The Heart Muscle and Valve Involvement in Marfan Syndrome, Loeys-Dietz Syndromes, and Collagenopathies.

The inherited connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome [LDS], and Ehlers-Danlos syndrome [EDS]) involve connective tissue of various organ systems. These pathologies share many common features, nonetheless compared to Marfan syndrome, LDS' cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis. The EDS are currently classified into thirteen subtypes. There is substantial symptoms overlap between the EDS subtypes, and they are associated with an increased incidence of cardiovascular abnormalities, such as mitral valve prolapse and aortic dissection.

Proximal aorta longitudinal strain predicts aortic root dilation rate and aortic events in Marfan syndrome.

AIMS: Life expectancy in Marfan syndrome patients has improved thanks to the early detection of aortic dilation and prophylactic aortic root surgery. Current international clinical guidelines support the use of aortic root diameter as a predictor of complications. However, other imaging markers are needed to improve risk stratification. This study aim to ascertain whether proximal aorta longitudinal and circumferential strain and distensibility assessed by cardiac magnetic resonance (CMR) predict the aortic root dilation rate and aortic events in Marfan syndrome. METHODS AND RESULTS: One hundred and seventeen Marfan patients with no previous aortic dissection, cardiac/aortic surgery, or moderate/severe aortic regurgitation were prospectively included in a multicentre protocol of clinical and imaging follow-up. At baseline, CMR was performed and proximal aorta longitudinal strain and ascending aorta circumferential strain and distensibility were obtained. During follow-up (85.7 [75.0-93.2] months), the annual growth rate of aortic root diameter was 0.62 ± 0.65 mm/year. Fifteen patients underwent elective surgical aortic root replacement and four presented aortic dissection. Once corrected for baseline clinical and demographic characteristics and aortic root diameter, proximal aorta longitudinal strain, but not circumferential strain and distensibility, was an independent predictor of the aortic root diameter growth rate (P = 0.001, P = 0.823, and P = 0.997, respectively), z-score growth rate (P = 0.013, P = 0.672, and P = 0.680, respectively), and aortic events (P = 0.023, P = 0.096, and P = 0.237, respectively). CONCLUSION: Proximal aorta longitudinal strain is independently related to the aortic root dilation rate and aortic events in addition to aortic root diameter, clinical risk factors, and demographic characteristics in Marfan syndrome patients.

Aortic flow dynamics and stiffness in Loeys-Dietz syndrome patients: a comparison with healthy volunteers and Marfan syndrome patients.

AIMS: To assess aortic flow and stiffness in patients with Loeys-Dietz syndrome (LDS) by 4D flow and cine cardiovascular magnetic resonance (CMR) and compare the results with those of healthy volunteers (HV) and Marfan syndrome (MFS) patients. METHODS AND RESULTS: Twenty-one LDS and 44 MFS patients with no previous aortic dissection or surgery and 35 HV underwent non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), and aortic diameters were obtained at 20 planes from the ascending (AAo) to the proximal descending aorta (DAo). IRF and SFRR were also quantified for aortic regions (proximal and distal AAo, arch and proximal DAo). Peak-systolic wall shear stress (WSS) maps were also estimated. Aortic stiffness was quantified using pulse wave velocity (PWV) and proximal AAo longitudinal strain. Compared to HV, LDS patients had lower rotational flow at the distal AAo (P = 0.002), arch (P = 0.002), and proximal DAo (P < 0.001) even after adjustment for age, stroke volume, and local diameter. LDS patients had higher SFRR in the proximal DAo compared to both HV (P = 0.024) and MFS patients (P = 0.015), even after adjustment for age and local diameter. Axial and circumferential WSS in LDS patients were lower than in HV. AAo circumferential WSS was lower in LDS compared to MFS patients. AAo and DAo PWV and proximal AAo longitudinal strain revealed stiffer aortas in LDS patients compared to HV (P = 0.007, 0.005, and 0.029, respectively) but no differences vs. MFS patients. CONCLUSION: Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys-Dietz and Marfan patients.

Aortic Branch Aneurysms and Vascular Risk in Patients With Marfan Syndrome.

BACKGROUND: Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown. OBJECTIVES: The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis. METHODS: MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up. RESULTS: A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had >1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter. CONCLUSIONS: Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.

Angiogenic Factors and Long-Term Cardiovascular Risk in Women That Developed Preeclampsia During Pregnancy.

Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment ≈12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein (r=0.341; P=0.006), and negatively with global longitudinal strain (r=-0.581; P<0.001), carotid intima-media thickness (r=-0.251; P=0.045), and mean arterial blood pressure (r=-0.252; P=0.045), when adjusted by study group. sFlt correlated negatively with high-density lipoprotein (r=-0.372; P=0.002) and apolipoprotein A-1 (r=-0.257; P=0.040), and positively with carotid intima-media thickness (r=0.269; P=0.032) and left ventricular posterior wall thickness (r=0.368; P=0.003). The antiangiogenic state present in preeclampsia is related to greater prevalence of cardiovascular risk factors ≈12 years after delivery. The knowledge of altered angiogenic factors may help detect women with a higher risk for premature cardiovascular disease, who will require earlier follow-up after delivery.

The current role of echocardiography in acute aortic syndrome.

Acute aortic syndrome (AAS) comprises a range of interrelated conditions caused by disruption of the medial layer of the aortic wall, including aortic dissection, intramural haematoma and penetrating aortic ulcer. Since mortality from AAS is high, a prompt and accurate diagnosis using imaging techniques is paramount. Both transthoracic (TTE) and transoesophageal echocardiography (TEE) are useful in the diagnosis of AAS. TTE should be the first imaging technique to evaluate patients with thoracic pain in the emergency room. Should AAS be suspected, contrast administration is recommended when images are not definitive. TEE allows high-quality images in thoracic aorta. The main drawback of this technique is that it is semi-invasive and the presence of a blind area that limits visualisation of the distal ascending aorta near. TEE identifies the location and size of the entry tear, secondary communications, true lumen compression and the dynamic flow pattern of false lumen. Although computed tomography (CT) is the most used imaging technique in the diagnosis of AAS, echocardiography offers complementary information relevant for its management. The best imaging strategy for appropriately diagnosing and assessing AAS is to combine CT, mainly ECG-gated contrast-enhanced CT, and TTE. Currently, TEE tends to be carried out in the operating theatre immediately before surgical or endovascular therapy and in monitoring their results. The aims of this review are to establish the current role of echocardiography in the diagnosis and management of AAS based on its advantages and limitations.

Implications of Asymmetry and Valvular Morphotype on Echocardiographic Measurements of the Aortic Root in Bicuspid Aortic Valve.

BACKGROUND: Transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI) have yielded excellent results in aortic root diameter measurement in patients with tricuspid aortic valve. However, accuracy in bicuspid aortic valve (BAV), often associated with aortic root asymmetry, is not fully defined. The aim of this study was to determine the agreement between TTE and MRI in proximal ascending aortic diameters in patients with BAVs. METHODS: Seventy-six consecutive patients with BAVs (mean age, 53 ± 15 years; 65% men) who underwent both TTE and MRI for ascending aortic assessment in a follow-up protocol were included in the study. Maximum aortic root and ascending aortic diameters were compared. RESULTS: For the whole population, TTE slightly underestimated aortic root diameter (difference, -0.8 ± 2.9 mm; P = .02). However, agreement was significantly better in BAV with fusion of the left and right coronary cusps than with fusion of the right coronary and noncoronary cusps, both with (type 1) and without (type 0) raphe (mean difference, 0.1 ± 2.5 vs -2.8 ± 2.8 mm, P < .001, respectively). In raphe BAV, mean absolute differences of maximum diameters between both techniques were significantly greater in asymmetric versus symmetric aortic roots (3.3 ± 2.2 vs 1.6 ± 1.9 mm, P = .002). BAV type and root asymmetry were independent related to measurement disagreement between both modalities. CONCLUSIONS: Although TTE is the technique of choice in the follow-up of patients with BAVs, aortic root diameter measurements may be inaccurate in the presence of root asymmetry and in BAV with fusion of the right coronary and noncoronary cusps. In these cases, cross-sectional imaging, with MRI or computed tomography, to confirm aortic diameters may be advisable.

Rapid ultrasound score as an indicator of atherosclerosis' clinical manifestations in a population of hypertensives: the interrelationship between flow-mediated dilatation of brachial artery, carotid intima thickness, renal resistive index and retina resistive index of central artery.

OBJECTIVE: Flow-mediated dilatation (FMD) of brachial artery, renal resistive index (RRI), retina resistive index of central artery (RRICA) and carotid intima-media thickness (IMT) have been used for ultrasound assessment of cardiovascular risk as good surrogate markers of pre-clinical atherosclerosis. We investigated the interrelationship of these four parameters and examined whether an integrated score is a good indicator of atherosclerotic disease in hypertensives. METHODS: One-hundred fifty-two consecutive subjects were enrolled in this study between April 2004 and April 2005. Each patient underwent cerebral computed tomography, coronarography, carotid, renal, central retinal and femoral arteries Doppler ultrasonographic evaluation. Statistical analysis was performed using ANOVA, Fisher test, Pearson correlation and stepwise regression analyses. RESULTS: FMD, RRICA, IMT and RRI were significantly correlated with each other. In multiple regression analysis age, pulse pressure, hypertension duration were independently related with the four parameters. Eighty-one findings of total atherosclerotic disease (ADAD were recorded overall (15 cerebrovascular disease, 20 coronary heart disease or myocardial infarction, 22 carotid plaques and 24 low limb plaques). Using an integrated score we were able to divide the population into three scoring bands. In the lowest band we classified 87 patients with 16% of total AD; in the intermediate 40 patients with 30% of total AD, in the highest 25 patients with 54% of total AD. Differences between groups were significant (p<0.05). CONCLUSION: A potential benefit of these integrated, low-cost and easy-to-detect parameters, is the stratification of patients with atherosclerotic risk. This method may prove useful in discovering those with atherosclerosis in a pre-clinical stage for whom therapy initiated before complications could reduce the risk for a cerebro-cardio-vascular event.