Coronary Pressure-derived Fractional Flow Reserve Research Articles

Complex Coronary Hemodynamics - Simple Analog Modelling as an Educational Tool

Objective:Invasive coronary angiography remains the cornerstone for evaluation of coronary stenoses despite there being a poor correlation between luminal loss assessment by coronary luminography and myocardial ischemia. This is especially true for coronary lesions deemed moderate by visual assessment. Coronary pressure-derived fractional flow reserve (FFR) has emerged as the gold standard for the evaluation of hemodynamic significance of coronary artery stenosis, which is cost effective and leads to improved patient outcomes. There are, however, several limitations to the use of FFR including the evaluation of serial stenoses.Method:In this article, we discuss the electronic-hydraulic analogy and the utility of simple electrical modelling to mimic the coronary circulation and coronary stenoses. We exemplify the effect of tandem coronary lesions on the FFR by modelling of a patient with sequential disease segments and complex anatomy.Results:We believe that such computational modelling can serve as a powerful educational tool to help clinicians better understand the complexity of coronary hemodynamics and improve patient care.

Identification of the State of Maximal Hyperemia in the Assessment of Coronary Fractional Flow Reserve Using Non-Invasive Electrical Velocimetry.

Previous research revealed that, in patients with coronary pressure-derived fractional flow reserve (FFR) in the 'grey zone' (0.75-0.85), repeated FFR assessments sometimes yield conflicting results. One of the causes of the fluctuations in FFR values around the grey zone may be imprecise identification of the point where maximal hyperemia is achieved. Identification of the state of maximal hyperemia during assessment of FFR can be challenging. This study aimed to determine whether non-invasive electrical velocimetry (EV) can be used to identify the state of maximal hyperemia.Stroke volume (SV), SV variation (SVV), and systemic vascular resistance index (SVRI) were determined by EV in 15 patients who underwent FFR assessment. Time intervals from initiation of adenosine infusion to achieving maximal hyperemia (timemFRR), as well as to achieving maximal cardiac output (CO), SV, SVV, and SVRI (timemCO, timemSV, timemSVV, and timemSVRI, respectively), were determined. TimemCO and timemSVV were closer to timemFRR than other values (timemSVV/timemFRR versus timemSVRI/timemFRR = 1.03 ± 0.2 versus 1.36 ± 0.4, P < 0.05). The maximum of SV was difficult to determine owing to considerable variations, but the maximum of SVV was clearly recognized. TimemCO and timemSVV were significantly correlated with timemFFR, with timemSVV showing a stronger correlation than timemSV (timemSVV: r = 0.92, P < 0.01; timemCO: r = 0.80, P < 0.01).Maximal SVV is reached close to maximal hyperemia. Monitoring of SVV with non-invasive EV during FFR assessment can help identify the state of maximal hyperemia.

TCT-336 Deferral Versus Performance of Coronary Intervention Based on Coronary Pressure-derived Fractional Flow Reserve: Systematic Review and Meta-analysis

TCT-336 Deferral Versus Performance of Coronary Intervention Based on Coronary Pressure-derived Fractional Flow Reserve: Systematic Review and Meta-analysis

Coronary pressure-derived fractional flow reserve in the assessment of coronary artery stenoses

Catheter-based angiography is the reference-standard to establish coronary anatomy. While routinely employed clinically, lumen assessment correlates poorly with physiological measures of ischaemia. Moreover, functional studies to identify and localise ischaemia before elective angiography are often not available. This article reviews fractional flow reserve (FFR) and its role in guiding patient management for patients with a potentially haemodynamic significant coronary lesion. This review discusses the theory, evidence, indications, and limitations of FFR. Also included are emerging non-invasive imaging FFR surrogates currently under evaluation for accuracy with respect to standard FFR. Coronary pressure-derived fractional flow reserve (FFR) rapidly assesses the haemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterisation laboratory. The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes. FFR is an invaluable modality in guiding coronary disease treatment decisions. It is safe, cost-effective and leads to improved patient outcomes. Non-invasive imaging modalities to assess the physiologic significance of CAD are currently being developed and evaluated.

Long-term clinical outcomes after deferral of percutaneous coronary intervention of intermediate coronary stenoses based on coronary pressure-derived fractional flow reserve

Coronary pressure-derived fractional flow reserve (FFR) has been used to evaluate functional severity of coronary artery stenoses. The cut-off point of 0.75 was considered to be the indication for percutaneous coronary intervention (PCI). In this study, we examined the prognosis of patients in whom PCI was deferred because the lesion was not significant by FFR (≥0.75). We measured FFR of 44 patients (50 lesions with angiographically intermediate stenoses by pressure wire between 2002 and 2009. Out of 44 patients (50 lesions), functionally non-significant stenoses with FFR≥0.75 were 29 patients (33 lesions) and PCI was deferred. In the remaining 15 patients (17 lesions), FFR was <0.75 and PCI was performed. Patients were followed up for an average period of 53 months with endpoints of major adverse cardiac events (MACE; cardiac death, acute coronary syndrome, PCI, and coronary artery bypass grafting). The rate of MACE was 2/29 (6.9%) in patients with FFR≥0.75 and 2/15 (13.3%) in those with FFR<0.75, and it was not statistically different between the two groups. Since long-term clinical outcomes after deferral of PCI of intermediate coronary stenoses based on FFR were excellent (annual event rate 1.6%/year), FFR is a useful index to judge the indication of PCI and risk-stratify patients for MACE.

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.

Aiming at a disorder's concept by 3D QCA vs. FFR: a case of advanced ballistics

This editorial refers to ‘Three-dimensional and two-dimensional quantitative coronary angiography, and their prediction of reduced fractional flow reserve’, by A.S.C. Yong et al. doi:10.1093/eurheartj/ehq259 ‘Oculo-stenotic reflex’ is a term which ridicules the variably developed attraction of interventional cardiologists to ‘seal’ coronary atherosclerotic bumps by balloon angioplasty. Its serious template relates to their daily business of estimating the functional relevance of a coronary stenosis by its structure. It is well known that even the experienced interventionalist may be ‘lost in translation’ when it comes to judging intermediate severity stenoses.1 Long before the development of intracoronary sensor guidewires for functional stenosis assessment, attempts were made to improve the structure–function translation by quantitative coronary angiography (QCA) as obtained in two (2D), but also as reconstructed in three dimensions (3D).2,3 The two principles of any coronary structure–function translation are (i) statistical comparison of single, physically important structural stenosis elements with a functional reference; and (ii) the mathematical integration of stenosis' geometric hallmarks to a single measure with subsequent statistical reference comparison. Ideally, both approaches would have to anticipate all the geometric patterns of a coronary atherosclerotic lesion, because it is the composite of all its finite structural elements which determines the drop in flow or perfusion pressure. Thus, the method would be aiming at a disorder's concept (i.e. recognition of how exactly and variably the epicardial stenoses grow in coronary artery disease; CAD). In philosophical terms, ‘a disorder's concept’ is an oxymoron and, therefore, pointing at it probably unsuccessful. In geometrical terms and as outlined below, it is challenging to model the structural elements of a stenosis accurately into a haemodynamic parameter. Notwithstanding these considerations, Yong and co-workers have observed, on a purely statistical basis, 2D- and 3D-QCA parameters and compared them with coronary pressure-derived fractional flow reserve (FFR) as … *Corresponding author. Tel: 41 31 632 36 93, Fax: +41 31 632 42 99, Email: christian.seiler{at}insel.ch

Relationship Between Functional Exercise Capacity and Functional Stenosis in Patients With Stable Angina and Intermediate Coronary Stenosis

Some stable angina patients with significant coronary function have low exercise capacity, whereas some have high exercise capacity. The aim of the present study was to determine whether coronary pressure-derived fractional flow reserve (FFRmyo), a functional index of coronary stenosis, is a better indicator of exercise capacity than angiographic stenosis. The 15 male (65.8 +/-8.9 years old) subjects with stable angina and 75% angiographic stenosis underwent a cardiopulmonary exercise test (CPX), and peak oxygen uptake (PeakVO(2)) and oxygen uptake at anaerobic threshold (AT) were measured. The relationship between FFRmyo and CPX values was assessed. The left anterior descending artery was affected in 8 patients, the left circumflex artery in 5, and the right coronary artery in 2. Percent diameter stenosis (%DS) was 61.7 +/-9.1% by quantitative coronary angiography. Mean FFRmyo, PeakVO(2), and AT was 0.84 +/-0.66, 17.1 +/-3.2 ml x kg(-1) x min(-1), and 11.1 +/-2.0 ml x kg(-1) x min(-1), respectively. There was no significant correlation between %DS and FFRmyo, PeakVO(2), or AT (r=0.12, 0.051, and 0.013, respectively; P=NS), but FFRmyo had a significant positive correlation with PeakVO(2) and AT (r=0.534 and 0.542, respectively; P<0.05). Exercise capacity reflects functional stenosis in stable angina patients.

Percutaneous Coronary Intervention of Functionally Nonsignificant Stenosis: 5-Year Follow-Up of the DEFER Study

The purpose of this study was to investigate the appropriateness of stenting a functionally nonsignificant stenosis. Percutaneous coronary intervention (PCI) of an intermediate stenosis without evidence of ischemia is often performed, but its benefit is unproven. Coronary pressure-derived fractional flow reserve (FFR) is an invasive index used to identify a stenosis responsible for reversible ischemia. In 325 patients scheduled for PCI of an intermediate stenosis, FFR was measured just before the planned intervention. If FFR was >or =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 5 years. There were no differences in baseline clinical characteristics between the 3 groups. Complete follow-up was obtained in 98% of the patients. Event-free survival was not different between the Defer and Perform groups (80% and 73%, respectively; p = 0.52), but was significantly worse in the Reference group (63%; p = 0.03). The composite rate of cardiac death and acute myocardial infarction in the Defer, Perform, and Reference groups was 3.3%, 7.9%, and 15.7%, respectively (p = 0.21 for Defer vs. Perform group; p = 0.003 for the Reference vs. both other groups). The percentage of patients free from chest pain at follow-up was not different between the Defer and Perform groups. Five-year outcome after deferral of PCI of an intermediate coronary stenosis based on FFR >/=0.75 is excellent. The risk of cardiac death or myocardial infarction related to this stenosis is <1% per year and not decreased by stenting.

Clinical outcome in patients with intermediate or equivocal left main coronary artery disease after deferral of surgical revascularization on the basis of fractional flow reserve measurements

Correct assessment of the significance of left main stem lesions is of pivotal importance to the patient with coronary artery disease. On the basis of clinical and angiographic information alone, this evaluation often cannot be done reliably. Limited data suggest that coronary pressure-derived fractional flow reserve (FFR) supports decision making in equivocal left main disease. All patients presenting to our institution between June 1999 and June 2004 with intermediate left main coronary artery disease (40%-80% diameter stenosis by angiography), or in whom left main coronary disease was suspected but could not be quantified angiographically, were included in this prospective single-center follow-up study. If FFR was <0.75 along the left main stem, surgical revascularization was recommended; if FFR was >0.80, medical treatment or percutaneous coronary intervention elsewhere in the coronary tree was chosen. If FFR was in the "gray zone," between > or = 0.75 and < or = 0.80 treatment recommendation was dependent on additional individual criteria. Primary end points were freedom from death, myocardial infarction, any coronary revascularization procedure, and stroke. Fifty-one patients (mean age 62.2 +/- 9.6 years, 41 male) were included. In 27 patients (53%), coronary artery bypass surgery was performed. The remaining 24 patients (47%) were treated nonsurgically. Mean follow-up was 29 +/- 16 months. Estimated survival after 4 years of follow-up was 81% among patients in the surgical group and 100% among patients in the nonsurgical group. Event-free survival was 66% in the surgical group and 69% in the nonsurgical group. Fractional flow reserve is helpful to identify patients with intermediate left main disease in whom deferral of surgical revascularization is associated with excellent survival and low event rates.

Optimizing revascularization strategies in patients with multivessel coronary disease: Impact of intracoronary pressure measurements

In patients with multivessel coronary disease, the functional significance of each lesion is often unclear, and preinterventional stress tests may be inconclusive. In this setting, intracoronary pressure measurements may be helpful to define the optimal revascularization strategy. Twenty-five consecutive patients (aged 64 +/- 11 years) with multivessel disease, inconclusive stress tests or not performed stress tests, and an angiographically intermediate coronary artery stenosis in at least 1 major vessel underwent intracoronary pressure measurements. Myocardial fractional flow reserve was measured for the intermediate lesions under the condition of maximum hyperemia induced by intravenous adenosine (140 microg x kg(-1) x min(-1). Revascularization strategies based on angiographic information alone were compared with treatment strategies based on fractional flow reserve results. The original recommendation of the revascularization procedure of choice (bypass operation or angioplasty) was changed in 9 patients (36%) on the basis of the results of fractional flow reserve measurements. In 6 more patients, pressure measurements led to a change in the recommended number of anastomoses to be aimed for during the operation. Within diffusely diseased vessels, fractional flow reserve provided an exact segmental resolution of pathologic vessel resistance for optimal graft placement. Significant left main disease was confirmed in 3 of 6 patients and was detected in 3 angiographically unsuspected cases. In patients with multivessel disease, coronary pressure-derived fractional flow reserve is a valuable tool to guide clinical decision making and support cardiologists and cardiovascular surgeons in the composition of optimal revascularization strategies.

Fractional flow reserve and complex coronary pathologic conditions.

Fractional flow reserve (FFR) is a well-validated index for assessing the physiologic significance of a coronary stenosis in most clinical conditions encountered in today's catheterisation laboratory. The aim of this paper is to provide a short overview of the theoretical background of the coronary pressure-derived FFR index and its clinical applicability in guiding complex coronary intervention procedures.

Correlation between thallium-201 myocardial perfusion defects and the functional severity of coronary artery stenosis as assessed by pressure-derived myocardial fractional flow reserve.

Although a relationship between the coronary pressure-derived fractional flow reserve (FFR) and the presence of myocardial ischemia as demonstrated by radionuclide imaging has been reported in a select group of patients, it remains to be established whether this relation also holds true in actual clinical settings with a heterogeneous group of patients. Accordingly, 194 coronary vessels and their supply territories were evaluated in 165 consecutive patients with suspected or known coronary artery disease. An FFR <0.75, which is regarded as indicative of functionally important stenosis, showed a significant correlation with the redistribution of (201)Tl (p<0.0001), with a sensitivity of 79% and specificity of 73%. In 70 infarct-related coronary arteries, the sensitivity and specificity were 79% and 75%, respectively, whereas in the 124 remaining vessels that were not related to the myocardial infarct, the sensitivity and specificity were 80% and 72%, respectively. In addition, the FFR exhibited a significant inverse correlation with the (201)Tl reversibility score (r=-0.62; p<0.0001). These results suggest that the FFR has a significant relationship with scintigraphic evidence of myocardial ischemia and can be regarded as a marker of its presence or absence in patients in actual clinical settings.

Coronary pressure-derived fractional flow reserve remains predictive of coronary stenosis in the presence of myocardial microvascular dysfunction

Coronary pressure-derived fractional flow reserve remains predictive of coronary stenosis in the presence of myocardial microvascular dysfunction