Risk Of Aortic Dissection Research Articles

Abstract 4123806: Early Findings on the Impact of Renin-Angiotensin-Aldosterone System Inhibitors on Bicuspid Aortic Valve Disease Progression: A Single Center Cohort Study

Introduction: Patients with a bicuspid aortic valve (BAV) often have an associated aortopathy, increasing their risk of aortic dissection. Currently, there is no proven therapy to stabilize the growth of BAV aortopathy. This study aimed to assess the effect of cardioprotective medications, specifically renin-angiotensin-aldosterone system inhibitors (RAASi), on the progression of aortic dilation in adult BAV patients. Methods: A retrospective cohort study was conducted including adult patients with BAV followed at our center between 1996-2020. All patients had echocardiography imaging with at least 5 years of follow-up. The cohort was divided based on the chronic use of RAASi, as determined by pharmacy check-out data. The primary endpoint was defined as either the progression of ascending aortic diameter ≥ 4.5 cm or surgery for ascending aortic replacement. Results: The study included 262 patients with a mean age of 54.3±19.5 years, of whom 75.2% (n=197) were male, and 34.7% (n=44) had a diagnosis of hypertension. At baseline, the average size of the ascending aorta was 4.2±4.1 mm and 3.5±4.0 mm at the level of the aortic sinuses. The average follow-up time was 5.8±0.8 years. During follow-up, 23 patients underwent ascending aortic replacement with concurrent aortic valve replacement, 66 patients experienced progression of ascending aortic diameter ≥ 4.5 cm, and 2 patients died. Patients using RAASi (n=40) had a lower incidence of the primary endpoint compared to those without RAASi chronic therapy (12.8% vs. 24.8%, p=0.147). Multivariate analysis indicated that patients without RAASi chronic therapy had a significantly increased risk of the primary endpoint (HR=2.87, 95% CI [1.03-8.01], p=0.43). Conclusions: Our early findings suggest that RAASi may have a preventative role in the progression of BAV aortopathy.

Abstract 4148073: Expect the Unexpected: Type A Aortic Dissection in Pregnant Patient with Marfan Syndrome

Case Description: A 26 yo woman with Marfan Syndrome (MFS, FBN1 ), ectopia lentis, aortic dilation and no family history of MFS or aortic dissection was evaluated for preconception counseling. She was asymptomatic, and the size of her aortic root (~4cm) and ascending aorta (~3.5cm) had been stable for over 5 years. She was counseled that risk of cardiac events during her pregnancy is high, but lower compared to those with aortic sizes >4.5cm. Once pregnant, she was followed closely with imaging every trimester (MRA at 25 weeks gestation showed stable aortic sizes). Cardio-obstetric recommendations included: CARPREG II score: 2, mWHO class: III, consideration of assisted second stage due to aortic root dilation. She was counseled on symptoms of aortic dissection and to seek emergency care should those symptoms arise. At 27 weeks gestation, she presented to the ED with intense chest and neck pain, shortness of breath, and headache. Emergent CT showed aortic root (4.1cm) and proximal ascending aortic dissection with propagation into the left main coronary artery (Figure 1). She underwent emergent C-section followed by aortic root and ascending aorta replacement and mechanical aortic valve replacement due to severe regurgitation. She was discharged in stable condition 8 days after an uncomplicated post-operative recovery. Her baby is recovering in the NICU. Discussion: While risk of aortic dissection in women with MFS is higher during pregnancy, recent studies suggest relative safety with aortic root diameters up to 4.5cm. Our case highlights that even at “lower risk” aortic sizes, aortic dissection remains an important risk for such women. Educating patients and providers about the acute symptoms of aortic dissection and forming an action plan for timely intervention can be lifesaving. Furthermore, some genetic mutations (e.g. TGBR1/2 or SMAD3 ) and sequence variants within the FBN1 gene may pose a higher risk of aortic dissection at smaller aortic diameters. Our patient’s pathogenic FBN1 mutation (-c.2114-5T>G, previously classified as a VUS) highlights the importance of genetic testing: prophylactic surgery at sizes <4.5cm may be considered with high-risk genetic variants or a family history of aortic dissection.

Abstract 4136604: Efficacy of angiotensin receptor blockers in thoracic aortic aneurysm: meta-analysis of randomized controlled trials

Background: Thoracic aortic aneurysm (TAA) poses a significant risk of aortic dissection and mortality. Angiotensin receptor blockers (ARBs) have been proposed as a potential therapeutic intervention to mitigate these risks but their effects are uncertain. Aim: To evaluate the efficacy of ARBs in patients with TAA. Methods: A comprehensive search of Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science yielded 2563 records, from which 8 unique randomized controlled trials (RCTs) (including 7 Marfan and 1 bicuspid aortic valve+TAA populations) comprising 1575 patients were included in the analysis. The primary outcome measures were aortic dissection and all-cause mortality. Pooled risk ratios (RR) or mean differences (MD) in an inverse variance random-effects model were generated and analyses were performed with “meta” package in R (version 4.3.2). Results: Our analysis reveals no significant beneficial effect of ARBs on aortic dissection (RR 0,62 [95%CI, 0,20; 1,92], I 2 :0%) and all-cause mortality (RR 0,61 [95%CI, 0,18; 2,05], I 2 :0%), irrespective of specific ARB agents (including losartan, irbesartan, and telmisartan), comparators (beta blocker, placebo, or no treatment), disease condition (Marfan syndrome or bicuspid aortic valve), and patient demographics (children or adults). Additionally, there were no significant differences observed between ARB and control groups in changes in ascending aorta and aortic annulus diameter, as well as aortic Z-score at the 3-year mark, including the annual change in ascending aorta (MD 0.04 mm/year [95% CI, -0.07 to 0.15], I 2 :0%) and aortic root diameter (MD -0.06 mm/year [95% CI, -0.22 to 0.10], I 2 :81%) by echocardiography. However, there was a significant reduction in aortic root diameter as assessed by MRI (MD -0.48 mm/year [95%CI, -0.89 to -0.08]) and echocardiography (MD -0.51 mm/3year [95%CI, -0.85 to -0.17]), with low heterogeneity when compared with control. Risk of aortic surgery and severe adverse events were also comparable. Conclusion: We found no significant beneficial effect of ARBs in reducing the risk of aortic dissection or all-cause mortality in patients with TAA. Despite observing a significant reduction in the aortic root diameter by MRI and echocardiography with ARB therapy, other imaging outcomes were comparable between ARB and control groups.

Abstract 4138455: Employing Bioinformatic Tools to Identify High-Risk Variants of Unknown Significance in Aortopathy Genes Associated with Aortic Dissection

Introduction: Pathogenic (P) or likely pathogenic (LP) aortopathy gene variants cause hereditary thoracic aortic aneurysm and dissection, but P/LP variants only explain approximately 20% of cases of thoracic aortic disease. Variants of unknown significance (VUS) are frequently identified among individuals undergoing genetic testing for thoracic aortic disease, however managing patients with VUSs remains clinically challenging. Hypothesis: Bioinformatic tools can be used to determine thresholds above which VUSs may be considered “high-risk.” Methods: Primary analyses were performed in the Penn Medicine Biobank (PMBB) which is composed of 43,731 participants who volunteered to have clinical information linked to biospecimen data including DNA which has undergone whole exome sequencing. PMBB participants were screened for VUSs in one of 11 aortopathy genes. VUS REVEL, AlphaMissense and minor allele frequency (MAF) high-risk thresholds were derived using cutpointR, a statistical package to optimize continuous variable thresholds based on binary outcomes. These thresholds were applied to VUS carriers in the PMBB and two independent validation cohorts. Logistic regression analysis was performed to test the association of high-risk VUSs with prevalent thoracic aortic disease. Results: There were 11,925 individuals in PMBB who carried at least one missense VUS. Carrying a VUS was associated with a modest increased risk of thoracic aortic aneurysm (TAA: OR=1.14, 95% confidence interval [CI] 1.01 to 1.29, P =0.034) but no increased risk of thoracic aortic dissection (OR=1.04, 95%CI 0.55 to 2.00, P =0.896). As VUS REVEL or AlphaMissense increased, or MAF decreased, the association between VUSs and thoracic aortic disease became statistically significant. Using cutpointR, we derived REVEL (>0.649), AlphaMissense (>0.2543), and MAF (<8.16x10 -6 ) thresholds that together identified 435 high-risk VUSs robustly associated with prevalent dissection (OR=7.85, 95%CI 4.73 to 13.03, P <0.001), though the association with TAA was attenuated (OR=2.35, 95%CI 1.62 to 3.42, P <0.001). Similar results were observed in the UK Biobank (UKB) and Early Onset Sporadic Thoracic Aortic Dissection (ESTAD) cohorts. Conclusions: VUSs that met high-risk bioinformatic thresholds were strongly associated with prevalent aortic dissection in the PMBB, UKB and ESTAD. Future investigation is warranted to determine if these thresholds can instruct clinical care of individuals carrying aortopathy gene VUSs.

Cardiovascular health in women with turner's syndrome: a 3-year single centre audit

Abstract Background Turner’s syndrome (TS) is the most common genetic abnormality affecting females and is characterised by complete or partial absence of the X chromosome. Mortality is predominantly related to cardiovascular disease (1). Risk of life-threatening aortic dissection is 40 per 100,000 (2). Indexed aorta size (ASI) to body surface area (BSA) >20mm/m² is considered abnormal. An ASI of ≥25mm/m² is associated with increased risk of aortic dissection (3). Despite this there is a paucity of data in the literature regarding TS cardiovascular disease and providing evidence-based care can be challenging. Purpose Define cardiovascular disease, with focus upon aortopathy in our TS Cardiovascular Clinic (TCC). Methods Single centre retrospective medical record analysis of 248 women with TS (2021-2024) Results Patient baseline characteristics; mean age 37 years (range 18-75yrs), height 150cm (132-169cm), weight 62kg (37-130kg), BSA 1.55m² (1.19-2.17m²). 65 patients (29%) had bicuspid aortic valve (BAV), 19 (8%) and 5 (3%) had repaired and un-repaired aortic coarctation (CoA) respectively. 30 (13%) had other congenital heart disease, with most common was partial anomalous pulmonary venous connection (12 patients: 5%). 22/248 patients had previous aortic root surgery; 20 elective (mean ASI 29mm/m², range 26-33mm/m², mean age at time of surgery 42 years); 2 presented with aortic dissection (ASI 21mm/m²; pregnant, BAV & 24mm/m²; tri-leaflet aortic valve, TAV). Data was available for 221 unoperated patients (figure 1). The site of maximal dimension was observed at the sinus of Valsalva in 70% compared to 30% at the ascending aorta. 130 patients (59%) had maximal ASI of <20mm/m². Dimensions of 20-23mm/m² and 23-25mm/m² were seen in 64 (29%) and 18 (8%) patients respectively. 7 patients (3%) had a maximal ASI of >25mm/m². 4 patients (2%) had an absolute maximal dimension of 40mm with ASI of 23mm/m² for all four. 9/11 patients with dimension ≥25mm/m² or 40mm had a body mass index (BMI) >25kg/m². Review of medical history for patients at and above threshold for risk of aortic dissection revealed referral to or previous discussion in an Aortic multi-disciplinary meeting (MDT) with a plan for ongoing surveillance. 57 patients (35%) with TAV had significant aortopathy (mean age 46years, range 19-75years) compared with 33 (51%) with BAV (mean age 39yrs, range 22-72 years) (figure 2). Review of patients >55years of age demonstrated a very similar burden of aortopathy in both TAV (14%) and BAV (15%) populations. Conclusions A high burden of cardiovascular disease exists within our TS population. There is a very high prevalence of aortopathy, increasingly with age and both with and without the presence of a bicuspid aortic valve. More published data is needed to help better define those at risk.

Efficacy of beta blockers in patients with thoracic aortic aneurysm: meta-analysis of randomized controlled trials

Abstract Studies investigating the efficacy of β-blocker agents on patients with thoracic aortic aneurysm have produced heterogeneous and conflicting results. This study was aimed to assess protective effects of β-blockers in terms of aortic events (dissection, rupture) and mortality in patients with thoracic aortic aneurysm. A systematic literature search was performed through Ovid MEDLINE, EMBASE, Web of Science, Pubmed and The Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), all from inception to May 10, 2022. Randomized controlled trials exploring the efficacy of β-blocker agents in patients with thoracic aortic aneurysm were considered for inclusion with no population restriction. Two independent reviewers performed the literature search. Two reviewers independently extracted all available prespecified relevant data in accordance with the International Prospective Register of Systematic Reviews protocol. Summary effect measures of the primary outcomes were obtained by pooling the data with an inverse variance–weighted random-effects model. The overall risk of bias assessment was conducted by using the Cochrane Risk of Bias 2 tool A sensitivity analysis was performed regarding whether the conclusions reached might differ substantially if a single study was omitted. The primary outcome was aortic events (aortic dissection/rupture). Secondary outcomes were death (all-cause mortality) and aortic dissection. Two independent reviewers identified 4 RCTs presented in 5 reports from 1494 unique studies screened. Three trials involving 129 eligible participants compared β blockers (propranolol and celiprolol) with no treatment. One trial involving 32 eligible participants compared β blocker (atenolol) with placebo. This systematic review and meta-analysis included 161 patients with thoracic aortic aneurysm (mean age, 27.6 years; 80 [49.7%] male, mean follow-up 6.7 years). The pooled risk ratio in the β-blocker arm for aortic events was 0.74 [95% CI (0.20; 2.71), I2: 0%, p=0.64] when comparing to the placebo or no treatment in patients with thoracic aortic aneurysm. The pooled risk ratio for death (all-cause mortality) and aortic dissection in the β-blocker arm were 0.45 [95% CI (0.10; 1.98), I2: 0%, p=0.29] and 0.58 [95% CI (0.15; 2.24), I2: 0%, p=0.43], respectively. The risk of aortic dissection, rupture, or death were essentially identical, regardless of treatment group and subgroup analysis. A sensitivity analysis revealed that none of the studies significantly influenced the pooled risk estimate to any great extent. We found no evidence of benefit from β-blocker treatment. More robust data regarding β-blocker use in patients with thoracic aortic aneurysms from randomized controlled trials are needed to establish evidence based recommendations and to determine whether current evidence comes from absense of evidence or evidence of absense.Forest plot for death (all-cause)

Association of lifelong exercise characteristics with aortic pathology in patients with Marfan syndrome

Abstract Background Marfan syndrome (MFS) is a genetic connective tissue disease with an increased risk for aortic root dilatation and aortic dissection. Current guidelines, based on expert consensus, recommend exercise restrictions due to concerns that exercise-induced hemodynamic stress may accelerate aortopathy. Studies examining exercise characteristics and their association with aortopathy in MFS patients are lacking. Purpose To assess the association of lifelong exercise characteristics (volume, intensity and type) with the presence of aortic dilatation in MFS patients. Methods An international multi-centre study was conducted in MFS adults. Patients were classified as sedentary (<500 metabolic equivalent of task minutes per week [MET-min/wk]), active (500-1000 MET-min/wk), or highly active (≥1000 MET-min/wk) based on lifelong exercise volumes assessed by a validated questionnaire. Patient’s dominant exercise intensity was classified as moderate (3-6 MET) or vigorous (≥6 MET), and sport type as skill, power, mixed, or endurance. Echocardiography was used to assess diameters at the sinuses of Valsalva (SoV) and ascending aorta (AA), and Campens Z-scores were calculated. Aortic dilatation was evaluated as a diameter ≥40, ≥45 mm, a Z-score ≥2 or ≥3 respectively. Results 315 patients (36[27-49] years, 53% male) were included of which 104 were sedentary, 77 active and 134 highly active (Fig. 1). 42 patients did not perform sport-related exercise, whereas 147 and 121 patients predominantly participated in moderate or vigorous intensity sports. Patients performing sports were allocated to the skill (n=13), power (n=27), mixed (n=158), endurance (n=66) or non-dominant (n=9) exercise type group. Mean SoV and AA diameters were 42.9±7.7 mm and 33.9±7.3 mm. SoV or AA diameters of ≥40 mm were present in 200 (64%) and 41 (13%) patients, whereas 223 (71%) and 81 (26%) patients had a Z-score ≥2 for the SoV or AA. Exercise volume was not associated with SoV dilatation (Fig. 2). Moderate and vigorous intensity sports were associated with a lower prevalence of SoV Z-score ≥3. Power sport was associated with a lower prevalence of all definitions of SoV dilatation, whereas mixed and endurance sports were associated with a lower prevalence of SoV Z-score ≥3. No associations were found with AA dilatation. Of the 17 (5%) patients who suffered from an aortic dissection, 1 case occurred during walking (type A dissection) whereas all other cases were not exercise-related. Conclusions Lifelong exercise volumes were not associated with aortic dilatation in MFS patients. Power sports and vigorous intensity exercise were inversely related to SoV dilatation. Further investigation is warranted to clarify whether this association reflects that patients engaging in these activities have a less severe cardiovascular phenotype, or that they are protected from exercise-related aortic complications, and if patients may miss health benefits due to too exercise restrictions.

The aortic paradox: a nationwide analysis of 523,994 individual echocardiograms exploring aortic dissection

Abstract Background Increasing aortic dilation increases risk of aortic dissection. Nevertheless, dissection occurs below guideline-directed cut-offs for prophylactic surgery. There is no current large-scale population imaging data assessing aortic dimensions before dissection. Purpose To examine the proportion of aortic dissections occurring in people with aortic diameters below guidelines for prophylactic intervention. Methods Patients within the National Echo Database of Australia (NEDA) were stratified according to absolute, height-indexed and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM code I79) were identified via linkage with the National Death Index. Results 524,994 individuals were assessed, comprising patients with normal aortic dimensions (n=460,992), mild dilation (n=53,402), moderate dilation (n=10,029) and severe dilation (n=572). 274,992 (52.4%) were male, with median age 64 years and median follow-up time 6.9 years. 899 fatal aortic dissections occurred (normal diameter=610, mildly-dilated aorta=215, moderately-dilated =53 and severely-dilated=21). Using normal aortas as the reference population, odds of fatal dissection increased with aortic diameter (mild=OR 3.05, 95% confidence interval (CI) 2.61-3.56; moderate=OR 4.0, 95% CI 3.02-5.30; severe=OR 28.72, 95% CI 18.44-44.72). Due to the much larger number of patients without severe aortic dilation, 97.7% of fatal aortic dissections occurred in non-severely dilated aortas. Following sensitivity analysis, severe aortic dilation was responsible for at most 24.4% of fatal aortic dissections. Results were robust for absolute, height-indexed or BSA-indexed aortic measurements. Conclusion Although severe aortic dilatation is associated with a thirty-fold increase in fatal dissection, severely dilated aortas are implicated in only 2.3-24.4% of fatal dissections. This highlights the ‘aortic paradox’ and limitations of current guidelines. Future studies should seek to refine risk predictors in patients without severe aortic dilation.

Association of triglyceride-glucose index and its combination with obesity indicators in predicting the risk of aortic aneurysm and dissection.

The association between the triglyceride-glucose (TyG) index and its combination with obesity indictors in aortic aneurysm and dissection (AAD) remains unclear. We aimed to investigate the association between TyG and TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist height ratio (TyG-WHtR) and AAD risk. This study included 387,483 baseline participants from the UK Biobank with complete data on TyG, TyG-BMI, TyG-WC and TyG-WHtR. Cox proportional hazard models evaluated the relationship between these four indicators and the risk of AAD occurrence. Restricted cubic spline (RCS) examined the non-linear relationship between these indicators and AAD risk, while receiver operating characteristic (ROC) curves assessed the predictive value of these four indicators for AAD risk. Over a median follow-up of 13.7 years, 3,041 AAD events were recorded. Multivariate Cox regression analysis indicated that for each standard deviation increase, the risk of AAD occurrence increased by 33% (HR: 1.33, 95%CI: 1.29-1.38), 25% (HR: 1.25, 95%CI: 1.21-1.29), 61% (HR: 1.61, 95%CI: 1.56-1.66) and 44% (HR: 1.44, 95%CI: 1.39-1.49) for TyG, TyG-BMI, TyG-WC and TyG-WHtR, respectively. RCS demonstrated a linear relationship between these indicators and AAD risk, with TyG-WC demonstrating the best performance in predicting AAD occurrence based on ROC curves. The present study, based on a large prospective cohort design, showed that higher TyG index and its combination with obesity indices were significantly associated with the risk of AAD. Moreover, AFT models further showed that elevation of these indicators significantly advanced the onset of AAD. In addition, RCS analyses demonstrated a linear association between these indicators and the risk of AAD, and the TyG-WC showed higher predictive ability for AAD. These findings emphasize the potential application of the TyG index and its combination with obesity indicators in the early identification of AAD.

A stented elephant trunk procedure with retrograde cerebral perfusion for a rare type of pseudoaneurysm with an aberrant right subclavian artery.

Aberrant right subclavian artery (ARSA) is a rare congenital vascular anomaly that increases the risk of aortic dissection (AD). Although several treatment options for cases of AD with ARSA have been proposed, such as traditional surgery, thoracic endovascular aortic repair, and a hybrid procedure, a consensus regarding the optimal treatment strategy has not yet been established. And there are no reported cases of pseudoaneurysm combined with ARSA. A 44-year-old male was admitted with a 7-days history of chest pain. A physical examination was almost normal. Computed tomography angiography (CTA) showed an ARSA arose from the distal aortic arch and pseudoaneurysm located distal to the origin of the ARSA. The stented elephant trunk (SET) procedure with retrograde cerebral perfusion (RCP) was performed under moderate hypothermic circulatory arrest. The postoperative CTA demonstrated a well-perfused ARSA, left subclavian artery (LSA), left common carotid artery (LCCA), and right common carotid artery (RCCA), and occluded pseudoaneurysm with no endoleaks. He was discharged on postoperative day 9 and was doing well during his 6-months follow-up. With a smaller incision, a simple cannulation method, shorter surgical and circulatory arrest times, fewer blood transfusion requirements, and effective brain protection, the SET procedure with RCP can be a safe and feasible treatment option for complicated aortic arch anomalies with ARSA.

Massive thoracic aortic dissection in the subacute postpartum period in a patient with Marfan syndrome

Aortic dissection is a life-threatening condition that can result in rupture, massive hemorrhage, and death. Parturients with Marfan syndrome are at increased risk of aortic dissection due to connective tissue dysfunction and physiologic changes secondary to pregnancy. Aortic dissection typically manifests during the intrapartum period, rather than the postpartum course. This article discusses a case of a parturient with Marfan syndrome who suffered a massive thoracic aortic dissection in the subacute postpartum period after an uncomplicated vaginal delivery. Abbreviations: CT - computerized tomography; AD - Aortic dissection; MFS - Marfan syndrome; PPD - postpartum day; TEVAR - thoracic endovascular aortic repair; TTE - transthoracic echocardiogram; VAVD - vacuum assisted vaginal delivery; VD - vaginal delivery Keywords: Marfan Syndrome; Pregnancy; Aortic Dissection; Neuraxial Anesthesia Citation: Dhoon T, Crain NA, Rahimian R, Rajan GR. Massive thoracic aortic dissection in the subacute postpartum period in a patient with Marfan syndrome. Anaesth. pain intensive care 2024;28(5):964−968; DOI: 10.35975/apic.v28i5.2564 Received: May 09, 2024; Reviewed: August 15, 2024; Accepted: August 15, 2024

Effects of age, elastin density, and glycosaminoglycan accumulation on the delamination strength of human thoracic and abdominal aortas

Aortic dissection is a life-threatening condition caused by layer separation. Despite extensive research, the relationship between the aortic wall's structural integrity and dissection risk remains unclear. Glycosaminoglycan (GAG) accumulation and elastin loss are suspected to play significant roles. We investigated how age-related changes in aortic structure affect dissection susceptibility. Peeling tests were performed on longitudinal and circumferential thoracic (TA) and abdominal aortic (AA) strips from 35 donors aged 13–76 years (mean 38 ± 15 years, 34 % female). GAG, elastin, collagen, and smooth muscle cell (SMC) contents were assessed using bidirectional histology. Young TAs resisted longitudinal peeling better than circumferential, with delamination strengths of 65.4 mN/mm and 44.2 mN/mm, respectively. Delamination strength decreased with age in both directions, more rapidly longitudinally, equalizing at ∼20–25 mN/mm in older TAs. Delamination strength in AAs was 22 % higher than in TAs. No sex differences were observed. GAG density increased, while elastin density decreased by 2.5 % and 4 % per decade, respectively. Collagen density did not change with age, while SMC density decreased circumferentially. GAGs partially mediated the reduction in longitudinal delamination strength due to aging, while circumferential strength reduction was not mediated by changes in either GAG or elastin densities. This study explains why aortic dissections are more common in TAs, especially in older individuals, and why they typically propagate spirally. TAs exhibit lower delamination strength compared to AAs and experience strength reduction with age, a phenomenon linked to increased GAG accumulation and elastin loss. These findings enhance our understanding of the pathophysiological mechanisms behind aortic dissection. Statement of significanceThis work explores the age-dependent relationships between delamination strength in human aortas and wall structural content. We investigated 35 human aortas from donors aged 13 to 76 years, providing new insights into the biomechanical and histological factors that influence aortic dissection risk. Our findings elucidate how variations in elastin, glycosaminoglycan, collagen, and smooth muscle cell densities impact the structural integrity of the aorta, contributing significantly to the understanding of aortic dissection mechanisms.

Genome-First Approach to Rare and Common Variant Risk of Thoracic Aortic Aneurysm and Dissection

Genome-First Approach to Rare and Common Variant Risk of Thoracic Aortic Aneurysm and Dissection

The potential protective effect of 3-Hydroxybutyrate against aortic dissection: a mendelian randomization analysis

Background3-Hydroxybutyrate, also called β-hydroxybutyrate, is a significant constituent of ketone bodies. Previous observational and experimental studies have suggested that ketogenic diet, especially 3-hydroxybutyrate, may have a protective effect against cardiovascular disease. However, the relationship between ketone bodies, especially 3-hydroxybutyrate, and aortic dissection remains uncertain.Materials and methodsPublicly accessible data from genome-wide association study (GWAS) was utilized to obtain information on ketone bodies, including 3-hydroxybutyrate, acetoacetate and acetone as exposure respectively, while GWAS data on aortic dissection was used as outcome. Subsequently, two-sample Mendelian randomization (MR) analysis was conducted to examine the potential relationship between ketone bodies and aortic dissection. Then, reverse and multivariate Mendelian randomization analyses were performed. Additionally, sensitivity tests were conducted to assess the robustness of MR study.ResultsThe inverse-variance weighted (IVW) method of Mendelian randomization analysis of gene prediction observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection (OR 0.147, 95% CI 0.053–0.410). Furthermore, consistent findings were obtained through the implementation of the weighted median, simple mode, Mendelian randomization-Egger (MR-Egger), and weighted mode methods. After adjusting acetoacetate (OR 0.143, 95% CI 0.023-0.900) or acetone (OR 0.100, 95% CI 0.025–0.398), MR analysis of gene prediction still observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection. No indications of heterogeneity or pleiotropy among the SNPs were detected.ConclusionThe findings from the MR analysis demonstrated that genetically predicted 3-hydroxybutyrate exhibits a protective effect against aortic dissection.

Unveiling the association between fluoroquinolones and aortic diseases using real-world database analysis and pharmacological experiments

Fluoroquinolones, which are widely used antibiotics, have been linked to aortic disease, which prompted an FDA warning in 2018. Recent reports have challenged the perception that fluoroquinolones pose a significant risk for vascular diseases. This study aimed to investigate whether fluoroquinolones increase the risk of aortic diseases by focusing on the onset of aortic dissection. Levofloxacin (LVFX), a fluoroquinolone, was studied in vitro using cultured vascular cells and in vivo using a mouse model prone to aortic dissection. Risk of adverse drug events was analyzed using VigiBase, a global safety database, and a retrospective cohort analysis was conducted using the JMDC Claims database. LVFX resulted in endothelial cell injury and increased matrix metalloproteinases in vitro. However, in vivo studies showed no significant effect on elastin degradation or aortic dissection incidence. The effect of LVFX on endothelial injury was altered during the onset of dissection, exacerbating injury before onset but inhibiting it afterward. Safety database analysis showed no significant risk signals for aortic dissection associated with fluoroquinolones, which was supported by findings in the receipt database. Inconsistencies were observed in the in vitro and in vivo actions of fluoroquinolones and differences in their effects on aortic dissection and aneurysms. Despite cytotoxicity, the risk of aortic dissection was not significantly increased in clinical scenarios. Based on our findings, concerns regarding aortic diseases do not justify discontinuation of fluoroquinolone use. Further studies are needed to elucidate the conflicting actions of fluoroquinolones, taking into account background pathophysiology such as infection and inflammation.

Serum metabolites and risk of aortic dissection: a two-sample Mendelian randomization study

Serum metabolites and risk of aortic dissection: a two-sample Mendelian randomization study

Psychiatric disorders and comorbidity in women with Turner Syndrome: a retrospective national cohort study

Turner syndrome (TS) is a genetic condition characterized by partial or complete monosomy X. A reduced life expectancy has been shown in TS, depending on an increased risk of aortic dissection, and ischemic heart disease. Studies covering the occurrence of psychiatric conditions are sparse within TS. Several case reports describe concomitant TS and neuropsychiatric abnormalities that may represent a pathogenetic link to genetics, as well as feature correlates of TS. The aim of this study was to determine the presence, and the frequency of psychiatric diagnosis in women with TS in a Swedish cohort followed during 25 years’ time. Statistics from the entire female population in Sweden of corresponding age was used as reference. Data were retrieved from clinical examinations and validated from the National Board of Health and Welfare registries for women with TS (n = 487), aged 16 to 84 years, with respect to mental health disorders. The most common diagnoses in TS were mood and anxiety disorders. There was no increase in psychiatric diagnosis within the group with time, nor correlation to specific karyotype or somatic comorbidity as congenital heart disease and hypothyroidism, hormonal treatment, or childbirth. In addition, the frequency of psychiatric diagnosis in TS was lower than in the population-based data. Further investigations are needed in the view of the fact that women with Turner syndrome should not be burdened with more severe diagnoses.

Elective root replacement increases the risk of type B dissection in patients with Marfan syndrome

ObjectiveMarfan syndrome is a genetic disorder with increased risk of aortic dissection. Currently, type A aortic dissection risk is mitigated by aortic root replacement with Dacron. It is unclear if root replacement increases the risk of distal aortic disease given the noncompliant nature of Dacron. MethodsAll adult patients with a diagnosis of Marfan syndrome at a single academic center, excluding those with history of dissection or concomitant arch repair, were studied (n = 322). Student t test or Wilcoxon Mann–Whitney test was used for continuous variables; chi-square or Fisher exact test was used for categorical variables. Propensity matching used age, sex, hypertension, race, body mass index, family history of Marfan syndrome, and genetic mutational class. Differences in freedom from type B aortic dissection were determined using the log-rank test. ResultsA total of 124 patients underwent root replacement compared with 198 patients with no prior aortic surgery. Median follow-up time was 9.90 years. Male sex, weight, and hypertension prevalence were higher in the root replacement group (P < .05). Distribution of fibrillin-1 mutations was homogenous (P > .9). Type B aortic dissection frequency in the root replacement group was higher (21% [n = 20] vs 4.2% [n = 4], P < .001). Aortic-related mortality was higher in the root replacement group (11% [n = 14] vs 3.5% [n = 7], P < .01). Distal aortic intervention frequency was higher in the root replacement group (P = .009). ConclusionsPatients with Marfan syndrome who undergo elective aortic root replacement appear to have a higher incidence of subsequent type B aortic dissection, independent of other risk factors. Careful consideration must be made to the management of the distal aorta in patients with Marfan syndrome who undergo root replacement.

Longitudinal echocardiography in pediatric patients with hypermobile Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos, Marfan and Loeys-Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers-Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric-based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z-scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z-score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z-scores. Repeat echocardiography in those with initial aortic root Z-score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z-score >2.0, not statistically different from the general population. No aortic dissection occurred in first- or second-degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS.

Cardiovascular Management of Aortopathy in Children: A Scientific Statement From the American Heart Association.

Aortopathy encompasses a spectrum of conditions predisposing to dilation, aneurysm, dissection, or rupture of the aorta and other blood vessels. Aortopathy is diagnosed commonly in children, from infancy through adolescence, primarily affecting the thoracic aorta, with variable involvement of the peripheral vasculature. Pathogeneses include connective tissue disorders, smooth muscle contraction disorders, and congenital heart disease, including bicuspid aortic valve, among others. The American Heart Association has published guidelines for diagnosis and management of thoracic aortic disease. However, these guidelines are predominantly focused on adults and cannot be applied adeptly to growing children with emerging features, growth and developmental changes, including puberty, and different risk profiles compared with adults. Management to reduce risk of progressive aortic dilation and dissection or rupture in children is complex and involves genetic testing, cardiovascular imaging, medical therapy, lifestyle modifications, and surgical guidance that differ in many ways from adult management. Pediatric practice varies widely, likely because aortopathy is pathogenically heterogeneous, including genetic and nongenetic conditions, and there is limited published evidence to guide care in children. To optimize care and reduce variation in management, experts in pediatric aortopathy convened to generate this scientific statement regarding the cardiovascular care of children with aortopathy. Available evidence and expert consensus were combined to create this scientific statement. The most common causes of pediatric aortopathy are reviewed. This document provides a general framework for cardiovascular management of aortopathy in children, while allowing for modification based on the personal and familial characteristics of each child and family.