Coronary angiography has been the gold standard for assessment of coronary artery disease (CAD) and guidance for percutaneous coronary interventions (PCI). However, coronary angiography is limited by its inability to provide information regarding the physiological significance of a given stenosis. The FAME (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation) and FAME 2 trials showed that routine measurement of fractional flow reserve (FFR) in patients with multivessel CAD undergoing PCI significantly reduced the mortality and incidence of myocardial infarction at 2 years compared with standard angiography-guided PCI (1, 2). Furthermore, physiology–guided PCI has shown increased safety and efficacy, improved resource utilization, and better clinical outcomes in patients with stable angina and acute coronary syndromes (3). Currently the most common methods to assess the functional severity of a coronary stenosis are either invasive techniques, including wire-based techniques [i.e., fractional flow reserve (FFR), instantaneous wave-free ratio (iFR, Philips, The Netherlands), diastolic hyperemia-free ratio (DFR, Boston Scientific Inc., Marlborough, Massachusets, USA), resting full-cycle ratio (RFR, Abbott, Chicago, Illinois, USA)], and non-wire-based techniques [angiography-derived FFR (vFFR, Pie Medical Imaging, The Netherlands; QFR from QAngio XA, Medis, The Netherlands; FFR_angio, CathWorks, Isarel)] or non-invasive techniques (FFR-computed tomography; FFR_CT, HeartFlow, Redwood City, CA, USA).

The three cases presented and discussed in this report illustrate the strengths and weaknesses of the above-mentioned invasive and non-invasive methods for the hemodynamic assessment of CAD. The cutoff value for a hemodynamically significant coronary stenosis is ≤ 0.80 for wire-based FFR, angiography-derived FFR and FFR_CT and ≤ 0.89 for iFR.

Increasing evidence strongly suggests that presence of ischemia should help guide treatment rather than just anatomic assessment (4). Coronary angiography is limited by its ability to assess the hemodynamic significance of a given stenosis. The use of FFR to guide revascularization in patients with angina and angiographically intermediate stenoses is a Class I recommendation according to the 2021 guidelines endorsed by the major cardiovascular societies worldwide (5, 6). Despite the clinical benefits and Class I recommendation for using invasive physiology to guide coronary revascularization, its utilization in cardiac catheterization laboratories has been low due to high costs, procedural complications, contrast use and adenosine-related contraindications (Table 1) (7). Alternatively, phase-specific indices, like iFR, are equally favorable with reduced procedural times and avoidance of the adenosine-related discomfort and adverse events (8, 9). However, both hyperemic indices (FFR) and resting indices (e.g., iFR) may result in complications related to their invasive nature (e.g., coronary dissection and perforation). Non-invasive (FFR_CT) and invasive wire-free techniques (angiographic FFR) have demonstrated comparable predictive values to FFR and iFR in determining functionally obstructive CAD with no wire-related risks, and reduced cost, contrast, and radiation exposure (10–12).

FFR_CT is based on the application of computational fluid dynamic analysis to a CCTA dataset under maximum computationally simulated hyperemia. FFR_CT is cost-effective and has lesser complication rates, thus decreasing the need for invasive coronary angiography (Table 1) (13, 14). FFR_CT has been noted to correlate very well with the reference standard invasive indices (i.e. FFR, iFR) (15). The biggest advantage of FFR_CT is that on top of the hemodynamic assessment of a given stenosis, it provides useful information on plaque morphology, and identification of high-risk plaques, which are the precursors of a significant portion of acute coronary syndromes (12). However, FFR_CT requires high quality CCTA images which are difficult in patients with large body habitus and suboptimal heart rates. Furthermore, FFR_CT might provide suboptimal results in cases with motion artifact or noise, severe coronary calcifications and prior stents.

Angiography-derived FFR software uses coronary angiography to calculate the pressure drop across the anatomical stenoses (Table 1). Multiple clinical trials including, the FAST I, FAVOR, and FAST-FFR study have validated the accuracy, reliability, and reproducibility of different angiography-derived FFR softwares, i.e., vFFR, QFR and FFR_angio, respectively (16–19). Angiography-derived FFR has consistently shown similar accuracy to the pressure wire–based FFR in large prospective trials and cohort studies (20). Angiography-derived FFR is an easier and potentially faster method for physiology-guided assessment of coronary vessels compared to wire-based techniques (17, 21). However, angiographic FFR requires high-quality angiography in specific orthogonal views without any vessel overlap. This high-quality imaging would be difficult in severely tortuous and very small caliber vessels, obese patients, and patients with chronic kidney disease where contrast use is limited (20).

Newer non-wire based modalities are being increasingly studied. For example, myocardial blush grade reserve has been noted to closely correlate with FFR (22). As technology evolves, invasive wire-free (angiographic FFR) and non-invasive (FFR_CT) modalities for the hemodynamic assessment of the CAD, appear to provide reliable and user-friendly alternatives to the gold standard invasive wire-based techniques. Interventional cardiologists and cardiovascular healthcare providers should be familiar with the strengths and weaknesses of the available hemodynamic assessment modalities.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

Written informed consent was obtained fromthe participants for the publication of this case report.

GG involved with the management of the patients and leading the write up of the manuscript. SS made significant contributions to writing the manuscript and proofreading. CH involved with processing of coronary CT and FFT CT images. YSC involved directly in treating the patient, mentored, and made suggestions in the preparation of the manuscript. All authors contributed to the article and approved the submitted version.

YSC has speaker honoraria, advisory board fees and a research grant from Boston Scientific Inc. and a research grant and advisory board fees from Medtronic Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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