TAVR for Aortic Regurgitation

Dec 21, 2017   |  Anna Franzone, MD; Thomas Pilgrim

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A marked heterogeneity of patients with aortic regurgitation (AR) reflects the wide etiological spectrum of this valvulopathy, which comprises genetic, inflammatory, infective, and degenerative processes resulting in AR through structural leaflet dysfunction or aortopathy. The prevalence of AR increases with advancing age, and moderate or severe AR has been documented in 1.6% of individuals ≥65 years in a community-based study.1 Optimal timing of intervention is challenging due to insidious left ventricular remodeling, eventually resulting in eccentric hypertrophy and reduction of systolic left ventricular function. Surgical aortic valve repair or replacement is the preferred therapeutic option for patient with severe AR; however, the Euro Heart Survey on Valvular Heart Disease reported that 7.8% of patients with severe AR for whom there was an indication according to the guidelines had no intervention mainly because of advanced age and multiple comorbidities yielding an excessive risk of peri-operative mortality.2,3 Boundaries to the extension of transcatheter aortic valve replacement (TAVR) to lower-risk patients with aortic stenosis are softening, and TAVR for bicuspid aortic stenosis and TAVR for degenerated bioprosthetic valves are under rigorous investigation. Meanwhile, TAVR for pure native AR is being explored as another off-label treatment alternative to surgery. TAVR for pure native AR has been discouraged because specific anatomic features can compromise device success and procedural safety. From a technical standpoint in particular, two main factors challenge TAVR in patients with pure AR: the absence of extensive calcification of the annulus and the frequent coexistence with dilatation of the aortic root and the ascending aorta. Potential risks for transcatheter heart valves (THV) in this setting are associated with malpositioning due to inadequate sealing, valve embolization, and significant residual paravalvular regurgitation.4 In addition, oversizing of the THV in an attempt to compensate for deficient anchoring involves a risk of valve dislocation, conduction disorders, and annulus rupture. Apart from these anatomic factors, peculiar clinical characteristics may also impair clinical efficacy of TAVR in patients with severe AR. Indeed, despite being younger than subjects with severe aortic stenosis, patients with AR are usually referred for intervention when the disease is at an advanced stage, with irreversible reduction of left ventricular function and severe pulmonary hypertension.5 Despite these clinical and technical challenges, several reports proved the feasibility of the procedure in high-risk patients with favorable impact on clinical outcomes.6-14

Among first generation THV, the use of the self-expanding Medtronic CoreValve prosthesis (Medtronic; Dublin, Ireland) has been preferred over balloon-expandable devices in patients with pure native AR for the possibility to oversize the prosthesis while preserving a low risk of annular rupture through relying on its radial force to ensure anchoring even in the absence of severe calcification. Roy et al. described the results of TAVR with the CoreValve THV in one of the first series of 43 high-risk (mean Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] risk score of 10.2%) patients with pure AR. Second valve implantation was required in 19% of cases; 79% of patients had post-procedural AR grade ≤1. At 30 days, rates of stroke and all-cause mortality were 4.7% and 9.3%, respectively.6

A systematic appraisal of available evidence supported the technical feasibility of the procedure with acceptable rates of early adverse events among 237 high-risk patients (logistic EuroSCORE ranging from 15.3 ± 8% to 34.0 ± 8.4%; mean STS-PROM score ranging from 5.4% to 13.1%) from 13 reports. The primary study endpoint, all-cause mortality at 30-days, ranged from 0% up to 30% with a summary estimate rate of 7%. Self-expanding bioprostheses were used in the majority of cases (79%), and device success ranged from 74% to 100%. The occurrences of cerebrovascular events, major bleeding, and vascular complications were relatively low. The incidence of moderate or severe residual AR was 9% (ranging from 0% to 28%); 7% of patients required the implantation of a second valve.15

The JenaValve (JenaValve Technology, Inc.; Munich, Germany) features a clipping mechanism that anchors positioning feelers into the native aortic annulus. It gained Conformité Européenne approval for use in patients with isolated AR in 2013 by demonstrating safety and feasibility of implantation through a transapical approach in 31 patients included in the JUPITER (The JenaValve Evaluation of Long Term Performance and Safety in Patients with Severe Aortic Stenosis or Aortic Insufficiency) registry: procedural success was 96.7% with only 1 patient requiring conversion to open surgery because of device embolization. At discharge, no patient had moderate or severe paravalvular AR. All-cause mortality was 10% and 20% at 1- and 2-years, respectively.7,16 Overall, newer devices have the potential to demonstrate greater efficacy in patients with AR. In a multicenter cohort of 146 patients undergoing TAVR (78 with native AR and 68 with failed surgical bioprostheses with AR), device success and clinical efficacy were significantly better with newer (Evolut R [Medtronic; Dublin, Ireland], SAPIEN S3 [Edwards Lifesciences, Inc.; Irvine, CA], LOTUS Valve System [Boston Scientific; Marlborough, MA], Direct Flow [Direct Flow Medical, Inc.; Santa Rosa, CA], and JenaValve) compared with first generation (CoreValve and SAPIEN XT [Edwards Lifesciences, Inc.; Irvine, CA]) THV: 85% versus 54% and 75% versus 46%, respectively, p < 0.05. This was mainly driven by lower rates of second valve implantation (10% vs. 24%) and moderate or severe paravalvular regurgitation (3% vs. 27%).14 Nevertheless, at variance with the TAVR experience for the treatment of aortic stenosis, in this study, the rate of all-cause mortality at 30-days exceeded mortality projected by the STS-PROM risk score. In a similar multicenter observational study of 331 patients with pure severe AR (mean age of 74.4 years, mean STS-PROM score of 6.7 ± 6.7%), the use of new-generation devices (64%: Evolut R, Sapien 3, JenaValve, Lotus, Direct Flow, Acurate [Boston Scientific; Marlborough, MA], Portico [Abbott Vascular; Santa Clara, CA], and J-Valve [JC Medical, Inc.; Quezon City, Philippines]) was associated with a significantly higher device success rate compared with early-generation devices (36%: CoreValve and Sapien XT): 81.1% versus 61.3%, p < 0.001. This was mainly driven by lower rates of second valve implantation (12.7% vs. 24.4%, p = 0.007) and post-procedural AR ≥ moderate (4.2% vs. 18.8%, p < 0.001). Cumulative rates of all-cause and cardiovascular mortality at 1-year were comparable between the groups and significantly higher in patients with post-procedural AR ≥ moderate compared with those with post-procedural AR ≤ mild.17

Current evidence supports the feasibility of TAVR in selected high-risk patients with pure severe AR whose clinical characteristics and procedural features are not identical to those of patients with severe aortic stenosis. Large studies employing newer and dedicated devices will be instrumental to definitively assess the performance of TAVR in patients with native AR.

References

  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;37:3515-22.
  2. Franzone A, Pilgrim T, Stortecky S, Windecker S. Evolving Indications for Transcatheter Aortic Valve Interventions. Curr Cardiol Rep 2017;19:107.
  3. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J 2003;24:1231-43.
  4. Puri R, Chamandi C, Rodriguez-Gabella T, Rodés-Cabau J. Future of transcatheter aortic valve implantation - evolving clinical indications. Nat Rev Cardiol 2018;15:57-65.
  5. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2017;38:2739-91.
  6. Roy DA, Schaefer U, Guetta V, et al. Transcatheter aortic valve implantation for pure severe native aortic valve regurgitation. J Am Coll Cardiol 2013;61:1577-84.
  7. Seiffert M, Bader R, Kappert U, et al. Initial German experience with transapical implantation of a second-generation transcatheter heart valve for the treatment of aortic regurgitation. JACC Cardiovasc Interv 2014;7:1168-74.
  8. Schofer J, Nietlispach F, Bijuklic K, et al. Transfemoral Implantation of a Fully Repositionable and Retrievable Transcatheter Valve for Noncalcified Pure Aortic Regurgitation. JACC Cardiovasc Interv 2015;8:1842-9.
  9. Testa L, Latib A, Rossi ML, et al. CoreValve implantation for severe aortic regurgitation: a multicentre registry. EuroIntervention 2014;10:739-45.
  10. Wei L, Liu H, Zhu L, et al. A New Transcatheter Aortic Valve Replacement System for Predominant Aortic Regurgitation Implantation of the J-Valve and Early Outcome. JACC Cardiovasc Interv 2015;8:1831-41.
  11. Wendt D, Kahlert P, Pasa S, et al. Transapical transcatheter aortic valve for severe aortic regurgitation: expanding the limits. JACC Cardiovasc Interv 2014;7:1159-67.
  12. Zhu D, Chen Y, Guo Y, et al. Transapical transcatheter aortic valve implantation using a new second-generation TAVI system - J-Valve™ for high-risk patients with aortic valve diseases: Initial results with 90-day follow-up. Int J Cardiol 2015;199:155-62.
  13. Schlingloff F, Schäfer U, Frerker C, Schmoeckel M, Bader R. Transcatheter aortic valve implantation of a second-generation valve for pure aortic regurgitation: procedural outcome, haemodynamic data and follow-up. Interact Cardiovasc Thorac Surg 2014;19:388-93.
  14. Sawaya FJ, Deutsch MA, Seiffert M, et al. Safety and Efficacy of Transcatheter Aortic Valve Replacement in the Treatment of Pure Aortic Regurgitation in Native Valves and Failing Surgical Bioprostheses: Results From an International Registry Study. JACC Cardiovasc Interv 2017;10:1048-56.
  15. Franzone A, Piccolo R, Siontis GC, et al. Transcatheter Aortic Valve Replacement for the Treatment of Pure Native Aortic Valve Regurgitation: A Systematic Review. JACC Cardiovasc Interv 2016;9:2308-17.
  16. Silaschi M, Conradi L, Wendler O, et al. The JUPITER registry: One-year outcomes of transapical aortic valve implantation using a second generation transcatheter heart valve for aortic regurgitation. Catheter Cardiovasc Interv 2017;Nov 24:[Epub ahead of print].
  17. Yoon SH, Schmidt T, Bleiziffer S, et al. Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation. J Am Coll Cardiol 2017;70:2752-63.

Keywords: Transcatheter Aortic Valve Replacement, Aortic Valve Insufficiency, Heart Valve Diseases, Aortic Valve, Bioprosthesis, Ventricular Function, Left, Ventricular Remodeling, Conversion to Open Surgery, Aortic Valve Stenosis, Aorta, Hypertension, Pulmonary, Stroke, Comorbidity, Hypertrophy, Treatment Outcome


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