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Aortic stenosis (AS) is an acute and chronic cardiovascular disease and If left untreated, 50% of these patients will die within two years of developing symptoms. AS is characterized as the stiffening of the aortic valve leaflets which restricts their motion and prevents the proper opening under transvalvular pressure. Assessments of the valve dynamics, if available, would provide valuable information about the patient's state of cardiac deterioration as well as heart recovery and can have incredible impacts on patient care, planning interventions and making critical clinical decisions with life-threatening risks. Despite remarkable advancements in medical imaging, there are no clinical tools available to quantify valve dynamics invasively or noninvasively. In this study, we developed a highly innovative ultrasound-based non-invasive computational framework that can function as a diagnostic tool to assess valve dynamics (e.g. transient 3-D distribution of stress and displacement, 3-D deformed shape of leaflets, geometric orifice area and angular positions of leaflets) for patients with AS at no risk to the patients. Such a diagnostic tool considers the local valve dynamics and the global circulatory system to provide a platform for testing the intervention scenarios and evaluating their effects. We used clinical data of 12 patients with AS not only to validate the proposed framework but also to demonstrate its diagnostic abilities by providing novel analyses and interpretations of clinical data in both pre and post intervention states. We used transthoracic echocardiogram (TTE) data for the developments and transesophageal echocardiography (TEE) data for validation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background Despite the proven benefits of transcatheter aortic valve replacement (TAVR) and its recent expansion toward the whole risk spectrum, coronary artery disease is present in more than half of the candidates for TAVR. Many previous studies do not focus on the longer-term impact of TAVR on coronary arteries, and hemodynamic changes to the circulatory system in response to the anatomical changes caused by TAVR are not fully understood. Methods and Results We developed a multiscale patient-specific computational framework to examine the effect of TAVR on coronary and cardiac hemodynamics noninvasively. Based on our findings, TAVR might have an adverse impact on coronary hemodynamics due to the lack of sufficient coronary blood flow during diastole phase (eg, maximum coronary flow rate reduced by 8.98%, 16.83%, and 22.73% in the left anterior descending, left circumflex coronary artery, and right coronary artery, respectively [N=31]). Moreover, TAVR may increase the left ventricle workload (eg, left ventricle workload increased by 2.52% [N=31]) and decrease the coronary wall shear stress (eg, maximum time averaged wall shear stress reduced by 9.47%, 7.75%, 6.94%, 8.07%, and 6.28% for bifurcation, left main coronary artery, left anterior descending, left circumflex coronary artery, and right coronary artery branches, respectively). Conclusions The transvalvular pressure gradient relief after TAVR might not result in coronary flow improvement and reduced cardiac load. Optimal revascularization strategy pre-TAVR and progression of coronary artery disease after TAVR could be determined by noninvasive personalized computational modeling.

In recent years, transcatheter aortic valve replacement (TAVR) has become the leading method for treating aortic stenosis. While the procedure has improved dramatically in the past decade, there are still uncertainties about the impact of TAVR on coronary blood flow. Recent research has indicated that negative coronary events after TAVR may be partially driven by impaired coronary blood flow dynamics. Furthermore, the current technologies to rapidly obtain non-invasive coronary blood flow data are relatively limited. Herein, we present a lumped parameter computational model to simulate coronary blood flow in the main arteries as well as a series of cardiovascular hemodynamic metrics. The model was designed to only use a few inputs parameters from echocardiography, computed tomography and a sphygmomanometer. The novel computational model was then validated and applied to 19 patients undergoing TAVR to examine the impact of the procedure on coronary blood flow in the left anterior descending (LAD) artery, left circumflex (LCX) artery and right coronary artery (RCA) and various global hemodynamics metrics. Based on our findings, the changes in coronary blood flow after TAVR varied and were subject specific (37% had increased flow in all three coronary arteries, 32% had decreased flow in all coronary arteries, and 31% had both increased and decreased flow in different coronary arteries). Additionally, valvular pressure gradient, left ventricle (LV) workload and maximum LV pressure decreased by 61.5%, 4.5% and 13.0% respectively, while mean arterial pressure and cardiac output increased by 6.9% and 9.9% after TAVR. By applying this proof-of-concept computational model, a series of hemodynamic metrics were generated non-invasively which can help to better understand the individual relationships between TAVR and mean and peak coronary flow rates. In the future, tools such as these may play a vital role by providing clinicians with rapid insight into various cardiac and coronary metrics, rendering the planning for TAVR and other cardiovascular procedures more personalized., (© 2023. The Author(s).)

Given the associated risks with transcatheter aortic valve replacement (TAVR), it is crucial to determine how the implant will affect the valve dynamics and cardiac function, and if TAVR will improve or worsen the outcome of the patient. Effective treatment strategies, indeed, rely heavily on the complete understanding of the valve dynamics. We developed an innovative Doppler-exclusive non-invasive computational framework that can function as a diagnostic tool to assess valve dynamics in patients with aortic stenosis in both pre- and post-TAVR status. Clinical Doppler pressure was reduced by TAVR (52.2 ± 20.4 vs. 17.3 ± 13.8 [mmHg], p < 0.001), but it was not always accompanied by improvements in valve dynamics and left ventricle (LV) hemodynamics metrics. TAVR had no effect on LV workload in 4 patients, and LV workload post-TAVR significantly rose in 4 other patients. Despite the group level improvements in maximum LV pressure (166.4 ± 32.2 vs 131.4 ± 16.9 [mmHg], p < 0.05), only 5 of the 12 patients (41%) had a decrease in LV pressure. Moreover, TAVR did not always improve valve dynamics. TAVR did not necessarily result in a decrease (in 9 out of 12 patients investigated in this study) in major principal stress on the aortic valve leaflets which is one of the main contributors in valve degeneration and, consequently, failure of heart valves. Diastolic stresses increased significantly post-TAVR (34%, 109% and 81%, p < 0.001) for each left, right and non-coronary leaflets respectively. Moreover, we quantified the stiffness and material properties of aortic valve leaflets which correspond with the reduced calcified region average stiffness among leaflets (66%, 74% and 62%; p < 0.001; N = 12). Valve dynamics post-intervention should be quantified and monitored to ensure the improvement of patient conditions and prevent any further complications. Improper evaluation of biomechanical valve features pre-intervention as well as post-intervention may result in harmful effects post-TAVR in patients including paravalvular leaks, valve degeneration, failure of TAVR and heart failure., (© 2023. The Author(s).)

Transcatheter aortic valve replacement (TAVR) is a frequently used minimally invasive intervention for patient with aortic stenosis across a broad risk spectrum. While coronary artery disease (CAD) is present in approximately half of TAVR candidates, correlation of post-TAVR complications such as paravalvular leakage (PVL) or misalignment with CAD are not fully understood. For this purpose, we developed a multiscale computational framework based on a patient-specific lumped-parameter algorithm and a 3-D strongly-coupled fluid-structure interaction model to quantify metrics of global circulatory function, metrics of global cardiac function and local cardiac fluid dynamics in 6 patients. Based on our findings, PVL limits the benefits of TAVR and restricts coronary perfusion due to the lack of sufficient coronary blood flow during diastole phase (e.g., maximum coronary flow rate reduced by 21.73%, 21.43% and 21.43% in the left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) respectively (N = 6)). Moreover, PVL may increase the LV load (e.g., LV load increased by 17.57% (N = 6)) and decrease the coronary wall shear stress (e.g., maximum wall shear stress reduced by 20.62%, 21.92%, 22.28% and 25.66% in the left main coronary artery (LMCA), left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) respectively (N = 6)), which could promote atherosclerosis development through loss of the physiological flow-oriented alignment of endothelial cells. This study demonstrated that a rigorously developed personalized image-based computational framework can provide vital insights into underlying mechanics of TAVR and CAD interactions and assist in treatment planning and patient risk stratification in patients., (© 2022. The Author(s).)

Background Despite ongoing advances in surgical techniques for coarctation of the aorta (COA) repair, the long-term results are not always benign. Associated mixed valvular diseases (various combinations of aortic and mitral valvular pathologies) are responsible for considerable postoperative morbidity and mortality. We investigated the impact of COA and mixed valvular diseases on hemodynamics. Methods and Results We developed a patient-specific computational framework. Our results demonstrate that mixed valvular diseases interact with COA fluid dynamics and contribute to speed up the progression of the disease by amplifying the irregular flow patterns downstream of COA (local) and exacerbating the left ventricular function (global) (N=26). Velocity downstream of COA with aortic regurgitation alone was increased, and the situation got worse when COA and aortic regurgitation coexisted with mitral regurgitation (COA with normal valves: 5.27 m/s, COA with only aortic regurgitation: 8.8 m/s, COA with aortic and mitral regurgitation: 9.36 m/s; patient 2). Workload in these patients was increased because of the presence of aortic stenosis alone, aortic regurgitation alone, mitral regurgitation alone, and when they coexisted (COA with normal valves: 1.0617 J; COA with only aortic stenosis: 1.225 J; COA with only aortic regurgitation: 1.6512 J; COA with only mitral regurgitation: 1.3599 J; patient 1). Conclusions Not only the severity of COA, but also the presence and the severity of mixed valvular disease should be considered in the evaluation of risks in patients. The results suggest that more aggressive surgical approaches may be required, because regularly chosen current surgical techniques may not be optimal for such patients.

One of the most common acute and chronic cardiovascular disease conditions is aortic stenosis, a disease in which the aortic valve is damaged and can no longer function properly. Moreover, aortic stenosis commonly exists in combination with other conditions causing so many patients suffer from the most general and fundamentally challenging condition: complex valvular, ventricular and vascular disease (C3VD). Transcatheter aortic valve replacement (TAVR) is a new less invasive intervention and is a growing alternative for patients with aortic stenosis. Although blood flow quantification is critical for accurate and early diagnosis of C3VD in both pre and post-TAVR, proper diagnostic methods are still lacking because the fluid-dynamics methods that can be used as engines of new diagnostic tools are not well developed yet. Despite remarkable advances in medical imaging, imaging on its own is not enough to quantify the blood flow effectively. Moreover, understanding of C3VD in both pre and post-TAVR and its progression has been hindered by the absence of a proper non-invasive tool for the assessment of the cardiovascular function. To enable the development of new non-invasive diagnostic methods, we developed an innovative image-based patient-specific computational fluid dynamics framework for patients with C3VD who undergo TAVR to quantify metrics of: (1) global circulatory function; (2) global cardiac function as well as (3) local cardiac fluid dynamics. This framework is based on an innovative non-invasive Doppler-based patient-specific lumped-parameter algorithm and a 3-D strongly-coupled fluid-solid interaction. We validated the framework against clinical cardiac catheterization and Doppler echocardiographic measurements and demonstrated its diagnostic utility by providing novel analyses and interpretations of clinical data in eleven C3VD patients in pre and post-TAVR status. Our findings position this framework as a promising new non-invasive diagnostic tool that can provide blood flow metrics while posing no risk to the patient. The diagnostic information, that the framework can provide, is vitally needed to improve clinical outcomes, to assess patient risk and to plan treatment.

Background Mixed valvular disease (MVD), mitral regurgitation (MR) from pre-existing disease in conjunction with paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR), is one of the most important stimuli for left ventricle (LV) dysfunction, associated with cardiac mortality. Despite the prevalence of MVD, the quantitative understanding of the interplay between pre-existing MVD, PVL, LV, and post-TAVR recovery is meager. Methods and Results We quantified the effects of MVD on valvular-ventricular hemodynamics using an image-based patient-specific computational framework in 72 MVD patients. Doppler pressure was reduced by TAVR (mean, 77%; N=72; P <0.05), but it was not always accompanied by improvements in LV workload. TAVR had no effect on LV workload in 22 patients, and LV workload post-TAVR significantly rose in 32 other patients. TAVR reduced LV workload in only 18 patients (25%). PVL significantly alters LV flow and increases shear stress on transcatheter aortic valve leaflets. It interacts with mitral inflow and elevates shear stresses on mitral valve and is one of the main contributors in worsening of MR post-TAVR. MR worsened in 32 patients post-TAVR and did not improve in 18 other patients. Conclusions PVL limits the benefit of TAVR by increasing LV load and worsening of MR and heart failure. Post-TAVR, most MVD patients (75% of N=72; P <0.05) showed no improvements or even worsening of LV workload, whereas the majority of patients with PVL, but without that pre-existing MR condition (60% of N=48; P <0.05), showed improvements in LV workload. MR and its exacerbation by PVL may hinder the success of TAVR.

Aortic stenosis (AS) management is classically guided by symptoms and valvular metrics. However, the natural history of AS is dictated by coupling of the left ventricle, aortic valve, and vascular system. We investigated whether metrics of ventricular and vascular state add to the appreciation of AS state above valve gradient alone. Seventy patients with severe symptomatic AS were prospectively followed from baseline to 30 days after transcatheter aortic valve replacement (TAVR). Quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire. Left ventricular stroke work (SW LV ) and vascular impedance spectrums were calculated noninvasively using in-house models based on central blood pressure waveforms, along with hemodynamic parameters from echocardiograms. Patients with higher preprocedural SW LV and lower vascular impedance were more likely to experience improved QOL after TAVR. Patients fell into two categories: those who did and those who did not exhibit increase in blood pressure after TAVR. In patients who developed hypertension (19%), vascular impedance increased and SW LV remained unchanged (impedance at zeroth harmonic: Z 0 , from 3964.4 to 4851.8 dyne·s/cm 3 , P = 0.039; characteristic impedance: Z c , from 376.2 to 603.2 dyne·s/cm 3 , P = 0.033). SW LV dropped only in patients who did not develop new hypertension after TAVR (from 1.58 to 1.26 J; P < 0.001). Reduction in valvular pressure gradient after TAVR did not predict change in SW LV ( r = 0.213; P = 0.129). Reduction of SW LV after TAVR may be an important metric in management of AS, rather than relying solely on the elimination of transvalvular pressure gradients., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Aortic valve bypass (AVB) has been shown to be a viable solution for patients with severe aortic stenosis (AS). Under this circumstance, the left ventricle (LV) has a double outlet. The objective was to develop a mathematical model capable of evaluating the hemodynamic performance following the AVB surgery. A mathematical model that captures the interaction between LV, AS, arterial system, and AVB was developed. This model uses a limited number of parameters that all can be non-invasively measured using patient data. The model was validated using in vivo data from the literature. The model was used to determine the effect of different AVB and AS configurations on flow proportion and pressure of the aortic valve and the AVB. Results showed that the AVB leads to a significant reduction in transvalvular pressure gradient. The percentage of flow through the AVB can range from 55.47% to 69.43% following AVB with a severe AS. LV stroke work was also significantly reduced following the AVB surgery and reached a value of around 1.2 J for several AS severities. Findings of this study suggest: 1) the AVB leads to a significant reduction in transvalvular pressure gradients; 2) flow distribution between the AS and the AVB is significantly affected by the conduit valve size; 3) the AVB leads to a significant reduction in LV stroke work; and 4) hemodynamic performance variations can be estimated using the model.

Aortic stenosis (AS), in which the opening of the aortic valve is narrowed, is the most common valvular heart disease. Cardiac catheterization is considered the reference standard for definitive evaluation of AS severity, based on instantaneous systolic value of transvalvular pressure gradient (TPG). However, using invasive cardiac catheterization might carry high risks knowing that undergoing multiple cardiac catheterizations for follow-up in patients with AS is common. The objective of this study was to suggest an analytical description of the AS that estimates TPG without a need for high risk invasive data collection. For this purpose, Navier-Stokes equation coupled with the elastic-deformation equation was solved analytically. The estimated TPG resulted from the suggested analytical description was validated against published in vivo and in vitro measurement data. Very good concordances were found between TPG obtained from the analytical formulation and in vivo (maximum root mean square error: 3.8 mmHg) and in vitro (maximum root mean square error: 9.4 mmHg). The analytical description can be integrated to non-invasive imaging modalities to estimate AS severity as an alternative to cardiac catheterization to help preventing its risks in patients with AS., (Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.)

Early detection and accurate estimation of aortic stenosis (AS) severity are the most important predictors of successful long-term outcomes in patients. Current clinical parameters used for evaluation of the AS severity have several limitations including flow dependency. Estimation of AS severity is specifically challenging in patients with low-flow and low transvalvular pressure gradient conditions. A proper diagnosis in these patients needs a comprehensive evaluation of the left ventricle (LV) hemodynamic loads. This study has two objectives: (1) developing a lumped-parameter model to describe the ventricular-valvular-arterial interaction and to estimate the LV stroke work (SW); (2) introducing and validating a new index, the normalized stroke work (N-SW), to assess the global hemodynamic load imposed on the LV. N-SW represents the global hemodynamic load that the LV faces for each unit volume of blood ejected. The model uses a limited number of parameters which all can be measured non-invasively using current clinical imaging modalities. The model was first validated by comparing its calculated flow waveforms with the ones measured using Cardiovascular Magnetic Resonance (CMR) in 49 patients and 8 controls. A very good correlation and concordance were found throughout the cycle (median root mean square: 12.21 mL/s) and between the peak values (r = 0.98; SEE = 0.001, p<0.001). The model was then used to determine SW using the parameters measured with transthoracic Doppler-echocardiography (TTE) and CMR. N-SW showed very good correlations with a previously-validated index of global hemodynamic load, the valvular arterial impedance ([Formula: see text]), using data from both imaging modalities (TTE: r = 0.82, SEE = 0.01, p<0.001; CMR: r = 0.74, SEE = 0.01, p<0.001). Furthermore, unlike , N-SW was almost independent from variations in the flow rate. This study suggests that considering N-SW may provide incremental diagnostic and prognostic information, beyond what standard indices of stenosis severity and provide, particularly in patients with low LV outflow.

Aortic stenosis (AS) severity contributes to the left ventricle (LV) deterioration due to the aortic valve narrowing and the alteration of systemic hemodynamic load. This load increment may also increase the LV stroke work (SW) which represent the required energy to deliver the blood at ejection. In this study, SW was derived from in-vivo cardiovascular magnetic resonance (CMR) velocity measurements (n=57) using a lumped-parametric model. Furthermore, normalized SW (N-SW) was evaluated as AS severity parameter. SW differentiated from normal flow (>35 mL/m(2)) and low flow (<35 mL/m(2)) states (p<0.05). N-SW showed a good association with valve effective orifice area (EOA, r=-0.5, p<0.001) and valvulo-arterial impedance (ZVA, r=0.65, p<0.001). A severity threshold for N-SW (1.5 cJ/mL) was found using an EOA=1 cm(2) as AS severity marker. CMR-derived SW and N-SW may be useful to the assessment and grading of AS patients.

Coarctation of the aorta (COA) is an obstruction of the aorta and is usually associated with bicuspid and tricuspid aortic valve stenosis (AS). When COA coexists with AS, the left ventricle (LV) is facing a double hemodynamic load: a valvular load plus a vascular load. The objective of this study was to develop a lumped parameter model, solely based on non-invasive data, allowing the description of the interaction between LV, COA, AS and the arterial system. First, a formulation describing the instantaneous net pressure gradient through the COA was introduced and the predictions were compared to in vitro results. The model was then used to determine LV work induced by coexisting AS and COA with different severities. The results show that LV stroke work varies from 0.98J (no-AS; no-COA) up to 2.15J (AS: 0.61cm(2)+COA: 90%). Our results also show that the proportion of the total flow rate that will cross the COA is significantly reduced with the increasing COA severity (from 85% to 40%, for a variation of COA severity from 0% to 90%, respectively). Finally, we introduced simple formulations capable of, non-invasively, estimating both LV peak systolic pressure and workload. As a conclusion, this study allowed the development of a lumped parameter model, based on non-invasive measurements, capable of accurately investigating the impact of coexisting AS and COA on LV workload. This model can be used to optimize the management of patients with COA and AS in terms of the sequence of lesion repair., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Coarctation of the aorta is a congenital heart disease defined as an obstruction of the aorta distal to the left subclavian artery (between the aortic arch and descending aorta). It is usually associated with other diseases such as bicuspid and tricuspid aortic stenosis. If the coarctation remains uncorrected it can lead to hypertension, left ventricular failure and aortic dissection. Numerous investigations pointed out that there is a relationship between the genesis and the progression of cardiovascular disease and the locally irregular flow occurring at the diseased zone. Therefore, to examine the relationship between arterial disease and hemodynamics conditions, detailed quantitative studies on flow dynamics in arterial models are clearly inquired. In this study we numerically investigate pulsatile blood flow in a simplified model of the aorta (curved pipe) with coexisting coarctation of the aorta and aortic stenosis. Three severities of aortic stenoses (0.61 cm(2), 1.0 cm(2) and 1.5 cm(2)) coexisting with aortic coarctations (50%, 75% and 90% by area) are investigated. An experimentally validated numerical model from literature is used and baseline results are validated against it. To ensure having a physiologically relevant model using this geometry, flow properties are set so that the Dean number falls in the physiological range for the aorta. The results show that the coexistence of these pathologies significantly modifies the flow in a curved pipe. The maximal velocity is shifted towards the outer wall and can reach values as high as 5m/s just downstream of the coarctation. The wall shear stress distribution is significantly modified compared to the normal, unobstructed case. Finally, a clinically significant pressure gradient is induced by the curvature of the tube (up to 36 mmHg). This can lead to an overestimation of the severity of the coarctation using catheterization., (Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.)

Coarctation of the aorta is an obstruction of the aorta and is usually associated with other concomitant cardiovascular abnormalities especially with bicuspid aortic valve stenosis. The objectives of this study are, (1) to investigate the effects of coarctation on the hemodynamics in the aorta to gain a better understanding of the cause of certain post-surgical coarctation problems, (2) to develop and introduce a new lumped parameter model, mainly based on non-invasive data, allowing the description of the interaction between left ventricle, coarctation of the aorta, aortic valve stenosis, and the arterial system.