Hemodynamic Factors Affecting the Fate of Valvular Bioprosthesis
Ce qui est simple est faux mais ce qui ne l’est pas est inutilisable.
— —Paul Valéry
Since their introduction in 1969, valvular bioprostheses (ie, glutaraldehyde-processed animal valves)1 have experienced a surprising increase in use as a result of progress in valve processing2 and growing patient desire for nonthrombogenic valve surgery.3 However, the persistent risk of structural valve deterioration, particularly in the young population, remains a major concern. The 2 main causes of valve failure are valve degeneration and calcification. Among the numerous factors influencing the fate of a bioprosthesis, hemodynamic factors are addressed more rarely than biological factors. In this issue of Circulation, Flameng and colleagues4 add important information to the understanding of how hemodynamic factors play a role in structural valve failure. To do so, they revive an old debate on the practical significance of prosthesis-patient mismatch. First introduced by Rahimtoola in 19785 and having fed numerous discussions for many years, this paradigm led to the simple conclusion that, in aortic valve replacement, the larger the valve is, the better the hemodynamics and therefore the clinical result are. Accordingly, surgeons were advised to carefully measure the aortic valve orifice and to select a valve by fitting the aortic valve orifice in correlation to body size. This recommendation is still valid today. A mismatch is defined by the authors as an orifice area index <0.85 cm2/m2, which is within the range of Rahimtoola’s6 moderately severe stenosis. It creates significant transvalvular gradient, residual clinical symptoms, and arrhythmias. The originality of this article lies in the fact that the authors make a distinction between 2 simple categories of valve structural deterioration, depending on whether the valve is stenotic or regurgitant as assessed by echocardiography.
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Stenotic valve deterioration is said to develop early, about 2 or 3 years after implantation, and to occur exclusively in patients having a prosthesis-patient mismatch. The stenosis is explained by leaflet thickening easily visible by echocardiography and defined as a pressure gradient 50% more than the original gradient. Although it is not indicated in the report, one can postulate that patients presenting with such a stenosis received a pericardial bioprosthesis, which is known to display leaflet thickening as a result of early platelet-fibrin deposition on the leaflets in the postoperative course. This leaflet thickening, well visible at echocardiography, is too often regarded as a pathological process, whereas it is actually a normal evolution unless it develops rapidly and leads to a significant stenosis caused by clot formation. Clot formation is seen in patients with coagulopathy, inflammatory process, or international normalized ratio <1.5. Having observed few cases of early bioprosthetic valve thrombosis, we systematically anticoagulate adult patients postoperatively with coumadin with an international normalized ratio of 2 to 2.5 for 1 month, the time necessary to obtain a regular covering of the leaflet by host tissue and pliable leaflets. Under this condition, very long-term results can be expected.
Another factor that may play a role in the early development of valve stenosis is inadequate rinsing of the valve before and during valve implantation in saline to clean residual glutaraldehyde. Progressive valve thickening and calcification reproduce the syndrome of calcified aortic valve stenosis. They are minimized by anticalcification treatments of the tissue.2
Valve regurgitation is said to develop at a much later stage in patients without prosthesis-patient mismatch. This assertion is not supported by a number of patients large enough to be significant, as underlined by the authors themselves. Although in this group little information could be collected on the mode of valve failure and its relationship to the type of valves, we can postulate, from our own experience, that the valves in this group are either stented porcine valves or unstented bioprostheses. Regurgitation of bioprostheses is generally due to tears initiated at a spot of calcification or more extensive extrinsic calcium formation usually located at the commissures. Failures may also result from another type of mismatch: “prosthesis-patient morphological mismatch” involving a deformed, bicuspid, or calcified orifice or an unstented bioprosthesis that is too large or too small. Morphological mismatch also includes valve malposition or suboptimal valve design such as excess inward bending of the struts of the valve that exposes the commissures to higher stress during systole as seen in the early models of porcine valves. With calcification being the major cause of structural valve failure of bioprosthesis, whether stenotic or regurgitant, improvements in valve durability depend mainly on improvements in valve processing. I agree with the authors that improved durability can be expected by paying close attention to prosthesis-patient mismatch. However, it is somewhat overoptimistic to state that “by avoiding prosthesis-patient mismatch, the incidence of structural valve degeneration should be reduced by ≥50%.” Significant progress in valve durability should actually be expected from improved valve processing as shown in the past decades. This is indirectly confirmed by the fact that, in the series reported by the authors, anticalcification treatment was found to be the most significant factor influencing valve deterioration.
In the era of transcutaneous aortic valve delivery, which can be achieved only with valvular bioprostheses, morphological mismatch is particularly important because it determines the long-term fate of the valve. We demonstrated a long time ago the strong correlation between flow turbulence and valve calcification7; thus, blood flow and stress should be analyzed carefully at different levels of the aortic root to assess the result and to predict the evolution.
The term xenograft bioprosthesis used once in Flameng’s article is an oxymoron; a bioprosthesis is a fixed tissue whereas a graft is a nonfixed tissue (eg, a homograft). The durability of the graft is based on cell survival or host cell ingrowth, whereas the durability of bioprosthesis is based on the stability of the biological material.8
In conclusion, the merit of the Flameng et al article is to recall that improvement in valve durability depends not only on progress in valve tissue processing but also on hemodynamic factors such as prosthesis-patient size mismatch. Morphological mismatch should also be recognized because it may contribute to improvements in bioprosthetic valve design and delivery.
Dr Carpentier is a consultant for Edwards Lifesciences.
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
Carpentier A, Nashef A, Carpentier S, Ahmed A, Goussef N. Techniques for prevention of calcification of valvular bioprostheses. Circulation. 1984; 70 (suppl 1): 165–168.
Flameng W, Herregods M-C, Vercalsteren M, Herijgers P, Bogaerts K, Meuris B. Prosthesis-patient mismatch predicts structural valve degeneration in bioprosthetic heart valves. Circulation. 2010; 121: 2123–2129.
Rahimtoola SH. The problem of valve prosthesis-patient mismatch. Circulation. 1978; 58: 20–24.
Carpentier A, Dubost C. From xenograft to bioprosthesis: evolution of concepts and techniques of valvular xenografts. In: Ionescu MI, Ross DN, Wooler GH, eds. Biological Tissue in Heart Valve Replacement. London, UK: Butterworth & Co Publishers; 1972; 515–541.