Virtual Coronary Intervention: A Treatment Planning Tool Based Upon the Angiogram

Objectives: This study sought to assess the ability of a novel virtual coronary intervention (VCI) tool based on invasive angiography to predict the patient's physiological response to stenting. Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is associated with improved clinical and economic outcomes compared with angiographic guidance alone. Virtual (v)FFR can be calculated based upon a 3-dimensional (3D) reconstruction of the coronary anatomy from the angiogram, using computational fluid dynamics (CFD) modeling. This technology can be used to perform virtual stenting, with a predicted post-PCI FFR, and the prospect of optimized treatment planning. Methods: Patients undergoing elective PCI had pressure-wire-based FFR measurements pre- and post-PCI. A 3D reconstruction of the diseased artery was generated from the angiogram and imported into the VIRTUheart workflow, without the need for any invasive physiological measurements. VCI was performed using a radius correction tool replicating the dimensions of the stent deployed during PCI. Virtual FFR (vFFR) was calculated pre- and post-VCI, using CFD analysis. vFFR pre- and post-VCI were compared with measured (m)FFR pre- and post-PCI, respectively. Results: Fifty-four patients and 59 vessels underwent PCI. The mFFR and vFFR pre-PCI were 0.66 ± 0.14 and 0.68 ± 0.13, respectively. Pre-PCI vFFR deviated from mFFR by ±0.05 (mean Δ = -0.02; SD = 0.07). The mean mFFR and vFFR post-PCI/VCI were 0.90 ± 0.05 and 0.92 ± 0.05, respectively. Post-VCI vFFR deviated from post-PCI mFFR by ±0.02 (mean Δ = -0.01; SD = 0.03). Mean CFD processing time was 95 s per case. Conclusions: The authors have developed a novel VCI tool, based upon the angiogram, that predicts the physiological response to stenting with a high degree of accuracy

The double-kissing nano-crush for bifurcation lesions : development, bioengineering, fluid dynamics and initial clinical testing

Background When possible, a single stent technique to treat coronary bifurcation disease is preferable. However, when two stents are required, there is scope to improve upon existing techniques. The crush technique has already been improved with the introduction of double kissing (DK) and mini-crush. We sought to refine and simplify the mini-crush technique, retaining its advantages whilst avoiding its disadvantages, by developing a DK nano-crush technique. Methods The DK nano-crush method allows complete lesion coverage of a bifurcation lesion without excessive metal layers. This is achieved by positioning the SB stent with minimal protrusion into the main branch (MB), implantation of the SB stent with an undeployed balloon in the MB, immediate kissing balloon inflation with formation of a minimal neocarina, stenting the MB, re-crossing the proximal part of the SB without crossing double metal layer, and final kissing. We demonstrate this technique with benchtop implantation, micro computed tomography reconstruction, computational fluid dynamics (CFD) modelling and clinically with angiographic and intravascular imaging. Results The DK nano-crush was practically feasible and resulted in full ostial coverage. CFD analysis demonstrated minimally disturbed blood flow. The technique was successfully utilised in nine patients with bifurcation lesions with excellent angiographic outcomes and no adverse events over twelve months. Conclusions The DK nano-crush technique may represent the ultimate refinement of the original ‘crush’ with a number of practical and theoretical advantages. It remains to be tested against other bifurcation techniques in prospective trials

Galaxy rotation curves: the effect of j x B force

Using the Galaxy as an example, we study the effect of j x B force on the rotational curves of gas and plasma in galaxies. Acceptable model for the galactic magnetic field and plausible physical parameters are used to fit the flat rotational curve for gas and plasma based on the observed baryonic (visible) matter distribution and j x B force term in the static MHD equation of motion. We also study the effects of varied strength of the magnetic field, its pitch angle and length scale on the rotational curves. We show that j x B force does not play an important role on the plasma dynamics in the intermediate range of distances 6-12 kpc from the centre, whilst the effect is sizable for larger r (r > 15 kpc), where it is the most crucial.Comment: Accepted for publication in Astrophysics & Space Science (final printed version, typos in proofs corrected

The relationship between coronary stenosis morphology and fractional flow reserve: a computational fluid dynamics modelling study

Aims: International guidelines mandate the use of fractional flow reserve (FFR) and/or non-hyperaemic pressure ratios to assess the physiological significance of moderate coronary artery lesions to guide revascularization decisions. However, they remain underused such that visual estimation of lesion severity continues to be the predominant decision-making tool. It would be pragmatic to have an improved understanding of the relationship between lesion morphology and haemodynamics. The aim of this study was to compute virtual FFR (vFFR) in idealized coronary artery geometries with a variety of stenosis and vessel characteristics. Methods and results: Coronary artery geometries were modelled, based upon physiologically realistic branched arteries. Common stenosis characteristics were studied, including % narrowing, length, eccentricity, shape, number, position relative to branch, and distal (myocardial) resistance. Computational fluid dynamics modelling was used to calculate vFFRs using the VIRTUheart™ system. Percentage lesion severity had the greatest effect upon FFR. Any ≥80% diameter stenosis in two views (i.e. concentric) was physiologically significant (FFR ≤ 0.80), irrespective of length, shape, or vessel diameter. Almost all eccentric stenoses and all 50% concentric stenoses were physiologically non-significant, whilst 70% uniform concentric stenoses about 10 mm long straddled the ischaemic threshold (FFR 0.80). A low microvascular resistance (MVR) reduced FFR on average by 0.05, and a high MVR increased it by 0.03. Conclusion: Using computational modelling, we have produced an analysis of vFFR that relates stenosis characteristics to haemodynamic significance. The strongest predictor of a positive vFFR was a concentric, ≥80% diameter stenosis. The importance of MVR was quantified. Other lesion characteristics have a limited impact

Incorporating clinical parameters to improve the accuracy of angiography-derived computed fractional flow reserve

Aims Angiography-derived fractional flow reserve (angio-FFR) permits physiological lesion assessment without the need for an invasive pressure wire or induction of hyperaemia. However, accuracy is limited by assumptions made when defining the distal boundary, namely coronary microvascular resistance (CMVR). We sought to determine whether machine learning (ML) techniques could provide a patient-specific estimate of CMVR and therefore improve the accuracy of angio-FFR. Methods and results Patients with chronic coronary syndromes underwent coronary angiography with FFR assessment. Vessel-specific CMVR was computed using a three-dimensional computational fluid dynamics simulation with invasively measured proximal and distal pressures applied as boundary conditions. Predictive models were created using non-linear autoregressive moving average with exogenous input (NARMAX) modelling with computed CMVR as the dependent variable. Angio-FFR (VIRTUheart™) was computed using previously described methods. Three simulations were run: using a generic CMVR value (Model A); using ML-predicted CMVR based upon simple clinical data (Model B); and using ML-predicted CMVR also incorporating echocardiographic data (Model C). The diagnostic (FFR ≤ or >0.80) and absolute accuracies of these models were compared. Eighty-four patients underwent coronary angiography with FFR assessment in 157 vessels. The mean measured FFR was 0.79 (±0.15). The diagnostic and absolute accuracies of each personalized model were: (A) 73% and ±0.10; (B) 81% and ±0.07; and (C) 89% and ±0.05, P < 0.001. Conclusion The accuracy of angio-FFR was dependent in part upon CMVR estimation. Personalization of CMVR from standard clinical data resulted in a significant reduction in angio-FFR error

The complementary value of absolute coronary flow in the assessment of patients with ischaemic heart disease

Fractional flow reserve (FFR) is the current gold standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown. In this study, we compared fractional CBF with absolute CBF (aCBF, in ml min−1), measured with a computational method during standard angiography and pressure wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r = 0.89 and Cohen’s kappa = 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%) but reduced when FFR was ≤0.80 (81%), 0.70–0.80 (68%) and, particularly, 0.75–0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR and may be valuable to assess CBF, particularly in cases within the FFR ‘gray zone’

Sex differences in coronary microvascular resistance measured by a computational fluid dynamics model

Background: Increased coronary microvascular resistance (CMVR) is associated with coronary microvascular dysfunction (CMD). Although CMD is more common in women, sex-specific differences in CMVR have not been demonstrated previously. Aim: To compare CMVR between men and women being investigated for chest pain. Methods and results: We used a computational fluid dynamics (CFD) model of human coronary physiology to calculate absolute CMVR based on invasive coronary angiographic images and pressures in 203 coronary arteries from 144 individual patients. CMVR was significantly higher in women than men (860 [650–1,205] vs. 680 [520–865] WU, Z = −2.24, p = 0.025). None of the other major subgroup comparisons yielded any differences in CMVR

The impact of virtual fractional flow reserve and virtual coronary intervention upon treatment decisions in the cardiac catheter laboratory

Background Using fractional flow reserve (FFR) to guide percutaneous coronary intervention for patients with coronary artery disease (CAD) improves clinical decision making but remains under-used. Virtual FFR (vFFR, computed from angiographic images) permits physiological assessment without a pressure wire and can be extended to virtual coronary intervention (VCI) facilitating treatment planning. This study investigated the effect of adding vFFR and VCI to angiography in patient assessment and management. Methods Two cardiologists independently reviewed clinical data and angiograms of 50 patients undergoing invasive management of coronary syndromes, and their management plans were recorded. The vFFRs were computed and disclosed, and the cardiologists submitted revised plans. Then, using VCI, the physiological results of various interventional strategies were shown, and further revision was invited. Results Disclosure of vFFR led to a change in strategy in 27%. VCI led to a change in stent size in 48%. Disclosure of vFFR and VCI resulted in an increase in operator confidence in their decision. Twelve cases were reviewed by six additional cardiologists. There was limited agreement in the management plans between cardiologists based upon either angiography (kappa=0.31) or vFFR (kappa=0.39). Conclusions vFFR has the potential to alter decision making, and VCI can guide stent sizing. However, variability in management strategy remains considerable between operators, even when presented with the same anatomical and physiological data

Quantifying myocardial blood flow and resistance using 4D-flow cardiac magnetic resonance imaging

Background. Ischaemia with nonobstructive coronary arteries is most commonly caused by coronary microvascular dysfunction but remains difcult to diagnose without invasive testing. Myocardial blood fow (MBF) can be quantifed noninvasively on stress perfusion cardiac magnetic resonance (CMR) or positron emission tomography but neither is routinely used in clinical practice due to practical and technical constraints. Quantifcation of coronary sinus (CS) fow may represent a simpler method for CMR MBF quantifcation. 4D fow CMR ofers comprehensive intracardiac and transvalvular fow quantifcation. However, it is feasibility to quantify MBF remains unknown. Methods. Patients with acute myocardial infarction (MI) and healthy volunteers underwent CMR. Te CS contours were traced from the 2-chamber view. A reformatted phase contrast plane was generated through the CS, and fow was quantifed using 4D fow CMR over the cardiac cycle and normalised for myocardial mass. MBF and resistance (MyoR) was determined in ten healthy volunteers, ten patients with myocardial infarction (MI) without microvascular obstruction (MVO), and ten with known MVO. Results. MBF was quantifed in all 30 subjects. MBF was highest in healthy controls (123.8 ± 48.4 mL/min), signifcantly lower in those with MI (85.7 ± 30.5 mL/min), and even lower in those with MI and MVO (67.9 ± 29.2 mL/min/) (P < 0.01 for both diferences). Compared with healthy controls, MyoR was higher in those with MI and even higher in those with MI and MVO (0.79 (±0.35) versus 1.10 (±0.50) versus 1.50 (±0.69), P = 0.02). Conclusions. MBF and MyoR can be quantifed from 4D fow CMR. Resting MBF was reduced in patients with MI and MVO

Operator-dependent variability of angiography-derived fractional flow reserve and the implications for treatment

Aims To extend the benefits of physiologically-guided percutaneous coronary intervention to many patients, angiography-derived or ‘virtual’ fractional flow reserve (vFFR) has been developed, in which FFR is computed, based upon the images, instead of being measured invasively. The effect of operator experience with these methods upon vFFR accuracy remains unknown. We investigated variability in vFFR results based upon operator experience with image-based computational modelling techniques. Methods vFFR was computed using a proprietary method (VIRTUheart) from the invasive angiograms of patients with coronary artery disease. Each case was processed by an expert (>100 vFFR cases) and a non-expert (<20 vFFR cases) operator and results were compared. The primary outcome was the variability in vFFR between experts and non-experts and the impact this had upon treatment strategy (PCI vs conservative management). Results 231 vessels (199 patients) were processed. Mean non-expert and expert vFFRs were similar overall (0.76 (0.13) and 0.77 (0.16)) but there was significant variability between individual results (variability coefficient 12%, intra-class correlation coefficient 0.58), with only moderate agreement (κ = 0.46), and this led to a statistically significant change in management strategy in 27% of cases. Variability was significantly lower, and agreement higher, for expert operators; a change in their recommended management occurred in 10% of repeated expert measurements and 14% of inter-expert measurements. Conclusions vFFR results are influenced by operator experience of vFFR processing. This had implications for treatment allocation. These results highlight the importance of training and quality assurance to ensure reliable, repeatable vFFR results