**6. TAVI treatment of pure aortic valve regurgitation**

The analysis of echocardiography data from Shanghai Zhongshan Hospital (including 0.3 million patients) indicates [55] that the incidence of aortic valve stenosis in China may be significantly lower than that in western countries, while aortic regurgitation (AR) is more common than aortic stenosis [56]. A retrospective data analysis from Shanghai Changhai Hospital in the past 20 years showed that the proportion of AR in patients undergoing surgical aortic valve replacement was significantly higher than that in patients with AS [57, 58]. The latest China-DVD multicenter study in 2019 showed that among the 8638 patients with valvular heart disease in China, there were 894 cases of aortic regurgitation, 430 cases of aortic stenosis, 286 cases of mitral stenosis, and 2248 cases of mitral regurgitation [59]. Patients with simple AR are still mainly treated by surgery. However, the influence of aortic regurgitation on the left ventricle and the induced symptoms of heart failure are very different from those of aortic stenosis. In patients with aortic regurgitation, the left ventricle enlarged more obviously, and the ejection fraction decreased more. But due to the late appearance of pulmonary congestion comparing with aortic stenosis, the clinical symptoms often appeared late, many patients went to see doctor very late when combined serious heart dysfunction. At this time, the patient's heart disease is not only aortic regurgitation but also left ventricular enlargement and heart failure. Even if aortic valve surgery solves valvular regurgitation, it will take longer time for heart function to recover. On the contrary, the cardiac function of many patients with aortic valve stenosis can recover in a short time after operation. Studies [60, 61] showed that about 10% AR patients are unable to undergo surgery because of old age and severe multiple organ dysfunction. Only 20% AR patients with a left ventricular ejection fraction ranging from 30% to 50% have received surgery. When the left ventricular ejection fraction is less than 30%, the proportion of patients undergoing surgery is as low as 3%. According to statistics, the annual mortality rate of patients treated with conservative medicines is as high as 10–20%, and the 10-year complication rate and mortality rate are not optimistic.

**93**

*Transcatheter Treatment of Aortic Stenosis and Regurgitation*

Because of the long stent structure design, the Medtronic CoreValve valve may be anchored at multiple points which may be helpful in the TAVI treatment of pure AR. In 2010, Ducrocq et al. reported that CoreValve was used to treat a high-risk AR patient with good results [62]. This is a self-expanding valve and can be implanted through the femoral artery. Its advantage lies in the long stent over 50 mm and the special three-stage fixation mechanism, in which the lower part squeezes the primary lobe through higher radial expansion, the middle part is compressed to avoid coronary artery blockage, and the upper part expands to fix to the ascending aorta and provides longitudinal coaxial stability. Therefore, even in the absence of valve calcification, the valve can theoretically be anchored in other positions. However, there are also some difficulties in the use of this valve [28, 63]. (1) Inadequate anchoring can easily lead to valve displacement, resulting in a higher incidence of secondary valve implantation and postoperative moderate and severe perivalvular leakage. Roy et al. [64] studied 43 AR patients with TAVI from 14 centers. The results showed that the rates of second valve implantation and the postoperative moderate perivalvular leakage were 19% and 21%, respectively. (2) Since the CoreValve is mainly fixed at the annulus with strong radial force, it is usually necessary to make the artificial valve diameter slightly larger than that of the autologous annulus in order to obtain sufficient radial support to make the anchoring more stable, which also leads to a

Since then, the second- generation TAVI valve has higher implantation rate due to the anchoring clip design which may help to locate and fix the valve. In 2013, Seiffert et al. [65] summarized the treatment effect of JenaValve in 5five patients with pure AR without calcification. The operation was performed through apical approach, and the success rate of valve implantation was 100%. There was no obvious residual regurgitation of aortic valve, and the cardiac function of the patients recovered satisfactorily after follow-up. In 2014, a Chinese team comprised of Da et al. [66] reported the excellent results of J-Valve, the China- designed secondgeneration TAVI valve, in the treatment of a high-risk AR case. J-Valve is designed to be implanted through the apical approach with three U-shaped positioning keys, which can be easily self-adjusted to enter the bottom of the aortic valve sinus. After the stent valve is released, the valve can be fixed and clamped together with the positioning key to assist the radial support to anchor the valve. Since 2017 J-Valve was officially put on the market for commercial use in China. In 2019, about 800 J-Valve TAVI procedures were performed in China, in which more than half was pure AR, and the clinical effect was very satisfied. At present, the transfemoral J-Valve system has begun clinical trials in Canada and the United States with prom-

In 2016 one meta-analysis [67] summarized 13 TAVI studies with 237 pure AR patients who could not tolerate surgical valve replacement. Among them, the utilization rate of self-expanding valve accounted for 79%, the implantation success rate was 77–100%, the 30-day all-cause mortality rate was 7%, and the incidence of postoperative moderate and severe valvular regurgitation was 9% (0% in JenaValve subgroup). It can be seen that although the study included JenaValve, a secondgeneration TAVI valve, the incidence of moderate and severe regurgitation and valve displacement after AR TAVI procedure was significantly higher than that of

In 2017 Yoon et al. [68] concluded that the new generation of TAVI valve with positioning-assisted anchoring system for the treatment of pure AR has higher implant success rate than the first-generation valve (81.1% vs. 61.3%), greatly reducing postoperative residual valvular regurgitation and perivalvular leakage (4.2% vs. 18.8%), and the probability of reimplantation of a second valve is greatly

*DOI: http://dx.doi.org/10.5772/intechopen.92997*

higher risk of annulus tear.

ising results [48].

aortic stenosis.

### *Transcatheter Treatment of Aortic Stenosis and Regurgitation DOI: http://dx.doi.org/10.5772/intechopen.92997*

*Advances in Complex Valvular Disease*

experience.

Some studies have shown that there are fewer postoperative adverse events in hospitals that perform more TAVI operations, and the accumulated TAVI experience is related to the improvement of postoperative outcomes. In 2018, the *Journal of the American Medical Association Cardiology* (JAMA Cardiol) published an observational cohort study [54] that included 60,538 TAVI operations performed in 438 hospitals from 2011 to 2016, with an average age of 82.3 years. Hospitals with a high amount of surgical valve replacement (annual average ≥ 97 / year) are more likely to start TAVI in the early stage, and the amount of TAVI increases faster with time. The average TAVI cases of hospitals with high surgical valve replacement volume to those with low volume was 32 vs. 19 in the first year, 48 vs. 28 in the second year, 82 vs. 38 in the third year, and 118 vs. 54 in the fourth year (P < 0.001). Combined with the analysis of hospital TAVI and surgical valve replacement volume, the 30-day mortality rate in high TAVI volume hospital was lower. When the hospital also has a high volume of surgical valve replacement, the effect is more obvious. Patients with high surgical valve replacement volume and high TAVI volume had the lowest 30-day mortality (for hospitals with low surgical valve replacement volume and TAVI volume: OR = 0.77; 95%CI, 0.66–0.89). Hospitals with both high volume of surgical valve replacement and TAVI cases may have the best outcome, which confirms the importance of hospital clinic

**6. TAVI treatment of pure aortic valve regurgitation**

The analysis of echocardiography data from Shanghai Zhongshan Hospital (including 0.3 million patients) indicates [55] that the incidence of aortic valve stenosis in China may be significantly lower than that in western countries, while aortic regurgitation (AR) is more common than aortic stenosis [56]. A retrospective data analysis from Shanghai Changhai Hospital in the past 20 years showed that the proportion of AR in patients undergoing surgical aortic valve replacement was significantly higher than that in patients with AS [57, 58]. The latest China-DVD multicenter study in 2019 showed that among the 8638 patients with valvular heart disease in China, there were 894 cases of aortic regurgitation, 430 cases of aortic stenosis, 286 cases of mitral stenosis, and 2248 cases of mitral regurgitation [59]. Patients with simple AR are still mainly treated by surgery. However, the influence of aortic regurgitation on the left ventricle and the induced symptoms of heart failure are very different from those of aortic stenosis. In patients with aortic regurgitation, the left ventricle enlarged more obviously, and the ejection fraction decreased more. But due to the late appearance of pulmonary congestion comparing with aortic stenosis, the clinical symptoms often appeared late, many patients went to see doctor very late when combined serious heart dysfunction. At this time, the patient's heart disease is not only aortic regurgitation but also left ventricular enlargement and heart failure. Even if aortic valve surgery solves valvular regurgitation, it will take longer time for heart function to recover. On the contrary, the cardiac function of many patients with aortic valve stenosis can recover in a short time after operation. Studies [60, 61] showed that about 10% AR patients are unable to undergo surgery because of old age and severe multiple organ dysfunction. Only 20% AR patients with a left ventricular ejection fraction ranging from 30% to 50% have received surgery. When the left ventricular ejection fraction is less than 30%, the proportion of patients undergoing surgery is as low as 3%. According to statistics, the annual mortality rate of patients treated with conservative medicines is as high as 10–20%, and the 10-year complication rate and mortality rate are

**92**

not optimistic.

Because of the long stent structure design, the Medtronic CoreValve valve may be anchored at multiple points which may be helpful in the TAVI treatment of pure AR. In 2010, Ducrocq et al. reported that CoreValve was used to treat a high-risk AR patient with good results [62]. This is a self-expanding valve and can be implanted through the femoral artery. Its advantage lies in the long stent over 50 mm and the special three-stage fixation mechanism, in which the lower part squeezes the primary lobe through higher radial expansion, the middle part is compressed to avoid coronary artery blockage, and the upper part expands to fix to the ascending aorta and provides longitudinal coaxial stability. Therefore, even in the absence of valve calcification, the valve can theoretically be anchored in other positions. However, there are also some difficulties in the use of this valve [28, 63]. (1) Inadequate anchoring can easily lead to valve displacement, resulting in a higher incidence of secondary valve implantation and postoperative moderate and severe perivalvular leakage. Roy et al. [64] studied 43 AR patients with TAVI from 14 centers. The results showed that the rates of second valve implantation and the postoperative moderate perivalvular leakage were 19% and 21%, respectively. (2) Since the CoreValve is mainly fixed at the annulus with strong radial force, it is usually necessary to make the artificial valve diameter slightly larger than that of the autologous annulus in order to obtain sufficient radial support to make the anchoring more stable, which also leads to a higher risk of annulus tear.

Since then, the second- generation TAVI valve has higher implantation rate due to the anchoring clip design which may help to locate and fix the valve. In 2013, Seiffert et al. [65] summarized the treatment effect of JenaValve in 5five patients with pure AR without calcification. The operation was performed through apical approach, and the success rate of valve implantation was 100%. There was no obvious residual regurgitation of aortic valve, and the cardiac function of the patients recovered satisfactorily after follow-up. In 2014, a Chinese team comprised of Da et al. [66] reported the excellent results of J-Valve, the China- designed secondgeneration TAVI valve, in the treatment of a high-risk AR case. J-Valve is designed to be implanted through the apical approach with three U-shaped positioning keys, which can be easily self-adjusted to enter the bottom of the aortic valve sinus. After the stent valve is released, the valve can be fixed and clamped together with the positioning key to assist the radial support to anchor the valve. Since 2017 J-Valve was officially put on the market for commercial use in China. In 2019, about 800 J-Valve TAVI procedures were performed in China, in which more than half was pure AR, and the clinical effect was very satisfied. At present, the transfemoral J-Valve system has begun clinical trials in Canada and the United States with promising results [48].

In 2016 one meta-analysis [67] summarized 13 TAVI studies with 237 pure AR patients who could not tolerate surgical valve replacement. Among them, the utilization rate of self-expanding valve accounted for 79%, the implantation success rate was 77–100%, the 30-day all-cause mortality rate was 7%, and the incidence of postoperative moderate and severe valvular regurgitation was 9% (0% in JenaValve subgroup). It can be seen that although the study included JenaValve, a secondgeneration TAVI valve, the incidence of moderate and severe regurgitation and valve displacement after AR TAVI procedure was significantly higher than that of aortic stenosis.

In 2017 Yoon et al. [68] concluded that the new generation of TAVI valve with positioning-assisted anchoring system for the treatment of pure AR has higher implant success rate than the first-generation valve (81.1% vs. 61.3%), greatly reducing postoperative residual valvular regurgitation and perivalvular leakage (4.2% vs. 18.8%), and the probability of reimplantation of a second valve is greatly reduced (12.7% vs. 24.4%). Totally 331 AR patients underwent TAVI, with an average STS score of 6.7%. 119 cases (36%) used early valves, and 212 cases (64%) used a new generation of valvular systems. The STS score of patients with new-generation valve implantation system was lower (6.2 ± 6.7 vs. 7.6 ± 6.7), but there was no statistical difference. The new generation of valves is more likely to get through the femoral artery access (87.4% vs. 60.8%). There was no significant difference in 30-day mortality between the two groups. The 1-year all-cause mortality rates of the two groups were 24.1% and 15.6%, respectively. The 1-year all-cause mortality was related to the degree of postoperative aortic regurgitation. The mortality rate of cases with moderate and severe regurgitation was 46.1%, while mild regurgitation decreased to 21.8%. Multivariate analysis showed that more than moderate postoperative regurgitation was an independent predictor of 1-year all-cause mortality (increased by 2.85 times). And this data is not included in China's J-Valve system reports.

In 2018, De Backer et al. [69] reported 254 high-risk AR patients in 46 centers, with an average age of 74 ± 12 years, a STS score of 6.6 ± 6.2%, with first-generation valve of 43%, and second-generation valve of 57%. The success rate of new generation valve implantation was significantly higher (82% vs. 47%), valve displacement decreased (9% vs. 33%), and aortic valve regurgitation decreased (4% vs. 31%). Both small or large valve size will easily lead to valve displacement. In 2019, Takagi et al. [70] summarized the TAVI efficacy of 11 studies with 911 pure AR patients. The overall valve implantation success rate was 80.4%, of which the early valve and the new-generation valve were 67.2% and 90.2%, respectively. Moderate and severe perivalvular leakage was 7.4% (early and new-generation valves were 17.3% and 3.4%, respectively). The 30-day all-cause mortality rate was 9.5% (early and new-generation valves were 14.7% and 6.1%, respectively). During the follow-up from 4 months to 1 year, the all-cause mortality rate was 18.8% (early and newgeneration valves were 32.2% and 11.8%, respectively). Vascular complications accounted for 3.9% (rates of early and new-generation valves were 6.2% and 3.0%, respectively). Life-threatening major bleeding was 5.7% (early and new-generation valves were 12.4% and 3.5%, respectively). In summary, the new generation of TAVI valve has a good therapeutic effect.

In China, there are also surgical high-risk cases in which the ascending aorta is not wide or the left ventricular outflow tract is small; some tried to use high stent self-expanding Venus A valve to treat pure AR patients. The results show that the valve displacement rate and the chance of reimplantation of the second valve are still very high (up to more than 50%). And there is also valve displacement into the ascending aorta or slipping in the left ventricle which may affect mitral valve function. These may result in doing open-chest surgery to remove the valve immediately. Therefore, this method is only suggested to be performed for highrisk patients and when other second-generation TAVI valves like J-Valve are not available.

The J-Valve valve with independent intellectual property rights in China is designed with three U-shaped positioning keys suitable for the anatomical structure of the aortic valve and sinus. The valve is released in two parts and then combined to play a role, which can more accurately locate the bottom of the aortic sinus and clamp the leaflet. J-Valve can effectively play a role in both aortic stenosis and regurgitation. A multicenter clinical study of trans-apical J-Valve in the treatment of high-risk noncalcified pure AR patients concluded data from 2014 to 2018 [71] in China. A total of 82 patients, aged 73.86.3 years, were included. The score of European cardiac surgery risk assessment system was 17.5 ± 8.1%. During the TAVI operation, four patients were converted to thoracotomy due to valve transposition, and the success rate of valve implantation was 95% (78/82). During hospitalization,

**95**

**7. Conclusion**

**Acknowledgements**

**Conflict of interest**

*Transcatheter Treatment of Aortic Stenosis and Regurgitation*

one case died of moderate perivalvular leakage complicated with multiple organ failure, and one case died of pulmonary infection. There was no residual aortic regurgitation in 82.1% (64/78) patients, mild perivalvular leakage in 16.7% (13/78) patients, and permanent pacemaker placement in 7.6% (6/78) patients due to III °atrioventricular block. The left ventricular end-diastolic volume decreased from (197.7 ± 66.8) ml to (147.2 ± 53.3) ml at 1 month after TAVI. The average transvalvular gradient was (9.5 ± 4.1) mmHg, which showed good hemodynamic performance. For the common problems of lack of calcification anchoring and aorta dilatation

in AR patients, the former has been solved to a certain extent by the continuous improvement of the second-generation TAVI valve with newly designed anchoring system, while the latter is still a difficult problem that cannot be solved at present. Therefore, many patients can only choose thoracotomy or even conservative medicine treatment. In addition, compared with patients with severe AS, patients with AR are often accompanied by more serious clinical symptoms, such as pulmonary hypertension, cardiac insufficiency, and so on. At the same time, late left ventricular hypertrophy, myocardial fibrosis, and cardiac insufficiency caused by AR may not be reversed even after TAVI, so these patients tend to have a poor prognosis and need longer time of medication treatment for the heart function recovery [29]. All these problems may take physicians more efforts in clinic to get good results for those AR patients with heart dysfunction besides of the TAVI procedure.

With the continuous development of interventional valve treatment technology, the interventional treatment of aortic stenosis and aortic insufficiency is more mature; many new generations of TAVI valves are emerging, which can be more convenient for clinicians to use, which can achieve more satisfactory treatment results. As for the development of TAVI technology and the extension of follow-up time, the indications of TAVI technology are also expanding. It is reasonable to believe that TAVI technology will be the main treatment technology in the future.

I would like to thank our heart valve center of cardiac surgery department of Beijing Anzhen Hospital, Capital Medical University. Their joint efforts made our center the first unit in China to successfully carry out interventional therapy technology for all four major heart valve diseases. Thanks to president Wei Yongxiang and vice president Zhou Yujie for their consistent strong support and trust in the development of new technology in our team. Thanks to professor Meng Xu, discipline director, for his planning and design, our center began to track the latest preface technology of TAVI technology as early as 2006 and kept close academic contact with the international advanced center. Thanks for the selfless dedication and support of our center's TAVI team, including cardiac surgery, cardiology, anesthesiology, imaging, hybrid operation room, intensive care unit, ultrasound department, interventional department, etc. At the same time, I also thank TAVI

teams of other heart centers in China for their support and help.

I confirm that there are no conflicts of interest.

*DOI: http://dx.doi.org/10.5772/intechopen.92997*

*Transcatheter Treatment of Aortic Stenosis and Regurgitation DOI: http://dx.doi.org/10.5772/intechopen.92997*

one case died of moderate perivalvular leakage complicated with multiple organ failure, and one case died of pulmonary infection. There was no residual aortic regurgitation in 82.1% (64/78) patients, mild perivalvular leakage in 16.7% (13/78) patients, and permanent pacemaker placement in 7.6% (6/78) patients due to III °atrioventricular block. The left ventricular end-diastolic volume decreased from (197.7 ± 66.8) ml to (147.2 ± 53.3) ml at 1 month after TAVI. The average transvalvular gradient was (9.5 ± 4.1) mmHg, which showed good hemodynamic performance.

For the common problems of lack of calcification anchoring and aorta dilatation in AR patients, the former has been solved to a certain extent by the continuous improvement of the second-generation TAVI valve with newly designed anchoring system, while the latter is still a difficult problem that cannot be solved at present. Therefore, many patients can only choose thoracotomy or even conservative medicine treatment. In addition, compared with patients with severe AS, patients with AR are often accompanied by more serious clinical symptoms, such as pulmonary hypertension, cardiac insufficiency, and so on. At the same time, late left ventricular hypertrophy, myocardial fibrosis, and cardiac insufficiency caused by AR may not be reversed even after TAVI, so these patients tend to have a poor prognosis and need longer time of medication treatment for the heart function recovery [29]. All these problems may take physicians more efforts in clinic to get good results for those AR patients with heart dysfunction besides of the TAVI procedure.
