Aortic Area Research Articles

Abstract 4140136: Aortic Valve Calcification Density Performs Better Compared to Absolute Aortic Valve Calcification in Aortic Stenosis Risk Stratification

Aortic valve calcification (AVC) scores can be used to stratify aortic stenosis (AS) severity. Current practice guidelines recommend use of absolute AVC scores without considering body surface area or aortic annulus size. We investigated whether size variation in aortic annular area should be considered in identifying optimal AVC cutoffs for patients with severe AS. This was a retrospective analysis of AS patients that underwent AVC assessment during 2018-2023. Outcomes were composite of valve intervention or all-cause mortality. AVC density was defined by dividing AVC by echo-derived left ventricular tract area. Receiver operator curve analysis determined optimal AVC density scores. Absolute AVC cutoffs of >1200AU for females and >2000AU for males were used to identify severe AS. The study included 749 patients (mean age 78 years, 46% female). Median CT-annulus area was larger for males compared with females (532mm 2 [Q1, Q3: 479, 582] vs. 413mm 2 [370, 458], p<0.001). There was a strong association of absolute AVC with CT-annulus area for both males and females (Spearman coefficient: 0.87 and 0.83, p<0.01 each) respectively (Figure 1). The optimal AVC density cutoffs for males and females were 427 and 326, respectively (accuracy 76%, sensitivity 83%, specificity 51%). Composite outcomes were better differentiated with AVC density (males: HR 2.48, 95% CI: 1.82-3.37, p<0.001; females: HR 2.37 (1.71-3.28), p<0.001) compared with absolute AVC scores (males: HR 1.81 (1.43-2.30), p<0.001; females: HR 2.11 (1.62-2.74), p<0.001) (Figure 2). AVC is strongly associated with CT-annulus area and risk stratification is improved with the use of AVC density compared with absolute AVC. This may be especially helpful in patients with extremes of annulus area sizes.

Effect of Oral Administration of Collagen Peptide OG-5 on Advanced Atherosclerosis Development in ApoE-/- Mice.

Atherosclerosis is a chronic inflammatory disease of the arterial wall, which involves multiple cell types. Peptide OG-5 is identified from collagen hydrolysates derived from Salmo salar and exhibits an inhibitory effect on early atherosclerosis. The primary objective of this study was to investigate the impact of OG-5 on advanced atherosclerotic lesions as well as its stability during absorption. In this study, the ApoE-/- mice were employed to establish advanced atherosclerosis model to investigate the treatment effect of peptide OG-5. The results showed that oral administration of OG-5 at a dosage of 150 mg/kg bw resulted in a 30% reduction in the aortic plaque formation area in ApoE-/- mice with few bleeding risks. Specifically, intervention with a low dose of OG-5 (50 mg/kg bw), initiated in the early stage of atherosclerosis, continues to provide benefits into the middle and late stages without bleeding risks. Furthermore, treatment of OG-5 increased expression levels of contractile phenotype markers and reduced the accumulation of lipoprotein in VSMCs induced by ox-LDL. Peptide OG-5 could ensure transport across Caco-2 cell monolayers, exhibiting a Papp value of 1.80 × 10-5 cm/s, and exhibited a robust stability in plasma with remaining content >70% after 8 h incubation. In vivo studies revealed that OG-5 reached maximum concentration in blood after 120 min. The present results demonstrate the potential efficacy of peptide OG-5 as a promising agent for intervention in anti-atherogenesis strategies.

Aortic valve tract dynamics in normal-flow low-gradient and normal-flow high-gradient severe aortic stenosis

Abstract Introduction Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Severe AS is defined as a mean pressure gradient (MG) ≥ 40 mmHg, a maximum aortic jet velocity≥4 m/s and an aortic valve area (AVA)≤1 cm2. However, classification of AS severity may be challenging due to discordant results on echocardiography. The normal-flow low-gradient severe AS (NFLG-AS) is defined as AVA≤1 cm2, MG<40 mmHg, left ventricular ejection fraction ≥ 50%, and stroke volume index (SVi) ≥ 35 ml/m2, whereas in the presence of MG > 40mmHg the condition is described as normal-flow high-gradient AS (NFHG-AS). Purpose The purpose of this study was to seek differences in the dynamic changes of the aortic valve tract throughout the cardiac cycle between the two clinical entities: NFHG-AS (Group 1) and NFLG-AS (Group 2). Methods In total, 130 patients with normal flow severe AS who underwent TAVI and had 3D transoesophageal echocardiographic data sets were screened. 38 patients with NFHG-severe AS and 40 patients with NFLG-severe AS with matching clinical characteristics and aortic valve area were identified. A custom-made semi-automated application developed by SQ was used. The application allows tracking of the aortic valve tract surface throughout the cardiac cycle in 3D transoesophageal echocardiograms and provides measurements of the geometrical planes at 4 levels: left ventricular outflow tract (LVOT), aortic annulus (AoA), sinuses of Valsalva (SoV) and sinotubular junction (STJ). Results The echocardiographic characteristics and the dynamic changes of the aortic valve tract between the two groups are shown in Tables 1 and 2. Both groups had comparable echocardiographic characteristic apart from the mean aortic valve pressure gradient as expected. With regards to the aortic valve tract geometrical dynamic changes, the relative LVOT and AoA area changes were bigger in Group 1 (36.8±15.9% vs 29.1±11.9%; p=0.017 and 21.0±8.39% vs 17.1±6.6%; p=0.028). The SoV and STJ relative changes were similar between the two groups. The same applies to aortic stiffness parameters, namely compliance and distensibility of the ascending aorta, systemic arterial compliance, and valvulo-arterial impedance. Conclusion The LVOT and aortic annulus area demonstrate more prominent dynamic changes in patients with normal-flow high-gradient severe AS compared to individuals with normal-flow low-gradient severe AS. While the SoV and the STJ geometry does not change significantly through the cardiac cycle, a more elastic outflow tract allows larger expansion in systole and higher pressure gradients across the aortic valve, whereas a stiffer outflow tract and annulus result in lower pressure gradients, despite the presence of severe aortic stenosis (AVA<1.0cm2). These differences in dynamic LVOT and aortic annulus changes may explain the discrepancy between aortic valve area and pressure gradients in patients with normal-flow low-gradient AS.

Aortic valve tissue quantification in bicuspid aortic valve stenosis

Abstract Background The relative contribution of calcific versus noncalcific aortic valve tissue volume to aortic stenosis (AS) in bicuspid aortic valve (BAV) is unclear. Purpose We aimed to assess the association of aortic valve tissue volume quantified by contrast-enhanced CT with echocardiographic AS severity, and diagnostic implication of noncalcific tissue volume for severe AS. Methods We retrospectively identified 234 patients with BAV who had echocardiographic AS severity and contrast-enhanced CT evaluation within six months and left ventricular ejection ≥50%, including 150 severe AS (aortic valve area≤1 cm2 or indexed valve area≤0.6cm2/m2 plus mean grdient≥40mmHg or peak velocity≥4 m/s), 84 nonsevere AS (61 with at least mild AS: peak veloicty≥2.0 m/s plus mean gradient ≥10mmHg, and 23 with normal aortic valve function). Contrast-enhanced CT aortic valve calcific volume and noncalcific (fibrosis) volume were quantified using patient-specific Hounsfield unit thresholds (Figure). Noncontrast CT aortic valve calcium score (AVCscore) was quantified by the Agaston method. CT measurements were indexed to echocardiographic aortic valve annulus area and square-root transformed for the analysis. Results Of 234 patients, the mean age was 64±11 years, and 64% were men. There were positive correlations of indexed calcific volume, noncalcific volume, and inverse correlations of percentages of noncalcific volume (noncalcific volume divided by the sum of calcific and noncalcific volume) with peak velocity and mean gradient (|r|=0.30 to 0.68). Among 150 patients with severe AS, 28 had an AVCscore below the severe AVC threshold (1200 AU in women and 2000 AU in men) while exhibited a higher percentage of noncalcific volume compared to 122 patients with severe AVCscore (67±15% vs. 39±15%, p<0.001). After excluding 122 patients with severe AS and severe AVCscore, the indexed noncalcific volume was associated with severe AS (β±S.E: 0.18±0.07, p=0.005) with an area under the curve of 0.71; in contrast, AVCscore was not (p=0.55). Conclusion Both calcific and noncalcific aortic valve tissue volume contribute to AS severity in patients with BAV. Notably, noncalcific tissue volume is a key factor in determining severe AS in patients without severe AVCscore, suggesting its potential diagnostic value.Figure

Large sample size MRI measurements to assess the relation between cardiac function and structure and white matter hyperintensity volumes

Abstract Background People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurological diseases such as dementia. CVD and neurological diseases share common risk factors, such as blood pressure, sedentary lifestyle, as well as genomic risk factors such as mutations in APOE4 [1]. It's unclear to what extent the co-occurrence of CVD and neurological diseases is explained by these risk factors, or whether there is a direct association where CVD is a first step towards poorer neurological health. White matter hyperintensities (WMH) of presumed vascular origin are damaged areas in the brain observed through magnetic resonance imaging (MRI). These lesions are associated with progressive neurological disease such as vascular dementia, as well with risk factors for CVD [2]. Purpose We set out to determine to what extent CMR measurements associated with WMH independent of known cerebrovascular risk factors. Methods Cardiac and brain MRI images were analysed for 23,963 UK biobank (UKB) participants. WMH analysis included 5 brain regions (Frontal[F], Parietal[P], Temporal[T], Occipital[O], Basal Ganglia and Thalami [BGT]) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas. Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for: age, difference between age at initial visit and imaging visit, sex, systolic and diastolic blood pressure, Hba1c, household income, educational status, Townsend score and family history of disease (Alzheimer’s, Parkinson's, high blood pressure, stroke, heart disease) . Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain 90% of the cardiac trait variability. Results For 5 cardiac traits (right ventricular stroke volume, left atrial stroke volume, left ventricular stroke volume, left ventricular ejection fraction and right ventricular end diastolic volume) higher values were associated with lower WMH volumes in all brain regions. Additionally, some cardiac traits such as LV cardiac output associated with specific brain regions (T, O, BGT). Additionally, APOE- ε4 stratified analyses indicated, homozygous carriers show a greater association between higher minimum LA and RA volumes and higher WMH volumes in the occipital lobe. Conclusions This study gives an insight into the WMH burden in a large population of adults. It highlights the associations of cardiac traits with white matter hyperintensity volumes in different brain regions independent of known risk factors. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between CVD and cerebrovascular disease.Figure 1Graphical Abstract

Genome-wide association study of CMR image-based aortic stiffness in 45,789 individuals identifies loci linked with cardiovascular diseases

Abstract Background The use of artificial intelligence on large-scale cardiac magnetic resonance (CMR) imaging data has enabled detailed characterisation of cardiac shape and function for use in genome-wide association studies (GWAS), leading to improved understanding of genetic aetiology of cardiovascular diseases (CVDs). Aortic stiffness is associated with increased risk of cardiovascular events in observational studies. Here, we present a novel CMR-based pressure-independent measure of aortic stiffness, identify genetic associations and explore links with CVDs. Purpose Identify genetic contributions to pressure-independent aortic stiffness and links to CVDs using large-scale GWAS analysis on the UK Biobank cohort. Methods A pre-trained neural network was used to segment CMR images of participants in the UK Biobank to quantify ascending aorta diameter, which together with contemporaneous systolic and diastolic blood pressure measurements (SBP, DBP, respectively) were used to calculate a pressure-independent measure of aortic stiffness (β0). The measurement assumes an exponential relationship between pressure and aortic diameter. We then performed a GWAS on β0 in 45,789 participants of European ancestry without CVDs. A multi-trait-based conditional & joint analysis (mtCOJO) was performed to estimate genetic effects independent of SBP, DBP and aortic area. We mapped the independent lead variants associated with aortic stiffness at P < 5x10-8 to nearest gene, and characterised shared genetic association across CVDs using Open Targets Platform database. Results The GWAS identified 17 independent lead variants, including 6 that remained significant in the conditional analysis. Four of these lead variants, not previously reported in GWAS of other aortic traits, were located near CTD-2203A3.1, MCF2L, CFDP1 and CDH13 genes (red annotations in the Figure). MCF2L, CFDP1 and CDH13 have been associated with coronary artery disease, and CFDP1 with myocardial infarction and coronary atherosclerosis in previous studies. Conclusion A GWAS of CMR-derived aortic stiffness identified 4 loci distinct from other aortic traits that also associate with other CVDs, suggesting genetic links between aortic stiffness and CVDs. Further analyses are required to explore biological mechanisms underlying these genetic associations.Aortic Stiffness Manhattan Plot

A new wearable cardiac acoustic monitoring technology for the evaluation of subclinical leaflet thrombosis after transcatheter aortic valve replacement: a pilot study

Abstract Background Subclinical leaflet thrombosis characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion (RLM) is a common complication after transcatheter aortic valve replacement (TAVR), whether it affects hemodynamic change is still debated. Purpose We attempted to use a novel wearable heart acoustic monitoring device, and combined multi-dimensional computed tomography (MDCT) and echocardiography to diagnose SLT and analyze the changes of transvalvular hemodynamics after TAVR. Methods Patients with severe symptomatic aortic stenosis and underwent successful TAVR were consecutively enrolled. Clinical data, acoustic cardiographic parameters including the frequency, amplitude, and energy of heart sounds , and imaging results were collected and analyzed by Core laboratory at pre- and post TAVR, and follow-up at one month and six month. According to severity of SLT at one month follow-up, we divided the patients into three groups: Group1: no SLT, Group2: mild SLT, defined as existed HALT did not qualify for Group 3, and Group 3: moderate to severe SLT, defined as at least 1 leaflet with HALT of grade 3 or 4 or RLM of ≥50%, or 2 leaflets with HALT of grade 2 or RLM of ≥50%. A consistency analysis of SLT presence between MDCT findings and acoustic cardiographic variables was performed using Kappa statistics. Results The study included 116 TAVR patients. The prevalence of SLT as detected by MDCT at one-month follow-up was 25%, with moderate to severe SLT representing 11.2% of cases. A significant decrease in aortic valve orifice area (AVA) (-0.2±0.48cm2 vs. -0.1±0.33cm2, p=0.009) and an increase in mean gradient (MG) (3.5±5.85 mmHg vs. 0.1±11.34mmHg, p=0.028) were observed in moderate to severe SLT group at one-month follow-up versus post-TAVR via echocardiography. However, no significant differences were found in the mild SLT or no SLT group. Acoustic cardiographic characteristics exhibited a distinct pattern with early systolic, baseless, and high-energy murmurs in patients with moderate to severe SLT, but not in the mild SLT or no SLT group. The sensitivity, specificity, and Kappa values for acoustic cardiography in diagnosing moderate to severe SLT were 81.82%, 83.33%, and 0.41, respectively. At the 6-month follow-up, MDCT showed that 11 (85%) patients with moderate to severe SLT who received anticoagulant therapy reached complete dissolution of SLT. Conclusion Moderate to severe SLT presented notably transvalvular hemodynamic influences following TAVR. Acoustic cardiography demonstrated specific characteristics of moderate to severe SLT, providing a valuable tool for SLT diagnosis and evaluation in clinical follow-up.Figure 1.Baseline characteristicsFigure 2.SLT and acoustic cardiography

Insights from the assessment of anatomic valve orifice area after transcatheter aortic valve implantation using transesophageal echocardiography

Abstract Background Although transthoracic echocardiography (TTE) is the gold standard for evaluating effective valve orifice area (EOA) after transcatheter aortic valve implantation (TAVI), the continuous formula is inherently different from anatomic valve orifice area because it implies a minimum jet width through the aortic valve. It has also been reported that the doppler method with TTE overestimates the mean gradient due to pressure recovery and is even less accurate after TAVI. On the other hand, recent technological developments have improved image resolution, making valve morphology possible using transesophageal echocardiography (TEE). Purpose The purpose of this study was to compare transcatheter aortic valve (TAV) area using TEE and TTE to evaluate whether there is a significant difference in each area and to explore factors that influence the difference in area. Methods Patients who underwent TEE-guided TAVI and SAPIEN3 implantation between February 2019 and March 2023 and had aortic valve evaluation with TTE before discharge were included. We retrospectively evaluated the TAV after TAVI using TTE and TEE. Aortic valve orifice area was calculated by two methods: EOA index (doppler-area: DA) calculated by the continuous doppler formula using TTE and t-AVA index (trace-area: TA) derived by the trace method using TEE. TAV tracing was performed in early systole on the short-axis image of the aortic valve. The TAV tracing was performed by physicians specializing in echocardiography, and multiple physicians were blinded to the same case to eliminate inter-rater error. The percentage change between the two groups was calculated from the difference in area by TTE and TEE, and the 75th percentile of the percentage change was defined as the cutoff value for the group with the large difference in TAV area. Results Patients whose TAV was difficult to observe by TEE were excluded, and 464 patients were finally analyzed. TA was significantly larger than DA (1.56±0.28 cm2/m2 vs 1.18±0.26 cm2, p<0.001) and similar for all TAV sizes. However, even though TA expanded as valve size increased, the largest area of DA was observed in the 26mm TAV, and the 29mm TAV was comparable to the 26mm TAV. Only a weak correlation was shown between DA and TA (correlation coefficient: 0.356). There were 43 cases of moderate prosthetic valve-patient mismatch (PPM: EOA-i<0.85cm) in DA, but only 1 case in TA. In multivariate logistic regression analysis, women (OR 2.25, 95% CI 1.17-4.34, p < 0.015) and LV mass index (OR 1.01, 95% CI 1.00-1.02, p < 0.041) were independent factors for the large difference in TAV area. Conclusion After TAVI, the TAV area with TEE was larger than the EOA-i with TTE, and PPM was rarely seen. Depending on valve size, patient background, and cardiac morphology, there are cases of overestimation of postoperative AS in TTE, which may need to be carefully evaluated in women and patients with larger LV mass index.

The orchestration of coding and non-coding genes at the CDH13 locus in coronary artery disease

Abstract Background The CDH13 locus was associated with coronary artery disease (CAD) by genome-wide association studies (GWAS). However, the causal gene(s) and underlying disease mechanisms at this locus remain undetermined. Purpose We intended to pinpoint and functionally validate the causal coding and non-coding genes at the CDH13 locus and delineate the underlying mechanisms for CAD. Methods and results We conducted the transcriptome-wide association analysis (TWAS) using nine types of CAD-relevant tissues from Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) and Genotyped Tissue Expression (GTEx) projects and identified CDH13 (T-cadherin) and four long non-coding RNA (lncRNA) genes as candidate causal genes at The CDH13 locus. One of the antisense(AS) lncRNAs, CDH13-AS2, was predicted to bind on the 3’ untranslated region (UTR) of CDH13 using LncRRIsearch and RNAup servers. The binding interaction was validated by dCas13-medicated RNA immunoprecipitation. Weighted correlation network analysis (WGCNA) using transcriptomic data from CAD-relevant tissues of ~600 human subjects suggested a positive expression correlation between CDH13 and CDH13-AS2 in artery tissues. CRISPR/Cas9-based knockout (KO) of CDH13 or CDH13-AS2 in human umbilical vein endothelial cells (HUVECs) indicated synergistically atherogenic phenotypes, including reduced proliferation and migration, and increased apoptosis and monocyte adhesion. The data matched with the downregulation of CDH13 in artery samples of atherosclerosis patients. The cellular phenotypes were also in line with our in vivo data of Cdh13 and Apoe double-KO (Cdh13-/-/Apoe-/-) mice, which showed increased aortic lesion areas when fed on a high-fat diet compared to Apoe-/- mice. Furthermore, prediction using TargetScan, miRWalk, and scanMiRApp databases identified the potential binding of several EC-expression microRNAs (mir) on 3’UTR of CDH13. Several disease-associated variants were mapped to the predicted binding sites of a few microRNAs, including mir-let7, mir-30, and mir-125. The dual luciferase-based RNA interference (RNAi) assay confirmed the binding of mir-let7 on 3’UTR of CDH13. Transcriptional activation of CDH13-AS2 by the enzymatically inactivated Cas9 (dCas9) system diminished the binding of mir-let7 and increased CDH13 expression. Conclusions At the CDH13 locus, CDH13 and CDH13-AS2 are two causal genes, whose downregulation likely contributes to CAD. CDH13-AS2 bound and stabilized CDH13 partially by preventing mir-let7 mediated degradation of CDH13 mRNA, suggesting therapeutic potentials.

Alisol A inhibits and stabilizes atherosclerotic plaques by protecting vascular endothelial cells.

Dysfunction of endothelial cells represents a crucial aspect in the pathogenesis of atherosclerosis. The aim of this study was to explore the protective effects of alisol A on vascular endothelial cells and its possible mechanisms. An atherosclerosis model was established by feeding ApoE-/- mice with high-fat chow. Alisol A (150mg/kg/d) or atorvastatin (15mg/kg/d) was administered, and the levels of blood lipids were evaluated. The effect of the drugs on atherosclerotic plaques was observed by staining the aorta with Sudan IV. In vitro experiments were conducted using human aortic endothelial cells (HAECs) to assess the effects of alisol A on cell proliferation, migration, tubulation, secretion, and cellular integrity by CCK-8 assay, wound healing assay, angiogenesis assay, NO secretion, and release of LDH. Transcriptomics and molecular docking were used to explore the mechanism of plaque inhibition and stabilization by alisol A. Alisol A significantly reduced the aortic plaque area in ApoE-/- mice fed with high-fat chow. In vitro, alisol A had a protective effect on HAECs, which was reflected in the inhibition of vascular endothelial cell proliferation, promotion of NO secretion by vascular endothelial cells, inhibition of vascular endothelial cell migration and angiogenesis, and the maintenance of cell membrane integrity. Therefore, alisol A inhibited and stabilized atherosclerotic plaques and slowed down the process of atherosclerosis. Transcriptomics studies showed 4,086 differentially expressed genes (DEGs) in vascular endothelial cells after alisol A treatment. Enrichment analysis indicated that many genes involved in TNF signaling pathway were differentially expressed, and inflammatory genes were suppressed. The molecular docking results verified the hypothesis that alisol A has a low binding energy after docking with TNF target, and TNF could be a potential target of alisol A. Alisol A produced protection on vascular endothelial cells, achieving inhibition and stabilization of atherosclerotic plaques.

Aortic root parameter analysis for transcatheter aortic valve implantation in the Pakistani population: a retrospective study

BackgroundTranscatheter aortic valve implantation (TAVI) is a growing treatment for aortic stenosis, but anatomical variations exist across populations. Asians tend to have smaller aortic annuli and higher bicuspid valve morphology compared to Westerners, potentially impacting TAVI valve selection and outcomes. This study analyzes aortic root parameters in Pakistani patients undergoing TAVI.ResultsWe conducted a retrospective analysis of 78 patients who underwent TAVI at the Peshawar Institute of Cardiology from January 2021 to March 2024. Pre-procedural CT scans were analyzed for aortic annulus diameters, area, and other relevant parameters. The mean age was 72.41 years (SD ± 11.99), and 61.5% were male. Aortic annulus diameters (minimum, mean, maximum) were 21.18 mm (SD ± 3.99), 24.21 mm (SD ± 3.93), and 27.49 mm (SD ± 4.43), respectively. Bicuspid aortic valves were present in 34.61% of patients.ConclusionsOur findings suggest that Pakistani patients undergoing TAVI may have aortic root dimensions comparable to Western populations, with a substantial prevalence of bicuspid valves. However, coronary heights were similar to those reported in Asian populations with smaller annuli. Further studies are needed to assess TAVI outcomes in Pakistani patients and determine if tailored valve sizing strategies are required.

Cerebral emboli detection and autonomous neuromonitoring using robotic transcranial Doppler with artificial intelligence for transcatheter aortic valve replacement with and without embolic protection devices: a pilot study

BackgroundPeriprocedural ischemic stroke remains a serious complication in patients undergoing transcatheter aortic valve replacement (TAVR). We used a novel robotic transcranial Doppler (TCD) system equipped with artificial intelligence (AI) for...

Automated Quantification of Simple and Complex Aortic Flow Using 2D Phase Contrast MRI

(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully automated segmentation of phase contrast velocity-encoded aortic root plane. (2) Materials and Methods: Aortic root images from 125 patients are segmented by artificial intelligence (AI), developed using convolutional neural networks and trained with a multicentre cohort of 160 subjects. Derived simple flow indices (forward and backward flow, systolic flow and velocity) and complex indices (aortic maximum area, systolic flow reversal ratio, flow displacement, and its angle change) were compared with those derived from manual contours. (3) Results: AI-derived simple flow indices yielded excellent repeatability compared to human segmentation (p < 0.001), with an insignificant level of bias. Complex flow indices feature good to excellent repeatability (p < 0.001), with insignificant levels of bias except flow displacement angle change and systolic retrograde flow yielding significant levels of bias (p < 0.001 and p < 0.05, respectively). (4) Conclusions: Automated flow quantification using aortic root images is comparable to human segmentation and has good to excellent repeatability. However, flow helicity and systolic retrograde flow are associated with a significant level of bias. Overall, all parameters show clinical repeatability.

Left Ventricular Outflow Tract Morphology as a Predictor of Conductance Disturbances Following Transcatheter Aortic Valve Replacement.

Conduction disturbances represent one of the most common complications following transcatheter aortic valve replacement (TAVR). We sought to investigate the role of left ventricular outflow tract (LVOT) morphology in the development of conduction disturbances following TAVR. Consecutive patients who underwent TAVR in our center were included. The ratio between the LVOT area and the aortic annulus area was calculated. Patients were then divided into 2 groups on the basis of this ratio: group 1, which included patients with an LVOT area/aortic annulus area ratio <0.9; and group 2, which included patients with an LVOT area/aortic annulus area ratio ≥0.9. The primary end point was to assess the relationship between LVOT shape and the rate of permanent pacemaker implantation following TAVR. A multivariable analysis was performed to identify predictors of permanent pacemaker implantation following TAVR. From January 2018 to December 2020, 276 patients were included. Ninety-one patients with tapered LVOT morphology were assigned to group 1 and the rest (n=185 patients), tubular LVOT or flared LVOT shape, to group 2. The mean age was 81.5±5.7 years and 57% were women. After adjusting by confounding factors, tapered morphology of the LVOT and prior right bundle-branch block were found to be independent predictors of permanent pacemaker implantation (hazard ratio [HR], 2.6 [95% CI, 1.2-5.7]; P=0.014; and HR: 4.3 [95% CI 2.4-7.6], P<0.001); at a median follow-up time of 15.5 (interquartile range, 15) months. A tapered-LVOT morphology was associated with increased risk for permanent pacemaker implantation. LVOT morphology may be an additional factor to consider when choosing prosthesis size.

Temporal geometric mapping defines morphoelastic growth model of Type B aortic dissection evolution

The human aorta undergoes complex morphologic changes that mirror the evolution of disease. Finite element analysis (FEA) enables the prediction of aortic pathologic states, but the absence of a biomechanical understanding hinders the applicability of this computational tool. We incorporate geometric information from computed tomography angiography (CTA) imaging scans into FEA to predict a trajectory of future geometries for four aortic disease patients. Through defining a geometric correspondence between two patient scans separated in time, a patient-specific FEA model can recreate the deformation of the aorta between the two time points, showing that pathologic growth drives morphologic heterogeneity. FEA-derived trajectories in a shape-size geometric feature space, which plots the variance of the shape index versus the inverse square root of aortic surface area (δS vs. AT−1), quantitatively demonstrate an increase in δS. This represents a deviation from physiologic shape changes and parallels the true geometric progression of aortic disease patients.

Transcriptome analysis of the aortic coarctation area

BackgroundCoarctation of the aorta (CoA) is a relatively common congenital heart defect. The underlying causes are not known, but a combination of genetic factors and abnormalities linked to embryonic development is suspected. There are only a few studies of the underlying molecular mechanisms in CoA. The aim of the current study was to expand our understanding of the pathogenesis of CoA by characterizing the transcriptome of the coarctation area. MethodsTissue samples from 21 pediatric patients operated for CoA were dissected into separate biopsies consisting of the localized coarctation itself, proximal/distal tissue and ductus. RNA was sequenced to evaluate gene expression in the different biopsies. ResultsWe observed an activation of acute phase response in samples from the localized coarctation compared to samples from distal or proximal tissue. However, we observed even bigger differences for patient age and sex than compared to biopsy location. A cluster of genes located at 1q21, including the S100 gene family, displayed contrasting expression depending on patient sex, and appeared to affect the balance between inflammatory and interferon pathways. Biopsies from patients <3 months old were characterized by a significantly higher fibrotic activity compared to samples from older patients. The ductus tissue was characterized by an upregulation of factors associated with proliferation. ConclusionsThe ongoing processes in the coarctation area are influenced by the age and sex of the patient, and possibly by differences in etiology between different patients. The impact of patient attributes must be taken into consideration when performing future studies.

Chronic exposure to E-cigarette aerosols potentiates atherosclerosis in a sex-dependent manner

Despite being designed for smoking cessation, e-cigarettes and their variety of flavors have become increasingly attractive to teens and young adults. This trend has fueled concerns regarding the potential role of e-cigarettes in advancing chronic diseases, notably those affecting the cardiovascular system. E-cigarettes contain a mixture of metals and chemical compounds, some of which have been implicated in cardiovascular diseases like atherosclerosis. Our laboratory has optimized in vivo exposure regimens to mimic human vaping patterns. Using these established protocols in an inducible (AAV-PCSK9) hyperlipidemic mouse model, this study tests the hypothesis that a chronic exposure to e-cigarette aerosols will increase atherosclerotic plaques. The exposures were conducted using the SCIREQ InExpose™ nose-only inhalation system and STLTH or Vuse products for 16 weeks. We observed that only male mice exposed to STLTH or Vuse aerosols had significantly increased plasma total cholesterol, triglycerides, and LDL cholesterol levels compared to mice exposed to system air. Moreover, these male mice also had a significant increase in aortic and sinus plaque area. Male mice exposed to e-cigarette aerosol had a significant reduction in weight gain over the exposure period. Our data indicate that e-cigarette use in young hyperlipidemic male mice increases atherosclerosis in the absence of significant pulmonary and systemic inflammation. These results underscore the need for extensive research to unravel the long-term health effects of e-cigarettes.

Aortic Uptake of 18F-NaF and 18F-FDG and Calcification Predict the Development of Abdominal Aortic Aneurysms and Is Attenuated by Drug Therapy.

Abdominal aortic aneurysms expand over time and increase the risk of fatal ruptures. To predict expansion, the isolated assessment of 18F-fluorodeoxyglucose (FDG) and sodium fluoride (NaF) uptake or calcification volume in aneurysms has been investigated with variability in results. We systematically evaluated whether 18F-FDG and 18F-NaF uptake was predictive of abdominal aortic aneurysm expansion. Seventy-four male Sprague-Dawley rat abdominal aortic aneurysm models were imaged using positron emission tomography-computed tomography with 18F-FDG and 18F-NaF at 1, 2, 4, 6, and 8 weeks after CaCl2 or saline stimulation. In the 1-week cohort (n=25), the correlation between 18F-FDG or 18F-NaF uptake and pathological markers was investigated. In the time course cohort (n=49), animals received either atorvastatin, losartan, aldactone, or risedronate to assess the effect of these drugs, and the relationship between aortic size and sequential 18F-FDG and 18F-NaF uptake or calcification volume was examined. In the 1-week cohort, the maximum standard unit value of 18F-FDG and 18F-NaF uptake correlated with CD68- (r=0.82; P=0.001) and von Kossa staining-positive areas (r=0.89; P<0.001), respectively. In the time course cohort, 18F-FDG and 18F-NaF uptake changed in a time-dependent manner and drugs attenuated this uptake. Specifically, 18F-FDG showed high uptake at weeks 1 and 2, whereas a high 18F-NaF uptake was noted throughout the study period. Atorvastatin and risedronate showed a decreased and increased aortic size, respectively. The final aortic area correlated well with 18F-FDG and 18F-NaF uptake and calcification volume, especially at 1 and 2 weeks (18F-NaF [1 week]: r=0.61, 18F-FDG [2 weeks]: r=0.51, calcification volume [1 week]: r=0.59; P<0.001). Multiple linear regression analysis showed that the combination of these factors predicted the final aortic size, with 18F-NaF uptake at 1 week being the strongest predictor. The uptake of 18F-NaF and 18F-FDG and the calcification volume at appropriate times correlated with the development of abdominal aortic aneurysms, with 18F-NaF uptake being the strongest predictor.

Percutaneous Valvular and Structural Heart Disease Interventions. 2024 Core Curriculum of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

The percutaneous treatment of structural, valvular, and non-valvular heart disease (SHD) is rapidly evolving. The Core Curriculum (CC) proposed by the EAPCI describes the knowledge, skills, and attitudes that define competency levels required by newly trained SHD interventional cardiologists (IC) and provides guidance for training centres. SHD ICs are cardiologists who have received complete interventional cardiology training. They are multidisciplinary team specialists who manage adult SHD patients from diagnosis to follow-up and perform percutaneous procedures in this area. They are competent in interpreting advanced imaging techniques and master planning software. The SHD ICs are expected to be proficient in the aortic, mitral, and tricuspid areas. They may have selective skills in either the aortic area or mitral/tricuspid areas. In this case, they must still have common transversal competencies in the aortic, mitral, and tricuspid areas. Additional SHD domain competencies are optional. Completing dedicated SHD training, aiming for full aortic, mitral, and tricuspid competencies, requires at least 18 months. For full training in the aortic area, with basic competencies in mitral/tricuspid areas, the training can be reduced to 1 year. The same is true for training in the mitral/tricuspid area, with competencies in the aortic area. The SHD IC CC promotes excellence and homogeneous training across Europe and is the cornerstone of future certifications and patient protection. It may be a reference for future CC for national associations and other SHD specialities, including imaging and cardiac surgery.

Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model.

Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.