Aims: To determine the prognosis of multivalvular disease in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis. Methods: Patients undergoing TAVR for aortic stenosis with covariate-adjusted risk of mortality associated with concomitant valve disease (mitral regurgitation [MR], mitral stenosis [MS] or tricuspid regurgitation [TR]) were included. Results: Moderate-to-severe MR was associated with increased mortality at 30 days (hazard ratio [HR]: 1.60; 95% CI: 1.11–2.30; p = 0.01) and 1 year (HR: 1.87; 95% CI: 1.22–2.87; p = 0.004). The presence of all-grade MS did not impact 30-day or 1-year mortality (HR, 30 days: 1.60; 95% CI: 0.71–3.63; p = 0.26; and HR, 1 year: 1.90; 95% CI: 0.98–3.69; p = 0.06); however, an increased risk of 1-year mortality (HR: 1.67; 95% CI: 1.03–2.70; p = 0.04) was observed with severe MS compared with no MS. Moderate-to-severe TR had a higher risk of all-cause mortality at 1 year (HR: 1.49; 95% CI: 1.24–1.78; p < 0.001) compared with no or mild TR. Conclusion: Moderate-to-severe MR or TR, and severe MS, significantly increase mid-term mortality after TAVR.

Plain language summary

Transcatheter aortic valve replacement (TAVR) is a minimally invasive heart procedure to replace a thickened aortic valve (aortic stenosis). In the current era, the use of TAVR has increased in patients suffering from uncomfortable and potentially life-threatening symptoms of severe aortic stenosis who are at increased risk for undergoing a surgical procedure to replace their valves. However, accompanying valve diseases like mitral regurgitation (mitral valve cannot close tightly), mitral stenosis (a narrowed mitral valve) and tricuspid regurgitation (tricuspid valve cannot close tightly) are highly common in these patients. Therefore in this paper we assessed the effect of accompanying valvular disorders on the likelihood of death following TAVR in this patient population. Our findings suggest that accompanying moderate-to-severe mitral regurgitation and tricuspid regurgitation leads to an increase in deaths post-TAVR. Likewise, severe mitral stenosis also increased the risk of deaths after TAVR.

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TAVR in patients with multivalvular disease.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Zoghbi WA, Asch FM, Bruce C et al. Guidelines for the evaluation of valvular regurgitation after percutaneous valve repair or replacement: a report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Japanese Society of Echocardiography, and Society for Cardiovascular Magnetic Resonance. J. Am. Soc. Echocardiogr. 32(4), 431–475 (2019).
MedlineGoogle Scholar
2. Chen J, Li W, Xiang M. Burden of valvular heart disease, 1990–2017: results from the Global Burden of Disease Study 2017. J. Glob Health 10(2), 020404 (2020).
MedlineGoogle Scholar
3. Rotman OM, Bianchi M, Ghosh RP, Kovarovic B, Bluestein D. Principles of TAVR valve design, modelling, and testing. Expert Rev. Med. Devices 15(11), 771–791 (2018).
Medline CASGoogle Scholar
4. Jones BM, Krishnaswamy A, Tuzcu EM et al. Matching patients with the ever-expanding range of TAVI devices. Nat. Rev. Cardiol. 14(10), 615–626 (2017).
MedlineGoogle Scholar
5. Alkhouli M, Alqahtani F, Ziada KM, Aljohani S, Holmes DR, Mathew V. Contemporary trends in the management of aortic stenosis in the USA. Eur. Heart J. 41(8), 921–928 (2020).
MedlineGoogle Scholar
6. Nathaniel S, Saligram S, Innasimuthu AL. Aortic stenosis: an update. World J. Cardiol. 2(6), 135–139 (2010).
MedlineGoogle Scholar
7. Unger P, Pibarot P, Tribouilloy C et al. European Society of Cardiology Council on Valvular Heart Disease. multiple and mixed valvular heart diseases. Circ. Cardiovasc. Imaging 11 (.8), e007862 (2018).
MedlineGoogle Scholar
8. Unger P, Clavel MA, Lindman BR, Mathieu P, Pibarot P. Pathophysiology and management of multivalvular disease. Nat. Rev. Cardiol. 13(7), 429–440 (2016).
MedlineGoogle Scholar
9. Khan SU, Riaz H, Khan MU et al. Meta-analysis of temporal and surgical risk dependent associations with outcomes after transcatheter versus surgical aortic valve implantation. Am. J. Cardiol. 124(10), 1608–1614 (2019).
MedlineGoogle Scholar
10. Mauri V, Körber MI, Kuhn E et al. Prognosis of persistent mitral regurgitation in patients undergoing transcatheter aortic valve replacement. Clin. Res. Cardiol. 109(10), 1261–1270 (2020).
MedlineGoogle Scholar
11. Vahanian A, Beyersdorf F, Praz F et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur. Heart J. 43(7), 561–632 (2022). • Highlights the lack of data regarding combined or multiple valve disease and will greatly interest readers.
MedlineGoogle Scholar
12. Masson JB, Forcillo J. Mixed-valve disease: management of patients with aortic stenosis and mitral regurgitation: thresholds for surgery versus percutaneous therapies. US Cardiol. Rev. 15, e26 (2021).
Google Scholar
13. Sannino A, Losi MA, Schiattarella GG et al. Meta-analysis of mortality outcomes and mitral regurgitation evolution in 4839 patients having transcatheter aortic valve implantation for severe aortic stenosis. Am. J. Cardiol. 114(6), 875–882 (2014). •• Important prior work similar to our analysis except that it pooled unadjusted data to demonstrate similar findings with respect to concomitant moderate or severe mitral regurgitation in transcatheter aortic valve replacement (TAVR) patients.
MedlineGoogle Scholar
14. Khan F, Okuno T, Malebranche D et al. Transcatheter aortic valve replacement in patients with multivalvular heart disease. JACC Cardiovasc. Interv. 13(13), 1503–1514 (2020).
MedlineGoogle Scholar
15. Hutton B, Salanti G, Caldwell DM et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann. Intern. Med. 162(11), 777–784 (2015).
MedlineGoogle Scholar
16. Wells GA, Shea B, O’Connell D et al. The Newcastle–Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. www.ohri.ca/programs/clinical_epidemiology/oxford.asp
Google Scholar
17. Toggweiler S, Boone RH, Rodés-Cabau J et al. Transcatheter aortic valve replacement: outcomes of patients with moderate or severe mitral regurgitation. J. Am. Coll. Cardiol. 59(23), 2068–2074 (2012).
MedlineGoogle Scholar
18. Barbanti M, Webb JG, Hahn RT 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 128(25), 2776–2784 (2013).
MedlineGoogle Scholar
19. Bedogni F, Latib A, De Marco F et al. Interplay between mitral regurgitation and transcatheter aortic valve replacement with the CoreValve Revalving System: a multicenter registry. Circulation 128(19), 2145–2153 (2013).
MedlineGoogle Scholar
20. Khawaja MZ, Wang D, Pocock S, Redwood SR, Thomas MR. The percutaneous coronary intervention prior to transcatheter aortic valve implantation (ACTIVATION) trial: study protocol for a randomized controlled trial. Trials 15, 300 (2014).
MedlineGoogle Scholar
21. O’Sullivan CJ, Stortecky S, Bütikofer A et al. Impact of mitral regurgitation on clinical outcomes of patients with low-ejection fraction, low-gradient severe aortic stenosis undergoing transcatheter aortic valve implantation. Circ. Cardiovasc Interv. 8(2), e001895 (2015).
MedlineGoogle Scholar
22. Feldt K, De Palma R, Bjursten H et al. Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement. Int. J. Cardiol. 294, 32–36 (2019). • Explains concomitant moderate/severe mitral regurgitation in TAVR patients to be associated with increased mortality at 5 years of follow-up.
MedlineGoogle Scholar
23. Miura M, Yamaji K, Shirai S et al. Clinical impact of preprocedural moderate or severe mitral regurgitation on outcomes after transcatheter aortic valve replacement. Can. J. Cardiol. 36(7), 1112–1120 (2020).
MedlineGoogle Scholar
24. Abramowitz Y, Kazuno Y, Chakravarty T et al. Concomitant mitral annular calcification and severe aortic stenosis: prevalence, characteristics and outcome following transcatheter aortic valve replacement. Eur. Heart J. 38(16), 1194–1203 (2017).
Medline CASGoogle Scholar
25. Joseph L, Bashir M, Xiang Q et al. Prevalence and outcomes of mitral stenosis in patients undergoing transcatheter aortic valve replacement: findings from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry. JACC Cardiovasc. Interv. 11(7), 693–702 (2018).
MedlineGoogle Scholar
26. Asami M, Windecker S, Praz F et al. Transcatheter aortic valve replacement in patients with concomitant mitral stenosis. Eur. Heart J. 40(17), 1342–1351 (2019).
MedlineGoogle Scholar
27. Fischer Q, Himbert D, Bernier M et al. Impact of moderate to severe mitral stenosis in patients undergoing transcatheter aortic valve replacement. Int. J. Cardiol. 286, 36–42 (2019).
MedlineGoogle Scholar
28. Al-Khadra Y, Alraies MC, Darmoch F et al. In-hospital outcomes of transcatheter aortic valve implantation in patients with mitral valve stenosis. Am. J. Cardiol. 123(9), 1510–1516 (2019).
MedlineGoogle Scholar
29. Sannino A, Potluri S, Pollock B et al. Impact of mitral stenosis on survival in patients undergoing isolated transcatheter aortic valve implantation. Am. J. Cardiol. 123(8), 1314–1320 (2019). • Explains that severe mitral stenosis (MS) is associated with a higher risk of long-term mortality than moderate MS in TAVR patients.
MedlineGoogle Scholar
30. Kato N, Padang R, Pislaru C et al. Hemodynamics and prognostic impact of concomitant mitral stenosis in patients undergoing surgical or transcatheter aortic valve replacement for aortic stenosis. Circulation 140(15), 1251–1260 (2019). • Explains how true concomitant MS was associated with increased risk of all-cause mortality in patients undergoing aortic valve replacement.
MedlineGoogle Scholar
31. Barbanti M, Binder RK, Dvir D et al. Prevalence and impact of preoperative moderate/severe tricuspid regurgitation on patients undergoing transcatheter aortic valve replacement. Catheter. Cardiovasc. Interv. 85(4), 677–684 (2015).
MedlineGoogle Scholar
32. Lindman BR, Maniar HS, Jaber WA et al. Effect of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the Placement of Aortic Transcatheter Valves II inoperable cohort. Circ. Cardiovasc. Interv. 8(4), 10.1161/CIRCINTERVENTIONS.114.002073 e002073 (2015).
Google Scholar
33. Schymik G, Lefèvre T, Bartorelli AL et al. European experience with the second-generation Edwards SAPIEN XT transcatheter heart valve in patients with severe aortic stenosis: 1-year outcomes from the SOURCE XT Registry. JACC Cardiovasc. Interv. 8(5), 657–669 (2015).
MedlineGoogle Scholar
34. Ito S, Pislaru SV, Soo WM et al. Impact of right ventricular size and function on survival following transcatheter aortic valve replacement. Int. J. Cardiol. 221, 269–274 (2016).
MedlineGoogle Scholar
35. Schwartz LA, Rozenbaum Z, Ghantous E et al. Impact of right ventricular dysfunction and tricuspid regurgitation on outcomes in patients undergoing transcatheter aortic valve replacement. J. Am. Soc. Echocardiogr. 30(1), 36–46 (2017).
MedlineGoogle Scholar
36. Cortés C, Amat-Santos IJ, Nombela-Franco L et al. Mitral regurgitation after transcatheter aortic valve replacement: prognosis, imaging predictors, and potential management. JACC Cardiovasc. Interv. 9(15), 1603–1614 (2016).
MedlineGoogle Scholar
37. Amat-Santos IJ, Castrodeza J, Nombela-Franco L et al. Tricuspid but not mitral regurgitation determines mortality after TAVI in patients with nonsevere mitral regurgitation. Rev. Esp. Cardiol. (Engl. Ed.) 71(5), 357–364 (2018).
MedlineGoogle Scholar
38. Abdelghani M, Abdel-Wahab M, Hemetsberger R et al. Fate and long-term prognostic implications of mitral regurgitation in patients undergoing transcatheter aortic valve replacement. Int. J. Cardiol. 288, 39–43 (2019).
MedlineGoogle Scholar
39. McCarthy FH, Vemulapalli S, Li Z et al. Association of tricuspid regurgitation with transcatheter aortic valve replacement outcomes: a report from the society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Ann. Thorac. Surg. 105, 1121–1128 (2018).
MedlineGoogle Scholar
40. Worku B, Valovska M-T, Elmously A et al. Predictors of persistent tricuspid regurgitation after transcatheter aortic valve replacement in patients with baseline tricuspid regurgitation. Innovations 13, 190–199 (2018).
MedlineGoogle Scholar
41. Shamekhi J, Stundl A, Al-Kassou B et al. P918 Tricuspid regurgitation in patients undergoing transcatheter aortic valve implantation. Eur. Heart J. 40(Suppl. 1), ehz747.0514 (2019).
Google Scholar
42. Stähli BE, Reinthaler M, Leistner DM, Landmesser U, Lauten A. Transcatheter aortic valve replacement and concomitant mitral regurgitation. Front. Cardiovasc. Med. 5, 74 (2018).
MedlineGoogle Scholar
43. Chakravarty T, Van Belle E, Jilaihawi H et al. Meta-analysis of the impact of mitral regurgitation on outcomes after transcatheter aortic valve implantation. Am. J. Cardiol. 115(7), 942–949 (2015).
MedlineGoogle Scholar
44. Nombela-Franco L, Eltchaninoff H, Zahn R et al. Clinical impact and evolution of mitral regurgitation following transcatheter aortic valve replacement: a meta-analysis. Heart 101(17), 1395–1405 (2015).
Medline CASGoogle Scholar
45. Sethi A, Kodumuri V, Prasad V, Chaudhary A, Coromilas J, Kassotis J. Does the presence of significant mitral regurgitation prior to transcatheter aortic valve implantation for aortic stenosis impact mortality? Meta-analysis and systematic review. Cardiology 145(7), 428–438 (2020).
MedlineGoogle Scholar
46. Stone GW, Lindenfeld J, Abraham WT et al. ranscatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 379(24), 2307–2318 (2018).
MedlineGoogle Scholar
47. Popma JJ, Deeb GM, Yakubov SJ et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N. Engl. J. Med. 380(18), 1706–1715 (2019).
MedlineGoogle Scholar
48. Mack MJ, Leon MB, Thourani VH et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N. Engl. J. Med. 380(18), 1695–1705 (2019).
MedlineGoogle Scholar
49. Takagi H, Hari Y, Kawai N, Ando T. Impact of concurrent tricuspid regurgitation on mortality after transcatheter aortic-valve implantation. Catheter. Cardiovasc. Interv. 993(5), 946–953 (2019).
Google Scholar
50. Fan J, Liu X, Yu L et al. Impact of tricuspid regurgitation and right ventricular dysfunction on outcomes after transcatheter aortic valve replacement: a systematic review and meta-analysis. Clin. Cardiol. 42(1), 206–212 (2019). •• Important prior work similar to our analysis except that it pooled unadjusted data to demonstrate similar findings with respect to concomitant tricuspid regurgitation in TAVR patients.
MedlineGoogle Scholar
51. Kammerlander AA, Marzluf BA, Graf A et al. Right ventricular dysfunction, but not tricuspid regurgitation, is associated with outcome late after left heart valve procedure. J. Am. Coll. Cardiol. 64(24), 2633–2642 (2014).
MedlineGoogle Scholar
52. Gulati A, Ismail TF, Jabbour A et al. The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy. Circulation 128(15), 1623–1633 (2013).
MedlineGoogle Scholar
53. Peltz M. Chapter 46 - Surgery for Valvular Heart Disease In: Cardiovascular Therapeutics: A Companion to Braunwald's Heart Disease (Fourth Edition). Antman EMSabatine MS (Eds). Elsevier, Philadelphia, PA, USA, 691–713 (2013).
Google Scholar
54. Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow, low gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation. 115, 2856–64 (2007).
MedlineGoogle Scholar
55. Mantovani F, Fanti D, Tafciu E et al. When aortic stenosis is not alone: epidemiology, pathophysiology, diagnosis and management in mixed and combined valvular disease. Front. Cardiovasc. Med. 8, 744497 (2021).
Medline CASGoogle Scholar
56. Worku B, Valovska MT, Elmously A et al. Predictors of Persistent Tricuspid Regurgitation After Transcatheter Aortic Valve Replacement in Patients With Baseline Tricuspid Regurgitation. Innovations (Phila). 13(3), 190–199 (2018).
MedlineGoogle Scholar
57. Dumonteil N. Transcatheter treatment of concomitant aortic stenosis and tricuspid regurgitation: are we there yet? JACC Cardiovasc. Interv. 14(20), 2257–2259 (2021). • Explains the potential and importance of transcatheter treatment of tricuspid regurgitation in TAVR patients.
MedlineGoogle Scholar
58. Haussig S, Pleissner C, Mangner N et al. Long-term follow-up after transcatheter aortic valve replacement. CJC Open 3(7), 845–853 (2021). • Explains the long-term results for high-risk patients up to 8 years following TAVR.
MedlineGoogle Scholar
59. Elmaraezy A, Ismail A, Abushouk AI et al. Efficacy and safety of transcatheter aortic valve replacement in aortic stenosis patients at low to moderate surgical risk: a comprehensive meta-analysis. BMC Cardiovasc. Disord. 17(1), 234 (2017).
MedlineGoogle Scholar
60. Coughlan JJ, Kiernan T, Mylotte D, Arnous S. Annular rupture during transcatheter aortic valve implantation: predictors, management and outcomes. Interv. Cardiol. 13(3), 140–144 (2018).
Medline CASGoogle Scholar

Vol. 18, No. 6

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Received 21 May 2021

Accepted 17 March 2022

Published online 29 April 2022

Published in print June 2022

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To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fca-2021-0061

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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