Can Coronary Flow Reserve After Stenting Be a Useful Predictor of Target Vessel Failure?

Ischemic heart disease remains the leading cause of death worldwide,¹ but recent randomized control trials have shown lack of superiority of revascularization over conservative strategies for treating chronic coronary syndrome (CCS).^2,3 Reducing the incidence of postoperative target vessel failure (TVF) is a major challenge for revascularization strategies, and it is still not well understood which patients are at higher risk after a revascularization procedure. Risk stratification with coronary physiology would allow clinicians to tailor management strategies more effectively, with the aim of reducing subsequent cardiovascular events in high-risk individuals.

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After percutaneous coronary intervention (PCI), the fractional flow reserve (FFR) is a prognostic marker for adverse events. In a recent meta-analysis, low post-PCI FFR was found to be common, and demonstrated a significant and inverse association with TVF.⁴ Post-PCI FFR is greatly influenced by pre-PCI conditions such as lesion location, lesion morphology and the pattern of coronary artery disease (focal vs. diffuse).^5,6 Currently, there is considerable interest in predictive models of post-PCI FFR (e.g., the pullback pressure gradient [PPG]).⁷

Coronary flow reserve (CFR) is another coronary hemodynamic parameter, reflecting both the epicardial vessels and the microvascular conditions. This parameter quantifies the ability of the coronary circulation to enhance blood flow under increased demand. Accumulated evidence from both invasive and noninvasive diagnostic methods suggests that a well-preserved CFR is associated with a favorable prognosis, whereas a diminished CFR is associated with an elevated risk of adverse outcomes, including death.⁸

FFR and CFR offer integrative insights into the coronary circulation, and their combined assessment enables comprehensive characterization of pathophysiology based on epicardial and microvascular functions. Moreover, the combined evaluation of FFR and CFR is reported to have significant clinical implications for the outcomes in patients with CCS (Table).^9–12 Those studies found that a combination of low FFR and low CFR poses the highest risk for TVF. Among lesions exhibiting normal FFR, low CFR presented an increased risk of TVF compared with normal CFR. Such findings underscore the incremental value of CFR in risk stratification for lesions with a normal FFR, particularly when PCI has not been conducted. However, the prognostic value of CFR in the post-PCI setting is not known.

Table.

Summary of FFR/CFR Combined Assessment Studies

	Van De Hoef et al9	Lee et al10	Johnson et al12	Van De Hoef et al11
Year	2014	2018	2021	2022
Patients, n	157	519	351	2,143
Vessels, n	157	737	433	2,725
Method for CFR	Doppler	Thermodilution	Doppler	Thermodilution or Doppler
FFR/CFR discordance	37%	31%	37%	34%
Follow-up duration, years	11.7	5.1	2.0	2.9
TVF
FFR >0.8, CFR ≥2.0	27%	2.9%	3.0%	5.2%
FFR >0.8, CFR <2.0	80%	9.8%	6.7%	14.2%
FFR ≤0.8, CFR ≥2.0	40%	9.9%	9.6%	17.6%
FFR ≤0.8, CFR <2.0	52%	17.6%	NAa	25.2%
Incidence of TVF

^aExcluded since revascularization as per protocol. CFR, coronary flow reserve; FFR, fractional flow reserve; TVF, target vessel failure.

This context sets the stage for the paper under discussion in this issue of the Journal.¹³ By exploring the relatively uncharted territory of post-PCI CFR assessment, this research provides important insights that deserve attention. Moreover, post-PCI CFR assessments are rarely performed in routine clinical practice, making this report particularly valuable to the medical community.

Ueno et al¹³ conducted a post-hoc pooled analysis of previously published registry data. A total of 466 patients with CCS and single-vessel disease underwent both FFR and CFR measurements after PCI. This approach allowed the investigators to capture residual epicardial disease and the microcirculatory status after PCI. During the median follow-up period of 4.2 years, 10.3% of patients experienced TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. Both post-PCI FFR and post-PCI CFR were associated with the occurrence of TVF. Notably, among the patients with low post-PCI FFR, those with low CFR demonstrated a significantly higher risk of TVF than those with normal CFR. This study highlights the incremental prognostic value of post-PCI CFR in addition to post-PCI FFR.

Nevertheless, CFR results should be interpreted judiciously, especially after PCI. Although FFR shows robust reproducibility, CFR’s reproducibility remains limited.¹⁴ CFR is defined as the ratio of maximal (hyperemic) coronary flow to resting coronary flow. Measuring resting coronary flow, especially immediately after PCI is challenging, as this quantity may be influenced further by submaximal reactive hyperemia secondary to vessel manipulation and PCI-induced left ventricular stunning.¹⁵ Excluding the epicardial component, low post-PCI CRF points to microvascular disease being either present before PCI or induced by the procedure. In any case, the lack of increase in blood flow after PCI was strongly associated with adverse outcomes.

Future Perspectives

Several key questions regarding the acquisition, interpretation, and response to post-PCI CFR remain unanswered, and include determining the specific patient population that would benefit most from post-PCI CFR measurements, identifying the factors that contribute to optimal post-PCI CFR values (e.g., baseline characteristics, disease pattern, and procedural aspects), understanding potential enhancement strategies for post-PCI CFR, and deciding on the appropriate course of action when faced with suboptimal post-PCI CFR outcomes.

In conclusion, further studies are required to fully understand post-PCI CFR. Our goal is to develop a comprehensive understanding of post-PCI CFR, and we are just beginning to get there.

Funding

None.

Disclosures

T.A. is a member of Circulation Journal’s Editorial Team.

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