Image-Based Computational Hemodynamics Analysis of Systolic Obstruction in Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is a pathological condition characterized by an abnormal thickening of the myocardium. When affecting the medio-basal portion of the septum, it is named Hypertrophic Obstructive Cardiomyopathy (HOCM) because it induces a flow obstruction in the left ventricular outflow tract. In any type of HCM, the myocardial function can become compromised, possibly resulting in cardiac death. In this study, we investigated with computational analysis the hemodynamics of patients with different types of HCM. The aim was quantifying the effects of this pathology on the intraventricular blood flow and pressure gradients, and providing information potentially useful to guide the indication and the modality of the surgical treatment (septal myectomy). We employed an image-based computational approach, integrating fluid dynamics simulations with geometric and functional data, reconstructed from standard cardiac cine-MRI acquisitions. We showed that with our approach we can better understand the patho-physiological behavior of intraventricular blood flow dynamics due to the abnormal morphological and functional aspect of the left ventricle. The main results of our investigation are: (a) a detailed patient-specific analysis of the blood velocity, pressure and stress distribution associated to HCM; (b) a computation-based classification of patients affected by HCM that can complement the current clinical guidelines for the diagnosis and treatment of HOCM.

Characterizing Tissue Remodeling and Mechanical Heterogeneity in Cerebral Aneurysms

Accurately assessing the complex tissue mechanics of cerebral aneurysms (CAs) is critical for elucidating how CAs grow and whether that growth will lead to rupture. The factors that have been implicated in CA progression – blood flow dynamics, immune infiltration, and extracellular matrix remodeling – all occur heterogeneously throughout the CA. Thus, it stands to reason that the mechanical properties of CAs are also spatially heterogeneous. Here, we present a new method for characterizing the mechanical heterogeneity of human CAs using generalized anisotropic inverse mechanics, which uses biaxial stretching experiments and inverse analyses to determine the local Kelvin moduli and principal alignments within the tissue. Using this approach, we find that there is significant mechanical heterogeneity within a single acquired human CA. These results were confirmed using second harmonic generation imaging of the CA’s fiber architecture and a correlation was observed. This approach provides a single-step method for determining the complex heterogeneous mechanics of CAs, which has important implications for future identification of metrics that can improve accuracy in prediction risk of rupture.

Effects of the atrium on intraventricular flow patterns during mechanical circulatory support

Simulations of the ventricular flow patterns during left ventricular assist device (LVAD) support are mainly performed with idealized cylindrical inflow, neglecting the influence of the atrial vortex. In this study, the influence of the left atrium (LA) on the intra-ventricular flow was investigated via Computational Fluid Dynamics (CFD) simulations. Ventricular flow was simulated by a combined Eulerian (carrier flow)/Lagrangian (particles) approach taking into account either the LA or a cylindrical inflow section to mimic a fully support condition. The flow deviation at the mitral valve, the blood low-velocity volume as well as the residence time and shear stress history of the particles were calculated. Inclusion of the LA deflects the flow at the mitral valve by 25°, resulting in an asymmetric flow jet entering the left ventricle. This reduced the ventricular low-velocity volume by 40% (from 6.4 to 3.9 cm3), increased (40%) the shear stress experienced by particles and correspondingly increased (27%) their residence time. Under the studied conditions, the atrial geometry plays a major role in the development of intraventricular flow patterns. A reliable prediction of blood flow dynamics and consequently thrombosis risk analysis within the ventricle requires the consideration of the LA in computational simulations.

Locus Coeruleus Noradrenergic Modulation of Diurnal Corticosterone, Stress Reactivity and Cardiovascular Homeostasis in Male Rats

Introduction: Activation of the locus coeruleus-noradrenergic (LC-NA) system during awakening is associated with an increase in plasma corticosterone and cardiovascular tone. These studies evaluate the role of the LC in this corticosterone and cardiovascular response. Methods: Male rats, on day 0, were treated IP with either DSP4 (50 mg/ kg body weight) (DSP), a LC-NA specific neurotoxin, or normal saline (SAL). On day 10, animals were surgically prepared with jugular vein [Hypothalamic–pituitary–adrenal (HPA) axis] or carotid artery (hemodynamics) catheters and experiments performed on day 14. HPA axis activity, diurnally (circadian) and after stress [transient hemorrhage (14 mL/kg body weight) or airpuff-startle], and basal and post-hemorrhage hemodynamics were evaluated. On day 16, brain regions from a subset of rats were dissected for norepinephrine and corticotropin-releasing factor (CRF) assay. Results: In DSP rats compared to SAL rats: 1) regional brain norepinephrine was decreased but there was no change in median eminence or olfactory bulb CRF content; 2) during HPA axis acrophase, the plasma corticosterone response was blunted; 3) after hemorrhage and airpuff-startle, the plasma adrenocorticotropic hormone response was attenuated, whereas the corticosterone response was dependent on stressor category; 4) under basal conditions, hemodynamic measures exhibited altered blood flow dynamics and systemic vasodilation; and 5) after hemorrhage, hemodynamics exhibited asynchronous responses. Conclusion: LC-NA modulation of diurnal and stress-induced HPA axis reactivity occurs via distinct neurocircuits. The integrity of the LC-NA system is important to maintain blood flow dynamics. The importance of increases in plasma corticosterone at acrophase to maintain short- and long-term cardiovascular homeostasis is discussed.

Investigation of the Pressure and Flow Dynamics during Aspiration Thrombectomy: A Mathematical Modelling Study

Aspiration thrombectomy is a life-saving interventional procedure to remove a blood clot from the brain of stroke patients. The pressure and blood flow dynamics during this procedure are crucial in determining the clinical outcomes. A mathematical model based on Hagen-Poiseuille law of fluid flow in a tube is adapted to simulate the pressure and fluid flow characteristics in an in vitro model of an occluded and unoccluded cerebrovascular network that mimics a poor (unilateral) and good (symmetrical) collateral flow within the Circle of Willis. The results show that in the absence of an occlusion, the pressure and pressure drop are higher in the symmetrical network compared to that in the unilateral network. This is due to the additional limb in the symmetrical network that must be supplied, which is absent in the unilateral network. In the presence of an occlusion, the flow reduces in the obstructed vessel, the collateral flow, overall pressure and pressure drop increases in both systems, but is higher for the symmetrical network. The results compare qualitatively with those observed in in vitro studies and with clinical observations. The theoretical framework lays the foundation for more advanced models for the pressure and blood flow dynamics towards clinical applicability.

Fluid-Structure Interaction in Coronary Stents: A Discrete Multiphysics Approach

Stenting is a common method for treating atherosclerosis. A metal or polymer stent is deployed to open the stenosed artery or vein. After the stent is deployed, the blood flow dynamics influence the mechanics by compressing and expanding the structure. If the stent does not respond properly to the resulting stress, vascular wall injury or re-stenosis can occur. In this work, a Discrete Multiphysics modelling approach is used to study the mechanical deformation of the coronary stent and its relationship with the blood flow dynamics. The major parameters responsible for deforming the stent are sorted in terms of dimensionless numbers and a relationship between the elastic forces in the stent and pressure forces in the fluid is established. The blood flow and the stiffness of the stent material contribute significantly to the stent deformation and affect its rate of deformation. The stress distribution in the stent is not uniform with the higher stresses occurring at the nodes of the structure. From the relationship (correlation) between the elastic force and the pressure force, depending on the type of material used for the stent, the model can be used to predict whether the stent is at risk of fracture or not after deployment.

Hypercoagulability States in COVID-19 Patients and Cutaneous Findings as Its Marker

Patients diagnosed with COVID-19 have a higher risk for thrombosis, which is the term used to denote an occlusion or blood clot that occurs in a vein [1-4]. These, in turn, can lead to detrimental consequences including motor impairments, as well as increased morbidity and mortality rates. Therefore, it is vital to assess routine laboratory and cutaneous findings to prevent any ensuing organ damage. German physician Rudolf Virchow identified some of the primary factors that may increase an individual’s susceptibility to developing thrombophilia [1-5]. Virchow’s triad comprises endothelial vessel wall injury, stasis or slowing down of the blood, and finally, hypercoagulability [2-4]. These three factors can be exacerbated by many components, including an individual’s genetic predisposition, or acquired factors like COVID-19, smoking, or hypertension [1,3,4]. Their contribution to hypercoagulability is discussed next. Endothelial injury can lead to turbulences in blood vessels, subsequently altering blood flow dynamics. If left unchanged, an inflammatory response is mounted via the complement system. Activation of the complement system results in an increased concentration of proinflammatory cytokines, thus promoting a hypercoagulable state [1,2]. As discussed above, stasis, which is used to describe immobilization of blood flow can result from prolonged stillness and directly increases hypercoagulability in patients [1,2]. Finally, prothrombic factors from the coagulation cascade system of our body can be altered, thus leading to a hypercoagulable state [1,2]. The correlation of Virchow’s triad as it relates specifically to COVID-19 patients will be discussed in detail below. Studies have shown that endothelial cell injury can occur as a direct response to the COVID-19 virus [1-4]. The damage created by the virus leads to activation of the complement-mediated system factors C5b-9, which subsequently leads to hypercoagulability [2,3]. In addition, endothelial injury can also result from the catheterization and intubation procedures implemented in severe COVID-19 cases, which can cause physical damage to blood vessels. Additionally, COVID-19 patients, especially those necessitating hospitalization and ICU care, are at an increased risk of thrombosis due to their prolonged immobility. This largely sedentary state directly impacts blood flow dynamics, for it promotes the genesis of stasis. Thirdly, the elevation of prothrombic factors such as fibrinogen and D-dimmer levels have been reported in COVID-19 patients, which directly lead to prolongation of Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) [1-3]. Routine monitoring of blood labs, including Complete Blood Count (CBC), platelet count, coagulation studies (PT and aPTT), fibrinogen, and D-dimer levels should be assessed to evaluate the coagulability state of COVID-19 patients. Moreover, given the fact that a hypercoagulable state can also manifest as a dermatological condition, physicians can also use this as a metric to diagnose hypercoagulability in patients [5]. Some of the most common cutaneous manifestations of hypercoagulability include purpura, livedo reticularis, livedo vasculopathy, chronic venous ulcers, and superficial venous thrombosis [4,5]. The clinical manifestation of Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), stroke, limb ischemia, bleeding, and any associated dermatological findings urge us to investigate the relationship between COVID-19 and increased susceptibility to bleeding and thrombosis [1-3]. This way, physicians can predict hypercoagulability state severity in COVID-19 patients and be better equipped to assess the overall risk of morbidity and mortality.