Change In Aortic Diameter Research Articles

Aortic luminal remodeling after intravascular stent therapy for coarctation of the aorta: intermediate results.

Outcomes after adult coarctation of the aorta (CoA) stenting is scant. We explored predictors of aortic remodeling after stent implantation and report early- and intermediate-term clinical outcomes. Adult patients who underwent stenting between July 2003 and December 2017 were included in this single-center retrospective study. We created a novel index of aortic volumetric and diameter changes using computed tomography (CT)/magnetic resonance (MR) images measured through TeraRecon and AngioQ. Predictors of aortic remodeling were explored using univariable linear regression analysis. One hundred and thirty-four patients (mean age 35.2 years, 58.2% men) underwent CoA stenting. Paired aortic diameter measurements were available in 20 patients, and 40 paired patients in volumetric measurements. There was significant reduction in aortic diameter immediately proximal to the left carotid and subclavian arteries, and the aorta distal to the stenosis (P less than .05) at follow-up. There was a significant volumetric reduction in the ascending aorta, aortic arch, and the aortic segment most proximal to the top of the stent (P less than .05). Univariate predictors of aortic remodeling included sex, age, presence of previous surgical repair, aortic valve morphology, and the number of antihypertensive medications. Mean follow-up time was 4.0 ± 3.8 years, where 5% of patients underwent reintervention due to complications, 3% developed aneurysms, and 3% had stent fractures. This study is the first to examine the anatomical changes that occur in the aorta post stent repair through analysis of serial imaging. Patients with stent-repaired coarctation demonstrated negative remodeling in multiple areas of the aorta with regards to the aortic diameter and volumetric measurements.

Abdominal aortic aneurysm monitoring via arterial waveform analysis: towards a convenient point-of-care device

Abdominal aortic aneurysms (AAAs) are lethal but treatable yet substantially under-diagnosed and under-monitored. Hence, new AAA monitoring devices that are convenient in use and cost are needed. Our hypothesis is that analysis of arterial waveforms, which could be obtained with such a device, can provide information about AAA size. We aim to initially test this hypothesis via tonometric waveforms. We study noninvasive carotid and femoral blood pressure (BP) waveforms and reference image-based maximal aortic diameter measurements from 50 AAA patients as well as the two noninvasive BP waveforms from these patients after endovascular repair (EVAR) and from 50 comparable control patients. We develop linear regression models for predicting the maximal aortic diameter from waveform or non-waveform features. We evaluate the models in out-of-training data in terms of predicting the maximal aortic diameter value and changes induced by EVAR. The best model includes the carotid area ratio (diastolic area divided by systolic area) and normalized carotid-femoral pulse transit time ((age·diastolic BP)/(height/PTT)) as input features with positive model coefficients. This model is explainable based on the early, negative wave reflection in AAA and the Moens-Korteweg equation for relating PTT to vessel diameter. The predicted maximal aortic diameters yield receiver operating characteristic area under the curves of 0.83 ± 0.04 in classifying AAA versus control patients and 0.72 ± 0.04 in classifying AAA patients before versus after EVAR. These results are significantly better than a baseline model excluding waveform features as input. Our findings could potentially translate to convenient devices that serve as an adjunct to imaging.

Natural history and clinical significance of aortic focal intimal flaps.

ObjectiveFocal intimal flaps (FIF) are a variety of defects of the aorta that result in a short, flap-like projection into the lumen, and are often encountered in asymptomatic patients undergoing computed tomography angiography (CTA) surveillance for aortic aneurysm, but the natural history and clinical significance of such lesions has not yet been studied.MethodsWe retrospectively identified patients with an asymptomatic FIF and available imaging follow-up (>1 year). FIF was defined as flap-like intimal irregularity < 4 cm in length involving the thoracic aorta (TA), abdominal aorta (AA) or common iliac arteries (CIA). FIF characteristics included length and circumferential extent as well as the presence and size (width and depth) of associated penetrating aortic ulcers (PAUs). Patient characteristics, adverse events and history of surgical repair was determined by chart review. FIFs and associated PAUs were assessed for progression by comparing baseline and follow-up CTA studies.ResultsA total of 84 FIFs were identified in 77 patients. Average age was 69.2 ± 10.1 years, and 81% were male (81%). Common co-morbidities included: hypertension (78%), hyperlipidemia (68%), smoking (60%), coronary artery disease (41%), aortic aneurysm (34%), type II diabetes mellitus (27%) and prior cardiovascular surgery (25%). FIFs were most commonly located in the abdominal aorta (n = 50, 60%). Nearly all FIFs were associated with local atherosclerotic plaque (93%). Mean follow-up interval was 3.5 ± 2.6 years (259 cumulative follow-up years). Change in FIF length and local aortic diameter over follow-up were 0.7 ± 2.3 mm and 0.8 ± 1.1 mm, respectively. Nearly half (47%) of FIFs were associated with penetrating aortic ulcers (PAU) with baseline depth of 7.3 mm (IQR: 6.1–10.2) and change in depth of 0.5 ± 1.4 mm. Only 12% of FIFs and 0% of associated PAUs demonstrated growth (≥3 mm) at follow-up. No acute pathology developed in the location of FIFs and no aortic interventions were performed specifically to treat FIFs.ConclusionFocal intimal flaps identified in asymptomatic patients with aortic disease were co-localized with atherosclerotic plaque and PAUs, and demonstrated indolent behavior, not leading to significant growth or acute aortic events, supporting a conservative management approach.

Long Term Results of Reduction Ascending Aortoplasty.

The aim of this retrospective study is to show medium-long-term results in terms of cardiac death and aortic events in patients undergoing reduction ascending aortoplasty between 1997 and 2009 in our hospital. The Fine and Grey model for competing risk analysis was performed for time to cardiac death, with non-cardiac death as the competing risk, and time to recurrence of both re-dilation (aortic diameter > 45 mm) and re-operation with overall death as the competing risk. Paired t-test was used to evaluate the change in aortic diameter from the post-operative values to follow-up. The population included 142 patients. The mean pre-operative aortic diameter and the diameter at follow-up were respectively 46.5 ± 5.11 mm vs. 41.4 ± 5.55 mm (p-value < 0.001). At a mean follow-up of 11.6 ± 4.15 years, 11 patients (7.7%) required re-operation on the ascending aorta. At 16 years, the CIF of aortic-related events was 29.4 ± 7.2%; the freedom from cardiac death was 89.2 ± 3.7%. Ten patients (7%) died from cardiac causes but no one was aortic-related. The Fine and Grey analysis did not identify any significant predictors. This procedure is safe but might be justified only in high-risk patients or in those with advanced age/short life expectancy.

Changes in aortic diameter induced by weight loss: The HELENA trial- whole-body MR imaging in a dietary intervention trial.

Obesity-related metabolic disorders such as hypertension, hyperlipidemia and chronic inflammation have been associated with aortic dilatation and resulting in aortic aneurysms in many cases. Whether weight loss may reduce the risk of aortic dilatation is not clear. In this study, the diameter of the descending thoracic aorta, infrarenal abdominal aorta and aortic bifurcation of 144 overweight or obese non-smoking adults were measured by MR-imaging, at baseline, and 12 and 50 weeks after weight loss by calorie restriction. Changes in aortic diameter, anthropometric measures and body composition and metabolic markers were evaluated using linear mixed models. The association of the aortic diameters with the aforementioned clinical parameters was analyzed using Spearman`s correlation. Weight loss was associated with a reduction in the thoracic and abdominal aortic diameters 12 weeks after weight loss (predicted relative differences for Quartile 4: 2.5% ± 0.5 and -2.2% ± 0.8, p < 0.031; respectively). Furthermore, there was a nominal reduction in aortic diameters during the 50-weeks follow-up period. Aortic diameters were positively associated with weight, visceral adipose tissue, glucose, HbA1c and with both systolic and diastolic blood pressure. Weight loss induced by calorie restriction may reduce aortic diameters. Future studies are needed to investigate, whether the reduction of aortic diameters via calorie restriction may help to prevent aortic aneurysms.

The predictive capability of aortic stiffness index for aortic dissection among dilated ascending aortas

ObjectiveWe created a finite element model to predict the probability of dissection based on imaging-derived aortic stiffness and investigated the link between stiffness and wall tensile stress using our model. MethodsTransthoracic echocardiogram measurements were used to calculate aortic diameter change over the cardiac cycle. Aortic stiffness index was subsequently calculated based on diameter change and blood pressure. A series of logistic models were developed to predict the binary outcome of aortic dissection using 1 or more series of predictor parameters such as aortic stiffness index or patient characteristics. Finite element analysis was performed on a subset of diameter-matched patients exhibiting patient-specific material properties. ResultsTransthoracic echocardiogram scans of patients with type A aortic dissection (n = 22) exhibited elevated baseline aortic stiffness index when compared with aneurysmal patients’ scans with tricuspid aortic valve (n = 83, P < .001) and bicuspid aortic valve (n = 80, P < .001). Aortic stiffness index proved an excellent discriminator for a future dissection event (area under the curve, 0.9337, odds ratio, 2.896). From the parametric finite element study, we found a correlation between peak longitudinal wall tensile stress and stiffness index (ρ = .6268, P < .001, n = 28 pooled). ConclusionsNoninvasive transthoracic echocardiogram–derived aortic stiffness measurements may serve as an impactful metric toward predicting aortic dissection or quantifying dissection risk. A correlation between longitudinal stress and stiffness establishes an evidence-based link between a noninvasive stiffness parameter and stress state of the aorta with clinically apparent dissection events.

Spinal Cord Ischemia following Simultaneous EVAR and TEVAR for Concomitant Thoracic and Abdominal Aortic Aneurysms

In patients with abdominal aortic aneurysms, 10-20% has concomitant thoracic aortic pathologies. These are typically managed with staged endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) due to a perceived higher risk of spinal cord ischemia from a simultaneous intervention. We aimed to determine the outcomes of patients undergoing simultaneous EVAR and TEVAR for concomitant aneurysms. A retrospective cohort study was performed using the Vascular Quality Initiative registry from December 2003 to January 2021. Patients undergoing same day EVAR and TEVAR were included and analyzed in accordance with the Society for Vascular Surgery reporting standards. Primary outcomes were technical success and spinal cord ischemia. Simultaneous EVAR and TEVAR were performed in 25 patients. Median age was 75.0 (interquartile range [IQR], 63.0-79.0) years and 20 (80.0%) patients were male. Two (4.0%) patients were symptomatic and 4 (16.0%) presented with rupture. Median maximum infrarenal and thoracic aortic diameter was 57.0 (IQR, 52.0-65.0). Infrarenal aortic neck length was 15.0mm (IQR, 10.0-25.0), and diameter was 27.0mm (IQR, 24.5-30.0). Median procedure time was 185.0min (IQR, 117.8-251.3), fluoroscopy time 32.7min (IQR, 21.8-63.1), and contrast volume 165mL (IQR, 115.0-207.0). There were 3 (12.0%) Type Ia endoleaks and 3 (12.0%) Type II endoleaks in EVAR's, with 1 (4.0%) Type Ia and 1 (4.0%) Type II endoleak in TEVARs. In-hospital mortality occurred in 3 (12.0%) patients (1 elective, 2 ruptures). Spinal cord ischemia occurred in 1 (4.0%) patient. This patient had a symptomatic aneurysm. Thoracic coverage extended from Zone 4 to Zone 5 and an emergent spinal drain was placed postoperatively. Symptoms were present on discharge. There was 1 (4.0%) conversion to open repair which occurred in a ruptured aneurysm. Technical success was achieved in 19 (76.0%) patients, however when excluding ruptured aneurysms, was achieved in 17 (81.0%) patients. Follow-up data was available for 19 (76.0%) patients at a median of 426.0 (IQR, 329.0-592.5) days postoperatively. A total of 3 (12.0%) patients died during the late mortality period, at a mean of 509.0 (±503.7) days. Median change in abdominal and thoracic aortic sac diameter was -1.35mm (IQR, -11.5 to 2.5) and 8.0 (IQR, -10.5 to 12.0), respectively. Simultaneous EVAR and TEVAR for concomitant abdominal and thoracic aortic aneurysms can be performed with low rates of spinal cord ischemia. Short- and mid-term outcomes are acceptable.

Individualized prediction of risk of ascending aortic syndromes.

ObjectivesAlthough ascending aortic diameter changes acutely after dissection, recommendation for prophylactic surgery of thoracic aortic aneurysms rely on data from dissected aortas. In this case-control study we aim to identify risk markers for acute and chronic aortic syndromes of the ascending aorta (ACAS-AA). Furthermore, to develop a predictive model for ACAS-AA.MethodsWe collected data of 188 cases of ACAS-AA and 376 controls standardized to age- and sex of the background population. Medical history and CT-derived aortic morphology were collected. For the dependent outcome ACAS-AA, potential independent risk factors were identified by univariate logistic regression and confirmed in multivariate logistic regression. As post-dissection tubular ascending aortic diameter is prone to expand, this factor was not included in the first model. The individual calculated adjusted odds ratios were then used in ROC-curve analysis to evaluate the diagnostic accuracy of the model. To test the influence of post-ACAS-AA tubular ascending aortic diameter, this was added to the model.ResultsThe following risk factors were identified as independent risk factors for ACAS-AA in multivariate analysis: bicuspid aortic valve (OR 20.41, p = 0.03), renal insufficiency (OR 2.9, p<0.01), infrarenal abdominal aortic diameter (OR 1.08, p<0.01), left common carotid artery diameter (OR 1.40, p<0.01) and aortic width (OR 1.07, p<0.01). Area under the curve was 0.88 (p<0.01). Adding post-ACAS-AA tubular ascending aortic diameter to the model, negated the association of bicuspid aortic valve, renal insufficiency, and left common carotid artery diameter. Area under the curve changed to 0.98 (p<0.01).ConclusionsA high performing predictive model for ACAS-AA, free of ascending aortic diameter, can be achieved. Furthermore, we have identified abdominal aortic ectasia as an independent risk factor of ACAS-AA. Integration of potential biomarkers and morphologic variables, derived from undissected aortas, would probably improve the model.

Quantifying sodium [18F]fluoride uptake in abdominal aortic aneurysms

BackgroundAortic microcalcification activity is a recently described method of measuring aortic sodium [18F]fluoride uptake in the thoracic aorta on positron emission tomography. In this study, we aimed to compare and to modify this method for use within the infrarenal aorta of patients with abdominal aortic aneurysms.MethodsTwenty-five patients with abdominal aortic aneurysms underwent an sodium [18F]fluoride positron emission tomography and computed tomography scan. Maximum and mean tissue-to-background ratios (TBR) and abdominal aortic microcalcification activity were determined following application of a thresholding and variable radius method to correct for vertebral sodium [18F]fluoride signal spill-over and the nonlinear changes in aortic diameter, respectively. Agreement between the methods, and repeatability of these approaches were assessed.ResultsThe aortic microcalcification activity method was much quicker to perform than the TBR method (14 versus 40 min, p < 0.001). There was moderate-to-good agreement between TBR and aortic microcalcification activity measurements for maximum (interclass correlation co-efficient, 0.67) and mean (interclass correlation co-efficient, 0.88) values. These correlations sequentially improved with the application of thresholding (intraclass correlation coefficient 0.93, 95% confidence interval 0.89–0.95) and variable diameter (intraclass correlation coefficient 0.97, 95% confidence interval 0.94–0.99) techniques. The optimised method had good intra-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.36 and limits of agreement − 0.43 to 0.43) and inter-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.47 and limits of agreement − 0.53 to 0.53) repeatability.ConclusionsAortic microcalcification activity is a quick and simple method which demonstrates good intra-observer and inter-observer repeatabilities and provides measures of sodium [18F]fluoride uptake that are comparable to established methods.

Outcomes and Ascending Aortic Diameter Change After Ascending Aortic Wrapping and Zone 0 Endografting

With the rapid progress of endovascular technology, hybrid aortic arch repair, consisting of supra-aortic re-routing and thoracic endovascular aortic repair into the ascending aorta (zone 0 TEVAR [thoracic endovascular aortic repair]), have demonstrated acceptable outcomes in a high risk population.1 Furthermore, ascending aortic wrapping may create a sufficient proximal landing zone when the ascending aorta is dilated.2,3 This retrospective single centre study describes 23 cases of zone 0 TEVAR with ascending aortic wrapping treated between January 2008 and March 2021.

Aortic Healing Appears to Occur Rapidly after Successful Endovascular Sealing of Blunt Thoracic Aortic Injury

The traumatic nature of blunt thoracic aortic injury (BTAI) would suggest that healing of the aorta would occur once the injured area is shielded from aortic pressure. This would be in contrast to degenerative aortic diseases which often continue to degenerate despite coverage. We hypothesize that after successful thoracic aortic endografting (TEVAR) that the aorta rapidly heals itself leaving minimal to no trace of the residual injury. BTAI that were successfully covered with TEVAR from 2006 to 2019 were collected. Those with failed sealing or a lack of follow-up scans were excluded. Centerline aortic diameters were measured at healthy aorta 1cm above (D1) and below the injury (D3) and at the widest point of injury (D2) on preoperative and initial postoperative computed tomography (CT) scans. Postoperative CTs were examined for residual signs of aortic injury including residual periaortic hematoma, persistent thrombosed pseudoaneurysm, or thickened aortic wall. Diameter changes in the healthy and injured aortic segments were compared pre and post TEVAR. Aortic diameter changes were analyzed with the Student's t-test. Twenty four patients were identified with sealed BTAI. The mean graft diameter was 24.2±3.2mm with oversizing of 10.74±6.1 % at D1 and 19.52±10.22 % at D3. Postoperative CTs occurred at 61.25±123.6days with one outlier at 602days. Injured aortic segments (D2) had significantly larger diameters compared to D1 (28.94±5.08mm vs. 22.14±3.08mm, P<0.001). After TEVAR, 23/24 (95.8%) had no residual radiographic evidence of aortic injury by 2months. One patient had a persistent thrombosed pseudoaneurysm likely due to more than 50% disruption of the aortic wall. Post TEVAR, there was a significant diameter reduction at D2 by 13.8% (29.10±5.27mm vs. 24.8±4.2mm, P<0.001) which was within 2.45% of the mean stent graft diameter. The healthy aorta dilated to accommodate the graft by 9% at D1 (21.9±3.0 vs. 23.7±2.5mm, P<0.001) and 17% at D3 (20.6±3.4mm vs. 23.6±3.2mm, P<0.001). TEVAR promotes rapid aortic healing in BTAI with no evidence of residual aortic injury suggesting that a long-term seal is not necessary. The healthy aorta dilates to the stent graft size, as expected, whereas the injured aortic segment heals around the stent graft and assumes its diameter as well. Massive disruption of the aortic wall may preclude early healing.

Late Outcomes of Transcatheter Coarctation Intervention in Infants with Biventricular Anatomy.

Determine outcomes of catheter intervention for aortic coarctation in infants. Aortic coarctation in infants following surgical repair and in high surgical risk native cases remains a challenging problem. Catheter intervention is an alternative to surgical intervention. Single-center, chart review of infants with biventricular anatomy who underwent coarctation stent placement or balloon angioplasty between 04/2004 and 04/2020. Outcomes of interest included change in aortic lumen diameter, peak gradient, number of re-interventions, time to re-intervention, and adverse events. Thirty-four patients were included in analysis, of those 16 underwent stent placement. Patients' mean age was 4.0 ± 3.0months and weight of 5.3 ± 1.9kg. Follow-up interval was 5.4 ± 5.1years (0.2-16.1years). Twelve (35%) patients underwent procedure due to ventricular dysfunction; the rest were for high resting gradient. Coarctation diameter increased from 2.4 ± 1.0 to 4.5 ± 1.3 (p < 0.01) and gradient decreased from 32.0 ± 18.4mmHg to 9.2 ± 8.8mmHg (p < 0.01). Thirteen (81%) of the stented patients required at least one re-intervention, at an average of 1.7 ± 3.2years from the index procedure. Five (28%) of those undergoing balloon angioplasty required repeat intervention. There was no mortality due to the procedure and one late mortality. One patient had a serious procedural adverse event. On follow-up, 12 (35%) were on anti-hypertensive medications. Catheter intervention, including stent placement, for aortic coarctation in infants is feasible with an acceptable adverse event profile. Repeat interventions are common.

Therapeutic efficacy of mesenchymal stem cells for abdominal aortic aneurysm: a meta-analysis of preclinical studies

BackgroundAbdominal aortic aneurysm (AAA) is life-threatening, surgical treatment is currently the only clinically available intervention for the disease. Mesenchymal stem cells (MSCs) have presented eligible immunomodulatory and regenerative abilities which showed favorable therapeutic efficacy in various cardiovascular diseases. However, current evidence summarizing the effectiveness of MSCs for AAA is lacking. Thus, a meta-analysis and systematic review was necessary to be performed to assess the therapeutic efficacy of MSCs for AAA in preclinical studies.MethodsComprehensive literature search restricted in English was conducted in PubMed, Cochrane Library, EBSCO, EMBASE and Web of Science from inception to Oct 2021. The primary outcomes were parameters about aortic diameter change during MSCs intervention. The secondary outcomes included elastin content and expression level of inflammatory cytokines, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Data were extracted and analyzed independently by two authors. The meta package with random effects model was used to calculate the pooled effect size and 95% confidence intervals in R (version 4.0.2).ResultsMeta-analysis of 18 included studies demonstrated that MSCs intervention has significant therapeutic effects on suppressing aortic diameter enlargement compared with the control group (diameter, SMD = − 1.19, 95% CI [− 1.47, − 0.91]; diameter change ratio, SMD = − 1.36, 95% CI [− 1.72, − 1.00]). Subgroup analysis revealed differences between MSCs and control group regarding to cell type, intervention route and cell compatibility. Moreover, the meta-analysis also showed that MSCs intervention had a significant effect on preserving aortic elastin content, reducing MCP-1, TNF-α, IL-6, MMP-2/9 and increasing TIMP-1/2 expression level compared with control group.ConclusionOur results suggested that MSC intervention is effective in AAA by suppressing aortic diameter enlargement, reducing elastin degradation, and modulating local immunoinflammatory reactions. These results are important for the systemic application of MSCs as a potential treatment candidate for AAA in further animal experiments and clinical trials.

Early aortic growth in acute descending aortic dissection.

OBJECTIVESAcute aortic dissection leads to the destabilization of the aortic wall, followed by an immediate increase in aortic diameter. It remains unclear how the aortic diameter changes during the dissection’s acute and subacute phases. The aim of this study was to evaluate the change in aortic geometry within 30 days after the onset of a descending aortic dissection.METHODSPatients with acute type B and non-A non-B dissection who had at least 2 computed tomography angiography scans obtained within 30 days after the onset of dissection were evaluated. Exclusion criteria were a thrombosed false lumen, connective tissue disorders and endovascular or open aortic repair performed prior to the second computed tomography angiography.RESULTSAmong 190 patients with acute aortic dissection, 42 patients met our inclusion criteria. Their aortic geometry was analysed according to the computed tomography angiography scans obtained between 0–3 (N = 35), 4–7 (N = 9) and 8–30 (N = 12) days after the dissection onset. The highest aortic diameter growth rate was observed in the first quartile of the thoracic aorta and measured 0.66 (0.06; 1.03), 0.29 (−0.01; 0.41) and 0.06 (−0.13; 0.26) mm/day at 0–3, 4–7 and 8–30 days after the dissection, respectively. Proximal entry location (P = 0.037) and entry located at the arch concavity (P = 0.008) were associated with a higher aortic diameter increase.CONCLUSIONSEarly rapid growth occurs during the first week after the descending aortic dissection—most intensely over the first 3 days, and this is associated with the location of the dissection’s entry.

Genome-wide methylation patterns in Marfan syndrome

BackgroundMarfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process.MethodsThe Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed.ResultsWe identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP’s that associated with clinical events. No significant associations at p < 10–8 or p < 10–6 were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18–22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before.ConclusionThis EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients.

Abstract 11618: Serum and Glucocorticoid Inducible Kinase-1 (SGK-1) Activity is Upregulated in Hypertension and Promotes IL-6 Expression to Drive Aortic Macrophage Accumulation

Introduction: The serum and glucocorticoid inducible kinase-1 (SGK-1) is a mechanosensitive kinase and it is hypothesized that SGK-1 activity is upregulated with elevated aortic tension to augment pro-inflammatory cytokine expression and promote macrophage accumulation to drive hypertensive remodeling. Methods: Hypertension (HTN) was induced in C57Bl/6 mice with AngiotensinII (AngII) infusion (1.46mg/kg/day x21days, n=4). Terminal procedure included blood pressure (SBP) quantification, aortic diameter (AoD) assessment, and harvest of infrarenal aorta. Abundance of SGK-1, pSGK-1, and the mature macrophage marker F4/80 was determined by immunoblot. The spontaneously hypertensive BPH/2 mice were also utilized and assessed for SBP, AoD, and target proteins (n=4). A subset of animals had systemic infusion of EMD638683, a selective SGK-1 inhibitor (2.5mg/kg/day x 21 days, n=4). Aortic VSMCs were subjected to 12% biaxial cyclic stretch for 3 and 12 hours +/- EMD638683 (10μM) with subsequent QPCR for IL-6 and MCP-1 expression. Statistical analysis included two-way ANOVA across treatment groups with significance at p&lt;0.05. Results: C57Bl/6+AngII mice and BPH/2 mice had significant elevation in SBP (p&lt;0.05) without change in AoD. The pSGK-1/SGK-1 and abundance F4/80 were increased in both models of HTN (p&lt;0.05) and decreased with systemic EMD638683 (p&lt;0.05), with no change in SBP. IL-6 expression was upregulated in VSMC that had Stretch for 3hrs (1.64 + 0.22 fold; p&lt;0.05) or 12hrs (1.99 + 0.33 fold; p&lt;0.05), and at both timepoints EMD638683 significantly inhibited IL-6 expression (p&lt;0.05 vs respective Stretch). MCP-1 expression was unchanged after 3hr Stretch, but it was significantly elevated following 12hr Stretch (2.05 + 0.38 fold; p&lt;0.05), and inhibited by EMD638683 (p&lt;0.05). This data suggests a biomechanical link between aortic VSMC mechanotransduction and cytokine production to promote macrophage accumulation, mediated in-part by SGK-1 activation. Conclusions: Mechanical stimuli can elevate SGK-1 activity and increase pro-inflammatory cytokine production to accumulate macrophages, which may lead to proteolytic aortic remodeling. Therefore, SGK-1 may represent a novel target to abrogate hypertensive aortic inflammation.

Predictors of Long-Term Aortic Growth and Disease Progression in Patients with Aortic Dissection, Intramural Hematoma, and Penetrating Aortic Ulcer

We aimed to identify predictors of long-term aortic diameter change and disease progression in a population cohort of patients with newly diagnosed aortic dissection (AD), intramural hematoma (IMH), or penetrating aortic ulcer (PAU). We used the Rochester Epidemiology Project record linkage system to identify all Olmsted County, MN-USA, residents diagnosed with AD, IMH, and PAU (1995-2015). The endpoints were aortic diameter change, freedom from clinical disease progression (any related intervention, aortic aneurysm, new aortic syndrome, rupture or death) and disease resolution (complete spontaneous radiological disappear). Linear regression was used to assess aortic growth rate; predictors of disease progression were identified with Cox proportional hazards. Of 133 incident cases, 46 ADs, 12 IMHs, and 28 PAUs with sufficient imaging data were included. Overall median follow-up was 8.1 years. Aortic diameter increase occurred in 40 ADs (87%, median 1.0 mm/year), 5 IMHs (42%, median 0.2 mm/year) and 14 PAUs (50%, median 0.4 mm/year). Symptomatic presentation (P=0.045), connective tissue disorders (P=0.005), and initial aortic diameter >42 mm (P=0.013) were associated with AD growth rate. PAU depth >9 mm (P=0.047) and female sex (P=0.013) were associated with aortic growth rate in PAUs and IMHs. At 10 years, freedom from disease progression was 22% (95% CI 12-41) for ADs, 44% (95% CI 22-92) for IMHs, and 46% (95% CI 27-78) for PAUs. DeBakey I/IIIB AD (HR 3.09; P=0.038), initial IMH aortic diameter (HR 1.4; P=0.037) and PAU depth >10 mm (HR 3.92; P=0.018) were associated with disease progression. No AD spontaneously resolved; resolution rate at 10 years was 22% (95% CI 0-45) for IMHs and 11% (95% CI 0-23) for PAUs. Aortic growth and clinical disease progression are observed in most patients with aortic syndromes, while spontaneous resolution is uncommon. Predictors of aortic growth and disease progression may be used to tailor appropriate follow-up and eventual early intervention.

Incident aortic root dilatation in the general population: findings from the Pamela study.

We sought to assess the long-term changes in aortic root diameter in a population-based sample, focusing on new-onset aortic root dilatation, as well as on the demographic and clinical variables independently related to this dynamic process. A total of 1122 participants with measurable echocardiographic parameters at baseline and after a 10-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute aortic root diameter, aortic root diameter indexed to body surface area (BSA) and to height were derived from 712 healthy normotensive PAMELA participants. Over the 10-year follow-up, new aortic root dilatation occurred in 3.4% (aortic root /BSA), 4.4% (aortic root /height) and 7.3% (absolute aortic root), respectively. No substantial relationship was observed between baseline office and ambulatory blood pressure (BP) or their changes over time and incident aortic root /BSA and aortic root /height dilatation. Baseline aortic root diameter and left ventricular mass index (LVMI) emerged as important predictors of aortic root dilation, regardless of the diagnostic criteria used. This was also the case for the 10-year change in LVMI. The strength of association between nonhemodynamic variables and new-onset aortic root dilatation was variable, depending on the definition of the aortic phenotype. The incidence of aortic root dilatation in a general middle-aged population is a relatively infrequent but not so rare event and scarcely influenced by both office and out-office BP. On the contrary, it is strongly related to LVMI (and its variations over time). From a clinical perspective, this underlines that LVH prevention and regression can reduce the risk of aortic root dilatation in the community.

Effect of stent graft fixation types on pararenal aortic diameter and renal function after endovascular aortic repair.

Background This study aims to identify pararenal aortic diameter changes following endovascular aortic repair and to investigate the effects of suprarenal fixation on renal function. Methods Between May 2006 and January 2019, a total of 168 patients (135 males, 33 females; mean age: 75.2±8.4 years; range, 48 to 93 years) who underwent endovascular aortic repair were retrospectively analyzed. To compare the effects of graft types, we measured the change in pararenal aortic diameter at four levels: below the celiac artery, below the superior mesenteric artery, at the lowest renal artery, and 1 cm below the lowest renal artery. To evaluate the effect of suprarenal fixation on renal function, serial measurements of serum creatinine, glomerular filtration rate, creatinine clearance rate, and estimated glomerular filtration rate were made. We examined the factors related to post-procedural aortic diameter. Results The mean change in the aortic diameter was statistically significant, being 12.9±10% in the suprarenal fixation group and 6.19±6.9% in the infrarenal fixation group only at the lowest renal artery level (p=0.001). There was no significant difference in the rate of type I endoleak (p=0.330) or renal function and adverse events (p>0.107) between the groups. The formula for calculating post-procedural aortic diameter was as follows: post-procedural aortic diameter (renal artery level, mm) =1.845 (in case of suprarenal fixation) + 1.012 × pre-procedural aortic diameter (renal artery level, mm) + 0.029 × follow-up time (months) + 0.039 × oversizing (%) (R2=0.773, p<0.001). Conclusion Suprarenal fixation affects the infrarenal aortic diameter at the lowest renal artery level without significant type I endoleak. However, it does not result in significant renal dysfunction. Pre-procedural aortic diameter, computed tomography follow-up time, suprarenal fixation type, and stent oversizing are the only definite independent correlation factors for postprocedural aortic diameter. This formula can predict the change of aortic diameter after endovascular aortic repair.

Changing of pulmonary artery diameter in accordance with severity of COVID-19 (assessment based on non-contrast computer tomography)

BACKGROUND: Computed tomography is the method of choice for assessing the volume of lung damage in viral pneumonia, including those associated with COVID-19. In addition, computed tomography can determine the main vessels size of the thorax. This allowed us to analyze the relationship between the severity of COVID-19 and the changes in the diameters of the pulmonary artery (PA) and ascending aorta (Ao). Dilation of the PA is a sign of pulmonary hypertension. The study of these patterns may be of clinical significance in determining the treatment tactics and prognosis of the course of COVID-19 disease.&#x0D; AIM: To evaluate the relationship between PA diameter and the severity of the COVID-19 course in patients of different ages.&#x0D; MATERIALS AND METHODS: This study is a single-centered, cross-section, continuous, uncontrolled study performed on a group of patients (n=511, 267 men, median 59 years, IQR 49.065.0, ages 3184 years) who were treated in a temporary hospital to treat patient with COVID-19. During hospitalization all patients were examined by CT scan of the chest. All studies were carried out using a mobile CT scan system Airo TruCT (Stryker, USA). The degree of damage to the lung tissue was assessed using the CT volume scale 14. Measurement of the LA and Ao diameters was carried out using standard instruments of the radiologists CT workstation perpendicular to the long axis of the vessel.&#x0D; RESULTS: The following statistically significant regularities were obtained: the detection of a dilated pulmonary artery (PA) and an increased PA/Ao ratio correlated to an increase in the degree of lung damage in COVID-19 (Kruskal-Wallis test, K-W p 0.001; median test, MT p 0.001), the diameter of the ascending aorta (Ao) significantly increases with the patients age (K-W p 0.001; MT p 0.001). An insignificant correlation between an increase in the diameter of the pulmonary artery (PA) and the patients age (K-W p=0.094; MT p=0.311) and an insignificant correlation between detection of a change in aortic (Ao) diameter and the degree of lung damage (K-W p=0.061; MT p=0.165) were shown. In groups with a severe course of the disease and a large volume of lung lesions (CT-3 and CT-4), a significantly greater number of patients with signs of pulmonary hypertension (detection of the dilated pulmonary artery: 29 mm and more) was shown for all age groups.&#x0D; CONCLUSION: The study showed that PA dilatation and increased PA/Ao diameter ratio were significantly associated with increased pulmonary lesion volume in COVID-19 in all age groups.