Sex Differences in the Histopathology of Acute Type A Aortic Dissections.

BACKGROUND: Although sex-related differences in cardiovascular surgery outcomes have increasingly garnered attention in the past decades, knowledge about sex disparities in the pathophysiology of acute type A aortic dissections (ATAADs) remains sparse. In this study, we evaluate the histopathologic and atherosclerotic lesions in female and male ATAAD patients. METHODS: A total of 68 patients were studied: 51 ATAAD patients (mean age: 62.5 ± 10.8 years; 49% women) and 17 control patients (mean age: 63 ± 5.5 years; 53% women). Cardiovascular risk factors were assessed clinically. Intimal and medial histopathological features were systematically evaluated in all. RESULTS: Compared to the control group, all ATAAD patients showed significantly more elastic fiber pathology, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration (p < 0.0001). The tunica intima was significantly thinner in the ATAAD patients than in the control group (p < 0.023), with the latter exhibiting significantly more progressive atherosclerotic lesions than the former. No difference in medial vessel wall pathology was seen between female and male patients. As compared to male ATAAD patients, atherosclerotic lesions were more severe in female ATAAD patients, independent of age and the cardiovascular risk factor hypertension. CONCLUSION: All ATAAD patients had a significantly thinner tunica intima and significantly diseased tunica media compared to the control patients. Our results suggest that the severity of medial aortic pathology is not sex specific in ATAAD patients. Intimal differences between females and males could, however, be considered a potential risk factor for the development of an aortic dissection.

Thoracic aortic atherosclerosis in patients with a bicuspid aortic valve; a case-control study.

INTRODUCTION: Bicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV ascending aortic wall. This study evaluates and compares the prevalence of thoracic aortic atherosclerosis in BAV and tricuspid aortic valve (TAV) patients. METHODS: Atherosclerosis was objectified using three diagnostic modalities in two separate BAV patient cohorts (with and without an aortic dilatation). Within the first group, atherosclerosis was graded histopathologically according to the modified AHA classification scheme proposed by Virmani et al. In the second group, the calcific load of the ascending aorta and coronary arteries, coronary angiographies and cardiovascular risk factors were studied. Patients were selected from a surgical database (treated between 2006-2020), resulting in a total of 128 inclusions. RESULTS: Histopathology showed atherosclerotic lesions to be more prevalent and severe in all TAV as compared to all BAV patients (OR 1.49 (95%CI 1.14 - 1.94); p = 0.003). Computed tomography showed no significant differences in ascending aortic wall calcification between all BAV and all TAV patients, although a tendency of lower calcific load in favor of BAV was seen. Coronary calcification was higher in all TAV as compared to all BAV (OR 1.30 (95%CI 1.06 - 1.61); p = 0.014). CONCLUSION: Ascending aortic atherosclerotic plaques were histologically more pronounced in TAV as compared to the BAV patients, while CT scans revealed equal amounts of calcific depositions within the ascending aortic wall. This study confirms less atherosclerosis in the ascending aortic wall and coronary arteries of BAV patients as compared to TAV patients. These results were not affected by the presence of a thoracic aortic aneurysm.

Evidence Accumulates: Patients with Ascending Aneurysms Are Strongly Protected from Atherosclerotic Disease.

Ascending thoracic aortic aneurysms may be fatal upon rupture or dissection and remain a leading cause of death in the developed world. Understanding the pathophysiology of the development of ascending thoracic aortic aneurysms may help reduce the morbidity and mortality of this disease. In this review, we will discuss our current understanding of the protective relationship between ascending thoracic aortic aneurysms and the development of atherosclerosis, including decreased carotid intima-media thickness, low-density lipoprotein levels, coronary and aortic calcification, and incidence of myocardial infarction. We also propose several possible mechanisms driving this relationship, including matrix metalloproteinase proteins and transforming growth factor-ß.

Histopathology of aortic complications in bicuspid aortic valve versus Marfan syndrome: relevance for therapy?

Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV (n = 36) and TAV (n = 23) without and with dilation and non-dilated MFS (n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin-1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients.

Practical Considerations of Remote Care in Thoracic Aortopathy in India.

Background: Thoracic aortopathy includes conditions like aortic aneurysms and dissections, posing significant management challenges. In India, care delivery is complicated by geographic vastness, financial constraints, and healthcare resource disparities. Telemedicine and digital health technologies offer promising solutions. Methods: A comprehensive review of literature and clinical experiences was conducted to explore the implementation of remote care strategies for thoracic aortopathy in India. The review included studies from 2000 to 2023 and insights from cardiothoracic specialists. Results: Remote care benefits include improved access to specialized expertise, enhanced patient engagement, and optimized resource utilization. Telemedicine enables consultations without travel, and remote monitoring facilitates early intervention. However, challenges like technology integration, digital literacy, patient engagement, privacy concerns, and regulatory compliance need addressing. Discussion: Telemedicine offers significant advantages but requires overcoming challenges to ensure effective, secure care. Careful planning for technology integration, patient education, robust privacy measures, and supportive regulatory policies are essential. Addressing these issues can bridge the healthcare access gap and improve outcomes in India's diverse landscape.

Is the intimal thickness a key contributor to thoracic aortopathy?

Background: An aortic dissection is the most devastating complication of thoracic aortic disease. Several non- and syndromic conditions such as a bicuspid aortic valve (BAV) and Marfan syndrome (MFS) have a severely increased risk to develop a thoracic aortic aneurysm and dissection. To date, the medial layer has been extensively studied in search of the pathogenetic mechanisms leading to aortic complications. Objective: We aim to determine whether intimal layer pathology is characteristic in all thoracic aortopathy regardless of the underlying etiology. Method: A total of 176 aortic wall specimen were studied for the intimal layer architecture including the intimal thickness, endothelial cell morphology, and atherosclerosis. Specimens were derived from four patient groups: BAV (n = 70, age 57 ± 8.9 years), isolated tricuspid aortic valve (TAV) (n = 38, age 64.9 ± 11.0 years), MFS with a TAV (n = 8, age 34.2 ± 11.0 years), type A dissections with a TAV (n = 60, age 62.7 ± 10 years). Results: The intimal layer is significantly thinner in BAV, MFS, and type A aortic dissection as compared to the isolated TAV patients (p < 0.001). Intimal atherosclerosis was also significantly less present in the three groups as compared to the isolated TAV (p < 0.05). Discussion: A thin intimal layer is a common finding in the thoracic aortopathy patients. Studies aiming at preventing future aortic complications should focus on the intimal pathology as a common effector pathway in thoracic aortopathy.

Intrinsic histological and morphological abnormalities of the pediatric thoracic aorta in bicuspid aortic valve patients are predictive for future aortopathy.

BACKGROUND: Patients with a bicuspid aortic valve (BAV) have an increased risk to develop aortic complications. Many studies are pointing towards a possible embryonic explanation for the development of both a bicuspid aortic valve as well as a defective ascending aortic wall in these patients. The fetal and newborn ascending aortic wall has however scarcely been studied in bicuspid aortic valve patients. We hypothesize that early histopathological defects might already be visible in the fetal and pediatric ascending aortic wall of bicuspid aortic valve patients, indicating at an early embryonic defect. METHODS: Non-dilated BAV ascending aortic wall samples were collected (n = 40), categorized in five age groups: premature (age range 17.5 weeks + days GA till 37.6 weeks + days GA) 2. neonate (age range 1 - 21 days) 3. infant (age range 1 month - 4 years) 4. adolescent (age range 12 years - 15 years) and 5. adult (age range 41 - 72 years). Specimen were studied for intimal and medial histopathological features. RESULTS: The premature ascending aortic wall has a significantly thicker intimal and significantly thinner medial layer as compared to all other age categories (p < 0.05). After birth the intimal thickness decreases significantly. The medial layer increases in thickness before adulthood (p < 0.05) with an increasing number of elastic lamellae (p < 0.01) and interlamellar mucoid extracellular matrix accumulation (p < 0.0001). Intimal atherosclerosis was scarce and medial histopathological features such as overall medial degeneration, smooth muscle cell nuclei loss and elastic fiber fragmentation were not appreciated in the BAV ascending aortic wall of any age. CONCLUSIONS: The main characteristics of a bicuspid ascending aortic wall are already present before adulthood, albeit not before birth. Considering the early manifestations of ascending aortic wall pathology in bicuspid aortic valve patients, the pediatric population should be considered while searching for markers predictive for future aortopathy.

Can transforming growth factor beta and downstream signalers distinguish bicuspid aortic valve patients susceptible for future aortic complications?

Patients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of deaths being preventable if individuals at risk are identified and properly managed. Risk stratification for TAADs in bicuspidy is so far solely based on the aortic diameter. Exclusive use of aortic wall dimension, as in the current guidelines, is however not sufficient in selecting patients vulnerable for future aortic wall complications. Moreover, there are no effective medical treatments for TAADs to retain progressive aortic dilatation and thus prevent or delay aortic complications. Only surgical replacement of the aorta increases life expectancy in patients with a risk for a TAAD. Therefore, the next major challenge in the management of TAADs is the development of a personalized patient-tailored risk stratification for early detection of patients with an increased risk for TAADs, who will benefit from surgical resection of the aorta. Several signaling pathways have been studied in recent times to develop a patient specific risk stratification model. In this paper we discuss TGF-ß signaling and downstream signalers as potential markers for future aortic complications in bicuspid aortic valve patients.

Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease.

Background: Thoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine. Objective: This study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals. Materials and methods: Bicuspid aortic valve (BAV; n = 36), TAV (n = 23), and MFS (n = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression. Results: The MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima (p < 0.0005), a lower expression of contractile VSMCs (p < 0.05), more elastic fiber thinning (p < 0.001), lack of inflammation (p < 0.001), and a decreased progerin expression (p < 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration (p < 0.0001), VSMC nuclei loss (p < 0.0001), apoptosis of the vessel wall (p < 0.03), and elastic fiber fragmentation and disorganization (p < 0.001), as compared to the MFS and dilated TAV. Conclusion: This study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.

Structural abnormalities in the non-dilated ascending aortic wall of bicuspid aortic valve patients.

BACKGROUND: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta, associated with structural differences in the bicuspid aorta. Here we describe the non-dilated ascending aortic wall in bicuspid aortic valve patients. METHODS: BAV (n=41) and tricuspid aortic valve (TAV) (n=18) non-dilated ascending aortic wall samples were studied. We investigated the following features of the aortic wall: vessel wall thickness, endothelial cell morphology, atherosclerosis, and elastic lamellae organization. Medial pathologic features encompassing elastic fiber thinning, fragmentation and degeneration, overall medial degeneration, mucoid extracellular matrix accumulation, and smooth muscle cell nuclei loss were studied. Furthermore, we included apoptosis, periaortic inflammation, and the level of expression of differentiated vascular smooth muscle cells. RESULTS: The non-dilated BAV ascending aortic wall is characterized by a significantly thinner intimal layer, without features of atherosclerosis (P<.001). The medial layer is significantly thicker (P<.001) with more mucoid extracellular matrix accumulation (P<.001). All other medial pathologic features were more prominent in the TAV (P<.001). The media has significantly less differentiated vascular smooth muscle cells (P<.001) between the neatly regulated elastic lamellae which are thinner in the BAV as compared to the TAV (P<.0001). CONCLUSIONS: The BAV ascending aorta without dilatation is characterized by a differentiation defect of vascular smooth muscle cells in the media and a significantly thinner intimal layer without overt pathologic features.

The role of transforming growth factor beta in bicuspid aortic valve aortopathy.

A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac deformity, which is associated with an increased risk to develop a thoracic aortic aneurysm and/or an aortic dissection as compared to persons with a tricuspid aortic valve. Due to the high prevalence of a BAV in the general population and the associated life-long increased risk for adverse vascular events, BAV disease places a considerable burden on the public health. The aim of the present review is to discuss the role of transforming growth factor beta (TGF-ß) signaling in the development of the vascular wall and on how this complex signaling pathway may be involved in thoracic aortic aneurysm formation in tricuspid and BAV patients.

The Prevalence of Coronary Artery Disease in Bicuspid Aortic Valve Patients: An Overview of the Literature.

The prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) patients is a debatable topic. Several studies have indicated that BAV patients have a lower prevalence of CAD compared with patients with a tricuspid aortic valve (TAV), but the effects of age and gender have not always been considered. This systematic review provides an overview of articles which report on CAD in BAV and TAV patients. Searches were executed in April 2021 and January 2022 according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines in three online databases: Medline, Embase, and Scopus. Screening and data extraction was done by two investigators separately. Primary and secondary outcomes were compared between BAV and TAV patients; a fixed effects model was used for correcting on confounders. Literature search yielded 1,529 articles with 44 being eligible for inclusion. BAV patients were younger (56.4 ± 8.3 years) than TAV patients (64 ± 10.3 years, p < 0.001). All CAD risk factors and CAD were more prevalent in TAV patients. No significant difference remained after correcting for age and gender as confounders. BAV patients have a lower prevalence of CAD and CAD risk factors compared with TAV patients. However, when the age differences between both groups are considered in the analyses, a similar prevalence of both CAD and CAD risk factors is found.

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve.

Background: Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown. Methods: In order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients were quantitatively analyzed. Results: Dilated aortas show a 4-fold increase of lymphocytes and a 25-fold increase in B lymphocytes in the adventitia compared to non-dilated aortas. Tertiary lymphoid structures with B cell follicles and helper T cell expansion were identified in dilated and dissected aortas. Dilated aortas were associated with an increase in M1-like macrophages in the aorta media, in contrast the number of M2-like macrophages did not change significantly. Conclusion: This study finds unexpected large numbers of immune cells in dilating aortas of BAV patients. These findings raise the question whether immune cells in BAV aortopathy are innocent bystanders or contribute to the deterioration of the aortic wall.

Acute aortic syndromes in India: The need for a nationwide program to increase awareness.

Acute aortic dissection is a rare, but potentially life-threatening and time-critical condition that is frequently misdiagnosed. Therefore, its prompt and proper diagnosis is vital to increase a patient's chance of survival and to prevent grievous complications. Raising awareness and educating the general population and healthcare professionals about an aortic dissection is mandatory, for early diagnosis and improving the chances of survival.

Accuracy of point-of-care coagulation testing during cardiopulmonary bypass in a patient post COVID-19 infection.

INTRODUCTION: Extracorporeal circulation (ECC) in cardiac surgery is performed under systemic heparinization. Adequacy of heparin therapy and anticoagulation during ECC is assessed by activated clotting time (ACT), although there are concerns regarding the reliability of this measure. The ACT can be affected by factors other than heparin anticoagulation. A novel factor that should be considered is the influence of a COVID-19 infection. More than half of the hospitalized COVID-19 patients develop coagulation abnormalities with dysregulated coagulation test results. Patients recently recovered from COVID-19 may still demonstrate some forms of coagulation disorder affecting the ACT. This case describes an inaccurate point-of-care ACT testing in a patient with previous COVID-19 infection undergoing cardiac surgery with ECC and the alternative coagulation testing performed. CASE PRESENTATION: A 77-years-old Caucasian male presented with symptomatic severe mitral valve regurgitation for which he underwent surgery. Medical history revealed a COVID-19 infection one month before surgery. Pre-operative hematological lab results were normal and baseline ACT during surgery was 100 s. To achieve an adequate ACT of > 400 s, multiple doses of heparin were needed and after administration of a triple dose (75,000 IE heparin in total) this adequate ACT was achieved. In the meanwhile we measured anti-Xa level and APTT, which were at adequate levels when ACT was still < 400 s. DISCUSSION: This case emphasizes the need of alternative methods for monitoring heparin therapy in case ACT does not respond adequately. Another point to highlight in this case is the poorly correlated relation between ACT and APTT and anti-Xa in light of the recent COVID-19 infection. Although studies have shown that COVID-19 infection can cause coagulopathy and altered hemostatic parameters, ACT has never been investigated in COVID-19 patient. Understanding the correlation between ACT, APTT and anti-Xa in COVID-19 patients is mandatory.

Are acute type A aortic dissections atherosclerotic?

Background: Type A aortic dissections (TAAD) are devastating aortic complications. Patients with Marfan syndrome, a bicuspid aortic valve or a thoracic aortic aneurysm have an increased risk to develop a TAAD. These predisposing conditions are characterized by a histologically thin intimal layer and hardly any atherosclerosis. Little is known about the susceptibility for atherosclerosis in patients with a type A aortic dissection. Objective: We aim to systematically describe atherosclerotic lesions in TAAD patients. Materials and methods: A total of 51 patients with a TAAD (mean age 62.5 ± 10.8 years, 49% females) and 17 control patients (mean age 63 ± 5.5 years, 53% females) were included in this study. Cardiovascular risk factors were assessed clinically. All sections were stained with Movat pentachrome and hematoxylin eosin. Plaque morphology was classified according to the modified AHA classification scheme proposed by Virmani et al. Results: In the TAAD group thirty-seven percent were overweight (BMI > 25). Diabetes and peripheral arterial disease were not present in any of the patients. Fifty-nine percent of the patients had a history of hypertension. The intima in TAAD patients was significantly thinner as compared to the control group (mean thickness 143 ± 126.5 µm versus 193 ± 132 µm, p < 0.023). Seven TAAD patients had a normal intima without any form of adaptive or pathological thickening. Twenty-three TAAD patients demonstrated adaptive intimal thickening. Fourteen had an intimal xanthoma, also known as fatty streaks. A minority of 7 TAAD patients had progressive atherosclerotic lesions, 4 of which demonstrated pathological intimal thickening, 3 patients showed early fibroatheroma, late fibroatheroma and thin cap fibroatheroma. In the control group the majority of the patients exhibited progressive atherosclerotic lesions: three pathologic intimal thickening, two early fibroatheroma, six late fibroatheroma, one healed rupture and two fibrotic calcified plaque. Discussion: This study shows that TAAD patients hardly exhibit any form of progressive atherosclerosis. The majority of TAAD patients showcase non-progressive intimal lesions, whereas the control group mostly demonstrated progressive intimal atherosclerotic lesions. Findings are independent of age, sex, or the presence of (a history of) hypertension.

Normal and abnormal development of the aortic valve and ascending aortic wall: a comprehensive overview of the embryology and pathology of the bicuspid aortic valve.

A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac anomaly, in which the valve has only two leaflets, instead of the normal three. Patients with a BAV have an increased risk of aneurysm formation and the development of an aortic dissection. Vascular smooth muscle cells in both the non- and dilated aortic wall are characterized by a maturation defect in all BAV patients, as compared to patients with a tricuspid aortic valve, which can contribute to inherent developmental susceptibility. Besides structural abnormalities of the vascular wall, a turbulent blood flow, caused by bicuspid valve geometry, could expedite the pathological process in the aortic wall, leading to aortopathy. Although the risk for aortopathy is significant, not all BAV patients experience (acute) aortic complications in their lifespan, highlighting the complexity of the pathogenetic process. Recent studies have focused on the embryonic development of semilunar valves and the ascending aortic wall. Their findings highlight that a defect in the embryogenesis could not only explain the development of a malformed aortic valve but also the increased risk for ascending aorta and arch pathology. This review presents an overview of the normal and abnormal development of the aortic valve and the aortic wall: a common defect in early embryogenesis causes the development of a BAV and associated aortopathy.

Are Thoracic Aortic Aneurysm Patients at Increased Risk for Cardiovascular Diseases?

Objectives: Abdominal aortic aneurysms are associated with a sharply increased cardiovascular risk. Cardiovascular risk management is therefore recommended in prevailing guidelines for abdominal aneurysm patients. It has been hypothesized that associated risk relates to loss of aortic compliance. If this hypothesis is correct, observations for abdominal aneurysms would also apply to thoracic aortic aneurysms. The objective of this study is to test whether thoracic aneurysms are also associated with an increased cardiovascular risk burden. Methods: Patients who underwent aortic valve or root surgery were included in the study (n = 239). Cardiovascular risk factors were studied and atherosclerosis was scored based on the preoperative coronary angiographies. Multivariate analyses were performed, controlling for cardiovascular risk factors and aortic valve morphology. Comparisons were made with the age- and gender-matched general population and non-aneurysm patients as control groups. A thoracic aortic aneurysm was defined as an aortic aneurysm of ≥45 mm. Results: Thoracic aortic aneurysm was not associated with an increased coronary atherosclerotic burden (p = 0.548). Comparison with the general population revealed a significantly higher prevalence of hypertension (61.4% vs. 32.2%, p < 0.001) and a lower prevalence of diabetes (1.4% vs. 13.1%, p = 0.001) in the thoracic aneurysm group. Conclusions: The extreme cardiovascular risk associated with abdominal aortic aneurysms is location-specific and not explained by loss of aortic compliance. Thoracic aortic aneurysm, in contrast to abdominal, is not part of the atherosclerotic disease spectrum and, therefore, cardiovascular risk management does not need to be implemented in treatment guidelines of isolated thoracic aneurysms. Hypertension should be treated.

Risk for acquired coronary artery disease in genetic vs. congenital thoracic aortopathy.

Objective: Patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) have a significantly increased risk to develop thoracic aortopathy. Both conditions share many pathophysiological mechanisms leading to aortic complications. Bicuspidy is known to have a low risk for acquired coronary artery sclerosis. The aim of this study is to determine the risk of coronary sclerosis in MFS patients. Methods: Marfan syndrome patients with an aortic root dilatation, which were surgically treated between 1999 and 2017, were included and matched with BAV and tricuspid aortic valves (TAV) patients based on sex and age. Cardiovascular risk profiles were determined in all three groups. Coronary sclerosis was graded in all patients on coronary imaging (coronary angiography or computed tomography) using a coronary artery scoring method, which divides the coronaries in 28 segments and scores non-obstructive (20-49% sclerosis) and obstructive coronary sclerosis (>49% sclerosis) in each segment. Results: A total of 90 matched patients (30 within each group) were included. MFS patients showed less cardiovascular risk factors compared to BAV and TAV patients. TAV patients had higher amounts of obstructive coronary sclerosis as compared to BAV patients (p = 0.039) and MFS patients (p = 0.032). No difference in non- and obstructive coronary artery disease (CAD) was found between the MFS and BAV population. Conclusion: Marfan syndrome and bicuspid aortic valve patients have a significantly lower risk for, and prevalence of CAD as compared to TAV individuals.