Aortic Area Research Articles

Echocardiographic parameters associated with less reverse left ventricular remodeling after transcatheter aortic valve implant in subjects with prosthesis patient mismatch.

Transaortic valve implant (TAVI) is the treatment of choice for severe aortic stenosis (AS). Some patients develop prosthesis patient mismatch (PPM) after TAVI. It is challenging to determine which patients are at risk for clinical deterioration. We retrospectively measured echocardiographic parameters of left ventricular (LV) morphology and function, prosthetic aortic valve effective orifice area (iEOA) and hemodynamics in 313 patients before and 1year after TAVI. Our objective was to compare the change in echocardiographic parameters associated with left ventricular reverse modeling in subjects with and without PPM. Our secondary objective was to evaluate echo parameters associated with PPM and the relationship to patient functional status and survival post-TAVI. We found that 82 (26.2%) of subjects had moderate and 37 (11.8%) had severe PPM post-TAVI. There was less relative improvement in LVEF with PPM (1.9±21.3% vs. 8.2+30.1%, p=.045). LV GLS also exhibited less relative improvement in those with PPM (13.4+34.1% vs. 30.9+73.3%, p=.012). NYHA functional class improved in 84.3% of subjects by one grade or more. Echocardiographic markers of PPM were worse in those without improvement in NYHA class (mean AT/ET was .29 vs. .27, p=.05; DVI was .46 vs. .51, p=.021; and iEOA was .8cm/m2 vs. .9cm/m2 , p=.025). There was no association with PPM and survival. There was no improvement in LVEF and less improvement in LV GLS in those with PPM post-TAVI. Echocardiographic markers of PPM were present in those with lack of improvement in NYHA functional class.

Mitochondrial dysfunction and metabolic reprogramming induce macrophage pro-inflammatory phenotype switch and atherosclerosis progression in aging.

Aging increases the risk of atherosclerotic vascular disease and its complications. Macrophages are pivotal in the pathogenesis of vascular aging, driving inflammation and atherosclerosis progression. NOX4 (NADPH oxidase 4) expression increases with age, correlating with mitochondrial dysfunction, inflammation, and atherosclerosis. We hypothesized that the NOX4-dependent mitochondrial oxidative stress promotes aging-associated atherosclerosis progression by causing metabolic dysfunction and inflammatory phenotype switch in macrophages. We studied atherosclerotic lesion morphology and macrophage phenotype in young (5-month-old) and aged (16-month-old) Nox4 -/-/Apoe -/- and Apoe -/- mice fed Western diet. Young Nox4-/-/Apoe-/- and Apoe-/- mice had comparable aortic and brachiocephalic artery atherosclerotic lesion cross-sectional areas. Aged mice showed significantly increased lesion area compared with young mice. Aged Nox4-/-/Apoe-/- had significantly lower lesion areas than Apoe-/- mice. Compared with Apoe-/- mice, atherosclerotic lesions in aged Nox4-/-/Apoe-/- showed reduced cellular and mitochondrial ROS and oxidative DNA damage, lower necrotic core area, higher collagen content, and decreased inflammatory cytokine expression. Immunofluorescence and flow cytometry analysis revealed that aged Apoe-/- mice had a higher percentage of classically activated pro-inflammatory macrophages (CD38+CD80+) in the lesions. Aged Nox4-/-/Apoe-/- mice had a significantly higher proportion of alternatively activated pro-resolving macrophages (EGR2+/CD163+CD206+) in the lesions, with an increased CD38+/EGR2+ cell ratio compared with Apoe-/- mice. Mitochondrial respiration assessment revealed impaired oxidative phosphorylation and increased glycolytic ATP production in macrophages from aged Apoe-/- mice. In contrast, macrophages from Nox4-/-/Apoe-/- mice were less glycolytic and more aerobic, with preserved basal and maximal respiration and mitochondrial ATP production. Macrophages from Nox4-/-/Apoe-/- mice also had lower mitochondrial ROS levels and reduced IL1β secretion; flow cytometry analysis showed fewer CD38+ cells after IFNγ+LPS treatment and more EGR2+ cells after IL4 treatment than in Apoe-/- macrophages. In aged Apoe-/- mice, inhibition of NOX4 activity using GKT137831 significantly reduced macrophage mitochondrial ROS and improved mitochondrial function, resulting in decreased CD68+CD80+ and increased CD163+CD206+ lesion macrophage proportion and attenuated atherosclerosis. Our findings suggest that increased NOX4 in aging drives macrophage mitochondrial dysfunction, glycolytic metabolic switch, and pro-inflammatory phenotype, advancing atherosclerosis. Inhibiting NOX4 or mitochondrial dysfunction could alleviate vascular inflammation and atherosclerosis, preserving plaque integrity.

Prognostic Relevance of Global Myocardial Work Index in Patients with Moderate Aortic Valve Stenosis.

A reduced global myocardial work index (GWI) ≤ 1951 mmHg% is associated with increased mortality in patients with severe aortic valve stenosis (AS). However, parameters predicting the outcome in patients with moderate AS are limited. Therefore, the aim of this study was to evaluate the prognostic value of the GWI in patients with moderate AS. In this prospective study, 103 patients with moderate AS (mean age 72 ± 10 years; male: 69%) underwent standardized transthoracic echocardiography. The primary endpoint was survival without an aortic valve replacement (AVR). After a median follow-up of 30 ± 5 months, 37 patients (36%) were referred for an AVR. Survival without an AVR was 96% at 12 months and 80% at 30 months (>1951 mmHg%) versus 96% and 68% (≤1951 mmHg%). A GWI ≤ 1951 mmHg% did not predict the need for an AVR (hazard ratio 1.31 (95% CI, 0.63-2.72), p = 0.49). Furthermore, there was no significant correlation between the mean GWI (1644 ± 448 mmHg%) and mean aortic valve pressure gradient (24.2 mmHg ± 6.2, p = 0.615) or effective aortic orifice area (1.24 cm2 ± 0.11, p = 0.678). There was no difference between the AVR and non-AVR groups in the occurrence of clinical symptoms. In contrast to patients with severe AS, a GWI ≤ 1951 mmHg% did not predict the need for an AVR. Further research is needed to improve the risk stratification in patients with moderate AS.

Highly accelerated, Dixon-based non-contrast MR angiography versus high-pitch CT angiography

ObjectivesTo compare a novel, non-contrast, flow-independent, 3D isotropic magnetic resonance angiography (MRA) sequence that combines respiration compensation, electrocardiogram (ECG)-triggering, undersampling, and Dixon water-fat separation with an ECG-triggered aortic high-pitch computed tomography angiography (CTA) of the aorta.Materials and methodsTwenty-five patients with recent CTA were scheduled for non-contrast MRA on a 3 T MRI. Aortic diameters and cross-sectional areas were measured on MRA and CTA using semiautomatic measurement tools at 11 aortic levels. Image quality was assessed independently by two radiologists on predefined aortic levels, including myocardium, proximal aortic branches, pulmonary veins and arteries, and the inferior (IVC) and superior vena cava (SVC). Image quality was assessed on a 5-point Likert scale.ResultsAll datasets showed diagnostic image quality. Visual grading was similar for MRA and CTA regarding overall image quality (0.71), systemic arterial image quality (p = 0.07–0.91) and pulmonary artery image quality (p = 0.05). Both readers favored MRA for SVC and IVC, while CTA was preferred for pulmonary veins (all p < 0.05). No significant difference was observed in aortic diameters or cross-sectional areas between native MRA and contrast-enhanced CTA (p = 0.08–0.94).ConclusionThe proposed non-contrast MRA enables robust imaging of the aorta, its proximal branches and the pulmonary arteries and great veins with image quality and aortic diameters and cross-sectional areas comparable to that of CTA. Moreover, this technique represents a suitable free-breathing alternative, without the use of contrast agents or ionizing radiation. Therefore, it is especially suitable for patients requiring repetitive imaging.

Ratio of left ventricular outflow tract area to aortic annulus area and complete atrioventricular block after transcatheter aortic valve replacement for aortic stenosis

BackgroundMechanical compression of cardiac conduction system by transcatheter heart valves leads to complete atrioventricular block (CAVB) after transcatheter aortic valve replacement (TAVR). Bulging of ventricular septum in the left ventricular outflow tract (LVOT) may be associated with greater compression of conduction system, leading to irreversible CAVB. ObjectiveThis study aimed to investigate the association of ventricular septal bulging with TAVR-related CAVB and permanent pacemaker implantation (PPI). MethodsAmong 294 consecutive patients with severe aortic stenosis who underwent TAVR between July 2017 and February 2023, 271 were included in the analysis. As a quantitative evaluation of bulging of the ventricular septum, the ratio of LVOT area to aortic annulus area (L/A ratio) was measured at the systolic phase of computed tomography images. ResultsTAVR-related CAVB occurred in 64 patients (23.6%). Twenty-eight patients (10.3%) required PPI. The optimal thresholds of L/A ratio for predicting TAVR-related CAVB and PPI were 1.0181 and 0.985, respectively. Patients with less than the cut-off values had higher rate of TAVR-related CAVB and PPI than those above (28.3% vs 13.1%, p = 0.0063; 14.7% vs 4.4%, p = 0.0077, respectively). A multivariate analysis showed that L/A ratio < 1.0181 was an independent predictor of TAVR-related CAVB (odds ratio [OR] 2.65, p = 0.011), in addition to prior right bundle branch block (OR 3.76, p = 0.0005), use of a self-expanding valve (OR 1.99, p = 0.030), and short membranous septum length (OR 0.96, p = 0.037). Only L/A ratio < 0.985 was independently associated with PPI (OR 3.70, p = 0.011). ConclusionLow L/A ratio is a predictor of TAVR-related CAVB and PPI.

Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice

The thromboxane A2 receptor (TP) has been shown to play a role in angiotensin II (Ang II)-mediated hypertension and pathological vascular remodeling. To assess the impact of vascular TP on Ang II-induced hypertension, atherogenesis, and pathological aortic alterations, i.e. aneurysms, we analysed Western-type diet-fed and Ang II-infused TPVSMC KO/Ldlr KO, TPEC KO/Ldlr KO mice and their respective wild-type littermates (TPWT/Ldlr KO). These analyses showed that neither EC- nor VSMC-specific deletion of the TP significantly affected basal or Ang II-induced blood pressure or aortic atherosclerotic lesion area. In contrast, VSMC-specific TP deletion abolished and EC-specific TP deletion surprisingly reduced the ex vivo reactivity of aortic rings to the TP agonist U-46619, whereas VSMC-specific TP knockout also diminished the ex vivo response of aortic rings to Ang II. Furthermore, despite similar systemic blood pressure, there was a trend towards less atherogenesis in the aortic arch and a trend towards fewer pathological aortic alterations in Ang II-treated female TPVSMC KO/Ldlr KO mice. Survival was impaired in male mice after Ang II infusion and tended to be higher in TPVSMC KO/Ldlr KO mice than in TPWT/Ldlr KO littermates. Thus, our data may suggest a deleterious role of the TP expressed in VSMC in the pathogenesis of Ang II-induced aortic atherosclerosis in female mice, and a surprising role of the endothelial TP in TP-mediated aortic contraction. However, future studies are needed to substantiate and further elucidate the role of the vascular TP in the pathogenesis of Ang II-induced hypertension, aortic atherosclerosis and aneurysm formation.

Exploring the Iceberg: Detection and Management of Isolated Interrupted Aortic Arch and Associated Hypertension- A Rare Entity

Objectives: Prompt diagnosis and management of hypertension, particularly in younger patients, are crucial to reducing complications, mortality, and expenses. A thorough history and careful physical examination are key steps. This article illustrates one such unusual case that had a subtle presentation and went undiagnosed until it was brought to our attention.&#x0D; Methodology: A 30-year-old male patient with a history of fatigue, poor exercise tolerance, and mild headaches was diagnosed with hypertension. He was commenced on amlodipine and had no family history of cardiac diseases or secondary hypertension. The patient appeared weak and thin, with a BMI of 16.6 kg/m2. His radial pulse was regular and 98 bpm, and his brachial blood pressure was recorded at 190/90 mmHg. Further examination revealed weak lower limb pulses, a radio-femoral delay, and an ankle blood pressure of 100/60 mmHg. A 3/6 systolic murmur was noted at the aortic area. Routine laboratory investigations revealed a chest x-ray showing notching of the ribs and an absent aortic knob. A transthoracic echocardiogram was performed, but it did not provide conclusive results. A CT angiography of the chest revealed a complete interruption of the aorta just below the left subclavian artery in a "rat tail fashion." The aortic valve was normal, and no other aortic or cardiac pathology was found. The patient was diagnosed with IAA type A and surgical correction was suggested. Antihypertensive medication was given to achieve blood pressure control, and surgical correction was done involving end-to-end anastomosis. The patient's postoperative period was uneventful, and at four weeks, his symptoms subsided, and his blood pressure was 130/80 mmHg without antihypertensive medications.&#x0D; Results: The patient had an interrupted Aortic Arch type A and underwent treatment with antihypertensive medications and surgical correction. After a month, symptoms subsided, blood pressure was 130/80 mmHg, and pulses were bilaterally normal. Post-op CT Aortogram showed good anatomic continuity and no complications.&#x0D; Conclusion: Mild symptoms might only be the tip of an iceberg, calling for further exploration. IAA, despite its rarity, should be considered a potential cause of hypertension.

Comparative Reproducibility Analysis of Thoracic Aorta Morphometric Parameters According to Computed Tomography and Magnetic Resonance Angiography

Objective: to compare intra- and inter-operator reproducibility of thoracic aorta (ThAo) morphometric parameters, calculated by multislice computed tomography (MSCT) and magnetic resonance imaging (MRI).Material and methods. The prospective study included 20 patients with ascending aorta (AAo) dilatation (≥45 mm). All patients underwent MSCT- and MRI-angiography in electrocardiogram-gated mode. Mean diameter (Dmean) and cross-sectional area (CSA) were measured at different ThAo levels in the systole and diastole along the inner contour of the vessel. All measurements were performed by two radiologists. Each of them took measurements twice at an interval of at least 1 month. The reproducibility of repeated measurements was studied using intraclass correlation coefficient. Results. The analysis of the systolic frame revealed significant differences between the methodsfor measuring Dmean (MRI: 42.5 (41.0–47.8) mm; MSCT: 37.7 (34.7–40.3) mm; p = 0.003) and CSA at the level of the sinotubular junction (MRI: 14.8 (12.7–17.9) cm2; MSCT: 11.4 (10.3–13.3) cm2; p = 0.009), AAo CSA(MRI: 17.6 (14.6–20.8) cm2; MSCT: 19.6 (16.7–21.5) cm2; p = 0.035) and Dmean at the level proximal to left subclavian artery (LSA) (MRI: 31.5 (31.0–34.0) mm; MSCT: 31.7 (27.3–32.9) mm; p = 0.041). For the diastolic frame, significant differences between the methods were observed when measuring AAo CSA (MRI: 17.0 (14.5–19.7) cm2; MSCT: 19.7 (15.3–21.8) cm2; p = 0.025), Dmean (MRI: 30.5 (29.3–32.8) mm; MSCT: 29.8 (27.1–31.3) mm; p = 0.05) and CSA at the level proximal to LSA (MRI: 7.5 (6.9–7.9) cm2; MSCT: 7.4 (5.9–7.8) cm2; p = 0.007), as well as CSA at the left atrium level (MRI: 4.9 (4.2–5.0) cm2; MSCT: 5.1 (4.67–5.5) cm2; p = 0.042). For MSCT-angiography, good intra- and inter-operator reproducibility of measurements at all ThAo levels was obtained. For MRI-angiography, there was a strong intra- and interoperator variability in determining Dmean and CSA at the levels of aortic arch and descending aorta.Conclusion. Aortic cross-sectional area showed the best intra- and inter-operator reproducibility and comparability of measurements between MSCT- and MRI-angiography

In-vivo validation of a nomogram with isostiffness-lines for the assessment of aortic stenosis severity

Abstract Background In patients with low-flow, low-gradient aortic stenosis, the aortic valve opening area (AVA) projected at a higher standardized transvalvular flow (Q) is used to assess the severity of aortic stenosis. It assumes a linear relation between Q and AVA. We investigated whether a sigmoid function better captured this relation and whether a nomogram could be constructed. Methods We measured instantaneous AVA and Q in 142 patients with the whole spectrum of AS including very low-flow situation on one ejection cycle. We defined a linear and a sigmoid function containing hyperparameters as well as the relative stiffness. Using a k-fold cross validation algorithm, we first trained the hyperparameters of each function on the subgroup of patients with normal aortic valve. Using the obtained hyperparameters, we then fitted the relative stiffness for each of the patients with AS on the lowest 70%, 50%, 30% and 10% Q of the {Q:AVA} data points of the ejection cycle. We then assessed the accuracy of the two models by computing the mean squared error (MSE) of the predicted AVA vs the measured AVA on the remaining 30%, 50%, 70% and 90% data points and the Akaike Information Criterion (AIC). A receiver operating characteristic (ROC) analysis with computation of its area under the curve (AUC) was performed on the entire range of possible threshold of the relative stiffness to discriminate between severe from non severe aortic stenosis. Results The sigmoid consistently better predicted the remaining 70%, 50%, 30% and 10% AVA than the linear model (MSE: 6.62e-6 vs 14.11e-6, 4.90e-6 vs 12.39e-6, 4.90e-6 vs 14.84e-6, 4.90e-6 vs 22.99e-6; AIC: -7933 vs -7428, -13341 vs -12328, -13341 vs -16990, -13341 vs -21031, respectively). The first figure depicts the assessment of the AVA predicted with the linear (left panel) and sigmoid (right panel) model with Q of the 30% highest Q values with linear regression. The black line on the linear regression graphs represent the identity function (f (x) = x). The closer to this line are the points, the more accurate is the prediction. In the ROC analysis, the calculated AUC was 0.88, performed on all patients with relative stiffness obtained on the first 70% Q of the {Q;AVA} data points. The most discriminative relative stiffness threshold was 1.51 with a corresponding accuracy of 0.85. The second figure depicts a nomogram with mean and confidence interval of iso-stiffness lines for each severity with the following color code: group of normal aortic valve in green, group of mild aortic stenosis in blue, group of moderate aortic stenosis in orange and group of severe aortic stenosis in red. The iso-stiffness line with most discriminant relative stiffness computed on the group of patients with moderate and severe aortic stenosis is depicted in black. Conclusion This study allows to construct a nomogram to compare the stiffness of the aortic valve of any patient at any Q, simplifying the severity grading system of AS.Accuracy of AVA predictionNomogram with iso-stiffness lines

Feasibility of remote screening for high risk valve disease using a new wearable cardiac monitoring patch with synchronized phonocardiogram and electrocardiogram in communities

Abstract Background The 2010 census data showed that the weighted prevalence rate of valvular disease was 3.8% in China. For many elderly people, COVID-19 pandemic has caused the situation that they have not received medical examination for years. Since many patients with moderate aortic/mitral stenosis/regurgitation do not have significant symptoms, early detection of high-risk groups of valve disease is essential. A new wearable cardiac monitoring patch with synchronized phonocardiogram(PCG) and electrocardiogram(ECG) function is introduced in this study. Unlike handheld auscultation, it minimizes the interference of the environment and the operator, and is not demanding for the operator. Methods We enrolled 3170 patients of over 65 years old. Patients with diagnosed moderate or severe aortic/mitral stenosis/regurgitation, congenital heart disease, hypertrophic cardiomyopathy were excluded. Data acquisition was done by social workers following strict instructions. The patch was attached to the mitral and aortic auscultation area on the patients. ECG and PCG signals can be detected simultaneously and sent to a phone or tablet via Bluetooth. The data would then be auto-uploaded to a cloud-based center for further analysis. The end-to-end algorithm for S1 and S2 heart sounds detection involves a CNN-LSTM model for R-peak detection and a 1-D CNN-based U-Net model for fine-grained segmentation based on the detected heartbeat. The segmentation network takes multi-modal PCG and ECG signals as inputs and applies Contrastive Learning as a pretraining technique for enhancement to a real-world problem: detecting heart murmur from high-risk valve disease. If the results indicate positive, the patient is recommended by family doctors to do ultrasonic cardiogram (UCG) and seek further medical advice (Figure 1). Results 3170 participants were recruited from March 2022 to December 2022 in different communities of Huangpu District in Shanghai(Figure 2). In total, 43.98% were men, and 85.81% of age distribution were among 65-79 years. Among 3170 participants, 119(3.8%) were suspected positive by ECG and PCG. Among 119 patients, 65.55% were among 65-79 years. After telephone follow-up 29(24.3%) patients finished clinical visit and UCG. About 66% were diagnosed as mild aortic/mitral stenosis/regurgitation, 24% were diagnosed as moderate aortic/mitral stenosis/regurgitation, 10% were diagnosed as hypertrophic cardiomyopathy. Conclusions This study demonstrated the feasibility of remote screening for high risk valve disease using a new wearable cardiac monitoring patch in community visit by social workers with no medical background. This technology may improve the efficacy of clinical diagnosis and reduce unnecessary examination, particularly in the absence of doctors' auscultation and UCG. Unfortunately, three quarters of the suspected positive patients lost contact or refused to do UCG due to COVID-19 pandemic. Further investigations are necessary to increase accuracy.Flow chart of community screeningbaseline and disease distribution

Progression of different echocardiographic parameters of aortic stenosis have different clinical associations

Abstract Background Previous reports have described the risk factors for progression of aortic stenosis (AS). However, AS is recognized as a condition of the aortic valve and ventricle, and the AS marker chosen for the assessment of progression may influence the determinants of progression. Purpose To assess whether different clinical and demographic characteristics have a different impact on the progression of echocardiographic parameters on which stroke volume has a lesser (aortic valvular area [AVA], dimensionless severity index [DSI]) or greater influence (mean pressure gradient [MPG], or peak velocity [Vmax]). Methods Patients diagnosed with at least mild AS without an aortic valvular intervention identified from an echocardiographic database from January 1, 2009, to July 26, 2022, from a tertiary level hospital were included. AS progression models were evaluated using univariable and multivariable linear regression or mixed effects. AS severity was defined based on international guidelines. Results A total of 8,720 patients with at least mild AS were included and followed for up to 13.7 years. Multivariable mixed effects models identified important clinical predictors in understanding AS progression. After adjustment for relevant covariates, AVA decreased by 0.02 cm per year (95% CI: -0.025, -0.016, p&amp;lt;0.001), DSI decreased by 0.006 per year (95% CI: -0.008, -0.005), MPG increased by 0.962 mmHg per year (95% CI: 0.818, 1.107, p&amp;lt;0.001), Vmax increased by 6.742 cm/s per year (95% CI: 5.934, 7.549, p&amp;lt;0.001). Age, calcification, revascularisation, ejection fraction below 50%, and rheumatic heart disease, were the most consistent associations of progression of all echocardiographic parameters (Figure 1). Sex was associated with progression of AVA and DSI but not gradients. Changes in gradients (but not AVA and DSI) were associated with ischemic heart disease, chronic kidney disease, and atrial fibrillation or atrial flutter. Conclusion This longitudinal data analysis demonstrates differences in impact of baseline risk factors on AS progression on different echocardiographic parameters.Figure 1.Colour map of clinical predictors

Cardiac magnetic resonance hemodynamic force patterns in patients with ST-segment elevation myocardial infarction and dilated cardiomyopathy as compared to healthy controls: an observational study

Abstract Background Intraventricular Pressure Gradients (IVPG) reflect the driving force behind blood motion in and out of the left ventricle (LV). IVPG can be computed non-invasively using Cardiac Magnetic Resonance (CMR) cine imaging. It is unknown how IVPG components change as a consequence of ST-segment Elevation Myocardial Infarction (STEMI) and in non-ischemic Dilated Cardiomyopathy (DCM). Aims We aimed to assess if LV dysfunction of an ischemic and non-ischemic origin translates into reduced IVPG. The IVPG values were compared to conventional CMR markers of LV systolic function, to evaluate potential future applications. Methods This analysis of prospectively included cohorts included patients with DCM (n=40), anterior (n=20) or inferior STEMI (n=19) with an LV ejection fraction (EF) ≤ 52%, and healthy control subjects (n=13). LV ejection fraction was measured on the short-axis cine images. LV global longitudinal strain (GLS) and IVPG were measured in the long-axis cine images, using feature tracking software. Contours were drawn manually and the mitral and aortic valve orifice areas were measured. The dimensionless IVPG were measured in the longitudinal direction, using feature tracking combined with valve orifice measurements. IVPG consisted of the A, B, C, and D-wave, see Figure 1. IVPG values were compared between controls and diseased cohorts by the Mann Whitney U test. Results LVEF and LV-GLS were significantly impaired in all diseased groups. DCM and anterior STEMI patients had lower overall IVPG (15.1 [IQR 12.6-17.9] vs 9.4 [IQR 7.8-13.4], p=0.001 for DCM and 11.1 [IQR 8.7-13.0], p=0.002 for anterior STEMI). DCM and anterior STEMI patients had a significantly reduced systolic ejection A-wave (21.8 [IQR 19.1-27.2] in controls vs. 13.5 [IQR 10.3-19.1] in DCM, p&amp;lt;0.001, and 16.9 [IQR 10.8-20.6] in anterior STEMI, p=0.004). Secondly, patients with DCM and inferior STEMI have significantly dampened E-wave decelerative C-waves (8.1 [IQR 6.5-12.3] in controls, vs. 3.7 [IQR 2.4-5.5], p&amp;lt;0.001 in DCM, and 6.4 [IQR 4.3-7.8], p=0.04 in inferior STEMI), due to impaired passive ventricular filling. Conclusions IVPG values are altered in patients with myocardial dysfunction due to anterior and inferior STEMI to a lesser extent than in DCM patients. Conventional measures for systolic function (i.e. LV-GLS and LV ejection fraction) were lower in all diseased groups as well. On the other hand, IVPG is a promising measure to quantify diastolic LV function on the ventricular level.

Comorbidity is the driver of adverse outcomes in patients with moderate aortic stenosis

Abstract Background Recent studies showed moderate aortic stenosis (AS) was associated with adverse cardiovascular outcomes. Ongoing studies are addressing whether moderate AS may benefit from early transcatheter aortic valvular replacement (TAVR). However, a high comorbidity burden is common, and may be the main driver of poor outcomes. Purpose We aimed to identify clusters of patients with moderate AS based on comorbidity and echocardiographic profiles. Methods Unsupervised clustering algorithms (including K means, partition around medoids (PAM), hierarchical clustering, Density-Based Spatial Clustering of Applications with Noise (DBSCAN), and Hierarchical Density-Based SCAN (HDBSCAN)) of comorbidities, demographics and echocardiographic parameters were conducted in patients diagnosed with moderate AS [aortic valvular area (AVA) 1-1.5 cm2 or peak velocity (Vmax) 3-4 m/s or dimensionless severity index (DSI) 0.25-0.5]. Cumulative hazard plots and Cox proportional hazards regression models were used to assess the difference in time to cardiac death, heart failure hospitalization or aortic valvular intervention between the clusters. Results Four distinct clusters were identified AS patients (n=2,409) using PAM algorithm. The highest risk of cardiovascular outcomes was found among patients in Cluster 4 (Comorbid cluster), followed by Cluster 3 (Risk factors cluster), and Cluster 2 (Valve morphology cluster) (Table 1, Figure 1). Comparing cardiac death outcomes between patients treated with TAVR vs. no TAVR in each cluster revealed that TAVR was of most benefit in Cluster 2 (HR = 0.05, 95% CI: 0.01-0.34, p=0.002). Conclusions Multiple comorbidities are the key driver of worse outcomes in patients with moderate AS, which can affect treatment outcomes from TAVR. Thus, careful attention to the comorbidities is imperative in the management of patients with moderate AS.Table 1.Characteristics of 4 clustersFig 1.Cumulative Hazard Plot

Derivation and validation of risk score to predict mortality or heart failure-related hospitalisation based on clinical and echocardiographic factors in moderate or severe aortic stenosis

Abstract Background Multiple studies from echocardiographic databases have investigated association between moderate or severe aortic stenosis (AS) and poor cardiovascular outcomes. However, outcomes and treatment response are also dependent on the clinical picture. Purpose To improve prognostication and management response of patients with moderate or severe AS by development and validation of a new risk score algorithm that combines clinical and echocardiographic parameters to predict 5-year all-cause mortality or heart failure (HF)-related hospitalisation. Methods 3,452 consecutive patients diagnosed with moderate or severe AS [aortic valvular area &amp;lt;1.5 cm2, peak velocity &amp;gt; 3 m/s or dimensionless severity index &amp;lt; 1.5] were included in this observational cohort study. The least absolute shrinkage and selection operator (LASSO) and logistic regression was used to develop a risk score. This score provided an estimated probability of 5-year composite outcomes of all-cause mortality or HF-related hospitalisation in moderate or severe AS patients. The risk score was then validated with a geographically separate independent test cohort (n=1,788). Results Among 3,452 patients with at least moderate AS with median follow up of 7.3 years, 41 variables were important predictive parameters to be included in risk score (Figure 1). The most significant independent predictors were non-cardiac (Table 1). Areas under the receiver operating characteristic curves for the score were 0.80 (95% CI: 0.79-0.82) in the training set and 0.76 (95% CI: 0.73-0.80) in the test dataset, demonstrating good discrimination. Conclusions A risk score algorithm based on demographics, echocardiography, and clinical features was developed and validated with over 1000 patients. This risk score can be useful to predict outcomes beyond conventional echocardiographic parameters in patients with moderate or severe AS.Fig 1.Score vs 5-yr composite outcomesTable 1.OR for predictors in risk score

Long-term pulmonary iron oxide nanoparticles exposure disrupts hepatic iron-lipid homeostasis and increases plaque vulnerability in ApoE−/− mice

Iron oxide nanoparticles (Fe3O4 NPs) have attracted great attention due to their extensive applications, which warranted their environmental concerns. Although recent advances have proposed the relevance of Fe3O4 NPs to cardiovascular disease, the intrinsic mechanisms underlying the effects of NPs remain indistinct. ApoE−/− mice were chosen as a long-term exposure model to explore the immanent association between respiratory exposure to Fe3O4 NPs and the development of cardiovascular diseases. Pulmonary exposure to 20 nm and 200 nm Fe3O4 NPS resulted in significant lung injury, and pulmonary histopathological examination displayed inflammatory cell infiltration, septal thickening and alveolar congestion. Intriguingly, liver iron deposition and variations in the hepatic lipid homeostasis were found in Fe3O4 NPs-exposed mice, eventually leading to dyslipidemia, hinting the potential cardiovascular toxicity of Fe3O4 NPs. In addition, we not only found that Fe3O4 NPs exposure increased aortic plaque area, but also increased M1 macrophages in the plaque, which yielding plaque vulnerability in ApoE−/− mice Of note, 20 nm Fe3O4 NPs showed enhanced capability on the progression of atherosclerosis than 200 nm Fe3O4 NPs. This study may propose the potential mechanism for adverse cardiovascular disease induced by Fe3O4 NPs and provide convincing evidence for the safety evaluation of Fe3O4 NPs.

Abstract 18861: Therapeutic Targeting of Rpl13a -Small Nucleolar RNAs Mitigates Atherosclerosis in Apoe -/- Mice

Specific non-coding, small nucleolar (sno) RNAs encoded within introns of the Rpl13a gene elevate cellular levels of reactive oxygen species (ROS), and ROS are known to aggravate atherosclerosis (athero). We found that genetic deficiency of Rpl13a -snoRNAs reduces brachiocephalic artery athero in Apoe -/- mice by 50%. We therefore tested the hypothesis that athero could be reduced by acute pharmacologic intervention targeting Rpl13a -snoRNAs in Apoe -/- mice. To that end, we injected male and female Apoe -/- mice subcutaneously with 48 mg/kg antisense oligonucleotides (ASOs) targeting (a) the four Rpl13a -snoRNAs (ASO-snoRNA), or (b) green fluorescent protein (ASO-control). We tested two distinct strategies: ( i ) preventive, in which ASO injections and Western diet were started in 10-wk-old mice, with 4 weekly and 5 bi-weekly ASO treatments over 14 wk, then sacrifice; and ( ii ) “therapeutic,” in which ASO injections were started in 24-wk-old mice that had been fed Western diet for 14 wk and then were continued on Western diet with 6 weekly ASO treatments and then sacrificed. ASO injections were administered as indicated until 1 wk prior to sacrifice. Compared with saline-injected mice, ASO-control and ASO-snoRNA showed no hepatotoxicity (as assessed by serum ALT and AST). Compared with ASO-control, ASO-snoRNA administration for 6 wk reduced Rpl13a -snoRNA levels in the aorta and spleen by 54-80% for snoRNAs U32a , U33 , and U34 (RT-qPCR). In the “therapeutic” cohort, brachiocephalic artery cross-sectional athero was reduced by 38% in ASO-snoRNA-treated as compared with ASO-control-treated mice (n=7/group, p &lt;0.03). Additionally, male ASO-snoRNA-treated mice exhibited a 98.1% decrease in circulating IL1-β transcripts (n=6-8/group, p&lt;0.003). In the “preventive” cohort, aortic athero was reduced by 40% (13±5 vs 7±3 % aortic lesion area, n= 11-13/group, p &lt;0.02) in ASO-snoRNA-treated as compared with ASO-control-treated mice. We conclude that therapeutic targeting of Rpl13a -snoRNAs with ASOs mitigates athero, both during the early and later stages of atherogenesis.

Abstract 16995: Distensibility and Aortic Growth Rate Predict Type B Aortic Dissection in Marfan Syndrome

Introduction: Marfan syndrome (MFS) is associated with high aortic growth rate (GR) and incidence of aortic dissection (AD), including delayed type B AD (TBAD) after prophylactic root repair. Elevated aortic stiffness has been investigated as a biomarker in MFS, but it remains uncertain how stiffness relates to GR and risk of AD. Vascular deformation mapping (VDM) is a technique that uses clinical CT angiography (CTA) to yield accurate, 3D maps of aortic growth over surveillance (VDM-G). This technique can also be used to assess aortic stiffness via quantification of cyclic wall stretch between systole and diastole (VDM-D) using multi-phasic dynamic CTA. Research Question: Is distensibility of the descending thoracic aorta associated with aortic GR or development of TBAD in MFS patients? Goal: The aim of this study was to analyze stiffness of the descending thoracic aorta in MFS and its association with aortic GR and occurrence of TBAD. Methods: We identified 36 adult MFS patients with dynamic CTA studies (&gt;1 year interval) between 2004-2020. Growth was quantified by VDM-G, and linearized descending aortic stiffness by VDM-D - via calculation of distensibility - as the ratio of cyclic aortic surface area change (AR) over pulse pressure [(AR-1)/PP]. Results: Patients were 38.9 ± 12.1 years old, 58% were male and 25 (69%) had prior ascending repair. Mean CT follow-up interval was 5.7 ± 3.4 years and 8 developed TBAD during follow-up with pre-dissection diameter of 31.12 ± 6.01 mm at tear location. Age (β -0.4, 95%CI: -0.07, -0.01, p=0.015) and baseline diameter (β 0.10, 95%CI: 0.02, 0.18, p=0.017 ) independently predicted GR on multivariable analysis, but distensibility did not (p=0.38). Both distensibility (OR 0.02, 95% CI: 0.00, 0.68, p=0.03) and GR (OR 8687.05, 95% CI: 1.43, 5x10^7, p=0.04) were independent predictors of TBAD during follow-up, but diameter was not (p=0.49). Conclusion: Aortic stiffness and growth rate are likely predictors of type B aortic dissection in MFS.

Abstract 15025: Impact of Type of Transcatheter Heart Valve and Anatomic Features on Complexity of Percutaneous Coronary Intervention in Patients After Transcatheter Aortic Valve Replacement

Introduction: Approximately half of the patients with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) present with concomitant coronary artery disease (CAD). Percutaneous coronary intervention (PCI) after TAVR is gaining increasing importance. Consequently, we investigated the factors that influence PCI procedures in patients following TAVR. Methods: We included consecutive 633 patients with severe aortic stenosis who underwent TAVR at our institution from 2016-2022. The primary endpoint was the time from puncture to initial coronary angiography. Results: The median age was 84 (81 - 87) years old, 39% were male, and 173 (27.3%) had concomitant coronary artery disease. Of these, 39 (22.2%) were treated conservatively, 22 (12.5%) underwent coronary artery bypass and TAVR, 64 (36.5%) underwent PCI before TAVR, and 46 (26.2%) underwent PCI after TAVR. The success rate of PCI after TAVR was 100% for both types of valves. The median initial angiography time from puncture was 16.2 minutes (10.6 - 29.1), significantly longer in the Self-expandable valve (SEV) group [22.0 minutes (14.1 - 59.2)] compared to the Balloon-expandable (BEV) group [14.9 minutes (8.1 - 21.1)] (p = 0.026). PCI to the right coronary artery [29.0 min (17.2 - 49.5)] took significantly longer than PCI to the left coronary artery [14.0 min (8.0 - 18.1)] (p = 0.001). Conversely, there was no significant association with CT measurements such as aortic angle, annulus area, coronary height, or valve size, and transcatheter heart valve size (p &gt; 0.05). Factors that predicted difficulty in engaging coronary arteries (&gt;30 min from puncture to first contrast) were SEV [odds ratio 6.4, 95% confidence interval (1.2 - 38.2), p = 0.024], RCA [odds ratio 6.0, 95% confidence interval (1.3 - 33.4), p = 0.020]. Conclusions: Despite the high completion rate of PCI after TAVR, the use of SEV and the approach to the right coronary artery can pose challenges.

Influence of moderate prosthesis–patient mismatch on long-term outcomes in patients with severe aortic stenosis with paradoxically reduced gradients against the background of reduced stroke volume after aortic valve replacement with a biological prosthesis: retrospective comparative study

OBJECTIVE: Our aim was to evaluate the impact of moderate prosthesispatient mismatch on long-term results after aortic valve replacement in patients with severe aortic stenosis with paradoxically reduced gradients against the background of a reduced stroke volume of the left ventricle.&#x0D; MATERIALS AND METHODS: We analyzed data from 88 patients with symptomatic severe aortic stenosis meeting the criteria: paradoxically reduced gradients against the background of a reduced stroke volume of the left ventricle. Patients were divided into 2 groups: Group 1 (n=42, mean age 674 years) with paradoxically reduced gradients against the background of reduced stroke volume of the left ventricle, with a moderate patientprosthesis mismatch; Group 2 (n=46, mean age 686 years) with paradoxically reduced gradients against the background of reduced stroke volume of the left ventricle, without patientprosthesis discrepancy. All patients underwent transthoracic echocardiographic evaluation.&#x0D; RESULTS: The average follow-up period was 84 (quarterly interval 7598) months, during the follow-up period 35 (40%) deaths were registered. There were no significant differences in in-hospital mortality: 2 (4.7%) and 2 (4.3%), respectively (p=0.2). In the long-term follow-up period, there was a significant difference in survival and hospitalization rates for exacerbation of heart failure between patients with and without patientprosthesis mismatch: 46 and 71%, 37 and 72%, respectively (p0.001). In the long-term follow-up period, patients with patientprosthesis mismatch showed a trend towards slower regression of left ventricle mass and left atrial volume, as well as a slower recovery of global longitudinal deformation of the left ventricle and exercise tolerance compared with patients without patientprosthesis mismatch. There were no significant differences in the incidence of stroke (90% and 91%; p=0.7). According to the results of Cox regression, the left ventricular stroke volume index and the aortic valve effective orifice area index were independent predictors of lethal events and the risk of hospitalization for exacerbation of heart failure.&#x0D; CONCLUSION: Moderate patientprosthesis mismatch in patients with paradoxically reduced gradients associated with reduced left ventricular stroke volume is independently associated with increased mortality and increased hospitalization for exacerbations of heart failure.

Impact of Variation in Commissural Angle between Fused Leaflets in the Functionally Bicuspid Aortic Valve on Hemodynamics and Tissue Biomechanics.

In subjects with functionally bicuspid aortic valves (BAVs) with fusion between the coronary leaflets, there is a natural variation of the commissural angle. What is not fully understood is how this variation influences the hemodynamics and tissue biomechanics. These variables may influence valvar durability and function, both in the native valve and following repair, and influence ongoing aortic dilation. A 3D aortic valvar model was reconstructed from a patient with a normal trileaflet aortic valve using cardiac magnetic resonance (CMR) imaging. Fluid-structure interaction (FSI) simulations were used to compare the effects of the varying commissural angles between the non-coronary with its adjacent coronary leaflet. The results showed that the BAV with very asymmetric commissures (120∘ degree commissural angle) reduces the aortic opening area during peak systole and with a jet that impacts on the right posterior wall proximally of the ascending aorta, giving rise to elevated wall shear stress. This manifests in a shear layer with a retrograde flow and strong swirling towards the fused leaflet side. In contrast, a more symmetrical commissural angle (180∘ degree commissural angle) reduces the jet impact on the posterior wall and leads to a linear decrease in stress and strain levels in the non-fused non-coronary leaflet. These findings highlight the importance of considering the commissural angle in the progression of aortic valvar stenosis, the regional distribution of stresses and strain levels experienced by the leaflets which may predispose to valvar deterioration, and progression in thoracic aortic dilation in patients with functionally bicuspid aortic valves. Understanding the hemodynamics and biomechanics of the functionally bicuspid aortic valve and its variation in structure may provide insight into predicting the risk of aortic valve dysfunction and thoracic aortic dilation, which could inform clinical decision making and potentially lead to improved aortic valvar surgical outcomes.