Carsten J. Beller

Role of Aortic Root Motion in the Pathogenesis of Aortic Dissection

Background—The downward movement of the aortic root during the cardiac cycle may be responsible for producing the circumferential tear observed in aortic dissections. Methods and Results—Contrast injections were investigated in 40 cardiac patients, and a finite element model of the aortic root, arch, and branches of the arch was built to assess the influence of aortic root displacement and pressure on the aortic wall stress. The axial displacement of the aortic root ranged from 0 to 14 mm. It was increased in patients with aortic insufficiency (22±13% of the sino-tubular junction diameter versus 12±9%) and reduced in patients with hypokinesis of the left ventricle (10±9% of sino-tubular junction versus 17±12%). The largest stress increase due to aortic root displacement was found approximately 2 cm above the sino-tubular junction, where the longitudinal stress increased by 50% to 0.32 Nmm−2 when 8.9-mm axial displacement was applied in addition to 120-mm Hg luminal pressure. A similar result was observed when the pressure load was increased to 180 mm Hg without axial displacement. Conclusions—Both aortic root displacement and hypertension significantly increase the longitudinal stress in the ascending aorta. For patients with hypertension who are at risk of dissection, aortic root movement may be monitored as an important risk factor.

The peroxynitrite decomposition catalyst FP15 improves ageing-associated cardiac and vascular dysfunction

Overproduction of oxidants and free radicals in ageing tissues induces nitro-oxidative stress, which has recently been implicated in the pathogenesis of cardiovascular dysfunction associated with ageing. Peroxynitrite, a strong cytotoxic oxidant damages proteins and DNA and activates several pathways causing tissue injury, including the peroxynitrite-poly(ADP-ribose) polymerase (PARP) pathway. In this study, we investigated the effectiveness of the peroxynitrite decomposition catalyst FP15 on ageing-associated cardiac and vascular dysfunction. Young and ageing rats were treated with vehicle or FP15 intraperitoneally. Using a microtip Millar pressure catheter we performed left ventricular blood pressure analysis to assess systolic and diastolic function. Endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine and sodium nitroprusside. Ageing animals showed a marked reduction of systolic and diastolic cardiac function and loss of endothelium-dependent relaxant responsiveness of aortic rings. FP15-treatment significantly improved cardiac performance and endothelial function. Immunohistochemical staining confirmed that FP15 effectively reduced nitrosative stress and prevented the activation of PARP in the aortic wall of ageing rats. Our results demonstrate the importance of endogenous peroxynitrite-overproduction in the pathogenesis of ageing-associated cardiovascular dysfunction. Pharmacological decomposition of peroxynitrite by FP15 may represent a novel therapeutic utility to improve cardiac and vascular dysfunction associated with ageing.

Structural analysis of the natural aortic valve in dynamics: from unpressurized to physiologically loaded.

A novel finite element model of the natural aortic valve was developed implementing anisotropic hyperelastic material properties for the leaflets and aortic tissues, and starting from the unpressurized geometry. Static pressurization of the aortic root, silicone rubber moulds and published data helped to establish the model parameters, while high-speed video recording of the leaflet motion in a left-heart simulator allowed for comparisons with simulations. The model was discretized with brick elements and loaded with time-varying pressure using an explicit commercial solver. The aortic valve model produced a competent valve whose dynamic behavior (geometric orifice area vs. time) closely matched that observed in the experiment. In both cases, the aortic valve took approximately 30 ms to open to an 800 mm(2) orifice and remained completely or more than half open for almost 200 ms, after which it closed within 30-50 ms. The highest values of stress were along the leaflet attachment line and near the commissure during diastole. Von Mises stress in the leaflet belly reached 600-750 kPa from early to mid-diastole. While the model using the unpressurized geometry as initial configuration was specially designed to satisfy the requirements of continuum mechanics for large deformations of hyperelastic materials, it also clearly demonstrated that dry models can be adequate to analyze valve dynamics. Although improvements are still needed, the advanced modeling and validation techniques used herein contribute toward improved and quantified accuracy over earlier simplified models.

Mechanical behavior of human aortas: Experiments, material constants and 3-D finite element modeling including residual stress

Segments of fresh human ascending, thoracic descending and abdominal aortas from eight male sexagenarians were pressurized under closed-end and free extension conditions. The median unpressurized inner radii for the ascending, thoracic and abdominal locations were 14.21, 9.67 and 7.16mm, respectively. The median thickness was similar in the ascending and thoracic regions, at about 1.6mm, while it was 1.2mm in the abdominal region. The opening angle was not statistically different between regions, with a median of -38 degrees . Under 13.3kPa pressure, the median circumferential stretch ratio was about 1.26 in all three aortic locations; the median longitudinal stretch ratio was similar in the ascending and thoracic regions, at about 1.13, while it was 1.05 in the abdominal region. Material constants for a three-dimensional hyperelastic anisotropic constitutive model were determined. Experimental, analytical and finite element results showed excellent agreement, validating the novel experimental approach and the numerical methods used. When residual stress was not taken into account, stresses were highest on the inside of the aorta, with a gradient across the wall of about 200 and 50kPa in the circumferential and longitudinal directions, respectively. When residual stress was included as described by negative opening angles, stresses were highest on the outside of the aorta, with a gradient across the wall in excess of 400kPa for the circumferential direction, and on the order of 150kPa for the longitudinal direction. The mechanical consequences of negative opening angles had not been appreciated so far, and deserve further investigation.

Finite element modeling of the thoracic aorta: including aortic root motion to evaluate the risk of aortic dissection

Objective: We propose that the aortic root motion plays an important role in aortic dissection. Methods and results: A finite element model of the aortic root, arch and branches of the arch was built to assess the influence of aortic root displacement and pressure on the aortic wall stress. The largest stress increase due to aortic root displacement was found at approximately 2 cm above the top of the aortic valve. There, the longitudinal stress increased by 50% to 0.32 MPa when 8.9 mm axial displacement was applied in addition to 120 mmHg luminal pressure. A similar result was observed when the pressure load was increased to 180 mmHg without axial displacement. Conclusions: Both aortic root displacement and hypertension significantly increase the longitudinal stress in the ascending aorta, which could play a decisive role in the development of various aortic pathologies, including aortic dissection.

Preoperative high leukocyte count: a novel risk factor for stroke after cardiac surgery

BACKGROUND Stroke after cardiac surgery is a devastating complication. The relationship between white blood cell count (WBC) and perioperative cerebrovascular accident (CVA) has not been investigated. An effort was made to identify how preoperative WBC may relate to CVA development during or after cardiac surgery. METHODS Prospective data were collected from 7,483 patients who underwent coronary artery bypass grafting or valvular surgery or both. WBC was determined preoperatively and postoperatively. Differentiation of WBC was examined only preoperatively. RESULTS There were a total of 125 CVAs (10 transient ischemic attacks [TIAs], 115 strokes). WBC was significantly higher preoperatively and directly postoperatively in patients with stroke. Qualitative changes in preoperative WBC were also found in these patients (chi2; p < 0.001). The predictive power of the stepwise logistic regression model for CVA was greater when preoperative WBC was included. The risk for perioperative CVA increased starting at preoperative WBC of 9 x 10(9)/L (p = 0.044) and progressed in higher WBC ranges. WBC had a significant impact on CVA outcome (analysis of variance, p = 0.001). CONCLUSIONS Our studies have established the correlation between high preoperative WBC and stroke during or after cardiac surgery. Furthermore, elevated preoperative WBC was related to the clinical outcome of CVA. Preoperative measures aimed at preventing or treating conditions such as infections that may cause elevated WBC may be beneficial in the prevention of stroke during or after cardiac surgery.

Mechanical characterization of human aortas from pressurization testing and a paradigm shift for circumferential residual stress.

Material properties needed for accurate stress analysis of the human aorta are still incompletely known, especially as many reports have ignored the presence of residual stresses in the aortic wall. To contribute new material regarding these issues, we carried out measurements and pressurization testing on ascending, thoracic and abdominal aortic samples from 24 human subjects aged 38-77 years, and evaluated the opening angle describing the circumferential residual stress level present in the aorta. We determined material constants for the aorta by gender, anatomic location and age group, according to a simple phenomenological constitutive model. The unpressurized aortic radius positively correlated with age, and the circumferential and longitudinal stretch ratios under systemic pressure negatively correlated with age, confirming the known enlargement and stiffening of the aorta with aging. The opening angle was measured to range from a minimum of 89° to above 360° for extreme cases. For given aortic dimensions and material properties, analysis of the in vivo circumferential and longitudinal mural stress distributions indicated a profound influence of the opening angle. For instance, in the thoracic aorta of males aged 38-66, opening angles in the range of 0° to 80° (resp. 60°) may equalize the gradient of in vivo circumferential (resp. longitudinal) stress between the inner and outer layers of the aorta, as commonly expected; however, opening angles above 160° (resp. 120°) may cause the gradient of circumferential (resp. longitudinal) stress to reverse and increase compared to the case without residual stress, putting the maximum stresses toward the adventitia instead of the intima. Even though the analysis of the aortic wall excluded possible longitudinal residual stresses as well as material inhomogeneities, such as constitutive differences between the intimal, medial and adventitial layers, the experimental data reported herein are important to aortic modeling at large and the better understanding of aortic pathophysiology in particular.

Treatment of ascending aortic aneurysms using different surgical techniques: a single-centre experience with 548 patients

OBJECTIVES The proper treatment of aneurysms of the ascending aorta is still under debate. Here, we describe the early and late outcomes after composite replacement (CR), supracommissural aortic replacement (SCR) and aortic valve-sparing (AVS) operations. METHODS Five hundred and fourty-eight patients were operated on for ascending aortic aneurysm from 1994 until 2011. Two hundred and ninety-eight (54%) patients had CR, 154 (28%) underwent SCR, 96 (18%) received AVS using Davids technique [83 (15%); after October 2006] and 13 (3%) using Yacoubs technique. The average size of the aneurysms was 5.8 ± 1.3 cm and differed between groups (P < 0.001). Patients in the SCR group were older (P < 0.001), and male gender was less frequent in the Yacoub group (P = 0.004). Marfans syndrome was present more often in the AVS group (P < 0.001). RESULTS Times for operation, extracorporeal circulation and aortic cross-clamping differed significantly (P < 0.001). In the SCR group, 40% of patients additionally underwent aortic valve replacement. Rethoracotomy for bleeding was required in 33 patients. Overall, 30-day mortality was 4.8% and did not differ between groups (SCR = 7.2%, CR = 4.8%, Davids technique = 0% and Yacoubs technique = 8.3%; P = 0.12). Six patients experienced cerebral accidents. The follow-up was complete for 93%, and mean follow-up time was 3.9 ± 3.9 (0-17.8) years. Kaplan-Meier analysis revealed a significantly reduced long-term survival for women (log-rank P = 0.0052). Reoperation on the aortic root was necessary in only 6 patients from the Yacoub and SCR groups. No aortic dissection occurred. By uni- or multivariate regression analysis, age and preoperative creatinine were risk factors for 30-day mortality, and age, gender, creatinine, New York Heart Association class and chronic obstructive pulmonary disease, for long-term survival. CONCLUSIONS All four applied techniques result in low mortality and low reoperation rate and prevent aortic dissection. The David procedure yields excellent mid-term results.

Modeling leaflet correction techniques in aortic valve repair: A finite element study

In aortic valve sparing surgery, cusp prolapse is a common cause of residual aortic insufficiency. To correct cusp pathology, native leaflets of the valve frequently require adjustment which can be performed using a variety of described correction techniques, such as central or commissural plication, or resuspension of the leaflet free margin. The practical question then arises of determining which surgical technique provides the best valve performance with the most physiologic coaptation. To answer this question, we created a new finite element model with the ability to simulate physiologic function in normal valves, and aortic insufficiency due to leaflet prolapse in asymmetric, diseased or sub-optimally repaired valves. The existing leaflet correction techniques were simulated in a controlled situation, and the performance of the repaired valve was quantified in terms of maximum leaflets stress, valve orifice area, valve opening and closing characteristics as well as total coaptation area in diastole. On the one hand, the existing leaflet correction techniques were shown not to adversely affect the dynamic properties of the repaired valves. On the other hand, leaflet resuspension appeared as the best technique compared to central or commissural leaflet plication. It was the only method able to achieve symmetric competence and fix an individual leaflet prolapse while simultaneously restoring normal values for mechanical stress, valve orifice area and coaptation area.

Is there any impact of the shape of aortic end-hole cannula on stroke occurrence? Clinical evaluation of straight and bent-tip aortic cannulae

Objective: To compare the impact of straight and bent-tip aortic cannulae on stroke occurrence, location, and severity. Methods: Prospective data were collected on 8129 patients (coronary artery bypass grafting (CABG) and/or valvular surgery). ‘Bent-tip’ aortic cannulae were used in 15.6% of cases and ‘straight’ end-hole cannulae in 84.4% of cases. Results: There were a total of 137 strokes: right anterior 52, left anterior 39, bilateral 23, posterior 18, and location not established5. With the use of bent-tip cannulae, the incidence of strokes was 0.9% versus 1.8% with straight cannulae (c2, p=0.026). Bilateral and posterior strokes occurred more often with the use of straight cannulae (c2, p = 0.015). Straight cannulae also related to the severity of strokes (c2, p = 0.003). Conclusions: There is an influence of the type of cannula on the occurrence, location, and severity of strokes. Straight cannulae cause significantly more often and more severe bilateral and posterior strokes than bent-tip cannulae.