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

Rapid virtual fractional flow reserve using 3D computational fluid dynamics

Aims Over the last ten years, virtual Fractional Flow Reserve (vFFR) has improved the utility of Fractional Flow Reserve (FFR), a globally recommended assessment to guide coronary interventions. Although the speed of vFFR computation has accelerated, techniques utilising full 3D computational fluid dynamics (CFD) solutions rather than simplified analytical solutions still require significant time to compute. Methods and results This study investigated the speed, accuracy and cost of a novel 3D-CFD software method based upon a graphic processing unit (GPU) computation, compared with the existing fastest central processing unit (CPU)-based 3D-CFD technique, on 40 angiographic cases. The novel GPU simulation was significantly faster than the CPU method (median 31.7 s (Interquartile Range (IQR) 24.0–44.4s) vs. 607.5 s (490–964 s), P < 0.0001). The novel GPU technique was 99.6% (IQR 99.3–99.9) accurate relative to the CPU method. The initial cost of the GPU hardware was greater than the CPU (£4080 vs. £2876), but the median energy consumption per case was significantly less using the GPU method (8.44 (6.80–13.39) Wh vs. 2.60 (2.16–3.12) Wh, P < 0.0001). Conclusion This study demonstrates that vFFR can be computed using 3D-CFD with up to 28-fold acceleration than previous techniques with no clinically significant sacrifice in accuracy

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 DP) 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

Validation of a novel numerical model to predict regionalized blood flow in the coronary arteries

Aims Ischaemic heart disease results from insufficient coronary blood flow. Direct measurement of absolute flow (mL/min) is feasible, but has not entered routine clinical practice in most catheterization laboratories. Interventional cardiologists, therefore, rely on surrogate markers of flow. Recently, we described a computational fluid dynamics (CFD) method for predicting flow that differentiates inlet, side branch, and outlet flows during angiography. In the current study, we evaluate a new method that regionalizes flow along the length of the artery. Methods and results Three-dimensional coronary anatomy was reconstructed from angiograms from 20 patients with chronic coronary syndrome. All flows were computed using CFD by applying the pressure gradient to the reconstructed geometry. Side branch flow was modelled as a porous wall boundary. Side branch flow magnitude was based on morphometric scaling laws with two models: a homogeneous model with flow loss along the entire arterial length; and a regionalized model with flow proportional to local taper. Flow results were validated against invasive measurements of flow by continuous infusion thermodilution (Coroventis™, Abbott). Both methods quantified flow relative to the invasive measures: homogeneous (r 0.47, P 0.006; zero bias; 95% CI −168 to +168 mL/min); regionalized method (r 0.43, P 0.013; zero bias; 95% CI −175 to +175 mL/min). Conclusion During angiography and pressure wire assessment, coronary flow can now be regionalized and differentiated at the inlet, outlet, and side branches. The effect of epicardial disease on agreement suggests the model may be best targeted at cases with a stenosis close to side branches

Individual variation in 3-methylbutanal: A putative link between human leukocyte antigen and skin microflora

The human derma emits volatile compounds whose interaction with a receiver's olfactory sensory system may affect individual recognition and mating preferences. Studies suggest that both genes and environmental factors determine characteristic odor of an individual. Here, we use solid phase micro-extraction and GC-MS to identify 3-methylbutanal (3-MB) in human axillary odor, show that the abundance of this volatile compound varies significantly between individuals and demonstrate in vitro that its formation may be influenced by interaction between human leukocyte antigen peptide and dermal microflora

Towards a model of contemporary parenting: The parenting behaviours and dimensions questionnaire

The assessment of parenting has been problematic due to theoretical disagreement, concerns over generalisability, and problems with the psychometric properties of current parenting measures. The aim of this study was to develop a comprehensive, psychometrically sound self-report parenting measure for use with parents of preadolescent children, and to use this empirical scale development process to identify the core dimensions of contemporary parenting behaviour. Following item generation and parent review, 846 parents completed an online survey comprising 116 parenting items. Exploratory and confirmatory factor analyses supported a six factor parenting model, comprising Emotional Warmth, Punitive Discipline, Anxious Intrusiveness, Autonomy Support, Permissive Discipline and Democratic Discipline. This measure will allow for the comprehensive and consistent assessment of parenting in future research and practice

Scent-marking by male mammals: Cheat-proof signals to competitors and mates

Scent-marking is a ubiquitous form of olfactory signaling in male mammals and both territorial males in resource-defense mating systems and dominant males in dominance mating systems scent-mark. A large body of evidence suggests a link between scent-marking by male mammals and intrasexual competition. Resource holders appear to mark to help establish and maintain their status. They may do this because scent marks allow potential opponents to assess the status or RHP of the signaler. Nonresource holding competitors benefit because they can adjust the level of escalation in relation to potential costs and benefits and avoid risky contests. Resource holders benefit through reduced costs because many nonresource holders withdraw to avoid escalated contests. Three basic mechanisms allow receivers to make decisions after detecting scent marks. Receivers may (1) detect intrinsic properties of scent marks (e.g., concentrations of androgen-dependent volatiles), (2) remember past contests and the odor of each individual involved and associate these with the odor of scent marks, and (3) remember the smell of marks recently encountered and match this smell with potential opponents that they meet subsequently. It is now known that all of these mechanisms are used, sometimes within one species (e.g., mice) and we argue that the mechanisms are used conditionally, depending on information available and potential costs and benefits to receivers. Game theoretical analysis has recently shown how territorial intruders may switch from using intrinsic properties of marks to scent-matching when making decision about whether to remain in a territory. Scent-marking may be a uniquely cheat-proof signal of status because males must be able to defend their territory or dominance status over the time taken to mark it. A pattern of marks is thus a signal of status that has been tested in intrasexual competition. It also seems likely that marks are intrinsically costly both in energetic terms and by increasing predation risk. Mice can detect whether urine is from a parasitized or nonparasitized individual and these odors could potentially signal immunocompetence if mediated by variation at the MHC region of the genome. This remains to be tested. It is known that mice can detect relatedness via urine volatiles mediated by the MHC and it has been predicted that males should modify their competitive behavior in the light of this information. Again this remains to be tested. Information about disease status and genetic relatedness does not explain why males maintain patterns of scent marks. Most, perhaps all, territories are scent-marked. This may be because most intruders are of lower RHP than resource holders and these males should usually withdraw after assessing the resource holder by its scent marks. The costs of defending a territory may thus be substantially reduced. The obligate link between scent-marking and territoriality suggests that resource-defense polygyny in mammals may not be economically viable without this reduction in the costs of area defense. A little information is available to show that females use information from patterns of scent marks and a great deal of information shows that they use intrinsic information. It is not known whether males signal to females to enable mate choice or if females eavesdrop on signals sent between male competitors. Most known responses are to male urine by female rodents. For example, females show physiological (priming) responses to male odors (e.g., advancing and synchronizing estrus, inducing abortion). Other research has identified factors responsible for female mate preferences in choice tests. For example, the dominance status of the signaling male is a predictor of female interest and such studies have identified androgen-dependent volatiles responsible for the response. More recently, females have been shown to use odor mediated by the MHC locus to choose mates in relation to their genetic relatedness and to use odor to distinguish healthy and diseased mates. Most of these studies have been on mice and most use male urine, but the effect of patterns of urine scent marks has not been investigated. The only studies that explicitly use scent marks are those showing that females match the odor of potential mates with marks previously found in the environment to select mates. Future research should aim to clarify how information about the quality of potential mates is transmitted and how females trade-off such information against genetic relatedness