Evaluation of the Relationship between Para-aortic Adipose Tissue and Ascending Aortic Diameter using a New Method

Purpose: Para-aortic adipose tissue (PAT) is the local adipose tissue that externally surrounds the aorta. It contributes significantly to aortic atherosclerosis and enlargement. Studies conducted with computed tomography and magnetic resonance have shown that individuals with aortic aneurysm had more PAT than healthy individuals. In this study, we measured PAT for the first time using transthoracic echocardiography (TTE).The aim of this study is to investigate the possible relationship of TTE measured PAT with ascending aortic width.Methods: PAT was defined as the hypoechoic space in front of ascending aortic 2 cm above the sinotubular junction at the end of the systole. Patients were divided into 2 groups according to the presence of dilatation in the ascending aorta using Roman's classification (aortic size index, ASI). ASI of less than 21 was considered no aortic dilation and an ASI of 21mm/m2 or greater was considered to have aortic dilation.Results: A total of 321 unselected patients were divided into the ascending aortic dilatation (AAD) group (n=96) and the normal ascending aorta diameter group (n=225 patients). PAT was significantly higher in the AAD group compared with the non-ADD group (0.9 (0.48) vs. 0.7 (0.91) mm, p < 0.0001). Univariate and multivariate logistic regression analysis revealed that PAT (OR: 3.005, 95%CI (1.445–6.251)) were significantly associated with AAD.Conclusion: Our results showed an association between PAT measured by transthoracic echocardiography and ascending aorta width. PAT appears to be an important follow-up parameter in patients at risk of developing aortic aneurysm.

Cardiovascular manifestations of hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders

Introduction: Mitral valve prolapse and aortic root dilatation are reported in association with hypermobile Ehlers–Danlos syndrome (hEDS), but the full phenotypic spectrum of cardiovascular complications in this condition has not been studied in the aftermath of updated nosology and diagnostic criteria. Methods: We performed a retrospective review of 258 patients (> 94% adults) referred to a multidisciplinary clinic for evaluation of joint hypermobility between January 2017 and December 2020 and diagnosed with hEDS or a hypermobility spectrum disorder (HSD) to determine the incidence and spectrum of cardiovascular involvement. Results: Mitral valve prolapse was present in 7.5% and thoracic aortic dilatation in 15.2%. Aortic dilatation was more frequent in individuals with hEDS (20.7%) than with HSD (7.7%) and similarly prevalent between males and females, although was mild in > 90% of females and moderate-to-severe in 50% of males. Five individuals (1.9%) with hEDS/HSD had extra-aortic arterial involvement, including cervical artery dissection (CeAD, n = 2), spontaneous coronary artery dissection (SCAD, n = 2), and SCAD plus celiac artery pseudoaneurysm ( n = 1). This is the first series to report the prevalence of CeAD and SCAD in hEDS/HSD. Conclusions: Cardiovascular manifestations in adults with hEDS/HSD, especially females, are typically mild and readily assessed by echocardiography. Since the risk of progression has not yet been defined, adults with hEDS/HSD who are found to have aortic dilatation at baseline should continue ongoing surveillance to monitor for progressive dilatation. Cardiovascular medicine specialists, neurologists, and neurosurgeons should consider hEDS/HSD on the differential for patients with CeAD or SCAD who also have joint hypermobility.

Bentall–De Bono procedure for aortic regurgitation and intraoperative rupture of moderately dilated ascending aorta: A case report

<p>We herein present a clinical case of root and ascending aortic replacement in a patient with borderline enlargement of the ascending aorta and aortic valve insufficiency. A 65-year-old man was admitted to our clinic with signs of heart failure. Subsequent echocardiography and contrast-enhanced computed tomography revealed hemodynamically significant aortic insufficiency, as well as expansion of the ascending aorta. Diameter at the levels of the sinuses of Valsalva, sinotubular junction and tubular portion of the ascending aorta were 48, 47 and 44 mm, respectively. Based on the aforementioned data, indications for isolated aortic valve replacement were determined. Although the main portion of the surgery was unremarkable, at its final stage, a rupture of a section of the ascending aorta occurred. The results of intraoperative express histological examination of the enlarged aorta revealed connective tissue dysplasia and cystic median necrosis. Replacement of the ascending aorta was performed using the modified Bentall–De Bono technique. This case demonstrated that a borderline aortic dilatation of 40–50 mm at the ascending aorta was associated with pathological changes in its wall, which can cause fatal complications (rupture and dissection) and may require a more aggressive approach during surgical correction. Intraoperative express histological examination of the wall of the ascending aorta in ambiguous situations can help determine the scope of the intervention.</p><p>Received 16 March 2021. Revised 14 September 2021. Accepted 15 September 2021.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> The authors declare no conflict of interest.</p><p><strong>Contribution of the authors<br /> </strong>Literature review: S.Yu. Boldyrev, M.A. Marukyan<br /> Drafting the article: S.Yu. Boldyrev, M.A. Marukyan, V.N. Suslova<br /> Critical revision of the article: S.Yu. Boldyrev, V.A. Porkhanov<br /> Surgical treatment: S.Yu. Boldyrev, M.A. Marukyan<br /> Final approval of the version to be published: S.Yu. Boldyrev, M.A. Marukyan, V.N. Suslova, K.O. Barbukhatti, V.A. Porkhanov</p>

Genome-wide methylation patterns in Marfan syndrome

Background Marfan 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. Methods The 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. Results We 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. Conclusion This 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.

The Role of Lymphocyte-To-Monocyte Ratio In Predicting The Severe Post-Calcific Stenotic Aortic Dilatation In A Chinese Case-Control Study

Background: Calcific aortic valve stenosis (CAVS) represents a serious public health threat to elderly patients. Post-calcific stenotic aortic dilatation, a common feature in CAVS patients, might progress into aneurysm and even dissection, potentially lethal consequences of CAVS, and predicts a dismal prognosis. This study sought to testify the role of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, in predicting the severe post-calcific stenotic aortic dilatation in a Chinese case-control study.Materials and Methods: 208 consecutive patients with CAVS were recruited retrospectively in a Chinese case- control study, from July 1, 2015 to June 31, 2018. The LMR was statistically analyzed for its prognostic value in the severe post-calcific stenotic aortic dilatation.Results: The LMR was significantly reduced in patients with severe post-calcific stenotic aortic dilatation (2.72 vs. 3.53, p=0.002<0.05) compared to patients without severe post- calcific stenotic aortic dilatation. There was an inverse correlation observed between the maximal diameter of ascending aorta and the LMR in the overall patients (r=-0.217, p=0.002<0.05). For severe post-calcific stenotic aortic dilatation, the incidence of high- LMR group was statistically lower than that of low-LMR group (19.7% vs. 43.9%, p<0.001). And maximal diameter of ascending aorta was significantly reduced in the high-LMR group (4.35vs. 4.76, p=0.003<0.05) compared to low-LMR group. Additionally, the LMR was identified in the multivariate analysis as an independent predictor of severe post-calcific stenotic aortic dilatation (OR 0.743, 95% CI: [0.573- 0.964], p=0.025).Conclusions: This study provided the evidence of an inverse correlation between the severe post- calcific stenotic aortic dilatation and LMR. And the LMR is potentially applied as an independent predictor of severe post-calcific stenotic aortic dilatation.

1p36 Deletion Syndrome and the Aorta: A Report of Three New Patients and a Literature Review

Background: Monosomy 1p36 syndrome is now considered the most common terminal deletion syndrome, with an estimated incidence of 1 in 5000. Cardiac involvement is well described in the literature mainly in terms of congenital heart defects (CHDs) and cardiomyopathies (CMPs). Few data in the literature describe the potential progressive nature of aortic dilatation (root and ascending aorta) in 1p36 deletion syndrome. SKI harboured in the deleted region might play a predisposing factor for this aspect. Methods: we reviewed the aortic aspect both in the literature and in our cohort, where major attention to the aortic abnormalities was given through dedicated echocardiographic measurements even in previously screened individuals. Results: aortic involvement in 1p36 deletion syndrome was described in the literature three times within the CHD context. We observed three additional patients from our cohort (three out of nine patients) with aortic dilatation. All patients with dilated aorta had SKI haploinsufficiency within the deleted region. Conclusions: at long-term outcome and with a growing population of this rare disease, this association (1p36 deletion and aortic dilatation) might represent a major concern especially in terms of risk stratification and the potential need for specific management (conservative pharmacologic and eventually surgical) whenever indicated. The present study suggests the need for detailed multicentric studies and indication to periodic echocardiographic screening in addition to baseline tests, especially in individuals with deletions harbouring SKI.

Hemodynamic Characteristics of Dilated Ascending Aorta in Patients with Bicuspid Aortic Valve

Objective: Aim of this study is to investigate the influence of aortic diameter on hemodynamic environment characteristics in patient with the bicuspid aortic valve (BAV) and dilated ascending aorta (AAo) .Methods: In this study, an MRI of one BAV patient with 4.5 cm AAo was collected and numerical model was constructed. Based on the images，the other three numerical models were constructed with different ascending aortic size with 4.0cm, 5.0cm and 5.5cm respectively while the size and the geometry of other parts were fixed. Then hemodynamics in these four models was simulated numerically and the flow patterns and loading distributions were investigated.Results: Hemodynamics environments in the AAo were simulated with different aortic size. As the aortic diameter increases, we find: 1. the blood flow becomes more disturbing;2.the wall pressure at ascending aortic is higher; 3. the wall shear stress at the ascending aortic decreases; 4.oscillatory shear index of the outer part on the proximal AAo increases;5. all these hemodynamic parameters described above are asymmetrically distributed in dilated AAo and more parts of aorta would be affected as the AAo dilatation progresses.Conclusions: The study revealed that the diameter of ascending aortic can significantly influence the magnitude and distribution of the dynamics. There are altered flow patterns, pressure difference, WSS and OSI distribution features in bicuspid aortic valve patients with vascular dilatation. As the extent of aortic dilatation increases especially exceed 5.5cm,this study support the recent guideline that aortic replacement should be considered .

Proximal Aortic Dilatation and Pulmonary Valve Replacement in Patients with Repaired Tetralogy of Fallot: Is There a Relationship? A Cardiac Magnetic Resonance Imaging Study

Aortopathy is a known complication whose incidence is growing within the population of tetralogy of Fallot (TOF) patients. Its pathology and relationship with other comorbidities remain unclear. This study was designed to determine the prevalence and predictors of proximal aortic dilatation after TOF repair. We retrospectively investigated all patients who underwent follow-up cardiac magnetic resonance imaging (CMR; at least 4 years after TOF repair) between March 2004 and December 2019. The dimensions at the ascending aorta (AAo) and sinus of Valsalva (SoV) levels were measured. Aortic dilatation was defined as an internal aortic diameter that was >2 standard deviation of the previously published normal values. We included 77 patients (mean age 28.9 ± 10.5 years, 41.5% female, mean follow-up of 24.5 ± 8.1 years). AAo and SoV were dilated in 19 (24.6%) and 43 (55.8%) patients, respectively. Patients with dilated AAo and SoV were older during the corrective surgery (p < 0.001 and p = 0.004, respectively) and during CMR (p = 0.002 and 0.024, respectively) than patients without AAo and SoV dilatation. Patients of the dilated AAo group were more likely to have prior palliative shunt (p = 0.008), longer shunt duration (p = 0.005), and a higher degree of aortic valve regurgitation (AR) fraction (p < 0.001) and to undergo pulmonary (PVR) and/or aortic valve replacement (p < 0.001 and p = 0.013, respectively). PVR (p = 0.048, odds ratio = 6.413, and 95% CI = 1.013–40.619) and higher AR fraction (p = 0.031, odds ratio = 1.194, and 95% CI = 1.017–1.403) were independent predictors for AAo dilatation. Aortopathy is a common progressive complication that may require reintervention and lifelong follow-up. Our study shows that proximal aortic dilatation may be attributed to factors that increase the volume overload across the proximal aorta, including late corrective surgery and palliative shunt. We also found that PVR and higher AR fraction are independent predictors of AAo dilatation.

Dynamic Aortic Aneurism Risk Factors

According to different systematic reviews incidence of thoracic aortic aneurysms (TAA) in the general population is increasing in frequency ranging from 5 to 10.4 per 100000 patients. However, only few studies have illustrated the role of different risk factors in the onset and progression of ascending aortic dilatation. Currently, noninvasive imaging techniques are used to assess the progression rate of aortic and aortic valve disease. Transthoracic (TT) Echocardiographic examination routinely includes evaluation of the aorta It is the most available screening method for diagnosis of proximal aortic dilatation. Since the predominant area of dilation is the proximal aorta, TT-echo is often sufficient for screening. We retrospectively analyzed the ECHO database with 78499 echocardiographic records in the Almazov National Medical Research Centre to identify patients with aneurysm. Detailed information including demographic characteristics, ECHO results and comorbidities were extracted from outpatient clinic and from hospital charts related to hospitalizations occurring within a year before index echocardiography was performed. Comorbid diseases were similarly extracted from outpatient clinic and/or hospital admissions. The classifier showed an AUC-ROC for predicting of aneurism detection after a repeated ECHO at 82%.