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BackgroundPhysicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR).ObjectivesThe purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial.MethodsMACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex.ResultsA total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06).ConclusionsiFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral.

Approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease, a condition associated with an increased incidence of recurrent ischaemic events and higher mortality. Based on recent evidences, a strategy of staged percutaneous coronary intervention (PCI) of obstructive non-culprit lesions should be considered the gold standard for the management of these patients. However, several issues remain still unresolved. Indeed, what is the optimal timing of staged PCI is not completely defined. Moreover, assessment of intermediate non-culprit lesions represent still a clinical conundrum, as pressure-wire indexes do not seem able to correctly identify those patients in whom deferral is safe. Intracoronary imaging may help to identify untreated non-culprit lesions containing vulnerable plaques that may portend a higher risk of future cardiovascular events. However, there are hitherto no studies demonstrating that preventive PCI of vulnerable plaques or more intensive pharmacological treatment is associated with an improved clinical outcome. In this review, we discuss the recent evolving concepts about management of non-culprit plaques in STEMI patients, proposing a diagnostic and therapeutic algorithm to guide physicians in clinical practice. We also underscore the several knowledge gaps to address in future studies. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Background The management of patients with angiographically intermediate coronary lesions is a major clinical issue. Fractional flow reserve provides validated functional insights while optical coherence tomography provides high resolution anatomic imaging. Both techniques may be applied to guide management in case of angiographically intermediate coronary lesions. Moreover, these techniques may be used to optimize the result of percutaneous coronary intervention. We aim to compare the clinical and economic impact of fractional flow reserve versus optical coherence tomography guidance in patients with angiographically intermediate coronary lesions. Methods/Design Patients with at least one angiographically intermediate coronary lesion will be randomized (ratio 1:1) to fractional flow reserve or optical coherence tomography guidance. In the fractional flow reserve arm, percutaneous coronary intervention will be performed if fractional flow reserve value is ⩽0.80, and will be conducted with the aim of achieving a post-percutaneous coronary intervention fractional flow reserve target value of ⩾0.90. In the optical coherence tomography arm, percutaneous coronary intervention will be performed if percentage of area stenosis (AS%) is ⩾75% or 50 to 75% with minimal lumen area <2.5 mm2, or if a major plaque ulceration is detected. In case of percutaneous coronary intervention, optical coherence tomography will guide the procedure in order to minimize underexpansion, malapposition, and edge dissections. Cost load and clinical outcome will be prospectively assessed at one and thirteen months. The assessed clinical outcome measures will be: major cardiovascular events and occurrence of significant angina defined as a Seattle Angina Questionnaire score <90 in the angina frequency scale. Discussion The FORZA trial will provide useful guidance for the management of patients with coronary artery disease by prospectively assessing the use of two techniques representing the gold standard for functional and anatomical definition of coronary plaques. Trial registration Clinicaltrials.gov NCT01824030 [ABSTRACT FROM AUTHOR]

Objectives: This study sought to compare increasing doses of intracoronary (IC) adenosine or IC sodium nitroprusside versus intravenous (IV) adenosine for fractional flow reserve (FFR) assessment. Background: Maximal hyperemia is the critical prerequisite for FFR assessment. Despite IV adenosine currently representing the recommended approach, IC administration of adenosine or other coronary vasodilators constitutes a valuable alternative in everyday practice. However, it is surprisingly unclear which IC strategy allows the achievement of FFR values comparable to IV adenosine. Methods: Fifty intermediate coronary stenoses (n = 45) undergoing FFR measurement were prospectively and consecutively enrolled. Hyperemia was sequentially induced by incremental boli of IC adenosine (ADN) (60 μg ADN60, 300 μg ADN300, 600 μg ADN600), by IC sodium nitroprusside (NTP) (0.6 μg/kg bolus) and by IV adenosine infusion (IVADN) (140 μg/kg/min). FFR values, symptoms, and development of atrioventricular block were recorded. Results: Incremental doses of IC adenosine and NTP were well tolerated and associated with fewer symptoms than IVADN. Intracoronary adenosine doses (0.881 ± 0.067, 0.871 ± 0.068, and 0.868 ± 0.070 with ADN60, ADN300, and ADN600, respectively) and NTP (0.892 ± 0.072) induced a significant decrease of FFR compared with baseline levels (p < 0.001). Notably, ADN600 only was associated with FFR values similar to IVADN (0.867 ± 0.072, p = 0.28). Among the 10 patients with FFR values ≤0.80 with IVADN, 5 were correctly identified also by ADN60, 6 by ADN300, 7 by ADN600, and 6 by NTP. Conclusions: Intracoronary adenosine, at doses higher than currently suggested, allows obtaining FFR values similar to IV adenosine. Intravenous adenosine, which remains the gold standard, might thus be reserved for those lesions with equivocal FFR values after high (up to 600 μg) IC adenosine doses. [Copyright &y& Elsevier]

The role of combined FFR/CFR measurements in decision-making on coronary revascularization remains unclear. DEFINE-FLOW prospectively assessed the relationship of FFR/CFR agreement with 2-year major adverse cardiac event (MACE) and target vessel failure (TVF) rates, and uniquely included core-laboratory analysis of all pressure and flow tracings. We aimed to document the impact of core-laboratory analysis on lesion classification, and the relationship between core-laboratory fractional flow reserve (FFR) and coronary flow reserve (CFR) values with clinical outcomes and angina burden during follow-up. In 398 vessels (348 patients) considered for intervention, ≥1 coronary pressure/flow tracing was approved by the core-laboratory. Revascularization was performed only when both FFR(≤0.80) and CFR(<2.0) were abnormal, all others were treated medically. MACE was lowest for concordant normal FFR/CFR, but was not significantly different compared with either discordant group (low FFR/normal CFR: HR:1.63; 95%CI:0.61–4.40; P = 0.33; normal FFR/low CFR: HR:1.81; 95%CI:0.66–4.98; P = 0.25). Moreover, MACE did not differ between discordant groups treated medically and the concordant abnormal group undergoing revascularization (normal FFR/low CFR: HR:0.63; 95%CI:0.23–1.73; P = 0.37; normal FFR/low CFR: HR:0.70; 95%CI:0.22–2.21; P = 0.54). Similar findings applied to TVF. Patients with concordantly normal FFR/CFR have very low 2-year MACE and TVF rates. Throughout follow-up, there were no differences in event rates between patients in whom revascularization was deferred due to preserved CFR despite reduced FFR, and those in whom PCI was performed due to concordantly low FFR and CFR. These findings question the need for routine revascularization in vessels showing low FFR but preserved CFR. Clinical trial registration: http://ClinicalTrials.gov NCT02328820 • Patients with both normal fractional flow reserve and coronary flow reserve have very low 2-year rates of adverse events. • Event rates are equivalent between patients in whom revascularization was deferred due to preserved coronary flow reserve despite reduced fractional flow reserve, and those in whom revascularization was performed • Event rates are equivalent between patients in whom revascularization was deferred due to preserved fractional flow reserve despite reduced coronary flow reserve, and those in whom revascularization was performed. • These findings question the need for routine revascularization in vessels showing discordance between fractional flow reserve and coronary flow reserve [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the diagnostic and prognostic value of non-hyperaemic Pd/Pa and to determine its additional value when combined with the gold standard hyperaemic pressure ratio (FFR) to guide revascularization. In a large, multi-center, retrospective registry, we included a total of 2141 patients with a clinical indication for coronary angiography providing physiological data in 2726 vessels. A classification was made based on the FFR (cut-off value: 0.80) and non-hyperaemic Pd/Pa (cut-off value: 0.92) values and the primary outcome was target-vessel failure (TVF) at 5-year follow-up. Mean age was 63 ± 10.0 and 75% of the study population were men. Regression analysis showed an overall good correlation between FFR and non-hyperaemic Pd/Pa (r = 0.73, p < 0.005) and discordance was present in 17% of the vessels. Resting Pd/Pa was independently associated with TVF at 5-year follow-up (HR 0.08, 95%CI: 0.02–0.27; p < 0.005). The risk for TVF was the lowest in vessles with concordant normal pressure ratio's, with the highest risk in vessels with any abnormal pressure ratio in which revascularization was deferred. In these vessels, there was no difference in risk for TVF between the discordant and concordant abnormal values. Abnormal pressure ratios in both non-hyperemic and hyperemic conditions portend important prognostic value. Combined application of FFR and non-hyperemic Pd/Pa efficiently identifies those vessels with concordant normal resting and hyperemic pressure ratios of which long-term clinical outcomes are excellent. These data lead to hypothesize that the decision to defer revascularization should potentially be based on combined non-hyperemic and hyperemic pressure ratios. Inclusive Invasive Physiological Assessment in Angina Syndromes Registry (ILIAS Registry), NCT04485234 • Abnormal pressure ratios in both non-hyperemic and hyperemic conditions portend important prognostic value for TVF at 5-year follow up. • Combined application of FFR and non-hyperemic Pd/Pa efficiently identifies those vessels with concordant normal resting and hyperemic pressure ratios of which long-term clinical outcomes are excellent. • Our data leads to hypothesize that the decision to defer revascularization should potentially be based on combined non-hyperemic and hyperemic pressure ratios, but require confirmation in prospective studies. [ABSTRACT FROM AUTHOR]

Contrast fractional flow reserve (cFFR) is a relatively new tool for the assessment of intermediate coronary artery stenosis and represents a reliable surrogate of FFR with the advantage of potentially simplifying functional evaluation. We aimed to compare the incidence of major adverse cardiac events (MACE) in patients undergoing functional evaluation with both FFR and cFFR based on the results of the two indexes. We retrospectively analyzed outcomes in 488 patients who underwent functional evaluation with FFR and cFFR. Patients were divided into four groups using the cutoff values of 0.80 for FFR and 0.85 for cFFR: −/− (n = 298), +/+ (n = 134), −/+(n = 31) and +/− (n = 25). All patients were treated according to FFR value. MACE rate was assessed in each group, including death, myocardial infarction and urgent target vessel revascularization (TVR). Mean follow-up time was 22 ± 15 months. Incidence of MACE at follow-up was 8.3% in FFR−/cFFR−, 14.0% in FFR+/cFFR+, 16.0% in FFR−/cFFR+ and 8.0% in FFR+/cFFR− without a significant difference amongst the 4 groups (p = 0.2). Nevertheless, a significant difference in the rate of TVR comparing FFR−/cFFR− (n = 17) and FFR−/cFFR+ (n = 5) was found at 24 months (5.7% vs 16.0%; p = 0.027). cFFR is accurate in predicting FFR and consequently reliable in guiding coronary revascularization. In the rare case of discordance, while FFR+/cFFR- patients show a prognosis similar to FFR-/cFFR- patients, FFR-/cFFR+ patients show a prognosis similar to FFR+/cFFR+ patients. • cFFR is a new tool in the assessment of intermediate coronary stenosis. • cFFR is accurate in predicting FFR and reliable in guiding revascularization. • In case of discordance, no significant difference in outcome choosing cFFR. • In patients with FFR > 0.80 and cFFR ≤ 0.85 TVR is higher. • cFFR could be a more sensitive index. [ABSTRACT FROM AUTHOR]

Microvascular resistance (MR) has prognostic value in acute and chronic coronary syndromes following percutaneous coronary intervention (PCI), however anatomic and physiologic determinants of the relative changes of MR and its association to target vessel failure (TVF) has not been investigated previously. This study aims to evaluate the association between changes in MR and TVF. This is a sub-study of the Inclusive Invasive Physiological Assessment in Angina Syndromes (ILIAS) registry which is a global multi-centre initiative pooling lesion-level coronary pressure and flow data. Paired pre-post PCI haemodynamic data were available in n = 295 vessels out of n = 828 PCI treated patients and of these paired data on MR was present in n = 155 vessels. Vessels were divided according to increase vs. decrease % in microvascular resistance following PCI (ΔMR % ≤ 0 vs. ΔMR > 0%). Decreased microvascular resistance ΔMR % ≤ 0 occurred in vessels with lower pre-PCI fractional flow reserve (0.67 ± 0.15 vs. 0.72 ± 0.09 p = 0.051), coronary flow reserve (1.9 ± 0.8 vs. 2.6 ± 1.8 p < 0.0001) and higher hyperemic microvascular resistance (2.76 ± 1.3 vs. 1.62 ± 0.74 p = 0.001) and index of microvascular resistance (24.4 IQ (13.8) vs. 15. 8 IQ (13.2) p = 0.004). There was no difference in angiographic parameters between ΔMR % ≤ 0 vs. ΔMR > 0%. In a cox regression model ΔMR % > 0 was associated with increased rate of TVF (hazard ratio 95% CI 3.6 [1.2; 10.3] p = 0.018). Increased MR post-PCI was associated with lesions of less severe hemodynamic influence at baseline and higher rates of TVF at follow-up. [Display omitted] • Increased microvascular resistance post-PCI is associated to a higher rate of TVF • Low TVF rate occurs in vessels lowest pre-PCI FFR and CFR, whereas vessels with highest TVF rate had higher pre-PCI FFR and CFR • The results emphasize the crucial role of the microcirculation in treating coronary artery disease • Post-PCI physiology of the target vessel is enables to identify lesions with highest risk of TVF • Changes in post-PCI microvascular resistance are not related to angiographic anatomic measures [ABSTRACT FROM AUTHOR]

Abstract Background Fractional Flow Reserve (FFR) in Stable Ischemic Heart Disease (SIHD) is universally accepted, while in Acute Coronary Syndromes (ACS) is less established. Aims of this retrospective study were: to compare in patients undergoing FFR assessment the prognostic impact of ACS vs SIHD, to evaluate the clinical relevance of the modality of utilization and timing of FFR assessment and to assess the different outcomes associated with an FFR> or ≤0.80. Methods Major cardiac adverse events were assessed at a follow up of 16.4 ± 10.5 months in 543 patients with SIHD and 231 with ACS needing functional evaluation. FFR was used for lesions of ambiguous significance in the absence of a clear culprit vessel (first intention, FI) and for incidental lesions in the presence of a clear culprit vessel (second intention, SI). The decision to perform FFR and the identification of the stenosis needing functional assessment were left to the operator's discretion. Revascularization was performed when FFR was ≤0.80. Results SIHD and ACS patients were not significantly different for principal clinical characteristics. ACS patients had significantly more events than SIHD, due to an excess of death and myocardial infarction. This was confirmed when FFR was used as FI, in particular if FFR was >0.80. On the contrary, when FFR was used as SI, event rates were similar between ACS and SIHD patients, regardless of FFR value. Conclusions Our study shows that using FFR the risk of recurrent events in ACS is significantly higher than in SIHD. This different outcome is confined to those patients in whom FFR is utilized for lesions of ambiguous significance in the absence of a clear culprit vessel. Highlights • Role of Fractional Flow Reserve (FFR) in Acute Coronary Syndromes (ACS) is matter of debate. • Our study shows that using FFR the risk of recurrent events in ACS is significantly higher than in SIHD. • The different outcome is confined to patients in whom FFR is utilized in absence of a clear culprit vessel. [ABSTRACT FROM AUTHOR]

Background The decision-making process of patients with angiographically-intermediate coronary lesions (ICL) is clinically challenging and may benefit from adjunctive invasive techniques. Fractional-flow-reserve (FFR) represents the gold standard to evaluate ICL but frequency-domain optical-coherence-tomography (OCT) is a novel, promising, high resolution coronary imaging technique, which allows physiopathologic assessment of coronary plaque. We investigated the possible relation between OCT and FFR in selected ICL patients. Methods Stable or unstable patients with ICL who underwent both FFR and OCT assessment at two large tertiary centers were retrospectively enrolled. FFR was performed according to standard methodology. OCT images were (on blind to clinical and FFR results) analyzed to assess minimal lumen area (MLA), percentage area stenosis (AS), thrombus and plaque ulceration. Results Forty patients were identified (62 ± 10 years, 93% symptomatic, 35% acute presentation, 93% left-anterior-descending artery ICL). Percentage diameter stenosis at quantitative coronary angiography was 40 ± 12% and FFR was 0.85 ± 0.07. MLA ( p = 0.009), AS ( p < 0.001) and plaque ulceration ( p = 0.02) were significantly associated with FFR values. An integrated assessment of AS (≥ or < 70%), MLA (≥ or < 2.5 mm 2 ) and presence or absence of thrombus and plaque ulceration was found to have the potential to accurately (sensitivity 91%, specificity 93%) predict FFR results. Conclusion In patients with ICL, a combination of different OCT parameters may help predict FFR results. These findings suggest that only a comprehensive assessment of lesion features by OCT can allow an accurate prediction of lesion severity assessed by FFR. [ABSTRACT FROM AUTHOR]

Aim To compare in patients with ACS (acute coronary syndromes) a PCI (percutaneous coronary intervention) approach based on FFR (fractional flow reserve) vs. one based on OCT (optical coherence tomography). Methods and results Consecutive patients admitted for ACS and treated with a PCI approach based on OCT or on FFR (recruited in two different studies) were compared and matched with propensity score analysis. Target Lesion revascularization (TLR) was the primary end point, while major adverse cardiovascular events [MACEs defined as the composite of death from cardiac causes, non-fatal MI, clinically driven target vessel revascularization (TVR), or re-hospitalization due to unstable angina] were the secondary ones. Sub-group analysis was performed for patients with FFR/OCT performed on culprit lesions and not. 285 patients were enrolled in the OCT-guided group and 335 in the FFR-guided group, 197 for each being selected after propensity score. After 25 months (range: 7–39 months), OCT-guided group were exposed to lower incidence of TLR (4.1% vs. 14.2% p < 0.01) compared with FFR-guided group without impact on MACEs (14.2% vs. 14.2%, p = 1) or all-cause death (3.6% vs. 1.1%, p = 0.34). At Kaplan-Maier curve analysis for MACEs OCT-guided and FFR-guided groups showed similar outcomes (HR 1.19, CI 0.65–2.2, p = 0.54). Subgroup analysis on culprit and not culprit vessel demonstrated consistent results. Conclusions An OCT based approach in ACS patients offers a reduction in TLR when compared to a PCI-FFR driven. These findings should be confirmed in randomized controlled trial. [ABSTRACT FROM AUTHOR]