Coronary Hemodynamics Research Articles

A practical risk model based on Lasso-Cox regression for angina with nonobstructive coronary arteries (ANOCA) patients

Abstract Background Coronary flow reserve (CFR) reduction is currently one of the main criteria for risk-stratifying patients with angina and nonobstructive coronary artery disease (ANOCA). However, CFR depends on resting and vasodilated coronary hemodynamics, and a theoretical concern remains that physiological changes may inadvertently affect the result. Purpose We aim to fit different risk models for patients with ANOCA, which further provides applicable guidance to clinical doctors for their patients. Methods Between May 2018 and October 2023, 251 consecutive patients who were diagnosed as ANOCA were enrolled from Qilu Hospital of Shandong University, and the median follow-up was 800 (493, 1221) days. Demographic characteristics, cardiovascular risk factors, cardiac structure and function index, echocardiography-derived coronary flow velocity, coronary flow velocity-time integral, and CFR were collected. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses were used to screen for significant parameters that were included to develop a novel predictive nomogram model. Receiver operating characteristic curve and calibration curve were used to evaluate the performance and clinical utility of the nomogram. Results In LASSO regression selection, five variables, diabetes, global work efficiency (GWE), global wasted work (GWW), decreased hyperemic coronary flow velocity (<0.63m/s), and peak flow velocity-derived CFR<2.5 (Figure 1) showed their correlation to the occurrence of major adverse cardiovascular events (MACE). Univariate Cox regression analysis shows that diabetes (hazard ratio [HR] = 4.108; 95% confidence interval [CI], 2.296–7.350; p = 0.001), GWE (HR = 0.890; 95% CI, 0.856–0.926; p = 0.001), GWW (HR = 1.005; 95% CI, 1.004–1.007; p = 0.012), decreased hyperemic coronary flow velocity (HR =3.405; 95% CI, 1.730–6.702; p = 0.001) and peak flow velocity-derived CFR<2.5 (HR =3.456; 95% CI, 1.898–6.292; p = 0.001) were predictors of recurrent chest pain. Multivariate analysis showed that the association of diabetes (HR = 2.735; 95% CI, 1.452–5.152; p = 0.002), GWW (HR = 1.004; 95% CI, 1.001–1.007; p = 0.010), and peak flow velocity-derived CFR<2.5 (HR = 2.650; 95% CI, 1.306–5.380; p = 0.007) with MACE remained statistically significant after adjusting for other variables. A nomogram incorporated the predictors mentioned above; it is presented in Fig.2. Internal validation showed that the model has good predictive performance. The areas under the curve (AUCs) for prediction of the risk of MACE was 0.849 (Fig.3). The calibration curve for predicting chest pain recurrence shows a good agreement between prediction and observation (Fig.4). Conclusions Diabetes, GWE, GWW, decreased hyperemic coronary flow velocity (<0.63m/s), and peak flow velocity-derived CFR<2.5 are significant in identifying the occurrence risk of MACE for ANOCA patients.

Establishing the longitudinal hemodynamic mapping framework for wearable-driven coronary digital twins

Understanding the evolving nature of coronary hemodynamics is crucial for early disease detection and monitoring progression. We require digital twins that mimic a patient’s circulatory system by integrating continuous physiological data and computing hemodynamic patterns over months. Current models match clinical flow measurements but are limited to single heartbeats. To this end, we introduced the longitudinal hemodynamic mapping framework (LHMF), designed to tackle critical challenges: (1) computational intractability of explicit methods; (2) boundary conditions reflecting varying activity states; and (3) accessible computing resources for clinical translation. We show negligible error (0.0002–0.004%) between LHMF and explicit data of 750 heartbeats. We deployed LHMF across traditional and cloud-based platforms, demonstrating high-throughput simulations on heterogeneous systems. Additionally, we established LHMFC, where hemodynamically similar heartbeats are clustered to avoid redundant simulations, accurately reconstructing longitudinal hemodynamic maps (LHMs). This study captured 3D hemodynamics over 4.5 million heartbeats, paving the way for cardiovascular digital twins.

A new understanding of coronary curvature and haemodynamic impact on the course of plaque onset and progression

The strong link between atherosclerosis and luminal biomechanical stresses is well established. Yet, this understanding has not translated into preventative coronary diagnostic imaging, particularly due to the under-explored role of coronary anatomy and haemodynamics in plaque onset, which we aim to address with this work. The left coronary trees of 20 non-stenosed (%diameter stenosis [%DS] = 0), 12 moderately (0 < %DS < 70) and 7 severely (%DS ≥ 70) stenosed cases were dissected into bifurcating and non-bifurcating segments for whole-tree and segment-specific comparisons, correlating nine three-dimensional coronary anatomical features, topological shear variation index (TSVI) and luminal areas subject to low time-average endothelial shear stress (%LowTAESS), high oscillatory shear index (%HighOSI) and high relative residence time (%HighRRT). We found that TSVI is the only metric consistently differing between non-stenosed and stenosed cases across the whole tree, bifurcating and non-bifurcating segments ( p < 0.002, AUC = 0.876), whereas average curvature and %HighOSI differed only for the whole trees ( p < 0.024) and non-bifurcating segments ( p < 0.027), with AUC > 0.711. Coronary trees with moderate or severe stenoses differed only in %LowTAESS ( p = 0.009) and %HighRRT ( p = 0.012). This suggests TSVI, curvature and %HighOSI are potential factors driving plaque onset, with greater predictive performance than the previously recognized %LowTAESS and %HighRRT, which appears to play a role in plaque progression.

Hemodynamic Evaluation of Coronary Artery Lesions after Kawasaki Disease: Comparison of Fractional Flow Reserve during Cardiac Catheterization with Myocardial Flow Reserve during 13N-Ammonia PET.

Coronary artery lesions (CALs) after Kawasaki disease present complex coronary hemodynamics. We investigated the relationship between coronary fractional flow reserve (FFR), myocardial flow reserve (MFR), and myocardial blood flow volume fraction (MBF) and their clinical usefulness in CALs after Kawasaki disease. Nineteen patients (18 men, 1 woman) who underwent cardiac catheterization and 13N-ammonia positron emission tomography, with 24 coronary artery branches, were included. Five branches had inconsistent FFR and MFR values, two had normal FFR but abnormal MFR, and three had abnormal FFR and normal MFR. The abnormal MFR group had significantly higher MBF at rest than the normal group (0.86 ± 0.13 vs. 1.08 ± 0.09, p = 0.001). The abnormal FFR group had significantly lower MBF at adenosine loading than the normal group (2.23 ± 0.23 vs. 1.88 ± 0.29, p = 0.021). The three branches with abnormal FFR only had stenotic lesions, but the MFR may have been normal because blood was supplied by collateral vessels. Combining FFR, MFR, and MBF will enable a more accurate assessment of peripheral coronary circulation and stenotic lesions in CALs and help determine treatment strategy and timing of intervention.

An Overview of Computational Coronary Physiology Technologies Based on Medical Imaging and Artificial Intelligence.

This article reviews four new technologies for assessment of coronary hemodynamics based on medical imaging and artificial intelligence, including quantitative flow ratio (QFR), optical flow ratio (OFR), computational fractional flow reserve (CT-FFR) and artificial intelligence (AI)-based instantaneous wave-free ratio (iFR). These technologies use medical imaging such as coronary angiography, computed tomography angiography (CTA), and optical coherence tomography (OCT), to reconstruct three-dimensional vascular models through artificial intelligence algorithms, simulate and calculate hemodynamic parameters in the coronary arteries, and achieve non-invasive and rapid assessment of the functional significance of coronary stenosis. This article details the working principles, advantages such as non-invasiveness, efficiency, accuracy, limitations such as image dependency, and assumption restrictions, of each technology. It also compares and analyzes the image dependency, calculation accuracy, calculation speed, and operation simplicity, of the four technologies. The results show that these technologies are highly consistent with the traditional invasive wire method, and shows distinct advantages in terms of accuracy, reliability, convenience and cost-effectiveness, but there are also factors that affect accuracy. The results of this review demonstrates that AI-based iFR technology is currently one of the most promising technologies. The main challenges and directions for future development are also discussed. These technologies bring new ideas for the non-invasive assessment of coronary artery disease, and are expected to promote the technological progress in this field.

Myocardial Blood Flow Reserve, Microvascular Coronary Health, and Myocardial Remodeling in Patients With Aortic Stenosis.

Coronary microvascular function and hemodynamics may play a role in coronary circulation and myocardial remodeling in patients with aortic stenosis (AS). We aimed to evaluate the relationship between myocardial blood flow and myocardial function in patients with AS, no AS, and aortic valve sclerosis. We included consecutive patients who had resting transthoracic echocardiography and clinically indicated positron emission tomography myocardial perfusion imaging to capture their left ventricular ejection fraction, global longitudinal strain (GLS), and myocardial flow reserve (MFR). The primary outcome was major adverse cardiovascular event (all-cause mortality, myocardial infarction, or late revascularization). There were 2778 patients (208 with aortic sclerosis, 39 with prosthetic aortic valve, 2406 with no AS, and 54, 49, and 22 with mild, moderate, and severe AS, respectively). Increasing AS severity was associated with impaired MFR (P<0.001) and GLS (P<0.001), even when perfusion was normal. Statistically significant associations were noted between MFR and GLS, MFR and left ventricular ejection fraction, and MFR and left ventricular ejection fraction reserve. After a median follow-up of 349 (interquartile range, 116-662) days, 4 (7.4%), 5 (10.2%), and 6 (27.3%) patients experienced a major adverse cardiovascular event in the mild, moderate, and severe AS groups, respectively. In a matched-control analysis, patients with mild-to-moderate AS had higher rates of impaired MFR (52.9% versus 39.9%; P=0.048) and major adverse cardiovascular event (11.8% versus 3.0%; P=0.002). Despite lack of ischemia, as severity of AS increased, MFR decreased and GLS worsened, reflecting worse coronary microvascular health and myocardial remodeling. Positron emission tomography-derived MFR showed a significant independent correlation with left ventricular ejection fraction and GLS. Patients with prosthetic aortic valve showed a high prevalence of impaired MFR.

Patient-Specific Numerical Simulations of Coronary Artery Hemodynamics and Biomechanics: A Pathway to Clinical Use.

Numerical models that simulate the behaviors of the coronary arteries have been greatly improved by the addition of fluid-structure interaction (FSI) methods. Although computationally demanding, FSI models account for the movement of the arterial wall and more adequately describe the biomechanical conditions at and within the arterial wall. This offers greater physiological relevance over Computational Fluid Dynamics (CFD) models, which assume the walls do not move or deform. Numerical simulations of patient-specific cases have been greatly bolstered by the use of imaging modalities such as Computed Tomography Angiography (CTA), Magnetic Resonance Imaging (MRI), Optical Coherence Tomography (OCT), and Intravascular Ultrasound (IVUS) to reconstruct accurate 2D and 3D representations of artery geometries. The goal of this study was to conduct a comprehensive review on CFD and FSI models on coronary arteries, and evaluate their translational potential. This paper reviewed recent work on patient-specific numerical simulations of coronary arteries that describe the biomechanical conditions associated with atherosclerosis using CFD and FSI models. Imaging modality for geometry collection and clinical applications were also discussed. Numerical models using CFD and FSI approaches are commonly used to study biomechanics within the vasculature. At high temporal and spatial resolution (compared to most cardiac imaging modalities), these numerical models can generate large amount of biomechanics data. Physiologically relevant FSI models can more accurately describe atherosclerosis pathogenesis, and help to translate biomechanical assessment to clinical evaluation.

Role of potassium as a coronary metabolic vasodilator

K+ release from the myocardium is associated with decreased coronary vascular resistance. Accumulation of extracellular K+ has been linked to mechanisms of vasodilation in the coronary circulation including activation of the electrogenic Na+-K+ pump in smooth muscle (Murray and Sparks, Circ. Res. 1977) and endothelial-mediated hyperpolarization via Kir2.1 channels (Zhao et al., PNAS 2020). Our objective was to examine K+ as a coronary metabolic vasodilator in vivo. Further, we addressed two potential shortcomings of previous studies: the short duration of the bolus K+ stimulus employed and the seemingly high concentrations required to produce vasodilation. We hypothesized that continuous, steady-state intracoronary infusions of K+ would produce sustained coronary vasodilation in a concentration-dependent manner. Our methods involved instrumenting anesthetized, open-chest Yorkshire swine (male and female, 60 kg) for measurements of coronary blood flow, as well as arterial and coronary venous blood sampling. The left anterior descending coronary artery was cannulated and perfused under the control of a pressure servo, allowing us to determine flow and infuse K+. Our results show small, but statistically significant (* represents p &lt; 0.05), effects of K+ on coronary hemodynamics. The coronary venous K+ concentration was 4.0 ± 0.1 mM at baseline. Infusing K+ into the coronary artery at increasing rates increased coronary venous K+ to 4.9 ± 0.2*, 6.4 ± 0.2*, and 7.9 ± 0.2* mM. Higher K+ concentrations caused fatal arrhythmias. Coronary blood flow was 0.73 ± 0.14 ml/min/g at baseline. Infusing K+ into the coronary artery at increasing rates increased coronary blood flow to 0.78 ± 0.14*, 0.82 ± 0.15*, and 0.86 ± 0.16* ml/min/g. These small coronary blood flow changes were sustained during continuous K+ infusion. We conclude that K+ is a coronary vasodilator, as has been demonstrated previously. Importantly, however, we emphasize that the effects of K+ are extremely modest and the concentrations required to produce physiologically significant vasodilation are life-threatening. With the assumption that the venous K+ concentration is in equilibrium with that surrounding the smooth muscle and cardiac muscle of the working heart, we urge caution in interpreting isolated artery studies that routinely use 15-20 mM K+ to elicit hyperpolarization and vasodilation. Our data do not support the idea that K+ plays a major role in regulating coronary vascular resistance. This work was supported by National Institutes of Health grant R01 HL158723. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mechanisms of coronary sinus reducer for treatment of myocardial ischemia: in silico study.

The coronary sinus reducer (CSR) is an emerging medical device for treating patients with refractory angina, often associated with myocardial ischemia. Patients implanted with CSR have shown positive outcomes, but the underlying mechanisms are unclear. This study sought to understand the mechanisms of CSR by investigating its effects on coronary microcirculation hemodynamics that may help explain the therapy's efficacy. We applied a validated computer model of the coronary microcirculation to investigate how CSR affects hemodynamics under different degrees of coronary artery stenosis. With moderate coronary stenosis, an increase in capillary transit time (CTT) [up to 69% with near-complete coronary sinus (CS) occlusion] is the key change associated with CSR. Because capillaries in the microcirculation can still receive oxygenated blood from the upstream artery with moderate stenosis, the increase in CTT allows more time for the exchange of gases and nutrients, aiding tissue oxygenation. With severe coronary stenosis; however, the redistribution of blood draining from the nonischemic region to the ischemic region (up to 96% with near-complete CS occlusion) and the reduction in capillary flow heterogeneity are the key changes associated with CSR. Because blood draining from the nonischemic region is not completely devoid of O2, the redistribution of blood to the capillaries in the ischemic region by CSR is beneficial especially when little or no oxygenated blood reaches these capillaries. This simulation study provides insights into the mechanisms of CSR in improving clinical symptoms. The mechanisms differ with the severity of the upstream stenosis.NEW & NOTEWORTHY Emerging coronary venous retroperfusion treatments, particularly coronary sinus reducer (CSR) for refractory angina linked to myocardial ischemia, show promise; however, their mechanisms of action are not well understood. We find that CSR's effectiveness varies with the severity of coronary stenosis. In moderate stenosis, CSR improves tissue oxygenation by increasing capillary transit time, whereas in severe stenosis, it redistributes blood from nonischemic to ischemic regions and reduces capillary flow heterogeneity.

Study on the related factors of TCM constitution and hemodynamics in patients with coronary heart disease.

The concepts of "individualization" and "preventive treatment" should be incorporated into the precise diagnosis and treatment of coronary heart disease (CHD). Both hemodynamics and Chinese medicine constitution studies align with these two concepts. This study utilized data from 81 patients with CHD, including 12 patients with balanced constitution (BC), 20 patients with blood stasis constitution (BSC), 17 patients with phlegm-dampness constitution (PDC), 15 patients with qi-deficiency constitution (QDC), and 17 patients with other constitutions. Clinical data provided information on the patients' blood property, heart function, degree of coronary stenosis, coronary hemodynamics, and so on. These parameters were compared between patients with balanced constitution vs. biased constitutions as well as between those with blood stasis constitution, phlegm-dampness constitution, and qi-deficiency constitution. Compared to biased constitution (BC), patients with balanced constitution exhibited lower total cholesterol (TC) levels and low-density lipoprotein (LDL) levels. Additionally, they had lighter stenosis degrees in the Left anterior descending branch (LAD) and Left circumflex branch (LCX) branches. The hemodynamic condition of the LAD and LCX was better for those with balanced constitution; however there was no difference in heart function. Among the groups categorized by blood stasis, phlegm dampness or qi deficiency constituions, patients classified under phlegm dampness had higher levels of LDL compared to those classified under blood stasis or qi deficiency, while patients classified under qi deficiency had higher levels of blood glucose compared to those classified under blood stasis or phlegm dampness. Hemodynamic environments also differed among the LAD and LCX for each group but there were no significant differences observed in heart function or degree of coronary stenosis among these three groups. The balanced constitution demonstrates superior blood property, degree of coronary artery stenosis, and coronary hemodynamics compared to the biased constitution. Furthermore, among the three constitutions with CHD, variations in blood property and certain hemodynamic parameters are observed. These findings emphasize the significant clinical value of incorporating physical factors into the diagnosis and treatment of patients with CHD.

Stenosis severity and heart rate effects on left coronary artery hemodynamics and myocardial oxygen balance: A comprehensive assessment using pressure gradient

The estimation of pressure drop across stenotic arteries can provide valuable information about the hemodynamic features. Nevertheless, the temporal behavior of pressure in stenotic arteries is not well reported for realistic pulsatile flows. This research investigates the pressure drop across a left coronary artery model for different degrees of stenotic severity and heart rates. The zones prone to further atherogenic degeneration are identified using time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI). A unique attempt has been made to quantify the effect of stenosis severity and elevated heart rate on coronary perfusion pressure (CPP) and endocardial viability ratio (EVR), which is an indicator of myocardial oxygen supply-demand balance. We have predicted reductions in both CPP and EVR as stenosis severity increases. The aforementioned metrics exhibit a notable drop when confronted with a moderate stenosis at an increased heart rate, implying that the hemodynamic consequences of a moderate stenosis during an elevated heart rate may be comparable to those of a severe stenosis during a state of rest. The current computational investigation has the potential to reduce the need for in vivo hemodynamic assessments of stenosis. In addition, the wall shear stress-based mechanical parameters, such as TAWSS and OSI, can indicate the atherogenic and thrombogenic regions in the stenosed vessels.

Left main coronary artery morphological phenotypes and its hemodynamic properties.

Atherosclerosis may be linked to morphological defects that lead to variances in coronary artery hemodynamics. Few objective strategies exit at present for generalizing morphological phenotypes of coronary arteries in terms of hemodynamics. We used unsupervised clustering (UC) to classify the morphology of the left main coronary artery (LM) and looked at how hemodynamic distribution differed between phenotypes. In this study, 76 LMs were obtained from 76 patients. After LMs were reconstructed with coronary computed tomography angiography, centerlines were used to extract the geometric characteristics. Unsupervised clustering was carried out using these characteristics to identify distinct morphological phenotypes of LMs. The time-averaged wall shear stress (TAWSS) for each phenotype was investigated by means of computational fluid dynamics (CFD) analysis of the left coronary artery. We identified four clusters (i.e., four phenotypes): Cluster 1 had a shorter stem and thinner branches (n = 26); Cluster 2 had a larger bifurcation angle (n = 10); Cluster 3 had an ostium at an angulation to the coronary sinus and a more curved stem, and thick branches (n = 10); and Cluster 4 had an ostium at an angulation to the coronary sinus and a flatter stem (n = 14). TAWSS features varied widely across phenotypes. Nodes with low TAWSS (L-TAWSS) were typically found around the branching points of the left anterior descending artery (LAD), particularly in Cluster 2. Our findings demonstrated that UC is a powerful technique for morphologically classifying LMs. Different LM phenotypes exhibited distinct hemodynamic characteristics in certain regions. This morphological clustering method could aid in identifying people at high risk for developing coronary atherosclerosis, hence facilitating early intervention.

Effect of alirocumab on quantitative flow ratio and diameter stenosis in non-infarct related arteries from patients with acute myocardial infarction: a PACMAN-AMI randomized clinical trial substudy

Abstract Introduction Treating hypercholesterolemia with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilization. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown. Quantitative Flow Ratio (QFR) is a novel method to assess coronary hemodynamics. Purpose We aimed to investigate the effects of the PCSK9 inhibitor alirocumab on QFR and 3D-Quantitative Coronary Angiography (3D-QCA) DS% in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients. Methods This was a pre-specified substudy of the PACMAN trial, a randomized, double-blind, placebo-controlled trial comparing alirocumab vs. placebo on top of high-intensity rosuvastatin among AMI patients. QFR and 3D-QCA were assessed at baseline and 1-year follow-up in any non-infarct related artery (non-IRA) with ≥2.0mm diameter and &amp;gt;25% 3D-QCA DS%. The pre-specified primary endpoint was the number of patients with mean QFR increase from baseline to follow-up, and the secondary endpoint the change in 3D-QCA DS%. Results Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. Baseline mean QFR was 0.96[IQR 0.91-0.98] and mean DS% 36.96±7.88% in the alirocumab group vs. 0.96[IQR 0.91-0.99] (p=0.593) and 36.63±8.46% (p=0.742) in the placebo group. At 1-year, QFR increased in 50/94 (53.2%) patients with alirocumab vs. 40/99 (40.4%) with placebo (Δ12.8%; OR=1.7, 95%CI 0.9-3.0; p=0.076). When excluding non-IRA with QFR &amp;gt;0.95, QFR increased in 37/57 (64.9%) patients with alirocumab vs. 22/50 (44.0%) with placebo (Δ20.9%; OR=2.4, 95%CI 1.1-5.2; p=0.031). DS% decreased by -1.03±7.28% with alirocumab and increased by +1.70±8.27% with placebo (Δ-2.54%, 95%CI -4.51 to -0.57; p=0.012). Conclusions Treatment of AMI patients with alirocumab vs. placebo for 1 year resulted in a significant regression in angiographic DS%. While no overall improvement of coronary hemodynamics was observed with alirocumab as compared to placebo, potential benefits were found in alirocumab treated patients with baseline QFR ≤0.95.Figure 1.Flowchart and primary endpointFigure 2.Secondary endpoint

Myocardial perfusion segmentation and partitioning methods in personalized models of coronary blood flow

Abstract In this work we present methods and algorithms for construction of a personalized model of coronary haemodynamics based on computed tomography images. This model provides estimations of fractional flow reserve, coronary flow reserve, and instantaneous wave-free ratio taking into account transmural perfusion ratio indices obtained from perfusion images. The presented pipeline consists of the following steps: aorta segmentation, left ventricle wall segmentation, coronary arteries segmentation, construction of 1D network of vessels, partitioning of left ventricle wall, and personalization of the model parameters. We focus on a new technique, which generates specific perfusion zones and computes transmural perfusion ratio according to the quality of available medical images with a limited number of visible terminal coronary vessels. Numerical experiments show that accurate evaluation of stenosis before precutaneous coronary intervention should take into account both fractional flow reserve indices and myocardial perfusion, as well as other indices, in order to avoid misdiagnosis. The presented model provides better understanding of the background of clinical recommendations for possible surgical treatment of a stenosed coronary artery.

Noninvasive Multimodality Imaging for the Assessment of Anomalous Coronary Artery.

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital coronary anomaly with the potential to cause myocardial ischemia and adverse cardiac events. The presence of AAOCA anatomy itself does not necessarily implicate a need for revascularization. Therefore, the purpose of this review is to assess how noninvasive comprehensive anatomic- and physiologic evaluation may guide patient management. The assessment of AAOCA includes an accurate description of the anomalous origin/vessel course including anatomical high-risk features such as a slit-like ostium, proximal narrowing, elliptic vessel shape, acute take-off angle, intramural course, and possibleconcomitant coronary atherosclerosis and hemodynamics. Various cardiac imaging modalities offer unique advantages and capabilities in visualizing these anatomical and functional aspects of AAOCA. This review explored the role of noninvasive multimodality imaging in the characterization of AAOCA by highlighting the strengths, limitations, and potential applications of the current different cardiac imaging methods, with a focus on the pathophysiology of myocardial ischemia and stress testing protocols.

A physics-based machine learning technique rapidly reconstructs the wall-shear stress and pressure fields in coronary arteries.

With the global rise of cardiovascular disease including atherosclerosis, there is a high demand for accurate diagnostic tools that can be used during a short consultation. In view of pathology, abnormal blood flow patterns have been demonstrated to be strong predictors of atherosclerotic lesion incidence, location, progression, and rupture. Prediction of patient-specific blood flow patterns can hence enable fast clinical diagnosis. However, the current state of art for the technique is by employing 3D-imaging-based Computational Fluid Dynamics (CFD). The high computational cost renders these methods impractical. In this work, we present a novel method to expedite the reconstruction of 3D pressure and shear stress fields using a combination of a reduced-order CFD modelling technique together with non-linear regression tools from the Machine Learning (ML) paradigm. Specifically, we develop a proof-of-concept automated pipeline that uses randomised perturbations of an atherosclerotic pig coronary artery to produce a large dataset of unique mesh geometries with variable blood flow. A total of 1,407 geometries were generated from seven reference arteries and were used to simulate blood flow using the CFD solver Abaqus. This CFD dataset was then post-processed using the mesh-domain common-base Proper Orthogonal Decomposition (cPOD) method to obtain Eigen functions and principal coefficients, the latter of which is a product of the individual mesh flow solutions with the POD Eigenvectors. Being a data-reduction method, the POD enables the data to be represented using only the ten most significant modes, which captures cumulatively greater than 95% of variance of flow features due to mesh variations. Next, the node coordinate data of the meshes were embedded in a two-dimensional coordinate system using the t-distributed Stochastic Neighbor Embedding (-SNE) algorithm. The reduced dataset for -SNE coordinates and corresponding vector of POD coefficients were then used to train a Random Forest Regressor (RFR) model. The same methodology was applied to both the volumetric pressure solution and the wall shear stress. The predicted pattern of blood pressure, and shear stress in unseen arterial geometries were compared with the ground truth CFD solutions on "unseen" meshes. The new method was able to reliably reproduce the 3D coronary artery haemodynamics in less than 10 s.

Modelling blood flow in coronary arteries: Newtonian or shear-thinning non-Newtonian rheology?

BackgroundThe combination of medical imaging and computational hemodynamics is a promising technology to diagnose/prognose coronary artery disease (CAD). However, the clinical translation of in silico hemodynamic models is still hampered by assumptions/idealizations that must be introduced in model-based strategies and that necessarily imply uncertainty. This study aims to provide a definite answer to the open question of how to properly model blood rheological properties in computational fluid dynamics (CFD) simulations of coronary hemodynamics. MethodsThe geometry of the right coronary artery (RCA) of 144 hemodynamically stable patients with different stenosis degree were reconstructed from angiography. On them, unsteady-state CFD simulations were carried out. On each reconstructed RCA two different simulation strategies were applied to account for blood rheological properties, implementing (i) a Newtonian (N) and (ii) a shear-thinning non-Newtonian (non-N) rheological model. Their impact was evaluated in terms of wall shear stress (WSS magnitude, multidirectionality, topological skeleton) and helical flow (strength, topology) profiles. Additionally, luminal surface areas (SAs) exposed to shear disturbances were identified and the co-localization of paired N and non-N SAs was quantified in terms of similarity index (SI). ResultsThe comparison between paired N vs. shear-thinning non-N simulations revealed remarkably similar profiles of WSS-based and helicity-based quantities, independent of the adopted blood rheology model and of the degree of stenosis of the vessel. Statistically, for each paired N and non-N hemodynamic quantity emerged negligible bias from Bland-Altman plots, and strong positive linear correlation (r > 0.94 for almost all the WSS-based quantities, r > 0.99 for helicity-based quantities). Moreover, a remarkable co-localization of N vs. non-N luminal SAs exposed to disturbed shear clearly emerged (SI distribution 0.95 [0.93, 0.97]). Helical flow topology resulted to be unaffected by blood rheological properties. ConclusionsThis study, performed on 288 angio-based CFD simulations on 144 RCA models presenting with different degrees of stenosis, suggests that the assumptions on blood rheology have negligible impact both on WSS and helical flow profiles associated with CAD, thus definitively answering to the question “is Newtonian assumption for blood rheology adequate in coronary hemodynamics simulations?”.

Sex Differences in Systemic and Coronary Arterial Hemodynamics in Heart Failure With Preserved Ejection Fraction

Heart failure (HF) with preserved ejection fraction (HFpEF) predominantly affects females. Systemic and coronary arterial abnormalities are present in HFpEF and may contribute to HFpEF in females. We performed a cross-sectional study of 32 participants with HFpEF and 26 controls. Arterial hemodynamics were noninvasively assessed by combining arterial tonometry with echocardiography. Coronary microvascular function was assessed by rubidium-82 positron emission tomography as the myocardial flow reserve. Coronary vascular resistance (CVR) at rest and vasodilator stress were calculated using positron emission tomography. CVR reserve was calculated as stress-rest CVR. Multivariable linear regression assessed the associations of female sex with arterial hemodynamics in participants with and without HF, and the association of HF with arterial hemodynamics within each sex stratum. Demographics and left ventricular systolic and diastolic function were similar between males and females. Among those with HFpEF, females had a higher steady and pulsatile arterial load and more impaired (less negative) CVR reserve than males. Conversely, in controls, females had similar hemodynamics to males. We then divided the sample based on sex. Femaleswith HFpEF had a higher pulsatile arterial load and higher stress CVR than control females. Among males, arterial hemodynamics were similar, regardless of HFpEF status. The measures of early pulsatile arterial load were independently associated with higher E/e' and lower myocardial flow reserve in females only. In conclusion, despite similar left ventricular function between sexes, older females with HFpEF are characterized by additional systemic and coronary arterial hemodynamic abnormalities compared with males with HFpEF and similarly aged females without HFpEF.

Coronary Atherosclerosis Phenotypes in Focal and Diffuse Disease

BackgroundThe interplay between coronary hemodynamics and plaque characteristics remains poorly understood. ObjectivesThe aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics. MethodsThis multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value. ResultsA total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87). ConclusionsAtherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688)

Non-invasive Endothelial Shear Stress Estimates Using CT-Derived Coronary Haemodynamics

Non-invasive Endothelial Shear Stress Estimates Using CT-Derived Coronary Haemodynamics