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21 June 2026

15 Pages

Intravascular Imaging Versus Physiology Assessment for Intermediate Lesions During PCI

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1
School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 106 79 Athens, Greece
2
Department of Cardiology, “Tzaneio” General Hospital of Piraeus, 185 36 Piraeus, Greece
3
Division of Cardiovascular Health and Disease, University of Cincinnati Medical Center, Cincinnati, OH 45219, USA
4
Women’s Heart Center, The Christ Hospital Heart and Vascular Institute, Cincinnati, OH 45219, USA
Biomedicines2026, 14(6), 1397;https://doi.org/10.3390/biomedicines14061397
This article belongs to the Section Biomedical Engineering and Materials
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Abstract

Coronary artery disease (CAD) is the leading cause of mortality, with percutaneous coronary intervention (PCI) constituting the gold standard treatment. However, in an important proportion of the cases, lesion severity is debatable since conventional angiography provides only a two-dimensional representation of the vessel lumen and fails to quantify ischemic significance or plaque morphology. In these cases, several adjunctive tools considering physiology and imaging guidance may assist in quantifying the severity of the disease. Imaging modalities such as intravascular ultrasonography (IVUS) and optical coherence tomography (OCT), as well as physiology such as fractional flow reserve (FFR) and instantaneous wave-free (iFR), revolutionized revascularization strategy by linking anatomical stenosis to its functional consequence on myocardial perfusion. The present review summarizes and contrasts the available evidence for physiology and imaging guidance, considering the assessment of intermediate lesions during PCI and providing insights for their use in specific lesion subsets.

1. Introduction

In patients with coronary artery disease (CAD), the degree of luminal narrowing, plaque characteristics and the physiologic significance of the lesion are prognostic indicators [1,2]. Conventional angiography provides only a two-dimensional representation of the vessel lumen and fails to quantify ischemic significance or plaque morphology. Imaging modalities such as intravascular ultrasonography (IVUS) and optical coherence tomography (OCT) are commonly used adjunctive techniques that can provide detailed anatomical information about the lumen, vessel, and plaque distribution. Both modalities can be used during the PCI procedure to aid in stent placement and minimize stent-related issues [3]. Several trials and meta-analyses presented improved clinical outcomes, with imaging-guided PCI compared with sole angiography-guided PCI [4,5,6,7]. Physiology, on the other hand, such as fractional flow reserve (FFR) and instantaneous wave-free (iFR), introduced as pressure-derived indexes of lesion-specific ischemia, revolutionized revascularization strategy by linking anatomical stenosis to its functional consequence on myocardial perfusion [8]. FFR is defined as the maximal blood flow to the myocardium in the presence of a stenosis in the supplying coronary vessel, divided by the theoretical normal maximal flow in the same distribution. This index constitutes the fraction of the normal maximal myocardial flow that can be achieved despite the coronary stenosis. The normal value of the index is 1.0, regardless of the patient or the specific vessel studied [9]. FFR values of less than 0.75 identify functionally important stenoses [10]. The same concept applies to iFR but without the need for hyperemia to induce ischemia. Numerous trials have shown that FFR- and iFR-guided PCI is associated with fewer clinical events than angiography-guided PCI and medical treatment [11,12,13,14,15].
Although the basic concepts underlying the use of physiology and imaging during PCI differ between each other, both are the most commonly used adjunctive tools in the diagnosis and treatment of CAD during cardiac catheterization. The present review summarizes and contrasts the available evidence for physiology and imaging guidance, focusing on head-to-head comparative studies, and discusses their respective significance across the spectrum of chronic and acute coronary syndromes. Understanding their relative advantages, limitations, and clinical contexts of each modality is essential for tailoring individualized revascularization strategies in the era of precision coronary intervention.

2. Invasive Physiological Assessment in Coronary Stenosis

Invasive physiological assessment has become a cornerstone in the evaluation and management of coronary artery disease (CAD), offering functional information that cannot be reliably obtained from angiography alone. The clinical rationale for performing physiological measurements during coronary catheterization is particularly strong in the context of intermediate lesions (~60–70% diameter stenosis), in which angiographic severity correlates poorly with hemodynamic significance. Physiological assessment enables identification of ischemia-producing lesions, reduces unnecessary revascularization, informs PCI strategy, and improves both procedural and long-term outcomes. Over the past two decades, indices such as fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and resting full-cycle ratio (RFR) have demonstrated substantial diagnostic and prognostic value, contributing significantly to contemporary revascularization practice [16,17,18,19,20,21,22,23,24].
FFR quantifies the ratio of maximal blood flow in a stenotic artery to the theoretical maximal flow if the vessel were normal. Achieving this requires pharmacologically induced hyperemia, most commonly using adenosine, to minimize microvascular resistance and maximize coronary flow [22,23,24]. Pressure-sensitive guidewires measure the distal coronary pressure (Pd) relative to aortic pressure (Pa), and FFR values ≤ 0.80 typically indicate hemodynamically significant stenosis [23,24]. Extensive evidence supports the prognostic and therapeutic utility of FFR-guided PCI. Randomized trials and meta-analyses demonstrate that FFR-guided revascularization reduces unnecessary stenting, lowers periprocedural complication rates, and improves long-term outcomes in stable CAD [22,23,24]. Beyond percutaneous treatment, FFR has also found utility in surgical planning for coronary artery bypass grafting (CABG), particularly for selecting optimal graft targets and improving long-term graft patency [21].
iFR was developed to overcome limitations associated with FFR, primarily the need for pharmacologic hyperemia. By measuring the pressure ratio during the diastolic wave-free period—when microvascular resistance is naturally minimized—iFR eliminates the need for vasodilators, reduces procedural time, and improves patient comfort [20]. Multiple studies have confirmed a strong correlation between iFR and FFR, although discordance may occur in patients with microvascular dysfunction or borderline lesions [17,18,19,20]. These characteristics have contributed to the widespread adoption of iFR in routine clinical use [16,17,18,19,20]. Hybrid strategies combining resting indices with FFR have further improved diagnostic accuracy and procedural efficiency, particularly in cases in which iFR results fall within a gray zone [25,26,27].
RFR represents another non-hyperemic physiological index, calculated as the lowest distal-to-aortic pressure ratio across the entire cardiac cycle [19,20]. Similar to iFR, RFR correlates strongly with FFR and provides an alternative assessment in patients for whom hyperemia is contraindicated [17,18,19,26]. Evidence suggests that RFR-guided revascularization yields outcomes comparable to those obtained with FFR; however, discrepancies may arise in the presence of microvascular dysfunction or in acute coronary syndromes (ACSs), necessitating careful interpretation [16,18,19,28]. Although RFR has shown good correlation with established physiological indices such as FFR and iFR, its evidence base remains comparatively limited, particularly regarding randomized clinical outcome data. This limitation is even more pronounced in ACSs, where the influence of microvascular dysfunction further restricts validation, and therefore RFR should not yet be considered equivalent to FFR or iFR in terms of clinical evidence and guideline-supported application.

2.1. Comparative Evidence for Intermediate Lesions Based on Physiology

In CCS, extensive evidence confirms that FFR-guided PCI is superior to angiography-guided management for reducing major adverse cardiovascular events (MACE), unnecessary stent placement, and long-term complications [22,23,24]. In the specific context of intermediate stenoses (~60–70%), FFR provides reliable discrimination between ischemia-producing and non-flow-limiting lesions. Several comparative studies have demonstrated that non-hyperemic indices, including iFR and RFR, achieve similar diagnostic performance in stable disease settings [16,17,20,26].
Additional studies such as the FiGARO trial [26] have examined sources of discordance between FFR and iFR and found that diffuse disease and microvascular dysfunction are primary contributors—situations highly relevant for borderline lesions [27]. Beyond this, large randomized trials have confirmed the long-term safety and efficacy of non-hyperemic indices in CCS. The iFR-SWEDEHEART trial was a multicenter, randomized study that compared iFR with fractional flow reserve (FFR) for guiding coronary revascularization in patients with stable angina or acute coronary syndromes. A total of 2037 patients with intermediate coronary stenoses were randomized to iFR- or FFR-guided PCI, using cut-off values of ≤0.89 for iFR and ≤0.80 for FFR; it was demonstrated that iFR-guided PCI was non-inferior to FFR-guided PCI for the composite endpoint of MACE over a 5-year follow-up, with similar rates of death, myocardial infarction, and repeat revascularization. Similarly, the DEFINE-FLAIR trial analyzed a total of 2492 patients with intermediate coronary lesions who were randomized to iFR- or FFR-guided strategies. It showed that iFR-based decision-making led to comparable long-term clinical outcomes to FFR-guided strategies, while additionally reducing the need for adenosine administration and procedural time [29,30]. These data support a pragmatic approach in CCS: non-hyperemic indices may be used for initial assessment in isolated intermediate lesions, with hyperemic confirmation recommended for gray-zone or anatomically complex lesions [25,26,27]. Limitations of the current evidence include methodological heterogeneity, inconsistent definitions of intermediate stenosis, and variable operator thresholds for physiological testing, all of which should be considered when interpreting study findings.
In ACS, physiological assessment poses specific challenges related to dynamic microvascular dysfunction, inflammation, and transient vasomotor disturbances, all of which may alter pressure-derived indices [18,19,28]. Although FFR remains the reference standard in ACS for assessing non-culprit lesions, early measurements may be affected by microvascular obstruction. Resting indices such as iFR and RFR may underestimate lesion severity in ACS conditions, contributing to higher rates of discordance with FFR [18,19,28]. Studies including Trøan et al. [28] have demonstrated that microcirculatory impairment significantly affects RFR measurements, reinforcing the need for caution. Additionally, studies indicate that microvascular “stunning” immediately post-ACS can transiently reduce hyperemic response, limiting FFR reliability and causing dynamic changes in coronary flow and microvascular resistance over the first 24 h post-PCI [31]. Comparative analyses consistently show that non-hyperemic indices have reduced reliability immediately following ACS, particularly for intermediate (~60–70%) lesions. Consequently, when resting indices yield borderline or discordant results, confirmatory hyperemic assessment is recommended, or physiological evaluation may be deferred until microvascular recovery if clinically acceptable [18,19,28].

2.2. Limitations of Physiological Indices

Despite their demonstrated value, all physiological indices have inherent limitations. FFR requires administration of hyperemic agents, which may cause discomfort and are contraindicated in patients with severe asthma, hypotension, or conduction disturbances [22,23]. Resting indices (iFR and RFR) avoid hyperemia but may be influenced by heart rate variability, diffuse atherosclerosis, or microvascular dysfunction, leading to occasional discordance with FFR [16,18,19]. Technical variables such as wire drift, calibration errors, and operator experience also affect accuracy [22,25]. Complex lesions, including left main stenosis, tandem lesions, and diffuse disease, remain challenging for pressure-based methods, reinforcing the need for individualized assessment strategies [19,22,32]. A hybrid diagnostic model—using resting indices for initial screening and FFR for borderline or complex lesions—is increasingly favored and supported by clinical evidence [25,26,27]. FFR remains particularly advantageous in complex anatomy, gray-zone resting-index values, and ACS with suspected microvascular dysfunction [17,19,26,28].

3. Intravascular Imaging (IVUS and OCT)

Intravascular imaging complements physiological assessment by providing high-resolution structural evaluation of the coronary arterial wall, plaque morphology, and stent–vessel interactions. IVUS and OCT share the objective of improving procedural planning and outcomes but differ notably in their imaging principles, resolution, and penetration capabilities.
IVUS employs high-frequency ultrasound (20–60 MHz) to provide 360° vessel wall visualization with axial resolution of 80–150 µm and penetration of 4–8 mm [33]. This allows comprehensive assessment of vessel dimensions, external elastic membrane boundaries, plaque burden, remodeling patterns, and detection of calcified or fibrotic lesions that may influence stent expansion. IVUS can assess minimal lumen area (MLA) and plaque composition, facilitating evidence-based decisions regarding the need for revascularization in intermediate lesions. IVUS is particularly valuable for assessing complex coronary anatomies, including bifurcation lesions, left main disease, and diffuse atherosclerosis, as it allows accurate sizing of stents, optimization of deployment, and reduction in malapposition. Additionally, it provides guidance in evaluating stent under-expansion, edge dissections, and late stent complications, which are major contributors to restenosis and stent thrombosis [33,34,35].
OCT uses near-infrared light to achieve superior axial resolution (10–20 µm), though penetration is limited to 1–2 mm and requires transient displacement of blood with contrast or saline [4,36]. OCT excels in characterizing superficial plaque components, including thin-cap fibroatheromas, lipid-rich cores, calcification patterns, macrophage infiltrates, thrombus, microchannels, and neovascularization [37,38]. OCT is particularly useful in acute coronary syndromes (ACSs), allowing precise identification of plaque rupture, erosion, or calcified nodules, which can inform timing and strategy for PCI. OCT also enables high-resolution assessment of stent apposition, tissue prolapse, strut coverage, and thrombus burden, facilitating immediate intraprocedural optimization and reducing the risk of adverse outcomes [37,39,40]. Moreover, it is essential in the evaluation of non-culprit lesions in cases of multivessel disease. By integrating detailed morphological information with clinical and procedural data, OCT may support increasingly personalized post-infarction management, including tailored antithrombotic, lipid-lowering, and anti-inflammatory therapies [41].
Randomized trials such as IVUS-XPL and ULTIMATE have demonstrated that IVUS-guided PCI significantly reduces MACE, stent thrombosis, and target vessel revascularization compared with angiography-guided PCI [4,34,36]. Large meta-analyses including more than 18,000 patients confirm reductions in all-cause mortality, cardiac death, MACE, and repeat revascularization with imaging-guided PCI [33]. OCT-guided trials, including ILUMIEN I–III and OCTIVUS, have shown improved stent optimization, reduced procedural complications, and outcomes comparable or superior to IVUS, particularly in ACS and complex lesion subsets [39,40,42]. Moreover, OCT provides mechanistic insight into lesion morphology that explains physiological discordance between FFR/iFR and anatomical severity, aiding in more precise, patient-tailored intervention strategies. IVUS and OCT are most effective when used in conjunction with physiological indices (FFR, iFR, and RFR). Imaging can clarify ambiguous functional measurements, detect focal versus diffuse disease, and guide stent sizing and optimization in lesions that demonstrate intermediate or borderline physiological significance. Hybrid approaches—using initial non-hyperemic or hyperemic physiological assessment followed by intravascular imaging for complex or gray-zone lesions—have been shown to improve procedural outcomes, reduce adverse events, and provide both mechanistic and prognostic information in real-world cohorts [4,34,35,36,37,38,43,44].

3.1. Comparative Evidence for Intermediate Lesions Based on Imaging

In intermediate lesions, intravascular imaging offers diagnostic and therapeutic advantages that complement physiological measurements. Imaging assists in distinguishing anatomic features and clarifies the true significance of coronary lesions in both chronic coronary syndrome (CCS) and acute coronary syndrome (ACS). In CCS, IVUS and OCT improve the assessment of lesion severity by identifying positive remodeling, plaque burden, and complex morphology that may appear severe angiographically but are not necessarily hemodynamically significant. In ACS, intravascular imaging additionally characterizes plaque pathology—such as rupture, erosion, calcified nodules, or thrombotic components—which can influence both the indication for PCI and the choice of interventional strategy. IVUS quantifies vessel dimensions and plaque burden, whereas OCT provides detailed plaque phenotyping, including fibrous, lipid-rich, calcified, or thrombotic features [29,32,35,36,40]. The use of intravascular imaging can also provide important insights in otherwise difficult cases where physiology is lagging. More particularly, it can identify cases of diffuse disease, significant calcification, or large luminal dimensions and explain discrepancies between resting indices and FFR. The FORZA trial [44] and the study by Yang et al. [43] highlight the complementary roles of physiology and intravascular imaging in the assessment of intermediate coronary stenoses. FORZA demonstrated that FFR-based guidance safely reduces the need for revascularization, whereas OCT-guided management leads to more frequent PCI and improved symptom control. In contrast, the large-scale analysis by Yang et al. showed comparable clinical outcomes between FFR- and IVUS-guided strategies while identifying IVUS-derived anatomical thresholds (e.g., MLA and plaque burden) that refine risk stratification for both deferred and treated lesions. Together, these findings support an integrated approach in which physiological assessment guides the decision to revascularize, and intravascular imaging optimizes lesion characterization and procedural results. Intravascular imaging may also assist the operator and guide the stenting technique. IVUS-guided stent sizing and expansion correlate with improved outcomes, as demonstrated in large-scale trials and criteria-evaluation studies [18,43]. OCT identifies malapposition, tissue prolapse, edge dissections, and thrombus burden, enabling immediate corrections that improve prognosis [37,39,40,42].
Considering ACS cases, OCT studies reveal the presence of plaque rupture in 59%, plaque erosion in 32%, and calcified nodules in 9% of culprit lesions [37]. These observations underscore the central role of intravascular imaging in defining the underlying mechanism of ACS, as angiography alone cannot reliably differentiate between rupture, erosion, or calcified nodules. Importantly, this mechanistic insight extends beyond the culprit lesion: in patients with ACS, intermediate non-culprit plaques frequently exhibit complex morphology, including large lipid pools, thin-cap fibroatheromas, or significant plaque burden, even in the absence of hemodynamically significant stenosis. Because microvascular dysfunction, diffuse disease, and dynamic changes in coronary tone can render physiological assessment unreliable in the acute setting, OCT- or IVUS-based characterization of plaque phenotype provides additional information that may influence the timing, strategy, and necessity of revascularization. Identifying high-risk morphological features in non-culprit lesions—such as thin fibrous caps, large lipid cores, macrophage accumulation, or microcalcifications—may help guide closer surveillance or staged intervention, whereas stable-appearing plaques (e.g., fibrotic or thick-cap lesions) may safely be managed conservatively. Thus, in ACS, plaque morphology assessment complements physiology and offers a more comprehensive approach to risk stratification and decision-making for intermediate lesions. This mechanistic insight is particularly relevant for intermediate non-culprit plaques, where physiology may be unreliable and plaque morphology may guide timing and need for revascularization [45,46,47,48,49].
Recent meta-analyses suggest that a more aggressive imaging-guided PCI strategy improves long-term outcomes without compromising procedural safety. An updated meta-analysis of 24 randomized trials including 14,037 patients demonstrated that intravascular imaging-guided PCI reduced MACE, MI, target vessel revascularization, and stent thrombosis compared with angiography-guided PCI [50]. Furthermore, a 2024 meta-analysis of OCT-guided PCI reported lower rates of cardiovascular death, stent thrombosis, and MACE despite more frequent procedural optimization maneuvers. These findings suggest that the additional interventions prompted by intravascular imaging may translate into improved long-term efficacy without an apparent increase in periprocedural complications [51].

3.2. Limitations of Imaging Indices

Given the context in which they are used, each technology has unique strengths and limitations. IVUS can provide excellent penetration for larger vessels but has lower microstructural resolution than OCT, making subtle plaque characterization less precise. OCT requires contrast injection, which may be limited in patients with renal insufficiency, and has reduced penetration in heavily calcified or large vessels. Operator experience remains a key determinant of image interpretation and clinical impact. Imaging is particularly advantageous in scenarios where angiography is insufficient, including long or complex lesions, left main and bifurcation disease, heavily calcified vessels, ACS mechanisms, and the evaluation of stent failure [4,34,35,36,43,52]. Combining physiological assessment with intravascular imaging yields the most comprehensive evaluation and supports truly patient-specific revascularization planning.
For angiographically intermediate coronary stenoses (~60–70%), a combined approach using physiological indices (FFR, iFR, and RFR) and intravascular imaging (IVUS and OCT) offers the most robust framework for clinical decision-making. FFR remains the gold standard, particularly in ACS, complex anatomy, or gray-zone resting-index scenarios. Non-hyperemic indices provide practical alternatives in stable patients and for initial triage. Intravascular imaging refines anatomic and morphological understanding, clarifies physiological discordance, and optimizes PCI outcomes. By providing detailed anatomical, morphological, and procedural guidance, IVUS and OCT enhance the precision of PCI, improve patient outcomes, and help reconcile discrepancies between functional and structural assessment. An individualized, evidence-based strategy integrating both functional and structural assessments ensures precise lesion evaluation, minimizes unnecessary interventions, and improves long-term cardiovascular outcomes.

4. Head-to-Head Comparisons

The comparative evidence between physiology-guided and imaging-guided PCI reflects two different philosophies of coronary assessment. Physiology identifies ischemia, whereas intravascular imaging characterizes plaque morphology and optimizes PCI. Although traditionally viewed as alternative strategies, the most robust evidence suggests that they are complementary to each other. PCI of intermediate size lesions has certainly undergone a paradigm shift in recent years as angiography alone frequently misclassifies intermediate lesions [13]. Specifically, on the one hand, up to 40% of angiographically intermediate lesions are not ischemic by FFR or iFR, and on the other hand, IVUS demonstrates that many stenoses judged “moderate” angiographically have large plaque burdens (>70%) indicative of high-risk morphology [13,14]. Thus, this sets the stage for comparative evaluation as each tool examines different dimensions of the same lesion.
Emerging evidence with a few studies in the past decade that compared FFR- and IVUS-guided coronary intervention strategies in patients with de novo coronary intermediate lesions is gaining attention. The very first direct comparison of physiology versus imaging-guided PCI was reported by Nam et al. back in 2010 with a comparison of FFR and IVUS [53]. It was a single-center, prospective cohort of 167 patients with intermediate lesions. The major findings in this study can be summarized as follows: (1) FFR- or IVUS-guided PCI in patients with intermediate coronary lesions was associated with favorable clinical outcomes; and (2) the rate of performed PCI in intermediate coronary lesions was much lower in the FFR-guided compared with the IVUS-guided group without any increase in adverse event rates according to established criteria [53]. The latter emphasizes a potential over-treatment tendency when IVUS is used as the primary gatekeeper [54].
The FLAVOUR trial represents the largest and most definitive head-to-head comparison to date. This multicenter RCT enrolled 1682 patients with angiographically intermediate stenoses (40–70%) and randomized them to FFR-guided or IVUS-guided PCI strategies [55]. At the 24-month follow-up, no significant difference was observed in hard clinical outcomes between FFR-guided and IVUS-guided PCI. PCI was performed significantly less often in the FFR group [55], confirming the already existing evidence [44,53,56]. Overall, the FLAVOUR trial emphasized the clinical non-inferiority of FFR guidance when compared to IVUS, as well as its role in deferring unnecessary interventions. The FLAVOUR II trial extended this comparison to involve angiography-derived FFR (AngioFFR), a specific wire-free physiology index derived from coronary angiography [57]. Approximately 1800 patients were randomized to AngioFFR-guided or IVUS-guided strategies. The primary endpoint (death, MI, or revascularization at 12 months) was similar between groups, with AngioFFR again yielding fewer PCIs and shorter procedural times. The study reinforced the fact that noninvasive physiology can match imaging in safety and efficacy in relatively stable patients with angiographically intermediate stenoses.
However, both studies revealed important nuances. First, in non-ischemic lesions, IVUS sometimes recommended PCI due to large plaque burden or ambiguous lumen loss, whereas in physiologically positive lesions, the IVUS-derived external elastic membrane (EEM) diameter frequently upstaged stent size compared to angiography or physiology-guided sizing. Thus, the existing comparative evidence of imaging vs. physiology-guided PCI suggests a strategic divergence rather than a superiority contest.
As to comparisons between OCT and FFR, robust data from large multicenter trials are lacking. However, in a single-center randomized study, the use of OCT was safe, causing a larger number of PCIs, but was also associated with a lower occurrence of the combined endpoint of MACE and significant angina, whereas FFR was associated with a higher rate of medically treated patients and lower costs. The conservative approach of patients in this trial with angiographically intermediate stenoses when using FFR guidance showed a benefit in terms of renal preservation [44].
Both physiological and intravascular imaging techniques rely on operator dependence, requiring expertise for image acquisition, interpretation, and integration into clinical decision-making. Their widespread adoption is also constrained by additional procedural costs, variable reimbursement policies, and limited availability of specialized equipment across healthcare systems. Furthermore, dedicated training and maintenance of procedural proficiency are essential to ensure optimal use of these technologies, highlighting the need for standardized education programs and broader accessibility.

5. Physiological vs. Imaging Guidance in Specific Lesion Subsets

In specific settings such as LM disease where FFR/iFR accuracy is influenced by downstream disease, imaging techniques and especially IVUS can be helpful. Although IVUS is a poor determinant of whether a stenosis requires PCI, in the case of left main coronary artery, its role is well established [58]. In bifurcation lesions where uncertainty about performing an intervention rises, physiology determines which side branches are truly ischemic [59], with imaging techniques contributing to carina shift visualization, stent malapposition, and ostial plaque identification. In an analogous fashion, imaging techniques and mainly OCT with its high-resolution capacities can characterize calcific lesions as they can penetrate calcium, evaluate calcium thickness, and identify the severity and pattern of calcium requiring additional lesion modification [60]. In diffuse stenoses throughout the entire epicardial vessels, in contrast, physiology shows superiority as it distinguishes focal vs. diffuse patterns of ischemia [61].
Thus, current practice supports combining both approaches, with physiology determining whether a lesion requires intervention and subsequently imaging tools optimizing the procedure. This integrated strategy reduces stent use while improving long-term outcomes—emerging as the standard for precision PCI. Physiological indices such as FFR, iFR, and RFR determine whether an intermediate stenosis is functionally significant and likely to benefit from revascularization, thereby preventing unnecessary interventions in lesions that do not cause ischemia. Intravascular imaging, particularly IVUS and OCT, provides detailed anatomical information regarding plaque burden, vessel dimensions, calcium distribution, and stent optimization, allowing operators to tailor PCI strategy and minimize procedural complications (Table 1).
Importantly, the relationship between ischemia and plaque vulnerability is complex and often discordant. Not all ischemia-producing lesions exhibit high-risk plaque characteristics, while some non-flow-limiting lesions may harbor features associated with future adverse events, including large plaque burden, positive remodeling, thin-cap fibroatheroma, lipid-rich plaque, or macrophage infiltration [62]. Landmark studies such as PROSPECT, COMBINE OCT-FFR, and PREVENT have demonstrated that vulnerable plaque morphology provides prognostic information beyond physiological assessment alone [62]. Consequently, physiology identifies lesions requiring treatment based on their hemodynamic significance, whereas imaging enables the characterization of the underlying substrate and the recognition of plaques at increased risk of future instability.
Table 1. Summary of the available evidence considering physiology and imaging devices.

6. Future Directions

Future directions in the assessment of intermediate coronary lesions increasingly focus on hybrid strategies that integrate intravascular imaging with physiological surrogates to provide a more comprehensive evaluation of lesion significance. Imaging-derived physiological indices, such as OCT-derived FFR and IVUS-based computational FFR, allow the estimation of lesion-specific ischemia using high-resolution anatomical data without the need for pressure wires or hyperemic agents [70]. Angiography-based techniques, including quantitative flow ratio (QFR) and its microvascular-adjusted iteration (μQFR), further simplify physiological assessment by enabling rapid, wire-free estimation of functional severity directly from routine angiographic images [71]. These approaches, particularly when combined with co-registration of imaging and angiography, have the potential to streamline PCI workflows while maintaining diagnostic accuracy, especially in patients with intermediate lesions or contraindications to hyperemia.
Concurrently, advances in intravascular imaging and pressure-based analytics are enhancing the understanding of lesion behavior beyond simple stenosis severity. Artificial intelligence-driven IVUS analysis (AI-IVUS) enables automated plaque characterization, vessel sizing, and outcome prediction, reducing operator variability and improving reproducibility. Near-infrared spectroscopy–IVUS (NIRS-IVUS) adds complementary information by identifying lipid-rich plaques, which may influence decision-making in lesions with borderline physiological significance [72,73]. Recent advancements in the diagnosis of MI with non-obstructive coronary arteries (MINOCA) highlight that although OCT remains the preferred modality for detecting subtle abnormalities, IVUS combined with NIRS may serve as a valuable alternative for identifying plaque rupture and erosion, particularly when OCT is not feasible. By providing complementary structural and compositional plaque assessment, the IVUS-NIRS approach may enhance the diagnostic evaluation of type 1 MINOCA and its underlying mechanisms [74]. In addition, novel physiological metrics such as the Pullback Pressure Gradient (PPG) provide insight into the spatial distribution of pressure loss along the vessel, helping to distinguish focal from diffuse disease and refine revascularization strategies [75]. As these technologies continue to evolve, their combined application may shift PCI guidance toward a precision-based paradigm that integrates anatomy, physiology, and plaque biology, with future randomized studies needed to define their optimal clinical implementation across both chronic and acute coronary syndromes.

7. Conclusions

In contemporary interventional cardiology, intravascular imaging and physiological indices should no longer be viewed as competing modalities, but rather as complementary tools providing distinct and synergistic information. Physiological assessment identifies the functional significance of intermediate lesions, whereas imaging characterizes plaque morphology, vulnerability, and procedural optimization. Experience and emerging evidence suggest that vulnerable plaques may not always produce ischemia, while functionally significant lesions may lack high-risk morphological features, highlighting the limitations of relying on a single modality alone. Therefore, the integration of both physiology and imaging is essential for comprehensive lesion assessment and for guiding individualized revascularization strategies in both CCS and ACS.

Author Contributions

Data Curation, M.S., A.M., A.G., N.K. and N.P.; Investigation, M.S., S.S., S.A., N.S. and A.T.; Methodology, E.K., N.S., D.T. and K.P. (Konstantinos Platanias).; Project Administration, N.P., D.T., K.T. and G.G.; Resources, N.K., M.S. and K.P. (Konstantinos Pamporis); Software, A.T., M.S. and K.P. (Konstantinos Platanias); Supervision, D.T., K.T., N.P. and E.K.; Validation, A.T., N.K., A.M. and M.S.; Visualization, G.G. and K.P. (Konstantinos Platanias); Writing—Original Draft, M.S., A.M. and S.A.; Writing—Review and Editing, M.S., A.M., S.A., S.S., A.G., K.P. (Konstantinos Platanias), A.T., N.K.; K.P. (Konstantinos Pamporis), N.S., G.G., E.K., N.P., D.T. and K.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Nicholls, S.J.; Hsu, A.; Wolski, K.; Hu, B.; Bayturan, O.; Lavoie, A.; Uno, K.; Tuzcu, E.M.; Nissen, S.E. Intravascular Ultrasound-Derived Measures of Coronary Atherosclerotic Plaque Burden and Clinical Outcome. J. Am. Coll. Cardiol. 2010, 55, 2399–2407. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  2. Johnson, N.P.; Tóth, G.G.; Lai, D.; Zhu, H.; Açar, G.; Agostoni, P.; Appelman, Y.; Arslan, F.; Barbato, E.; Chen, S.-L.; et al. Prognostic value of fractional flow reserve: Linking physiologic severity to clinical outcomes. J. Am. Coll. Cardiol. 2014, 64, 1641–1654. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  3. Mintz, G.S.; Guagliumi, G. Intravascular imaging in coronary artery disease. Lancet 2017, 390, 793–809. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  4. Hong, S.-J.; Kim, B.-K.; Shin, D.-H.; Nam, C.-M.; Kim, J.-S.; Ko, Y.-G.; Choi, D.; Kang, T.-S.; Kang, W.-C.; Her, A.-Y.; et al. Effect of Intravascular Ultrasound–Guided vs Angiography-Guided Everolimus-Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial. JAMA 2015, 314, 2155–2163. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  5. Buccheri, S.; Franchina, G.; Romano, S.; Puglisi, S.; Venuti, G.; D’aRrigo, P.; Francaviglia, B.; Scalia, M.; Condorelli, A.; Barbanti, M.; et al. Clinical Outcomes Following Intravascular Imaging-Guided Versus Coronary Angiography–Guided Percutaneous Coronary Intervention With Stent Implantation: A Systematic Review and Bayesian Network Meta-Analysis of 31 Studies and 17,882 Patients. JACC Cardiovasc. Interv. 2017, 10, 2488–2498. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  6. Ali, Z.A.; Maehara, A.; Généreux, P.; Shlofmitz, R.A.; Fabbiocchi, F.; Nazif, T.M.; Guagliumi, G.; Meraj, P.M.; Alfonso, F.; Samady, H.; et al. Optical coherence tomography compared with intravascular ultrasound and with angiography to guide coronary stent implantation (ILUMIEN III: OPTIMIZE PCI): A randomised controlled trial. Lancet 2016, 388, 2618–2628. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  7. Ali, Z.A.; Landmesser, U.; Maehara, A.; Matsumura, M.; Shlofmitz, R.A.; Guagliumi, G.; Price, M.J.; Hill, J.M.; Akasaka, T.; Prati, F.; et al. Optical Coherence Tomography–Guided versus Angiography-Guided PCI. N. Engl. J. Med. 2023, 389, 1466–1476. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  8. Pijls, N.H.; de Bruyne, B.; Peels, K.; van der Voort, P.H.; Bonnier, H.J.; Bartunek, J.; Koolen, J.J. Measurement of Fractional Flow Reserve to Assess the Functional Severity of Coronary-Artery Stenoses. N. Engl. J. Med. 1996, 334, 1703–1708. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  9. Pijls, N.H.; Van Gelder, B.; Van der Voort, P.; Peels, K.; Bracke, F.A.; Bonnier, H.J.; El Gamal, M.I. Fractional flow reserve. A useful index to evaluate the influence of an epicardial coronary stenosis on myocardial blood flow. Circulation 1995, 92, 3183–3193. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  10. De Bruyne, B.; Bartunek, J.; Sys, S.U.; Heyndrickx, G.R. Relation between myocardial fractional flow reserve calculated from coronary pressure measurements and exercise-induced myocardial ischemia. Circulation 1995, 92, 39–46. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  11. De Bruyne, B.; Pijls, N.H.; Kalesan, B.; Barbato, E.; Tonino, P.A.; Piroth, Z.; Jagic, N.; Mobius-Winckler, S.; Rioufol, G.; Witt, N.; et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N. Engl. J. Med. 2012, 367, 991–1001. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  12. Mangiacapra, F.; Paolucci, L.; De Bruyne, B.; Rioufol, G.; Hahn, J.-Y.; Chen, S.-L.; Koo, B.-K.; Tonino, P.A.L.; Veer, M.v.‘.; Motreff, P.; et al. Fractional flow reserve vs angiography to guide percutaneous coronary intervention: An individual patient data meta-analysis. Eur. Heart J. 2025, 46, 3851–3859. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  13. Tonino, P.A.L.; De Bruyne, B.; Pijls, N.H.J.; Siebert, U.; Ikeno, F.; van’t Veer, M.; Klauss, V.; Manoharan, G.; Engstrøm, T.; Oldroyd, K.G.; et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N. Engl. J. Med. 2009, 360, 229–230. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  14. Götberg, M.; Christiansen, E.H.; Gudmundsdottir, I.J.; Sandhall, L.; Danielewicz, M.; Jakobsen, L.; Olsson, S.-E.; Öhagen, P.; Olsson, H.; Omerovic, E.; et al. Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI. N. Engl. J. Med. 2017, 376, 1813–1823. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  15. Davies, J.E.; Sen, S.; Dehbi, H.-M.; Al-Lamee, R.; Petraco, R.; Nijjer, S.S.; Bhindi, R.; Lehman, S.J.; Walters, D.; Sapontis, J.; et al. Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI. N. Engl. J. Med. 2017, 376, 1824–1834. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  16. Götberg, M.; Berntorp, K.; Jeremias, A.; Yndigegn, T.; von Koch, S.; Linder, R.; Koul, S.; Fröbert, O.; Erlinge, D.; Mohammad, M.A. Long-Term Clinical Outcomes After IFR- vs FFR-Guided Coronary Revascularization: Insights From the SWEDEHEART National Registry. JACC Cardiovasc. Interv. 2025, 18, 455–467. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  17. Yamazaki, T.; Saito, Y.; Nakamura, S.; Tanabe, Y.; Kitahara, H.; Kobayashi, Y. Combined assessment of fractional flow reserve, resting full-cycle ratio, and resting ratio of distal coronary to aortic pressure for clinical outcomes. J. Cardiol. 2025, 85, 315–320. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  18. Lee, O.H.; Roh, J.W.; Kim, Y.; Heo, S.J.; Im, E.; Cho, D.K. Invasive physiologic assessment of coronary artery stenosis by resting full-cycle ratio and fractional flow reserve: A prospective observational study. Sci. Rep. 2023, 13, 15783. [Google Scholar] [CrossRef] [Scilit]
  19. Lei, Y.; Zhang, S.; Li, M.; Wang, J.; Wang, Y.; Zhao, L.; Yan, W.; Chen, M.; Su, Y.; Yu, J.; et al. The guiding value of hybrid resting full-cycle ratio and fractional flow reserve strategy for percutaneous coronary intervention in a Chinese real-world cohort with non-ST elevation acute coronary syndrome. Front. Cardiovasc. Med. 2022, 9, 991161. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  20. Sen, S.; Nijjer, S.; Petraco, R.; Malik, I.S.; Francis, D.P.; Davies, J. Instantaneous Wave-Free Ratio. J. Am. Coll. Cardiol. 2022, 62, 566. [Google Scholar] [CrossRef] [Scilit]
  21. Abbasciano, R.G.; Layton, G.R.; Torre, S.; Abbaker, N.; Copperwheat, A.; Lucarelli, C.; Bhandari, S.; Nijjer, S.; Mikhail, G.; Casula, R.; et al. Fractional flow reserve and instantaneous wave-free ratio in coronary artery bypass grafting: A meta-analysis and practice review. Front. Cardiovasc. Med. 2024, 11, 1348341. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  22. Briceno, N.; Lumley, M.; Perera, D. Fractional flow reserve: Conundrums, controversies and challenges. Interv. Cardiol. 2015, 7, 543–552. [Google Scholar] [CrossRef]
  23. Boutaleb, A.M.; Ghafari, C.; Ungureanu, C.; Carlier, S. Fractional flow reserve and non-hyperemic indices: Essential tools for percutaneous coronary interventions. World J. Clin. Cases. 2023, 11, 2123–2139. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  24. Balanescu, S. Fractional flow reserve assessment of coronary artery stenosis. Eur. Cardiol. Rev. 2016, 11, 77–82. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  25. Rodriguez-Leor, O.; Hernandez, J.M.d.l.T.; Camarero, T.G.; del Blanco, B.G.; Lopez-Palop, R.; Fernandez-Nofrerias, E.; Ramón, C.C.; Jiménez-Kockar, M.; Jimenez-Mazuecos, J.; Salinas, F.F.; et al. Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations with Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study. Circ. Cardiovasc. Interv. 2022, 15, 861–871. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  26. Kovarnik, T.; Hitoshi, M.; Kral, A.; Jerabek, S.; Zemanek, D.; Kawase, Y.; Omori, H.; Tanigaki, T.; Pudil, J.; Vodzinska, A.; et al. Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study. J. Am. Heart Assoc. 2022, 11, 21490. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  27. Patel, P.A.; Malkin, C.J.; Ali, N. Assessment of coronary physiology—The evidence and implications. Clin. Med. 2019, 19, 364–368. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  28. Trøan, J.; Hansen, K.N.; Noori, M.; Ellert-Gregersen, J.; Junker, A.; Veien, K.T.; Hougaard, M.; Fallesen, C.O.; Hansen, H.S.; Jensen, L.O. The Influence of Microcirculatory Dysfunction on the Resting Full Cycle Ratio Compared to Fractional Flow Reserve. Cardiovasc. Revascularization Med. 2023, 54, 41–46. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  29. Escaned, J.; Travieso, A.; Dehbi, H.-M.; Nijjer, S.S.; Sen, S.; Petraco, R.; Serruys, P.W.; Davies, J.; DEFINE FLAIR Investigators; E Davies, J.; et al. Coronary Revascularization Guided With Fractional Flow Reserve or Instantaneous Wave-Free Ratio: A 5-Year Follow-Up of the DEFINE FLAIR Randomized Clinical Trial. JAMA Cardiol. 2025, 10, 25–31. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  30. Berntorp, K.; Rylance, R.; Yndigegn, T.; Koul, S.; Fröbert, O.; Christiansen, E.H.; Erlinge, D.; Götberg, M. Clinical Outcome of Revascularization Deferral With Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A 5-Year Follow-Up Substudy From the iFR-SWEDEHEART Trial. J. Am. Heart Assoc. 2023, 12, e028423. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  31. Hennigan, B.; Layland, J.; Fearon, W.F.; Oldroyd, K.G. Fractional flow reserve and the index of microvascular resistance in patients with acute coronary syndromes. EuroIntervention 2014, 10, T55–63. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  32. Yock, P.G.; Fitzgerald, P.J. Intravascular ultrasound: State of the art and future directions. Am. J. Cardiol. 1998, 81, 27E–32E. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  33. Tearney, G.J.; Regar, E.; Akasaka, T.; Adriaenssens, T.; Barlis, P.; Bezerra, H.G.; Bouma, B.; Bruining, N.; Cho, J.-M.; Chowdhary, S.; et al. Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies: A Report From the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J. Am. Coll. Cardiol. 2012, 59, 1058–1072. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  34. Gao, X.-F.; Ge, Z.; Kong, X.-Q.; Kan, J.; Han, L.; Lu, S.; Tian, N.-L.; Lin, S.; Lu, Q.-H.; Wang, X.-Y.; et al. 3-Year Outcomes of the ULTIMATE Trial Comparing Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation. JACC Cardiovasc. Interv. 2021, 14, 247–257. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  35. Sreenivasan, J.; Reddy, R.K.; Jamil, Y.; Malik, A.; Chamie, D.; Howard, J.P.; Nanna, M.G.; Mintz, G.S.; Maehara, A.; Ali, Z.A.; et al. Intravascular Imaging–Guided Versus Angiography-Guided Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Trials. J. Am. Heart Assoc. 2024, 13, 31111. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  36. Kume, T.; Uemura, S. Current clinical applications of coronary optical coherence tomography. Cardiovasc. Interv. Ther. 2017, 33, 1–10. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  37. Yip, A.; Saw, J. Spontaneous coronary artery dissection―A review. Cardiovasc Diagn. Ther. 2015, 5, 37–48. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  38. Jang, I.-K.; Bouma, B.E.; Kang, D.-H.; Park, S.-J.; Park, S.-W.; Seung, K.-B.; Choi, K.-B.; Shishkov, M.; Schlendorf, K.; Pomerantsev, E.; et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: Comparison with intravascular ultrasound. J. Am. Coll. Cardiol. 2002, 39, 604–609. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  39. Kang, D.-Y.; Ahn, J.-M.; Yun, S.-C.; Hur, S.-H.; Cho, Y.-K.; Lee, C.H.; Hong, S.J.; Lim, S.; Kim, S.-W.; Won, H.; et al. Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound. J. Am. Coll. Cardiol. 2024, 83, 401–413. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  40. Kang, D.-Y.; Ahn, J.-M.; Yun, S.-C.; Hur, S.-H.; Cho, Y.-K.; Lee, C.H.; Hong, S.J.; Lim, S.; Kim, S.-W.; Won, H.; et al. Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: The OCTIVUS Randomized Clinical Trial. Circulation 2023, 148, 1195–1206. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  41. Buonpane, A.; Trimarchi, G.; Ciardetti, M.; Coceani, M.A.; Alagna, G.; Benedetti, G.; Berti, S.; Andò, G.; Burzotta, F.; De Caterina, A.R. Optical Coherence Tomography in Myocardial Infarction Management: Enhancing Precision in Percutaneous Coronary Intervention. J. Clin. Med. 2024, 13, 5791. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  42. Jiang, Y.; Wang, J.; Murthy, R.S.; Patel, P.; Chen, Z. Intracoronary Optical Coherence Tomography: Technological Innovations and Clinical Implications in Cardiology. Curr. Treat. Options Cardiovasc. Med. 2025, 27, 44. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  43. Yang, S.; Kang, J.; Hwang, D.; Zhang, J.; Jiang, J.; Hu, X.; Hahn, J.-Y.; Nam, C.-W.; Doh, J.-H.; Lee, B.-K.; et al. Physiology- or Imaging-Guided Strategies for Intermediate Coronary Stenosis. JAMA Netw. Open 2024, 7, e2350036. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  44. Burzotta, F.; Leone, A.M.; Aurigemma, C.; Zambrano, A.; Zimbardo, G.; Arioti, M.; Vergallo, R.; De Maria, G.L.; Cerracchio, E.; Romagnoli, E.; et al. Fractional Flow Reserve or Optical Coherence Tomography to Guide Management of Angiographically Intermediate Coronary Stenosis: A Single-Center Trial. JACC Cardiovasc. Interv. 2020, 13, 49–58. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  45. Kobayashi, N.; Takano, M.; Tsurumi, M.; Shibata, Y.; Nishigoori, S.; Uchiyama, S.; Okazaki, H.; Shirakabe, A.; Seino, Y.; Hata, N.; et al. Features and Outcomes of Patients with Calcified Nodules at Culprit Lesions of Acute Coronary Syndrome: An Optical Coherence Tomography Study. Cardiology 2018, 139, 90–100. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  46. Onea, H.-L.; Spinu, M.; Homorodean, C.; Olinic, M.; Lazar, F.-L.; Ober, M.C.; Stoian, D.; Itu, L.M.; Olinic, D.M. Distinctive Morphological Patterns of Complicated Coronary Plaques in Acute Coronary Syndromes: Insights from an Optical Coherence Tomography Study. Diagnostics 2022, 12, 2837. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  47. Gupta, A.; Shrivastava, A.; Vijayvergiya, R.; Chhikara, S.; Datta, R.; Aziz, A.; Meena, D.S.; Nath, R.K.; Kumar, J.R. Optical Coherence Tomography: An Eye Into the Coronary Artery. Front. Cardiovasc. Med. 2022, 9, 854554. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  48. Toutouzas, K.; Karanasos, A.; Tousoulis, D. Optical Coherence Tomography For the Detection of the Vulnerable Plaque. Eur. Cardiol. 2016, 11, 90–95. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  49. Jia, H.; Abtahian, F.; Aguirre, A.D.; Lee, S.; Chia, S.; Lowe, H.; Kato, K.; Yonetsu, T.; Vergallo, R.; Hu, S.; et al. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. J. Am. Coll. Cardiol. 2013, 62, 1748–1758. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  50. Wang, Y.; Yang, X.; Wu, Y.; Li, Y.; Zhou, Y. Optical coherence tomography (OCT)—Versus angiography-guided strategy for percutaneous coronary intervention: A meta-analysis of randomized trials. BMC Cardiovasc. Disord. 2024, 24, 262. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  51. Ahmed, M.; Javaid, H.; Maniya, M.T.; Shafiq, A.; Shahbaz, H.; Singh, P.; Jain, H.; Basit, J.; Hamza, M.; Nashwan, A.J.; et al. Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention: A meta-analysis of randomized controlled trials. IJC Heart Vasc. 2024, 52, 101405. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  52. Lee, J.M.; Kim, H.; Hong, D.; Hwang, D.; Zhang, J.; Hu, X.; Jiang, J.; Nam, C.-W.; Doh, J.-H.; Lee, B.-K.; et al. Clinical Outcomes of Deferred Lesions by IVUS Versus FFR-Guided Treatment Decision. Circ. Cardiovasc. Interv. 2023, 16, E013308. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  53. Nam, C.-W.; Yoon, H.-J.; Cho, Y.-K.; Park, H.-S.; Kim, H.; Hur, S.-H.; Kim, Y.-N.; Chung, I.-S.; Koo, B.-K.; Tahk, S.-J.; et al. Outcomes of percutaneous coronary intervention in intermediate coronary artery disease: Fractional flow reserve-guided versus intravascular ultrasound-guided. JACC Cardiovasc. Interv. 2010, 3, 812–817. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  54. Costa, M.A.; Sabate, M.; Staico, R.; Alfonso, F.; Seixas, A.C.; Albertal, M.; Crossman, A.; Angiolillo, D.J.; Zenni, M.; Sousa, J.E.; et al. Anatomical and physiologic assessments in patients with small coronary artery disease: Final results of the Physiologic and Anatomical Evaluation Prior to and After Stent Implantation in Small Coronary Vessels (PHANTOM) trial. Am. Heart J. 2007, 153, 296.e1–296.e7. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  55. Koo, B.-K.; Hu, X.; Kang, J.; Zhang, J.; Jiang, J.; Hahn, J.-Y.; Nam, C.-W.; Doh, J.-H.; Lee, B.-K.; Kim, W.; et al. Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI. N. Engl. J. Med. 2022, 387, 779–789. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  56. Puymirat, E.; Cayla, G.; Simon, T.; Steg, P.G.; Montalescot, G.; Durand-Zaleski, I.; le Bras, A.; Gallet, R.; Khalife, K.; Morelle, J.-F.; et al. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N. Engl. J. Med. 2021, 385, 297–308. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  57. Hu, X.; Zhang, J.; Yang, S.; Jiang, J.; Peng, X.; Lu, D.; Pan, Y.; Guo, L.; Li, J.; He, W.; et al. Angiography-derived fractional flow reserve versus intravascular ultrasound to guide percutaneous coronary intervention in patients with coronary artery disease (FLAVOUR II): A multicentre, randomised, non-inferiority trial. Lancet 2025, 405, 1491–1504. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  58. Räber, L.; Mintz, G.S.; Koskinas, K.C.; Johnson, T.W.; Holm, N.R.; Onuma, Y.; Radu, M.D.; Joner, M.; Yu, B.; Jia, H.; et al. Clinical use of intracoronary imaging. Part 1: Guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur. Heart J. 2018, 39, 3281–3300. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  59. Koo, B.-K.; Park, K.-W.; Kang, H.-J.; Cho, Y.-S.; Chung, W.-Y.; Youn, T.-J.; Chae, I.-H.; Choi, D.-J.; Tahk, S.-J.; Oh, B.-H.; et al. Physiological evaluation of the provisional side-branch intervention strategy for bifurcation lesions using fractional flow reserve. Eur. Heart J. 2008, 29, 726–732. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  60. Fujino, A.; Mintz, G.S.; Lee, T.; Hoshino, M.; Usui, E.; Kanaji, Y.; Murai, T.; Yonetsu, T.; Matsumura, M.; Ali, Z.A.; et al. Predictors of Calcium Fracture Derived From Balloon Angioplasty and its Effect on Stent Expansion Assessed by Optical Coherence Tomography. JACC Cardiovasc. Interv. 2018, 11, 1015–1017. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  61. Scarsini, R.; Fezzi, S.; Leone, A.M.; De Maria, G.L.; Pighi, M.; Marcoli, M.; Tavella, D.; Pesarini, G.; Banning, A.P.; Barbato, E.; et al. Functional Patterns of Coronary Disease: Diffuse, Focal, and Serial Lesions. JACC Cardiovasc. Interv. 2022, 15, 2174–2191. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  62. Stone, G.W.; Maehara, A.; Lansky, A.J.; de Bruyne, B.; Cristea, E.; Mintz, G.S.; Mehran, R.; McPherson, J.; Farhat, N.; Marso, S.P.; et al. A Prospective Natural-History Study of Coronary Atherosclerosis. N. Engl. J. Med. 2011, 364, 226–235. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  63. Tsimikas, S.; Kiechl, S.; Willeit, J.; Mayr, M.; Miller, E.R.; Kronenberg, F.; Xu, Q.; Bergmark, C.; Weger, S.; Oberhollenzer, F.; et al. Oxidized Phospholipids Predict the Presence and Progression of Carotid and Femoral Atherosclerosis and Symptomatic Cardiovascular Disease. Five-Year Prospective Results From the Bruneck Study. J. Am. Coll. Cardiol. 2006, 47, 2219–2228. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  64. Park, S.-J.; Ahn, J.-M.; Kang, S.-J.; Yoon, S.-H.; Koo, B.-K.; Lee, J.-Y.; Kim, W.-J.; Park, D.-W.; Lee, S.-W.; Kim, Y.-H.; et al. Intravascular ultrasound-derived minimal lumen area criteria for functionally significant left main coronary artery stenosis. JACC Cardiovasc. Interv. 2014, 7, 868–874. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  65. Reidelberger, R.D.; Heimann, D.; Kelsey, L.; Hulce, M. Effects of peripheral CCK receptor blockade on feeding responses to duodenal nutrient infusions in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003, 284, R389–R398. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  66. Majouli, K.; Hamdi, A.; Hlila, M.B. Phytochemical analysis and biological activities of Hertia cheirifolia L. roots extracts. Asian Pac. J. Trop. Med. 2017, 10, 1134–1139. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  67. Kobayashi, M.; Chijimatsu, R.; Yoshikawa, H.; Yoshida, K. Extracorporeal shock wave therapy accelerates endochondral ossification and fracture healing in a rat femur delayed-union model. Biochem. Biophys. Res. Commun. 2020, 530, 632–637. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  68. Givertz, M.M.; DeFilippis, E.M.; Colvin, M.; Darling, C.E.; Elliott, T.; Hamad, E.; Hiestand, B.C.; Martindale, J.L.; Pinney, S.P.; Shah, K.B.; et al. HFSA/SAEM/ISHLT clinical expert consensus document on the emergency management of patients with ventricular assist devices. J. Heart Lung Transplant. 2019, 38, 677–698. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  69. Carew, A.S.; Levy, A.P.; Ginsberg, H.N.; Coca, S.; Lache, O.; Ransom, T.; Byington, R.; Rimm, E.B.; Sapp, J.; Gardner, M.; et al. Haptoglobin Phenotype Modifies the Influence of Intensive Glycemic Control on Cardiovascular Outcomes. J. Am. Coll. Cardiol. 2020, 75, 512–521. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  70. Mizukami, T.; Sonck, J.; Sakai, K.; Ko, B.; Maeng, M.; Otake, H.; Koo, B.; Nagumo, S.; Nørgaard, B.L.; Leipsic, J.; et al. Procedural Outcomes After Percutaneous Coronary Interventions in Focal and Diffuse Coronary Artery Disease. J. Am. Heart Assoc. 2022, 11, e026960. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  71. Amponsah, D.K.; Fearon, W.F. From Evidence to Practice: The Growing Role of Angiography-Derived Physiology. J. Clin. Med. 2025, 14, 8219. [Google Scholar] [CrossRef] [Scilit]
  72. Brugaletta, S.; Sabaté, M. Assessment of plaque composition by intravascular ultrasound and near-infrared spectroscopy: From PROSPECT I to PROSPECT II. Circ. J. 2014, 78, 1531–1539. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  73. Castaldi, G.; Zormpas, G.; Frederiks, P.; Adriaenssens, T.; Bennett, J. The Rise of Optical Coherent Tomography in Intracoronary Imaging: An Overview of Current Technology, Limitations, and Future Perspectives. Rev. Cardiovasc. Med. 2025, 26, 38123. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  74. Buonpane, A.; De Caterina, A.R.; Trimarchi, G.; Di Muro, F.M.; Galante, D.; Zella, S.; Pizzino, F.; Ciardetti, M.; Paradossi, U.; Concistrè, G.; et al. Unveiling the Causes of Acute and Non-Acute Myocardial Ischemic Syndromes: The Role of Optical Coherence Tomography. Medicina 2025, 61, 1218. [Google Scholar] [CrossRef] [Scilit] [PubMed]
  75. Sonck, J.; Mizukami, T.; Johnson, N.P.; Nagumo, S.; Gallinoro, E.; Candreva, A.; Mileva, N.; Munhoz, D.; Shinke, T.; Svanerud, J.; et al. Development, validation, and reproducibility of the pullback pressure gradient (PPG) derived from manual fractional flow reserve pullbacks. Catheter Cardiovasc. Interv. 2022, 99, 1518–1525. [Google Scholar] [CrossRef] [Scilit] [PubMed]
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