Expert consensus statement on the use of fractional flow reserve, intravascular ultrasound, and optical coherence tomography

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Abstract

The rationale for use of intracoronary physiology assessment and imaging arises from the limitations of coronary angiography, the traditional method for determining the severity of coronary stenoses. The visual assessment of percent diameter reduction has significant interobserver variability 1-3, even among experienced angiographers 4. Computer-assisted quantitative coronary angiography only marginally improves diagnostic accuracy and its estimate of functional significance 5. Fractional flow reserve (FFR) is used to determine the functional significance of a coronary stenosis 6. Intravascular ultrasound (IVUS) offers excellent visualization of intraluminal and transmural coronary anatomy. Optical coherence tomography (OCT) further improves vascular visualization. There is now persuasive evidence regarding intracoronary diagnostic lesion assessments using physiology and anatomy. These adjunctive diagnostic procedures may influence the decision for coronary revascularization, guide the performance of percutaneous coronary interventions (PCI), and optimize procedural outcomes. There are substantial long-term outcome data showing benefit associated with FFR-guided decision-making. However, these techniques are underutilized in contemporary practice: the rates of use of IVUS and FFR during PCI for intermediate coronary stenoses (40–70% diameter stenosis) are 20.3% and 6.1% respectively 7. In 2011, the ACCF/AHA/SCAI PCI guidelines 8 assigned levels of evidence for the use of these modalities in various clinical situations (Table 1). The purpose of this consensus statement is to review recent studies, to develop a consensus of how these procedures are best utilized in practice, and to support their incorporation into guideline and appropriate use documents. A trans-lesional functional assessment is an important adjunct to coronary angiography for providing an objective evaluation of stenosis severity. FFR is the ratio of mean distal coronary pressure (Pd) to mean aortic pressure (Pa) during maximum hyperemia, usually induced by adenosine i.c. bolus or i.v. infusion, and represents the percentage of normal flow across a coronary stenosis. If the patient has active obstructive airways disease, i.c. adenosine can be used safely instead of IV adenosine. Alternative pharmacologic agents include nitroprusside, dobutamine, and regadenoson. Physiologic stenosis assessment by FFR is a lesion-specific index of epicardial conductance, which is independent of the microvasculature and hemodynamic changes induced by variations in heart rate, blood pressure or myocardial contractility. The FFR threshold for detecting ischemia has been corroborated by multiple tests for myocardial ischemia and reflects the functional significance (i.e. ischemic potential) of an epicardial stenosis. To establish an ischemic threshold, FFR was validated in patients with single vessel intermediate lesions and compared with the combination of three different noninvasive stress tests 9. FFR was first validated using a cutoff value of 0.75. With further experience with the technique, investigators appreciated that by extending the cutoff value to 0.80, the sensitivity of FFR could be improved without greatly compromising the specificity. For this reason, a cutoff value of ≤0.80 was used in FAME 1 and FAME 2 and shown to be clinically valid. This is now the recommended ischemic reference standard for the invasive assessment of myocardial ischemia 10 (Fig. 1). Three prospective randomized trials have demonstrated the clinical utility of FFR. To determine the safety of deferring PCI based on nonsignificant FFR, the Percutaneous Coronary Intervention of Functionally Non-significant Stenosis (DEFER) Study 12 randomized 181 patients with stable ischemic heart disease (SIHD) with FFR ≥0.75 across an intermediate stenosis to PCI or to deferral of PCI with medical treatment. At 5-year follow-up, the deferred group had a rate of death or myocardial infarction (MI) that was less than half the rate in the PCI group. To evaluate the utility of FFR for guiding the performance of PCI, the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial 12 randomized 1005 patients with multivessel disease (including SIHD, unstable angina, and NSTEMI) to either FFR-guided PCI or to angiography-guided PCI. The primary outcome, the composite rate of death, MI, or repeat revascularization at 1 year, was significantly lower (13.2% vs. 18.3%, P = 0.02) in patients who received FFR-guided PCI (Fig. 2). This was due to non-significant reductions in each component of the primary endpoint and a significant reduction in the combined rate of death or MI (7.3% vs. 11.1%, P = 0.04) in the FFR-guided group. At 2-year follow-up, the combined rate of death and MI remained significantly lower. An economic evaluation verified that FFR-guided PCI is a cost-saving strategy 13, with significantly fewer stents deployed and significantly less contrast media used. Additionally, patients treated with the FFR-guided strategy had similar rates of freedom from angina compared with the angiography-guided strategy. To compare outcomes in ischemia-guided PCI with medical therapy, the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) trial 14 randomized 888 patients with single or multivessel SIHD to FFR-guided PCI with optimal medical therapy or optimal medical therapy alone. The key difference between FAME 2 and other studies evaluating PCI for SIHD, such as COURAGE 15, is that to be included in the randomized portion of FAME 2, patients had to have at least one lesion with FFR ≤0.80. Enrollment in FAME 2 was stopped early because there was a highly significant difference in the primary endpoint of death, MI and urgent revascularization favoring the FFR-guided PCI arm. This was due to a significantly greater rate of urgent revascularization in the medical therapy arm (11.1% vs. 1.6%, P 70% (sensitivity = 96.8%, specificity = 83.9%) had the best cutoff values for a FFR 0.90. In a study of 55 intermediate LMCA lesions, an MLA 6.0 mm2 identified patients at low risk for adverse events with deferred revascularization 32. A prospective application of these criteria was tested in the LITRO study 62. LMCA revascularization was performed in 90.5% (152 of 168) of patients with an MLA 6 mm2. In a 2-year follow-up period, cardiac death-free survival was 97.7% in the deferred group versus 94.5% in the revascularized group (P = ns), and event-free survival was 87.3% versus 80.6%, respectively (P = ns). At 2-year follow-up, only eight (4.4%) patients in the deferred group required subsequent LMCA revascularization, none of who had an MI. Thus, it is safe to defer LMCA revascularization with MLA >6 mm2. Additionally, the data confirms that MLA2.9 mm2 had an FFR 0.80. FFR measurement of the culprit vessel in a patient with an acute ST segment elevation myocardial infarction or any unstable acute coronary syndrome presentation should not be performed. IVUS is an accurate method for determining optimal stent deployment (complete stent expansion and apposition and lack of edge dissection or other complications after implantation), and the size of the vessel undergoing stent implantation. IVUS can be used to appraise the significance of LMCA stenosis and, employing a cutoff MLA = 6 mm2, assess whether revascularization is warranted. IVUS can be useful for the assessment of plaque morphology. IVUS measurements for determination of non-LMCA lesion severity should not be relied upon, in the absence of additional functional evidence, for recommending revascularization. of optimal stent deployment and lack of edge with improved resolution compared with IVUS. OCT can be useful for the assessment of plaque morphology. OCT should not be performed to determine stenosis functional The writing group with guidelines that these modalities are not indicated when imaging and angiographic data are or when the result of the additional procedure will not the treatment strategy or of stent implantation.

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