Brief Reports

Aortic elastic properties in patients with repaired coarctation of aorta

The mechanical and structural behavior of the aorta depend on physiological functions and vary from proximal to distal. Understanding the relation between regionally varying mechanical and multi-scale structural response of aorta can be helpful to assess the disease outcomes. Therefore, this study investigated the variation in mechanical and multi-scale structural properties among the major segments of aorta such as ascending aorta (AA), descending aorta (DA) and abdominal aorta (ABA), and established a relation between mechanical and multi-structural parameters. The obtained results showed significant increase in anisotropy and nonlinearity from proximal to distal aorta. The change in periphery length and radii between load and stress free configuration was also found increasing far from the heart. Opening angle was significantly large for ABA than AA and DA (AA/DA vs ABA; p = 0.001). Mean circumferential residual stretch (ratio of mean periphery length at load and stress free configurations) was found decreasing between AA and DA, and then increasing between DA to ABA and its value was significantly more for ABA (AA vs DA; p = 0.041, AA vs ABA; p = 0.001, DA vs ABA; p = 0.001). The waviness of collagen fibers, collagen fiber content, collagen fibril diameter and total protein content were found significantly increasing from proximal to distal. Pearson correlation test showed a significant linear correlation between variation in mechanical and multi-scale structural parameters over the aortic length. Residual stretch was found positively correlated with collagen fiber content (r = 0.82) whereas opening angel was found positively correlated with total protein content (TPC) (r = 0.76).

This study sought to investigate the impact of transcatheter intervention on left ventricular function and aortic hemodynamics in patients with mild coarctation of the aorta (COA).

The optimal method and timing of transcatheter intervention for COA remains unclear, especially when the severity of COA is mild (peak-to-peak transcoarctation pressure gradient <20 mm Hg). Debate rages regarding the risk/benefit ratio of intervention versus long-term effects of persistent minimal gradient in this heterogeneous population with differing blood pressures, ventricular function, and peripheral perfusion.

We developed a unique computational fluid dynamics and lumped parameter modeling framework based on patient-specific hemodynamic input parameters and validated it against patient-specific clinical outcomes (before and after intervention). We used clinically measured hemodynamic metrics and imaging of the aorta and the left ventricle in 34 patients with mild COA to make these correlations.

Despite dramatic reduction in the transcoarctation pressure gradient (catheter and Doppler echocardiography pressure gradients reduced by 75% and 47.3%, respectively), there was only modest effect on aortic flow and no significant impact on aortic shear stress (the maximum time-averaged wall shear stress in descending aorta was reduced 5.1%). In no patient did transcatheter intervention improve left ventricular function (e.g., stroke work and normalized stroke work were reduced by only 4.48% and 3.9%, respectively).

Transcatheter intervention that successfully relieves mild COA pressure gradients does not translate to decreased myocardial strain. The effects of the intervention were determined to the greatest degree by ventricular–vascular coupling hemodynamics and provide a novel valuable mechanism to evaluate patients with COA that may influence clinical practice.

Early detection and accurate estimation of the extent of coarctation of the aorta (COA) is critical to long-term outcome. Peak-to-peak trans-coarctation pressure gradient (P_KdP) higher than 20 mmHg is an indication for interventional/surgical repair. Patients with COA have reduced proximal and distal aortic compliances. A comprehensive study investigating the effects of variations of proximal COA and systemic compliances on P_KdP, and consequently on the COA severity evaluation has never been done. This study evaluates the effect of aortic compliance on diagnostic accuracy of P_KdP. Lumped parameter modeling and in vitro experiments were performed for COA severities of 50%, 75% and 90% by area. Modeling and in vitro results were validated against retrospective clinical data of P_KdP, measured in 54 patients with COA. Modeling and in vitro. P_KdP increases with reduced proximal COA compliance (+36%, +38% and +53% for COA severities of 50%, 75% and 90%, respectively; p<0.05), but decreases with reduced systemic compliance (−62%, −41% and −36% for COA severities of 50%, 75% and 90%, respectively; p<0.01). Clinical study. P_KdP has a modest correlation with COA severity (R=0.29). The main determinants of P_KdP are COA severity, stroke volume index and systemic compliance. Systemic compliance was found to be as influential as COA severity in P_KdP determination (R=0.30 vs. R =0.34). In conclusion, P_KdP is highly influenced by both stroke volume index and arterial compliance. Low values of P_KdP cannot be used to exclude the severe COA presence since COA severity may be masked by reduced systemic compliance and/or low flow conditions.

Cardiovascular events are the main cause of premature death after successful repair of aortic coarctation (CoA). The aim of this study was to assess the selected biochemical markers of atherosclerosis in normotensive CoA repaired patients and to establish its relation to ultrasound indexes of vascular pathology.

62 patients after CoA repair (37 males, age: 34.1 ± 1.4 yrs) and 20 control individuals (10 males, age: 34.8 ± 2.2 yrs) were enrolled in the study. The serum markers: asymmetric dimethylarginine (ADMA), nitrites/nitrates (NOx), high-sensitivity C-reactive protein (hsCRP), and following vascular parameters: flow-mediated dilatation (FMD), intima-media thickness (IMT) and pulse wave velocity (PWV) were analyzed.

33 CoA repaired patients were normotensive, and compared to controls, they presented higher serum ADMA concentrations (0.59 ± 0.04 umol/l vs. 0.46 ± 0.03 umol/l, p = 0.035). An analysis of the vascular parameters revealed decreased FMD (4.75 ± 0.5%), NMD (11.86 ± 0.8%) and increased PWV (6.90 ± 0.2 m/s) values in the normotensive patients as compared with the control group (FMD: 8.6 ± 0.9%, p < 0.001, NMD: 20.94 ± 1.7%, p < 0.001; PWV: 5.49 ± 0.2, p = 0.023). There were no differences in the serum levels of NOx, hsCRP as well as IMT values between normotensive patients and the control group. A multivariate regression analysis revealed that serum ADMA level was a factor independently associated with the FMD value (r = −0.334; p = 0.031) in normotensive CoA repaired group.

Early biochemical and vascular indices of atherosclerosis such as increased serum ADMA concentration as well as impaired vasodilatation and increased arterial stiffness are observed in patients after CoA repair. Serum ADMA is a strong predictor of endothelial dysfunction in patients with CoA repair.

HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful coarctation repair. The effect of statins on cardiovascular risk in adults after successful coarctation repair has not yet been established.

We designed a multicentre, prospective, randomised, open label trial to evaluate the effect of the HMGcoA-reductase-inhibitor (Atorvastatin) on atherosclerotic progression in adult post-coarctectomy patients. The primary endpoint in this study is the carotid intima-media thickness as measured by Bmode ultrasonography of the carotid arteries.

This large prospective, randomised, open label trial will establish the effect of HMG-coA-reductase inhibitors (Atorvastatin) on cardiovascular risk in adult patients after successful coarctation repair.