Lower estimates of myocardial perfusion are associated with greater aortic perivascular adipose tissue density in humans independent of aortic stiffness.

Aortic perivascular adipose tissue (aPVAT) density is associated with age-related aortic stiffness in humans and therefore, may contribute to cardiovascular dysfunction. A lower subendocardial viability ratio (SEVR), an estimate of myocardial perfusion, indicates greater cardiovascular disease (CVD) risk and is associated with aortic stiffness in clinical populations. However, the influence of aortic stiffness on the relation between aPVAT density and SEVR/cardiovascular (CV) hemodynamics in apparently healthy adults is unknown. We hypothesize that greater aPVAT density will be associated with lower SEVR and higher CV hemodynamics independent of aortic stiffness. Fourteen (6 males/8 females; mean age, 55.4 ± 5.6 yr; body mass index, 25.5 ± 0.6 kg/m2) adults completed resting measures of myocardial perfusion (SEVR), CV hemodynamics (pulse wave analysis), aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)], and a computed tomography scan to acquire aPVAT and visceral adipose tissue (VAT) density. Greater aPVAT density (i.e., higher density) was associated with lower SEVR (r = -0.78, P < 0.001) and a higher systolic pressure time integral (r = 0.49, P = 0.03), forward pulse height (r = 0.49, P = 0.03), reflected pulse height (r = 0.55, P = 0.02), ejection duration (r = 0.56, P = 0.02), and augmentation pressure (r = 0.69, P = 0.003), but not with the diastolic pressure time integral (r = -0.22, P = 0.22). VAT density was not associated with SEVR or any CV hemodynamic endpoints (all, P > 0.05). Furthermore, the relation between aPVAT density and SEVR remained after adjusting for aortic stiffness (r = -0.66, P = 0.01) but not age (r = -0.24, P > 0.05). These data provide initial evidence for aPVAT as a novel yet understudied local fat depot contributing to lower myocardial perfusion in apparently healthy adults with aging.NEW & NOTEWORTHY Aortic perivascular adipose tissue (aPVAT) density is associated with aging and aortic stiffness in humans and, therefore, may contribute to lower myocardial perfusion. We demonstrate that greater aPVAT, but not visceral adipose tissue density is associated with lower myocardial perfusion and augmentation pressure independent of aortic stiffness, but not independent of age. These data provide novel evidence for aPVAT as a potential therapeutic target to improve myocardial perfusion and cardiovascular function in humans with aging.

Using a Mock Circulatory Loop as a Regulatory Science Tool to Simulate Different Heart Failure Conditions.

Mechanical circulatory support (MCS) device therapy is one of the primary treatment options for end-stage heart failure (HF), whereby a mechanical pump is integrated with the failing heart to maintain adequate tissue perfusion. The ISO 14708-5:2020 standard prescribes generic guidelines for nonclinical device evaluation and system performance testing of MCS devices using a mock circulatory loop (MCL). However, the utility of MCLs in premarket regulatory submissions of MCS devices is ambiguous, and the specific disease states that the device is intended to treat are not usually simulated. Hence, we aim to outline the potential of MCLs as a valuable regulatory science tool for characterizing MCS device systems by adequately representing target clinical-use HF conditions on the bench. Target pathophysiologic hemodynamics of HF conditions (i.e., cardiogenic shock (CS), left ventricular (LV) hypertrophy secondary to hypertension, and coronary artery disease), along with a healthy adult at rest and a healthy adult during exercise are provided as recommended test conditions. The conditions are characterized based on LV, aorta, and left atrium pressures using recommended cardiac hemodynamic indices such as systolic, diastolic, and mean arterial pressure, mean cardiac output (CO), cardiac cycle time, and systemic vascular resistance. This study is a first step toward standardizing MCLs to generate well-defined target HF conditions used to evaluate MCS devices.

Acute cardiovascular responses to unilateral bicep curls with blood flow restriction.

A consensus on the acute cardiovascular responses to low intensity (LI) resistance exercise (RE) combined with blood flow restriction (BFR) has not yet been reached. This study was designed to compare acute cardiovascular responses to a single bout of LIRE, high intensity (HI) RE, and LIRE with BFR in physically active young males. Participants completed 3 RE sessions in random order, where each session consists of 4 sets of unilateral dumbbell bicep curls. Cardiovascular hemodynamics were measured at baseline and right after each set of RE. Aortic augmentation index (AIx) was significantly higher after set 2,3,4 of RE in LI + BFR session compared to LI session (P < 0.05). Brachial systolic blood pressure (SBP), heart rate (HR), brachial rate pressure product (RPP), and central RPP responses did not differ between LI and LI + BFR sessions (P > 0.05). HI session had a higher central SBP, brachial RPP, central RPP, and aortic AIx compared to LI session after each set of RE (P < 0.05), but not brachial SBP (P > 0.05). Taken together, this study showed that LIRE combined with BFR acutely augmented aortic stiffness, as also observed in HI session, but myocardial oxygen consumption was only higher in HI session when compared to LI session. Thus, although BFR did not exaggerate cardiovascular responses nor cause extra myocardial oxygen consumption, it should be prescribed with caution when control of acute aortic stiffening is necessary during RE.

Finite state machine implementation for left ventricle modeling and control.

BACKGROUND: Simulation of a left ventricle has become a critical facet of evaluating therapies and operations that interact with cardiac performance. The ability to simulate a wide range of possible conditions, changes in cardiac performance, and production of nuisances at transition points enables evaluation of precision medicine concepts that are designed to function through this spectrum. Ventricle models have historically been based on biomechanical analysis, with model architectures constituted of continuous states and not conducive to deterministic processing. Producing a finite-state machine governance of a left ventricle model would enable a broad range of applications: physiological controller development, experimental left ventricle control, and high throughput simulations of left ventricle function. METHODS: A method for simulating left ventricular pressure-volume control utilizing a preload, afterload, and contractility sensitive computational model is shown. This approach uses a logic-based conditional finite state machine based on the four pressure-volume phases that describe left ventricular function. This was executed with a physical system hydraulic model using MathWorks' Simulink® and Stateflow tools. RESULTS: The approach developed is capable of simulating changes in preload, afterload, and contractility in time based on a patient's preload analysis. Six pressure-volume loop simulations are presented to include a base-line, preload change only, afterload change only, contractility change only, a clinical control, and heart failure with normal ejection fraction. All simulations produced an error of less than 1 mmHg and 1 mL of the absolute difference between the desired and simulated pressure and volume set points. The acceptable performance of the fixed-timestep architecture in the finite state machine allows for deployment to deterministic systems, such as experimental systems for validation. CONCLUSIONS: The proposed approach allows for personalized data, revealed through an individualized clinical pressure-volume analysis, to be simulated in silico. The computational model architecture enables this control structure to be executed on deterministic systems that govern experimental left ventricles. This provides a mock circulatory system with the ability to investigate the pathophysiology for a specific individual by replicating the exact pressure-volume relationship defined by their left ventricular functionality; as well as perform predictive analysis regarding changes in preload, afterload, and contractility in time.

Maternal hemodynamics: a method to classify hypertensive disorders of pregnancy.

BACKGROUND: The classification of hypertensive disorders of pregnancy is based on the time at the onset of hypertension, proteinuria, and other associated complications. Maternal hemodynamic interrogation in hypertensive disorders of pregnancy considers not only the peripheral blood pressure but also the entire cardiovascular system, and it might help to classify the different clinical phenotypes of this syndrome. OBJECTIVE: This study aimed to examine cardiovascular parameters in a cohort of patients affected by hypertensive disorders of pregnancy according to the clinical phenotypes that prioritize fetoplacental characteristics and not the time at onset of hypertensive disorders of pregnancy. STUDY DESIGN: At the fetal-maternal medicine unit of Ziekenhuis Oost-Limburg (Genk, Belgium), maternal cardiovascular parameters were obtained through impedance cardiography using a noninvasive continuous cardiac output monitor with the patients placed in a standing position. The patients were classified as pregnant women with hypertensive disorders of pregnancy who delivered appropriate- and small-for-gestational-age fetuses. Normotensive pregnant women with an appropriate-for-gestational-age fetus at delivery were enrolled as the control group. The possible impact of obesity (body mass index ≥30 kg/m2) on maternal hemodynamics was reassessed in the same groups. RESULTS: Maternal age, parity, body mass index, and blood pressure were not significantly different between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and hypertensive disorders of pregnancy/small-for-gestational-age groups. The mean uterine artery pulsatility index was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group. The cardiac output and cardiac index were significantly lower in the hypertensive disorders of pregnancy/small-for-gestational-age group (cardiac output 6.5 L/min, cardiac index 3.6) than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group (cardiac output 7.6 L/min, cardiac index 3.9) but not between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and control groups (cardiac output 7.6 L/min, cardiac index 4.0). Total vascular resistance was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group and the control group. All women with hypertensive disorders of pregnancy showed signs of central arterial dysfunction. The cardiovascular parameters were not influenced by gestational age at the onset of hypertensive disorders of pregnancy, and no difference was observed between the women with appropriate-for-gestational-age fetuses affected by preeclampsia or by gestational hypertension with appropriate-for-gestational-age fetuses. Women in the obese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and obese/hypertensive disorders of pregnancy/small-for-gestational-age groups showed a significant increase in cardiac output, as well as significant changes in other parameters, compared with the nonobese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and nonobese/hypertensive disorders of pregnancy/small-for-gestational-age groups. CONCLUSION: Significantly low cardiac output and high total vascular resistance characterized the women with hypertensive disorders of pregnancy associated with small for gestational age due to placental insufficiency, independent of the gestational age at the onset of hypertension. The cardiovascular parameters were not significantly different in the women with appropriate-for-gestational-age or small-for-gestational-age fetuses affected by preeclampsia or gestational hypertension. These findings support the view that maternal hemodynamics may be a candidate diagnostic tool to identify hypertensive disorders in pregnancies associated with small-for-gestational-age fetuses. This additional tool matches other reported evidence provided by uterine Doppler velocimetry, low vascular growth factors in the first trimester, and placental pathology. Obesity is associated with a significantly higher cardiac output and outweighs other determinants of hemodynamics in pregnancy; therefore, in future studies on hypertensive disorders, obesity should be studied as an additional disease and not simply as a demographic characteristic.

Prony Analysis of Left Ventricle Pressure and Volume.

Direct measurement of cardiac pressure-volume (PV) relationships is the gold standard for assessment of ventricular hemodynamics, but few innovations have been made to "multi-beat" PV analysis beyond traditional signal processing. The Prony method solves the signal recovery problem with a series of dampened exponentials or sinusoids. It achieves this by extracting the amplitude, frequency, dampening, and phase of each component. Since its inception, application of the Prony method to biologic and medical signal has demonstrated a relative degree of success, as a series of dampened complex sinusoids easily generalizes to multifaceted physiological processes. In cardiovascular physiology, the Prony analysis has been used to determine fatal arrythmia from electrocardiogram signals. However, application of the Prony method to simple left ventricular function based on pressure and volume analysis is absent. We have developed a new pipeline for analysis of pressure volume signals recorded from the left ventricle. We propose fitting pressure-volume data from cardiac catheterization to the Prony method for pole extraction and quantification of the transfer function. We implemented the Prony algorithm using open-source Python packages and analyzed the pressure and volume signals before and after severe hemorrhagic shock, and after resuscitation with stored blood. Each animal (n = 6 per group) underwent a 50% hemorrhage to induce hypovolemic shock, which was maintained for 30 min, and resuscitated with 3-week-old stored RBCs until 90% baseline blood pressure was achieved. Pressure-volume catheterization data used for Prony analysis were 1 s in length, sampled at 1000 Hz, and acquired at the time of hypovolemic shock, 15 and 30 min after induction of hypovolemic shock, and 10, 30, and 60 min after volume resuscitation. We next assessed the complex poles from both pressure and volume waveforms. To quantify deviation from the unit circle, which represents deviation from a Fourier series, we counted the number of poles at least 0.2 radial units away from it. We found a significant decrease in the number of poles after shock (p = 0.0072 vs. baseline) and after resuscitation (p = 0.0091 vs. baseline). No differences were observed in this metric pre and post volume resuscitation (p = 0.2956). We next found a composite transfer function using the Prony fits between the pressure and volume waveforms and found differences in both the magnitude and phase Bode plots at baseline, during shock, and after resuscitation. In summary, our implementation of the Prony analysis shows meaningful physiologic differences after shock and resuscitation and allows for future applications to broader physiological and pathophysiological conditions.

Latest Developments in Adapting Deep Learning for Assessing TAVR Procedures and Outcomes.

Aortic valve defects are among the most prevalent clinical conditions. A severely damaged or non-functioning aortic valve is commonly replaced with a bioprosthetic heart valve (BHV) via the transcatheter aortic valve replacement (TAVR) procedure. Accurate pre-operative planning is crucial for a successful TAVR outcome. Assessment of computational fluid dynamics (CFD), finite element analysis (FEA), and fluid-solid interaction (FSI) analysis offer a solution that has been increasingly utilized to evaluate BHV mechanics and dynamics. However, the high computational costs and the complex operation of computational modeling hinder its application. Recent advancements in the deep learning (DL) domain can offer a real-time surrogate that can render hemodynamic parameters in a few seconds, thus guiding clinicians to select the optimal treatment option. Herein, we provide a comprehensive review of classical computational modeling approaches, medical imaging, and DL approaches for planning and outcome assessment of TAVR. Particularly, we focus on DL approaches in previous studies, highlighting the utilized datasets, deployed DL models, and achieved results. We emphasize the critical challenges and recommend several future directions for innovative researchers to tackle. Finally, an end-to-end smart DL framework is outlined for real-time assessment and recommendation of the best BHV design for TAVR. Ultimately, deploying such a framework in future studies will support clinicians in minimizing risks during TAVR therapy planning and will help in improving patient care.

Lifetime prevalence and correlates of syncope in five ancestry groups. The HELIUS study.

Aim: To explore the lifetime prevalence and correlates of syncope in the general population. Methods: Through stratified random sampling, we included 14,937 White-European, Asian, Turkish, Moroccan, and West-African ancestry adults (18-70 y) in the cross-sectional Healthy Life in an Urban Setting (HELIUS) population study. We assessed syncope history by ancestry, and the potential correlates body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP), resting plasma activity of creatine kinase (CK), the ATP-generating enzyme that facilitates cardiovascular contractility and sodium retention, and in a subgroup, supine cardiac contractility (dP/dt), cardiac output (CO) and systemic vascular resistance (SVR). Results: Mean age of the participants (39% men) was 43.3 y (SD12.9). Lifetime prevalence of syncope in women/men was respectively (%), White-European 42/24; Asian 34/19; Moroccan 32/16; Turkish 30/17; and West-African 20/14. Mean age at first syncope was 24 y (SD13). Participants with syncope history had lower SBP, DBP, BMI, CK, and modestly lower dP/dt and CO, but not SVR. In multivariable regression analysis, male sex (OR 0.52 [0.48 to 0.57]), West-African ancestry (0.59 [0.54 to 0.65]), and CK (0.56 [0.46 to 0.69]/log CK increase) were negatively associated with syncope. Conclusion: This study indicates that West-African ancestry, male sex, and high activity of the pressor enzyme CK are associated with lower syncope prevalence. These findings may inform further studies on the hemodynamics of syncope.

Cardiovascular Diseases in Pregnancy - A Brief Overview.

Even though, there have been many advances in maternal medical care and fertility treatments, the presence of cardiovascular disease has a significant impact on pregnancy. In pregnant women, several heart conditions, such as valvular heart disease, chronic hypertension, congenital heart defects and non-ischemic cardiomyopathies are linked to increased risk of fetal as well as maternal morbidity and mortality. To date, the management of the co-existing conditions of pregnancy and heart disease has been challenging. Therefore, in-depth information may be beneficial to tackle a difficult case scenario. Towards this end, this paper provides an overview of the recent updated knowledge of pregnancy-related cardiovascular diseases in women.

Evaluation of the effects of gabapentin on the physiologic and echocardiographic variables of healthy cats: a prospective, randomized and blinded study.

OBJECTIVES: The aim of this study was to evaluate, using echocardiography, the effects of oral administration of a single dose of gabapentin on the physiologic variables (heart rate [HR], respiratory rate [RR] and systolic blood pressure [SBP]) and systolic and diastolic cardiac function of healthy cats. METHODS: This was a prospective, randomized and blinded study with 40 healthy cats aged between 6 months and 2 years. The cats' health status was assessed on the first appointment (T1) when they underwent a physical examination, complete blood count, biochemical profile, assessment of physiologic variables and echocardiogram. The echocardiogram was used to measure the left ventricle's (LV) internal diameter during systole and diastole, isovolumic relaxation time, transmitral flow, E-wave deceleration time and HR. The cats were randomly divided into two groups: (1) a treatment group with 20 cats that received a single oral dose of gabapentin (100 mg/cat); and (2) a control group with 20 cats that received a single oral dose of placebo. All variables of the physiologic and echocardiographic variables were re-evaluated 1-3 weeks after T1 (T2), 90 mins after medication or placebo administration. RESULTS: There was no difference in the physiologic variables evaluated in both groups. The proportion of cats in the treatment group that had their ventricular filling waves fused on T1 but did not have them fused on T2 was significantly higher (45%) compared with cats in the control group (15%; P = 0.0384). CONCLUSIONS AND RELEVANCE: There was no difference between the groups in regard to SBP, HR, RR and echocardiographic variables. Gabapentin improved evaluation of diastolic function on echocardiogram because it reduced the fusion of ventricular filling waves during the evaluation of the diastolic function of the LV. Gabapentin did not cause adverse effects on the cardiovascular hemodynamics of young healthy cats.

A method of parameter estimation for cardiovascular hemodynamics based on deep learning and its application to personalize a reduced-order model.

Precise model personalization is a key step towards the application of cardiovascular physical models. In this manuscript, we propose to use deep learning (DL) to solve the parameter estimation problem in cardiovascular hemodynamics. Based on the convolutional neural network (CNN) and fully connected neural network (FCNN), a multi-input deep neural network (DNN) model is developed to map the nonlinear relationship between measurements and the parameters to be estimated. In this model, two separate network structures are designed to extract the features of two types of measurement data, including pressure waveforms and a vector composed of heart rate (HR) and pulse transit time (PTT), and a shared structure is used to extract their combined dependencies on the parameters. Besides, we try to use the transfer learning (TL) technology to further strengthen the personalized characteristics of a trained-well network. For assessing the proposed method, we conducted the parameter estimation using synthetic data and in vitro data respectively, and in the test with synthetic data, we evaluated the performance of the TL algorithm through two individuals with different characteristics. A series of estimation results show that the estimated parameters are in good agreement with the true values. Furthermore, it is also found that the estimation accuracy can be significantly improved by a multicycle combination strategy. Therefore, we think that the proposed method has the potential to be used for parameter estimation in cardiovascular hemodynamics, which can provide an immediate, accurate, and sustainable personalization process, and deserves more attention in the future.

Comparison of Three-Month HIIT and CMT Effects on Left Ventricle Echocardiography Observations in Male Employees.

The present study aimed to identify changes in echocardiographic parameters before and after three-month high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) in male employees. For this purpose, using a convenience sampling method, 33 male employees of the Islamic Republic of Iran Army (office workers with a sedentary lifestyle) aged 30 through 40 were selected. Participants were divided into three groups of HIIT, CMT, and control (11 for each group) including all anthropometric data (body fat percentage, body mass index, height, weight, and VO2 max) with no history of chronic diseases, metabolic syndrome, confirmed heart disease or congenital heart defect, and hospitalization due to chronic diseases or consumption of medication affecting cardiovascular indicators. A one-way ANOVA was conducted to compare the groups. The results demonstrated that the end-systolic volumes (ESVs) (p < 0.01) and relative wall thickness (RWT) in the CMT group (p < 0.01) and the end-diastolic volumes (EDVs) (p < 0.01), stroke volumes (SVs) (p < 0.01), end-systolic and diastolic diameters (ESD, EDD) (p < 0.01), as well as the RWT and left ventricle diastolic function (E/A ratio) in the HIIT group (p < 0.05) were significantly different before and after the 12-week training (Bonferroni correction was used for pairwise comparisons). The results revealed a significant increase in the end-systolic diameters (ESDs) of the HIIT group, whereas no such increase was observed in the ESDs of the CMT group (p < 0.51). Moreover, a significant increase was observed in left ventricular (LV) RWT and aerobic power of both training groups. The significant decrease of ESVs and the significant increase in E/A ratio, ESDs, EDDs following HIIT (two to three sessions per week) may indicate beneficial and optimal LV structural adaptations and improved LV function in nonathletes (even with a sedentary lifestyle).

Use of Ballistocardiography to Monitor Cardiovascular Hemodynamics in Preeclampsia.

Objective: Pregnancy requires a complex physiological adaptation of the maternal cardiovascular system, which is disrupted in women with pregnancies complicated by preeclampsia, putting them at higher risk of future cardiovascular events. The measurement of body movements in response to cardiac ejection via ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. Methods: Using a previously validated, modified weighing scale for assessment of cardiovascular hemodynamics through measurement of BCG and electrocardiogram (ECG) signals, we collected serial measurements throughout pregnancy and postpartum and analyzed data in 30 women with preeclampsia and 23 normotensive controls. Using BCG and ECG signals, we extracted measures of cardiac output, J-wave amplitude × heart rate (J-amp × HR). Mixed-effect models with repeated measures were used to compare J-amp × HRs between groups at different time points in pregnancy and postpartum. Results: In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2; p = 0.016) and third trimester (T3; p = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1; p = 0.026). In the preeclampsia group, there was a trend toward an increase in J-amp × HR from T1 to T2 and then a drop in J-amp × HR at T3 and further drop at E-PP. Conclusions: We observe cardiac hemodynamic changes consistent with those reported using well-validated tools. In pregnancies complicated by preeclampsia, the maximal force of contraction is lower, suggesting lower cardiac output and a trend in hemodynamics consistent with the hyperdynamic disease model of preeclampsia.

MRI-based comprehensive analysis of vascular anatomy and hemodynamics.

BACKGROUND: Standardized methods for mapping the complex blood flow in vessels are essential for processing the large data volume acquired from 4D Flow MRI. We present a method for systematic and efficient analysis of anatomy and flow in large human blood vessels. To attain the best outcomes in cardiac surgery, vascular modifications that lead to secondary flow patterns such as vortices should be avoided. In this work, attention was paid to the undesired cancelation of vortices with opposite directions of rotation, known as Dean flow patterns, using hemodynamic parameters such as circulation and helicity density. METHODS: Our approach is based on the multiplanar reconstruction (MPR) of a multi-dimensional feature-space along the blood vessel's centerline. Hemodynamic parameters and anatomic information were determined in-plane from the reconstructed feature-space and from the blood vessel's centerline. A modified calculation of circulation and helicity density and novel parameters for quantifying Dean flow were developed. To test the model performance, we applied our methods to three test cases. RESULTS: Comprehensive information on position, magnitude and interrelation of vascular anatomy and hemodynamics were extracted from 4D Flow MRI datasets. The results show that the Dean flow patterns can be efficiently assessed using the novel parameters. CONCLUSIONS: Our approach to comprehensively and simultaneously quantify multiple parameters of vascular anatomy and hemodynamics from 4D Flow MRI provides new insights to map complex hemodynamic conditions.

Demonstration of Patient-Specific Simulations to Assess Left Atrial Appendage Thrombogenesis Risk.

Atrial fibrillation (AF) alters left atrial (LA) hemodynamics, which can lead to thrombosis in the left atrial appendage (LAA), systemic embolism and stroke. A personalized risk-stratification of AF patients for stroke would permit improved balancing of preventive anticoagulation therapies against bleeding risk. We investigated how LA anatomy and function impact LA and LAA hemodynamics, and explored whether patient-specific analysis by computational fluid dynamics (CFD) can predict the risk of LAA thrombosis. We analyzed 4D-CT acquisitions of LA wall motion with an in-house immersed-boundary CFD solver. We considered six patients with diverse atrial function, three with either a LAA thrombus (removed digitally before running the simulations) or a history of transient ischemic attacks (LAAT/TIA-pos), and three without a LAA thrombus or TIA (LAAT/TIA-neg). We found that blood inside the left atrial appendage of LAAT/TIA-pos patients had marked alterations in residence time and kinetic energy when compared with LAAT/TIA-neg patients. In addition, we showed how the LA conduit, reservoir and booster functions distinctly affect LA and LAA hemodynamics. Finally, fixed-wall and moving-wall simulations produced different LA hemodynamics and residence time predictions for each patient. Consequently, fixed-wall simulations risk-stratified our small cohort for LAA thrombosis worse than moving-wall simulations, particularly patients with intermediate LAA residence time. Overall, these results suggest that both wall kinetics and LAA morphology contribute to LAA blood stasis and thrombosis.

Optimization of combined measures of airway physiology and cardiovascular hemodynamics in mice.

Pulmonary hypertension may arise as a complication of chronic lung disease typically associated with tissue hypoxia, as well as infectious agents or injury eliciting a type 2 immune response. The onset of pulmonary hypertension in this setting (classified as Group 3) often complicates treatment and worsens prognosis of chronic lung disease. Chronic lung diseases such as chronic obstructive lung disease (COPD), emphysema, and interstitial lung fibrosis impair airflow and alter lung elastance in addition to affecting pulmonary vascular hemodynamics that may culminate in right ventricle dysfunction. To date, functional endpoints in murine models of chronic lung disease have typically been limited to separately measuring airway and lung parenchyma physiology. These approaches may be lengthy and require a large number of animals per experiment. Here, we provide a detailed protocol for combined assessment of airway physiology with cardiovascular hemodynamics in mice. Ultimately, a comprehensive overview of pulmonary function in murine models of injury and disease will facilitate the integration of studies of the airway and vascular biology necessary to understand underlying pathophysiology of Group 3 pulmonary hypertension.

Healthy Aging and Cardiovascular Function: Invasive Hemodynamics During Rest and Exercise in 104 Healthy Volunteers.

OBJECTIVES: The aim of this study was to evaluate the association between age and invasive cardiovascular hemodynamics during upright exercise among healthy adults. BACKGROUND: The marked age-related decline in maximal exercise oxygen uptake (peak VO2) may contribute to the high burden of heart failure among older individuals and their greater severity of exertional symptoms. However, the mechanisms underlying this decline are not well understood. METHODS: A total of 104 healthy community-dwelling volunteers age 20 to 76 years well screened for cardiovascular disease underwent exhaustive upright exercise with brachial and pulmonary artery catheters; radionuclide ventriculography; and expired gas analysis for the measurement of peak VO2, cardiac output, left ventricular stroke volume, end-diastolic volume, end-systolic volume, ejection fraction, pulmonary capillary wedge pressure, and arteriovenous oxygen difference. RESULTS: Over a 5.5-decade age range, there was a 40% decline in peak VO2 due primarily to reduced peak exercise cardiac output; peak arteriovenous oxygen difference was unaffected by age. The lower age-related exercise cardiac output was related to lower peak exercise heart rate and stroke volume. Aging was also associated with lower peak exercise ejection fraction, indicating reduced inotropic reserve. Peak exercise end-diastolic volume was lower with aging despite similar left ventricular filling pressure, suggesting age-related reduced diastolic compliance limiting the use of the Frank-Starling mechanism to compensate for reduced chronotropic and inotropic reserves. These age relationships were unaffected by sex. CONCLUSIONS: The age-related decline in exercise capacity among healthy persons is due predominantly to cardiac mechanisms, including reduced chronotropic and inotropic reserve and possibly reduced Frank-Starling reserve. Peak exercise left ventricular filling pressure and arteriovenous oxygen difference are unchanged with healthy aging.

Practical Use of Regularization in Individualizing a Mathematical Model of Cardiovascular Hemodynamics Using Scarce Data.

Individualizing physiological models to a patient can enable patient-specific monitoring and treatment in critical care environments. However, this task often presents a unique "practical identifiability" challenge due to the conflict between model complexity and data scarcity. Regularization provides an established framework to cope with this conflict by compensating for data scarcity with prior knowledge. However, regularization has not been widely pursued in individualizing physiological models to facilitate patient-specific critical care. Thus, the goal of this work is to garner potentially generalizable insight into the practical use of regularization in individualizing a complex physiological model using scarce data by investigating its effect in a clinically significant critical care case study of blood volume kinetics and cardiovascular hemodynamics in hemorrhage and circulatory resuscitation. We construct a population-average model as prior knowledge and individualize the physiological model via regularization to illustrate that regularization can be effective in individualizing a physiological model to learn salient individual-specific characteristics (resulting in the goodness of fit to individual-specific data) while restricting unnecessary deviations from the population-average model (achieving practical identifiability). We also illustrate that regularization yields parsimonious individualization of only sensitive parameters as well as adequate physiological plausibility and relevance in predicting internal physiological states.

Development of an adaptive pulmonary simulator for in vitro analysis of patient populations and patient-specific data.

BACKGROUND AND OBJECTIVE: Patient-specific modeling (PSM) is gaining more attention from researchers due to its ability to potentially improve diagnostic capabilities, guide the design of intervention procedures, and optimize clinical management by predicting the outcome of a particular treatment and/or surgical intervention. Due to the hemodynamic diversity of specific patients, an adaptive pulmonary simulator (PS) would be essential for analyzing the possible impact of external factors on the safety, performance, and reliability of a cardiac assist device within a mock circulatory system (MCS). In order to accurately and precisely replicate the conditions within the pulmonary system, a PS should not only account for the ability of the pulmonary system to supply blood flow at specific pressures, but similarly consider systemic outflow dynamics. This would provide an accurate pressure and flow rate return supply back into the left ventricular section of the MCS (i.e. the initial conditions of the left heart). METHODS: Employing an embedded Windkessel model, a control system model was developed utilizing MathWorks' Simulink® Simscape™. Following a verification and validation (V&V) analysis approach, a PI-controlled closed-loop hydraulic system was developed using Simscape™. This physical system modeling tool was used to (1) develop and control the in silico system during verification studies and (2) simulate pulmonary performance for validation of this control architecture. RESULTS: The pulmonary Windkessel model developed is capable of generating the left atrial pressure (LAP) waveform from given pulmonary factors, aortic conditions, and systemic variables. Verification of the adaptive PS's performance and validation of this control architecture support this modeling methodology as an effective means of reproducing pulmonary pressure waveforms and systemic outflow conditions, unique to a particular patient. Adult and geriatric with and without Heart Failure and a Normal Ejection Fraction (HFNEF) are presented. CONCLUSIONS: The adaptability of this modelling approach allows for the simulation of pulmonary conditions without the limitations of a dedicated hardware platform for use in in vitro investigations.

A computer simulation of short-term adaptations of cardiovascular hemodynamics in microgravity.

Astronauts in the microgravity environment experience significant changes in their cardiovascular hemodynamics. In this study, a system-level numerical model has been utilized to simulate the short-term adaptations of hemodynamic parameters due to the gravitational removal in space. The effect of lower body negative pressure (LBNP) as a countermeasure has also been simulated. The numerical model was built upon a lumped-parameter Windkessel model by incorporating gravity-induced hydrostatic pressure and transcapillary fluid exchange modules. The short-term (in the time scale of seconds and minutes) adaptations of the cardiac functions, blood pressure, and fluid volumes have been analyzed and compared with physiological data. The simulation results suggest microgravity induces a decrease in aortic pressure, heart rate, lower body capillary pressure and volume, and an increase in stroke volume, upper body capillary pressure and volume. The activation of LBNP causes an immediate increase in lower body blood volume and a gradual decrease in upper body blood volume. As a result, the fluid shift due to microgravity could be reversed by the LBNP application. LBNP also counters the impacts of microgravity on the cardiac functions, including heart rate and stroke volume. The simulation results have been validated using available physiological data obtained from spaceflight and parabolic flight experiments.