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Current research focuses on surgical ventricular remodeling, FE modeling, passive constraint, and cell transplantation.
Areas of Focus
Ascending Aortic Aneurysm & Dissection
In developing new treatment options for ascending thoracic aneurysms and / or aortic dissection, precise characterization of the disease process is a necessary foundation to aid in improvements of surgical therapies and to test potential new treatment options.
It has been known since the mid 1980s that systolic performance (systolic shortening and wall thickening) is depressed in the non-ischemic borderzone (BZ) after antero-apical myocardial infarction (MI). It was initially thought that the reduced BZ function was due to mechanical tethering by the infarct. However, finite element based inverse calculations of regional contractility (i.e., active force/stress development), in which optimization routines attempt to match computed and experimentally measured LV volume and strain, suggest that BZ contractility is reduced by more than 50%. Moreover, BZ contractility appears to vary linearly across the BZ and the BZ may be as much as 3 cm in width after antero-apical MI. Finally, preliminary calculations in a single sheep suggest that borderzone contractility is depressed after postero-lateral MI.
Ischemic Mitral Regurgitation
Ischemic mitral regurgitation (MR) affects 1.2 to 2.1 million patients in the United States, with more than 400,000 patients having moderate-to-severe MR. Chronic ischemic MR of 2+ severity discovered at cardiac catheterization for symptomatic coronary artery disease has a 1-year mortality of approximately 17% and the one year mortality for 3+ and 4+ ischemic MR is approximately 40%.
Ischemmic MR is usually managed with mitral annuloplasty alone. However, the need for surgical therapy and the type of surgical therapy remains unclear. For instance, the type of annuloplasty (flexible vs. rigid, complete vs. incomplete) is controversial and the role of surgical remodeling with devices including the Acorn CorCap and Coapsys is unclear.
The Acorn CorCap TM Cardiac Support Device (CSD) (Acorn Cardiovascular, Inc., St.Paul, MN) is a bidirectional woven polyester yarn jacket placed over the left (LV) and right ventricles (RV) in patients with dilated cardiomyopathy and heart failure. The underlying hypothesis is that the CSD will reduce strain and stress associated with progressive ventricular dilation. As a consequence, LV remodeling will halt or reverse cardiac remodeling, and systolic LV function will be chronically improved.
Pre-clinical studies showed that the Acorn CSD reduced end-diastolic volume without an increase in end-diastolic pressure or chamber stiffness. Surprisingly, the Acorn CSD also reduced end-systolic volume, improved isolated myocyte contraction, improved the affinity of the sarcoplasmic calcium pump SERCA2a for calcium, and increased the ejection fraction response to dobutamine. There was also evidence that the Acorn CSD altered post myocardial infarction remodeling, presumably by decreasing stress on the infarct border zone.
A randomized clinical trial of the Acorn CSD has been completed. As in pre-clinical studies, both end-diastolic and end-systolic volumes were decreased and there was an improvement in heart failure class. These findings occurred when the Acorn CSD was used alone or with mitral valve surgery. Despite the numerous pre-clinical and clinical findings, the exact mechanical effects of the Acorn CSD on ventricular wall stress remain unknown.
Surgical Ventricular Remodeling
Initially described by Dor in 1989, endoventricular patch plasty (Dor procedure) is used to reduce left ventricular (LV) volume after myocardial infarction (MI) and subsequent LV remodeling. Briefly, the infarct is incised and a purse-string suture (Fontan Stitch) is used to reduce the circumference of the aneurysm "neck". A patch of either autologous or synthetic material is then sewn to the edge of the aneurysms neck thereby reducing LV volume.
The Dor procedure can be performed safely. However, the NIH-sponsored Surgical Treatment for Ischemic Heart failure (STICH) trial recently found no difference in composite outcome between coronary bypass (CABG) and CABG plus Dor procedure. The authors speculated that improved systolic function was balanced by worsened diastolic function. On the other hand, even if pump function is not improved, the Dor procedure may have important effects on stress, strain and contractility in the infarct borderzone (BZ)
Transcatheter Aortic Valves
Aortic stenosis (AS), due to accumulation of calcium in the valve leaflets, is a major heart valve disease encountered in the elderly. Surgical aortic valve replacement (AVR) is still the gold standard to treat patients with severe AI or AS. AVR is performed with excellent results, including low mortality and good long-term survival. Recently, percutaneous aortic stent valves have been implanted clinically in select patients. However, they have not been rigorously evaluated with respect to their biomechanical interactions and effect on blood flow.
The first human percutaneous TAV implantation was performed in 2002 by Alain Cribier. Two TAV designs have since been investigated in clinical trials: Edwards Sapien, a balloon-expandable, stainless steel stent housing bovine pericardial valve leaflets; and CoreValve, a self-expanding nitinol stent with 21 mm pericardial valve. Overall, TAV has 73-100% implant success and procedural mortality of 2-14% in patients with predicted surgical mortalities of 12-31%.
Studies done on endovascular aortic grafts for abdominal aortic aneurysm on cadaveric aorta has provided insight into the properties and migration forces of various endovascular aortic grafts. Percutaneous valves may have a substantial impact on the care of patients clinically with aortic stenosis. These valves are being tested clinically in humans, but little research has been performed experimentally in pulse duplicators or with computational simulations to determine more long-term effects. In addition, these valves have been proposed to treat bioprosthetic degeneration.
We utilize a custom made biaxial stretcher to determine the biaxial stiffness of certain biologic [Gundiah et al, J Mech Behav Biomed Mater, 2: 288, 2009] and device related materials [Gundiah et al, Ann Thorac Surg, 85, 1631, 2008].
Finite Element Modeling & Analysis
a.Left ventricular (LV) model
More important finite element models of this sort can simulate the effect of 'virtual' surgical procedures. For instance, we recently determined the effect of adjustable passive ventricular constraint on wall stress and pump function [Jhun et al, Ann Thorac Surg, 89:132, 2010].
Also, we have recently described a method for determining myocardial material properties non-invasively using FE modeling and optimization [Sun et al, J Biomech Eng, 131: 111001, 2009]. That method was subsequently used to determine the effect of the Dor Procedure (above) on the contractility of infarct borderzone [Sun et al, J Thorac and Cardiovasc Surg, 140: 233, 2010].
b. Model of the LV + Mitral Valve
Our experimental method is cardiac MR imaging with tags. MR images are contoured and used as the basis for finite element models.
In addition, 3D strain is calculated from the tag lines. 3D myocardial strain before and after surgical remodeling has inherent value [Zhang, et al, J Thorac Cardiovasc Surg, 134: 1017, 2007] but we also use the calculated strain as the 'gold standard' when optimizing material properties.