Quantification of functional hemodynamics in aortic valve disease using cardiac computed tomography angiography.

BACKGROUND AND OBJECTIVE: Cardiac computed tomography angiography (CTA) is the preferred modality for preoperative planning in aortic valve stenosis. However, it cannot provide essential functional hemodynamic data, specifically the mean transvalvular pressure gradient (MPG). This study aims to introduce a computational fluid dynamics (CFD) approach for MPG quantification using cardiac CTA, enhancing its diagnostic value. METHODS: Twenty patients underwent echocardiography, cardiac CTA, and invasive catheterization for pressure measurements. Cardiac CTA employed retrospective electrocardiographic gating to capture multi-phase data throughout the cardiac cycle. We segmented the region of interest based on mid-systolic phase cardiac CTA images. Then, we computed the average flow velocity into the aorta as the inlet boundary condition, using variations in end-diastolic and end-systolic left ventricular volume. Finally, we conducted CFD simulations using a steady-state model to obtain pressure distribution within the computational domain, allowing for the derivation of MPG. RESULTS: The mean value of MPG, measured via invasive catheterization (MPGInv), echocardiography (MPGEcho), and cardiac CTA (MPGCT), were 51.3 ± 28.4 mmHg, 44.8 ± 19.5 mmHg, and 55.8 ± 25.6 mmHg, respectively. In comparison to MPGInv, MPGCT exhibited a higher correlation of 0.91, surpassing that of MPGEcho, which was 0.82. Moreover, the limits of agreement for MPGCT ranged from -27.7 to 18.7, outperforming MPGEcho, which ranged from -40.1 to 18.0. CONCLUSIONS: The proposed method based on cardiac CTA enables the evaluation of MPG for aortic valve stenosis patients. In future clinical practice, a single cardiac CTA examination can comprehensively assess both the anatomical and functional hemodynamic aspects of aortic valve disease.

Dimensionless index and outcome in patients with aortic valve disease.

PURPOSE: Assessment of aortic stenosis (AS) is based on aortic valve (AV) gradients and calculation of aortic valve area (AVA). These parameters are influenced by flow and dependent on geometric assumptions. The dimensionless index (DI), the ratio of the LVOT time-velocity integral to that of the AV jet, is simple to perform, and is less susceptible to error but has only been examined in small selected groups of AS patients. The objective of this study was to assess the DI and prognosis in a large cohort. METHODS: All subjects who underwent echocardiography with an assessment of the AV that included DI were included. Association between AV parameters including mean gradient, AVA, DI and AV resistance and mortality and cardiovascular hospitalizations was examined. RESULTS: A total of 9393 patients (mean age 71 ± 16 years; 53% male) were included. 731 (7.7%) patients had DI less than .25. Increasing age and a diagnosis of heart failure were significantly associated with lower DI. Subjects with low DI had significantly lower ventricular function, a higher incidence of mitral and tricuspid regurgitation, worse diastolic function and more elevated pulmonary pressures. Decreasing DI was associated with significantly decreased survival and event-free survival which remained highly significant on multivariate analysis. CONCLUSIONS: In a large population of patients with AV disease, decreased DI, was associated with increased mortality and decreased event-free survival. The easily obtained DI identifies a broad range of AS subjects with worse prognosis and should be integrated into the assessment of these complex patients.

Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients With Transcatheter Aortic Valve Implantation.

BACKGROUND: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). METHODS: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. RESULTS: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2-1.7] versus 1.3 [1.2-1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, P<0.001) and SAVR (r=0.7, P<0.001). On multivariable analysis, 18F-NaF uptake was the only predictor of peak velocity progression (P<0.001). CONCLUSIONS: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02304276.

Diagnostic performance of quantitative and qualitative parameters for the diagnosis of aortic graft infection using [18F]-FDG PET/CT.

PURPOSE: The aim of this study was the evaluation of quantitative and qualitative parameters for the diagnosis of aortic graft infection (AGI) using [18F]-FDG PET/CT. METHODS: PET/CT was performed in 50 patients with clinically suspected AGI. 12 oncological patients with aortic repair but without suspicion of AGI were included in the analysis to serve as control cohort. The [18F]-FDG uptake pattern around the graft was assessed using (a) a five-point visual grading scale (VGS), (b) SUVmax and (c) different graft-to-background ratios (GBRs). The diagnostic performance of VGS, SUVmax and GBRs was assessed and compared by ROC analysis. RESULTS: 28 infected and 34 uninfected grafts were identified by standard of reference. SUVmax and VGS were the most powerful predictors for the diagnosis of AGI according to the area under the curve (AUC 0.988 and 0.983, respectively) without a significant difference compared to GBRs. SUVmax and VGS showed congruent and accurate findings in 54 patients (i.e. either both positive or negative), yielding sensitivity and specificity (100%) in this subgroup of patients. CONCLUSION: Quantitative analysis by SUVmax and qualitative analysis by VGS are highly effective in the diagnosis of AGI and should be tested as an outcome measure in prospective trials.

Are there any subclinical myocardial dysfunctions in subjects with aortic valve sclerosis? A 3D-speckle tracking echocardiography study.

Aortic valve sclerosis (AVS) is defined as calcified and thickened aortic leaflets without restriction of leaflet motion. We have not found any studies that previously assessed the effect of AVS on myocardial functions with three dimensional-speckle tracking echocardiography (3D-STE). Therefore, we aimed to identify any early changes in left atrial (LA) myocardial dynamics and/or left ventricular (LV) systolic functions in patients with AVS using 3D-STE. Seventy-five patients with AVS and 80 age- and gender-matched controls were enrolled into the study. The baseline clinical characteristics of the study patients were recorded. Conventional 2D echocardiographic and 3D-STE analyses were performed. The LV-global longitudinal strain (LV-GLS) and LV-global circumferential strain (LV-GCS) were significantly decreased in the AVS (+) group than in the control group (p < 0.001 and p = 0.013, respectively). In multivariate logistic regression analysis; LV-GLS (p < 0.001, odds ratio (OR) = 3.16, 95% confidence interval (CI) 1.42-5.63) and Triglyceride (TG) (p = 0.033, OR = 1.29, 95% CI 1.11-1.72) were found to be independent predictors of AVS. ROC analysis was performed to find out the ideal LV-GLS cut-off value for predicting the AVS. A LV-GLS value of > - 18 has 85.8% sensitivity, 67.5% specificity for the prediction of the AVS. Our results support that subjects with AVS may have subclinical LV deformation abnormalities even though they have not LV pressure overload. According to our findings, patients with AVS should be investigated in terms of atherosclerotic risk factors, their dysmetabolic status should be evaluated and closely followed up for their progression to calcific aortic stenosis.

Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease.

Mapping the gene-regulatory networks dysregulated in human disease would allow the design of network-correcting therapies that treat the core disease mechanism. However, small molecules are traditionally screened for their effects on one to several outputs at most, biasing discovery and limiting the likelihood of true disease-modifying drug candidates. Here, we developed a machine-learning approach to identify small molecules that broadly correct gene networks dysregulated in a human induced pluripotent stem cell (iPSC) disease model of a common form of heart disease involving the aortic valve (AV). Gene network correction by the most efficacious therapeutic candidate, XCT790, generalized to patient-derived primary AV cells and was sufficient to prevent and treat AV disease in vivo in a mouse model. This strategy, made feasible by human iPSC technology, network analysis, and machine learning, may represent an effective path for drug discovery.

Calcified Aortic Valve Disease in Patients With Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is a rare autosomal gene deficiency disease with increased low-density lipoprotein cholesterol, xanthoma, and premature coronary heart disease. Calcified aortic valve disease (CAVD) is prevalent in FH patients, resulting in adverse events and heavy health care burden. Aortic valve calcification is currently considered an active biological process, which shares several common risk factors with atherosclerosis, including aging, hypertension, dyslipidemia, and so on. Unfortunately, the pathogenesis and therapy of CAVD in FH are still controversial. There is no pharmacological intervention recommended to delay the development of CAVD in FH, and the only effective treatment for severe CAVD is aortic valve replacement. In this review, we summarize the detailed description of the pathophysiology, molecular mechanism, risk factors, and treatment of CAVD in FH patients.

Focus on a rare clinical entity: unicuspid aortic valve disease.

INTRODUCTION: While the understanding of the pathophysiology and clinical implication of bicuspid aortic valves evolves rapidly, the natural history of unicuspid aortic valves is still poorly understood. Hence, a universally accepted diagnostic work-up process and therapy recommendations for UAV still have to be established. AREAS COVERED: This article aims to give an overview on the most recent literature addressing the pathophysiology, the diagnostic tools and appropriate surgical therapy options of unicuspid aortic valve. Due to the rare prevalence, the understanding of pathophysiology is still missing. Further, symptomatic aortic valve disease are seen much earlier life stage in this cohorts. Thus, it highlights the several surgical treatment options with pro and contra especially for the young adult cohorts. EXPERT OPINION: Large scale prospective observational studies using standardized diagnostic criteria are needed to reveal the clinical course. Further appropriate treatment strategies of unicuspid aortic valve patients is demanded.

Detecting Aortic Valve-Induced Abnormal Flow with Seismocardiography and Cardiac MRI.

Cardiac MRI (CMR) techniques offer non-invasive visualizations of cardiac morphology and function. However, imaging can be time-consuming and complex. Seismocardiography (SCG) measures physical vibrations transmitted through the chest from the beating heart and pulsatile blood flow. SCG signals can be acquired quickly and easily, with inexpensive electronics. This study investigates relationships between CMR metrics of function and SCG signal features. Same-day CMR and SCG data were collected from 28 healthy adults and 6 subjects with aortic valve disease history. Correlation testing and statistical median/decile calculations were performed with data from the healthy cohort. MR-quantified flow and function parameters in the healthy cohort correlated with particular SCG energy levels, such as peak aortic velocity with low-frequency SCG (coefficient 0.43, significance 0.02) and peak flow with high-frequency SCG (coefficient 0.40, significance 0.03). Valve disease-induced flow abnormalities in patients were visualized with MRI, and corresponding abnormalities in SCG signals were identified. This investigation found significant cross-modality correlations in cardiac function metrics and SCG signals features from healthy subjects. Additionally, through comparison to normative ranges from healthy subjects, it observed correspondences between pathological flow and abnormal SCG. This may support development of an easy clinical test used to identify potential aortic flow abnormalities.

Truncus arteriosus with retrograde aortic flow: a unique case.

Truncus arteriosus is a rare cyanotic congenital heart defect that involves septation failure of the heart's main arterial outflow tract. Varying morphologies of the truncal valve and aorta have been reported; however, the ascending aorta is typically supplied via anterograde blood flow through the truncal valve. We present the first reported case of neonatal truncus arteriosus with the ascending aorta being supplied entirely by retrograde flow.

A computational study on the influence of aortic valve disease on hemodynamics in dilated aorta.

A computational hemodynamics method was employed to investigate how the morphotype and functional state of aortic valve would affect the characteristics of blood flow in aortas with pathological dilation, especially the intensity and distribution of flow turbulence. Two patient-specific aortas diagnosed to have pathological dilation of the ascending segment while differential aortic valve conditions (i.e., one with a stenotic and regurgitant RL bicuspid aortic valve (RL-BAV), whereas the other with a quasi-normal tricuspid aortic valve (TAV)) were studied. When building the computational models, in addition to in vivo data-based reconstruction of geometrical model and boundary condition setting, the large eddy simulation method was adopted to quantify potential flow turbulence in the aortas. Obtained results revealed the presence of complex flow patterns (denoted by time-varying changes in vortex structure), flow turbulence (indicated by high turbulent eddy viscosity (TEV)), and regional high wall shear stress (WSS) in the ascending segment of both aortas. Such hemodynamic characteristics were significantly augmented in the aorta with RL-BAV. For instance, the space-averaged TEV in late systole and the wall area exposed to high time-averaged WSS (judged by WSS> two times of the mean WSS in the entire aorta) in the ascending aortic segment were increased by 176% and 465%, respectively. Relatively, flow patterns in the descending aortic segment were less influenced by the aortic valve disease. These results indicate that aortic valve disease has profound impacts on flow characteristics in the ascending aorta, especially the distribution and degree of high WSS and flow turbulence.