The incidence of valvular heart disease increases with age. The prevalence rate of moderate or severe aortic stenosis (AS) is 0.02% in adults aged between 18 and 44 years and about 2.8% in those ≥75. Traditional management of AS includes conservative medication treatment and open heart surgery. However, medication treatment does not significantly improve the prognosis of AS. Surgical aortic valve replacement (SAVR) can significantly improve the prognosis; but many patients are not surgical candidates due to old age, history of open chest surgery, and cardiopulmonary dysfunction. Thus, the development of transcatheter aortic valve replacement (TAVR) represents the major progress in the diagnosis and treatment of valvular heart disease. TAVR technology was introduced later in China than in other countries, and its clinical application is still in its infancy. However, with the development of China's economy and technology, the domestic investment in TAVR has gradually increased. In this paper, we present the current status and progress of TAVR in China.
Transcatheter Aortic Valve Replacement Status
Transcatheter aortic valve replacement (TAVR) technology originated in Europe. In the 1980s, research data suggested that there is great risk in surgical valve replacement for elderly patients. In 1989, Andersen et al. completed the first TAVR experiment in animals. In 2002, Dr. Alain Cribier performed the first TAVR in a human. Since then, TAVR technology has developed rapidly, and more than 300,000 TAVR procedures have been performed in 65 countries. Data from clinical trials and large registry studies have shown that TAVR is safe and effective for patients with high-risk AS. In 2010, Prof. Ge Junbo performed the first TAVR in China, which prompted the subsequent rapid development of TAVR technology. Currently, TAVR is offered by 28 centers and more than 800 procedures have been performed. Four hospitals have independent TAVR procedural capability including Beijing Fuwai Hospital, Shanghai Zhongshan Hospital, West China Hospital of Sichuan, and the Second Affiliated Hospital of Zhejiang University. These hospitals serve as national TAVR technology training centers and promote the development of TAVR technology in China.
China has Made Major Breakthroughs in Research and Development of Prosthetic Aortic Valves
Valve selection is critically important in TAVR and closely related to the success rate of the procedure and the incidence of postoperative complications. At present, there are three main types of valves used worldwide: self-expanding valves, balloon-expandable valves, and mechanical expandable valves. Each has its advantages and disadvantages. In China, the Medtronic Core Valve was first used clinically, followed by the Sapien XT and Lotus valves.
China is also studying and developing a domestic valve to ensure the intellectual property rights which have resulted in a major breakthrough. The Venus-A valve is the first to be registered under the direction of principal investigator Prof. Gao Runlin, Fuwai Hospital, Beijing. Our hospital is mainly involved in research and development of this valve. The Venus-A is self-expanding and composed of a support structure of nickel-titanium alloy with porcine pericardium. A total of 101 procedures with 1-year follow-ups have been completed, pending approval by the China Food and Drug Administration. To date, the operative success rate of the Venus-A is 96.3%, the 30-day mortality rate is 4.94%, the pacemaker implantation rate is 17.3%, the degree of aortic stenosis, and physical activity according to the New York Heart Association Functional Classification have improved significantly. These outcomes were similar to the findings in the PARTneR Trial and CoreValve US Pivotal Trial. The VitaFlow valve (MicroPort, Shanghai), with bovine pericardium, is also self-expanding. The valgus double-skirt design of the VitaFlow helps to reduce the incidence of perivalvular leakage. To date, the VitaFlow has been used in 110 cases in a clinical registry study. The J-Valve was developed by the Suzhou JieCheng Medical Technology company. In contrast to the valves above, the J-Valve is implanted through a transapical approach. In addition to AS, the design of this prosthesis may be useful in the treatment of aortic regurgitation. The clinical registration study and 1-year follow-up of the J-Valve have been completed.
A transfemoral approach is the most widely used access technique for TAVR. It has been reported that the transfemoral approach can reduce 30-day and 1-year mortality rates. Despite the availability of the transapical approach, 96.5% of TAVR cases in China are performed using the transfemoral approach. However, when the femoral artery diameter is too small, or there is significant atherosclerosis, calcification, and distortion in the femoral artery, the interventional cardiologist must choose an alternative approach for TAVR. In China, 1.5% of TAVR cases are performed through a transaortic approach, and 1.5% through a transcarotid approach, with only 0.5% of cases through a transubclavian approach. With device modifications resulting in smaller delivery catheters, more patients will be able to undergo the transfemoral approach.
Although TAVR technology in China started relatively late and the number of clinical cases has been small, the results have been similar to those of large-scale clinical research and registration studies in other countries. Our center has performed more than 200 TAVR cases, with a 30-day mortality rate of 4%, an immediate surgical success rate of 98.9%, and a pacemaker implantation rate of 20.7%. In our preliminary experience, TAVR has been shown to be safe and effective in the Chinese population.
Bicuspid Aortic Valve
Bicuspid aortic valve (BAV) is a condition in which two leaflets of the valve fuse together during development. Severe aortic valve dysfunction is driven by much more rapidly progressive valvular stenosis is the most common cause of morbidity in BAV patients. The presence of a BAV has long been regarded as a relative contraindication for TAVR since the unfavorable anatomy of BAV may impede the positioning and expansion of the prosthetic valve. Theoretically, this would increase the incidence of procedural complications and decrease the efficacy and durability of the prosthetic valve.[12,13] It is worth noting that in patients undergoing TAVR surgery in China, the proportion with BAV is significantly higher than that in other countries. Many centers have reported a BAV ratio of patients undergoing TAVR of about 50%. Using our center as an example, the BAV ratio was 31.6%. The research data in China also showed that TAVR is equally effective for patients with BAV. Our center has developed a new technology named “sequential balloon sizing,” to help cardiologists treat BAV. We have completed 66 TAVR procedures in BAV patients, with an immediate operative success rate of 97%, a 30-day mortality rate of 4.5%, and a pacemaker implantation rate of 10.6%. Our current guideline supported Chinese TAVR experts consensus, states that patients can undergo TAVR in experienced centers if they have BAV with the relative indications of severe calcific stenosis, surgical contraindications, AS symptoms, a postoperative life expectancy of more than 1 year, and anatomy suitable for TAVR.
Unresolved Problems in China
Although the results with TAVR in China and the research and development of domestic valves are encouraging, unresolved problem still remain. First: progress is slow. The overall number of TAVR cases is relatively small. Although 28 hospitals have performed TAVR, the lack of professional imaging teams and hybrid operating rooms prevent most facilities from performing TAVR independently. Currently, only four centers can perform TAVR independently. Second: the design of the prosthetic aortic valve still requires improvement. Internationally developed prosthetic valves have entered a second or third generation, and the incidence of postoperative complications has been significantly reduced. The overall performance of the domestic prosthetic valve is satisfactory however compared to foreign products; there is room for improvement. Third: the proportion of BAV is high. As noted above, the proportion of BAV patients undergoing TAVR in China is significantly higher than that in other countries. However, due to the lack of epidemiological data on BAV, cardiologists cannot accurately determine the incidence, which impedes the development and popularization of TAVR technology in China. Fourth: the cost is high. One imported prosthetic valve costs about 240,000 yuan. If the domestic valve is not covered by medical insurance, its clinical use will be limited. Fifth: a lack of health awareness. In China, the vast majority of severe AS patients are elderly. Due to high costs and/or surgical risk, many patients and their families refuse surgery, resulting in a poor prognosis. The state, society, medical and health management departments, doctors, and hospitals must determine how the benefits of TAVR can be extended to more AS patients.
The Future of Transcatheter Aortic Valve Replacement in China
The incidence of valvular heart disease is increasing in China as a result of the development of the economy and society and an aging population. TAVR has been proven safe and effective for severe AS. Although TAVR is still in the initial stages in China, the continuous efforts of the government, doctors, patients, and research institutions will promote rapid advancement of the technology, and TAVR will become an important method for the treatment of patients with severe AS.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
1. Hu P, Liu XB, Liang J, Zhu QF, Pu CX, Tang MY, et al.
A hospital-based survey of patients with severe valvular heart disease in China. Int J Cardiol 2017;231:244-7.
2. Thaden JJ, Nkomo VT, Enriquez-Sarano M. The global burden of aortic stenosis. Prog Cardiovasc Dis 2014;56:565-71.
3. Cribier A. Development of transcatheter aortic valve implantation (TAVI): A 20-year odyssey. Arch Cardiovasc Dis 2012;105:146-52.
4. Andersen HR, Knudsen LL, Hasenkam JM. Transluminal implantation of artificial heart valves. Description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. Eur Heart J 1992;13:704-8.
5. Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, et al.
Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: First human case description. Circulation 2002;106:3006-8.
6. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd
, Guyton RA, et al.
2014 AHA/ACC guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438-88.
7. Xianbao L, Feng G, Jubo J, Wei H, Chaoxia P, Qijing Z, et al
. First two cases of transcatheter aortic valve replacement with Lotus valve system in China. Chin J Emerg Med 2015;24:1349-52.
8. Dong AQ, Kong MJ, Liu XB, Jiang JB, He YX, Chen JF, et al
. Trans-apical transcatheter aortic valve replacement for patient with severe pure aortic regurgitation. Chin J Emerg Med 2016;25:1237-9.
9. Chandrasekhar J, Hibbert B, Ruel M, Lam BK, Labinaz M, Glover C, et al.
Transfemoral vs non-transfemoral access for transcatheter aortic valve implantation: A systematic review and meta-analysis. Can J Cardiol 2015;31:1427-38.
10. Mulder BJ. Epidemiology of adult congenital heart disease: Demographic variations worldwide. Neth Heart J 2012;20:505-8.
11. Michelena HI, Khanna AD, Mahoney D, Margaryan E, Topilsky Y, Suri RM, et al.
Incidence of aortic complications in patients with bicuspid aortic valves. JAMA 2011;306:1104-12.
12. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, et al.
Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597-607.
13. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, et al.
Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98.
14. Liu XB, Jiang JB, Zhou QJ, Pu ZX, He W, Dong AQ, et al.
Evaluation of the safety and efficacy of transcatheter aortic valve implantation in patients with a severe stenotic bicuspid aortic valve in a Chinese population. J Zhejiang Univ Sci B 2015;16:208-14.
15. Junbo G, Jianan W, Bo Y, Daxin Z, Yongjian W, Xiangqing K, et al
. Consensus of Chinese experts on TAVR. Chin J Int Cardiol 2015;23:661-7.