Refining Our Understanding of the Flow Through Coronary Artery Branches; Revisiting Murray's Law in Human Epicardial Coronary Arteries

Background: Quantification of coronary blood flow is used to evaluate coronary artery disease, but our understanding of flow through branched systems is poor. Murray’s law defines coronary morphometric scaling, the relationship between flow (Q) and vessel diameter (D) and is the basis for minimum lumen area targets when intervening on bifurcation lesions. Murray’s original law (Q α D(P)) dictates that the exponent (P) is 3.0, whilst constant blood velocity throughout the system would suggest an exponent of 2.0. In human coronary arteries, the value of Murray’s exponent remains unknown. Aim: To establish the exponent in Murray’s power law relationship that best reproduces coronary blood flows (Q) and microvascular resistances (Rmicro) in a bifurcating coronary tree. Methods and Results: We screened 48 cases, and were able to evaluate inlet Q and Rmicro in 27 branched coronary arteries, taken from 20 patients, using a novel computational fluid dynamics (CFD) model which reconstructs 3D coronary anatomy from angiography and uses pressure-wire measurements to compute Q and Rmicro distribution in the main- and side-branches. Outputs were validated against invasive measurements using a Rayflow™ catheter. A Murray’s power law exponent of 2.15 produced the strongest correlation and closest agreement with inlet Q (zero bias, r = 0.47, p = 0.006) and an exponent of 2.38 produced the strongest correlation and closest agreement with Rmicro (zero bias, r = 0.66, p = 0.0001). Conclusions: The optimal power law exponents for Q and Rmicro were not 3.0, as dictated by Murray’s Law, but 2.15 and 2.38 respectively. These data will be useful in assessing patient-specific coronary physiology and tailoring revascularisation decisions

The Role of Computational Fluid Dynamics in the Management of Unruptured Intracranial Aneurysms: A Clinicians' View

Objective. The importance of hemodynamics in the etiopathogenesis of intracranial aneurysms (IAs) is widely accepted. Computational fluid dynamics (CFD) is being used increasingly for hemodynamic predictions. However, alogn with the continuing development and validation of these tools, it is imperative to collect the opinion of the clinicians. Methods. A workshop on CFD was conducted during the European Society of Minimally Invasive Neurological Therapy (ESMINT) Teaching Course, Lisbon, Portugal. 36 delegates, mostly clinicians, performed supervised CFD analysis for an IA, using the @neuFuse software developed within the European project @neurIST. Feedback on the workshop was collected and analyzed. The performance was assessed on a scale of 1 to 4 and, compared with experts' performance. Results. Current dilemmas in the management of unruptured IAs remained the most important motivating factor to attend the workshop and majority of participants showed interest in participating in a multicentric trial. The participants achieved an average score of 2.52 (range 0–4) which was 63% (range 0–100%) of an expert user. Conclusions. Although participants showed a manifest interest in CFD, there was a clear lack of awareness concerning the role of hemodynamics in the etiopathogenesis of IAs and the use of CFD in this context. More efforts therefore are required to enhance understanding of the clinicians in the subject

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

BackgroundIncreased 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.AimTo compare CMVR between men and women being investigated for chest pain.Methods and resultsWe 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.ConclusionCMVR was significantly higher in women compared with men. These sex-specific differences may help to explain the increased prevalence of CMD in women

Evaluation of models of sequestration flow in coronary arteries—Physiology versus anatomy?

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

Rethinking the Neolithic from Iberian Archaeology

European Journal of Archeology, 3 (2):283-284. (año 2000)[ES] Reseña bibliográfica del libro de Almudena Hernado, 'Los primeros agricultores de la Península Ibérica. Una historiografía crítica del Neolítico' (Madrid: Editorial Síntesis, 1999, 315 pp.). [EN]bliographic Almudena Hernando book, 'The first farmers in the Iberian Peninsula. A critical historiography of the Neolithic '(Madrid: Editorial Síntesis, 1999, 315 pp.)Peer reviewe

Contribution of Mechanical and Fluid Stresses to the Magnitude of In-stent Restenosis at the Level of Individual Stent Struts

Structural and fluid stresses acting on the artery wall are proposed as mechanical mediators of in-stent restenosis (ISR). This study reports an investigation of the correlation between stresses obtained from computational simulations with the magnitude of ISR at the level of individual stent struts observed in an in vivo model of restenosis. Structural and fluid dynamic analyses were undertaken in a model based on volumetric micro-CT data from an in vivo stent deployment in a porcine right coronary artery. Structural and fluid mechanics were compared with histological data from the same stented vessel sample. Interpretation of the combined data at the level of individual stent struts was possible by identifying the location of each 2-D histological section within the 3-D micro-CT volume. Linear correlation between structural and fluid stimuli and neointimal thickness at the level of individual struts is less clear when individual stimuli are considered [compressive force (CF), R 2 = 0.19, wall shear stress (WSS), R 2 = 0.25, oscillatory shear index (OSI), R 2 = 0.28]. Closer correlation is observed if combined structural and fluid stimuli are assumed to stimulate ISR (CF/WSS, R 2 = 0.64). The use of micro-CT to characterise stent geometry after deployment enhances the clinical relevance of computational simulations, allowing direct comparison with histology. The results support the combined role of both structural and fluid mechanics to determine the magnitude of ISR at the level of individual struts. This finding is consistent with other studies which consider these stimuli averaged over a transverse section of the vessel

Comparison of stenosis models for usage in the estimation of pressure gradient across aortic coarctation

Non-invasive estimation of the pressure gradient in cardiovascular stenosis has much clinical importance in assisting the diagnosis and treatment of stenotic diseases. In this research, a systematic comparison is conducted to investigate the accuracy of a group of stenosis models against the MRI- and catheter-measured patient data under the aortic coarctation condition. Eight analytical stenosis models, including six from the literature and two proposed in this study, are investigated to examine their prediction accuracy against the clinical data. The two improved models proposed in this study consider comprehensively the Poiseuille loss, the Bernoulli loss in its exact form, and the entrance effect, of the blood flow. Comparison of the results shows that one of the proposed models demonstrates a cycle-averaged mean prediction error of −0.15 ± 3.03 mmHg, a peak-to-peak prediction error of −1.8 ± 6.89 mmHg, which is the best among the models studied

"Virtual" (Computed) Fractional Flow Reserve Current Challenges and Limitations

AbstractFractional flow reserve (FFR) is the “gold standard” for assessing the physiological significance of coronary artery disease during invasive coronary angiography. FFR-guided percutaneous coronary intervention improves patient outcomes and reduces stent insertion and cost; yet, due to several practical and operator related factors, it is used in <10% of percutaneous coronary intervention procedures. Virtual fractional flow reserve (vFFR) is computed using coronary imaging and computational fluid dynamics modeling. vFFR has emerged as an attractive alternative to invasive FFR by delivering physiological assessment without the factors that limit the invasive technique. vFFR may offer further diagnostic and planning benefits, including virtual pullback and virtual stenting facilities. However, there are key challenges that need to be overcome before vFFR can be translated into routine clinical practice. These span a spectrum of scientific, logistic, commercial, and political areas. The method used to generate 3-dimensional geometric arterial models (segmentation) and selection of appropriate, patient-specific boundary conditions represent the primary scientific limitations. Many conflicting priorities and design features must be carefully considered for vFFR models to be sufficiently accurate, fast, and intuitive for physicians to use. Consistency is needed in how accuracy is defined and reported. Furthermore, appropriate regulatory and industry standards need to be in place, and cohesive approaches to intellectual property management, reimbursement, and clinician training are required. Assuming successful development continues in these key areas, vFFR is likely to become a desirable tool in the functional assessment of coronary artery disease

Computational modelling and evaluation of cardiovascular response under pulsatile impeller pump support

This study presents a numerical simulation of cardiovascular response in the heart failure condition under the support of a Berlin Heart INCOR impeller pump-type ventricular assist device (VAD). The model is implemented using the CellML modelling language. To investigate the potential of using the Berlin Heart INCOR impeller pump to produce physiologically meaningful arterial pulse pressure within the various physiological constraints, a series of VAD-assisted cardiovascular cases are studied, in which the pulsation ratio and the phase shift of the VAD motion profile are systematically changed to observe the cardiovascular responses in each of the studied cases. An optimization process is proposed, including the introduction of a cost function to balance the importance of the characteristic cardiovascular variables. Based on this cost function it is found that a pulsation ratio of 0.35 combined with a phase shift of 200° produces the optimal cardiovascular response, giving rise to a maximal arterial pulse pressure of 12.6 mm Hg without inducing regurgitant pump flow while keeping other characteristic cardiovascular variables within appropriate physiological ranges