**8. Clinical results**

#### **8.1. Survival**

Risk of death is highest immediately after AVR in patients with severe aortic stenosis, decreased to its nadir approximately 1 year postoperatively (early hazard period), and then gradually increased (late hazard period) [83]. From approximately 2 years after operation, survival is similar to that of matched population estimates. Early outcome of patients with aortic stenosis after AVR is primarily influenced by severity of the stenosis, left ventricular hypertrophy and dysfunction at operation. Severity of aortic stenosis, severe left ventricular hypertrophy, left ventricular dysfunction, older age and patient-prosthesis mismatch worsen also long-term survival. Furthermore, stentless AVR requires longer cross-clamp and cardio‐ pulmonary bypass times.

Several meta-analysis studies confirm that stentless AVR does not worsen the early and late outcome when compared to stented bioprostheses. Also, longer operation times do not have any adverse effect on the intra-operatively mortal complications and postoperative outcomes. Contrarily, early recovery of hemodynamic malfunctions caused by calcific stenotic native aortic valve brings better early and late outcomes.

Hospital mortality rate of stentless bioprostheses is lower than those of stented xenografts [84,85]. Early hospital or 30-day mortality is similar between stentless and stented biopros‐ thesis replacement in a meta-analysis (3.2% versus 2.4%; p = 0.39), and further analysis of 30 days mortality is subgroups included predominantly patients with aortic stenosis shows still no significant difference between two types of aortic bioprosthesis (3.7% versus 2.6%; p = 0.44) [86]. Only one retrospective multicenter study has shown if stentless valves are used only in selected patients (older age, female, full-root replacement) the 30-day mortality is increased when compared with stented valves (7.5% versus 3.3%; p = 0.026), but if stentless valves are used widely there is no significant difference in operative mortality between stentless and stented groups [87].Using autologous pericardium does not worse the early hospital outcome and early mortality is not seen [11].

Several studies showed an improved mid-term (< 10 years) survival after stentless AVR compared to stented valves [88,89]. A meta-analysis shows that mortality at the first year is lower after stentless aortic bioprosthesis replacement than stented bioprosthesis, but not significant: 7.5% versus 8.9%; p = 0.73 [15]. Another meta analysis also confirm no significant difference for valve-related mortality between stentless and stented xenograft replacement in the first postoperative year [86]. Lehmann and associates [89] showed in a randomized trial that 8-year survival was 78.1% ± 3.8% stentless versus 66.7% ± 4.9% stented (p = 0.03). They concluded that there was no difference in survival when compared stentless patients with an age-matched German control population.

The long-term results (≥ 10 years) with stentless valves are excellent [90]. The overall 10- and 15-year survival rates of Freestyle bioprosthesis are 60.7% and 35%, respectively [91]. The 10 year actuarial survival (44.1% ± 4.3% in subcoronary, 47.3% ± 8.15 in full-root, and 45.4% ± 13.7% in root inclusion groups; p = 0.89) and freedom from valve-related death (94.5% ± 2.9% in subcoronary, 92.9% ± 5.8% in full-root, and 87.8% ± 12.5% in root inclusion groups; p = 0.17) are similar between implants techniques with the Freestyle stentless bioprosthesis [92]. Longer follow-up (> 15 years) of stentless valves is also necessary to compare the excellent results of stented valves to establish that stentless xenografts are significantly superior than stented devices.

#### **8.2. Durability**

**7.6. Reoperation of a stentless aortic bioprosthesis**

patients.

436 Calcific Aortic Valve Disease

**8.1. Survival**

**8. Clinical results**

pulmonary bypass times.

aortic valve brings better early and late outcomes.

Stentless aortic valve reoperations may become more common as these bioprostheses reach the limits of their durability, which are a challenging procedure with an increased risk of death [80].The current generation of stentless valves have been implanted since the early 1990s and are therefore starting to reach the limits of their durability. Reoperation for stentless valves is a complex procedure, especially root inclusion or full-root replacement was preferred. The risk of trauma to the coronary ostia, aortic wall, aortic annulus, anterior mitral valve, and mem‐ branous septum can all occur when severe adhesions or calcification are present around the stentless valve. Reoperation after a stentless valve is more complex than after a stented tissue or mechanical valve if root replacement techniques is used in the first operation. However, reoperation of subcoronary implanted stentless bioprosthesis is easier than any stented prosthesis because cutting only the suture line is enough to remove the degenerated biopros‐ thesis. Valve-in-valve replacement with transfemoral [81] or transapical [82] AVI is a more conservative alternative strategy for re-replacement of degenerated xenograft in high risk

Risk of death is highest immediately after AVR in patients with severe aortic stenosis, decreased to its nadir approximately 1 year postoperatively (early hazard period), and then gradually increased (late hazard period) [83]. From approximately 2 years after operation, survival is similar to that of matched population estimates. Early outcome of patients with aortic stenosis after AVR is primarily influenced by severity of the stenosis, left ventricular hypertrophy and dysfunction at operation. Severity of aortic stenosis, severe left ventricular hypertrophy, left ventricular dysfunction, older age and patient-prosthesis mismatch worsen also long-term survival. Furthermore, stentless AVR requires longer cross-clamp and cardio‐

Several meta-analysis studies confirm that stentless AVR does not worsen the early and late outcome when compared to stented bioprostheses. Also, longer operation times do not have any adverse effect on the intra-operatively mortal complications and postoperative outcomes. Contrarily, early recovery of hemodynamic malfunctions caused by calcific stenotic native

Hospital mortality rate of stentless bioprostheses is lower than those of stented xenografts [84,85]. Early hospital or 30-day mortality is similar between stentless and stented biopros‐ thesis replacement in a meta-analysis (3.2% versus 2.4%; p = 0.39), and further analysis of 30 days mortality is subgroups included predominantly patients with aortic stenosis shows still no significant difference between two types of aortic bioprosthesis (3.7% versus 2.6%; p = 0.44) [86]. Only one retrospective multicenter study has shown if stentless valves are used only in selected patients (older age, female, full-root replacement) the 30-day mortality is increased The rate of structural valve deterioration increases over time, especially after the initial 7 to 8 years after implantation. Structural degeneration increases long-term events and the rate of failure is < 1% at 10 years in patients older than 65 years [93]. Pericardial valves might be better than porcine valves, but all newer-generation bioprostheses are more durable. In spite of the rate of failure of any bioprosthesis decreases with the age of the patient at the time of implan‐ tation (< 10% at 10 years in patients older > 70 years), the number of implanted stentless xenografts has increased due to improved hemodynamic performance and long-term dura‐ bility during last decade. Theoretically, xenogenic stentless aortic valves have better durability than stented valves. But in real life, the freedom rate from structural valve deterioration is similar in stentless and stented bioprostheses (> 90% at 10 years). CryoLife O'Brien and St Jude Toronto SPV valves have worst durability compared the other stentless valves (Medtronic Freestyle, Edwards Prima, St Jude Biocor, Sorin Pericarbon and Solo, ATS 3f).

When we focus on the implantation techniques, there are very rare papers in the literature. The overall freedom from reoperation with Freestyle stentless bioprosthesis is 91.0% and 75.0% at 10 and 15 years, whereas freedom from reoperation for structural valve deterioration was 95.9% and 82.3%, respectively. At 10 and 15 years, freedom from reoperation for structural valve deterioration is 94.0% and 62.6% for patients < 60 years of age and 96.3% and 88.4% for patients ≥ 60 years of age (p = 0.002) [90]. The actuarial freedom from reoperation (91.7% ± 3.5% in subcoronary, 92.3% ± 6.0% in full-root, and 92.0% ± 10.7% in root inclusion groups; p = 0.82) and from structural valve deterioration (97.0% ± 2.2% in subcoronary, 96.0% ± 4.5% in full-root, and 90.9% ± 11.2% in root inclusion groups; p = 0.54) are similar between implants techniques with the Freestyle stentless valves [91].

respectively), which regress with significant improvement at 1 year (25 ±7 and 12 ±4 mmHg, respectively) and concomitant regression of left ventricular hypertrophy [100]. The Edwards Prima Plus stentless xenograft implanted with intact non-coronary sinus technique prevents the geometry of the device and has excellent long-term result (mean gradient < 10 mmHg) in

Stentless Bioprostheses for Aortic Valve Replacement in Calcific Aortic Stenosis

http://dx.doi.org/10.5772/55373

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There are some studies showing different results regarding transaortic gradient, which might be a result of different stentless xenografts or implantation methods. There is no any significantly difference among implantation techniques when the same stentless xeno‐ graft is used with different implantation techniques, but full root (4.8 mmHg) or root in‐ clusion technique (5.1 mmHg) has lower mean transvalvular gradient than the subcoronary technique (7.2 mmHg) [102]. Transvalvular gradient and EOA are significant‐ ly worse in subcoronary groups in the first postoperative period, but this difference will be insignificant due to decreasing EOA and root inclusion approach will have the worst

Stentless valves are the best choice in patients with small aortic annuli than large annuli, because the lower transaortic pressure difference of stentless valves has no any significant advantage over stented bioprostheses if a valve larger than 23 mm will be used [103]. The difference will be significantly when a stentless valve sized 23 mm is used (Freestyle in‐ clusion 11 mmHg versus Perimount 25 mmHg) [21]. The Freedom SOLO stentless bio‐ prosthesis seems to have better hemodynamics even in patients received a small aortic bioprosthesis with a lower mean transvalvular gradient (9 ± 2.9 mmHg for 21 mm, and

Physically active patients might benefit from stentless valves. Several studies showed that the gradient difference between different aortic stentless and stented bioprostheses of similar size with different implantation techniques increased significantly at each exercise level in favour

Aortic valve replacement means that native valve disease is replaced with prosthetic valve inadequacy affected by prosthetic valve hemodynamics, durability, and thrombogenicity. Stentless bioprostheses have better hemodynamic properties because of larger effective orifice area, better coronary flow, lower transvalvular gradient and better left ventricular mass regression than stented bioprostheses. They have also better biomechanical properties and the preserved distensibility may diminish stress considerably. Valve-related morbidity and structural valve degeneration are not worse than stented valves, but their implantation is demanding and required experience in this field. Although experienced centers give excellent results with stentless xenografts, most surgeons also prefer a stented xenograft to keep the procedure quick, safe, and simple. But, there is a trend to favor stentless valves nowadays because these valves provide larger effective orifice area, lower transvalvular gradients and excellent hemodynamics which stimulate rapid and effective reduction in left ventricular

all sizes (21-29 mm) [101].

hemodynamics at 10th postoperative year [90].

7.6 ± 5 mmHg for 23 mm) [97].

of stentless valves [104-105106].

**9. Conclusion**

The truly stentless autologous pericardial aortic valve may be better choice in patients who cannot or do not want to take anticoagulation, especially young population, because excellent long-term durability and easier reoperation, which is technically undemanding compared to other stentless bioprostheses. The use of autologous pericardium avoids any immune reaction between the host and the implanted valve, and minimizes tissue calcification and pannus formation, which are important causes of structural valve deterioration. The absence of a stent and sewing ring is also helpful for long-term durability with a freedom from structural valve deterioration of 100% at 7.5 years [11]. Long-term durability seems better than the other bioprostheses because it has been reported that there is no calcification, no structural dys‐ function on the autologous pericardium used for aortic leaflet extension at 13 years [94]. Reoperation must be easier because there is no calcification on the aorta and pericardial aortic valve.

#### **8.3. Echocardiographic outcomes**

The advantage of stentless xenografts is providing a greater EOA index for a given valve size, which results lower transvalvular gradients compared with stented valves. These improve‐ ments have been reported in a meta analysis: lower mean aortic valve gradient (-3.57 mmHg; p < 0.01), lower peak gradient (-5.8 mmHg; p< 0.01), but higher EOA index in stentless group compared with the stented [15]. It has been shown in an experimental porcine model that the annular cross-sectional area of stentless valves is significantly larger than stented valves [23]. The EOA will increase after first postoperative year in stentless valves and significant differ‐ ences in mean and/or peak pressure differences between stentless and stented valves will continue during long-term follow-up [95,96].

The Freedom SOLO stentless bioprosthesis with all size-number has a lower mean (10.6 ± 3.6 mmHg) and peak (15.9 ± 9.1 mmHg) transvalvular gradient at discharged, and below 10 mmHg in all sizes (21-27 mm) at the first postoperative year [97]. The similar results have been shown by other groups: lower mean gradient (6.7 +/- 4.1 mmHg) and a significant regression of left ventricular hypertrophy (23%) at 12 months [98].

3f aortic bioprosthesis has a satisfactory hemodynamic performance with substitutes larger than 23 mm (< 10 mmHg), but smaller valves have a significant higher mean transvalvular gradient at the 4-postoperative year (18 mmHg for 21 mm and 14 mmHg for 23 mm devices) [36]. The left ventricular mass index decreases during follow-up (showed 18% regression), but cannot reach the normal range, especially with small devices. In another study with a mean valve size 26.0 ± 1.9 mm has shown that the mean transvalvular gradient of 3f bioprostheses has increased at 5 years (15.2 ± 5.3 mmHg) [99].

The Edwards Prima Plus stentless valve bioprosthesis is a porcine aortic root cylinder and is associated with high early peak and mean transprosthetic gradients (37 ± 16 and 18 ±8 mmHg, respectively), which regress with significant improvement at 1 year (25 ±7 and 12 ±4 mmHg, respectively) and concomitant regression of left ventricular hypertrophy [100]. The Edwards Prima Plus stentless xenograft implanted with intact non-coronary sinus technique prevents the geometry of the device and has excellent long-term result (mean gradient < 10 mmHg) in all sizes (21-29 mm) [101].

There are some studies showing different results regarding transaortic gradient, which might be a result of different stentless xenografts or implantation methods. There is no any significantly difference among implantation techniques when the same stentless xeno‐ graft is used with different implantation techniques, but full root (4.8 mmHg) or root in‐ clusion technique (5.1 mmHg) has lower mean transvalvular gradient than the subcoronary technique (7.2 mmHg) [102]. Transvalvular gradient and EOA are significant‐ ly worse in subcoronary groups in the first postoperative period, but this difference will be insignificant due to decreasing EOA and root inclusion approach will have the worst hemodynamics at 10th postoperative year [90].

Stentless valves are the best choice in patients with small aortic annuli than large annuli, because the lower transaortic pressure difference of stentless valves has no any significant advantage over stented bioprostheses if a valve larger than 23 mm will be used [103]. The difference will be significantly when a stentless valve sized 23 mm is used (Freestyle in‐ clusion 11 mmHg versus Perimount 25 mmHg) [21]. The Freedom SOLO stentless bio‐ prosthesis seems to have better hemodynamics even in patients received a small aortic bioprosthesis with a lower mean transvalvular gradient (9 ± 2.9 mmHg for 21 mm, and 7.6 ± 5 mmHg for 23 mm) [97].

Physically active patients might benefit from stentless valves. Several studies showed that the gradient difference between different aortic stentless and stented bioprostheses of similar size with different implantation techniques increased significantly at each exercise level in favour of stentless valves [104-105106].
