly attributable to stenoses where CFVR is abnormal. This emphasizes the requirement of intracoronary flow assessment in addition to coronary pressure for optimal risk stratification in stable coronary artery disease. (Circ Cardiovasc Interv. 2014;7:301-311.)Key Words: coronary flow velocity reserve ◼ coronary microcirculation ◼ fractional flow reserve ◼ stable coronary artery disease

Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC

“…FFR can appear falsely normal in the presence of microvascular dysfunction or disease, since elevated pressure distal to a critical stenosis, associated with increased resistance due to a microvascular abnormality, may result in a normal pressure drop across a hemodynamically significant lesion. 193,194 Further, in the presence of diffuse atherosclerosis, FFR may be abnormal even without focal stenosis. 195 Finally, in the setting of excellent flow capacity, the clinical significance of a reduced FFR across a moderate lesion may be overestimated if peak flow is still sufficient to meet myocardial oxygen demand.…”

Significance of Microvascular Function in Visual—Functional Mismatch Between Invasive Coronary Angiography and Fractional Flow Reserve

“…In other words, the present study suggests that FFR >0.80 and QCA‐DS >50% not only identify vessels without the need for revascularization, but also include vessels with impaired and nonimpaired coronary flow. This potential abnormality in coronary physiology beyond the FFR assumption might provide reasons for why patients with revascularization deferral in randomized trials were not free from long‐term cardiac events, such as in DEFER and FAME follow‐up data, why 12% of patients with FFR >0.80 required revascularization within 2 years of deferral9, 10, 11 and, conversely, why some patients with FFR ≤0.80 but with preserved CFR have a low rate of major adverse cardiac events at follow‐up 33…”

Prevalence and Clinical Significance of Discordant Changes in Fractional and Coronary Flow Reserve After Elective Percutaneous Coronary Intervention

“…Mehta et al reported that lower FFR values among acute coronary syndrome patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events 23. The principle of CFR has been vigorously applied to a number of diagnostic tests, although its sensitivity toward resting hemodynamic relevance has been considered an important limitation in its use to consider myocardial flow impairment, despite reported evidence of powerful efficacy to stratify the risk of adverse cardiac events 7, 16, 24, 25. Our results indicated that CFR decrease after successful PCI was not uncommon, and CFR decrease was associated with pre‐PCI physiological indices including high CFR, high FFR, low IMR, and no significant coronary flow increase after successful PCI.…”

“…The purpose of PCI is to increase coronary flow by modifying epicardial stenosis, and FFR‐guided PCI results in better outcome compared with angiographic guidance,2, 3 suggesting that FFR‐guided PCI may benefit from hyperemic coronary flow increase. Recently, recognition of the significant relevance of myocardial blood flow with adverse clinical outcome urges a comprehensive approach to ischemic heart disease with incorporation of coronary flow impairment and microvascular resistance as well as FFR 6, 7, 8, 9, 10. Given that PCI is optimally performed without significant complications, post‐PCI FFR and CFR may similarly increase with less influence from epicardial stenosis, provided that microvascular resistance is minimized and constant before and after PCI and that basal coronary flow is not significantly different before and after PCI 11, 12.…”

“…Coronary flow reserve (CFR) is a well‐validated index that can assess coronary flow impairment originating from epicardial stenosis, diffuse coronary disease, or microvascular dysfunction 13, 14. Furthermore, CFR has been shown to provide a substantial ability to stratify the risk for cardiac events 7, 15, 16. PCI increases FFR value; however, post‐PCI CFR change and its relationship with FFR improvement remains elusive.…”