Increase In Aortic Root Diameter Research Articles

Clinical Risk Factors for Aortic Root Dilation in Patients with 22q11.2 Deletion Syndrome: A Longitudinal Single-Center Study.

Aortic root dilation (ARD) has been described in 22q11.2DS, even without congenital heart disease (CHD). However, the clinical implications and longitudinal course are unclear. In this study, we evaluated aortic root (AR) dimensions in 22q112.DS adolescents/adults without major intracardiac CHDs, analyzed the progression over time and investigated correlations with extracardiac comorbidities. AR dimensions were evaluated in 74 patients, measuring the sinus of Valsalva (VS) and proximal ascending aorta (AA), using Z-score to define mild, moderate and severe degrees. Changes in AR dimensions during longitudinal echocardiographic follow-up were investigated. Phenotypic characteristics have been collected. Twenty-four patients (32.4%) showed ARD in terms of VS Z-score (2.43; IQR 2.08-3.01), eight (33.3%) of a moderate/severe degree. Thirteen (54.2%) had concomitant AAD (Z-score 2.34; IQR 1.60-2.85). The risk of ARD was significantly directly related to skeletal/connective tissue disorders (OR 12.82, 95% CI 1.43-115.31; p = 0.023) and inversely related to BMI (OR 0.86, 95% CI 0.77-0.97; p = 0.011). A significant increase in AR diameter's absolute value (p = 0.001) over time has been detected. Isolated ARD is common in 22q11.2DS. Although some clinical risk factors have been identified, pathogenetic mechanisms and risk of complications are undefined. Regular cardiac evaluations should be part of the 22q11.2DS follow-up, and also in non-CHDs patients, to improve long-term outcome.

Increased Mobility of the Atrial Septum in Aortic Root Dilation: An Observational Study on Transesophageal Echocardiography

Background: There is a growing interest in the relationship between atrial septal anatomy and cardioembolic stroke. Anecdotal reports suggest that the enlargement of the aortic root could interfere with atrial septal mobility (ASM). We sought to investigate the association between ASM and aortic root dilation.Methods and Findings: From all consecutive clinically requested transesophageal echocardiogram (TEE) studies performed during the study period in a single institution, we were able to review and evaluate the ASM and anteroposterior length, aortic root diameter, and the prevalence of atrial septal aneurysm (ASA) and of patent foramen ovale (PFO) in 336 studies. Additional variables, such as left ventricular ejection fraction, left atrial diameter, diastolic dysfunction, age, sex, weight, height, previous stroke, atrial fibrillation, and TEE indication, were extracted from patient medical records and echocardiographic clinical reports. In 336 patients, we found a mean ASM of 3.4 mm, ranging from 0 to 21 mm; 15% had ASA and 14% had PFO. There was a 1.0 mm increase in ASM for every 10-mm increase in aortic root diameter adjusted for age, sex, weight, height, ejection fraction, and left atrial size (B = 0.1; P = 0.04). Aortic diameter was not associated with a smaller septal length (B = 0.03; P = 0.7).Conclusion: An increased motion of the atrial septum can occur in association with aortic dilation. These findings deserve attention for the relevance of aortic root anatomy in future studies involving atrial septal characteristics and embolic stroke risk.

Localized Antileptin Therapy Prevents Aortic Root Dilatation and Preserves Left Ventricular Systolic Function in a Murine Model of Marfan Syndrome.

BackgroundMarfan syndrome (MFS) is a genetically transmitted connective tissue disorder characterized by aortic root dilatation, dissection, and rupture. Molecularly, MFS pathological features have been shown to be driven by increased angiotensin II in the aortic wall. Using an angiotensin II–driven aneurysm mouse model, we have recently demonstrated that local inhibition of leptin activity restricts aneurysm formation in the ascending and abdominal aorta. As we observed de novo leptin synthesis in the ascending aortic aneurysm wall of patients with MFS, we hypothesized that local counteracting of leptin activity in MFS may also prevent aortic cardiovascular complications in this context.Methods and Results Fbn1 C1039G/+ mice underwent periaortic application of low‐dose leptin antagonist at the aortic root. Treatment abolished medial degeneration and prevented increase in aortic root diameter (P<0.001). High levels of leptin, transforming growth factor β1, Phosphorylated Small mothers against decapentaplegic 2, and angiotensin‐converting enzyme 1 observed in saline‐treated MFS mice were downregulated in leptin antagonist–treated animals (P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Leptin and angiotensin‐converting enzyme 1 expression levels in left ventricular cardiomyocytes were also decreased (P<0.001) and coincided with prevention of left ventricular hypertrophy and aortic and mitral valve leaflet thickening (P<0.01 and P<0.05, respectively) and systolic function preservation.ConclusionsLocal, periaortic application of leptin antagonist prevented aortic root dilatation and left ventricular valve remodeling, preserving left ventricular systolic function in an MFS mouse model. Our results suggest that local inhibition of leptin may constitute a novel, stand‐alone approach to prevent MFS aortic root aneurysms and potentially other similar angiotensin II–driven aortic pathological features.

Association of Aortic Root Dilation from Early Adulthood to Middle Age with Cardiac Structure and Function: The CARDIA Study

The human aorta dilates with advancing age. However, the association between progressive aortic dilation with aging and cardiac remodeling has not been established in studies of community-dwelling adults. The aim of this study was to test the hypothesis that there would be a relationship between aortic size increase over the early adult life span with left ventricular (LV) structural remodeling and subclinical LV dysfunction in middle age, even in the absence of overt cardiovascular and valvular disease. Included were Coronary Artery Risk Development in Young Adults study participants (N=2,933) aged 23 to 35years with available transthoracic echocardiographic measurements during 20years of follow-up. Multivariate linear regression models assessed sex-specific associations between 20-year change in aortic root diameter with LV structure and function. Larger aortic root diameter at 20-year follow-up was associated with greater LV mass (2.77 vs 2.18g/mm in men and women, respectively, P<.001). In longitudinal analyses, increase in aortic root diameter over 20-year follow-up was associated with a greater 20-year increase in LV mass and ratio of LV mass to LV end-diastolic volume ratio in both sexes. In women but not in men, increased aortic root diameter over 20years was associated with increased left atrial dimension, impaired E/E', and impaired early diastolic longitudinal and circumferential strain rates assessed by speckle-tracking echocardiography. Progressive increase in aortic root diameter from early adulthood to middle age was associated with increased LV mass and LV concentric remodeling in both sexes and impaired diastolic function predominantly in women.

Variation in Outcome Reporting in Cardiac Arrhythmias and Aortopathies in Pregnancy [17K

INTRODUCTION: Variation in outcome reporting undermines the usefulness of research as comparisons cannot be drawn when definitions are not standardized. This study aimed to review outcomes reported in studies on pregnant women with cardiac arrhythmias and aortopathies, with a view to developing a core outcome set for future studies in this area. METHODS: A search strategy was designed for MEDLINE, Embase and Cochrane Central databases from 1980 to 2015 to identify studies in pregnant women with arrhythmias and aortopathies. Two reviewers independently assessed titles and abstracts and discrepancies were reviewed by a third reviewer for the final decision on inclusion. RESULTS: After removing duplicates, 3118 titles and abstracts were reviewed and 485 articles involving pregnant women with congenital or acquired cardiac disease were identified. Of these, there were 12 studies on aortopathies and ten on arrhythmias. Overall, 77 outcomes were listed in the arrhythmia group, the most common being: cardiac event (7), syncope (4) and spontaneous abortion (3); 83 outcomes were used in studies on aortopathies, preterm delivery (8), increase in aortic root diameter (6), and abortion (6) being the three most common. The definition of outcomes differed significantly between studies. CONCLUSION: A large number of inconsistently reported outcomes were identified in studies involving pregnant women with arrhythmias and aortopathies. A core outcome set for cardiac disease in pregnancy, in particularly arrhythmias and aortopathies is in the process of being developed for international use in clinical and research settings.

Risk of Aortic Dissection in Pregnant Patients With the Marfan Syndrome

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

Proximal thoracic aorta dimensions after continuous-flow left ventricular assist device implantation: Longitudinal changes and relation to aortic valve insufficiency

In this study we examined the impact of continuous-flow left ventricular assist device (CF-LVAD) support on proximal thoracic aorta dimensions. Aortic root and ascending aorta diameter were measured from serial echocardiograms before and after CF-LVAD implantation in patients with ≥6 months of support, and correlated with the development of >mild aortic valve insufficiency (AI). Of 162 patients included, mean age was 58 ± 11 years and 128 (79%) were male. Seventy-nine (63%) were destination therapy patients. Mean aortic root and ascending aorta diameters at baseline, 1 month, 6 months, 12 months and long-term follow-up (mean 2.0 ± 1.4 years) were 3.5 ± 0.4, 3.5 ± 0.3, 3.9 ± 0.3, 3.9 ± 0.2 and 4.0 ± 0.3, and 3.3 ± 0.2, 3.3 ± 0.3, 3.6 ± 0.2, 3.6 ± 0.3 and 3.6 ± 0.3 cm, respectively. Only change in aortic root diameter from 1-month to 6-month follow-up reached statistical significance (p = 0.03). Nine (6%) patients had accelerated proximal thoracic aorta expansion (>0.5 cm/year), occurring predominantly in the first 6 months after implantation. These patients were older and more likely to have hypertension and baseline proximal thoracic aorta dilation. Forty-five (28%) patients developed >mild AI at long-term follow-up, including 7 of 9 (78%) of those with accelerated proximal thoracic aorta expansion. All 7 had aortic valves that remained closed throughout the cardiac cycle, and this, along with duration of CF-LVAD support and increase in aortic root diameter, were significantly associated with developing >mild AI. CF-LVAD patients have small increases in proximal thoracic aorta dimensions that predominantly occur within the first 6 months after implantation and then stabilize. Increasing aortic root diameter was associated with AI development.

COMPARE and Pediatric Heart Network Investigator trials: Losartan finally validated in humans with Marfan, but much work remains!

A landmark study by Habashi et al1 in 2006 documented for the first time both the prevention and reversal of structural changes in the aorta associated with Marfan syndrome, via pharmacological means. This study, carried out in a rat model, concluded that such results were due to an inhibitor effect by the drug losartan on TGB-β1 (Figure 1).Habashi's paper prompted some physicians, in the absence of human trials, to begin the clinical off-label use of losartan on Marfan patients, arguing that this was justified due to the drug's excellent safety profile. This has caused some controversy.Two significant randomized human trials of losartan in Marfan patients have since been conducted, which contribute different but valuable elements to the debate; the COMPARE trial demonstrated a significantly lower increase in aortic root diameter among study subjects receiving losartan compared with a placebo group after 3 years, although no significant differences were observed in aortic diameter beyond the root itself. A more recently concluded trial by Lacro et al2 from the Paediatric Heart Network, comparing losartan with atenolol (and no placebo group), appeared to show no comparative benefit with respect to the rate of aortic dilatation over three years among the losartan users compared with study patients given atenolol, with both groups of patients experiencing a similar decrease in the rate of dilatation over the 3 year follow-up.Both studies suggest a positive impact of losartan on aortic dilation in humans with Marfan, but they also highlight a number of important questions that remain unanswered. Further trials are clearly needed in order to assess optimal dosing and to guide timing of therapy, and also to further assess the potential and comparative effectiveness of both losartan and β-blockers, individually and in combination, as therapeutic treatments for aortic protection of different groups of patients with Marfan syndrome.

Abstract 18061: Attenuated Aortic Dilatation, Not Increased Wall Stiffness Best Explains the Rise in Pulse Pressure in Women With Aging: Results From the Baltimore Longitudinal Study of Aging

BACKGROUND: While women have a greater increase in pulse pressure (PP) with aging, aortic pulse wave velocity (PWV), a direct measure of arterial stiffness, is not higher in women than men. We hypothesized that a slower increase in aortic root diameter (AoD), rather than greater arterial wall stiffening per se, best explains the rise of PP in women with aging compared to men. METHODS AND RESUTLS: A total of 257 men and 310 women from the Baltimore Longitudinal Study of Aging, aged 25 to 93 years, had 2-8 repeated measures of PP, PWV, and AoD by echocardiography between 1988 and 2013. Linear Mixed-effects (LME) models were used to examine the longitudinal changes in PP, PWV, and AoD indexed to BSA. Age was expressed as First-age (age at entry), and Time (follow up time), to differentiate cross-sectional differences from longitudinal changes over time. Model-predicted values were plotted to illustrate concurrent trajectories of PP, PWV, and AoD (Fig. 1). Men had a pronounced acceleration in PWV increase, but a deceleration in PP increase with age beyond the 5 th decade [β= 0.21, P= 0.0004, and β= - 0.12, P= 0.0419, for (Time х First-age 2 ) in PWV and PP, respectively]; note the changes of the solid line’s slope in Fig.1A, B. On the other hand, women had an acceleration in PWV increase with age [β= 0.19, P= 0.0318, for Time х First-age] concordant with a steady increase in PP [β= 4.7, P&lt; .0001, for Time]. These trajectories resulted in a higher PWV, but a lower PP in men than women beyond the 5 th decade (Fig 1A, B). The dissociation between PP and PWV longitudinal changes in men was accompanied by a steeper increase in AoD in men than women resulting in greater AoD in men beyond the 5 th decade (β=0.04, P= 0.0146) (Fig1C). CONCLUSION: The greater acceleration in AoD in men likely offsets the effect of elevated arterial stiffness blunting the increases in pulse pressure; lesser AoD dilatation in women potentially leaves arterial wall stiffness unopposed, giving rise to a greater increase in PP in women with aging.

Pulse Pressure Is Inversely Related to Aortic Root Diameter Implications for the Pathogenesis of Systolic Hypertension

Hypertension accelerates the age-associated increase in aortic root diameter (AoD), likely because of chronically elevated distending pressures. However, the pulsatile component of blood pressure may have a different relationship with AoD. We sought to assess the relationship between AoD and pulse pressure (PP) while accounting for left ventricular and central arterial structural and functional properties, which are known to influence PP. The study population was composed of 1256 individuals, aged 30 to 79 years (48% women and 48% hypertensive), none of whom were on antihypertensive medications. Blood pressure was measured in the sitting position with conventional sphygmomanometry. PP was calculated as the difference between systolic and diastolic blood pressures. AoD was measured at end diastole at the level of the sinuses of Valsalva with echocardiography. The relationship between AoD and PP was evaluated with multiple regression analyses. PP was 50+/-14 mm Hg in men and 54+/-18 mm Hg in women, and AoD was 31.9+/-3.5 mm in men and 28.9+/-3.5 mm in women. After adjusting for age, age(2), height, weight, and mean arterial pressure, AoD was independently and inversely associated with PP in both sexes. After further adjustments for central arterial stiffness and wall thickness, reflected waves, and left ventricular geometry, AoD remained inversely associated with PP in both men (coefficient=-0.48; P=0.0003; model R(2)=0.51) and women (coefficient=-0.40; P=0.01; model R(2)=0.61). Thus, AoD is inversely associated with PP, suggesting that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility.

Abstract 3431: Pulse Pressure Is Inversely Related to Aortic Root Diameter: Implications for the Pathogenesis of Systolic Hypertension

Background: The age-associated increase in central arterial stiffness manifests as a rise in pulse pressure, which leads to a marked increase in the prevalence of systolic hypertension among older individuals. Aortic root diameter (AoD) also increases with advancing age. According to the prevailing views, hypertension contributes to a further increase in AoD. Conversely, it has been suggested that the age-associated increase in AoD may partially compensate for the increased arterial stiffness. We tested the hypothesis that AoD is inversely associated with pulse pressure. Methods: The study population comprised 1256 individuals, aged 30 –79 years (48% women, 48% hypertensive), none of whom were on antihypertensive medications. Brachial pulse pressure (bPP) was calculated as the difference between sphygmomanometric systolic and diastolic blood pressures. Central pulse pressure (cPP) was derived from calibrated carotid artery pressure waveforms. AoD was measured by echocardiography at the level of the Sinuses of Valsalva. The relationships of AoD with bPP and cPP were evaluated with multiple regression analyses. Results: bPP was 54 ± 18 mmHg in women and 50 ± 14 mmHg in men, and AoD was 28.9 ± 3.5 mm in women and 31.9 ± 3.5 mm in men. After adjusting for age, age 2 , height, weight, and mean arterial pressure, bPP was inversely associated with AoD in both sexes. This inverse association persisted even after adjusting for aortic pulse wave velocity, carotid intima-media thickness, reflected waves, and left ventricular end-diastolic diameter and wall thickness. In the fully adjusted models predicting bPP, the regression coefficients for AoD were −0.48 in men (p = 0.0003, model R 2 =0.51) and −0.40 in women (p = 0.01, model R 2 = 0.61). Similarly, cPP was inversely associated with AoD in both men (coefficient = −0.45, p = 0.0007, model R 2 =0.50) and women (coefficient = −0.40, p = 0.01 model R 2 = 0.61). Thus, each 1 mm increase in AoD was associated with a 0.4 – 0.5 mmHg decrease in bPP and cPP in both sexes. Conclusions: Contrary to the prevailing views, AoD is independently and inversely associated with both bPP and cPP. These findings suggest that a small AoD may contribute to the pathogenesis of systolic hypertension. Longitudinal studies are needed to examine this possibility.

Usefulness of Enalapril Versus Propranolol or Atenolol for Prevention of Aortic Dilation in Patients With the Marfan Syndrome

Despite variable clinical results, beta blockers have become the primary therapy for prevention of aortic dilation in patients with the Marfan syndrome. This study examines the use of the angiotensin-converting enzyme inhibitor enalapril for treatment of these patients. We sought to examine the effects of enalapril versus beta-blocker therapy in patients with the Marfan syndrome and noted improved aortic distensibility (3.0 +/- 0.3 vs 1.9 +/- 0.4 cm2 dynes(-1); p <0.02) and a reduced aortic stiffness index (8.0 +/- 2.9 vs 18.4 +/- 3.8; p <0.05) in patients receiving enalapril compared with those receiving beta blockers. These favorable hemodynamic changes were associated with a smaller increase in aortic root diameter (0.1 +/- 1.0 vs 5.8 +/- 5.2 mm) and fewer clinical end points during follow-up.

Effects of ascending aorta replacement on aortic root dilatation

Because of an increase of aortic root wall stress, prosthetic replacement of the ascending aorta might be a risk factor for the progressive increase of the aortic root dimension. Aim of the present study was to evaluate the aortic root diameter change and the progression of aortic valve regurgitation late after ascending aorta replacement for different ethiology. Sixty-three late survivors after supracoronary ascending aortic replacement were evaluated. Forty-one patients were operated on for acute aortic dissecting aneurysm (group I) and 22 for chronic atherosclerotic non-dissecting aneurysm (group II). Aortic root diameter and aortic valve regurgitation were assessed echocardiografically after a mean follow-up of 63+/-31 months and were compared with those early after surgery. Seven patients of group I (17%) needed reoperation for aortic root dilatation or dissection. Twenty-five percent of the patients (15 of group I and 1 of group II) showed at least a 10% increase in aortic root diameter at follow-up (46.8+/-6.1 vs. 38.1+/-6.1mm, P<0.0001). Aortic root diameter increased almost exclusively in patients operated on for acute dissecting aneurysm. A significant worsening of aortic valve insufficiency with time was evident only in patients operated on for acute dissecting aneurysm with an higher incidence in those with progressive root dilatation. Both the increase of aortic root diameter and the progressive worsening of aortic valve insufficiency seem to justify a more aggressive treatment of the aortic root at the time of surgery for acute aortic dissecting aneurysm but not for chronic atherosclerotic non-dissecting aneurysms.

The marfan syndrome in early childhood: Analysis of 15 patients diagnosed at less than 4 years of age

The clinical, cardiac and echocardiographic features were reviewed of 15 consecutive Infants and children with the Marfan syndrome who presented at < 4 years of age. The 10 females and 5 males were diagnosed at a mean age of 18 months (range 2 days to 3.5 years); 13 were followed up for a mean of 45 months (range 8 to 109 months) and 2 were lost to follow-up. On first evaluation, 5 patients had mitral regurgitation (MR) and none had aortic regurgitation (AR). Echocardiography showed aortic root dilatation in 9 and mitral valve prolapse (MVP) in 9; only 2 patients had a normal echocardiogram. At follow-up examination, all patients had aortic root dilatation; the rate of increase in aortic root diameter was generally greater than predicted on the basis of body surface area. One patient had AR at age 10 years. All 13 patients had MVP; 9 had progressive mitral valve dysfunction and 4 had mitral valve replacement. One patient died immediately postoperatively. Thus, aortic root dilatation is usually present in early childhood and serves as an objective indicator of the Marfan syndrome. MVP is common and MR, which may require valve replacement, is the leading cause of cardiovascular morbidity in childhood. Echocardiography is useful in the diagnosis and routine management of infants and children in whom the Marfan syndrome is suspected.