Exploration of the application of transcatheter aortic valve replacement for moderate aortic stenosis_West China Medical Journal

Authors：

LI Xi , Gesangwangmu ,  WEI Xin

Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

WEI Xin, Email: weizhang_1985812@163.com

Keywords：

Transcatheter aortic valve replacement; moderate aortic stenosis; indication; prognostic stratification; intervention timing

DOI：

10.7507/1002-0179.202502190

Video：

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Abstract Full text Figures/Tables Video References Cited by

Current guidelines recommend follow-up observation for moderate aortic stenosis (MAS), but clinical evidence shows that its prognosis is poor, especially when combined with left ventricular systolic dysfunction, the risk of death and hospitalization for heart failure is significantly increased. With the technical maturity and device development of transcatheter aortic valve replacement (TAVR), its therapeutic potential in MAS has attracted attention. This paper systematically reviewes the risk stratification indicators of MAS and the clinical research results of early TAVR intervention, and analyzes the key clinical issues such as patient selection and operation timing. It points out that early TAVR may improve the prognosis and quality of life of some high-risk MAS patients, but its wide clinical application still needs more evidence-based medical evidence support.

1.	d’Arcy JL, Coffey S, Loudon MA, et al. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur Heart J, 2016, 37(47): 3515-3522.
2.	Zheng X, Guan Q, Lin X. Changing trends of the disease burden of non-rheumatic valvular heart disease in China from 1990 to 2019 and its predictions: findings from global burden of disease study. Front Cardiovasc Med, 2023, 9: 912661.
3.	Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J, 2022, 43(7): 561-632.
4.	Jean G, Van Mieghem NM, Gegenava T, et al. Moderate aortic stenosis in patients with heart failure and reduced ejection fraction. J Am Coll Cardiol, 2021, 77(22): 2796-2803.
5.	Stassen J, Ewe SH, Pio SM, et al. Managing patients with moderate aortic stenosis. JACC Cardiovasc Imaging, 2023, 16(6): 837-855.
6.	Pibarot P, Messika-Zeitoun D, Ben-Yehuda O, et al. Moderate aortic stenosis and heart failure with reduced ejection fraction: can imaging guide us to therapy?. JACC Cardiovasc Imaging, 2019, 12(1): 172-184.
7.	Strange G, Stewart S, Celermajer D, et al. Poor long-term survival in patients with moderate aortic stenosis. J Am Coll Cardiol, 2019, 74(15): 1851-1863.
8.	Delesalle G, Bohbot Y, Rusinaru D, et al. Characteristics and prognosis of patients with moderate aortic stenosis and preserved left ventricular ejection fraction. J Am Heart Assoc, 2019, 8(6): e011036.
9.	Murphy KR, Khan OA, Rassa AC, et al. Clinical and echocardiographic predictors of outcomes in patients with moderate (mean transvalvular gradient 20 to 40 mm Hg) aortic stenosis. Am J Cardiol, 2019, 124(12): 1924-1931.
10.	Benfari G, Nistri S, Marin F, et al. Excess mortality associated with progression rate in asymptomatic aortic valve stenosis. J Am Soc Echocardiogr, 2021, 34(3): 237-244.
11.	Ito S, Miranda WR, Nkomo VT, et al. Prognostic risk stratification of patients with moderate aortic stenosis. J Am Soc Echocardiogr, 2021, 34(3): 248-256.
12.	Stassen J, Ewe SH, Butcher SC, et al. Moderate aortic stenosis: importance of symptoms and left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging, 2022, 23(6): 790-799.
13.	Amanullah MR, Pio SM, Ng ACT, et al. Prognostic implications of associated cardiac abnormalities detected on echocardiography in patients with moderate aortic stenosis. JACC Cardiovasc Imaging, 2021, 14(9): 1724-1737.
14.	Cairns BJ, Coffey S, Travis RC, et al. A replicated, genome-wide significant association of aortic stenosis with a genetic variant for lipoprotein(a): meta-analysis of published and novel data. Circulation, 2017, 135(12): 1181-1183.
15.	Tsimikas S. Potential causality and emerging medical therapies for lipoprotein(a) and its associated oxidized phospholipids in calcific aortic valve stenosis. Circ Res, 2019, 124(3): 405-415.
16.	Samad Z, Vora AN, Dunning A, et al. Aortic valve surgery and survival in patients with moderate or severe aortic stenosis and left ventricular dysfunction. Eur Heart J, 2016, 37(28): 2276-2286.
17.	刘雨杭, 宋来春, 肖勇, 等. 主动脉瓣狭窄伴低射血分数值患者行外科瓣膜置换术的疗效评价. 中国体外循环杂志, 2024, 22(2): 126-130.
18.	Cribier A, Eltchaninoff H, Tron C, et al. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol, 2004, 43(4): 698-703.
19.	Jørgensen TH, Thyregod HGH, Savontaus M, et al. Transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis aged 70 years or younger: A NOTION-2 substudy. Am Heart J, 2025, 284: 67-70.
20.	Mehaffey JH, Jagadeesan V, Kawsara M, et al. Transcatheter vs surgical aortic valve replacement in bicuspid aortic valves. Ann Thorac Surg, 2025, 119(6): 1261-1269.
21.	Ahmed M, Ahsan A, Shafiq A, et al. Meta-analysis of longitudinal comparison of transcatheter versus surgical aortic valve replacement in patients at low to intermediate surgical risk. Int J Surg, 2024, 110(12): 8097-8106.
22.	Généreux P, Schwartz A, Oldemeyer JB, et al. Transcatheter aortic-valve replacement for asymptomatic severe aortic stenosis. N Engl J Med, 2025, 392(3): 217-227.
23.	Kleiman NS, Van Mieghem NM, Reardon MJ, et al. Quality of life 5 years following transfemoral TAVR or SAVR in intermediate risk patients. JACC Cardiovasc Interv, 2024, 17(8): 979-988.
24.	Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement in low-risk patients at five years. N Engl J Med, 2023, 389(21): 1949-1960.
25.	Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med, 2010, 363(17): 1597-1607.
26.	Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med, 2011, 364(23): 2187-2198.
27.	van Gils L, Clavel MA, Vollema EM, et al. Prognostic implications of moderate aortic stenosis in patients with left ventricular systolic dysfunction. J Am Coll Cardiol, 2017, 69(19): 2383-2392.
28.	Spitzer E, Ren B, Kroon H, et al. Moderate aortic stenosis and reduced left ventricular ejection fraction: current evidence and challenges ahead. Front Cardiovasc Med, 2018, 5: 111.
29.	Liu X, Zhu Q, Liu Q, et al. Prognostic value of left ventricular systolic function on moderate aortic stenosis: the China-VHD study. Sci Bull (Beijing), 2023, 68(22): 2717-2720.
30.	Rassi AN, Pibarot P, Elmariah S. Left ventricular remodelling in aortic stenosis. Can J Cardiol, 2014, 30(9): 1004-1011.
31.	Everett RJ, Tastet L, Clavel MA, et al. Progression of hypertrophy and myocardial fibrosis in aortic stenosis: a multicenter cardiac magnetic resonance study. Circ Cardiovasc Imaging, 2018, 11(6): e007451.
32.	Chin CWL, Everett RJ, Kwiecinski J, et al. Myocardial fibrosis and cardiac decompensation in aortic stenosis. JACC Cardiovasc Imaging, 2017, 10(11): 1320-1333.
33.	Bull S, White SK, Piechnik SK, et al. Human non-contrast T1 values and correlation with histology in diffuse fibrosis. Heart, 2013, 99(13): 932-937.
34.	Everett RJ, Treibel TA, Fukui M, et al. Extracellular myocardial volume in patients with aortic stenosis. J Am Coll Cardiol, 2020, 75(3): 304-316.
35.	Treibel TA, Kozor R, Schofield R, et al. Reverse myocardial remodeling following valve replacement in patients with aortic stenosis. J Am Coll Cardiol, 2018, 71(8): 860-871.
36.	Musa TA, Treibel TA, Vassiliou VS, et al. Myocardial scar and mortality in severe aortic stenosis. Circulation, 2018, 138(18): 1935-1947.
37.	Dweck MR, Joshi S, Murigu T, et al. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol, 2011, 58(12): 1271-1279.
38.	Saijo Y, Isaza N, Conic JZ, et al. Left ventricular longitudinal strain in characterization and outcome assessment of mixed aortic valve disease phenotypes. JACC Cardiovasc Imaging, 2021, 14(7): 1324-1334.
39.	Zhu D, Ito S, Miranda WR, et al. Left ventricular global longitudinal strain is associated with long-term outcomes in moderate aortic stenosis. Circ Cardiovasc Imaging, 2020, 13(4): e009958.
40.	Hayward C, Thornton G, Asher A, et al. Determinants of outcome in patients with left ventricular impairment and moderate aortic stenosis. JACC Cardiovasc Imaging, 2020, 13(6): 1449-1450.
41.	Stassen J, Ewe SH, Hirasawa K, et al. Left ventricular remodelling patterns in patients with moderate aortic stenosis. Eur Heart J Cardiovasc Imaging, 2022, 23(10): 1326-1335.
42.	Stassen J, Ewe SH, Butcher SC, et al. Prognostic implications of left ventricular diastolic dysfunction in moderate aortic stenosis. Heart, 2022, 108(17): 1401-1407.
43.	Ito S, Miranda WR, Jaffe AS, et al. Prognostic value of n-terminal pro-form b-type natriuretic peptide in patients with moderate aortic stenosis. Am J Cardiol, 2020, 125(10): 1566-1570.
44.	Chin CW, Shah AS, McAllister DA, et al. High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis. Eur Heart J, 2014, 35(34): 2312-2321.
45.	Ludwig S, Schofer N, Abdel-Wahab M, et al. Transcatheter aortic valve replacement in patients with reduced ejection fraction and nonsevere aortic stenosis. Circ Cardiovasc Interv, 2023, 16(5): e012768.
46.	Van Mieghem NM, Elmariah S, Spitzer E, et al. Transcatheter aortic valve replacement in patients with systolic heart failure and moderate aortic stenosis: TAVR UNLOAD. J Am Coll Cardiol, 2025, 85(9): 878-890.
47.	Thyregod HGH, Jørgensen TH, Ihlemann N, et al. Transcatheter or surgical aortic valve implantation: 10-year outcomes of the NOTION trial. Eur Heart J, 2024, 45(13): 1116-1124.

1. d’Arcy JL, Coffey S, Loudon MA, et al. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study. Eur Heart J, 2016, 37(47): 3515-3522.
2. Zheng X, Guan Q, Lin X. Changing trends of the disease burden of non-rheumatic valvular heart disease in China from 1990 to 2019 and its predictions: findings from global burden of disease study. Front Cardiovasc Med, 2023, 9: 912661.
3. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J, 2022, 43(7): 561-632.
4. Jean G, Van Mieghem NM, Gegenava T, et al. Moderate aortic stenosis in patients with heart failure and reduced ejection fraction. J Am Coll Cardiol, 2021, 77(22): 2796-2803.
5. Stassen J, Ewe SH, Pio SM, et al. Managing patients with moderate aortic stenosis. JACC Cardiovasc Imaging, 2023, 16(6): 837-855.
6. Pibarot P, Messika-Zeitoun D, Ben-Yehuda O, et al. Moderate aortic stenosis and heart failure with reduced ejection fraction: can imaging guide us to therapy?. JACC Cardiovasc Imaging, 2019, 12(1): 172-184.
7. Strange G, Stewart S, Celermajer D, et al. Poor long-term survival in patients with moderate aortic stenosis. J Am Coll Cardiol, 2019, 74(15): 1851-1863.
8. Delesalle G, Bohbot Y, Rusinaru D, et al. Characteristics and prognosis of patients with moderate aortic stenosis and preserved left ventricular ejection fraction. J Am Heart Assoc, 2019, 8(6): e011036.
9. Murphy KR, Khan OA, Rassa AC, et al. Clinical and echocardiographic predictors of outcomes in patients with moderate (mean transvalvular gradient 20 to 40 mm Hg) aortic stenosis. Am J Cardiol, 2019, 124(12): 1924-1931.
10. Benfari G, Nistri S, Marin F, et al. Excess mortality associated with progression rate in asymptomatic aortic valve stenosis. J Am Soc Echocardiogr, 2021, 34(3): 237-244.
11. Ito S, Miranda WR, Nkomo VT, et al. Prognostic risk stratification of patients with moderate aortic stenosis. J Am Soc Echocardiogr, 2021, 34(3): 248-256.
12. Stassen J, Ewe SH, Butcher SC, et al. Moderate aortic stenosis: importance of symptoms and left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging, 2022, 23(6): 790-799.
13. Amanullah MR, Pio SM, Ng ACT, et al. Prognostic implications of associated cardiac abnormalities detected on echocardiography in patients with moderate aortic stenosis. JACC Cardiovasc Imaging, 2021, 14(9): 1724-1737.
14. Cairns BJ, Coffey S, Travis RC, et al. A replicated, genome-wide significant association of aortic stenosis with a genetic variant for lipoprotein(a): meta-analysis of published and novel data. Circulation, 2017, 135(12): 1181-1183.
15. Tsimikas S. Potential causality and emerging medical therapies for lipoprotein(a) and its associated oxidized phospholipids in calcific aortic valve stenosis. Circ Res, 2019, 124(3): 405-415.
16. Samad Z, Vora AN, Dunning A, et al. Aortic valve surgery and survival in patients with moderate or severe aortic stenosis and left ventricular dysfunction. Eur Heart J, 2016, 37(28): 2276-2286.
17. 刘雨杭, 宋来春, 肖勇, 等. 主动脉瓣狭窄伴低射血分数值患者行外科瓣膜置换术的疗效评价. 中国体外循环杂志, 2024, 22(2): 126-130.
18. Cribier A, Eltchaninoff H, Tron C, et al. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol, 2004, 43(4): 698-703.
19. Jørgensen TH, Thyregod HGH, Savontaus M, et al. Transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis aged 70 years or younger: A NOTION-2 substudy. Am Heart J, 2025, 284: 67-70.
20. Mehaffey JH, Jagadeesan V, Kawsara M, et al. Transcatheter vs surgical aortic valve replacement in bicuspid aortic valves. Ann Thorac Surg, 2025, 119(6): 1261-1269.
21. Ahmed M, Ahsan A, Shafiq A, et al. Meta-analysis of longitudinal comparison of transcatheter versus surgical aortic valve replacement in patients at low to intermediate surgical risk. Int J Surg, 2024, 110(12): 8097-8106.
22. Généreux P, Schwartz A, Oldemeyer JB, et al. Transcatheter aortic-valve replacement for asymptomatic severe aortic stenosis. N Engl J Med, 2025, 392(3): 217-227.
23. Kleiman NS, Van Mieghem NM, Reardon MJ, et al. Quality of life 5 years following transfemoral TAVR or SAVR in intermediate risk patients. JACC Cardiovasc Interv, 2024, 17(8): 979-988.
24. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement in low-risk patients at five years. N Engl J Med, 2023, 389(21): 1949-1960.
25. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med, 2010, 363(17): 1597-1607.
26. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med, 2011, 364(23): 2187-2198.
27. van Gils L, Clavel MA, Vollema EM, et al. Prognostic implications of moderate aortic stenosis in patients with left ventricular systolic dysfunction. J Am Coll Cardiol, 2017, 69(19): 2383-2392.
28. Spitzer E, Ren B, Kroon H, et al. Moderate aortic stenosis and reduced left ventricular ejection fraction: current evidence and challenges ahead. Front Cardiovasc Med, 2018, 5: 111.
29. Liu X, Zhu Q, Liu Q, et al. Prognostic value of left ventricular systolic function on moderate aortic stenosis: the China-VHD study. Sci Bull (Beijing), 2023, 68(22): 2717-2720.
30. Rassi AN, Pibarot P, Elmariah S. Left ventricular remodelling in aortic stenosis. Can J Cardiol, 2014, 30(9): 1004-1011.
31. Everett RJ, Tastet L, Clavel MA, et al. Progression of hypertrophy and myocardial fibrosis in aortic stenosis: a multicenter cardiac magnetic resonance study. Circ Cardiovasc Imaging, 2018, 11(6): e007451.
32. Chin CWL, Everett RJ, Kwiecinski J, et al. Myocardial fibrosis and cardiac decompensation in aortic stenosis. JACC Cardiovasc Imaging, 2017, 10(11): 1320-1333.
33. Bull S, White SK, Piechnik SK, et al. Human non-contrast T1 values and correlation with histology in diffuse fibrosis. Heart, 2013, 99(13): 932-937.
34. Everett RJ, Treibel TA, Fukui M, et al. Extracellular myocardial volume in patients with aortic stenosis. J Am Coll Cardiol, 2020, 75(3): 304-316.
35. Treibel TA, Kozor R, Schofield R, et al. Reverse myocardial remodeling following valve replacement in patients with aortic stenosis. J Am Coll Cardiol, 2018, 71(8): 860-871.
36. Musa TA, Treibel TA, Vassiliou VS, et al. Myocardial scar and mortality in severe aortic stenosis. Circulation, 2018, 138(18): 1935-1947.
37. Dweck MR, Joshi S, Murigu T, et al. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol, 2011, 58(12): 1271-1279.
38. Saijo Y, Isaza N, Conic JZ, et al. Left ventricular longitudinal strain in characterization and outcome assessment of mixed aortic valve disease phenotypes. JACC Cardiovasc Imaging, 2021, 14(7): 1324-1334.
39. Zhu D, Ito S, Miranda WR, et al. Left ventricular global longitudinal strain is associated with long-term outcomes in moderate aortic stenosis. Circ Cardiovasc Imaging, 2020, 13(4): e009958.
40. Hayward C, Thornton G, Asher A, et al. Determinants of outcome in patients with left ventricular impairment and moderate aortic stenosis. JACC Cardiovasc Imaging, 2020, 13(6): 1449-1450.
41. Stassen J, Ewe SH, Hirasawa K, et al. Left ventricular remodelling patterns in patients with moderate aortic stenosis. Eur Heart J Cardiovasc Imaging, 2022, 23(10): 1326-1335.
42. Stassen J, Ewe SH, Butcher SC, et al. Prognostic implications of left ventricular diastolic dysfunction in moderate aortic stenosis. Heart, 2022, 108(17): 1401-1407.
43. Ito S, Miranda WR, Jaffe AS, et al. Prognostic value of n-terminal pro-form b-type natriuretic peptide in patients with moderate aortic stenosis. Am J Cardiol, 2020, 125(10): 1566-1570.
44. Chin CW, Shah AS, McAllister DA, et al. High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis. Eur Heart J, 2014, 35(34): 2312-2321.
45. Ludwig S, Schofer N, Abdel-Wahab M, et al. Transcatheter aortic valve replacement in patients with reduced ejection fraction and nonsevere aortic stenosis. Circ Cardiovasc Interv, 2023, 16(5): e012768.
46. Van Mieghem NM, Elmariah S, Spitzer E, et al. Transcatheter aortic valve replacement in patients with systolic heart failure and moderate aortic stenosis: TAVR UNLOAD. J Am Coll Cardiol, 2025, 85(9): 878-890.
47. Thyregod HGH, Jørgensen TH, Ihlemann N, et al. Transcatheter or surgical aortic valve implantation: 10-year outcomes of the NOTION trial. Eur Heart J, 2024, 45(13): 1116-1124.

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