Non-invasive Angiographic-based Fractional Flow Reserve:Technical Development,Clinical Implications,and Future Perspectives

New non-and less-invasive techniques have been developed to overcome the procedural and operator related burden of the fractional flow reserve(FFR)for the assessment of potentially significant stenosis in the coronary arteries.Virtual FFR-techniques can obviate the need for the additional flow or pressure wires as used for FFR measurements.This review provides an overview of the developments and validation of the virtual FFR-algorithms,states the challenges,discusses the upcoming clinical trials,and postulates the future role of virtual FFR in the clinical practice.

Fractional flow reserve measured via left internal mammary artery after coronary artery bypass grafting:Two case reports

BACKGROUND The fractional flow reserve(FFR)has made the treatment of coronary heart disease more precise.However,there are few reports on the measurement of FFR via the left internal mammary artery(LIMA).Herein,we described the determination of further treatments by measuring FFR via the LIMA in 2 cases after coronary artery bypass grafting(CABG).CASE SUMMARY Case 1 was a 66-year-old male who was admitted due to“chest tightness after CABG.”The patient underwent CABG 7 years prior due to coronary heart disease.Coronary artery angiography showed complete occlusion of the left anterior descending artery(LAD),and subtotal occlusion of the third segment of the right coronary artery.On arterial angiography,there was 85%stenosis at the distal end of the anastomosis of the LIMA-LAD graft.FFR via LIMA was determined at 0.75.Thus,balloon dilation was performed in Case 1.FFR after balloon dilation was 0.94.Case 2 was a 60-year-old male who was admitted due to“chest tightness after CABG.”The patient underwent CABG 6 years prior due to coronary heart disease.There was 60%segmental stenosis in the middle segment of LAD and 75%anastomotic stenosis.FFR measured via LIMA was 0.83(negative);thus the intervention was not performed.Case 2 was given drug treatments.At the 3-mo follow-up,there was no recurrence of chest tightness or shortness of breath in both cases.They are currently under continual follow-up.CONCLUSION We provided evidence that FFR measurement via grafted blood vessels,especially LIMA,after CABG is a good method to determine the intervention course.

Comparative efficacy and safety of adenosine and regadenoson for assessment of fractional flow reserve:A systematic review and meta-analysis

BACKGROUND Adenosine is a coronary hyperemic agent used to measure invasive fractional flow reserve(FFR)of intermediate severity coronary stenosis.AIM To compare FFR assessment using adenosine with an alternate hyperemic agent,regadenoson.METHODS PubMed,Google Scholar,CINAHL and Cochrane databases were queried for studies comparing adenosine and regadenoson for assessment of FFR.Data on FFR,correlation coefficient and adverse events from the selected studies were extracted and analyzed by means of random effects model.Two tailed P-value less than 0.05 was considered significant.Heterogeneity was assessed using I2 test.RESULTS Five studies with 248 patients were included in the final analysis.All included patients and coronary lesions underwent FFR assessment using both adenosine and regadenoson.There was no significant mean difference between FFR measurement by the two agents[odds ratio(OR)=-0.00;95%confidence interval(CI):(-0.02)-0.01,P=0.88].The cumulative correlation coefficient was 0.98(0.96-0.99,P<0.01).Three of five studies reported time to FFR with cumulative results favoring regadenoson(mean difference 34.31 s;25.14-43.48 s,P<0.01).Risk of adverse events was higher with adenosine compared to regadenoson(OR=2.39;95%CI:1.22-4.67,P=0.01),which most commonly included bradycardia and hypotension.Vast majority of the adverse events associated with both agents were transient.CONCLUSION The performance of regadenoson in inducing maximal hyperemia was comparable to that of adenosine.There was excellent correlation between the FFR measurements by both the agents.The use of adenosine,was however associated with higher risk of adverse events and longer time to FFR compared to regadenoson.

Modes of failure with fractional flow reserve guidewires:Insights from the manufacturer and user facility device experience database

BACKGROUND Fractional flow reserve(FFR)measurement is commonly used in the cardiac catheterization laboratory to assess the functional significance of coronary arterial plaques.Robust real-world data on complications and modes of failure of FFR guidewires are limited.AIM To characterize these outcomes by analyzing the post-marketing surveillance data from the United States Food and Drug Administration Manufacturer and User Facility Device Experience(MAUDE)database for commonly used FFR guidewires.METHODS The MAUDE database was queried from January 2010 through April 2020 for 3 FFR guidewires[PressureWireTM X(Abbott),CometTM(Boston Scientific),and VerrataTM(Philips)]by searching for the following events:“Injury”,“malfunction”,“death”,and“other”.This yielded 544 reports.After excluding incomplete reports,486 reports were analyzed.RESULTS Guidewire tip fracture was the most commonly reported mode of failure,in 174(35.8%)cases followed by guidewire kinking(n=152,31.3%),communication failure(n=141,29.0%),and shaft fracture(n=67,13.8%).In total,133(27.4%)device failures resulted in patient adverse events.The most common adverse event was retained guidewire tip,in 71(53.4%)cases,followed by freshly deployed stent dislodgment(n=26,19.6%)and coronary artery dissection(n=23,17.3%).Seven deaths were reported.CONCLUSION FFR guidewire failures can occur because of various mechanisms and cause patient adverse events.The MAUDE database serves as an important platform for improved collaboration among clinicians,device manufacturers,and regulators to improve device performance and optimize patient outcomes.Our analysis provides mechanistic insights of FFR guidewire failure and associated adverse events but cannot verify causality or provide a comparison among different guidewires.

Usefulness of Fractional Flow Reserve during Routine Clinical Procedures in All-Comer Coronary Artery Disease Patients

Background: Fractional flow reserve (FFR)-guided interventions, though proved to be safe, continue to be a much-underutilized modality in determining treatment strategy, and data is lacking in Indian population. Objective: We aimed to determine the use of FFR-guided PCI and assess the overall impact on treatment decisions and clinical outcomes in patients with acute coronary syndrome (ACS) or chronic coronary syndromes (CCS). Methods: In this single-center retrospective and prospective observational study, FFR had been performed for the evaluation of treatment reclassification and clinical outcomes, as per physician’s clinical practice. Results: Data was obtained for 250 subjects (mean age 60.45 ± 9.6 years) with 324 lesions. The treatment plan based on angiography alone changed in 28% of lesions post-hyperemic FFR. The initial treatment plan based on angiography vs. the final treatment plan post-FFR (>0.80) was medical management 56.5% vs. 66.0%;CABG 11.1% vs. 7.7%;and PCI 32.4% vs. 26.2%. In subjects initially assigned to medical management, 14% had changed to PCI, and for subjects initially assigned to PCI, 44% had changed to medical therapy. Receiver operating characteristics (ROC) curve analysis revealed a good correlation between a resting FFR value of <0.87 and hyperemic FFR value of <0.80. The rate of 2-year major adverse cardiovascular events (MACE) was 0.9%. Conclusion: This study supports the use of FFR in determining treatment strategy in ACS or CCS patients with low MACE. Resting FFR value of <0.87 may be an alternative to intracoronary nitroglycerine/adenosine/Nikorandil-induced FFR in predicting positive FFR particularly in hemodynamically unstable patients, and who are intolerant to hyperemic drugs.

Fractional Flow Reserve Guided Percutaneous Coronary ntervention Improves Clinical Outcome with Reduced Cost in Contemporary Clinical Practice

Background：Fractional flow reserve （FFR） is currently considered as the gold standard for evaluating the functional significance of coronary stenosis.However,its potential benefits in real-world practice remain unknown in China.This study aimed to test the hypothesis that the use of FFR is associated with improved outcome and reduced cost in Chinese real-world clinical practice.Methods：A retrospective cohort study was carried out using the database of Second Affiliated Hospital of Zhejiang University,a tertiary and high-volume center in China.Clinical events were compared using the Cox proportional hazards model during a median follow-up of 13 months.Results：The study cohort consisted of 366 consecutive patients referred for coronary revascularization with adjunct FFR and 366 matched controls,from 2010 to 2014.Major adverse cardiac events （MACEs） （death,myocardial infarction,repeated revascularization,or hospitalization for angina） at 4 years were found in 12.0% ofangiography-guided patients and 4.9% in the FFR-guided group （P 〈 0.001）.The mean number of implanted stents was significantly lower in FFR treated subjects （0.52 ± 0.82 stents） compared with the angiography-guided group （0.93 ± 0.96 stents） （P 〈 0.001）.No difference in overall costs at initial hospitalization was observed between angiography-guided percutaneous coronary intervention （PCI） compared with FFR-guided PCI （RMB 33,000 Yuan,range：RMB 7393-44,700 Yuan） versus RMB 21,200 Yuan （RMB 19,100-47,100 Yuan） （P =0.54）.However,costs for MACEs during follow-up were significantly reduced in the FFR-guided arm （P 〈 0.001）.Conclusions：In the contemporary clinical practice,FFR-guided PCI is associated with decreased use of stents,improved clinical outcome,and reduced costs,compared with angiography-guided PCI.

Hemodynamic changes of fractional flow reserve after double kissing crush and provisional stenting technique for true bifurcation lesions

Background Fractional flow reserve （FFR）-guided percutaneous coronary intervention （PCI） is associated with fewer unfavorable events. However, the hemodynamic change in FFR after different stenting approaches for bifurcation lesions is still not fully studied. The aim of this study was to analyze the hemodynamic changes in FFR after double kissing （DK） crush and provisional side branch （SB） stenting （PS） for true coronary bifurcation lesions. Methods Seventy-five patients with true bifurcated lesions were randomly divided into DK （n=38） and PS （n=37） groups. Additional SB stenting in the PS group was required if there was any pinched SB ostium 〉70% stenosis, or ≥ type B dissection, or TIMI flow 〈grade 3. FFR at hyperemia in the main vessel （MV） and SB was measured prior- and post-stenting, and at 8 months follow-up. Results Baseline clinical, angiographic and lesion characteristics were matched well between the two groups, with the exception of the final kissing balloon inflation （FKBI, 100.0% in the DK vs. 83.8% in the PS group, P 〈0.001）. Baseline FFR was comparable between the DK and the PS groups, however, the acute gain and late loss of SB FFR at 8-month follow-up in the DK group were 0.18±0.15 and -0.06±0.11, compared to 0.12±0.18 （P=0.044） and -0.002±0.07 （P=-0.037） in the PS group, respectively. MV FFR post-stenting 〉0.94 was seen in about 40% of patients. There was no significant difference in the clinical events at 1-year follow-up between the two groups. Conclusions DK crush was associated with improved acute gain and late loss of SB FFR. The lower rate of FFR 〉0.94 after stenting underscored the further improvement of stentinq quality.

Current status of assessment of fractional flow reserve

Coronary angiography presently remains the main method tor the diagnosis and instruction of epicardial coronary disease. However, precise characterization of the significance for any given stenosis is limited by the inability to identify intermediate coronary lesions responsible for ischemia. In clinical practice, in addition to the assessment of the anatomical details of vessel narrowing, a more impediment to coronary precise assessment of the blood flow has become extremely important. At present, several physiological parameters have been introduced to improve discrimination in functional coronary lesion severity during cardiac catheterization. Of these parameters, myocardial fractional flow reserve （FFR） has been the most frequently used and is being increasingly applied to assess the functional significance of intermediate lesions. FFR can provide important information, both for decision making in diagnostic angiography and for monitoring and evaluating coronary interventions.

Clinical Relevance of Coronary Fractional Flow Reserve： Art-of-state

Objective：The objective was to delineate the current knowledge of fractional flow reserve （FFR） in terms of definition,features,clinical applications,and pitfalls of measurement of FFR.Data Sources：We searched database for primary studies published in English.The database of National Library of Medicine （NLM）,MEDLINE,and PubMed up to July 2014 was used to conduct a search using the keyword term ＂FFR＂.Study Selection：The articles about the definition,features,clinical application,and pitfalls of measurement of FFR were identified,retrieved,and reviewed.Results：Coronary pressure-derived FFR rapidly assesses the hemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterization laboratory.The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes.Conclusions：FFR is a valuable tool to determine the functional significance of coronary stenosis.It combines physiological and anatomical information,and can be followed immediately by percutaneous coronary intervention （PCI） if necessary.The technique of FFR measurement can be performed easily,rapidly,and safely in the catheterization laboratory.By systematic use of FFR in dubious stenosis and multi-vessel disease,PCI can be made an even more effective and better treatment than it is currently.The current clinical evidence for FFR should encourage cardiologists to use this tool in the catheterization laboratory.

Noninvasive assessment of renal fractional flow reserve： are we there yet？

The highly diagnostic performance of renal transstenotic pressure gradients （TSPG） and fractional flow reserve （FFR） has been well validated for assessment of the hemodynamic renal artery stenosis （RAS）.1-4 Accordingly,an expert consensus panel of the American Heart Association recommended that a peak systolic gradient of at least 20 mmHg （1 mmHg=0.133 kPa）,or a mean pressure gradient of 10 mmHg,be used to identify candidate lesions for revascularization in symptomatic patients with RAS.

Noninvasive Measurement of Coronary Fractional Flow Reserve： An Under-exploiting Newland

INTRODUCTION In patients with coronary artery disease （CAD）, the most important factors regarding to both symptoms and outcomes are the presence and extent of inducible ischemia. Alleviation of ischemia with percutaneous coronary intervention （PCI） can improve symptoms and clinical outcomes.

Fractional Flow Reserve： From Homeland to Colony

In current catheter research, there are 3 main directions with respect to fractional flow reserve （FFR）, including instantaneous wave-tree ratio, noninvasive measurement of FFR, and FFR transferred from coronary circulation to other ischemia-inducing circulation. Recently, an interesting study was published, in which FFR was performed to diagnose and guide stenting in chronic mesenteric ischemia （CMI）. We herein highlighted, the implications and limitations of FFR from coronary artery to renal artery and mesenteric artery for future investigations, respectively.

Role of fractional flow reserve in guiding intervention for borderline coronary lesions

Objective:This study investigated the clinical efficacy and value of fractional flow reserve(FFR)in guiding the treatment of borderline coronary lesions.Methods:Forty-three patients with borderline coronary lesions,as demonstrated by coronary angiography,and who had FFR measurements were selected.The patients were grouped accord-ing to FFR values.All patients were evaluated 6 months after surgery to record major adverse cardiac events(MACE[sudden cardiac death,non-fatal myocardial infarction,or revasculariza-tion])and recurrence of angina pectoris.Results:After the 6-month follow-up,no sudden cardiac deaths or myocardial infarctions occurred in either group,and there were no statistically significant differences(P>0.05).Inter-group comparisons showed that in the groups with a FFR<0.75,the recurrence rate of angina pectoris in the PCI group was significantly lower than the drug therapy group(0.08%vs.0.27%,P<0.05).In contrast,the recurrence rate of angina pectoris in the PCI group among the groups with a FFR<0.75 revealed no statistical significance when compared to the groups with a FFR≥0.75(0.08%vs.0.05%,P>0.05).The recurrence rate of angina pectoris in the simple drug therapy group among the groups with a FFR<0.75 was higher than the same groups with a FFR≥0.75(0.27%vs.0.05%,P<0.05).Conclusion:When coronary intervention is used to treat borderline lesions,guiding inter-ventional therapy with measurement of FFR does not increase the incidence of adverse cardiovas-cular events in the short term and can better guide PCI therapy.

Relationship between fibrinogen and fractional flow reserve in coronary intermediate lesions

Objective To study the relationgship and the clinical significance between plasma fibrinogen and fractional flow reserve(FFR)in coronary intermediate lesions.Methods The patients were from The Department of Cardiovascular of Affiliated Hospital of Xuzhou Medical College.Their coronary artery lesions were assessed by

Deferred revascularization in diabetic patient according to combined invasive functional and intravascular imaging data:A case report

BACKGROUND Invasive functional evaluation by fractional flow reserve(FFR)is considered as a gold standard for the evaluation of intermediate coronary stenosis.However,in patients with diabetes due to accelerated progression of atherosclerosis the outcome may be worse even in the presence of negative functional testing.CASE SUMMARY We present a case of 55-year-old male diabetic patient who was admitted for chest pain.Diagnostic coronary angiography disclosed 2 intermediate stenoses of the obtuse marginal branch with no evidence of restenosis on previously implanted stent.Patient undergone invasive functional testing of intermediate lesion with preserved FFR(0.88),low coronary flow reserve(1.2)and very high index of microvascular resistance(84).Due to discrepancy in invasive functional parameters,intravascular imaging with optical coherence tomography showed fibrotic stenoses without signs of thin-sup fibroatheroma.Because of the preserved FFR and no signs of vulnerable plaque,the interventional procedure was deferred and the patient continued with optimal medications.CONCLUSION Combined functional and anatomic imaging of intermediate coronary stenosis in diabetic patients represent comprehensive contemporary decision pathway in the management of the patients.

Coronary Physiology in the Management of CAD Patients: Position Paper Regarding the Current Scenario in India

Fractional flow reserve (FFR), a physiology-based diagnostic method, has emerged as an important decision-making tool in determining the borderline or intermediate coronary lesions requiring revascularization. As per the guidelines recommended by European and American cardiology associations, functional assessment of indeterminate lesions is to be considered strongly prior to PCI. However, in India, FFR continues to be a much-underutilized tool due to limited facilities, and many times, physicians are reluctant to advise FFR because of its time-consuming nature with additional cost implications of simple diagnostic tests. Notably, for stenoses ranging between 50% - 70% where the choice between revascularization and medication becomes ambiguous, FFR provides invaluable insight. Without such guidance, there is a risk of improper decisions and strategies while planning revascularization procedures, which might adversely influence clinical outcomes, escalation of the cost due to unnecessary procedures, and prolonged hospitalization as a result of simple vs complex procedures. Landmark studies have validated the efficacy of FFR in enhancing outcomes in coronary artery disease (CAD) patients, especially when paired with a coronary angiogram. This combination provides robust evidence of the functional significance of stenosis in stable CAD. Additionally, non-hyperemic pressure ratio indices correlate well with conventional FFR. Hence, adopting FFR-guided management can have transformative effects on the clinical and economic facets of treating severe CAD with intermediary lesions in Indian settings.

Coronary physiology assessment in the catheterization laboratory

Physicians cannot rely solely on the angiographic appearance of epicardial coronary artery stenosis when evaluating patients with myocardial ischemia. Instead, sound knowledge of coronary vascular physiology and of the methods currently available for its characterization can improve the diagnostic and prognostic accuracy of invasive assessment of the coronary circulation, and help improve clinical decision-making. In this article we summarize the current methods available for a thorough assessment of coronary physiology.

Effect of the Wall Thickness of the Vessel on FFRCT of Carotid Artery Stenosis

Fractional flow reserve(FFR)computed from computed tomography angiography(CTA),i.e.,FFRCT has been used in the clinic as a noninvasive parameter for functional assessment of coronary artery stenosis.It has also been suggested to be used in the assessment of carotid artery stenosis.The wall thickness of the vessel is an important parameter when establishing a fluid-structure coupling model of carotid stenosis.This work studies the effect of the vessel wall thickness on hemodynamic parameters such as FFRCT in carotid stenosis.Models of carotid stenosis are established based on CTA image data using computer-aided design software.It is assumed that the vessel wall is a linear elastic and isotropic material,and the blood an incompressible Newtonian fluid.Under the pulsating flow condition,ANSYS Transient Structural and CFX are used to simulate the blood flow of fluid-structure coupling in the carotid stenosis model in order to obtain hemodynamic parameters and the corresponding FFRCT.The results show that when the elastic modulus of the vessel wall is fixed,FFRCT will decrease with the increase of the wall thickness.Similarly,FFRCT will decrease with the increase of the elastic modulus when the wall thickness is fixed.The difference in hemodynamic parameters such as FFRCT,however,is relatively small if the stiffness of the two models are close.The results demonstrate that the effect of the vessel wall thickness,especially for a model with small elastic modulus,should be taken into account in using FFRCT for functional assessment of carotid stenosis.Moreover,under the linear elasticity and isotropic material assumptions,the stiffness coefficient may replace the elastic modulus and wall thickness as a parameter reflecting material property of the vessel wall in the carotid stenosis model.

A case report of significant progression after FFR-guided deferred PCI

In recent years,the use of coronary functional evaluation derived by fractional flow reserve(FFR)to guide percutaneous coronary intervention(PCI)treatment has been recommended by several mainstream guidelines.Typically,FFR>0.80 in coronary artery indicates the lesions do not affect the coronary blood flow.

Impact of Revascularization on the Distal to Proximal Pressure Ratio in Case of Multiple Coronary Stenoses

Objective: In order to take a decision about the revascularization approach to be adopted, it is of fundamental importance to determine whether coronary artery stenoses induce ischemia or not. An index, named (Fractional Flow Reserve), based on pressure measurements has been proposed to this aim and is usually interpreted in terms of flows. The objective of this work is to compute simultaneously pressures and flow rates in the coronary network of patients with three-vessel disease, in order to study more precisely the relationship between these two quantities. Approach: 22 patients have been included in the study. Some pressure and flow rate measurements were collected during by-pass surgery. These clinical data allow determining parameters for a patient’s specific model, based on the electric/hydraulic analogy. Collateral pathways are included in the model, as well as the severity of the disease and the impact of revascularization. Main Results: For patients with stenoses on LAD, LCx, LMCA and occlusion of the RCA, the flow rate delivered to the right territory is of course a function of the aortic pressure, the left stenoses severity, and the pressure distal to the thrombosis. But it mainly depends on the capillary and collateral resistances, and on the proportion between them. Abnormal microvascular hemodynamics, may be present in patients with non-hemodynamic significant lesions as assessed by the pressure ratio. Complete revascularization with the 3 grafts is demonstrated to be fully justified. The direction of collateral flows may be reversed, depending on the pressure gradient. In any case, they remain low and become negligible when the 3 grafts are operating. Significance: Surgical decision based only on pressure measurements may miss some real hemodynamic problems due to the considered stenosis. This risk is even greater in case of serial stenoses.