Plenary Session

1.  Transapical Aortic Valve Implantation: Single Center Experience
Michael A. Borger;   Thomas . Walther;   Volkmar . Falk;   Joerg . Kempfert;   Sven . Lehmann;   Axel . Linke;   Gerhard . Schuler;   * Friedrich W. Mohr
Leipzig Heart Center, Leipzig, , Germany

OBJECTIVES: To evaluate the feasibility and outcome of minimally invasive transapical placement (TAP) of an aortic valve xenograft using an oversizing technique for high risk patients with aortic stenosis at a single institution.

METHODS: TAP was performed via a small anterolateral minithoracotomy with or without femoro-femoral CPB on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (SAPIEN THV, Edwards Lifesciences, Irvine, CA, USA) was used. 44 consecutive patients (82 ± 5 years, 34 (77%) female) were operated on since February 2006 using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27 ± 12%.

RESULTS: TAP valve positioning was performed successfully in 43 patients (11 x 23 mm and 32 x 26 mm valves). Early conversion to full sternotomy was required in 2 patients. Implantation was performed on the beating heart during brief periods of rapid ventricular pacing. Femoral CPB support was applied in 15 patients. Neither coronary artery obstruction nor migration of the prosthesis was observed. All valves had good hemodynamic function. Echocardiography revealed paravalvular leakage in 20 patients (mild in 13 and trace in 5). Total 30-day mortality was 7% (three patients), all confirmed as non-valve related deaths by autopsy. During follow up (1 - 353 days post-procedure) five patients died, all due to non-valve related reasons. Actuarial survival at 9 months was 72%.

CONCLUSIONS: TAP is feasible using an off pump technique. Initial results are very good, especially considering the high risk patient profile. Further evaluation, including longer term follow up, is required.

2.  Influence Of Concomitant Mitral Valve Dysfunction On Survival After Aortic Valve Replacement
Anelechi C. Anyanwu;   Farzan . Filsoufi;   Parwis B. Rahmanian;   Javier G. Castillo;   David H. Adams
Mount Sinai School of Medicine, New York, NY, United States

OBJECTIVES: To examine the influence of treated (mitral valve repair/replacement) or untreated mitral dysfunction on survival after AVR.

METHODS: We retrospectively analyzed 1097 patients who underwent AVR or Bentall over 6 years in single institution, comparing patients without mitral dysfunction (Group A, 870 pts), with treated mitral dysfunction (Group B, 181 pts), and untreated mitral dysfunction (Group C, 46 pts). The primary indication for AVR was stenosis (n=419), insufficiency (n=453), both (n=128), root aneurysm (n=58) and other (n=39). Mitral dysfunction was defined as moderate or severe regurgitation or stenosis.

RESULTS: Group C patients were older (median age 73 years Vs 69 Group A, 66 Group B, P= 0.02) and sicker with a higher predicted mortality (logistic euroSCORE A=12%, B=14%, C=20%). Early mortality was highest in untreated mitral dysfunction (Group A 4.7%, Group B 8.3%, Group C13.0%; P=0.01) as was one year survival (92%; 84% and 70% in Groups A, B and C respectively). Although greater operative risk may partly explain poorer survival, we still found significant survival difference, when only patients with predicted mortality >5% were considered (1-year survival 90%, 80%, 66% respectively P<0.0001). On multivariate analysis, untreated mitral dysfunction remained predictive of one-year mortality (hazard ratio 2.5, P=0.003). Mitral valve dysfunction or mitral valve surgery per se were not independent predictors of mortality on multivariate analysis.

CONCLUSIONS: Untreated mitral dysfunction is independently associated with poorer survival after aortic valve surgery. Concomittant mitral valve surgery should be considered in patients undergoing aortic valve/root surgery who have significant mitral dysfunction.

3.  Effects Of Aortic Valve Elasticity On Leaflet Stresses
Reetu . Singh;   * Joel A. Strom;   Leo . Ondrovic;   Babu . Joseph;   Michael D. VanAuker
University of South Florida, Tampa, FL, United States

OBJECTIVES: Degeneration of aortic valve (AV) leaflets occurs because of high mechanical stresses resulting from altered leaflet dynamics. Leaflet elasticity, which determines the leaflet compliance, plays a major role in valve dynamics and stress distributions. In this study, we sought to evaluate the effects of AV leaflet compliance on valve dynamics and leaflet stress patterns and its implications for valve degeneration.

METHODS: A three dimensional finite element model of the AV and root was developed using Ansys® (Fig. 1a) employing optimal valve geometry (courtesy: Dr. Michel R. Labrosse, University of Ottawa, Canada). A dynamic analysis of valve opening was performed using a transient pressure pulse. AV leaflet moduli ranged from 2 to 5 MPa, leaflet and root thicknesses of 0.5 mm and 1.5 mm respectively, and a root elastic modulus of 6 MPa were used. Leaflets and root were modeled as linear, isotropic, and incompressible.

RESULTS: The opening cycle consisted of two phases: an initial rapid opening phase followed by a slower one. Maximum leaflet stresses occurred along the leaflet-root attachment (Fig 1b), analogous to the spatial distribution of calcific deposits in the AV. Increasing leaflet stiffness slowed valve opening; and a 50% and 150% increase in stiffness increased mechanical stress by 43.1% and 97.3%, respectively.

CONCLUSIONS: Loss of leaflet compliance leads to altered leaflet dynamics and increased stresses. This emphasizes the role of loss of leaflet elasticity on the development of degenerative AV disease and its progression and it has implications in the design of bioprosthesis for valve replacement.

4.  The Fate Of The Preserved Aortic Valve And Aortic Root In Patients After Surgery With The Yacoub And David Technique
Thorsten . Hanke;   Ulrich . Stierle;   Katrin . Meyer;   Armin . Erasmi;   * Hans-Hinrich . Sievers;   * Misfeld . Martin
Clinic for Cardiac and Thoracic Aortic Surgery University Clinic Schleswig Holstein Campus Luebeck, Luebeck, , Germany

OBJECTIVES: Autograft regurgitation (AR) and aortic root dilatation following aortic valve preservation surgery (AVP) is an issue of major interest among the cardiothoracic society. We reviewed patient records from our institution in order to document the development of AR and aortic root dimensions with time and compared two different techniques of aortic valve preservation.

METHODS: Between 1990 and 2006 191 patients (131m, 60f; mean age 53±15.8y) underwent replacement of the ascending aorta with AVP utilising 2 different techniques (Yacoub=Y, n=108, David I=DI, n=83). Clinical and serial echocardiographic follow-up was performed (mean follow-up 4.5±2.7y). For statistical analysis of serial measurements over time a hierarchical multilevel modeling technique was applied.

RESULTS: Initial AR grade was 0.43 (Y=0.49, DI=0.34,p<0.013) with an annual increase of 0.082 (Y=0.099, DI=0.04, p=n.s.). Annulus and sinus diameters differed significantly among both groups (Y=22.6/31.3, DI=20.7/28.4mm,p<0.05). Bicuspid aortic valve morphology and type-A dissection did not have any impact on AR grade and root dimensions with time, irrespective of the surgical technique. In patients with Marfan´s syndrome initial AR grade did not differ significantly among both surgical groups, but annual increase thereof (Y=0.132, DI=0.075, p<0.049). Aortic root dimensions and the annual sinus diameter increased significantly in Y (annulus Y=25.1, DI=19.9,p<0.024, sinus Y=1.256, DI=-1.023,p<0.0001).

CONCLUSIONS: AVP showed favourable clinical and hemodynamic results in both surgical techniques. Development of AR over time was minor and the annual progression thereof is currently not substantial. In Marfan´s pts, use of the Yacoub technique is associated with a higher risk of AR progression and sinus dilatation in the long run.

5.  A Novel Role Of Beta 2-adrenergic Receptor Agonists In Regulating Valve Calcification
Lana . Osman;   Adrian H. Chester;   Najma . Latif;   Padmini . Sarathchandra;   Wenfang . Meng;   Patricia M. Taylor;   Magdi H. Yacoub
Imperial College London, Harefield, Middlesex, United Kingdom

OBJECTIVES: Aortic valve Calcification is a progressive process resembling ossification. Beta 2-adrenergic receptors (β2-ARs) have been shown to regulate bone remodelling. However, the role of these receptors in calcification of the aortic valve is unknown. We aimed to determine the expression of β-ARs in human valve interstitial cells (ICs) and investigate their influence on osteoblastic differentiation of the cells.

METHODS: Real-time TaqMan PCR was used to determine β-AR gene expression in the valve ICs, while immunohistochemistry was used to determine the level of expression of β-ARs in valve leaflet. Cells were treated with osteogenic medium and the resultant change in the phenotype of the cells was assessed with an alkaline phosphatase (ALP) activity assay, immunocytochemistry and western blotting.

RESULTS: The expression of β1-AR and β2-AR was observed in human valve leaflets leaflets and primary cultures of human valve ICs. Valve ICs treated with salmeterol in the presence of osteogenic medium significantly reduced the ALP activity from 10.2±2.9 nmol/min/mg protein in the osteogenic treated cells, to 4.7±1.9 nmol/min/mg protein (P<0.04, n=3). Salmeterol alone had no effect. Staining for osteocalcin was evident in valve ICs treated with osteogeneic medium, which was reduced when the cells were treated with salmeterol in the presence of osteogenic medium. In addition, other β2-AR agonists also caused a reduction in the protein expression of bone markers including ALP, Cbfa-1 and periostin.

CONCLUSIONS: These findings suggest a novel role of the β2-ARs in preventing valve calcification and may identify potential therapeutic targets.

6.  The Digital Leaflet: Quantitative Image Analysis And 3d Digital Reconstruction Of The Aortic Valve Leaflet
John . Stella;   * Michael S. Sacks
University of Pittsburgh, Pittsburgh, PA, United States

OBJECTIVES: The current study utilizes histological sectioning techniques to reconstruct and quantify the 3D microstructure of the complete aortic valve leaflet (AVL). In addition to gaining further insight into leaflet structure function relationships, the current study will lay the basis for the development of analytical tools involving ~10 micron-scale anatomically accurate 3D finite element representations.

METHODS: After fixation (10% buffered formalin), leaflets were paraffin embedded, 5 micron thick radially oriented sections were cut at 15 micron intervals, and stained with Movat’s Pentachrome. Digitized section images were then quantified with the biological image analysis software package MetaMorph™. An additional software package, AutoAligner™, was used to automatically translate and rotate each section relative to the previous section image creating a registered 3D volume.

RESULTS: The methods employed in the current study produced a detailed mapping of the complex structural organization exhibited by native AVL tissues. Results suggest that layer specific cell densities remain relatively constant across the leaflet while thickness and ECM composition varies. Also, the AutoAlign™ software was capable of accurately registering the histological sections to create a 3D volume.

CONCLUSIONS: The 3D reconstruction of the AVL will permit the development of a microstructure guided finite element mesh central to future modeling endeavors. Developing a comprehensive modeling framework incorporating cellular properties, tissue level characteristics, and their relation to organ level function will advance our understanding of the subtle but important characteristics of native valve function.