High Risk Of Aortic Dissection Research Articles

Central vs peripheral vascular factors determining risk of aortic dissection

Hypertension is the commonest cause of “central” aortic dissection, despite being an “peripheral” arteriole disease. We hypothesised that known regional variations in peripheral organ perfusion, due to variation in arteriole tone, via its effect on differential head and neck vessel flows can alter the risk and location of central aortic dissection. This might help to explain why some hypertensive patients dissect their aorta and others don't despite having similar aortic geometry. We utilised a simple 2D computational fluid dynamic model to test our hypothesis. We hypothesise (1) that variations in “peripheral” organ flow can alter the site of “central” aortic dissection, despite the blood pressure and cardiac output being identical, (2) variations in cardiac output at rest may also help to explain the risk of dissection but not the site of the initial intimal tear, and (3) atrial fibrillation, a known factor for aortic dissection, increases the risk via stroke volume variation. MRI scanning, via regional aortic branch flow quantification, may help to identify individuals who have a family history of dissection/aneurysm, who are normotensive with normal aortic anatomy that have a high potential risk for dissection due to calculated high wall velocity/shear stresses. This may allow selective beta blocker prescriptions in an asymptomatic patient population that is at a predicted high risk of aortic dissection – a hither to unidentified patient subpopulation.

Fluoroquinolones increase susceptibility to aortic aneurysm and aortic dissection: Molecular mechanism and clinical evidence.

Aortic aneurysm (AA) and aortic dissection (AD) are prevalent severe cardiovascular diseases that result in catastrophic complications and unexpected deaths. Owing to the lack of clinically established and effective medications, the only treatment options are open surgical repair or endovascular therapy. Most researchers have focused on the development of innovative medications or therapeutic targets to slow the progression of AA/AD or lower the risk of malignant consequences. Recent studies have shown that the use of fluoroquinolones (FQs) may increase susceptibility to AA/AD to some extent, especially in patients with aortic dilatation and those at a high risk of AD. Therefore, it is crucial for doctors, particularly those in cardiovascular specialties, to recognize the dangers of FQs and adopt alternatives. In the present review, the main clinical observational studies on the correlation between FQs and AA/AD in recent years are summarized, with an emphasis on the relative physiopathological mechanism incorporating destruction of the extracellular matrix (ECM), phenotypic transformation of vascular smooth muscle cells, and local inflammation. Although additional data are required, it is anticipated that the rational use of FQs will become the standard of care for the treatment of aortic diseases.

Can 10 000 Healthy Steps a Day Slow Aortic Root Dilation in Pediatric Patients With Marfan Syndrome?

Background Stiffer aortas are associated with a faster rate of aortic root (AoR) dilation and higher risk of aortic dissection in patients with Marfan syndrome. We have previously shown that mild aerobic exercise reduces aortic stiffness and rate of AoR dilation in a Marfan mouse model. In this study, we investigated if these results could be translated to pediatric patients with Marfan syndrome. Methods and Results We enrolled 24 patients with Marfan syndrome aged 8 to 19 years to participate in a 6-month physical activity intervention, excluding those with ventricular dysfunction or prior history of aortic surgery. We instructed patients to take 10 000 steps per day, tracked by an activity tracker. At baseline and 6 months, we measured AoR dimension, arterial stiffness, endothelial function, physical activity indices, inflammatory biomarkers, and coping scores. Controls consisted of 15 age-matched patients with Marfan syndrome. Twenty-four patients with Marfan syndrome (median age, 14.4 years [interquartile range {IQR}, 12.2-16.8], 14 male patients) were enrolled. Baseline assessment demonstrated that the majority of these patients were sedentary and had abnormal arterial health. Twenty-two patients completed the intervention and took an average of 7709±2177 steps per day (median, 7627 [IQR, 6344-9671]). Patients wore their Garmin trackers at a median of 92.8% (IQR, 84%-97%) of their intervention days. AoR Z score in the intervention group had a significantly lower rate of change per year compared with the controls (rate of change, -0.24 versus +0.008; P=0.01). Conclusions In this clinical intervention in pediatric patients with Marfan syndrome, we demonstrated that a simple physical activity intervention was feasible in this population and has the potential to decrease the AoR dilation rate. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03567460.

Non-Dissecting Distal Aortic and Peripheral Arterial Aneurysms in Patients With Marfan Syndrome.

BackgroundIn Marfan syndrome (MFS), an aortic or peripheral arterial dilatation is usually the consequence of aortic dissection. Non-dissecting distal aortic and peripheral aneurysms (DAPA) are barely described. We sought to determine the incidence and prognostic impact of non-dissecting DAPA, requiring a surgical repair in a large population of patients with MFS.MethodsThe patients referred to the French MFS reference center were included in a prospective database, and the patients treated for a non-dissecting DAPA between 2013 and 2020 were retrospectively reviewed. The first-line therapy was open surgery. The patients unfit for open repair or experiencing life-threatening complications underwent endovascular repair.ResultsAmong 1,575 patients with MFS, 19 (1.2%) were operated for 25 non-dissecting DAPA. The mean age was 42.4 ± 11.5 years. Non-dissecting DAPA involved the subclavian or axillary artery (n = 12), the descending or thoracoabdominal aorta (n = 6), the abdominal aorta andiliac arteries (n = 6), and the popliteal artery (n = 1). Open and endovascular repairs were performed in 22 and three cases, respectively. After a median follow-up of 54.2 months, no local recurrence was noticed and no secondary procedure was performed. Eight patients presented a new aortic event, including two aortic dissections and seven new aortic surgeries. Compared to the overall MFS population, the non-dissecting DAPA group presented a significantly higher risk of an aortic event (100 vs. 28%, p < 0.0001), a higher risk of aortic dissection (53 vs. 8%, p < 0.0001), and a higher rate of pejorative genetic mutations (68 vs. 40%, p = 0.011).ConclusionAmong the patients with MFS, the diagnosis of non-dissecting DAPA is infrequent but is associated with a significant adverse outcome, thus, advocating for a specific follow-up.

Blood Pressure, Hypertension, and the Risk of Aortic Dissection Incidence and Mortality: Results From the J-SCH Study, the UK Biobank Study, and a Meta-Analysis of Cohort Studies.

Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies on this topic have been published. We investigated the association between hypertension/elevated BP and AD in 2 cohorts and conducted a meta-analysis of published prospective studies, including these 2 studies. We analyzed data from the J-SHC study (Japan-Specific Health Checkups) and UK Biobank, which prospectively followed up 534 378 and 502 424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks were calculated with random-effects models. A potential nonlinear dose-response relationship between BP and AD was tested with fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. In the J-SHC study and UK Biobank, there were 84 and 182 ADs during the 4- and 9-year follow-up, and the adjusted hazard ratios of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI, 1.78-4.04) in hypertensive individuals, 1.33 (95% CI, 1.05-1.68) and 1.27 (95% CI, 1.11-1.48) per 20-mm Hg increase in systolic BP (SBP), and 1.67 (95% CI, 1.40-2.00) and 1.66 (95% CI, 1.46-1.89) per 10-mm Hg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary relative risks were 3.07 (95% CI, 2.15-4.38, I2=76.7%, n=7 studies, 2818 ADs, 4 563 501 participants) for hypertension and 1.39 (95% CI, 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2 = 57.0%, n=3) per 20-mm Hg increase in SBP and per 10-mm Hg increase in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mm Hg and DBP >75 mm Hg. Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

Hemodynamic forces and myocardial deformation using cine MRI in Marfan syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction. Cardiovascular assessment of Marfan syndrome (MS) patients has normally focused on the aortic root and vascular manifestations due to the high risk of aortic dissection. Although primary myocardial impairment has long been suspected, the evidence has been controversial. Advanced in CMR may support the early detection of cardiac dysfunction. Beyond left ventricle ejection fraction (EF) and myocardial strain (S), a new parameter is emerging, the hemodynamic forces (HF) exchanged between the blood flowing in the heart and the myocardium. The application of these techniques to MS could be useful in demonstrating the presence of primary myocardial impairment. Aim. The aim of this study is to explore myocardial function in MS through the evaluation in cine CMR of EF, S and cardiac HF exchanged between the blood and the myocardium and compare these data with those of a control group (C). Methods. We retrospectively analysed CMR cine images of MS (diagnosed according revised Ghent criteria) without valvular disease or previous cardio surgery, and C, in standard long-axis projections, to define endocardial borders for subsequent quantification of left ventricular volumes, EF, longitudinal, circumferential and radial S, apex-to-base and lateral-to-septum HF (expressed in mN and as a percentage of gravity acceleration). The analysis were performed on Medical Imaging Systems (QStrain version 1.3.0.79; MEDIS) (Figure 1). Results. 108 MS and 44 C had a good quality study, suitable for MEDIS analysis. The mean age was 33 ± 13 ys in MS, 35 ± 12 ys in C; 39% were male in MS, 50% in C. The results of left ventricular function were: EF 63 ± 7% in MS vs 66 ± 5% in C group, p .008, global longitudinal S -24.5 ± 4.1% in MS vs -26.2 ± 4.1 in C, p .014; global circumferential S -30.6 ± 6.3% in MS vs -33.8 ± 4.4 in C, p .002; radial S 64.5 ± 16.2% in MS vs 72.7 ± 15.9 in C, p .005; apex-to-base HF 13.2 ± 4.7% in MS vs 17.8 ± 7.6% in C, p .000; lateral-to-septum 2.6 ± 1.3% in MS vs 3.1 ± 1.4% in C, p .048. Moreover, 4.6% MS patients had mid reduced EF (40-50%); 9.2% had global longitudinal S reduction (cut off -19.3%); 7.4% had global circumferential S reduction (cut-off -21.7%). Conclusion. These data provide support for the existence of a cardiomyopathy in MS. In our opinion, the term "primary cardiomyopathy" is not appropriate to describe this condition: patients with MS have changes in aortic stiffness and probably in cardiac afterload. The HF data are the most interesting of this study, both in the validation of this new parameter and in early detection a cardiomyopathy in MS Moreover, the reduction of global circumferential S, as wall as global longitudinal S, in MS patients may help provide new elements to characterize the MS cardiomyopathy: sure enough, in literature, circumferential strain abnormalities are related to afterload increase. HF analysis is really a new challenge of cardiac imaging, as sensitive markers of subtle systolic dysfunction. Abstract Figure. Figue 1. Analisis exemple.

Management and Outcomes of Aortic Dissection in Pregnancy with Marfan Syndrome: A Systematic Review.

In Marfan Syndrome (MFS), aortic dilatation is one of the main cardiovascular manifestations which deteriorate due to the physiological changes during pregnancy. We aimed to assess the up-to-date management and outcomes of aortic root dilation and dissection (AoD) in pregnancy with MFS. A systematic review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Original studies published between January 1, 2001 and December 31, 2018 and which described the management and/or outcomes of AoD during or after pregnancy in women with MFS were included. Literature searches were conducted. The PubMed search was performed using terms "Marfan Syndrome" [Mesh] and "Pregnancy" [Mesh] whereas the Google Scholar search was for "Marfan" and "Pregnancy", all words anywhere in the article. The literature search yielded 177 articles on PubMed and 13,900 articles on Google Scholar. Assessment of full-text articles for eligibility after removal of duplicates from both databases yielded 12 eligible studies to be included in the final review. Women with MFS are at high risk of aortic dissection during pregnancy and women with aortic root 41-45 mm should consider avoiding pregnancy. Guideline-specific management of aortic aneurysms in pregnancy will reduce the risk of dissection. Diagnosis and Management of MFS need a multidisciplinary approach and team that should start working early in pregnancy. Further studies are needed to optimize medical and surgical approaches in addition to preconception counselling in highrisk subjects.

Differences in Aortopathy in Patients with a Bicuspid Aortic Valve with or without Aortic Coarctation.

Objective: The combination of aortic coarctation (CoA) and bicuspid aortic valve (BAV) is assumed to be associated with a higher risk of ascending aortic dilatation and type A dissection, and current European Society of Cardiology (ESC) guidelines advise therefore to operate at a lower threshold in the presence of CoA. The aim of our study is to evaluate whether the coexistence of CoA in BAV patients is indeed associated with a higher risk of ascending aortic events (AAE). Methods: In a retrospective study, all adult BAV patients visiting the outpatient clinic of our tertiary care center between February 2003 and February 2019 were included. The primary end point was an ascending aortic event (AAE) defined as ascending aortic dissection/rupture or preventive surgery. The secondary end points were aortic dilatation and aortic growth. Results: In total, 499 BAV patients (43.7% female, age 40.3 ± 15.7 years) were included, of which 121 (24%) had a history of CoA (cBAV). An aortic event occurred in 38 (7.6%) patients at a mean age of 49.0 ± 13.6 years. In the isolated BAV group (iBAV), significantly more AAE occurred, but this was mainly driven by aortic valve dysfunction as indication for aortic surgery. There was no significant difference in the occurrence of dissection or severely dilated ascending aorta (>50 mm) between the iBAV and cBAV patients (p = 0.56). The aortic diameter was significantly smaller in the cBAV group (30.3 ± 6.9 mm versus 35.7 ± 7.6 mm; p < 0.001). The median aortic diameter increase was 0.23 (interquartile range (IQR): 0.0–0.67) mm/year and was not significantly different between both groups (p = 0.74). Conclusion: Coexistence of CoA in BAV patients was not associated with a higher risk of aortic dissection, preventive aortic surgery, aortic dilatation, or more rapid aorta growth. This study suggests that CoA is not a risk factor in BAV patients, and the advice to operate at lower diameter should be reevaluated.

Risk of aortic dissection, congestive heart failure, pneumonia and acute respiratory distress syndrome in patients with clinical vertebral fracture: a nationwide population-based cohort study in Taiwan

ObjectiveStudies on the association between clinical vertebral fractures (CVFs) and the subsequent risk of cardiopulmonary diseases, including aortic dissection (AD), congestive heart failure (CHF), pneumonia and acute respiratory distress syndrome...

Thoracic Aortic Aneurysm Growth in Bicuspid Aortic Valve Patients: Role of Aortic Stiffness and Pulsatile Hemodynamics.

BackgroundBicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. A thoracic aortic aneurysm (TAA) is present in ≈50% of BAV patients, who also have an 8‐fold higher risk of aortic dissection than the general population. Because the health of the aorta is directly reflected in its stiffness and pulsatile hemodynamics, we hypothesized that measures of aortic stiffness and arterial load would be associated with TAA growth in BAV.Methods and ResultsTwenty‐nine unoperated participants with TAA due to BAV who had serial imaging were recruited. Aortic stiffness and steady and pulsatile arterial load were evaluated with validated methods that integrate arterial tonometry with echocardiography. TAA growth was assessed retrospectively based on available imaging, blinded to hemodynamic status. Multivariable linear regression assessed associations of aortic stiffness and hemodynamic variables with TAA growth, adjusting for potential confounders. Overall, 66% of participants were men. Mean±SD for age, baseline aneurysm size, growth rate, and follow‐up time were 57.2±8.3 years, 46.9±3.6 mm, 0.75±0.81 mm/y, and 2.9±3.3 years, respectively. We found that greater aortic stiffness (β±SE for carotid‐femoral pulse wave velocity: 0.30±0.13. P=0.03) and aortic characteristic impedance (β±SE: 0.46±0.18, P=0.02), as well as lower total arterial and proximal aortic compliance (β±SE: −0.44±0.21, P=0.05, and −0.63±0.16, P=0.001, respectively) were independently associated with faster aneurysm growth.ConclusionsIn patients with TAA due to BAV, measures of greater aortic stiffness and pulsatile arterial load indicate an association with accelerated aneurysm expansion. Assessing arterial hemodynamics may be useful for risk stratification and disease monitoring in TAA patients with BAV.

Sex Differences in the Associations of Arterial Stiffness and Pulsatile Hemodynamics with Thoracic Aortic Aneurysm Size

Although women with thoracic aortic aneurysm (TAA) have faster aneurysm growth and higher risk of aortic dissection and death than men, reasons for this remain unclear.

Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study.

To investigate pregnancy outcomes, especially the risk of pregnancy-related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR). Retrospective case series study. Tertiary perinatal care centre at a university hospital. Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute. The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records. Obstetrical management and complication including the incidence of AD throughout the peripartum period. Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P<0.05, Chi-square test). Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre-pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm. MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.

Positive family history of aortic dissection dramatically increases dissection risk in family members

ObjectivesAlthough family members of patients with aortic dissection (AoD) are believed to be at higher risk of AoD, the prognostic value of family history (FH) of aortic dissection (FHAD) in family members of patients with AoD has not been studied rigorously. We seek examine how much a positive FHAD increases the risk of developing new aortic dissection (AoD) among first-degree relatives. MethodsPatients with AoD at our institution were analyzed for information of FHAD. Positive FHAD referred to that AoD occurred in index patient and one or more first-degree relatives. Negative FHAD was defined as the condition in which only one case of AoD (the index patient) occurred in the family. The age at AoD, exposure years in adulthood before AoD, and annual probability of AoD among first-degree relatives were compared between patients with negative and positive FHADs. ResultsFHAD was positive in 32 and negative in 68 among the 100 AoD patients with detailed family history information. Mean age at dissection was 59.9±14.7years. Compared to negative FHAD, patients with positive FHAD dissected at significantly younger age (54.7±16.8 vs 62.4±13.0years, p=0.013), had more AoD events in first-degree relatives (2.3±0.6 vs 1.0±0.0, p<0.001), and shorter exposure years per AoD event (18.3±6.7 vs 43.1±8.5, p<0.001). Annual probability of AoD per first-degree relative was 2.77 times higher in patients with positive than negative FHADs (0.0100±0.0057 vs 0.0036±0.0014, p<0.001). ConclusionsA positive FHAD confers a significantly increased risk of developing aortic dissection on family members, with a higher annual probability of aortic dissection, a shorter duration of “exposure time” before dissection occurs and a lower mean age at time of dissection.

The role of advanced echocardiography and cardiovascular magnetic resonance in the assessment of myocardial function in Marfan syndrome-An update.

Cardiovascular assessment of patients with Marfan syndrome has normally focused on the aortic root and vascular manifestations of the disease due to the high risk of aortic dissection. Although primary myocardial impairment has long been suspected in these patients, the evidence has been controversial. Advanced echocardiography and cardiovascular magnetic resonance imaging have proven to be effective, accurate, and more sensitive in the detection of subtle cardiac dysfunction. The application of these techniques to Marfan syndrome over the last 10years has made significant progress in demonstrating the presence of primary myocardial impairment in these patients, but further work is still required to obtain confirmatory molecular, pathophysiological, and prognostic clinical data. Phenotypic expression of the disease has prognostic value, also suggesting potential effective medical therapy.

Risk of Aortic Dissection in Pregnant Patients With the Marfan Syndrome

Patients with Marfan syndrome (MS) face a high risk of aortic dissection during pregnancy. A dilated aortic root (>40 to 45mm) is considered a relative contraindication for pregnancy. We investigated the risk for aortic dissection and pregnancy outcome in patients with MS. Women with MS who attended our cardiology high-risk pregnancy clinic from 2006 to 2015 were followed clinically and with serial echocardiograms by a multidisciplinary team. Beta blockers were offered and titrated by blood pressure and heart rate. Patients with aortic root dilation ≥40mm were considered high-risk patients with MS. A consistent increase in aortic root diameter of >1mm during pregnancy was classified as dilation during pregnancy; 31 pregnancies in 19 patients with MS were followed. Four pregnancies were terminated early because of prenatal diagnosis of fetal MS and 4 additional babies born with MS. Eight pregnancies were in patients with a dilated aortic root (40 to 46mm); 21 patients (68%) were treated with β blockers. There were 2 cases of postpartum aortic dissection (6.5%): 1 type A dissection in a woman with a dilated aortic root who declined β blockers (1 of 8, 12.5%) and 1 type B dissection. Increasing aortic root diameter (>1mm) in pregnancy was significantly associated with later aortic dissection (2 of 6 vs 0 of 21, p= 0.04). No maternal deaths occurred. All high-risk women with MS gave birth by cesarean section, whereas in the non-high-risk group mode of delivery was by obstetric indication. Preterm delivery rate was 41% (11 of 27). One antenatal fetal death and no major neonatal morbidity or mortality were observed. In conclusion, pregnant patients with MS, especially those with a dilating aortic root, are at high risk of aortic dissection, even with tight control of blood pressure and heart rate.

SHERESHEVSKY-TURNER SYNDROME IN AORTIC SURGERY: AN EXAMPLE OF HYBRID ANEURISM TREATMENT AND DISSECTION OF THORACOABDOMINAL AORTA

Shereshevsky-Turner syndrome — is chromosome anomaly, the monosomia by X-chromosome (cariotype 45, X0) that has prevalence 1:2000-1:2500 newborn girls. It is well known that these patients very often have cardiovascular pathology. Aortic aneurysm is 100 times more common than in general population. Another significant specifics is the high risk of aortic dissection even with relatively small diameter of aorta, than in average for the dissections. Currently it is common to concern a variety of aortic pathology treatment ways in patients with the syndrome: traditional open-chest interventions, endovascular treatment, hybrid operations. The article provides an example of successful usage of the hybrid method in women 58 years old with Shereshevsky-Turner syndrome, thoracoabdominal aortic aneurysm and dissection of descending thoracal and abdominal aorta parts. The clinical example shows that hybrid method makes it to perform radical intervention on aorta, decreasing traumaticity of operation, mortality and complications rate in postoperation period.

Biomarkers for diagnosis and prognostic stratification of aortic dissection: challenges and perspectives.

Aortic dissection (AD) is a severe vascular disease associated with major morbidity and mortality. The diagnosis of AD requires the performance of urgent aortic imaging exams such as computed tomography angiography, but the decision to perform these exams now essentially relies on clinical judgment. Several studies have identified a range of potential biomarkers stemming from the aortic extracellular matrix (matrix metalloproteinases, TGF-β, soluble elastin fragments), vascular smooth muscle cells (smooth muscle myosin heavy chain, creatine kinase, calponin), coagulation (D-dimer, platelets) and inflammation (C-reactive protein), whose circulating levels increase in patients affected by AD. Biomarkers of AD could be potentially used to screen patients with compatible symptoms, to identify patients at higher risk of AD, to rule out AD in patients with non-high clinical probability of AD and/or to obtain prognostic stratification of affected patients. This review will summarize available data and discuss present and future perspectives of circulating biomarkers for the diagnosis and prognostic stratification of AD.

Prediction of aortic dilation in Turner syndrome - enhancing the use of serial cardiovascular magnetic resonance

BackgroundIdentification of the subset females with Turner syndrome who face especially high risk of aortic dissection is difficult, and more optimal risk assessment is pivotal in order to improve outcomes. This study aimed to provide comprehensive, dynamic mathematical models of aortic disease in Turner syndrome by use of cardiovascular magnetic resonance (CMR).MethodsA prospective framework of long-term aortic follow-up was used, which comprised diameters of the thoracic aorta prospectively assessed at nine positions by CMR at the three points in time (baseline [n = 102, age 38 ± 11 years], follow-up [after 2.4 ± 0.4 years, n = 80] and end-of-study [after 4.8 ± 0.5 years, n = 78]). Mathematical models were created that cohesively integrated all measurements at all positions, from all visits and for all participants, and using these models cohesive risk factor analyses were conducted based on which predictive modeling was performed on which predictive modelling was performed.ResultsThe cohesive models showed that the variables with effect on aortic diameter were aortic coarctation (P < 0.0001), bicuspid aortic valves (P < 0.0001), age (P < 0.0001), diastolic blood pressure (P = 0.0008), body surface area (P = 0.015) and antihypertensive treatment (P = 0.005). Oestrogen replacement therapy had an effect of borderline significance (P = 0.08). From these data, mathematical models were created that enabled preemption of aortic dilation from CMR derived aortic diameters in scenarios both with and without known risk factors. The fit of the models to the actual data was good.ConclusionThe presented cohesive model for prediction of aortic diameter in Turner syndrome could help identifying females with rapid growth of aortic diameter, and may enhance clinical decision-making based on serial CMR.

Annuloaortic ectasia in a 16 year-old boy with Loeys–Dietz syndrome

Loeys-Dietz syndrome (LDS) is a rare genetic disorder with an autosomal dominant inheritance due to mutations in the transforming growth factor beta-receptor type 1 or type 2. The disease is characterised by the triad of hypertelorism, bifid uvula or cleft palate, arterial tortuosity and aortic aneurysms. These phenotypic characteristics distinguish LDS from other connective tissue disorders related to transforming growth factor beta-receptor. Patients with LDS have a high risk of aortic dissection or rupture at a younger age and smaller aortic diameters. So, clinical suspicion of LDS followed by genotyping is important to prevent aortic dissection, leading cause of death, by surgical treatment.

Dexamethasone normalizes aberrant elastic fiber production and collagen 1 secretion by Loeys–Dietz syndrome fibroblasts: a possible treatment?

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by facial dysmorphism, cleft palate, dilation of the aortic arch, blood vessel tortuosity and a high risk of aortic dissection. It is caused by mutations in the transforming growth factor β-receptor 1 and 2 (TGFβ-R1 and TGFβ-R2) genes. Fibroblasts derived from 12 Loeys-Dietz syndrome patients, six with TGFB-R1 mutations and six with TGFB-R2 mutations, were analyzed using RT-PCR, biochemical assays, immunohistochemistry and electron microscopy for production of elastin, fibrillin 1, fibulin 1 and fibulin 4 and deposition of collagen type I. All LDS fibroblasts with TGFβ-R1 mutations demonstrated decreased expression of elastin and fibulin 1 genes and impaired deposition of elastic fibers. In contrast, fibroblasts with TGFβ-R2 mutations consistently demonstrated intracellular accumulation of collagen type I in the presence of otherwise normal elastic fiber production. Treatment of the cell cultures with dexamethasone induced remarkable upregulation in the expression of tropoelastin, fibulin 1- and fibulin 4-encoding mRNAs, leading to normalization of elastic fiber production in fibroblasts with TGFβ-R1 mutations. Treatment with dexamethasone also corrected the abnormal secretion of collagen type I from fibroblasts with TGFβ-R2 gene mutations. As the organogenesis-relevant elastic fiber production occurs exclusively in late fetal and early neonatal life, these findings may have implications for treatment in early life. Further studies are required to determine if dexamethasone treatment of fetuses prenatally diagnosed with LDS would prevent or alleviate the connective tissue and vascular defects seen in this syndrome.