Physiology-Based Revascularization

Coronary physiological assessment using fractional flow reserve or nonhyperemic pressure ratios has become a standard of care for patients with coronary atherosclerotic disease. However, most evidence has focused on the pre-interventional use of physiological assessment to aid revascularization decision-making, whereas post-interventional physiological assessment has not been well established. Although evidence for supporting the role of post-interventional physiological assessment to optimize immediate revascularization results and long-term prognosis has been reported, a more thorough understanding of these data is crucial in incorporating post-interventional physiological assessment into daily practice. Recent scientific efforts have also focused on the potential role of pre-interventional fractional flow reserve or nonhyperemic pressure ratio pullback tracings to characterize patterns of coronary atherosclerotic disease to better predict post-interventional physiological outcomes, and thereby identify the appropriate revascularization target. Pre-interventional pullback tracings with dedicated post-processing methods can provide characterization of focal versus diffuse disease or major gradient versus minor gradient stenosis, which would result in different post-interventional physiological results. This review provides a comprehensive look at the current evidence regarding the evolving role of physiological assessment as a functional optimization tool for the entire process of revascularization, and not merely as a pre-interventional tool for revascularization decision-making.

In this context, efforts to establish the novel role of physiological assessments in functionally optimized revascularization have been undertaken. The concept of "FFR gain" (degree of changes in FFR after PCI) has emerged, and studies have found that both post-PCI FFR value and absolute or relative FFR gain after PCI are significantly associated with improvement of angina severity, quality of life, and future prognosis after revascularization (9,10,12). In addition, recent reports have consistently shown the clinical and prognostic implications of NHPRs in post-PCI physiologic assessment (13)(14)(15)(16).
Achievement of optimal physiological results after PCI should be considered as a fundamental goal of functionally optimized revascularization. Moreover, researchers have tried to characterize disease patterns of coronary atherosclerosis prior to PCI (e.g., focal vs. diffuse disease) using pullback tracings of physiological indexes. Studies have found that the lesions with a major gradient or focal disease determined by pre-PCI pullback tracings have a higher probability of optimal physiological results after PCI than those with a minor gradient or diffuse disease (17)(18)(19). Therefore, this new technique may enable the prediction of expected post-PCI physiological results in the pre-PCI phase, and thereby, improve the selection of more appropriate revascularization targets that would benefit from PCI the most. These recent   Figure 1) (6)(7)(8)(9)(10)(11)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42).
Earlier studies evaluated optimal cut-off values of post-PCI FFR to predict major adverse cardiac event (MACE) in patients who underwent PCI using BMS (28)(29)(30)(31)(32). In these studies, patients with post-PCI FFR #0.90 to 0.95 showed significantly higher risk of MACE than those with higher post-PCI FFR.
The FFR Post Stent registry evaluated the largest number of patients in the BMS era and first demonstrated the continuous association of higher post-PCI FFR with lower risk of subsequent clinical events after PCI (29 (35)(36)(37)(38). Similar findings were also demonstrated in acute coronary syndrome patients excluding ST-segment elevation myocardial infarction (39).
In studies in which second-generation DES were mainly used (7)(8)(9)11,41), the optimal cut-off values of post-PCI FFR to predict TVF were slightly lower than earlier reports with BMS or mainly first-generation                In resting condition, changes in coronary flow and trans-stenotic pressure gradient after PCI are relatively stable compared with hyperemic condition (17,70). This study demonstrated that functional significance of each stenosis in tandem stenoses can be intuitively approximated by adding iFR step-up amount in pullback recording into pre-PCI iFR value without the need for measuring balloon occlusion pressure or using complex equations. This study demonstrated the significant difference between predicted post-PCI iFR and observed post-PCI iFR in real world practice. As with Kikuta et al. (70), the correlation between the predicted and observed value was modest. Residual iFR gradient across the implanted stent could be major cause of difference between predicted and observed values of post-PCI iFR. This study demonstrated that manual FFR pullback-derived dFFR(t)/dt could discriminate disease patterns into major, minor, and mixed FFR gradient group and post-PCI physiologic results (post-PCI FFR and percent FFR increase) can be predicted according to dFFR(t)/dtbased classifications. Furthermore, the results using dFFR(t)/dt were not different according to motorized pullback (1 mm/s), constant manual pullback from single center, and heterogenous pullback from multicenter registry data, which support clinical usability and generalizability of this method. Further study is warranted to evaluate the prognostic impact of dFFR(t)/dtbased treatment strategy.      has re-emphasized the value of optimal medical treatment in patients with SIHD (19). However, the use of physiology-guided revascularization in the ISCHEMIA trial was relatively low (20.3% of initial invasive strategy arm and 9.3% of the total trial population). Because part of the relative superiority of optimal medical treatment resulted from higher periprocedural myocardial infarction rates in the revascularization arm, better planning and guidance of PCI with physiological assessment might have resulted in lower rates of that endpoint. This hypothesis is supported by the marked reduction in periprocedural myocardial infarction noted in SYNTAX II, a physiology-based revascularization trial, compared with the original SYNTAX study in which revascularization was mostly performed by angiographic planning (20). Furthermore, it should be noted that no previous study, including the ISCHEMIA trial, evaluated comparative prognosis between functionally optimized revascularization and optimal medical treatment. As discussed in the previous text, angiographically successful PCI does not necessarily result in functionally optimized PCI, which was consistently shown to have significantly better prognosis than functionally suboptimal PCI. Whether "ischemiaresolving PCI" would enhance patient prognosis still needs further clarification through future trials. Whether procedural planning guided by pre-PCI pullback analysis or further intervention guided by post-PCI physiological assessment will lead to improved clinical outcomes awaits the results of randomized clinical trials.

HIGHLIGHTS
Post-PCI physiological assessment provides information about the functional results of revascularization and prognosis after PCI.
Relative contribution of disease burden in stented and nonstented segments determines the post-PCI physiological indexes and physiological gain from PCI.
Practical pitfalls of post-PCI FFR or NHPRs should be considered.
Pre-PCI pullback analysis to characterize the coronary atherosclerotic disease patterns enables better identification of the revascularization target.