Aortic Growth Research Articles (Page 1)

Abdominal aortic aneurysm (AAA) rupture remains a significant cause of morbidity and mortality, but predictors of continued growth and rupture risk remain limited. The aim of this study was to investigate the relationship between abdominal aortic calcification and AAA growth via a secondary cohort analysis of the Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA3CT), a prospective multicenter randomized study. Arterial calcification Agatston scores and maximum transverse diameter were measured in non-contrast computed tomography (CT) scans in patients enrolled in N-TA3CT. Uni- and multi-variable linear regression were used to assess the association of anatomic calcium burden and comorbid conditions with rate of aneurysm growth. Of the 261 randomized patients in the trial, 136 patients met inclusion criteria for analysis. On univariable analysis, baseline calcium score at all assessed anatomic locations- the superior mesenteric artery (spearman correlation coefficient (SCC) -0.20, p = 0.0176), renal artery (-0.22, p = 0.0120, infrarenal aorta (-0.26, p = 0.0020), common iliac artery (-0.19, p = 0.024), external iliac artery (-0.26, p = 0.003), and sum of all measured sites (-0.28, p = 0.001)- was significantly associated with lower AAA diameter growth rates. Of individually measured sites, baseline infrarenal aortic calcification had the strongest negative association with aneurysm growth. Interestingly, infrarenal calcium score was not significantly associated with baseline aneurysm diameter (R2 0.0001, spearman correlation p = 0.94), or diabetes status (p = 0.59). In a multivariable regression model, factors significantly associated with faster diameter growth included baseline volume and current tobacco use. Factors associated with reduced growth rate included diabetes and baseline infrarenal aorta calcium score thereby establishing aneurysmal calcification as a marker for slower aneurysm growth.

Marfan syndrome is an inherited disorder caused by FBN1 gene mutations, which can lead to thoracic aortic aneurysm and dissection. Selective AT1 (angiotensin II type 1) receptor blockade is a preventive option against Marfan syndrome aortopathy, and recent clinical studies demonstrated that the inhibitory effect of an ARB (AT1 receptor blocker) losartan on aortic aneurysm growth is equivalent to that of β-blockers. At present, several ARBs are clinically available, and they have drug-specific differences in pharmacological properties. Especially, inverse agonism of ARBs has potential benefits for cardiovascular protection, but its impact on Marfan syndrome aortopathy remains poorly understood. Candesartan-7H is a candesartan derivative that lacks the carboxyl group critical for inverse agonist activity and works as a neutral antagonist for the AT1 receptor. Candesartan cilexetil (1 mg/kg per day), candesartan-7H (1 or 20 mg/kg per day), or vehicle was administered to Fbn1C1041G/+ mice, and aortic dilatation was analyzed using echocardiography, histological staining, and in situ MMP (matrix metalloproteinase) assay. Activation of TGF-β (transforming growth factor β) signaling and mechanosensitive signaling was studied using Western blot and immunohistochemical analysis. Candesartan cilexetil (1 mg/kg per day) and candesartan-7H (20 mg/kg per day) lowered blood pressures equally in Fbn1C1041G/+ mice. Progressive dilatation of the aorta in association with aortic wall thickening, degeneration of elastic fibers, deposition of collagen, MMP activation, and TGF-β signaling activation in Fbn1C1041G/+ mice was significantly suppressed by treatment with candesartan cilexetil (1 mg/kg per day), but not by candesartan-7H, even at 20 mg/kg per day. In addition, candesartan cilexetil, but not candesartan-7H, suppressed activation of mechanosensitive signaling involving focal adhesion kinase, p38 mitogen-activated protein kinase, and early growth response-1 in the ascending aorta of Fbn1C1041G/+ mice. Our findings support a crucial role of inverse agonist activity of ARB for the prevention of mechanical stress-induced AT1 receptor activation and aortic aneurysm progression in Marfan syndrome mice.

Background: Predicting ascending aortic growth remains challenging, with few robust clinical predictors beyond known genetic aortopathies. Most current models assume linear growth and assess change over the longest available imaging interval. While convenient, these methods may miss plausible non-linear relationships between size and growth, especially in the context of known compensatory wall remodeling. Research question: Are there non-linear associations between baseline ascending aortic diameter—indexed for body size, age, and sex—and future aortic growth? Methods: We conducted a single-center, retrospective study of patients with ≥2 chest CT/MR angiograms and double-oblique measurements of the mid-ascending aorta. Z-scores normalized aortic diameter by sex, age, and body surface area. Generalized Additive Models (GAMs) with smoothing splines were used to predict aortic growth based on baseline characteristics (maximal diameter, demographics, and clinical risk factors including hypertension, smoking status, and Marfan syndrome). Results: Among 3,349 patients (11,840 scans; 15,103 person-years of follow-up), mean age was 61 ± 13 years; 68% were male; 85% had hypertension; and 2.6% had Marfan syndrome. Both linear models and initial GAMs using clinical variables showed limited predictive power (R2 < 0.01). However, baseline Z-score exhibited a significant non-linear relationship with future growth (Figure 1), with two inflection points (arrows): one below Z = 0 (~36 mm) and another above Z = 5 (~49 mm). This relationship persisted after excluding patients with known genetic aortopathy. Conclusion: Indexed baseline aortic size is non-linearly associated with future ascending aortic growth rate, likely in a quadratic fashion. While accelerated growth was observed above surgical thresholds (Z > 5, diameter > ~49 mm), fast growth also occurred at “normal” aortic sizes (Z < 0, diameter < ~36 mm), a range that accounts for ~1/3 of type A dissections. These findings highlight both the indolent nature of mild-moderate dilation (Z = +2–+5) and the shortcomings of current surveillance strategies, which often overlook patients with rapid growth at non-dilated sizes—underscoring the need for non-size-based risk metrics such as aortic shape, wall biology, and genetics.

Background: Type B aortic dissection (TBAD) occurs when a tear develops in the intimal layer of the descending aorta. Aortic expansion remains a major factor limiting acuate uncomplicated TBAD patients’ survival outcomes. Accurately predicting aortic diameter growth may guide the selection of optimal treatment strategies on a patient-specific basis, improving patient survival. We developed a voxel-based statistical shape modeling (SSM) approach for complex, multi-label TBAD anatomies and hypothesized that the extracted shape features could predict aortic growth. Methods: 55 clinical CT scans from 22 patients at diagnosis and follow-up were obtained. The true and false lumens, dissection flap, fenestrations, and thrombus were segmented from the CT images. Each patient’s geometry included three anatomical components: (1) true and false lumens represented by voxel segmentations, (2) thrombus modeled with a voxel grid within the false lumen, and (3) fenestrations mapped onto a surface pixel grid of the dissection flap. This representation enabled construction of three independent statistical shape models (SSMs) for the individual components. Principal component analysis was applied to each component after converting the voxel- and pixel-based representations into continuous forms. The resulting SSM-derived shape features were used to predict aortic diameter growth rates via linear regression with leave-one-out (LOO) cross-validation. Results: The first eight SSM shape modes from each of the true and false lumen, thrombus, and fenestration models explained 88%, 92%, and 66% of shape variation, respectively. Figure (A) shows the mean TBAD shape and the first mode of variation from each SSM. These anatomical shape features derived from the SSMs were used to predict aortic growth rates using linear regression. Fig. (B) shows the actual versus predicted growth rates from leave-one-out cross-validation. The results demonstrated a root mean square error (RMSE) of 1.29 mm, with 87.5% of the predicted growth rates falling within one standard deviation of the actual growth rates. Conclusion: The novel voxel-based shape representation enabled the construction of independent SSMs for distinct anatomical components of TBAD, allowing for detailed modeling of complex shape features. The combination of SSM-derived shape features from voxel-based representations with linear regression presents a promising strategy for predicting aortic growth rates.

Introduction: Hemodynamics and wall biomechanics jointly drive ascending-aortic remodeling in bicuspid aortic valve (BAV) disease, yet most in silico studies model only flow or strain. Manual segmentations yield noisy meshes, impeding strain and computational fluid dynamics (CFD) analyses. We present an end-to-end framework integrating patient-specific CFD and dynamic strain mapping via our Bayesian remeshing algorithm, preserving geometry and eliminating manual mesh edits. Objective: Develop and validate an end-to-end approach to automate mesh generation, quantify surface strain, and enable strain mapping and patient-specific CFD in ascending aortas of normal and bicuspid aortic valves. Methods: We retrospectively analyzed 12 ECG-gated 4D CT datasets from 11 adults in a BAV study. Two observers performed semi-automated segmentation in ITK-SNAP using manual annotation, random forest voxel classification, and contour evolution; interobserver agreement—Dice coefficient, mean surface distance (MSD)—is reported as median [IQR]. Segmentations were converted to surface meshes and remeshed via a Bayesian adaptive algorithm. A reference mesh was propagated across cardiac phases using deformable registration; registration accuracy was assessed by MSD against meshes from manual segmentations. Areal strain was computed as fractional area change from end-diastole (Figure 1). Transient-dynamic CFD was performed on three patients to simulate flow and wall shear stress (WSS); aortic growth, reported in Figure 2, was derived from follow-up CT-based maximum diameters. Results: Table 1 summarizes patient characteristics. Manual segmentations showed strong interobserver agreement (Dice 0.96 [0.95–0.99]; MSD 0.45 mm [0.17–0.70]). Propagated meshes had a median MSD of 0.42 mm [IQR 0.34–0.74] (n = 24) against manual references. Peak areal strain ranged 7–23%, and WSS 2–6 Pa. Figure 2 shows strain and WSS maps for two representative BAV cases. In these cases, lower peak WSS/velocity coincided with faster radial growth over subsequent scans, mirroring inverse WSS-growth trends seen in larger BAV cohorts. Conclusions: Our 4D CT workflow produces spatially aligned WSS and areal-strain maps, without manual mesh edits. Preliminary results suggest higher peak WSS may be negatively associated with aortic growth rate, consistent with prior studies. This proof-of-concept demonstrates technical feasibility and motivates further study of WSS-strain interaction as a predictor of BAV aortic remodeling.

Background: Imaging surveillance for ascending thoracic aortic aneurysm (aTAA) relies on serial diameter measurements to guide management. However, measurement variability can lead to uncertain growth assessments and inaccurate risk stratification. Research Question: What is the prevalence and stability of distinct growth trajectories among patients with ascending aortic dilation undergoing routine surveillance? Methods: Single-center, retrospective study of 3,363 patients with ≥2 chest CT/MR angiograms. Latent Profile Analysis (LPA), an unsupervised clustering technique, was applied to double-oblique measurements of the mid-ascending aorta to classify growth trajectories based on each patient’s first 3 scans (“Early” n=1997) and first 5 scans (“Extended” n=757). We analyzed patient characteristics, outcomes (i.e., TAAD, repair) and rates of growth re-classification. Results: Median surveillance was 3.5 years, and the median aortic growth rate was 0.08 mm/y. Only 1.1% of patients met guideline criteria for repair based on growth rate alone. LPA at the Early time-point (3-scans) identified 4 classes: Stable (74%, median 0.05 mm/y), Growth (23%, median 0.58 mm/y), Dramatic Growth (2%, median 2.0 mm/y), and Non-physiologic (1%). For those at Extended surveillance, growth re-classification was observed in 38% of patients ( Figure 1 ). The Non-physiologic (noise-predominant) class grew from 1.3% to 8.3% between Early and Extended timepoints (p<0.001), with 59% originating from the Early Stable group. Most of the population was Stable at 5-scans, with this subgroup composed of 81% Stable and 18% Growth from the 3-scan time point. The Dramatic Growth class had smaller baseline diameters than the Stable class (34.0 vs 41.0 mm, p<0.001). Re-classification from Stable to Dramatic Growth was rare (<0.3%) and associated with Marfan syndrome (p=0.006). Among the patients that experienced type A dissection, the median pre-dissection diameter was 42.0 mm and 50% had been classified as Stable. Conclusion: A large majority of patients with ascending aortic dilation have indolent disease and outside of heritable causes, extended surveillance shows little added value for identifying those with rapid growth or at risk for type A dissection. Our findings raise question of the utility of life-long imaging surveillance for initially stable patients who are far from repair size thresholds and without high-risk features.

Ascending aortic dilation is monitored with serial imaging, yet event rates are low, with type A dissections often occurring at non-surgical sizes. We aimed to characterize ascending aortic growth trajectories in a real-world population to understand their clinical consequences and better inform surveillance strategies. We conducted a retrospective, single-center study of adults with ≥2 thoracic CTA/MRA examinations. Mid-ascending diameters from clinical reports were used to analyze real-world surveillance effectiveness. Growth trajectories were clustered using latent profile analysis (LPA). Early (first 3 scans; n= 1,997) and Extended (first 5 scans; n= 757) LPA models each yielded four classes: Stable, Growth, Dramatic Growth and Fluctuation (an unstable trajectory attributed to measurement noise). We studied 3,363 adults (median age 62 years; 68% men). Stable class was most common (74 % Early; 70 % Extended); Growth and Dramatic Growth classes comprised 23% and 2% respectively. Only 1.1% met guideline growth-based criteria for repair, and this subgroup had smaller baseline diameters (37.0 mm vs. 40.3 mm, p=0.009). At Extended follow-up, 80% of those initially Stable remained Stable. Reclassification into a Growth class was associated with younger age and Marfan syndrome (50.0% vs 3.0%, p=0.006). Acute type A dissection was rare (0.45%) and not clearly linked to any trajectory. Most patients with a dilated ascending aorta show negligible growth and low complication rates during routine surveillance. Repeated imaging beyond 3 scans may amplify uncertainty without clear improvements in risk stratification, suggesting that imaging surveillance may be safely de-escalated for stable patients.

The aorta, the largest artery in the body, exhibits anisotropy and heterogeneity along its length. Over the past several decades, researchers have characterized the positional differences in various geometric and mechanical properties such as wall thickness, diameter, extracellular matrix composition, mechanical properties, opening angle, and axial stretch. These regional adaptations arise in response to various biochemical and mechanobiological stimuli helping the vessel maintain efficient and resilient blood flow. Early studies, often limited to canine models and uniaxial testing, laid the groundwork for recognizing how composition and mechanics vary with location. Subsequent efforts broadened into comprehensive investigations that included parameters such as wall thickness, diameter, opening angle, and axial stretch, employing diverse animal models and, more recently, human samples. Technological advances in experimental and computational methods have deepened our understanding of these spatial variations, underscoring the aorta?s critical role in overall cardiovascular function and its vulnerability to conditions like aneurysms and atherosclerosis. This review seeks to consolidate and interpret these diverse studies on region-specific geometry and mechanics of the aorta, examining how spatial variations arise and how they support normal circulatory function. Further, we argue that any model of aortic growth and remodeling in disease should be able to predict the observed property variation with position in healthy individuals.

The role of doxycycline in reducing MMP-9 and acute-phase reactants to limit abdominal aortic aneurysm growth: A systematic review.

Artificial intelligence (AI) and machine learning (ML) are emerging tools in the management of abdominal aortic aneurysms (AAA). They have offered new tools to develop advanced imaging analysis and prediction models. This narrative review summarizes studies exploring AI/ML models to evaluate the risk of AAA growth and rupture. We provide an overview and critical analysis on methodology used, identify current limits and propose future directions for research and implementation in surgical practice.

Aortic luminal contrast attenuation varies with dissection morphology and is associated with need for intervention.

Background—Predicting ascending aortic (AsAo) growth is challenging. Conventional paradigms often assume a linear and monotonic relationship between baseline size and future growth that occurs continuously–assumptions that may oversimplify biology-driven disease progression. We first evaluated whether body size–indexed baseline AsAo diameter shows a non-linear association with subsequent growth at the population-level, and second whether patient-level growth trajectories are predominantly continuous or episodic.Methods—We performed a single-center, retrospective study (2012–2024). The Primary Cohort (n=3,315; ≥2 CT/MR scans) was used to model the relationship between baseline indexed AsAo size (Z-score) and subsequent annualized growth using multivariable linear regression and generalized additive models (GAMs), adjusting for clinical covariates. A Sub-Cohort (n=1,055; ≥4 scans) was used to classify longitudinal phenotypes as: Stable (Total Growth <2.0 mm), Stable-with-Noise (Total Growth <2.0 mm with alternating small changes), Continuous Growth (Total Growth ≥2.0 mm without a qualifying event), or Discontinuous/Episodic Growth (Total Growth ≥2.0 mm with ≥1 “growth event”). A growth event was defined as a diameter increase ≥2.0 mm within a single imaging interval or across two adjacent intervals (combined 0.5–5 years).Results—In the Primary Cohort, baseline Z-score demonstrated a significant non-linear (U-shaped) association with subsequent growth in the GAM (p<0.001), with higher growth at both small (Z<0) and severely dilated (Z>5) sizes. In the Sub-Cohort examining growth trajectory, the distribution was: Stable: 50.4% (532/1,055), Stable-with-Noise: 21.6% (228/1,055), Continuous: 5.4% (57/1,055), and Discontinuous/Episodic 22.6% (238/1,055). Among patients with measurable growth (Total Growth ≥2.0 mm, n=295), 81%(n=238) exhibited episodic growth and 58.3% (172/295) had a non-dilated baseline aorta (Z<2). Group differences (e.g., younger age and smaller baseline Z-scores in the Growth vs. Stable groups) were consistent across sensitivity analyses.Conclusions—AsAo growth is not well described by linear, continuous assumptions. Baseline size relates to future growth in a non-linear (U-shaped) manner, and nearly one-quarter of patients exhibit discrete growth bursts separated by periods of quiescence, with episodic behavior dominating among those who enlarge. These findings support a punctuated growth paradigm and argue for re-examining surveillance intervals, risk communication, and threshold-based decision pathways in thoracic aortic disease.

This review summarizes mechanistic, preclinical, and emerging clinical evidence on whether glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) may modify aortic disorders. In addition to metabolic effects, GLP-1 RAs have anti-inflammatory, antioxidant, and antiatherogenic properties and reduce major cardiovascular events in large trials. Since inflammation and extracellular matrix remodeling contribute to aortic valve calcification, root dilation, aneurysm growth, and aorto-occlusive disease, GLP-1 RAs may offer a unified therapeutic approach. A narrative review was performed using animal studies, population data, and cardiovascular outcome trials published up to May 2025, focusing on mechanisms, disease outcomes, and translational gaps. In vitro and rodent studies show that GLP-1 RAs inhibit IL-1β, TNF-α, and matrix metalloproteinases, preserve elastin structure, and promote M2 macrophage activity, slowing both thoracic and abdominal aneurysm growth. Similar antiosteogenic signaling may reduce valve calcification, though clinical validation is lacking. Observational data and post hoc analyses report fewer adverse limb events and improved walking distance in peripheral artery disease, suggesting benefit in aorto-occlusive syndromes. However, evidence for aortic regurgitation is currently absent. Overall, mechanistic and early clinical findings support GLP-1 RAs as potential disease-modifying agents along the aortic tree. Further imaging-based studies in calcific valve disease and aneurysms and trials focused on peripheral artery disease are now warranted. If confirmed, these agents could extend their benefits beyond metabolic disease to patients at risk of serious aortic complications.

Abdominal aortic aneurysm growth profiles over time: Prognostic implications and biological insights.

Data on cardiovascular outcomes and aortic growth in pregnant women with Turner syndrome is limited. We examine the cardiovascular and pregnancy outcomes in these women and analyze aortic growth throughout pregnancy. The ROPAC III is a global, prospective, observational registry that enrolled pregnancies of women pre-pregnancy known with Turner syndrome from 2018 to 2023. We compared baseline characteristics and outcomes between women at low and moderate-to-high risk of aortic events and between women with a pregnancy conceived with assisted reproductive technology (ART) and those who conceived spontaneously. Linear mixed models were used to analyze aortic growth with the examinations and aortic diameter as independent and dependent variable, respectively, and random effects were used to account for repeated measurements. In total, 47 pregnancies were included, of which 49% were classified as moderate-to-high risk (bicuspid aortic valve, aortic dilatation and/or hypertension), and 60% occurred after ART. No maternal mortality or dissection occurred during or after pregnancy. Hypertensive disorders occurred in 26%. No differences in pregnancy outcomes were found when comparing the risk groups, but women who conceived after ART were delivered by Cesarean section more often (65% vs 42%; p=0.011) and had earlier deliveries (38 vs. 39 weeks; p=0.010) compared to women with a spontaneous conception. We observed a significant aortic growth at the sinus of Valsalva during pregnancy, however, aortic diameters during a median follow-up of seven months were not different from pre-pregnancy diameters. Pregnancy outcomes in women known with Turner syndrome are better than reported before. While aortic dilatation may occur during pregnancy, it appears reversible postpartum. Attention for hypertension remains warranted.

Thoracic aortic aneurysms (TAAs) are worrisome for their propensity to dissect. Previous studies have demonstrated the potential benefits of statin use, particularly with slowing aortic aneurysm growth. The aim of this meta-analysis was to consolidate existing research to ascertain if statins effectively reduce TAA growth. Multiple databases were searched to identify studies assessing TAA growth in patients on statins (cases) and those not on statins (controls). The primary outcome was TAA (ascending/ aortic arch) growth rate per year. Standard mean difference (SMD) and 95% confidence intervals (95% CI) were estimated with a random-effects model using the inverse-variance technique. We assigned I2>50% as an indicator of statistical heterogeneity. P-value <0.05 was considered significant. Data analysis was performed using SPSS v.25.0. Four studies comprising 757 cases (male 64%, mean age 65±14 years) and 1,696 controls (male 62%, mean age 61±18 years) were included. The baseline diameters of TAA for cases and controls were 40.35±8.75 mm and 42.39±12.60 mm, respectively. Pooled results suggested statins to be associated with slower growth of TAAs with pooled SMD -0.70 mm/year [95% CI (-1.23 - -0.16); p=0.01]. Heterogeneity statistics among 4 studies was 95%. This pooled meta-analysis showed statins as associated with slower growth of TAAs. However, given the heterogeneity of the included studies in this meta-analysis, results should be interpreted with caution.

Pharmacological interventions to inhibit the progression of aortic aneurysm (AA) have not yet been established. We previously reported that mesenchymal stem cells (MSCs) provide a potential foundation for less invasive treatment of AA. In this study, we investigated the secretory proteins from MSC supernatants to clarify the therapeutic effects of MSCs. Furthermore, we treated thoracoabdominal aortic aneurysm (TAAA) mice with two anti-inflammatory proteins from among these secretory proteins to confirm their therapeutic effects. Protein profiles of MSC-secreted factors were analyzed using protein microarrays, and two anti-inflammatory proteins, namely progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI), were identified. Apolipoprotein E-deficient mice were continuously infused with angiotensin II via an osmotic pump for 4weeks to induce TAAA formation, and then recombinant rPGRN and/or rSLPI were administered intraperitoneally. Mice were sacrificed at 8weeks, and aortas were analyzed for protein expression and also stained with Elastica van Gieson and immunofluorescence to detect inflammatory cells. Intraperitoneal administration of rSLPI inhibited TAAA growth more than rPGRN alone or the combination of rPGRN and rSLPI, by inducing the following effects: downregulation of inflammatory cytokines and chemokines, specifically IL-1β, IL-6, TNF-α, and MCP-1; reduced NO production; decreased phosphorylated NF-κB levels; and decreased elastin destruction and infiltration of inflammatory cells. We identified anti-inflammatory proteins, including PGRN and SLPI, in the MSC supernatants and showed that the administration of rSLPI inhibited TAAA progression in mice. These promising preliminary data present a new approach for the treatment of less invasive TAAA.

Marfan Syndrome (MFS) often leads to thoracic aortic aneurysm (TAA), for which angiotensin (II) receptor blockers (ARBs) are prescribed to reduce aneurysm growth. Although recent pooled analyses demonstrated a statistically significant reduction in aortic growth with ARBs under a frequentist framework, the clinical relevance of this effect remains uncertain. Moreover, ARB therapy is notably burdensome for patients due to significant side-effects. Therefore, this study re-analyses randomised ARB versus comparator trials in MFS patients, under a Bayesian statistical framework. The trials included by the Marfan Treatment Trialists' Collaboration were re-analysed using fixed- and random-effects Bayesian models comparing ARBs to controls. The primary outcome was the mean difference in the annual rate of change of aortic root dimension, adjusted for body surface area (z-score). The minimal clinically important difference (MCID) was applied to assess the clinical relevance of the pooled posterior effect, based on previous consensus and available literature (at 0.12 adjusted z-scores/year). Four randomised trials, comprising 626 patients, were included. Under the fixed-effects model, the pooled mean difference was -0.07 z-score/year [95% CrI, -0.12; -0.01] in favour of ARBs, though with a posterior probability of a clinically relevant treatment effect of only 7.3%. Using a Bayesian random-effects model, the pooled mean difference was -0.06 z-score/year [95% CrI, -0.22 to 0.11] in favour of ARBs, with a similarly low probability of achieving the MCID (18.1%). The findings of this Bayesian analysis suggest that ARBs are unlikely to achieve clinically meaningful reductions in aortic growth for MFS patients.

Late toxicity after upper abdominal radiotherapy in pediatric Wilms tumor and neuroblastoma survivors. A systematic review on behalf of SIOPEN and SIOP-RTSG.

An abnormal accumulation of immune cells and inflammation has been described in ascending aortic aneurysm, but the factor driving disease initiation remains elusive. Interestingly, ascending aortic dilatation often occurs alongside aortic regurgitation but rarely with aortic stenosis. We sought to investigate ascending aortic aneurysm initiation by assessing the relation between aortic regurgitation and vascular activation and inflammation. In this prospective cohort study, patients with tricuspid aortic valves undergoing elective open-heart surgery were included. Aortic specimens from organ donors were obtained through the University of Miami Tissue Bank. Spatial transcriptomics measured gene expression in nondilated aortic endothelium, intima, and subintima. Immunohistochemistry determined protein expression. Aortic dimensions were recorded preoperatively and 10 years after surgery using echocardiography. Aortic gene expression affected by physiological blood flow was previously measured in Wistar rats. We show a mesenchymal activation of endothelial cells, possibly mediated by bidirectional flow, in the nondilated ascending aorta of patients with aortic regurgitation, accompanied by intimal infiltration, retention, and oxidation of apoB-containing lipoproteins. We further observed intimal upregulation of genes coding for core proteins of lipoprotein-binding proteoglycans and the OLR1 (oxidized low-density lipoprotein receptor 1), the latter by infiltrating macrophages and in association with progressive inflammation and dilatation. None of the above was observed in patients with aortic stenosis. Notably, surgical replacement of regurgitant valves, but not stenotic valves, mitigated 10-year aortic growth. Our results highlight a distinct pathological role of aortic regurgitation in ascending aortic aneurysm formation by promoting mesenchymal activation of endothelial cells and lipoprotein-related immune cell infiltration and inflammation in patients with tricuspid aortic valves. We also provide novel insights into the long-term impact of surgical aortic valve replacement on ascending aortic growth and suggest a diagnostic or therapeutic target in oxidized low-density lipoprotein cholesterol.