Structural valve deterioration is primarily caused by cyclic fatigue but not immune rejection

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Materials Science

Background:

• Chronic immune rejection is a key factor in bioprosthetic heart valve (BHV) structural valve degeneration (SVD).
• The distinct hemodynamic loads on bioprosthetic mitral valves (BMVs) versus bioprosthetic tricuspid valves (BTVs) may influence SVD development.
• The relative contributions of leukocyte infiltration and mechanical stress to SVD in BMVs and BTVs are not fully understood.

Purpose of the Study:

• To investigate the mechanisms driving structural valve degeneration (SVD) in bioprosthetic mitral valves (BMVs) and bioprosthetic tricuspid valves (BTVs).
• To compare the roles of immune cell infiltration and mechanical factors in SVD between BMVs and BTVs.

Main Methods:

• Pairwise explantation of BMVs and BTVs from patients undergoing BHV replacement.
• Quantification of valvular calcification using multislice computed tomography and Pydicom.
• Histological analysis (hematoxylin and eosin, Oil Red O) and ultrastructural examination (EM-BSEM) to assess immune cell infiltration, lipid deposition, and tissue integrity.

Main Results:

• Bioprosthetic mitral valves (BMVs) exhibited significant lipid deposition, hemorrhages, and tears, leading to mechanical failure.
• BMVs showed less immune cell infiltration compared to BTVs.
• These findings suggest mechanical fatigue is a predominant factor in SVD development.

Conclusions:

• Mechanical fatigue, rather than immune cell infiltration, appears to be the primary driver of structural valve degeneration (SVD) in bioprosthetic heart valves (BHVs), particularly in the mitral position.
• Understanding these mechanisms is crucial for developing more durable bioprosthetic heart valve replacements.