5 DISCUSSION
To our knowledge, this is the first report of the FLS technique being applied in treating severe aortic valve calcification. Compared with the conventional technique, the FLS technique was associated with: (1) shorter cross-clamp time, CPB time and operative time, (2) shorter hospital stay, and (3) superior hemodynamic performance of the bioprosthetic aortic valves.
The incidence of calcific AS increases with age, with an average of 0.2% in patients of 50-59 years old and 9.8% in patients of 80-89 years old.17 Calcific AS occurs 10-15 years earlier in population with congenital bicuspid aortic valves than normal controls.18 Calcification of the aortic valve is progressive and involves multiple mechanisms, including lipoprotein deposition, chronic inflammation, mineralization, osteoblastic transition of interstitial cells and active leaflet calcification.10-11 Pathological analysis of diseased valves revealed that fibrocalcific changes predominantly occur in the fibrosa layer and extend to the aortic side of the valve, which maybe associated with the spatial distribution of several anti-osteogenic genes expressed by endothelium. The endothelium covering the aortic side of leaflets shows lower expression of anti-osteogenic genes than that on the ventricular side.10 Based on these pathological characteristics of calcified aortic valve, we designed the new technique that thoroughly removes calcified tissue by stripping the fibrosa layer of the diseased valve and the annulus, namely, the FLS technique.
Our study showed that the FLS technique reduced cross-clamp time, CPB time and operation time in MIAVR. This can be attributed to two factors: (1) the FLS technique requires significantly shorter time to remove calcified tissue, (2) the FLS technique causes less damage to the aortic annulus and leaves less residual calcified tissue, which allows use of continuous sutures that takes less time. MIAVR offers several advantages over full sternotomy AVR, including reduced trauma and pain, shorter ICU and hospital stay, improved cosmesis, and lower rate of atrial fibrillation. However, the cross-clamp time and CPB time are prolonged in MIAVR than full sternotomy AVR,19-20 which is associated with increased mortality and mobility.21-22 By implementing the FLS technique, we have overcome these limitations and promoted the application of MIAVR in treating severe AS.
In current study, 1 patient had severe, 2 patients had moderate and 1 patient had mild PVL postoperation in conventional group but only 1 patient in FLS group had mild PVL. However, there was no significant difference between groups regarding the incidence and constituent ratio of the degree of PVL. Conventional methods of mechanically crushing calcified tissue can destroy the normal fibrous tissue in the annulus and reduce its strength and tensile force, which causes the annulus to be damaged by sutures. Moreover, calcified tissue in the aortic annulus and residual valve is also difficult to be completely cleared by conventional method, which may also contribute to PVL.
The prevalence of cerebrovascular events varies from 1% to 17% among patients with calcific AS who underwent AVR.23-24 Leker RR et.al reported that the risk factors for cerebrovascular events after AVR include longer bypass duration, older age, and larger pre-existing lesion burdens.25 Moreover, debris produced by mechanical crushing of calcified tissue is easy to fall into the left ventricle and hidden in intricate muscle bundles, which may enter the arterial system through left ventricular ejection and induce cerebro-arterial embolism. In this study, the incidence of cerebrovascular events and permanent strokes were 20.7% and 6.9% in conventional group in per-protocol analysis, while that in FLS group were 7.1% and 0 respectively. However, there was no differences between the two groups, probably due to the small number of enrolled patients and the fact that we only performed the neurological examinations on symptomatic patients, thus silent cerebral events may have been missed.26
Patients in FLS group obtained a significantly larger indexed EOA postoperatively than conventional group whether analyzed by intention-to-treat or per-protocol. The reason maybe that leaflets and annular calcification can be completely removed by FLS technology, so diameter and elasticity of aortic annular can be restored to normal state. Therefore, we can implant a aortic bioprothesis of optimal annulus size but not an undersized. However, small aortic root has remained a challenge. Small aortic root was observed in 17% of asymptomatic patients with mild to moderate AS, who had a significantly smaller annulus diameter in comparison with those with a normal aortic root. Enlargement is necessary to increase the indexed EOA during AVR for patients with small aortic annular. However, only 5% of patients received an annular enlargement procedure during AVR due to increased operative mortality and major morbidity.27 The residual calcification on aortic annulus or valve is the main cause for aborted annular enlargement during AVR, especially when the calcium extends down into the left ventricular outflow tract or the mitral valve. In this study, all patients with small aortic root in the FLS group received annular enlargement before implantation of a proper sizing of the prosthetic valve. In contrast, 2 patients with small aortic root in the conventional group did not receive concomitant annular enlargement due to the residual calcified tissue. As a result, oversized bioprostheses were implanted in order to avoid prosthesis-patient mismatch (PPM). Compared with annular enlargement, bioprosthesis oversizing can only increase a very limited valve size. In addition, oversizing alters aortic annular configuration and valvular hemodynamics, which leads to decreased EOA and increased pressure gradients.28 Therefore we conclude that using FLS technique in annular enlargement should be conducted on more patients with small aortic root in order to achieve better hemodynamic performance and patient outcome.
There remain several limitations in current study. First, it is a single-center trial with a small cohort size. Second, Patients are limited to bioprosthetic valve replacement, so most of them are frail elderly who have higher average age and more comobidities than the real world, which may cause selection bias. Third, all operations were performed by one surgeon who may have more experience with the FLS technique than the conventional technique. Fourth, we only followed up for one year, and long-term effect has not be established. Therefore, long-term safety and efficacy study of FLS in a larger cohort of patients is needed in the future.