FFR-guided Intervention Research Articles

Three-Year Clinical Impact of Murray Law-Based Quantitative Flow Ratio and OCT- or FFR-Guidance in Angiographically Intermediate Coronary Lesions.

The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (μQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of μQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up. μQFR was assessed at baseline and, in the case of a decision to intervene, after (FFR- or OCT-guided) PCI. The baseline μQFR was considered the final μQFR for deferred lesions, and post-PCI μQFR value was taken as final for stented lesions. The primary end point was target vessel failure ([TVF]; cardiac death, target-vessel-related myocardial infarction, and target-vessel-revascularization) at a 3-year follow-up. A total of 419 vessels (199 OCT-guided and 220 FFR-guided) were included in the FORZA trial. μQFR was evaluated in 256 deferred lesions and 159 treated lesions (98 OCT-guided PCI and 61 FFR-guided PCI). In treated lesions, post-PCI μQFR was higher in OCT-group compared with FFR-group (median, 0.93 versus 0.91; P=0.023), and the post-PCI μQFR improvement was greater in FFR-group (0.14 versus 0.08; P<0.0001). At 3-year follow-up, OCT- and FFR-guided treatment decisions resulted in comparable TVF rate (6.7% versus 7.9%; P=0.617). Final μQFR was the only predictor of TVF. μQFR ≤0.89 was associated with 3× increase in TVF (11.6% versus 3.7%; P=0.004). PCI was a predictor of higher final μQFR (odds ratio, 0.22 [95% CI, 0.14-0.34]; P<0.001). In vessels with angiographically intermediate coronary lesions, OCT-guided PCI resulted in comparable clinical outcomes as FFR-guided PCI. μQFR estimated at the end of diagnostic or interventional procedure predicted 3-year TVF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01824030.

Clinical Outcomes of Deferred Lesions by IVUS Versus FFR-Guided Treatment Decision.

There are limited data regarding the safety of deferral of percutaneous coronary intervention based on intravascular ultrasound (IVUS) findings. The current study sought to compare the prognosis between deferred lesions based on IVUS and fractional flow reserve (FFR)-guided treatment decision. This study is a post hoc analysis of the FLAVOUR randomized trial (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients With Intermediate Stenosis) that compared 2-year clinical outcomes between IVUS- and FFR-guided treatment decision on intermediate coronary artery lesions using predefined criteria. In both IVUS and FFR groups, vessels were classified into deferred or revascularized vessels, and patients were classified as those with or without deferred lesions. Vessel-oriented composite outcomes (cardiac death, target vessel myocardial infarction, or target vessel revascularization) in deferred vessels and patient-oriented composite outcomes (death, myocardial infarction, or any revascularization) in patients with deferred lesions were compared between the IVUS and FFR groups. A total of 1682 patients and 1820 vessels were analyzed, of which 922 patients and 989 vessels were deferred. At 2 years, there was no difference in the cumulative incidence of vessel-oriented composite outcomes in deferred vessels between IVUS (n=375) and FFR (n=614) groups (3.8% versus 4.1%; hazard ratio, 0.91 [95% CI, 0.47-1.75]; P=0.77). The risk of vessel-oriented composite outcomes was comparable between deferred and revascularized vessels following treatment decision by IVUS (3.8% versus 3.5%; hazard ratio, 1.09 [95% CI, 0.54-2.19]; P=0.81) and FFR (4.1% versus 3.6%; hazard ratio, 1.14 [95% CI, 0.56-2.32]; P=0.72). In comparison of patient-oriented composite outcomes in patients with deferred lesions, there was no significant difference between the IVUS (n=357) and FFR (n=565) groups (6.2% versus 5.9%; hazard ratio, 1.05 [95% CI, 0.61-1.80]; P=0.86). In patients with intermediate coronary artery stenosis, deferral of percutaneous coronary intervention based on IVUS-guided treatment decision showed comparable risk of clinical events with FFR-guided treatment decision. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02673424.

Clinical outcomes of deferred lesions by IVUS versus FFR-guided treatment decision: the FLAVOUR trial substudy

Abstract Background There is limited data regarding the safety of deferral of percutaneous coronary intervention (PCI) based on intravascular ultrasound (IVUS) findings. Current study sought to compare the prognosis between deferred lesions based on IVUS and FFR (fractional flow reserve)-guided treatment decision. Methods Study population was derived from FLAVOUR trial which is a multinational, open-label, randomized, and non-inferiority trial that compared 2-year clinical outcomes between IVUS and FFR-guided treatment decision using predefined criteria. In both IVUS and FFR groups, vessels were classified into deferred or revascularized vessels, and patients into those with or without deferred lesion. Vessel-oriented composite outcomes (VOCO) (cardiac death, target-vessel myocardial infarction, or target-vessel revascularization) in deferred vessels and patient-oriented composite outcomes (POCO) (death, myocardial infarction, or any revascularization) in patients with deferred lesion were compared between IVUS and FFR group. Results A total of 1682 patients and 1820 vessels were analyzed. At 2 years, there is no difference in cumulative incidence of VOCO in deferred vessels between IVUS and FFR groups (3.8% vs. 4.1%; hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.47-1.75; P=0.771). The risk of VOCO was comparable between deferred and revascularized vessels following both IVUS (3.8% vs. 3.5%; HR 1.09; 95% CI 0.54-2.19; P=0.813) and FFR-guided treatment decision (4.1% vs. 3.6%; HR 1.14; 95% CI 0.56-2.32; P=0.715). In comparison of POCO in patients with deferred lesion, there was no significant difference between IVUS and FFR groups (6.2% vs. 5.9%; HR 1.05; 95% CI 0.61-1.80; P=0.856). Conclusion In patients with intermediate coronary artery stenosis, deferral of PCI based on IVUS-guided treatment decision showed comparable risk of clinical events with FFR-guided treatment decision.

Impact of height difference between coronary ostium and location of intracoronary pressure sensor on fractional flow reserve measurements

Abstract Background Fractional flow reserve (FFR) is the most verified index to date in invasively evaluating lesion-specific myocardial ischemia. During FFR measurements, distal coronary pressure (Pd) can be influenced by hydrostatic pressure change resulted from the height difference (HD) between coronary ostium and location of distal pressure sensor. We aimed to investigate the impact of aorto-coronary HD on FFR measurement in each coronary artery. Methods We retrospectively analyzed 257 patients who underwent FFR measurement and coronary computed tomography angiography (CCTA) within a year. HD was measured by CCTA as the vertical distance between coronary ostium and a matched point of distal coronary pressure sensor identified on coronary angiography. Results The location of Pd sensor was higher in left anterior descending artery (LAD) (-4.47±1.33cm), whereas lower in left circumflex artery (LCX) (2.54±1.05cm) and right coronary artery (RCA) (2.05±1.25cm) than the coronary ostium. Compared with the original FFR values, corrected FFR by HD was higher in LAD (0.79±0.09, 0.82±0.09, P&amp;lt;0.05) and tended to be lower in LCX and RCA (0.87±0.07, 0.85±0.08, p=0.21; 0.87±0.10, 0.86±0.10, p=0.49, respectively). Based on FFR cut-off value of 0.8, the concordance rate between the FFR and corrected FFR was 77.8%, 92.5%, and 100% in LAD, LCX, and RCA, respectively. Conclusion During FFR measurements, HD between coronary ostium and distal pressure sensor may affect interpretation of disease severity and FFR-guided treatment decision of coronary artery disease.

Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease

BackgroundThere is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. ObjectivesThe FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. MethodsThe FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. ResultsThe trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months’ extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). ConclusionsIn patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555)

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes

Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.

392Systematic review and meta-analysis on the diagnostic accuracy for the detection of relevant coronary artery stenosis of vasodilator myocardial perfusion CMR and dobutamine stress echocardiography

Abstract Background Relevance of coronary artery stenosis in patients with stabile coronary artery disease (SCAD) is defined by myocardial ischemia due to flow limitation. While FFR-guided treatment of SCAD is a class IA recommendation. The initial risk stratification with detection of relevant CAD can be facilitated by several myocardial imaging methods without any preference mentioned in current guidelines. Objectives This study aimed to systematically assess and to compare the diagnostic accuracy of vasodilator myocardial perfusion cardiovascular magnetic resonance imaging (pCMR) and dobutamine stress echocardiography (DSE) for the non-invasive detection of relevant SCAD through a meta-analysis, to enable an evidential preference in risk stratification. In contrast to previously published work, this meta-analysis explicitly included only studies with rigorous eligibility criteria and a narrowly prespecified definition of their invasive reference tests. Selection criteria A study was included if (1) CCA or FFR was used as a reference standard for diagnosing relevant SCAD, defined as &gt;70% stenosis or a value &lt;0.80 on FFR recordings, respectively; (2) sufficient data to permit analysis and to reconstruct contingency tables (explicitly true-positive, false-positive, false-negative and true-negative findings) was provided; (3) there was a minimal sample size of 20 patients; (4) assessment of myocardial perfusion reserve was performed using vasodilators adenosine or regadenoson for pCMR, and dobutamine used for echocardiography; and (5) the studies were of prospective design. Data collection and analysis: From the 5,634 studies identified, 1,306 relevant articles were selected after title screening. Just 47 fulfilled all inclusion criteria on full-text review, resulting in a total sample size of 4,742 patients. Data extraction was performed for each study by two reviewers independently.Pooled analysis was performed based on a random effects models. Results The sensitivity, specificity and diagnostic odds ratio (DOR) for pCMR were 0.88 (95% confidence interval (CI): 0.85–0.90), 0.84 (95% CI: 0.81–0.87), and 38 (95% CI: 29–49), and for DSE 0.72 (95% CI: 0.61–0.81), 0.89 (95% CI: 0.83–0.93), and 20 (95% CI: 9–46), respectively. Post-test probability was augmented by positive (likelihood ratio) LR of 5.5 (95% CI: 4.7–6.5) and negative LR of 0.14 (95% CI: 0.12–0.18) based on Bayes' theorem, as compared to LR of 6.3 (95% CI: 3.8, 10.4) and negative LR of 0.31 (95% CI: 0.21, 0.46) for DSE. The size of the prediction region on the hierarchical summary receiver operating characteristic (HSROC) plot for pCMR (0.29; 95% CI 0.11–0.77) was significantly smaller compared to the one of DSE (1.07; 95% CI 0.27–4.19; p&lt;0.01). Forrest plot pCMR Conclusion The results of this systematic review and meta-analysis show that pCMR is characterized by a superior diagnostic test accuracy of relevant SCAD compared to DSE and that it can refine the post-test probability of SCAD. Acknowledgement/Funding European Heart Academy of the European Society of Cardiology

Comparison of Major Adverse Cardiac Events Between Instantaneous Wave-Free Ratio and Fractional Flow Reserve–Guided Strategy in Patients With or Without Type 2 Diabetes

Invasive physiologic indices such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are used in clinical practice. Nevertheless, comparative prognostic outcomes of iFR-guided and FFR-guided treatment in patients with type 2 diabetes have not yet been fully investigated. To compare 1-year clinical outcomes of iFR-guided or FFR-guided treatment in patients with and without diabetes in the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization (DEFINE-FLAIR) trial. The DEFINE-FLAIR trial is a multicenter, international, randomized, double-blinded trial that randomly assigned 2492 patients in a 1:1 ratio to undergo either iFR-guided or FFR-guided coronary revascularization. Patients were eligible for trial inclusion if they had intermediate coronary artery disease (40%-70% diameter stenosis) in at least 1 native coronary artery. Data were analyzed between January 2014 and December 2015. According to the study protocol, iFR of 0.89 or less and FFR of 0.80 or less were used as criteria for revascularization. When iFR or FFR was higher than the prespecified threshold, revascularization was deferred. The primary end point was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. The incidence of MACE was compared according to the presence of diabetes in iFR-guided and FFR-guided groups. Among the total trial population (2492 patients), 758 patients (30.4%) had diabetes. Mean age of the patients was 66 years, 76% were men (1868 of 2465), and 80% of patients presented with stable angina (1983 of 2465). In the nondiabetes population (68.5%; 1707 patients), iFR guidance was associated with a significantly higher rate of deferral of revascularization than the FFR-guided group (56.5% [n = 477 of 844] vs 46.6% [n = 402 of 863]; P < .001). However, it was not different between the 2 groups in the diabetes population (42.1% [n = 161 of 382] vs 47.1% [n = 177 of 376]; P = .15). At 1 year, the diabetes population showed a significantly higher rate of MACE than the nondiabetes population (8.6% vs 5.6%; adjusted hazard ratio [HR], 1.88; 95% CI, 1.28-2.64; P < .001). However, there was no significant difference in MACE rates between iFR-guided and FFR-guided groups in both the diabetes (10.0% vs 7.2%; adjusted HR, 1.33; 95% CI, 0.78-2.25; P = .30) and nondiabetes population (4.7% vs 6.4%; HR, 0.83; 95% CI, 0.51-1.35; P = .45) (interaction P = .25). The diabetes population showed significantly higher risk of MACE than the nondiabetes population, even with the iFR-guided or FFR-guided treatment. The iFR-guided and FFR-guided treatment showed comparable risk of MACE and provided equal safety in selecting revascularization target among patients with diabetes. ClinicalTrials.gov identifier: NCT02053038.

TCTAP A-003 Sex Differences in Instantaneous Wave-free Ratio (iFR) or Fractional Flow Reserve (FFR) Guided Strategy

Instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided strategy showed comparable clinical outcomes in patients with coronary artery disease. This study sought to evaluate impact of sex on iFR- and FFR-guided treatment. In this DEFINE-FLAIR (Functional Lesion Assessment of

Anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS), fractional flow reserve‐ and intravascular ultrasound‐guided management in adult patients

To describe the use of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) in the evaluation of patients with anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS). ACAOS of the right and left coronary are rare, but may lead to symptoms and impose a risk for sudden cardiac death, depending on several anatomical features. Assessment and risk estimation is challenging in (nonathlete) adults, especially if they present without symptoms or with atypical complaints. The team retrospectively studied 30 consecutive patients with ACAOS with interarterial course, who received IVUS- and FFR-guided treatment at our institution between October 2010 and September 2017. FFR was abnormal in only seven patients. IVUS showed the typical slit-like anatomy of the orifice in 23 patients. Based on FFR and/or IVUS results, in conjunction with the clinical presentation, clinical decision was made. A decision for intervention was made if at least two out of three entities were abnormal. Intervention implied unroofing of the coronary artery (n = 10) or coronary artery bypass grafting (n = 1). In all other patients a conservative strategy was followed. No adverse events occurred in the total population after a median of 37 (0-62) months of follow-up. Conservative treatment may be justifiable in adult patients with ACAOS in the presence of normal FFR and nonsuspicious symptoms, despite the presence of an interarterial course and/or slitlike orifice on IVUS. We recommend the use of FFR and IVUS in the standard work-up for adult patients with ACAOS and propose the use of a flowchart to aid in decision-making.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Impact of Routine Fractional Flow Reserve on Management Decision and 1-Year Clinical Outcome of Patients With Acute Coronary Syndromes: PRIME-FFR (Insights From the POST-IT [Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease] and R3F [French FFR Registry] Integrated Multicenter Registries - Implementation of FFR [Fractional Flow Reserve] in Routine Practice).

Fractional flow reserve (FFR) is not firmly established as a guide to treatment in patients with acute coronary syndromes (ACS). Primary goals were to evaluate the impact of integrating FFR on management decisions and on clinical outcome of patients with ACS undergoing coronary angiography, as compared with patients with stable coronary artery disease. R3F (French FFR Registry) and POST-IT (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease), sharing a common design, were pooled as PRIME-FFR (Insights From the POST-IT and R3F Integrated Multicenter Registries - Implementation of FFR in Routine Practice). Investigators prospectively defined management strategy based on angiography before performing FFR. Final decision after FFR and 1-year clinical outcome were recorded. From 1983 patients, in whom FFR was prospectively used to guide treatment, 533 sustained ACS (excluding acute ST-segment-elevation myocardial infarction). In ACS, FFR was performed in 1.4 lesions per patient, mostly in left anterior descending (58%), with a mean percent stenosis of 58±12% and a mean FFR of 0.82±0.09. In patients with ACS, reclassification by FFR was high and similar to those with non-ACS (38% versus 39%; P=NS). The pattern of reclassification was different, however, with less patients with ACS reclassified from revascularization to medical treatment compared with those with non-ACS (P=0.01). In ACS, 1-year outcome of patients reclassified based on FFR (FFR against angiography) was as good as that of nonreclassified patients (FFR concordant with angiography), with no difference in major cardiovascular event (8.0% versus 11.6%; P=0.20) or symptoms (92.3% versus 94.8% angina free; P=0.25). Moreover, FFR-based deferral to medical treatment was as safe in patients with ACS as in patients with non-ACS (major cardiovascular event, 8.0% versus 8.5%; P=0.83; revascularization, 3.8% versus 5.9%; P=0.24; and freedom from angina, 93.6% versus 90.2%; P=0.35). These findings were confirmed in ACS explored at the culprit lesion. In patients (6%) in whom the information derived from FFR was disregarded, a dire outcome was observed. Routine integration of FFR into the decision-making process of ACS patients with obstructive coronary artery disease is associated with a high reclassification rate of treatment (38%). A management strategy guided by FFR, divergent from that suggested by angiography, including revascularization deferral, is safe in ACS.

Real-world use of fractional flow reserve in Germany: results of the prospective ALKK coronary angiography and PCI registry

There is growing evidence for beneficial prognostic and economic effects of FFR-guided treatment of stable coronary artery disease. We sought to evaluate the real-world use of FFR measurements in patients undergoing elective coronary angiography. We analyzed the data of the prospective ALKK coronary angiography and PCI registry including data of 38 hospitals from January 2010 to December 2013. A total of 100,977 patients undergoing coronary angiography were included. In 3240 patients (3.2%) intracoronary pressure measurement was performed. There was a wide range of use of FFR measurement in the different analyzed ALKK hospitals from 0.1 to 8.8% in elective patients with suspected or known coronary artery disease (median 2.7%, quartiles 0.9 and 5.3%), with a successive increase of use over time during the study period. Overall, it was performed in 3.2% of coronary angiographies. Use in patients with three-vessel disease (2.5%) and recommendation for bypass surgery (1.6%) was less frequent. In procedures without PCI, dose area product was higher in the FFR group (2641cGy×cm2 vs. 2368cGy×cm2, p<0.001), while it was lower in procedures with ad hoc PCI (4676cGy×cm2 vs. 5143cGy×cm2, p<0.001). The performing center turned out to be the strongest predictor. The use of FFR measurement was very heterogeneous between different hospitals and in general relatively low, in particular in patients with multivessel disease or recommendation for bypass surgery, but there was a positive trend during the study period. Technically, FFR measurement was not associated with an increased periprocedural complication rate.

Long-term outcome of FFR-guided PCI for stable coronary artery disease in daily clinical practice: a propensity score-matched landmark analysis.

Our aim was to investigate the strength of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) in daily practice. For this study, 3,512 patients with stable CAD and at least one 50-89% coronary stenosis were identified; those patients thought to require PCI (n=1,716) were selected. Of these, 962 (56%) were treated based on angiography (XA) alone, whereas 754 patients (44%) had an FFR-guided treatment. In the latter group, 321 patients (43%) were reallocated to another treatment, predominantly medical treatment. After propensity score matching, the number of indicated lesions was 957 in the XA-guided group and 947 in the FFR-guided group. FFR guidance resulted in PCI deferral in 462 lesions (48.8%). In a seven-day landmark analysis, the rate of periprocedural myocardial infarction (MI) was less than half in the FFR-guided group (p>0.05). For the eight-day to four-year follow-up period, FFR guidance resulted in a significantly lower rate of the combined endpoint of death/MI (hazard ratio [HR] 0.63) and MI-driven target lesion revascularisation (HR 0.35). This large, retrospective study shows that performing FFR has a significant impact on therapeutic strategy and demonstrates the favourable long-term outcome of FFR-guided PCI in an "all-comers" population of patients with stable CAD in daily clinical practice.

Instantaneous Wave-Free Ratio versus Fractional Flow Reserve guided intervention (iFR-SWEDEHEART): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial

Instantaneous wave-free ratio (iFR) is a new hemodynamic resting index for assessment of coronary artery stenosis severity. iFR uses high frequency sampling to calculate a gradient across a coronary lesion during a period of diastole. The index has been tested against fractional flow reserve (FFR) and found to have an overall classification agreement of 80% to 85%. Whether the level of disagreement is clinically relevant is unknown. Clinical outcome data on iFR are scarce. This study is a registry-based randomized clinical trial, which is a novel strategy using health quality registries as on-line platforms for randomization, case record forms, and follow-up. iFR-SWEDEHEART is a multicenter, prospective, randomized, controlled, clinical open-label clinical trial. Two thousand patients with stable angina or acute coronary syndrome and an indication for physiology-guided assessment of one or more coronary stenoses will be randomized 1:1 to either iFR- or FFR-guided intervention. The randomization will be conducted online in the Swedish web-based system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) registry. The trial has a non-inferiority design, with a primary combined end point of all-cause death, non-fatal myocardial infarction, and unplanned revascularization at 12 months. End points will be identified through national registries and undergo central blind adjudication to ensure data quality. The iFR-SWEDEHEART trial is an registry-based randomized clinical trial evaluating the safety and efficacy of the diagnostic method iFR compared to FFR.

Fractional Flow Reserve in Acute Myocardial Infarction: A Guide for Non-Culprit Lesions?

In patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD), the optimal therapy for non-culprit lesions is still a matter of debate. While guidelines discourage a concomitant treatment of infarct- and non-infarct-related arteries, recent studies document advantages of a complete (preventive) revascularization during primary percutaneous coronary intervention. Such an approach, however, may result in overtreatment, because angiography does not provide robust information about the functional severity of MVD. Fractional flow reserve (FFR) measurements can be a valuable guide for non-culprit lesions in acute myocardial infarction, but so far, only the reliability and safety of FFR measurements have been established in this setting. The clinical implications of an FFR-guided treatment strategy in STEMI patients with MVD are currently being tested in a large randomized trial.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-015-0040-4) contains supplementary material, which is available to authorized users.

050 FFR-GUIDED CORONARY REVASCULARISATION: IMPLICATIONS OF ITS BIOLOGICAL VARIABILITY ON CLINICAL DECISIONS

Background Based on FAME and FAME II trials, current appropriateness guidelines recommend the utilisation of fractional flow reserve (FFR) to guide coronary revascularisation based on a fixed cut-off of 0.8. However, this does not take into account the intrinsic measurement variability of a single FFR result. We evaluate the effects of the FFR measurement variability on FFR-guided treatment strategy. Methods FFR reproducibility data from DEFER was digitised (2 repeated FFR measurements in the same lesion, 10 min apart) and the SD of the difference (SDD) between repeated measurements was calculated. The measurement certainty (probability that the FFR-guided revascularisation strategy will not change if the test is repeated 10 min later) was subsequently established across the whole range of FFR values, from 0.2 to 1. Results Outside the (0.75–0.85) FFR range, measurement certainty of a single FFR result is >95%. However, closer to its cut-off, certainty falls to less than 80% within (0.77–0.83), reaching a nadir of 50% around 0.8. In clinical practice, that means that each time a single FFR value falls between 0.75 and 0.85, there is a chance that the FFR-derived revascularisation recommendation will change if the measurement is repeated 10 min later, with this chance increasing to the closer the FFR result is to 0.8. Conclusions A measurement FFR grey-zone is found between (0.75–0.85). Therefore, clinicians should make revascularisation decisions based on broadened clinical judgement when FFR falls within this measurement grey-zone, particularly between (0.77–0.83), when measurement certainty falls to less than 80%.

Fractional Flow Reserve–Guided Revascularization: Practical Implications of a Diagnostic Gray Zone and Measurement Variability on Clinical Decisions

This study sought to evaluate the effects of fractional flow reserve (FFR) measurement variability on FFR-guided treatment strategy. Current appropriateness guidelines recommend the utilization of FFR to guide coronary revascularization based on a fixed cut-off of 0.8. This rigid approach does not take into account the intrinsic biological variability of a single FFR result and the clinical judgment of experienced interventional cardiologists. [corrected]. FFR reproducibility data from the landmark Deferral Versus Performance of PTCA in Patients Without Documented Ischemia (DEFER) trial was analyzed (two repeated FFR measurements in the same lesion, 10 min apart) and the standard deviation of the difference (SDD) between repeated measurements was calculated. The measurement certainty (probability that the FFR-guided revascularization strategy will not change if the test is repeated 10 min later) was subsequently established across the whole range of FFR values, from 0.2 to 1. Outside the [0.75 to 0.85] FFR range, measurement certainty of a single FFR result is >95%. However, closer to its cut-off, certainty falls to less than 80% within 0.77 to 0.83, reaching a nadir of 50% around 0.8. In clinical practice, that means that each time a single FFR value falls between 0.75 and 0.85, there is a chance that the FFR-derived revascularization recommendation will change if the measurement is repeated 10 min later, with this chance increasing the closer the FFR result is to 0.8. A measurement FFR gray-zone is found between 0.75 and 0.85]. Therefore, clinicians should make revascularization decisions based on broadened clinical judgment when a single FFR result falls within this uncertainty zone, particularly between 0.77 and 0.83, when measurement certainty falls to less than 80%.

Long-term outcomes of fractional flow reserve-guided vs. angiography-guided percutaneous coronary intervention in contemporary practice

Fractional flow reserve (FFR) is the reference standard for the assessment of the functional significance of coronary artery stenoses, but is underutilized in daily clinical practice. We aimed to study long-term outcomes of FFR-guided percutaneous coronary intervention (PCI) in the general clinical practice. In this retrospective study, consecutive patients (n = 7358), referred for PCI at the Mayo Clinic between October 2002 and December 2009, were divided in two groups: those undergoing PCI without (PCI-only, n = 6268) or with FFR measurements (FFR-guided, n = 1090). The latter group was further classified as the FFR-Perform group (n = 369) if followed by PCI, and the FFR-Defer group (n = 721) if PCI was deferred. Clinical events were compared during a median follow-up of 50.9 months. The Kaplan-Meier fraction of major adverse cardiac events at 7 years was 57.0% in the PCI-only vs. 50.0% in the FFR-guided group (P = 0.016). Patients with FFR-guided interventions had a non-significantly lower rate of death or myocardial infarction compared with those with angiography-guided interventions [hazard ratio (HR): 0.85, 95% CI: 0.71-1.01, P = 0.06]; the FFR-guided deferred-PCI strategy was independently associated with reduced rate of myocardial infarction (HR: 0.46, 95% CI: 0.26-0.82, P = 0.008). After excluding patients with FFR of 0.75-0.80 and deferring PCI, the use of FFR was significantly associated with reduced rate of death or myocardial infarction (HR: 0.80, 95% CI: 0.66-0.96, P = 0.02). In the contemporary practice, an FFR-guided treatment strategy is associated with a favourable long-term outcome. The current study supports the use of the FFR for decision-making in patients undergoing cardiac catheterization.

Usefulness of Coronary Pressure Measurement for Functional Evaluation of Drug-Eluting Stent Restenosis

Despite the widespread adoption of drug-eluting stent (DES) implantation, the optimal treatment of DES failures remains challenging. The present study evaluated the relation between quantitative angiography and the fractional flow reserve (FFR) in restenotic lesions after DES implantation and the efficacy of FFR in determining whether to treat these lesions. To assess their functional significance, the coronary pressure-derived FFR was measured in 50 DES restenotic lesions (49 patients). Additional intervention was performed in lesions with a FFR <0.8. Major adverse cardiac events were assessed at 12 months after the reintervention procedure. The mean percent diameter stenosis (%DS) was 58 ± 13%. Of the 50 lesions, 20 (40%) were deferred without additional intervention. The FFR and %DS had a negative correlation (r = -0.61, p <0.001). However, when only the lesions with diffuse-type restenosis (15 lesions) were analyzed, the degree of correlation decreased (r = -0.56, p = 0.12). Although most lesions (89%) with a %DS of ≥70 had significant functional ischemia, among 41 lesions with a %DS <70, only 20 (49%) had demonstrated functional patency. The incidence of adverse events during the 12 months of follow-up after FFR-guided treatment was 18.0% (23.3% in the FFR <0.80 group and 10.0% in FFR ≥0.80 group). In conclusion, a discrepancy was found between functional ischemia measured by the FFR and the angiographic %DS, in particular, in moderate- or diffuse-type restenotic lesions after DES implantation. The outcome of FFR-guided deferral in patients with DES in-stent restenosis seems favorable.