Despite the marked improvements in prosthetic valve design and surgical procedures over the past decades, valve replacement does not provide a definitive cure to the patient. Instead, native valve disease is traded for “prosthetic valve disease,” and the outcome of patients undergoing valve replacement is affected by prosthetic valve hemodynamics, durability, and thrombogenicity. Nonetheless, many of the prosthesis-related complications can be prevented or their impact minimized through optimal prosthesis selection in the individual patient and careful medical management and follow-up after implantation.
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Structural Valve Deterioration
Incidence of SVD
Mechanical prostheses have an excellent durability, and SVD is extremely rare with contemporary valves, although mechanical failure (eg, strut fracture, leaflet escape, occluder dysfunction caused by lipid adsorption) has occurred with some models in the past (Figure 6C).
The rate of SVD in bioprosthetic valves (Figure 6D) increases over time, particularly after the initial 7 to 8 years after implantation. With conventional stented bioprostheses, the freedom from structural valve failure is 70% to 90% at 10 years and 50% to 80% at 15 years.6,43,50,62,66
Predictors of SVD
Risk factors previously found to be associated with bioprosthetic SVD include younger age, mitral valve position, renal insufficiency, and hyperparathyroidism.43,62,66 Hypertension, LV hypertrophy, poor LV function, and prosthesis size also have been reported as predictors of SVD in bioprostheses implanted in the aortic position.66
Host-Related Factors
Bioprosthetic SVD is strongly influenced by the age of the patient at the time of implantation.43,62 The rate of failure of bioprostheses is <10% at 10 years in elderly patients (>70 years of age) but is ˜20% to 30% in patients <40 years of age.43,62 Several studies also suggest that bioprosthetic structural failure is more frequent in the mitral than in the aortic position.43,66 This difference is likely related to the higher mechanical stress imposed on the valve leaflets of mitral bioprostheses during systole. Likewise, SVD of aortic bioprostheses may be accelerated by systemic hypertension, possibly as a result of a chronically increased diastolic closure stress.
Valve-Related Factors
Several studies tend to show that newer-generation bioprostheses are more durable than older ones.43,62,66 Some reports also suggest that pericardial valves might be better than porcine valves in this regard,67 but other recent studies show no appreciable difference between these 2 types of prosthesis.68
Pathogenesis of SVD
Degenerative Process
Bioprosthetic valve tissues are cross-linked in glutaraldehyde to reduce its antigenicity and to ensure chemical stabilization; however, this chemical treatment may predispose to bioprosthetic tissue degeneration (Figure 8).62 Indeed, tissue fixation with glutaraldehyde induces a calcium influx as a result of membrane damage, which provides, along with the residual phospholipids of the membranes, an environment prone to calcium crystal nucleation. Host factors and mechanical stress then contribute to calcium crystal growth. Such findings have prompted manufacturers to try different anticalcifying treatments on bioprosthetic tissue in the hope of avoiding or slowing SVD. Opposing previous beliefs, recent studies69–74 suggest that SVD may not be a purely passive degenerative process but may also involve active mechanisms such as immune rejection and atherosclerosis (Figure 8).
Figure 8. Hypothetical model for the structural deterioration of bioprosthetic valves. OxLDL indicates oxidized low-density lipoprotein.
Immune Process
Recent studies suggest that bioprosthetic valves are not in fact completely immunologically inert (Figure 8).73 Hence, residual animal antigens could elicit humoral and cellular immune responses, leading to tissue mineralization and/or disruption. A more robust immune system might also explain the more rapid SVD usually observed in younger patients.
Atherosclerotic Process
Recent studies also demonstrate an association between bioprosthetic SVD and several atherosclerotic risk factors, including hypercholesterolemia, diabetes, metabolic syndrome, and smoking.66,70,72Moreover, 1 retrospective study reported that statin therapy is associated with slower progression of SVD.71 These recent findings support the hypothesis that similar to the native aortic valve, the SVD of bioprostheses may be related, at least in part, to an atherosclerotic process (Figure 8). The infiltration of low-density lipoproteins within the bioprosthetic tissue and their oxidation may trigger an inflammatory process and the formation of foam cells.74 In turn, the inflammatory cytokines and oxidized low-density lipoproteins may induce an osteoblastic differentiation of stem/progenitor cells that have colonized the bioprosthetic tissue.75
