Congestive heart failure is characterized by suppressed cardiac output and arterial filling pressure, leading to renal retention of salt and water, contributing to further volume overload. Mathematical modeling provides a means to investigate the integrated function and dysfunction of heart and kidney in heart failure. This study updates our previously reported integrated model of cardiac and renal functions to account for the fluid exchange between the blood and interstitium across the capillary membrane, allowing the simulation of edema. A state of heart failure with reduced ejection fraction (HF-rEF) was then produced by altering cardiac parameters reflecting cardiac injury and cardiovascular disease, including heart contractility, myocyte hypertrophy, arterial stiffness, and systemic resistance. After matching baseline characteristics of the SOLVD clinical study, parameters governing rates of cardiac remodeling were calibrated to describe the progression of cardiac hemodynamic variables observed over one year in the placebo arm of the SOLVD clinical study. The model was then validated by reproducing improvements in cardiac function in the enalapril arm of SOLVD. The model was then applied to prospectively predict the response to the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin, which has been shown to reduce heart failure events in HF-rEF patients in the recent DAPAHF clinical trial by incompletely understood mechanisms. The simulations predict that dapagliflozin slows cardiac remodeling by reducing preload on the heart, and relieves congestion by clearing interstitial fluid without excessively reducing blood volume. This provides a quantitative mechanistic explanation for the observed benefits of SGLT2i in HF-rEF. The model also provides a tool for further investigation of heart failure drug therapies. Recently, the DAPAHF and EMPA-REG clinical trials showed that the Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) class of drugs are beneficial in reducing the heart failure with reduced ejection fraction (HFrEF) hospitalization and lowering the risk of PLOS COMPUTATIONAL BIOLOGY

One-dimensional (1D) simulation of the complete vascular network, so called THINkS (Total Human Intravascular Network Simulation) is developed to investigate changes of blood flow characteristics caused by the variation of CoW. THINkS contains 158 major veins, 85 major arteries, and 77 venous and 43 arterial junctions. THINkS is validated with available in vivo blood flow waveform data. The overall trends of flow rates in variations of the CoW, such as the missing anterior cerebral artery (missing-A1) or missing posterior cerebral artery (missing-P1), are confirmed by in vivo experimental data. It is demonstrated that the CoW has the ability to shunt blood flow to different areas in the brain. Flow rates in efferent arteries remain unaffected under the variation of CoW, while the flow rates in afferent vessels can be subject to substantial changes. The redistribution of blood flow can cause particular vessels to undergo extra flow rate and hemodynamic stresses.

A 1-dimensional (1D)-3-dimensional (3D) multiscale model for the human vascular network was proposed by combining a low-fidelity 1D modeling of blood circulation to account for the global hemodynamics with a detailed 3D simulation of a zonal vascular segment. The coupling approach involves a direct exchange of flow and pressure information at interfaces between the 1D and 3D models and thus enables patient-specific morphological models to be inserted into flow network with minimum computational efforts. The proposed method was validated with good agreements against 3 simplified test cases where experimental data and/or full 3D numerical solution were available. The application of the method in aneurysm and stenosis studies indicated that the deformation of the geometry caused by the diseases may change local pressure loss and as a consequence lead to an alteration of flow rate to the vessel segment.

Detailed blood velocity map in the vascular system can be obtained by applying the optical flow method (OFM) in processing fluoroscopic digital subtracted catheter angiographic images; however, there are still challenges with the accuracy of this method. In the present study, a divergence compensatory optical flow method (DC-OFM), in which a nonzero divergence of velocity is assumed due to the finite resolution of the image, was explored and applied to the digital subtraction angiography (DSA) images of blood flow. The objective of this study is to examine the applicability and evaluate the accuracy of DC-OFM in assessing the blood flow velocity in vessels. First, an Oseen vortex flow was simulated on the standard particle image to generate an image pair. Then, the DC-OFM was applied on the particle image pair to recover the velocity field for validation. Second, DSA images of intracranial arteries were used to examine the accuracy of the current method. For each set of images, the first image is the in vivo DSA image, and the second image is generated by superimposing a given flow field. The recovered velocity map by DC-OFM agrees well with the exact velocity for both the particle images and the angiographic images. In comparison with the traditional OFM, the present method can provide more accurate velocity estimation. The accuracy of the velocity estimation can also be improved by implementing preprocess techniques including image intensification, Gaussian filtering, and "image-shift."

Age-associated alterations in cardiovascular structure and function induce cardiovascular disease in elderly subjects. To investigate the effects of normal vascular aging (NVA) and early vascular aging (EVA) on hemodynamic characteristics in the circle of Willis (CoW), a closed-loop one-dimensional computational model was developed based on fluid mechanics in the vascular system. The numerical simulations revealed that higher central pulse pressure and augmentation index (AIx) appear in the EVA subjects due to early arrival of reflected waves, resulted in the increase of cardiac afterload compared with the NVA subjects. Moreover, the hemodynamic characteristics in the CoW show that the EVA subjects in an older age display a higher blood pressure than that of the NVA with a complete CoW. Herein, the increased blood pressure and flow rate coexist in the subjects with an incomplete CoW. In conclusion, the hemodynamic characteristics in the aortic tree and CoW related to aging appear to play an important role in causing cardiovascular and intravascular disease.