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Background: Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as 'leak'. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models., Methods and Results: The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; -5.2 mL/min, 95% CI -52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI -325 to ＋2549)., Conclusion: Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data. The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This independent research was carried out at the National Institute for Health and Care Research (NIHR) Sheffield Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: The treatment of a coronary bifurcation with a single stent (the provisional stenting technique) is associated with a good outcome in most cases. In the majority of cases, after provisional stenting technique, a residual significant angiographic stenosis is associated with the absence of ischemia when fractional flow reserve (FFR) is measured. Jailing an optical pressure guidewire in the side branch (SB) could potentially reduce unnecessary SB interventions after provisional stenting technique. The aim of this study was to compare distal pressure to aortic pressure ratio (Pd/Pa) measurements between 2 second-generation optical pressure guidewires in bifurcation treatment-a jailed wire (JW) and a second free-floating wire (FW) advanced into the SB after stenting., Methods: In an in vitro bifurcation hydrodynamic model with pressure sensors, a JW was advanced into the SB and the FW into the main branch. Bifurcation stenting is performed with the proximal optimization technique (POT)-side-POT technique using a 3.0 x 22-mm stent, a 4.0 x 12-mm noncompliant balloon for the POT, and a 2.5 x 12-mm semicompliant balloon for the SB opening. The same steps were performed in a second model where a surgical clamp was placed in the main vessel to lower overall absolute values pressures., Results: A strong correlation was found between JW and FW values (Pearson's coefficient, r=0.91). All wires could be safely retrieved., Conclusion: In bifurcation stenting, the Pd/Pa value of a second-generation optical pressure guidewire jailed in the SB is reliable compared with a FW inserted after stent implantation.

Objectives: It is unknown whether computed tomographic coronary angiography (CTCA) can be used to perform ultraselective invasive coronary angiography (ICA) by only visualizing the abnormal coronary artery on CTCA and defer visualization of the normal contralateral coronary artery. This study assessed the accuracy of CTCA in patients with coronary artery disease (CAD) on CTCA limited to either the left (LCA) or right coronary artery (RCA) in predicting a contralateral coronary artery without abnormalities on CTCA determined to be normal by ICA., Methods: This retrospective analysis included patients with CAD limited to the LCA or RCA on CTCA. Primary endpoint was the accuracy of CTCA to predict a contralateral coronary artery without abnormalities on CTCA to be normal by ICA. Secondary endpoints were potential reductions in procedure time and radiation exposure if an ultraselective ICA approach would be used compared to standard ICA., Results: In total, 202 patients were included. CTCA was correct in predicting a normal contralateral coronary artery in 201 of the 202 patients (99.5%). Deferring ICA of the normal contralateral coronary artery on CTCA resulted in a potential reduction in procedure time and dose area product of 4.22 ± 2.67 minutes (61 ± 16% reduction) and 1501 ± 1304 mGy•cm² (29 ± 13% reduction)., Conclusions: In this retrospective study, CTCA was extremely accurate in predicting a normal contralateral coronary artery in patients with LCA- or RCA-limited CAD on CTCA. A potential CTCA-guided ultraselective ICA approach was feasible and would have led to a considerable decrease in procedure time and radiation exposure.

Objectives: Performing percutaneous coronary intervention (PCI) for fractional flow reserve (FFR) positive coronary lesions improves clinical outcomes and is recommended by international guidelines. It has been hypothesized that lesions with a positive FFR but a preserved coronary flow reserve (CFR) are less likely to be flow limiting and might best be treated medically. We investigated the association of CFR in FFR-positive lesions with clinical outcomes when treated medically, as well as the treatment effect of PCI vs medical therapy in FFR-positive lesions and a preserved CFR., Methods: We performed a substudy of the randomized, multicenter Compare-Acute trial, in which stabilized ST-segment elevation myocardial infarction (STEMI) patients with non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperemic pressure gradients, we computed physiologic limits of CFR, the so-called pressure-bounded CFR (pb-CFR), and classified lesions as low (<2) or preserved (≥2). The primary endpoint was 12-month major adverse cardiac and cerebrovascular event (MACCE) rate, defined as a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events., Results: A total of 980 lesions from 885 patients were included in this substudy. In lesions with FFR ≤0.80, a total of 249 patients had a pb-CFR <2 and 29 patients had a preserved CFR (pb-CFR ≥2). The rate of MACCE at 1 year was not significantly different between patients with FFR ≤0.80 and pb-CFR <2 vs patients with FFR ≤0.80 and pb-CFR ≥2 (25% vs 17%, respectively; P=.39). Because of randomization, baseline characteristics were well balanced between patients with FFR ≤0.80 and pb-CFR ≥2 treated by either by PCI or medical therapy. Importantly, in patients with FFR ≤0.80 and pb-CFR ≥2, MACCE occurred more frequently in patients treated medically vs patients treated by PCI (44% vs 0%, respectively; P=.01)., Conclusions: Preserved or low pb-CFR did not alter clinical outcomes in patients with a positive FFR. Patients with FFR-positive coronary lesions but a preserved CFR had more clinical events when treated medically vs those treated with PCI.

Background: Invasive functional assessment is a mainstay in the management of patients with coronary artery disease (CAD), but there is uncertainty on the comparative accuracy of diagnostic indices of functional significance. We aimed to validate the diagnostic performance of a novel non-hyperemic diastolic pressure ratio (dPR)., Methods: We performed a retrospective analysis including two separate registries (VERIFY 2, Latina, Italy) of patients in whom functional indices were measured for lesions with angiographically moderate severity. On top of fractional flow reserve, distal coronary pressure (Pd)/aortic pressure (Pa) ratio, instantaneous wave-free ratio (iFR) and diastolic pressure ratio (dPR) were computed using a novel dedicated algorithm over 4 consecutive beats. Agreement/discrepancy between indexes was appraised Bland-Altman analysis, area under the receiver operating characteristic curve (AUC), and unsupervised machine learning., Results: A total of 525 lesions from 479 patients were included. The novel dPR was highly correlated with iFR (R 2 =0.99, P<0.001), with a mean difference of -0.004±0.014. The diagnostic performance of dPR (best cutoff value: ≤0.89) against iFR was as follows: accuracy =96%; sensitivity =94%; specificity =97%; positive-predictive value =94%; and negative-predictive value =96%. Additionally, AUC to predict iFR≤0.89 was 0.99, which was significantly higher than that of Pd/Pa (0.97, P<0.001). In the iFR range of 0.85-0.93 ("grey zone"), the diagnostic performance was well maintained (accuracy =91%; sensitivity =87%; specificity =93%; and AUC=0.96). Results were supported also by unsupervised learning analysis., Conclusions: This multicenter registry suggests this novel dPR algorithm provides results that are numerically equivalent to iFR. Pending further studies, physicians may consider using this novel dPR algorithm to gauge the functional significance of a coronary lesion.

Background: The principle of continuous thermodilution can be used to calculate absolute coronary blood flow and microvascular resistance (R). The aim of the study is to explore the safety, feasibility, and reproducibility of coronary blood flow and R measurements as measured by continuous thermodilution in humans., Methods and Results: Absolute coronary flow and R can be calculated by thermodilution by infusing saline at room temperature through a dedicated monorail catheter. The temperature of saline as it enters the vessel, the temperature of blood and saline mixed in the distal part of the vessel, and the distal coronary pressure were measured by a pressure/temperature sensor-tipped guidewire. The feasibility and safety of the method were tested in 135 patients who were referred for coronary angiography. No significant adverse events were observed; in 11 (8.1%) patients, bradycardia and concomitant atrioventricular block appeared transiently and were reversed immediately on interruption of the infusion. The reproducibility of measurements was tested in a subgroup of 80 patients (129 arteries). Duplicate measurements had a strong correlation both for coronary blood flow (ρ=0.841, P <0.001; intraclass correlation coefficient=0.89, P <0.001) and R (ρ=0.780, P <0.001; intraclass correlation coefficient=0.89, P <0.001). In Bland-Altman plots, there was no significant bias or asymmetry., Conclusions: Absolute coronary blood flow (in L/min) and R (in mm Hg/L/min or Wood units) can be safely and reproducibly measured with continuous thermodilution. This approach constitutes a new opportunity for the study of the coronary microcirculation., (© 2018 American Heart Association, Inc.)

Background: In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up., Methods: The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥ 18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267774., Findings: After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75-1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 [SD 1·2] vs 1·9 [1·3], p<0·0001)., Interpretation: The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients., Funding: St Jude Medical, Friends of the Heart Foundation, and Medtronic., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to assess the validity of measuring fractional flow reserve (FFR) of the left main (LM) coronary artery in the setting of concomitant left anterior descending (LAD) or left circumflex (LCX) stenoses., Background: The theoretical impact of a stenosis in the LAD on the FFR assessment of intermediate LM disease with the pressure wire in an unobstructed LCX is currently unknown., Methods: A previously validated in vitro model of the coronary circulation was used to create a fixed intermediate stenosis of the LM and a variable downstream LAD or LCX stenosis. The true LM FFR (FFR(LM true)), with no concomitant downstream disease, was compared to the apparent LM FFR (FFR(LM apparent)), with concomitant downstream disease measured with different degrees of LAD or LCX disease. Additionally, an equation based on a resistors model was derived to predict the effect of downstream stenosis on LM FFR (FFR(LM predicted))., Results: In the setting of isolated moderate LM disease (FFR 0.72 ± 0.08), mild to moderate proximal LAD or LCX lesions did not significantly affect LM FFR. Lesions with a composite FFR (LM + downstream disease) ≥0.65 resulted in an FFR(LM apparent) that was not significantly different from FFR(LM true) (0.76 ± 0.06 vs. 0.76 ± 0.05, p = 0.124). Our equation for FFR(LM predicted) accurately modeled the effects of concomitant disease (r = 0.95, p < 0.001)., Conclusions: These data suggest that in the presence of proximal mild to moderate LAD or LCX disease, LM FFR can be reliably measured with the pressure wire placed in the uninvolved epicardial artery., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to study whether there is a difference in benefit of fractional flow reserve (FFR) guidance for percutaneous coronary intervention (PCI) in multivessel coronary disease in patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI), compared with stable angina (SA)., Background: The use of FFR to guide PCI has been well established for patients with SA. Its use in patients with UA or NSTEMI has not been investigated prospectively., Methods: In the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study 1,005 patients with multivessel disease amenable to PCI were included and randomized to either angiography-guided PCI of all lesions ≥50% or FFR-guided PCI of lesions with an FFR ≤0.80. Patients admitted for UA or NSTEMI with positive troponin but total creatine kinase <1,000 U/l were eligible for inclusion. We determined 2-year major adverse cardiac event rates of these patients and compared it with stable patients., Results: Of 1,005 patients, 328 had UA or NSTEMI. There was no evidence for heterogeneity among the subgroups for any of the outcome variables (all p values >0.05). Using FFR to guide PCI resulted in similar risk reductions of major adverse cardiac events and its components in patients with UA or NSTEMI, compared with patients with SA (absolute risk reduction of 5.1% vs. 3.7%, respectively, p = 0.92). In patients with UA or NSTEMI, the number of stents was reduced without increase in hospital stay or procedure time and with less contrast use, in similarity to stable patients., Conclusions: The benefit of using FFR to guide PCI in multivessel disease does not differ between patients with UA or NSTEMI, compared with patients with SA., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)