Negative Fractional Flow Reserve Research Articles

Single centre experience using vessel Fractional Flow Reserve (vFFR) and diagnostic performance compared with invasive Fractional Flow Reserve (FFR)

Abstract Background Fractional flow reserve (FFR) is a diagnostic gold standard in the functional assessment of coronary artery stenoses (1). Alternative invasive and non-invasive methods have been developed in an attempt to avoid limitations associated with FFR including added procedural risk, patient discomfort, time and cost. Vessel fractional flow reserve (vFFR) is a novel software using two angiographic projections to generate a 3D vessel reconstruction which has shown high diagnostic accuracy in predicting a positive FFR (2-4). Methods All patients undergoing coronary angiography between 01/10/2022 and 08/03/2023, where FFR was performed, were assessed. Patients were included where images met requirements necessary to use vFFR software. vFFR measurements were taken retrospectively by a single investigator and not used to inform patient care. Data were expressed as mean +/- standard deviation and %. The correlation of vFFR to FFR was compared using Pearson’s correlation coefficient. Receiving operator characteristic (ROC) area under the curve (AUC) analysis was used to determine diagnostic performance. Statistical analysis was performed using SPSS v27. Results 28 of 37 patients and 32 of 44 vessels were included and analysed with vFFR software. Excluded vessels were unsuitable due to insufficient frame rate or projection angulation during angiography. Mean age was 63 +/- 3.8 years and 75% of patients were male. Of 32 vessels assessed, 20 were LAD, 5 RCA, 5 LCx and 2 LMS. 29 of 32 vFFR values agreed with positive or negative FFR. Positive vFFR values were seen in all 15 vessels with positive FFR. 3 vessels received a positive vFFR where FFR values were negative. Mean vFFR was 0.76 +/- 0.1 and mean FFR was 0.81 +/- 0.09. vFFR correlated significantly with FFR (R=0.777, p<0.001). vFFR demonstrated good diagnostic accuracy in discriminating "positive" (>0.8) and "negative" (≤0.8) FFR with an AUC of 0.758 (95% CI 0.61-0.91, p<0.01). Conclusion vFFR correlated significantly with FFR and all positive FFR values also received positive vFFR values. vFFR demonstrated good diagnostic accuracy in predicting a positive FFR result. Thus, these data support a strategy of using a negative vFFR to avoid further testing.Pearson correlation of vFFR to invFFRROC curve: vFFR predicting invFFR

Clinical outcomes of patients with deferred revascularisation based on fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) negative coronary artery lesions in Pakistani population.

To assess long-term clinical outcomes and factors associated with target vessel revascularisation in patients with deferred revascularisation based on negative fractional flow reserve and negative instantaneous wave-free ratio. The longitudinal, retrospective study was conducted from July 1, 2020, to January 1, 2022, at the Aga Khan University Hospital, Karachi, and comprised medical records from January 2012 to January 2020 of patients with deferred revascularisation having intermediate to severe coronary lesions on coronary angiogram and had negative fractional flow reserve >0.80 or instantaneous wave-free ratio >0.89 and had not undergone immediate or planned revascularisation on the basis of negative physiological assessment. Data was collected from the institutional records, while final follow-up was taken by reviewing the medical records or telephonic interviews regarding any major adverse cardiac event after the index procedure. Data was analysed using Stata 14.2. Of the 345 patients, 245(71%) were males. The overall mean age was 62±11 years. There were 194(56%) patients who presented with stable angina and 151(44%) presented with acute coronary syndrome. Mean fractional flow reserve was 0.87±0.04 and mean instantaneous wave-free ratio was 0.93±0.03. Multivessel disease was present in 223(65%) patients. Median follow-up period was 29 months (IQR: 24-36 months). Major adverse cardiovascular events occurred in 22(6%) patients, and target vessel revascularisation was required in 11(3%). Diabetes and percentage of stenosis were found to be independent predictors of major adverse cardiovascular events (p<0.05). Deferral of revascularisation and opting for medical treatment for coronary artery stenosis with higher fractional flow reserve or instantaneous wave-free ratio could be considered a safe and reasonable strategy.

Development of machine learning models for fractional flow reserve prediction in angiographically intermediate coronary lesions.

Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables. A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off. ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR.

Comparison of Fractional Flow Reserve and Resting Full-Cycle Ratio in the Functional Assessment of Coronary Artery Stenosis in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome.

This study investigated factors influencing discrepancies between fractional flow reserve (FFR) and resting full-cycle ratio (RFR) in the functional assessment of coronary artery stenosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We included 320 diseased vessels from 253 consecutive patients with NSTE-ACS. Vessels were categorized into four groups based on FFR 0.80 and RFR 0.89 thresholds: group 1 concordant negative (RFR-/FFR-), group 2 positive RFR and negative FFR (RFR+/FFR-), group 3 negative RFR and positive FFR (RFR-/FFR+), and group 4 concordant positive (RFR+/FFR+). Univariate and multivariate logistic regression analyses were conducted to identify predictors of diagnostic discrepancy between FFR and RFR. Of the 320 diseased vessels, 182 (56.9%) were in group 1 (RFR-/FFR-), 33 (10.3%) in group 2 (RFR+/FFR-), 31 (9.7%) in group 3 (RFR-/FFR+), and 74 (23.1%) in group 4 (RFR+/FFR+). The concordance between FFR and RFR was 80.0%. Notably, left anterior descending artery (LAD) lesions exhibited significantly lower consistency compared to non-LAD lesions (p = 0.001), with distinct differences in FFR and RFR values between these groups (p 0.001). The presence of a LAD lesion emerged as an independent predictor of diagnostic inconsistency between positive RFR and negative FFR measurements (p = 0.001). LAD involvement independently predicts diagnostic discrepancies between FFR and RFR in evaluating functional coronary artery stenosis in NSTE-ACS patients.

Multivessel disease in patient with acute myocardial infarction: current treatment strategies and future perspectives

Patients who present with acute myocardial infarction (AMI) often suffer from coronary multivessel disease (MVD). This condition is associated with an increased mortality rate; it is, therefore, important to improve clinical outcomes through appropriate treatment strategies. Over the past decades, extensive research in AMI and MVD patients has consistently shown that complete revascularization is superior to treatment of the only culprit lesion. Another controversial issue concerns the most appropriate timing for percutaneous coronary intervention in non-culprit lesions. Fractional flow reserve (FFR) is considered the best method for identifying ischemic coronary lesions in the context of acute coronary syndromes, but the detection of vulnerable plaques in non-culprit vessels could further improve clinical outcomes. Intravascular imaging goes beyond physiology and it is potentially useful to recognize patients who are vulnerable, despite negative FFR. Therefore, we analyzed the most relevant studies that have investigated the relationship between physiological indexes and plaque vulnerability. However, ongoing trials aim to clarify how coronary physiology can be combined with the benefits of intracoronary imaging.

Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial.

Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions. This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months. The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294). The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months. ClinicalTrials.gov Identifier: NCT02673424.

Inter-corelab agreement of angiography-derived wall shear stress distribution

Abstract Aims Wall shear stress (WSS) estimated in models reconstructed from intravascular imaging and 3D-quantitative coronary angiography (QCA) data provides important prognostic information and enables the identification of high-risk lesions. However, these analyses are time-consuming and require expertise limiting WSS applications and adoption in clinical practice. Recently, a novel software has been developed for real-time computation of WSS and multidirectional WSS distribution. The aim of this study is to examine its inter-corelab reproducibility. Methods and results Sixty lesions (20 in coronary bifurcations) with a borderline negative fractional flow reserve were selected and processed using the CAAS Workstation WSS prototype (version 6.0 PIE MEDICAL) to estimate WSS and multi-directional WSS. Analysis was performed by two Core laboratories; the estimations of the two corelabs for the WSS in 3 mm segments across each reconstructed vessel were extracted and compared. To examine the concordance between inter-observer analysis of clinically relevant values, the scatterplot was divided into 4 quadrants with AS 61.3% and maximum WSS 8.24 Pa based on the previous publications and Cohen’s Kappa value was presented using these cut-off values. In total 700 segments (256 located in bifurcated vessels) were included in the present analysis. Average analysis time on the software was 219±45s in straight model and 291±61s in bifurcation model. A high intraclass correlation was noted for all the WSS metrics for the estimations of the two core labs irrespective of the presence (range: 0.90 – 0.92) or absence (range: 0.89 - 0.90) of a coronary bifurcation, while the ICC was good-moderate for the multidirectional WSS (range: 0.72-0.86). In addition, the bias between the WSS estimations was low and the limits of agreement were narrow in Bland-Altman analyses (Figure 1). When using the cut-off value of maximum WSS and % AS, a substantial agreement was noted between the two estimations of the two core labs; κ=0.77 for identifying maximum WSS &amp;gt;8.24Pa and κ=0.71 for identifying AS &amp;gt;61.3% (Figure 2). Conclusion The CAAS workstation enables reproducible 3D-QCA reconstruction and computation of WSS metrics. Further research is needed to explore its efficacy in predicting cardiovascular events.Figure 1Figure 2

Influence of sex on the functional assessment of myocardial ischemia.

Fractional flow reserve (FFR) and non-hyperemic resting pressure ratios, such as instantaneous wave-free ratio (iFR) and resting full-cycle ratio (RFR), are recommended for evaluating the significance of angiographically intermediate coronary stenoses. Despite their usefulness, approximately 20% of assessed lesions exhibit discordance between FFR and iFR/RFR. The role of sex in this discrepancy remains uncertain; thus, we aimed to investigate its impact on the discordance between FFR and iFR/RFR. We reviewed 417 consecutive intermediate stenotic lesions from 381 patients, stratified by sex and assessed with both FFR and iFR/RFR. FFR≤0.80 and iFR/RFR ≤0.89 were considered positive for ischemia. Among the 381 patients, 92 (24.1%) were women. Women were older, had lower estimated glomerular filtration rate (eGFR), a higher ejection fraction, and were more likely to have peripheral artery disease than men. Median FFR and iFR/RFR values were lower in men than in women (FFR 0.86 vs. 0.80; P < 0.001; iFR 0.92 vs. 0.90; P = 0.049). However, overall discordance prevalence was similar for both sexes (20.6% vs. 15.1%; P = 0.22). In men, eGFR, insulin-treated diabetes mellitus, and arterial hypertension were predictors of positive FFR | negative iFR/RFR discordance, while eGFR, insulin-treated diabetes mellitus, atrial fibrillation, and chronic obstructive pulmonary disease were predictors of negative FFR | positive iFR/RFR discordance. No factors associated with either discordance were identified in women. FFR and iFR/RFR results indicating significant ischemia were more common in men than women when assessing intermediate coronary stenoses. Nevertheless, sex did not predict discordant results.

Vessel-Specific Outcomes of Deferred Revascularization Following Negative Fractional Flow Reserve

Variations in myocardial supply area and hydrostatic pressure gradients result in greater likelihood of positive fractional flow reserve (FFR) in the left anterior descending (LAD) compared with the circumflex (Cx) and right coronary artery (RCA). However, the same FFR threshold for deferral of revascularization is applied to all arteries, without evidence that this results in equivalent outcomes. We assessed vessel-specific outcomes of deferred revascularization for the 3 major coronary arteries based on FFR > 0.8. In this retrospective study, data were obtained on consecutive patients who underwent indicated FFR assessment across 2 tertiary institutions. Patients with deferred revascularization were followed for 36 months for the primary end point of vessel-specific target lesion failure (TLF). Of 1,916 major coronary arteries (1,579 patients), the odds ratio of positive FFR was highest in the LAD (odds ratio 3.36, p<0.001). In total, 867 vessels (733 patients) with FFR > 0.8 had complete 3-year medical record follow-ups. The TLF rate for deferred vessels was 10.21%, 11.52%, and 10.96% for the LAD, Cx, and RCA respectively. In a multivariate analysis, there was no significant difference in the odds of TLF for the 0.84 (0.53 to 1.33, p=0.459), 1.17 (0.68 to 2.01, p=0.582), and 1.11 (0.62 to 2.00, p=0.715) in the LAD, Cx, and RCA, respectively. In a multivariate analysis, diabetes mellitus was the only baseline characteristic significantly associated at risk of TLF (1.43 [1.01 to 2.02], p=0.043). In conclusion, despite greater likelihood of positive FFR in the LAD, the FFR threshold for deferred revascularization resulted in equivalent outcomes in all 3 major coronary arteries, and patients with diabetes mellitus may represent a group that requires aggressive surveillance and risk factor modification after deferred revascularization.

Two-Year Vessel-Specific Outcomes of Deferred Revascularisation Based on Negative Fractional Flow Reserve

Two-Year Vessel-Specific Outcomes of Deferred Revascularisation Based on Negative Fractional Flow Reserve

Agreement of wall shear stress distribution between two core laboratories using three-dimensional quantitative coronary angiography.

Wall shear stress (WSS) estimated in models reconstructed from intravascular imaging and 3-dimensional-quantitative coronary angiography (3D-QCA) data provides important prognostic information and enables identification of high-risk lesions. However, these analyses are time-consuming and require expertise, limiting WSS adoption in clinical practice. Recently, a novel software has been developed for real-time computation of time-averaged WSS (TAWSS) and multidirectional WSS distribution. This study aims to examine its inter-corelab reproducibility. Sixty lesions (20 coronary bifurcations) with a borderline negative fractional flow reserve were processed using the CAAS Workstation WSS prototype to estimate WSS and multi-directional WSS values. Analysis was performed by two corelabs and their estimations for the WSS in 3mm segments across each reconstructed vessel was extracted and compared. In total 700 segments (256 located in bifurcated vessels) were included in the analysis. A high intra-class correlation was noted for all the 3D-QCA and TAWSS metrics between the estimations of the two corelabs irrespective of the presence (range: 0.90-0.92) or absence (range: 0.89-0.90) of a coronary bifurcation, while the ICC was good-moderate for the multidirectional WSS (range: 0.72-0.86). Lesion level analysis demonstrated a high agreement of the two corelabls for detecting lesions exposed to an unfavourable haemodynamic environment (WSS > 8.24Pa, κ = 0.77) that had a high-risk morphology (area stenosis > 61.3%, κ = 0.71) and were prone to progress and cause events. The CAAS Workstation WSS enables reproducible 3D-QCA reconstruction and computation of WSS metrics. Further research is needed to explore its value in detecting high-risk lesions.

Outcomes of deferred revascularisation following negative fractional flow reserve in diabetic and non-diabetic patients: a meta-analysis

BackgroundFractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR.MethodsWe performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR > 0.8 were included. The primary end point was MACE.ResultsThe meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35–2.04, p = < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06–2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20–2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07–4.05, p = 0.03).ConclusionsFor patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients.Trail registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022367312.

An automated software for real-time quantification of wall shear stress distribution in quantitative coronary angiography data

BackgroundWall shear stress (WSS) estimated in 3D-quantitative coronary angiography (QCA) models appears to provide useful prognostic information and identifies high-risk patients and lesions. However, conventional computational fluid dynamics (CFD) analysis is cumbersome limiting its application in the clinical arena. This report introduces a user-friendly software that allows real-time WSS computation and examines its reproducibility and accuracy in assessing WSS distribution against conventional CFD analysis. MethodsFrom a registry of 414 patients with borderline negative fractional flow reserve (0.81–0.85), 100 lesions were randomly selected. 3D-QCA and CFD analysis were performed using the conventional approach and the novel CAAS Workstation WSS software, and QCA as well as WSS estimations of the two approaches were compared. The reproducibility of the two methodologies was evaluated in a subgroup of 50 lesions. ResultsA good agreement was noted between the conventional approach and the novel software for 3D-QCA metrics (ICC range: 0.73–0-93) and maximum WSS at the lesion site (ICC: 0.88). Both methodologies had a high reproducibility in assessing lesion severity (ICC range: 0.83–0.97 for the conventional approach; 0.84–0.96 for the CAAS Workstation WSS software) and WSS distribution (ICC: 0.85–0.89 and 0.83–0.87, respectively). Simulation time was significantly shorter using the CAAS Workstation WSS software compared to the conventional approach (4.13 ± 0.59 min vs 23.14 ± 2.56 min, p < 0.001). ConclusionCAAS Workstation WSS software is fast, reproducible, and accurate in assessing WSS distribution. Therefore, this software is expected to enable the broad use of WSS metrics in the clinical arena to identify high-risk lesions and vulnerable patients.

Factors associated with discordance between fractional flow reserve and resting full-cycle ratio

BackgroundResting full-cycle ratio (RFR), a non-hyperemic pressure ratio, is alternative to fractional flow reserve (FFR) for the evaluation of coronary artery stenoses. Although FFR and RFR results are often discordant using the cut-off values (0.80 and 0.89), factors associated with the discordance are unclear. The aim of this study was to explore factors related to the discordant results. MethodsWe performed FFR and RFR measurements in a total of 408 vessels with intermediate coronary artery stenosis in 277 patients. Positive FFR and RFR were defined based on the cut-off values of 0.80 and 0.89. The discordance was determined as positive FFR and negative RFR (FFR ≤0.80 and RFR >0.89) or negative FFR and positive RFR (FFR >0.80 and RFR ≤0.89). ResultsOverall, FFR and RFR were significantly correlated (r = 0.76, p < 0.001), while positive FFR and negative RFR and negative FFR and positive RFR were observed in 44 (10.8%) and 45 (11.0%) of 408 vessels, respectively. Smaller body surface area, diabetes, chronic kidney disease including hemodialysis, severe aortic stenosis, higher E/e', and lower left ventricular ejection fraction on echocardiography, and lower hemoglobin and higher brain natriuretic peptide levels were identified as factors associated with the negative FFR and positive RFR discordance. ConclusionsDiscordant results between FFR and RFR were often found in more than 20% of vessels with intermediate coronary stenosis. Clinical characteristics such as renal function, heart failure, and anemia may be considered in clinical decision-making when using FFR and RFR.

Prevalence of myocardial perfusion scintigraphy derived ischemia in coronary lesions with discordant fractional flow reserve and non-hyperemic pressure ratios

BackgroundWhether a coronary lesion with discordant fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) causes myocardial ischemia remains unclear. This study investigates the prevalence of myocardial ischemia as assessed by myocardial perfusion scintigraphy (MPS) in coronary lesions with discordant FFR and instantaneous wave-free ratio (iFR), and, additionally, other NHPRs: resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and resting Pd/Pa. MethodsA total of 484 coronary arteries in 295 patients with stable coronary artery disease that underwent MPS and invasive physiological pressure measurements were categorized into four groups (FFR+/NHPR+, FFR+/NHPR-, FFR-/NHPR+, and FFR-/NHPR-) using the respective cut-off values of FFR ≤ 0.80, iFR ≤ 0.89, RFR ≤ 0.89, dPR < 0.89, and Pd/Pa ≤ 0.92. The proportions of MPS-derived myocardial ischemia in a relevant myocardial territory were compared between the four groups. ResultsIn total, 175 (36%), 61(13%), 35(7%) and 213(44%) vessels were classified into FFR+/iFR+, FFR+/iFR-, FFR-/iFR+ and FFR-/iFR- groups, respectively. The FFR+/iFR+ group had the highest proportion of MPS-derived ischemia (70%), followed by the FFR+/iFR- group (38%), the FFR-/iFR+ group (23%), and the FFR-/iFR- group (10%) (P < 0.001). Similar proportions of MPS-derived ischemia were found when RFR.(70%, 34%, 24%, and 10%, P < 0.001), dPR (70%, 38%, 26%, and 10%, P < 0.001), and Pd/Pa (70%, 31%, 22%, and 10%, P < 0.001) were used in place of iFR. ConclusionsThe prevalence of MPS-derived myocardial ischemia in coronary lesions with discordance between FFR and NHPRs is lower than those with concordantly positive FFR and NHPRs, but higher than those with concordantly negative FFR and NHPRs.

734 Have I lost my large rupture cavity? The fingerprint of atherosclerotic plaque healing detected by serial optical coherence tomography imaging

Abstract A 64-year-old man, prior smoker, with a history of paroxysmal atrial fibrillation was referred to our hospital due to worsening dyspnoea, progressively worsening angina, and a positive stress EKG testing. Coronary angiography (CAG) showed an angiographically intermediate stenosis of the mid left anterior descending (LAD) artery and a focal, complex lesion of the distal right coronary artery (RCA) (Figure 1A and B, red arrow). Treatment of the LAD stenosis was deferred based on a negative fractional flow reserve value (i.e. 0.85). Optical coherence tomography (OCT) imaging (ILUMIEN OPTIS, Abbott Vascular, Santa Clara, CA) was performed to better characterize the RCA lesion, which disclosed a ruptured thin-cap fibroatheroma (TCFA) with a large ‘empty’ cavity (Figure 1C–G, red arrows) and overlying ‘layered’ tissue (Figure 1H, white arrowheads). Based on these OCT findings, suggestive of initial plaque healing, and on a large residual lumen dimension (i.e. minimum lumen area, MLA, at the rupture site: 7.7 mm2), this lesion was not treated with percutaneous coronary intervention. The patient was discharged on aspirin, edoxaban, metoprolol, rosuvastatin, and ezetimibe, and remained clinically stable for more than 1 year. Due to angina recurrence, a new CAG was performed 18 months after the first admission, revealing a progression of the mid LAD stenosis that was treated with a 2.5/28 mm drug-eluting stent, and an improvement of the RCA lesion angiographic appearance (smooth contour) (Figure 1A′–B′). RCA OCT imaging was repeated demonstrating a complete healing of the large rupture cavity with all the hallmarks of the reparative process (Figure 1C′–H′): (1) re-established fibrous cap integrity and smooth vessel lumen profile; (2) thickening of the fibrous cap and reduction of lipid burden (i.e., transformation of TCFA into thick-cap fibroatheroma, ThCFA); (3) replacement of the ‘empty’ cavity with new ‘granulation tissue’; (4) initial calcification of the plaque; (5) heterogeneous signal-rich layers with distinct optical-signal intensity (layered, ‘onion-like’ pattern); and (6) mild lumen narrowing (MLA at the rupture site: 6.9 mm2).

Discordant resting and hyperaemic coronary physiology among unselected patients referred for coronary angiography: a single centre experience

Abstract Background Physiological assessment of intermediate coronary artery lesions to guide therapy is well established. Recently, the use of non-hyperaemic pressure ratios (NHPRs) has been suggested as a reliable alternative to hyperaemic assessment, such as fractional flow reserve (FFR). However certain patient / lesion subsets, including proximal lesion location, young patient age and assessment of non-LAD vessels, have been associated with discordance of resting and hyperaemic measurements which has led to some confusion over their interpretation and integration into routine clinical practice. Purpose To evaluate the frequency of discordant resting and hyperaemic measurements among patients undergoing assessment of intermediate coronary artery stenoses, and to identify common lesion-specific features within patients with discordant data. Methods From our coronary physiology database, we identified consecutive lesions which had been assessed between October 2020 and March 2021 with both resting (resting full-cycle ratio; RFR) and hyperaemic (wire-based FFR with peripheral adenosine) indices. Positive RFR defined as &amp;lt;0.89 (negative RFR &amp;gt;0.93, grey zone RFR 0.89–0.93). Positive FFR defined as &amp;lt;0.80 (negative FFR ≥0.80). Concordance between measurements was assessed: Group 1 (RFR -ve, FFR +ve: positive discordance); Group 2 (RFR -ve, FFR -ve: normal concordance), Group 3 (RFR +ve, FFR +ve: abnormal concordance) and Group 4 (RFR +ve, FFR -ve: negative discordance). Results 100 lesions were identified as being assessed with both RFR and FFR, in 83 patients (67% male), mean age 67 (±12) years, vessel assessed; LAD 66, RCA 19, LCx 13, LMCA 1 and radial graft 1; with 45 being proximal lesions. 30 RFR measurements were in the grey zone. Of the remaining 70 lesions, 55 results (79%) were concordant (Group 2 = 31, Group 3 = 24), with 15 results (21%) being discordant (Group 1 = 3, Group 4 = 12). Negative predictive value (NPV) of RFR (for FFR &amp;lt;0.80) was 91%, when grey zone RFR measurements were excluded. Discordance was not related to age (69 vs 68 years, p=0.75), lesion location (proximal lesion with discordance (6/15) vs proximal lesion with concordance (27/55), p=0.91, figure 1) or non-LAD vessel (non-LAD with discordance (9/15) vs non-LAD lesion with concordance (20/55), p=0.77, figure 2). Conclusion Overall within our patient group, there appeared to be a good association of RFR to FFR. In particular, RFR had a high NPV for an FFR &amp;lt;0.80. The clinical relevance of discordant measurements requires further investigation. However, our data suggest that a positive RFR (&amp;lt;0.89) measurement may not always correlate with a significant FFR measurement (&amp;lt;0.80), and the mechanism for this is unclear. Consequently, caution should be applied when including these measures in every day practice, in particular within patients with a positive RFR measurement. Funding Acknowledgement Type of funding sources: None.

Predictors of fractional flow reserve/instantaneous wave-free ratio discordance: impact of tailored diagnostic cut-offs on clinical outcomes of deferred lesions.

Patient-related and lesion-related factors may influence instantaneous wave-free ratio (iFR)/fractional flow reserve (FFR) concordance, potentially affecting the safety of revascularization deferral. Consecutive patients with at least an intermediate coronary stenosis evaluated by both iFR and FFR were retrospectively enrolled. The agreement between iFR and FFR at their diagnostic cut-offs (FFR 0.80, iFR 0.89) was assessed. Predictors of discordance were assessed using multivariate analyses. Tailored iFR cut-offs according to predictors of discordance best matching an FFR of 0.80 were identified. The impact of reclassification according to tailored iFR cut-offs on major cardiovascular events (MACE: cardiovascular death, myocardial infarction or target-lesion revascularization) among deferred lesions was investigated. Two hundred and ninety-nine intermediate coronary stenosis [FFR 0.84 (0.78-0.89), iFR 0.91 (0.87-0.95), 202 left main/left anterior descending (LM/LAD) vessels, 67.6%] of 260 patients were studied. Discordance rate was 23.4% (n = 70, 10.7% iFR-negative discordant, 12.7% iFR-positive discordant). Predictors of discordance were LM/LAD disease, multivessel disease, non-ST-elevation myocardial infarction, smoking, reduced eGFR and hypertension. Lesion reclassification with tailored iFR cut-offs based on patient-level predictors carried no prognostic value among deferred lesions. Reclassification according to lesion location, which was entirely driven by LM/LAD lesions (iFR cut-offs: 0.93 for LM/LAD, 0.89 for non-LM/LAD), identified increased MACE among lesions deferred based on a negative FFR, between patients with a positive as compared with a negative iFR (19.4 vs. 6.1%, P = 0.044), whereas the same association was not observed with the conventional 0.89 iFR cut-off (15 vs. 8.6%, P = 0.303). Tailored vessel-based iFR cut-offs carry prognostic value among FFR-negative lesions, suggesting that a one-size-fit-all iFR cut-off might be clinically unsatisfactory.

Wall shear stress estimated by 3D-QCA can predict cardiovascular events in lesions with borderline negative fractional flow reserve

Background and aimsThere is some evidence of the implications of wall shear stress (WSS) derived from three-dimensional quantitative coronary angiography (3D-QCA) models in predicting adverse cardiovascular events. This study investigates the efficacy of 3D-QCA-derived WSS in detecting lesions with a borderline negative fractional flow reserve (FFR: 0.81–0.85) that progressed and caused events. MethodsIn this retrospective cohort study, we identified 548 patients who had at least one lesion with an FFR 0.81–0.85 and complete follow-up data; 293 lesions (286 patients) with suitable angiographic characteristics were reconstructed using a dedicated 3D-QCA software and included in the analysis. In the reconstructed models blood flow simulation was performed and the value of 3D-QCA variables and WSS distribution in predicting events was examined. The primary endpoint of the study was the composite of cardiac death, target lesion related myocardial infarction or clinically indicated target lesion revascularization. ResultsDuring a median follow-up of 49.4 months, 37 events were reported. Culprit lesions had a greater area stenosis [(AS), 66.1% (59.5–72.3) vs 54.8% (46.5–63.2), p<0.001], smaller minimum lumen area [(MLA), 1.66 mm2 (1.45–2.30) vs 2.10 mm2 (1.69–2.70), p=0.011] and higher maximum WSS [9.0 Pa (5.10–12.46) vs 5.0 Pa (3.37–7.54), p < 0.001] than those that remained quiescent. In multivariable analysis, AS [hazard ratio (HR): 1.06, 95% confidence interval (CI): 1.03–1.10, p=0.001] and maximum WSS (HR: 1.08, 95% CI: 1.02–1.14, p=0.012) were the only independent predictors of the primary endpoint. Lesions with an increased AS (≥58.6%) that were exposed to high WSS (≥7.69Pa) were more likely to progress and cause events (27.8%) than those with a low AS exposed to high WSS (7.4%) or those exposed to low WSS that had increased (12.8%) or low AS (2.7%, p<0.001). ConclusionsThis study for the first time highlights the potential value of 3D-QCA-derived WSS in detecting, among lesions with a borderline negative FFR, those that cause cardiovascular events.

Stenting "Vulnerable" But Fractional Flow Reserve-Negative Lesions: Potential Statistical Limitations of Ongoing and Future Trials.

Can imaging provide sufficient risk stratification to warrant revascularization of a stable plaque with negative fractional flow reserve (FFR)? Prophylactic stenting could at best be applied selectively since the composite group of FFR-negative lesions has a death or myocardial infarction rate of approximately 1%/year or less but modern stents have a rate of 2% to 3.5%/year. Because vulnerable features exist in a minority of lesions, at least 9,000 patients must be screened in order to enroll a cohort with sufficient risk. While several ongoing randomized trials are testing the concept of plaque sealing in FFR-negative lesions, preventive stenting depends on such a small effect that sample sizes to validate or refute its benefit become prohibitive. Since FFR provides a quantitative, straightforward, and reproducible metric of plaque vulnerability and burden without the need for or expense of additional catheter devices, intracoronary imaging cannot meaningfully guide prophylactic stenting when faced with a negative FFR.