Member Login

Untitled Document
Untitled Document


Valve Replacement Repair


Valve repair


Tricuspid and, in particular, mitral valves are the most likely to be repaired. Aortic valve, if damaged, is usually and preferably replaced.

Focusing on the mitral valve (MV), repair is currently the gold standard for treating MV dysfunction and involves open heart surgery. Depending on the underlying cause of MV dysfunction, different types of MV repair techniques are applied. MV repair in degenerative MV regurgitation is associated with very good short- and long-term outcomes (Gillinov et al., 1998; Spiegelstein et al., 2007). Repair techniques used to treat this condition include quadrangular(Figure 1.17), trapezoid, ortriangular resection of the segment of the posterior leaflet demonstrating prolapse or ruptured chords (Carpentier et al., 1983; Deloche et al., 1990; Braunberger et al., 2001; Daimon et al., 2006; Spiegelstein et al., 2007). The posterior leaflet is repaired with either plication of the annulus, or with sliding plasty. The former involves the suturing of the annulus at the level of the resection in order to make the two leaflet remnants come in close apposition with a little overlap. The latter is associated with excess tissue and involves the detachment of part of the two remnants of the posterior leaflet from the annulus, followed by the reattachment of the segments to the annulus, allowing the close apposition of the leaflet remnants with a little overlap (Perier, 2005). Commonly, after a quadrangular resection the insertion of a ring completes the repair.


In anterior leaflet prolapse or ruptured chords, polytetrafluoroethylene (ePTFE) chord replacements have become quite popular in the past decade (Von Oppel and Mohr, 2000; David, 2004; Dreyfus et al., 2006; Lawrie, 2006). Chordal transfer is performed in patients with myxomatous disease and involves the transfer of chords from a healthy portion of the leaflet to the prolapsing one. This technique has demonstrated excellent clinical outcomes (Smedira et al., 1996; Salati et al., 1997; Duran et al., 1999; Gillinov et al., 2005a). Shortening of the anterior leaflet (Quigley et al. 2005), or anterior leaflet chord (Dreyfus et al., 2006), have also been used.

Annuloplasty of the posterior part of the annulus has been performed using untreated (Salatiet al., 1991) and glutaraldehyde-treated (Borghetti et al., 2000) autologous pericardium. Comparative studies with rigid prosthetic rings have shown that autologous pericardium provided more favourable annulus dynamics (Borghetti et al., 2000). Prosthetic annuloplasty rings have also been used in conjunction with glutaraldehyde-treated autologous pericardium for the augmentation of the anterior leaflet (Acar et al., 2004; Chavaud et al., 1998). Studies have shown that this technique is associated with decreased re-operation risk compared to using an annuloplasty ring alone. Further studies with glutaraldehyde-treated autologous pericardium used in MV leaflet extension, have shown late deterioration and calcification of the tissue with minimal risk of thromboembolic events (Chauvad et al., 1991; 2001). Autologous pericardium has the most favourable characteristics for cardiovascular implantation since it is a low-cost biomaterial, free of donor derived pathogens, non-immunogenic, easily accessed (Duran and Gometza, 1993; Mirsadraee et al., 2006) and may remodel in the patient. However, it is not an ideal solution since it requires sacrifice of the pericardium of the patient, and involves inflammatory changes after pericardiotomy (Duran and Gometza, 1993). Glutaraldehyde-treated bovine pericardium has also been used to close MV leaflet perforations (Muhercke et al., 1997). However, glutaraldehyde-treated tissue with cell remnants can cause calcification. The calcific deposits enlarge and coalesce, leading to the formation of mineralized nodules, which can cause tissue stiffening and weakening, ultimately leading to deterioration of the bioprosthesis (Boskey et al., 1981).

In the case of chronic ischemic MVR, the most commonly used surgical procedure is restrictive mitral annuloplasty(Dion et al., 1995; Bolling et al., 1998; Daimon et al., 2006; Spiegelstein et al., 2007; Braun et al., 2008). Generally, almost all MV repairs are completed with annuloplasty, which involves the reconstruction of the annulus. Its role is to reduce the size of the annulus and the tension caused by the repairing sutures (Tuladhar et al., 2006). Different types of annuloplasty rings have been employed clinically. These include rigid or flexible and complete or incomplete rings (Spiegelstein et al., 2007). Additional MV repair techniques include the edge-to-edge, or Alfieri technique, and commisuroplasty. The former involves the localised suturing of the two leaflets at the site of regurgitation (Alfieri et al., 1999, 2004; Spiegelstein et al., 2007) (Figure 1.18). The latter is used for patients with small leaflet prolapse, adjacent to the commissure, and provides a localised closure of the commissure without altering the valve orifice (Gillinov et al., 2005b; Aubert et al., 2005). The recently-developed Mitraclip system, which has been adapted to the edge-to-edge technique (Gaemperliet al., 2013), and has been shown to be less invasive by employing a catheter inserted in the femoral vein to reach the heart.


MV repair has many advantages over mitral replacement including, lower operative mortality, reduced incidence of thromboembolism and reduced need for anticoagulation (Perier et al., 1984; Gillinov et al., 1998; Yau et al., 2000), lower risk of endocarditis (Galloway et al., 1988; Duran, 1993), and improved long-term results (Galloway et al., 1989; Akins et al., 1994). Nevertheless, there are several cases of recurrent MV dysfunction following MV repair, which require reoperation (Shekaret al., 2005; Dumont et al., 2007).

Valve replacement
Heart valve replacement involves the substitution of the diseased valve with either a mechanical or a tissue valve. Mechanical prostheses are made entirely of artificial components. Based on their design, these valves are classified into three types, including ball and cage, tilting disc and bileaflet valves. Mechanical valves are associated with enhanced durability, but generate large regurgitation volumes during valve closing and require life-long anticoagulation treatment (Warfarin). The latter is necessary in order to avoid thromboembolic complications associated with blood clotting caused by turbulent-flow-induced high fluid stresses (Edmunds et al., 1987; Wurzinger and Schmid-Schönbein, 1990; Korossis et al., 2002). Owing to the need of anticoagulation, one of the major problems with mechanical heart valves are haemorrhagic disorders (Grunkemeier and Rahimtoola, 1990; Schoen et al., 1992). The use of mechanical valves in children and young adults is problematic due to their inability to grow with the patient, leading to costly re-operations. In addition, patients with mechanical prosthesis are prone to increased incidence of endocarditis (Otto and Bonow, 2009).


                                       Mechanical valves: (a) ball & cage; (b) tilting disc; (c) bileaflet. From Korossis (2002).

Tissue valves include bioprosthetic valves, made of chemically-treated porcine or bovine tissue (xenografts), and cadaveric valves (allografts or homografts). Tissue valves are associated with significantly lower thromboembolic risks, thus they do not require anticoagulation treatment, and have a haemodynamic performance comparable to that of the native valve (Russo et al., 2008). However, tissue deterioration and structural dysfunction, due to both calcification and non-calcific mechanisms, represent serious drawbacks with tissue valves (Hammermeister et al., 1993). In addition, valve infection and non-structural dysfunction affect both tissue and mechanical valves almost equally (Korossis, 2002).

Bioprosthetic valves are cross-linked with low-concentration glutaraldehyde solutions in order to reduce their antigenicity and to stabilise the tissue against structural degradation (Korossis, 2002). In addition, studies have described treatment of these valves with anticalcific agents to minimize the risk of calcification (Schoen et al., 2005a, 2005b). Porcine bioprosthetic valves are usually made from intact pig aortic valves (with or without the valve root). These valves are cross-linked under various boundary conditions (degree of valve pressurisation), which have shown to affect the haemodynamic performance of the prostheses (Korossis et al., 2002). Stinson et al. (1974, 1977) reported that the use of glutaraldehyde-treated porcine aortic valves for MV replacement provided overall durability comparable to that of mechanical prostheses. Other works reported on the use of porcine and bovine xenografts for MV replacement and concluded that bovine pericardial valves were associated with lower risk of thromboembolism, due to their superior haemodynamics (Gonzalez-Lavin et al., 1984).

Bioprosthetic valves are subjected to structural deterioration due to chemical, mechanical, and morphological changes occurring during cross-linking and fabrication. This, in conjunction with the lack of a regeneration mechanism makes these valves prone to structural dysfunction. In addition, the lack of an endothelial barrier, causes increase permeability of the xenograft tissue (Schoen et al., 2008), whereas internal rearrangements, involving collagen crimp and alignment, are not possible due to the fixation of the ECM proteins (Vesely et al., 1988; Fisher and Davies, 1989). Moreover, cell remnants in the tissue act as foci for calcification. However, new generation bioprostheses have demonstrated 64 - 98 % freedom from structural valve deterioration after 10 years (Marchand et al., 1998; Masters et al., 2004). In addition, recent studies have suggested that development of improved GAG cross-linking techniques, to limit GAG degradation, may improve valve longevity (Lovekamp et al., 2006; Shah et al., 2008).

Homografts are usually intact mitral, aortic and pulmonary valves, obtained from human donors and cryopreserved. Homografts have been reported to demonstrate good haemodynamics, low thrombogeneicity and low infection rates. However, although homografts are subject to decreased degeneration compared to bioprostheses, their long-term performance is limited by progressive degeneration due to absence of a repair mechanism.

According to Schoen et al. (1982), the criteria for an ideal valve substitute is ease of implantation, quick healing in the implanted position, long life cycles with minimal wear or degenerative change, high flow with minimal turbulence when opened and no regurgitation when closed, limited risk of thrombosis and biocompatibility. None of the currently available valve substitutes meet all these criteria. In addition, none of the current valve replacements, or indeed valve repair materials (with the exception of autologous pericardium), have an inherent remodelling/repair mechanism and thus, they cannot regenerate or grow with the patient.


Heart Valve Tissue Engineering

Over the past few years, there has been a considerable interest in the TE of heart valves, especially for the aortic and pulmonary positions. Rabkin-Aikawa et al. (2005) reported that to achieve the challenge of heart valve TE, a deep understanding of both normal and pathological tissue function is necessary, including mechanisms of embryological development and functional tissue biomechanics.


To date, there have been two main strategies for the development of TE heart valves. These include the transplantation of unseeded scaffolds, with a view to attracting endogenous cells, and cell-seeded scaffolds, which have been physically conditioned in vitro, with a view to developing valve-equivalent functionality prior to implantation.


Decellularised scaffolds have been implanted to investigate the in vivo autologous regeneration potential of the unseeded scaffolds. Theodoridis et al. (2013) compared the recellularisation potential of decellularised pulmonary valves, unseeded or seeded, prior to implantation into elderly sheeps. Ovine pulmonary valves decellularised unseeded and decellularised re-endothelialized with autologous endothelial cells, were implanted in the orthotopic position in sheep. Explantation after six and twelve months showed no signs of degradation of the ECM, minimal calcification and cell repopulation, but to various degrees. Only one valve showed complete repopulation, and a slight tendency of better repopulation was observed in the re-endothelialized pulmonary valves implants, however no significant difference in the cell densities was found among the groups. Elkins et al. (2001) decellularised human and sheep pulmonary valves using the SynerGraft treatment process and implanted these in human patients and sheeps, respectively. The decellularised sheep allograft valves were monitored echocardiographically and histologically at 3 and 6 months; they became functional during the implantation period, and were progressively repopulated with recipient cells. The decellularised human allografts implanted in humans did not seem to provoke reactive antibody response.


According to the cell-seeded scaffolds approach, mechanical loading has been considered to be necessary to stimulate the growth and maturation of the seeded cells and the formation of the ECM. As such valvular constructs have been conditioned using dynamic flow or strain, or a combination of both (Filova et al., 2009). Engelmayr et al. (2006) reported that mechanical stimulation had fundamental effects on the differentiation of sheep bone-marrow-derived stem cells on polyglycolic acid/ poly L-lactic acid (PGA/PLLA) valvular scaffolds. Moreover, fibrin-based valvular constructs cultivated with porcine VICs under 15% cyclic distension were shown to have increased collagen content and ultimate strength (Syedain et al., 2008). In a study by Ku et al. (2006), VICs and MSCs stretched on collagen-coated substrates increased their collagen synthesis. In general, mechanical conditioning has been demonstrated to improve the properties of valvular constructs when compared to static cultures (Hoerstrup et al., 2002; Mol et al., 2003; Engelmayr et al., 2005). Moreover, cell-seeded and in-vitro-conditioned valvular scaffolds were shown to be fully functional in the pulmonary position in the study of Hoerstrup et al. (2000a). They seeded ovine myofibroblasts and ECs onto fabricated bioresorbable polymeric scaffolds and cultured them in a pulse duplicator prior to implantationt. They reported the formation of a layered leaflet tissue structure and efficient functionality after 20 weeks in lambs.





« Go back to Research
Untitled Document


TECAS-ITN End-of-Network Conference

 Padua, November 28-30, 2016

The TECAS-ITN European Doctoral Academy in Regenerative Engineering, is organising the End-of-Network Conference in Padua, Italy.

read more