Aortic valve replacement for aortic regurgitation and stenosis, in patients with severe left ventricular dysfunction.

OBJECTIVE: Aortic valve replacement for aortic valve stenosis (AS) and regurgitation (AR) in patients with severe left ventricular (LV) dysfunction contains an increased risk. Few data are available on the outcome of such patients. METHODS: Fifty-five consecutive patients with severe LV dysfunction (ejection fraction, EF; <30%) and aortic valve replacement for AS (n=35) or AR (n=20) were investigated between 1994 and 2001. EF was 25+/-5%, mean transvalvular gradient 26+/-6mmHg (AS), aortic valve area 0.66+/-0.18cm(2) (AS), cardiac index (CI) 2.4+/-0.9l/min/m(2), enddiastolic LV diameter (LVEDD) 64+/-8mm and endsystolic LV diameters (LVESD) was 55+/-3mm. Ninety percent of patients were in New York Heart Association (NYHA) functional class III/IV at admission to the hospital. Concomitant coronary artery bypass grafts (CABG) were performed in 14 patients. Follow-up examinations including chest X-ray, echocardiography, exercise testing, were performed among survivors. RESULTS: The survival rates for AS were: 1-year 76%, 2-year 68.8%, 5-year 64.2%; for AR: 1-year 94.4%, 2-year 86.5%, 5-year 74.2%. NYHA functional class improved from 90% in class III/IV to 45 (AR group) and 24% (AS group) at follow-up (P<0.02). The LVEDD decreased to 54+/-8mm after 1 year. The EF improved to 38+/-4 (AR group) and 40+/-5% (AS group) at follow-up. CONCLUSIONS: Despite severe LV dysfunction, increased 1-year mortality especially in the AS group, aortic valve replacement was associated with improved functional status, symptoms and EF in both groups and in most patients. We, therefore, conclude that aortic valve replacement in patients with severe LV dysfunction can be performed with acceptable risk.

Tissue engineering of heart valves: formation of a three-dimensional tissue using porcine heart valve cells.

Tissue engineering is a promising approach to obtaining lifetime durability of heart valves. The goal of this study was to develop a heart valve-like tissue and to compare the ultrastructure with normal valves. Myofibroblasts and endothelial cells were seeded on a type I collagen scaffold. The histologic organization and extracellular matrix were compared in light and electron micrographs. Radiolabeled proteoglycans were characterized by enzymatic degradation experiments. In tissue engineered specimens, cross sectional evaluation revealed that the scaffold (300 microm) was consistently infiltrated with myofibroblasts. Both sides were covered with a multicellular layer of myofibroblasts and overlaid by endothelial cells (50 microm). A newly formed extracellular matrix containing collagen fibrils and proteoglycans was found in the interstitial space. Collagen fibrils with a 60 nm banding pattern were found in both specimens. Small sized proteoglycans (65 nm) were associated and aligned at intervals of 60 nm with collagen fibrils. Large sized proteoglycans (180 nm) were located outside the collagen bundles in amorphous compartments of the extracellular matrix. The majority of glycosaminoglycans were chondroitin/dermatan sulfate, and a minority were heparan sulfate. The morphology and topography of cells and the organization of extracellular matrix in artificial tissues strongly resembles those of native valve tissues.

Ultrastructure of proteoglycans in tissue-engineered cardiovascular structures.

Proteoglycans such as versican, decorin, and perlecan are important components of the extracellular matrix in various tissues. They play an important role in water homeostasis, tissue elasticity, prevention of calcification, and thrombogenicity. The aim of our study was to detect such proteoglycans in engineered tissue and compare them with the proteoglycans of native porcine heart valves. Myofibroblasts were seeded on a type I collagen scaffold. Thereafter, endothelial cells were seeded onto the presettled myofibroblasts. The newly formed tissue was histologically and immunohistochemically examined. Cupromeronic blue was used for ultracytochemical staining of proteoglycans. Radiolabeled proteoglycans were isolated by ion-exchange chromatography and characterized by enzymatic degradation. Three differently sized proteoglycan precipitates were found. The large-sized proteoglycan (154 nm) was located outside the collagen bundles in a rarely structured extracellular matrix compound. The small-sized proteoglycan (46 nm) was aligned along the collagen bundles at intervals of 60 nm. The intermediate-sized proteoglycan (56 nm) was detected on the cell surface of myofibroblasts. The glycosaminoglycans included 80% chondroitin and dermatan sulfate and 20% heparan sulfate. We conclude that proteoglycans play an important role in the functional integrity of cardiovascular tissues. This study shows the successful production of a heart valve-like tissue with proteoglycans resembling, in terms of type, production, and distribution, proteoglycans of native heart valves.