Prevention of calcification in bioprosthetic heart valves: challenges and perspectives

Surgical replacement with artificial devices has revolutionised the care of patients with severe valvular diseases. Mechanical valves are very durable, but require long-term anticoagulation. Bioprosthetic heart valves (BHVs), devices manufactured from glutaraldehyde-fixed animal tissues, do not need long-term anticoagulation, but their long-term durability is limited to 15 - 20 years, mainly because of mechanical failure and tissue calcification. Although mechanisms of BHV calcification are not fully understood, major determinants are glutaraldehyde fixation, presence of devitalised cells and alteration of specific extracellular matrix components. Treatments targeted at the prevention of calcification include those that target neutralisation of the effects of glutaraldehyde, removal of cells, and modifications of matrix components. Several existing calcification-prevention treatments are in clinical use at present, and there are excellent mid-term clinical follow-up reports available. The purpose of this review is to appraise basic knowledge acquired in the field of prevention of BHV calcification, and to provide directions for future research and development.