Tissue heart valve mineralization: Review of calcification mechanisms and strategies for prevention

Attempts to replace diseased human valves with prostheses began more than 30 yrs ago. Heart valve prostheses can be broadly classified into mechanical prostheses (made out of non-biological materials) and bioprostheses made out of biological tissue. Biological valves are made from animal tissue bovine pericardium and porcine valves. The use of these tissues became commercially available after the introduction of the glutaraldehyde (GA) fixation technique. GA reacts with tissue proteins to form inter- and intramolecular crosslinks, resulting in improved durability. The advantage of bioprostheses compared with mechanical valves is the freedom from thromboembolism; and therefore, the avoidance of long-term anticoagulation therapy. These prostheses are preferable in elderly people and in patients who do not tolerate anticoagulants. However, tissular calcification and primary tissue failure (caused by the mechanical stress) are the main unresolved problems. The causes of calcification are numerous and, to date, a satisfactory solution to this question has not been found, although chemical treatments with metal cations, diphosphonates and treatments eliminating phospholipids have proved to mitigate calcification. In addition, alterna-tive approaches to GA chemical treatment fixation are being proposed to provide the tissue with greater resistance to this process. Studies are under way using polyepoxy compounds, derivates of amino oleic acid (AOA), agents such as diphenylphosphorylazide, carbodiimide, amino acids etc. Further improvements in fixation techniques, as well as in bioprosthesis design (stentless valves) are being made to improve the durability and functional characteristics of bioprosthetic heart valves. The development of a biomaterial capable of withstanding calcification and mechanical stress, while being as durable as mechanical prostheses, would convert the bioprostheses into the replacement of choice by eliminating the need for anticoagulation therapy.