Treatment Strategy for Severe Aortic Stenosis With Moderate/Severe Mitral Regurgitation

The selection of transcatheter or surgical aortic valve replacement (TAVR/SAVR) is one of the most important topics in the management of severe aortic stenosis (AS), and current treatment strategies are mainly based on the results of previous large-scale randomized controlled trials (RCTs).^1–5 However, those RCTs were primarily designed to evaluate the efficacy of AS treatment alone, making it challenging to interpret the results into treatment strategies for cases of concomitant heart disease such as coronary disease or mitral regurgitation (MR), which are commonly encountered in daily clinical practice.⁶

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Among the combined valvular diseases, AS with MR is the most frequent, and the results of numerous clinical studies conducted to investigate the clinical outcomes of this group of patients^7–11 and have been incorporated into major guidelines.^12,13 A commonality of these guidelines is the recommendation of a concomitant mitral valve procedure for SAVR-eligible patients considering the extended surgical risk, and for SAVR-ineligible patients (high-risk cases), TAVR followed by mitral transcatheter edge-to-edge repair (TEER) as needed. However, in cases of patients who fall into the group suitable for either TAVR or SAVR, there is insufficient evidence to make clear recommendations. It is hoped that future studies will adequately verify the progression of MR and its impact on prognosis after SAVR/TAVR.

In this issue of the Journal, Obayashi et al¹⁴ describe the results of the CURRENT AS Registry-2 (a prospective registry of AS at 21 facilities in Japan), which involved 2,239 cases of severe AS. A notable aspect of their study is the analysis of 3 groups undergoing TAVR, SAVR, and conservative treatment, comparing the prognosis of patient cohorts with and without preoperative moderate/severe MR in each group. The SAVR group (591 cases) and TAVR group (1,148 cases) were of particular interest, with moderate/severe MR observed in 68 (11.5%) and 126 (11.0%) cases, respectively. In the SAVR group, 27 of 68 cases (40.9%) underwent concurrent mitral valve surgery, with 84.7% of moderate/severe MR cases improving to mild MR or less postoperatively. In the TAVR group, 47.6% of moderate/severe MR cases improved to mild MR or less postoperatively, and 7 cases underwent mitral TEER during follow-up. In the comparison of long-term prognosis, the primary outcome (all-cause death or hospitalization for heart failure) in the SAVR group was significantly worse for moderate/severe MR cases, with this difference remaining after risk adjustment (odds ratio 1.92). On the other hand, in the TAVR group, although a difference in the primary outcome was also observed in moderate/severe MR cases, statistical significance disappeared after risk adjustment.

Most previous studies have compared the prognosis of moderate/severe MR cohorts in either SAVR or TAVR treatment groups, consistently reporting poor prognosis for moderate/severe MR cohorts.^7,9–11 A subanalysis of the PARTNER trial Cohort A, a valuable RCT targeting high-risk groups, reported poor prognosis for moderate/severe MR cases in SAVR, but not in TAVR,⁸ which is consistent with Obayashi et al’s findings. Although it is necessary to consider the treatment selection bias for TAVR/SAVR in the CURRENT registry, it is noteworthy to consider the consistency of the CURRENT AS registry with the PARTNER trial in the results showing the difference in the prognosis of MR cohorts in surgical and transcatheter AVR. In both reports, the long-term prognosis for preoperative mild or less MR cases was relatively best in the SAVR treatment cohort, but relatively worst for SAVR with moderate/severe MR cohort. Conversely, the prognosis was equivalent regardless of MR severity in the TAVR group. Although there is a need for further research to fully understand the prognosis of MR post-SAVR/TAVR and its impact on long-term outcomes, these findings point towards the future selection of treatment strategies.

Acknowledgment

The authors used Chat GPT 4.0 for English language proofreading purpose only.

Disclosures

The authors have No COI to disclose.

IRB Information

None.

References

• 1.   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: 1597–1607.
• 2.   Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016; 374: 1609–1620.
• 3.   Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, Russo M, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019; 380: 1695–1705.
• 4.   Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Sondergaard L, Mumtaz M, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med 2017; 376: 1321–1331.
• 5.   Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, O’Hair D, et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med 2019; 380: 1706–1715.
• 6.   Sannino A, Grayburn PA. Mitral regurgitation in patients with severe aortic stenosis: Diagnosis and management. Heart 2018; 104: 16–22.
• 7.   Jeong DS, Park PW, Sung K, Kim WS, Yang JH, Jun TG, et al. Long-term clinical impact of functional mitral regurgitation after aortic valve replacement. Ann Thorac Surg 2011; 92: 1339–1345; discussion 1345.
• 8.   Barbanti M, Webb JG, Hahn RT, Feldman T, Boone RH, Smith CR, et al. Impact of preoperative moderate/severe mitral regurgitation on 2-year outcome after transcatheter and surgical aortic valve replacement: Insight from the Placement of Aortic Transcatheter Valve (PARTNER) Trial Cohort A. Circulation 2013; 128: 2776–2784.
• 9.   Cortes C, Amat-Santos IJ, Nombela-Franco L, Munoz-Garcia AJ, Gutierrez-Ibanes E, De La Torre Hernandez JM, et al. Mitral regurgitation after transcatheter aortic valve replacement: Prognosis, imaging predictors, and potential management. JACC Cardiovasc Interv 2016; 9: 1603–1614.
• 10.   Ruel M, Kapila V, Price J, Kulik A, Burwash IG, Mesana TG. Natural history and predictors of outcome in patients with concomitant functional mitral regurgitation at the time of aortic valve replacement. Circulation 2006; 114(Suppl): I541–I546.
• 11.   Matsuura K, Kumamaru H, Kohsaka S, Kanda T, Yamashita D, Kitahara H, et al. Impact of concomitant mitral regurgitation during transcatheter aortic valve replacement on 1-year survival outcomes. J Cardiol 2023; 82: 16–21.
• 12.   Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, et al. 2020 ACC/AHA Guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021; 143: e72–e227.
• 13.   Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2022; 43: 561–632.
• 14.   Obayashi Y, Takeji Y, Taniguchi T, Morimoto T, Shirai S, Kitai T, et al. Concomitant mitral regurgitation in severe aortic stenosis: Insights from the CURRENT AS Registry-2. Circ J 2024, doi:10.1253/circj.CJ-24-0103.