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.

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. Conclusion: CMVR was significantly higher in women compared with men. These sex-specific differences may help to explain the increased prevalence of CMD in women.

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.

The Complementary Value of Absolute Coronary Flow in the Assessment of Patients with Ischaemic Heart Disease (the COMPAC-Flow Study).

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. Here we compared fractional CBF with the absolute CBF (aCBF in mL/min), 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, 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 'grey-zone'.

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.

The British Cardiovascular Society and clinical studies in ischaemic heart disease: from RITA to ORBITA, and beyond.

In this article, we provide a historical view of key aspects of British Cardiovascular Society (BCS) influence in clinical trials of ischaemic heart disease (IHD) followed by key research and developments, notable publications and future perspectives. We discuss the role of the BCS and its members. The scope of this article covers clinical trials in stable IHD and acute coronary syndromes, including interventions relating to diagnosis, treatment and management. We discuss the role of the BCS in supporting the original RITA trials. We highlight the changing face of angina and its management providing contemporary and future insights into microvascular disease, ischaemic symptoms with no obstructive coronary arteries and, relatedly, myocardial infarction with no obstructive coronary arteries. The article is presented as a brief overview of the BCS in IHD research, relationships with stakeholders, patient and public involvement and clinical trials from the perspective of past, present and future possibilities.

A novel method for measuring absolute coronary blood flow and microvascular resistance in patients with ischaemic heart disease.

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 MVR using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, three-dimensional 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% confidence interval (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.

Blood pressure response to patterns of weather fluctuations and effect on mortality.

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, Q(1)-Q(4) did not show significant changes in blood pressure. Temperature-sensitive subjects had significantly higher mortality (1.35 [95% confidence interval, 1.06-1.71]; P=0.01) and higher follow-up systolic blood pressure (1.85 [95% confidence interval, 0.24-3.46]; P=0.02) compared with temperature-nonsensitive subjects. Blood pressure response to temperature may be one of the underlying mechanisms that determine long-term blood pressure variability. Knowing a patient's blood pressure response to weather can help reduce unnecessary antihypertensive treatment modification, which may in turn increase blood pressure variability and, thus, risk.