Basis Of Fractional Flow Reserve Research Articles

Combined Assessment of FFR and CFR for Decision Making in Coronary Revascularization

The aim of this study was to demonstrate the clinical implications of combined assessment of fractional flow reserve (FFR) and coronary flow reserve (CFR).Combined assessment of FFR and CFR allows detailed characterization of pathophysiology in chronic coronary syndromes. Data on the clinical implications of distinct FFR and CFR patterns are limited, leading to uncertainty regarding their relevance.Patients with chronic coronary syndromes and obstructive coronary artery disease were selected from the multicenter ILIAS (Inclusive Invasive Physiological Assessment in Angina Syndromes) registry. Patients were classified into 4 groups on the basis of FFR ≤0.80 and CFR <2.0. The endpoint was the 5-year target vessel failure (TVF) rate.A total of 2,143 patients with 2,725 lesions were included. Compared with normal FFR/normal CFR, low FFR/low CFR carried the highest risk for TVF (HR: 5.4; 95% CI: 3.2-9.3; P < 0.001), significantly higher than in revascularized vessels (P = 0.007). Discordance, with either low FFR/normal CFR or normal FFR/low CFR, was associated with increased TVF rates compared with normal FFR/normal CFR (low FFR/normal CFR: HR: 3.5 [95% CI: 2.2-5.4; P < 0.001]; normal FFR/low CFR: HR: 3.0 [95% CI: 1.9-4.7; P < 0.001]). No difference in 5-year TVF was observed between the 2 discordant groups (P = 0.57) or between the discordant groups and the revascularized group (P = 0.26 vs low FFR/normal CFR; P = 0.60 vs normal FFR/low CFR).Impaired coronary hemodynamics are uniformly associated with increased 5-year TVF rates. Nonrevascularized vessels with discordant FFR and CFR are associated with 5-year event rates that are equivalent to those of vessels that undergo revascularization, whereas vessels with combined low FFR and CFR exhibit event rates that are significantly higher than after revascularization. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry]; NCT04485234).

Thrombotic Risk and Cardiovascular Events in Patients With Revascularization Deferral After Fractional Flow ReserveAssessment.

The aim of this study was to evaluate the impact of thrombotic risk on the occurrence of cardiovascular events in patients with coronary artery disease with deferred revascularization after fractional flow reserve (FFR) measurements. Deferral of revascularization on the basis of FFR is generally considered to be safe, but after deferral, some patients have cardiovascular events over time. From J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1,263 patients with deferral of revascularization on the basis of FFR were evaluated. The association between thrombotic risk as assessed by CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) thrombotic score and 5-year target vessel failure (TVF) and major adverse cardiac and cerebrovascular events (MACCE) was investigated. FFR and high thrombotic risk (HTR) were associated with increased risk for 5-year TVF (FFR per 0.01-unit decrease: HR: 1.08; 95%CI: 1.05-1.11; P< 0.001; HTR: HR: 2.16; 95%CI: 1.37-3.39; P< 0.001) and MACCE (FFR per 0.01-unit decrease: HR: 1.05; 95%CI: 1.02-1.06; P< 0.001; HTR: HR: 2.11; 95%CI: 1.56-2.84; P=0.001). Patients with HTR had higher risk for 5-year TVF (HR: 2.30; 95%CI: 1.45-3.66; P< 0.001) and MACCE (HR: 2.34; 95%CI: 1.75-3.13; P< 0.001) than those without HTR, even when they had negative FFR. Assessment of thrombotic risk provides additional prognostic value to FFR in predicting 5-year TVF and MACCE in patients with deferral of revascularization after FFR measurements. (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry; UMIN000014473).

Ischaemic risk stratification after deferral of revascularisation on the basis of fractional flow reserve.

Ischaemic risk stratification after deferral of revascularisation on the basis of fractional flow reserve.

Revascularization Deferral of Nonculprit Stenoses on the Basis of Fractional Flow Reserve: 1-Year Outcomes of 8,579 Patients

BackgroundIntracoronary physiology is increasingly used in nonculprit stenoses of patients with acute coronary syndromes (ACS). However, evidence regarding the safety of fractional flow reserve-based deferral in patients with ACS, compared with patients with stable angina pectoris (SAP), is scarce. ObjectivesThe aim of this study was to evaluate the safety of revascularization deferral on the basis of fractional flow reserve interrogation of nonculprit lesions in patients with ACS. MethodsA pooled analysis was performed of individual patient data included in 5 large international published studies on physiology-guided revascularization. The primary endpoint was major adverse cardiac events (MACE) (a composite of death, nonfatal myocardial infarction, or unplanned revascularization) at 1-year follow-up. Clinical outcomes of patients with ACS and SAP were compared in both the deferred and the revascularized groups. ResultsA total of 8,579 patients were included in the analysis, 6,461 with SAP and 2,118 with ACS and nonculprit stenoses. Using fractional flow reserve, revascularization was deferred in 5,129 patients (59.8%) and performed in 3,450 patients (40.2%). In the deferred ACS group, a higher MACE rate was observed compared with the deferred SAP group (4.46% vs. 2.83%; adjusted hazard ratio [HR]: 1.72; 95% confidence interval [CI]: 1.17 to 2.53; p < 0.01). In particular, early unplanned revascularization (3.34% and 2.04% in ACS and SAP; adjusted HR: 1.81; 95% CI: 1.09 to 3.00; p = 0.02) contributed to this excess in MACE but the difference between the ACS and SAP groups did not reach statistical significance. On the contrary, no differences in outcomes linked to clinical presentation were found in treated patients (MACE rate 6.51% vs. 6.20%; adjusted HR: 1.21; 95% CI: 0.88 to 1.26; p = 0.24). ConclusionsPatients with ACS in whom revascularization of nonculprit lesions was deferred on the basis of fractional flow reserve have more MACE at 1 year compared with patients with SAP with deferred revascularization. Unplanned revascularization mainly contributed to this excess of MACE.

TCT-579 2-Year Outcomes After Deferral of Revascularization Based on Fractional Flow Reserve: The J-CONFIRM Registry

The safety of deferral of revascularization on the basis of fractional flow reserve (FFR) remains to be fully established in real-world practice. We sought to assess clinical outcomes of Japanese patients after FFR-based deferral of revascularization. The J-CONFIRM registry (Long-Term Outcomes of

Safety of intermediate left main stenosis revascularization deferral based on fractional flow reserve and intravascular ultrasound: A systematic review and meta-regression including 908 deferred left main stenosis from 12 studies

BackgroundCurrent guidelines recommend intravascular ultrasound (IVUS) or fractional flow reserve (FFR) to decide upon ambiguous left main (LM) disease. However, no study has compared the safety of LM revascularization deferral based on FFR or IVUS. MethodsMEDLINE/PubMed was systematically screened for studies reporting on deferred treatment of angiographically ambiguous LM based upon FFR or IVUS evaluation. Baseline, angiographic and outcome data were appraised and pooled separately for each strategy according to random-effect models with inverse-variance weighting. ResultsA total of 908 LM stenoses from 7 FFR and 5 IVUS studies were included with median follow-up of 29.0 and 31.5 months respectively. Per year of follow-up occurrence of overall MACE were 5.1% in FFR group and 6.4% in IVUS group while death, myocardial infarction, LM revascularization were respectively 2.6%, 1.5% and 1.8% vs. 3.0%, 0.5% and 2.2%. Meta-regression analysis suggested the influence of a distal LM stenosis on MACE in FFR group (β = 0.06, p = 0.01) and age in IVUS group (β = 0.4, p = 0.001). In individual studies several independent predictors of MACE were identified including use of lower doses of intracoronary adenosine (OR 1.39, p = 0.04) in FFR group and plaque burden (OR 1.34, p = 0.025), number of other diseased vessels (OR 1.39, p = 0.04) and any untreated stenosis (OR 3.80; p = 0.037) in IVUS- studies. ConclusionsDeferring LM intermediate stenosis on the basis of FFR or IVUS showed an acceptable and similar risk of events in a mid-term follow-up. Conversely, several different variables related to each technique showed an interaction on outcome.

Fractional Flow Reserve-Guided Strategy in Acute Coronary Syndrome. A Systematic Review and Meta-Analysis.

BackgroundThere are limited data on the prognosis of deferral of lesion treatment in patients with acute coronary syndrome (ACS) based on fractional flow reserve (FFR).ObjectivesTo provide a systematic review of the current evidence on the prognosis of deferred lesions in ACS patients compared with deferred lesions in non-ACS patients, on the basis of FFR.MethodsWe searched Medline, EMBASE, and the Cochrane Library for studies published between January 2000 and September 2017 that compared prognosis of deferred revascularization of lesions on the basis of FFR in ACS patients compared with non-ACS patients. We conducted a pooled relative risk meta-analysis of four primary outcomes: mortality, cardiovascular (CV) mortality, myocardial infarction (MI) and target-vessel revascularization (TVR).ResultsWe identified 7 studies that included a total of 5,107 patients. A pooled meta-analysis showed no significant difference in mortality (relative risk [RR] = 1.44; 95% CI, 0.9-2.4), CV mortality (RR = 1.29; 95% CI = 0.4-4.3) and TVR (RR = 1.46; 95% CI = 0.9-2.3) after deferral of revascularization based on FFR between ACS and non-ACS patients. Such deferral was associated with significant additional risk of MI (RR = 1.83; 95% CI = 1.4-2.4) in ACS patients.ConclusionThe prognostic value of FFR in ACS setting is not as good as in stable patients. The results demonstrate an increased risk of MI but not of mortality, CV mortality, and TVR in ACS patients.

Deferral vs. performance of percutaneous coronary intervention of functionally non-significant coronary stenosis: 15-year follow-up of the DEFER trial.

Stenting an angiographically intermediate but functionally non-significant stenosis is controversial. Nevertheless, it has been questioned if deferral of a functionally non-significant lesion on the basis of fractional flow reserve (FFR) measurement, is safe, especially on the long term. Five-year follow-up of the DEFER trial showed that outcome after deferral of percutaneous coronary intervention (PCI) of an intermediate coronary stenosis based on FFR ≥ 0.75 is excellent and was not improved by stenting. The aim of this study was to investigate the validity of this position on the very long term. In 325 patients scheduled for PCI of an intermediate stenosis, FFR was measured just before the planned intervention. If FFR was ≥0.75, patients were randomly assigned to deferral (Defer group; n = 91) or performance (Perform group; n = 90) of PCI. If FFR was <0.75, PCI was performed as planned (Reference group; n = 144). Clinical follow-up was 15 years. There were no differences in baseline clinical characteristics between the randomized groups. Complete 15-year follow-up was obtained in 92% of patients. After 15 years of follow-up, the rate of death was not different between the three groups: 33.0% in the Defer group, 31.1% in the Perform group, and 36.1% in the Reference group (Defer vs. Perform, RR 1.06, 95% CI: 0.69-1.62, P = 0.79). The rate of myocardial infarction was significantly lower in the Defer group (2.2%) compared with the Perform group (10.0%), RR 0.22, 95% CI: 0.05-0.99, P = 0.03. Deferral of PCI of a functionally non-significant stenosis is associated with a favourable very long-term follow-up without signs of late 'catch-up' phenomenon.

Fractional Flow Reserve-Guided Percutaneous Coronary Intervention: Does Coronary Pressure Never Lie?

Fractional flow reserve (FFR)-guided coronary revascularization is associated with an unequivocal clinical benefit compared with angiographic guidance. However, the well-documented clinical merit of FFR-guided revascularization has resulted in several misunderstandings as to its diagnostic characteristics. Moreover, it has led to the use of FFR as a gold-standard reference test for the identification of stenosis-related inducible myocardial ischemia. Frequently overlooked is the fact that FFR was originally validated against noninvasive stress-testing to document its ability to identify ischemia-generating stenoses, as well as its optimal cut-off value to do so, which illustrates the paradox of using FFR as a gold-standard reference for this purpose. The diagnostic characteristics of FFR are more complex than is widely understood, and its conceptual validity is based on multiple assumptions that are not considered in clinical practice. In contrast, the validity of FFR as a clinical tool is based on empirical evidence derived from multiple large-scale randomized controlled trials. It is, therefore, of great importance to understand the fundamental physiological basis of FFR, and to be aware of the underlying assumptions and their implications, for appropriate application and interpretation of FFR on an individual basis. This review aims to elucidate the assumptions that underlie the concept of FFR, to provide insight into their consequences for daily practice, and to highlight the practical methodology that is critical for its interpretation in clinical practice.

One-year outcome of patients with intermediate coronary lesions assessed by fractional flow reserve in addition to diagnostic coronary angiogram

Background: Routine measurement of Fractional Flow Reserve (FFR) reduces adverse events in patients with Coronary Artery Disease (CAD) undergoing Percutaneous Coronary Intervention (PCI). Objectives: The aim of the study was to investigate the clinical outcomes between deferral versus performance of PCI based on FFR measurements of intermediate coronary stenosis after a diagnostic Coronary Angiogram (CAG). Methods: The FFR was measured with a coronary pressure guidewire through 4 or 5 Fr diagnostic catheters approached by radial (92.4%) or brachial (7.6%) artery in addition to CAG. Maximal hyperemia was obtained after administration of intravenous adenosine (150 – 180 μg/kg/min). In 70 patients including 98 intermediate coronary lesions, measurements of FFR was successful in 67 patients (95.7%) and 93 lesions (94.9%). Patients were divided into defer group (n=55) and PCI group (n=12) on the basis of FFR <0.75. Clinical event was defined as a composite of death, myocardial infarction, or any repeat revascularization. Results: The FFR measurements could be safely performed with no complications related to diagnostic catheters, except one mild coronary spasm due to guidewire. Complete 1-year follow-up was obtained in 97.0% of patients (2 were lost to follow-up in the defer group). There was significantly better 1-year outcome in defer group (p<0.01). The rate of revascularization of deferred lesion was 2.5% (2 lesions). ![Figure][1] Kaplan-Meier Survival Curves Conclusions: The outcome of CAD patients with functionally nonsignificant lesions on the basis of FFR was excellent. Measurement of FFR at CAG could evaluate simultaneously anatomic and functional information and make an efficient decision of revascularization. [1]: pending:yes

Revascularization in multivessel CAD: a functional approach

The primary objective of invasive treatment strategies for multivessel coronary artery disease is complete anatomical revascularization--traditionally considered the strongest predictor of improved clinical outcome in this setting. This concept, however, is being challenged by evidence suggesting that addressing ischemia is the key to reducing mortality, myocardial infarction, and life-limiting angina. As objective evidence of ischemia can be provided by a functional assessment on the basis of fractional flow reserve, the focus of contemporary treatment should arguably shift from anatomical to functional revascularization. Moreover, the decision to revascularize specific lesions should be made after consideration of the degree of myocardial viability, ischemic burden, overall clinical risk, and technical feasibility. Most importantly, however, the revascularization strategy should be tailored to the individual patient and the expertise of the institution, and use contemporary techniques combined with modern pharmacotherapy. This Perspectives article summarizes the data supporting contemporary functional revascularization and its applicability to real-world practice.

From SYNTAX to FAME, a paradigm shift in revascularization strategies

In patients with chest pain, noninvasive functional assessment prior to cardiac catheterization is often missing or it is inadequate to guide percutaneous coronary revascularization. This is particularly frequent in patients with complex coronary atherosclerotic disease, such as left main stenosis or multivessel disease. Interventional cardiologists are therefore often confronted with diagnostic dilemmas as to which revascularization strategy should be adopted in these patients. A revascularization strategy based on drug-eluting stent (DES) implantation of all the lesions deemed anatomically significant has been increasingly adopted, thanks to the availability of DESs. The down side of this strategy is that DESs are being liberally used even to treat lesions that are not responsible for patients' symptoms (e.g. not ischemic), just on the basis of their angiographic appearance. An alternative approach consists in limiting DES implantation to only the lesions that are indeed responsible for patients' symptoms, like those inducing ischemia, on the basis of fractional flow reserve (FFR). Following the results of important randomized clinical trials, this article discusses the pros and cons of both strategies, underscoring the key role of functional assessment of coronary stenosis severity by FFR.

Fractional Flow Reserve Versus Angiography for Guiding Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease: 2-Year Follow-Up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Study

The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) in patients with multivessel coronary artery disease (CAD). In patients with multivessel CAD undergoing PCI, coronary angiography is the standard method for guiding stent placement. The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year. It is unknown if these favorable results are maintained at 2 years of follow-up. At 20 U.S. and European medical centers, 1,005 patients with multivessel CAD were randomly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements. Before randomization, lesions requiring PCI were identified based on their angiographic appearance. Patients randomized to angiography-guided PCI underwent stenting of all indicated lesions, whereas those randomized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was ≤0.80. The number of indicated lesions was 2.7 ± 0.9 in the angiography-guided group and 2.8 ± 1.0 in the FFR-guided group (p = 0.34). The number of stents used was 2.7 ± 1.2 and 1.9 ± 1.3, respectively (p < 0.001). The 2-year rates of mortality or myocardial infarction were 12.9% in the angiography-guided group and 8.4% in the FFR-guided group (p = 0.02). Rates of PCI or coronary artery bypass surgery were 12.7% and 10.6%, respectively (p = 0.30). Combined rates of death, nonfatal myocardial infarction, and revascularization were 22.4% and 17.9%, respectively (p = 0.08). For lesions deferred on the basis of FFR >0.80, the rate of myocardial infarction was 0.2 % and the rate of revascularization was 3.2 % after 2 years. Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infarction at 2 years when compared with standard angiography-guided PCI. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774 )

Coronary pressure measurement based decision making for percutaneous coronary intervention.

The fractional flow reserve (FFR) is a simple, reliable, and reproducible physiologic index of lesion severity. In patients with intermediate stenosis, FFR≥0.75 can be used to safely defer percutaneous coronary intervention (PCI), and patients with FFR≥0.75 have a very low cardiac event rate. Coronary pressure measurement can determine which lesion should be treated with PCI in patients with tandem lesions, and PCI on the basis of FFR has been demonstrated to result in an acceptably low repeat PCI rate. FFR can identify patients with equivocal left main coronary artery disease who benefit from coronary bypass surgery. Coronary pressure measurement distinguishes patients with an abrupt pressure drop pattern from those with a gradual pressure drop pattern, and the former group of patients benefit from PCI. Coronary pressure measurement is clinically useful in evaluating sufficient recruitable coronary collateral blood flow for prevention of ischemia, which affects future cardiac events. FFR is useful for the prediction of restenosis after PCI. As an end-point of PCI, FFR ≥0.95 and ≥0.90 would be appropriate for coronary stenting and coronary angioplasty, respectively. In summary, if you encounter a coronary stenosis in doubt you should measure pressure rather than dilate it.

Outcome of patients with acute coronary syndromes and moderate coronary lesions undergoing deferral of revascularization based on fractional flow reserve assessment

To determine the outcome of consecutive patients with and without acute coronary syndromes (ACS) in whom revascularization was deferred on the basis of fractional flow reserve (FFR). FFR < 0.75 correlates with ischemia on noninvasive tests and deferral of treatment on the basis of FFR is associated with low event rates in selected populations. Whether these low event rates apply to patients undergoing assessment of moderate stenoses in association with an ACS is not known and is an important clinical question. Retrospective analysis and 12 month follow-up of consecutive, moderate (50-70%) de novo coronary lesions assessed with FFR. Revascularization was deferred in 120 lesions (111 patients) with FFR > or = 0.75. ACS was present in 35 patients (40 lesions). The clinical, angiographic and coronary hemodynamic characteristics of patients with and without ACS were similar. Among the 35 patients with ACS, there were 3 deaths, 1 MI, and 6 target vessel revascularizations (TVRs) (15% of lesions). Among the 76 patients without ACS, there were 5 deaths, 1 MI, and 7 TVR's (9% of lesions). Deferral of revascularization based on FFR in patients with ACS and moderate coronary stenoses is associated with acceptable and low event rates at 1 year.

Long-Term Clinical Outcome After Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease

In the present study, we analyzed the clinical outcome of patients with multivessel coronary artery disease in whom at least one vessel was treated by percutaneous coronary intervention (PCI) and at least one other vessel was deferred on the basis of fractional flow reserve (FFR) measurements during the same session. Myocardial FFR is an established tool for assessing the severity of epicardial stenoses. It has been shown that it is safe to defer an intervention in single vessel disease patients when FFR >0.75. One hundred two patients (66 +/- 10 years) with multivessel coronary artery disease were included in the study. In all patients, PCI of at least two vessels was contemplated. Yet in all of them at least one vessel was treated by PCI, whereas at least one other vessel was deferred based on an FFR >0.75. Major adverse cardiac events (MACE) were recorded during an average follow-up of 29 +/- 18 months. In 102 patients, 113 coronary arteries underwent PCI. In these arteries FFR was 0.57 +/- 0.13 and mean diameter stenosis was 68 +/- 14%. One hundred twenty-seven coronary arteries had an FFR >0.75 and PCI was deferred. In these arteries FFR was 0.86 +/- 0.06 and mean diameter stenosis was 47 +/- 12%. No death occurred during the follow-up. A MACE occurred in 9% and 13% of patients after 12 and 36 months, respectively. These MACE were related to 22 (9.2%) arteries. Among them, 8 (6.3%) MACE were related to one of the initially deferred vessels, whereas 14 (12.3%) MACE were related to one of the initially treated coronary artery. In patients with multivessel disease, PCI of hemodynamically non-significant stenoses can be safely deferred, even if initially planned on the basis of the angiogram.