Presence Of Aortic Dilatation Research Articles

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.

Circulating Matrix Metalloproteinases for Prediction of Aortic Dilatation in Children with Bicuspid Aortic Valve: A Single-Center, Observational Study

Circulating biomarkers have been proposed for early identification of aortic dilatation progression associated with bicuspid aortic valve (BAV), but matrix metalloproteinases (MMPs) are distinguished as signatures of increased extracellular matrix degradation, a landmark of aneurysm formation. The current study aims to identify the role of MMP-1, MMP-2, MMP-9, and the MMP inhibitor, TIMP-1, in identifying aortic dilation in children with BAV. We conducted a study on 73 children divided into two study groups, depending on the presence of aortic dilatation (group 1–43 BAV controls and group 2–30 children with BAV and aortic dilatation). Each patient underwent a cardiac ultrasound and, in each case, serum MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology. Comparison of the MMPs between the two study groups revealed significantly higher values only in the case of TIMP-1, among BAV controls. Moreover, the same TIMP-1 inversely correlated with aortic annulus absolute size and z score, as well as with ascending aorta z score. No particular correlation between the aortic phenotype and the presence of aortic dilatation was found. Future longitudinal research starting at pediatric ages could show the significance of MMPs screening in BAV individuals as predictors of aortic aneurysm formation.

Ascending aorta dilatation is associated to hard cardiovascular events, follow-up from multicentric ARGO-Perspective project.

Aortic root dilatation has been proposed as hypertension-mediated organ damage (HMOD). Nevertheless, the role of the aortic root dilatation as a possible additional HMOD is still unclear since studies conducted so far are quite heterogeneous regarding the type of population analyzed, the aortic tract considered, and the type of outcomes accounted for. The aim of the present study is to assess whether the presence of aortic dilatation is associated with strong cardiovascular (CV) events (MACE: heart failure, CV death, stroke, acute coronary syndrome, myocardial revascularization) in a population of patients affected by essential hypertension. Four hundred forty-five hypertensive patients from six Italian hospitals were recruited as part of ARGO-SIIA study1. For all centers, follow-up was obtained by re-contacting all patients by telephone and through the hospital's computer system. Aortic dilatation (AAD) was defined through absolute sex-specific thresholds as in previous studies (41 mm for males, 36 mm for females). Median follow-up was 60 months. AAD was found to be associated with the occurrence of MACE (HR = 4.07 [1.81-9.17], p < 0.001). This result was confirmed after correction for main demographic characteristics such as age, sex and BSA (HR = 2.91 [1.18-7.17], p = 0.020). At penalized Cox regression, age, left atrial dilatation, left ventricular hypertrophy and AAD were identified as best predictor of MACEs and AAD resulted a significant predictor of MACEs even after correction for these confounders (HR = 2.43 [1.02-5.78], p = 0.045). The presence of AAD was found to be associated with an increased risk of MACE independently of for major confounders, including established HMODs. AAD ascending aorta dilatation, LAe left atrial enlargement, LVH left ventricular hypertrophy, MACEs major adverse cardiovascular events, SIIA Società Italiana dell'Ipertensione Arteriosa (Italian Society for Arterial Hypertension).

The Presence of Ascending Aortic Dilatation in Patients Undergoing Transcatheter Aortic Valve Replacement Is Negatively Correlated with the Presence of Diabetes Mellitus and Does Not Impair Post-Procedural Outcomes.

A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study. AA was measured, and dilatation was defined as a diameter ≥ 40 mm. Thirty-two patients had dilatation of the AA. A further 32 patients from the present population with a normal AA were matched to the aortic dilatation group with respect to gender, age, body mass index and body surface area, and the resulting study groups were compared with each other. In addition to echocardiographic and clinical characteristics, the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR) was analyzed. Kaplan-Meier curves for short- and long-term survival were obtained, and Pearson's and Spearman's correlations were calculated to identify the predictors between the diameter of the AA and clinical parameters. A total of 19% of the total cohort had dilatation of the AA. The study group with an AA diameter ≥ 40 mm showed a significantly low comorbidity with respect to diabetes mellitus in contrast to the comparison cohort with an AA diameter < 40 mm (p = 0.010). This result continued in the correlation analyses performed, as the presence of diabetes mellitus correlated negatively not only with the diameter of the AA (r = -0.404; p = 0.001) but also with the presence of aortic dilatation (r = -0.320; p = 0.010). In addition, the presence of AA dilatation after TAVR was shown to have no differences in terms of patient survival at 1, 3 and 5 years. There were no relevant differences in the cardiovascular biomarkers studied between the patients with dilated and normal AAs. The presence of AA dilatation before successful TAVR was not associated with a survival disadvantage at the respective follow-up intervals of 1, 3 and 5 years. Diabetes mellitus in general seemed to have a protective effect against the development of AA dilatation or aneurysm in patients with severe AS.

Monocyte-to-HDL-cholesterol ratio is associated with Ascending Aorta Dilatation in Patients with Bicuspid Aortic Valve.

The importance of monocyte count-to-HDL-cholesterol ratio (MHR) in cardio- vascular diseases has been shown in various studies. Ascending aortic dilatation (AAD) is a common complication in the patients with bicuspid aortic valve. In this study, we aimed to investigate the relationship between MHR and the presence of aortic dilatation in the patients with bicuspid aortic valve. The study population included totally 347 patients with bicuspid aortic valve.169 patients with aortic dilatation (ascending aorta diameter ≥ 4.0 cm) and 178 patients with no aortic dilatation. Echocardiographic and laboratory measurement was done and compared between groups. The mean age of the participants was 44.7 ± 15.4 years and average ascending aorta diameter was 3.2 ± 0.3 cm in dilatation negative group and 4.4 ± 0.4 cm in positive group. MHR was significantly increased in in patients with aortic dilatation. MHR and uric acid level was independently associated with the presence of aortic dilatation in the patients with bicuspid aortic valve. We found a significant relationship between MHR and aortic dilatation in the patients with bicuspid aortic valve.

Relationship between sporting discipline and aortic dimensions in middle-aged sportsmen

Abstract Funding Acknowledgements Type of funding sources: None. Background A previous study reported a high prevalence (21%) of clinically relevant aortic dilatation (≥40 mm) in competitive veteran runners and rowers. It is uncertain whether this also applies to middle-aged sportsmen performing other sporting disciplines. Purpose To relate aortic dimensions to sporting disciplines in middle-aged sportsmen. Methods Middle-aged sportsmen, ≥45 years of age, underwent coronary CT angiography. Aortic size was measured at the sinus of Valsalva (cusp-cusp) and the ascending aorta (at the height of the pulmonary trunk). Dominant sporting discipline was categorized as running, cycling or other. Analysis of variance was used to compare baseline characteristics and aortic dimensions across sporting disciplines. Multivariable linear regression was used to adjust for baseline characteristics. Results A total of 260 sportsmen (mean age 55.1 ± 6.4 years; 64 runners, 75 cyclists and 121 other sporting disciplines) were included (Table). Clinically relevant aortic dilatation was found in 5.0% (n = 13). Aortic size or presence of aortic dilatation did not differ across sporting disciplines. Ascending aorta and aortic root size were significantly related to age, body surface area, diastolic blood pressure and exercise tolerance, but not sporting disciplines. Conclusions We found clinically relevant aortic dilatation in 5% of middle-aged sportsmen. Aortic size was not different between sporting disciplines. Aortic size may be more related to level of exercise performance rather than sporting discipline. Running (n = 64) Cycling (n = 75) Other (n = 121) p value Participant characteristics Age, yrs 54.6 ± 6.4 56.1 ± 6.8 54.8 ± 6.2 0.30 Systolic BP, mmHg 129 ± 12 128 ± 13 129 ± 12 0.95 Diastolic BP, mmHg 80 ± 8 79 ± 8 80 ± 9 0.32 Body surface area, m2 2.03 ± 0.14 2.02 ± 0.15 2.07 ± 0.15 0.08 Exercise tolerance, Watt 310 ± 42* 329 ± 47 307 ± 48 0.003 Aortic dimensions Ascending aorta maximum diameter, mm 32.5 ± 3.1 33.0 ± 3.8 32.5 ± 3.6 0.64 SoV mean diameter, mm 34.3 ± 2.8 34.1 ± 2.8 33.7 ± 3.2 0.46 SoV, NCC-RCC diameter, mm 34.2 ± 2.9 34.0 ± 2.9 33.7 ± 3.4 0.61 Any aortic diameter ≥40 mm, n (%) 3 (4.7) 2 (2.7) 8 (6.6) 0.46 Values are mean SD or n (%). *significantly different from cycling and other. BP = blood pressure; SoV = sinus of Valsalva; NCC = non-coronary cusp; RCC = right coronary cusp

Spontaneous Right Ventricular Pseudoaneurysms and Increased Arrhythmogenicity in a Mouse Model of Marfan Syndrome

Patients with Marfan syndrome (MFS), a connective tissue disorder caused by pathogenic variants in the gene encoding the extracellular matrix protein fibrillin-1, have an increased prevalence of primary cardiomyopathy, arrhythmias, and sudden cardiac death. We have performed an in-depth in vivo and ex vivo study of the cardiac phenotype of Fbn1mgR/mgR mice, an established mouse model of MFS with a severely reduced expression of fibrillin-1. Using ultrasound measurements, we confirmed the presence of aortic dilatation and observed cardiac diastolic dysfunction in male Fbn1mgR/mgR mice. Upon post-mortem examination, we discovered that the mutant mice consistently presented myocardial lesions at the level of the right ventricular free wall, which we characterized as spontaneous pseudoaneurysms. Histological investigation demonstrated a decrease in myocardial compaction in the MFS mouse model. Furthermore, continuous 24 h electrocardiographic analysis showed a decreased heart rate variability and an increased prevalence of extrasystolic arrhythmic events in Fbn1mgR/mgR mice compared to wild-type littermates. Taken together, in this paper we document a previously unreported cardiac phenotype in the Fbn1mgR/mgR MFS mouse model and provide a detailed characterization of the cardiac dysfunction and rhythm disorders which are caused by fibrillin-1 deficiency. These findings highlight the wide spectrum of cardiac manifestations of MFS, which might have implications for patient care.

Lower prevalence of aortic dilatation among preemptive pediatric renal transplant recipients - A cross-sectional cohort study.

Aortic dilatation is a cardiovascular complication in pediatric renal transplant recipients and may have an increased risk of aortic dissection, aortic rupture, and death. Studies failed to show an association between blood pressure and aortic dilatation; however, 24-hours ambulatory blood pressure monitoring (ABPM) was not performed. There was also no comparison between preemptive transplantation and dialysis. After ethics approval, a retrospective cross-sectional study was performed on all prevalent pediatric renal transplant recipients from a single tertiary care center. The presence of aortic dilatation was determined using standard echocardiographic measurements, and those with other risk factors for aortic dilatation were excluded. Associations between 24-hours ABPM, renal function, dialysis history, and aortic dimensions were determined. We enrolled 37 participants with the following characteristics: 46% female, mean age 14.5±3.7years, 16% preemptive transplantation, and median end-stage renal disease (ESRD) combined vintage (time from ESRD onset to echocardiogram) 597days (range 289-1290days). We found 16/37 patients (43%) with aortic dilatation at any level, mostly mild. There was no association between 24-hours ABPM measurements and aortic dilatation. None of the preemptively transplanted children had aortic dilatation. This study confirms a high prevalence of aortic dilatation among pediatric renal transplant recipients, which appears to be independent of hypertension on 24-hour ABPM. Patients with preemptive renal transplantation did not have aortic dilatation, suggesting that the effects of dialysis may contribute to the high prevalence of this complication. Pediatric cardiologists need to carefully assess aortic dimensions in these at-risk patients.

Elasticity of ascending aorta and left ventricular myocardial functions in children with bicuspid aortic valve.

The aim of the study was to determine the aortic elasticity parameters (EPs) and myocardial function in children with bicuspid aortic valve (BAV). Additionally, we evaluated the effect of aortic leaflet phenotype (ALP) and aortic dilatation on elasticity parameters. Sixty-two children diagnosed with isolated BAV (mean age 9.3years old; patient group) and 63 healthy children (control group) have been evaluated for this study. Patient group was divided into three age subgroups: between 0-6, 7-11 and 12-17 age intervals. Distensibility (DI) and stiffness index (SI) of ascending aorta were calculated by M-mode echocardiographic data. The myocardial functions were evaluated by tissue Doppler echocardiography. Patient group exhibited significantly lower DI and higher SI than control group (SI: 3.8±1.7 vs 2.4±0.8, P<.0001). The aortic elasticity indexes in patient group with different age subgroups were different from those in control subgroups. Patient group had significantly lower E' velocity at mitral lateral annulus and septum than control group (P<.017 and P<.001). There was no statistically significant correlation between E' velocities and DI/SI values. We, however, found a weak correlation between septal E' velocities and strain values (r=.255, P=.046). EP did not show statistically significant difference with regard to ALP and presence of aortic dilatation. Abnormality of aortic elasticity and myocardial functions can be detected in children with BAV from infantile to adolescent. Myocardial functions are not related to SI and DI. We considered the possibility of intrinsic aortic wall abnormality in children with BAV.

Abstract 307: Circulating sRAGE is Associated With Aortic Dysfunction in Mice Models of Thoracic Aortic Aneurysm

Backgound: The Receptor for Advanced Glycation End products (RAGE) and its ligands are associated with vascular remodeling and trigger the release of a soluble receptor (sRAGE). We demonstrated that sRAGE is elevated in patients with thoracic aortic disease such as patients with bicuspid aortic valve and Marfan syndromes. Circulating sRAGE in these patients correlates with the presence of a dysfunctional aortic structure without linearly correlating with increasing aortic diameter. We hypothesized that elevated sRAGE levels are the result of structural degeneration during aortic aneurysm formation and that they are affected by pharmacological treatments aimed to inhibit vascular remodeling. Methods: Circulating sRAGE was tested by ELISA in two mouse models of thoracic aortic aneurysm (TAA): the AngII chronic infusion model and the hypomorphic FBN1 mgR/mgR . C57BL6 mice were treated with AngII via osmotic pump for 28 days with or without losartan in drinking water. FBN1 mgR/mgR mice were treated with losartan starting from postnatal day 16 (p16). Ascending aorta and blood were collected at day 28 of AngII infusion or at p60 in the hypomorphic model. Aortic dilatation and degeneration were tested by echocardiography and histological analysis. Results: Plasma sRAGE is significantly higher in AngII treated animals when compared to controls (118.1± 8.3 vs 45.6±5.01 pg/ml, p &lt;0.0001) and is associated with aortic aneurysm formation and increased medial thickening. Similarly, sRAGE levels are higher in FBN1 mgR/mgR mice compared to age-matched wild type (1939 ± 320.5 vs 45.6±5.01 pg/ml, p &lt;0.0001) in concomitance with elastin degradation (media score 3.5± 0.8 vs 1.03.5± 0.2, p &lt;0.05) and proximal aorta enlargement. Plasma sRAGE decreases in AngII and FBN1 mgR/mgR mice treated with losartan when compared to age matched untreated or wild type mice (73±24.5 vs 118.1 ± 8.296 pg/ml, p&lt;0.05 and 260.7 ± 4.333 vs 1939 ± 320.5 pg/ml, p&lt;0.001) together with reduced aorta dilatation, medial thickening and elastin fragmentation. Conclusion: sRAGE is elevated in the presence of aortic dilatation in mouse models of TAA, as seen in human aneurysmal patients. These results suggest that sRAGE may be used as a circulating biomarker to assess disease severity in patients with TAA.

The new Ghent criteria for Marfan syndrome: what do they change?

The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.

The Use of Echocardiographic Contrast-Enhanced Rapid Diagnosis of Ruptured Aortic Dissection with Transthoracic Echocardiography

Aortic dissection is an uncommon but often fatal condition if not promptly managed. Although the diagnosis is generally established by transesophageal echocardiography, contrast computed tomography, or magnetic resonance imaging, clinical and radiologic assessment and transthoracic echocardiography represent the first-line approach to patients with sudden onset of severe tearing thoracic pain. Although surface image quality and spatial resolution may prevent detection of an intimal flap, the presence of aortic dilatation, aortic regurgitation, segmental ventricular dysfunction, and effusions indicate a greater likelihood of a lethal outcome and hasten urgent management. Because an aortic rupture may be the cause of an effusion, rapid diagnosis is crucial. We report an unusual case of Stanford type B aortic dissection with rupture that was diagnosed by transthoracic echocardiography and confirmed with an ultrasound contrast injection.

Preservation of the Bicuspid Aortic Valve

Bicuspid anatomy of the aortic valve is a common reason for aortic regurgitation and is associated with aortic dilatation in more than 50% of patients. We have observed different patterns of aortic dilatation and used different approaches preserving the valve. Between October 1995 and February 2006, a regurgitant bicuspid valve was repaired in 173 patients. The aorta was normal in 57 patients who underwent isolated repair. Aortic dilatation mainly above commissural level (n = 38) was treated by separate valve repair plus supracommissural aortic replacement. In 78 patients, aortic dilatation involved the root and was treated by root remodeling. Hospital mortality and perioperative morbidity were low in all three groups. Myocardial ischemia was significantly shorter in repair plus aortic replacement than remodeling (p < 0.001). Freedom from aortic regurgitation II or greater at 5 years varied between 91% and 96%. Freedom from reoperation at 5 years was 97% after remodeling, but only 53% after repair plus aortic replacement (p = 0.33). Symmetric prolapse was the most frequent cause for reoperation. The long-term stability of bicuspid aortic valve repair is excellent in the absence of aortic pathology. In the presence of aortic dilatation, root remodeling leads to equally stable valve durability. In patients with less pronounced root dilatation, separate valve repair plus aortic replacement may be a less complex alternative. Symmetric prolapse should be avoided if the ascending aorta is replaced.

Prevalence of abdominal aortic aneurysm in the offspring of patients dying from aneurysm rupture.

The prevalence of abdominal aortic aneurysm (AAA) is high in the brothers of patients with aneurysm. A genetic component in the development of AAA has, therefore, been postulated. In this study the offspring of patients who had died from AAA rupture were invited to undergo ultrasonography of the abdominal aorta. The attendance rate was 69 per cent. Thirty-nine sons of median age 60 (range 45-75) years and 23 daughters of median age 62 (range 42-80) years were examined. Abdominal aortic dilatation was found in eight men and one woman. The presence of aortic dilatation in these nine cases was not related to age, hypertension, smoking or symptoms of occlusive arterial disease. It is concluded that the sons of those who have died from ruptured AAA constitute a high-risk group for the development of this condition and should be considered for further screening.