Aims Ischaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease, but is only a surrogate of flow and only predicts percentage flow changes. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory. Methods and Results A computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary microvascular resistance (MVR) using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, 3-D printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates (bias +2.08 mL/min; 95% CI (error range) -4.7 to + 8.8 mL/min; R2=0.999, p < 0.001; variability coefficient <1%). In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2=0.92, P < 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs ± 34 mL/min) and in vivo (±0.9 vs ± 24.4 mmHg). Conclusions Absolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management. Translational Perspective Current pressure wire-based methods of assessing coronary disease cannot assess absolute flow or microvascular disease. Our novel QCFD method, using only angiography-based CFD and a pressure wire, simultaneously measures FFR, absolute coronary blood flow rate, microvascular resistance and coronary flow reserve. QCFD is suitable for use in the catheter laboratory and requires no dedicated catheters, wires or infusions. QCFD measures blood flow and microvascular resistance in absolute units and allows microvascular and epicardial disease to be differentiated, quantified and separately assessed, with the potential to improve diagnostic accuracy and clinical management.

T here is growing evidence that outdoor temperature is a major determinant of the observed seasonal fluctuations in blood pressure (BP) with higher and lower BP in winter and summer, respectively. [1][2][3][4][5][6] An inverse association between ambient temperature and BP has been observed in several studies.7-9 Thermoregulatory vasoconstriction, which increases arterial BP significantly, 10 is an adaptive response to provide enhanced circulatory function for the protective mechanisms that are activated to maintain temperature in cold weather (nonshivering thermogenesis and increased metabolic rate). 2,11Elevation of BP induced by a longer period of cold exposure is not reversible after return to a thermo-neutral temperature in animal studies 12 and may result in cold-induced hypertension. Although several studies explored the effects of seasonal variations on BP, few studies have looked at longitudinal BP changes in relation to fluctuations in weather patterns. To our knowledge, there are no studies that examined the role of sunshine, rain, or air frost on BP. It is unclear whether BP response to weather parameters like temperature, rainfall, frost, and sunshine is similar in everybody. If there is heterogeneity in weather-related BP response, it would be important to know whether intraindividual and interindividual responsiveness to weather changes can predict long-term risk. The aim of this study was to determine the within-subject changes in BP in response to a range of weather patterns and test whether individual BP response to the weather is predictive of long-term mortality and BP control in a large hypertensive cohort. Methods Study PopulationThe Glasgow Blood Pressure Clinic provides secondary and tertiary level service to individuals with hypertension from the West of Scotland. The details of the study population and settings, clinical Abstract-Very few studies have looked at longitudinal intraindividual blood pressure responses to weather conditions.There are no data to suggest that specific response to changes in weather will have an impact on survival. We analyzed >169 000 clinic visits of 16 010 Glasgow Blood Pressure Clinic patients with hypertension. Each clinic visit was mapped to the mean West of Scotland monthly weather (temperature, sunshine, rainfall) data. Percentage change in blood pressure was calculated between pairs of consecutive clinic visits, where the weather alternated between 2 extreme quartiles (Q 1 -Q 4 or Q 4 -Q 1 ) or remained in the same quartile (Q n -Q n ) of each weather parameter. Subjects were also categorized into 2 groups depending on whether their blood pressure response in Q 1 -Q 4 or Q 4 -Q 1 were concordant or discordant to Q n -Q n . Generalized estimating equations and Cox proportional hazards model were used to model the effect on longitudinal blood pressure and mortality, respectively. Q n -Q n showed a mean 2% drop in blood pressure consistently, whereas Q 4 -Q 1 showed a mean 2.1% and 1.6% rise in systolic and diastolic blood pressure, respectively. However,...

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.

Background 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 catheterisation 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 regionalises 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 homogenous model with flow loss along the entire arterial length; and a regionalised 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: homogenous (r 0.47, P 0.006; zero bias; 95% CI -168 to +168 mL/min); regionalised method (r 0.43, P 0.013; zero bias; 95% CI -175 to +175 mL/min). Conclusions During angiography and pressure-wire assessment, coronary flow can now be regionalised 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.

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.