Access options for transcatheter mitral valve implantation in patients with prior surgical bioprosthesis

Introduction

Structural valve deterioration (SVD) is reported in up to 30% of patients who underwent surgical mitral valve replacement (MVR) with a bioprosthesis at 10–15 years after the index procedure (1,2). Historically, the only treatment option for SVD has been surgical redo MVR, however this procedure is associated with moderately high mortality and prohibitive in some, including the elderly and patients with multiple comorbidities (3,4). For this reason, based on the encouraging outcomes of transcatheter aortic valve replacement (TAVR), transcatheter mitral valve-in-valve implantation (TMVIV) has become a valuable alternative in particularly high-risk patients (5-9). Back in 2007, Walther et al. described their preclinical experience with TMVIV with a transatrial approach (10). Shortly thereafter our group performed the first in human TMVIV transapically (11) and more recently via a percutaneous fashion transfemorally and trans-septally (12,13). In the last few years, the transfemoral (TF) approach has gained more and more relevance, with operator familiarity and advance in technology that allowed the development of smaller and highly steerable delivery systems (12). Other approaches have been proposed, as direct left transatrial and transjugular puncture, however these options were abandoned because of their invasiveness or complexity in favour of more reliable and safer accesses. Indeed, the transapical (TA) and trans-septal (TS) accesses are well known to cardiac surgeons and interventional cardiologists since they were widely used to perform TAVR and transcatheter mitral valve (MV) interventions (Table 1). The aim of the present article is to discuss the available accesses to perform TMVIV and to report our fourteen-year institutional experience.

Methods

Population and patient selection

We retrospectively collected clinical and procedural data of all patients who underwent MIVIV in our institution between July 1^st, 2007 and July 31^st, 2020. Periprocedural and 30-day clinical outcomes were assessed. Patients were considered for MVIV in case of bioprosthesis dysfunction resulting in symptomatic prosthetic stenosis, regurgitation or mixed pathology when conventional redo surgery was deemed too high-risk. Feasibility and candidacy were confirmed by the Heart Team after careful review of clinical data, transthoracic (TTE) and transesophageal (TEE) echocardiography, coronary angiography and gated MV computed tomography (CT). Patients with significant mitral paravalvular leak (PVL), active endocarditis or needing other cardiac procedures were turned down. Cardiac CT provides valuable information, including prosthesis dimensions and predicting the risk of left ventricular outflow tract (LVOT) obstruction. The risk of LVOT obstruction was assessed preoperatively by mean of virtual valve implant of the desired device using dedicated software and measuring the residual neo-LVOT (Circle cvi42, Circle Cardiovascular Imaging Inc., Calgary, AB, Canada) (14,15). TA MVIV through mini left anterolateral thoracotomy was the only approach until 2016, when TF access with transseptal puncture became the preferred access approach. Exclusion criteria for the TF transseptal approach were previous atrial septal defect (ASD) closure, previous MVR via transseptal incision and the presence of thrombus in the left atrium (LA) and inferior vena cava (IVC) interruption.

Different transcatheter prosthesis types have been used by different groups, however, the most commonly used are the balloon-expandable Edwards valves (Edwards LifeSciences Corp., Irvine, CA, USA) followed by the self-expandable devices as Lotus (Boston Scientific, Natick, MA, USA) and Direct Flow (Direct Flow Medical Inc., Santa Rosa, CA, USA). Cribier-Edwards prostheses were used in our initial experience, and shortly after Sapien and Sapien XT, and since 2017 Sapien 3 were used exclusively with respectively the Ascendra and Certitude delivery sheaths for TS and TA accesses respectively. Prosthesis sizes ranges between 20 and 29 mm for the Sapien XT and for the Sapien 3 valve. The Certitude introducer sheath has an 18-Fr size for the 20–26 mm delivery systems and a 20-Fr size for the 29 mm system. The Ascendra introducer sheath (eSheath) is smaller, sizing 14 Fr for the 20–26 mm valves and 16 Fr for the 29 mm valves and with a special hydrophilic coating easing the insertion and advancement through the femoral system.

Procedures

Direct transatrial and transjugular access have been described before. In our center, transatrial approach was attempted once in our first in-human case in 2007, but ultimately abandoned and converted to apical access (11). Briefly, transatrial MVIV is performed through a small right anterior thoracotomy in the 4^th intercostal space, the pericardium is opened and the LA surgically exposed. Two hemostatic purse strings sutures are placed. Heparin is administered to achieve an activated clotting time (ACT) >300 seconds. The LA is punctured within the purse-strings using the classic Seldinger technique. A 6-Fr sheath is placed inside the LA and then a soft J-guidewire is advanced in the LV crossing the mitral prosthesis in an antegrade fashion. The J-guidewire is then replaced by a Safari wire (Boston Scientific, Marlborough, Massachusetts, USA) over a 6-Fr pigtail catheter and the transcatheter heart valve (THV) delivery system is then advanced over it and crossing the failed prosthesis. The THV is then deployed under rapid pacing with fluoroscopic and TEE guidance. Post implant valve performance and position is evaluated TEE.

TA MVIV was used exclusively until 2015 since our operators had extensive experience with TA TAVR. All the procedures were performed in the hybrid operating room with stand-by cardiopulmonary bypass machine. All patients were performed under general anesthesia. LV apex is approached through a mini left anterolateral thoracotomy usually in the 5^th–6^th intercostal space. The proper incision site is confirmed using fluoroscopy and TTE. Once the apex is exposed, the operator confirms the puncture site to achieve the best possible alignment to the MV with TEE. Two U-shaped perpendicular purse-strings are placed and after systemic heparinization, the apex is punctured, a short soft J-guidewire is inserted in the LV crossing the mitral prosthesis and followed by a 6-Fr sheath. A 0.035’’ Amplatz Extra Stiff wire (Cook Medical, Bloomington, Indiana) was exchanged by Seldinger technique, followed by the introduction of the delivery sheath. The THV is positioned 1–5 mm atrially relative to the sewing cuff of the failed valve and deployed under rapid pacing with fluoroscopic and TEE guidance. No contrast is used during the procedure. Proper positioning, transvalvular gradient and the presence of paravalvular leakage are checked with TEE. In rare occasions, post-deployment balloon dilatation was performed in cases of incomplete deployment and presence of significant PVL despite optimal positioning (Video 1).

TF/TS TMVIV is performed in the same manner as the TA procedure other than the access. In this case, a temporary pacemaker is first placed into the right ventricle with a 7-Fr femoral venous access and the MV is approached puncturing the contralateral femoral vein and placing a 7-Fr short sheath via Seldinger technique. The 7-Fr sheath is then exchanged for a Baylis Medical system (Baylis Medical, Burlington, MA, USA) over a Baylis guidewire and advanced up to the superior vena cava under fluoroscopy. The Baylis wire is then retracted inside the sheath and redirected toward the interatrial septum at the level of the fossa ovalis and ideally positioned superior and posteriorly. The transeptal puncture is then performed using radiofrequency to allow the introduction of the wire into the LA under fluoroscopic and transesophageal echography guidance. The patient is then fully heparinized to reach an ACT of greater than 300 seconds. The Baylis system is then steered toward the MV and subsequently crossing of the MV with a 6-Fr pigtail over a soft J-guidewire. The J-guidewire is then exchanged with a Safari wire (Boston Scientific Corp., Marlborough, MA, USA) and positioned over the LV apex. The Edwards eSheath is then introduced and a 12- or 14-mm balloon septostomy was performed. The Edwards Commander delivery system is advanced into the right atrium, the balloon is loaded and alignment is performed in the IVC. The THV is then advanced toward the MV and the SAPIEN 3 prosthesis is positioned. The flex catheter is retracted and the final positioning of the THV is made and deployed under rapid ventricular pacing. The iatrogenic ASD is closed with a percutaneous closure device only in case of a significant residual shunt, pre-existing pulmonary hypertension and right ventricle dysfunction (Video 2).

Statistical analysis

Continuous variables were summarized using mean ± standard deviation (SD) or median with interquartile range (IQR) and compared between the type of access (TS vs. TA) with the use of the Student’s t-test or Wilcoxon rank sum test. Categorical variables were summarized using frequencies and percentages and compared between access type with the use of the Fisher exact test or Chi-square test. All tests were two-sided, and a P value <0.05 was considered statistically significant. All statistical analyses were performed using SPSS software, version 20 (IBM Corp., Armonk, New York, USA).

Results

From July 2007 to July 2020, 82 TMVIV were performed in our institution, of those 42 (51.2%) were male. Sixty (73.2%) patients had their procedure done through the apical access while 22 patients (26.8%) were treated with TF/TS approach. Mean age was 77.3±9.0, mean STS Risk Score and EuroSCORE II for reoperative MVR were 11.4±6.2 and 11.5±6.5 respectively. Complete baseline features were reported in Table 2.

Median time between the surgical MVR and TMVIV was 9.3 years (IQR, 7.9–12.0 years). There were no significant differences in terms of baseline characteristics between TA and TF groups. Our early experience was exclusively TA and since 2017, 65% of the procedures were performed in a TF fashion. In 46 patients (56.1%), a SAPIEN XT THV was used while SAPIEN3 THV was implanted in 24 (29.3%) patients. Prior to 2011, SAPIEN prostheses were implanted in 11 (13.4%) patients and the very first (1.2%) patient received a Cribier-Edwards valve. Nine (11.0%) patients had concomitant TMVIV and TAVR. Technical success was achieved in 80 patients (97.6%) and there were two (2.4%) periprocedural death (within 72 hours from the procedure) secondary to massive stroke and the other to severe LVOT obstruction requiring conversion to sternotomy. We observed two other cases of LVOT obstruction but both were partial with no significant hemodynamical consequence. Complete periprocedural data were listed in Table 3. There were no significant differences in perioperative complications and clinical outcomes between TA and TS patients. Median length of stay (LOS) was six days (IQR, 4–12 days) with shorter hospitalization time for TS patients. (1.5 vs. 7.0 days, P=0.001). At 30 days there was one additional death with heart failure requiring new hospitalization and resulting multiorgan failure. We observed four (4.9%) repeat hospitalization and two patients (2.4%) developed THV thrombosis. SVD was observed in three patients (3.7%), in two cases caused by THV thrombosis and one by valve endocarditis. One patient (1.2%) required redo surgery at two months for late valve migration with significant PVL and successfully underwent a repeat TA TMVIV. Even though complications were observed more frequently in the TA group, they were not statistically significant (Table 4). At 30-day echocardiographic follow-up (FU), mean transmitral valve gradient was 7.3±2.7 mmHg and one patient (1.2%) had mitral regurgitation greater than mild.

Discussion

TAVR performed through the TA and the TF access are well established procedures to treat severe aortic stenosis in all surgical risk classes with satisfying early and mid-term outcomes (16,17). Following this encouraging results and experience acquired from TA access, transcatheter replacement of degenerated bioprosthetic valves has been developed, first performed for the aortic position (18,19) and shortly after for the MV (5,8). Preclinical TMVIV was first described by Walther et al. (10) through a direct LA puncture to avoid the retrograde access to the mitral prosthesis and the potential interference of the subvalvular apparatus. However, this route was quickly abandoned in favour of the more direct TA access (6,7,11). Moreover, surgeons were already familiar with the LV access favoured by years of experience with TAVR and TAVIV. In our population, TA was the preferred access (67.2% vs. 32.8%). After 2016, TS access became the predominate access route with nearly 70% of cases. This evolution is probably related to the increasing knowledge and skills of operators in managing the femoral and transseptal access as the result of the experience acquired with transcatheter MV repair with MitraClip device. In addition, the improvement in THV delivery system that are lower profile reduces the size of the iatrogenic ASD and fully steerable sheath, allowing the operator to achieve a better coaxiality and alignment with the MV plane. Similar findings were described by Whisenant et al. (20) from the VIVID Registry who evaluated a large population of patients who underwent TMVIV between 2015 and 2019 and found the number of TS cases surpasses TA ones after 2016. Whisenant and investigators reported higher incidence of access complications, bleeding, conversion to open surgery and 30-day and one-year mortality observed in TA patients (21-23). On the other hand, access site and other complications are mainly operator-dependent and can be safely managed by increased experience. Suri et al. showed that the learning curve for TA procedures is around 30–45 procedures resulting in improvement in outcomes (24); Tabata et al. showed that after performing at least 40 procedures, surgeons in his institution had optimal results with no open surgery conversion, major apical bleeding, permanent pace-maker (PPM) implantation and no intraoperative and 30-day mortality (25). In our 10-year experience we report a 97% technical success, 3% intraoperative mortality and a 4.5% 30-day mortality with no difference between TS and TA patients. Our technical success rate is similar to that previously reported in literature, however, our periprocedural and 30-day mortality is lower (8,9). We believe that our better results can be explained by our long experience with THV with first TAVR procedures started in 2005 (26). Similarly, perioperative complications were low and comparable between the two groups. The incidence of new hospitalization was low at 6%, and the majority was valve-related following THV thrombosis or endocarditis.

Most of the patients had significant symptomatic improvement with New York Heart Association (NYHA) class I–II at FU with no difference between TA and TS patients. Patients in the TS had a significantly shorter LOS in respect to TA patients and is consistent with previously reported results (9,12,13).

Concerns have risen about the impact of apical puncture on LV function in particular in patients with reduced LV ejection fraction (LVEF). Some studies reported a higher LVEF improvement after TS TMVR respect to TA TMVR (27). However, D’Onofrio et al. showed that TA TAVR is associated with good outcomes as TF TAVR in patients with LVEF <35% with similar postoperative LVEF improvement in the two groups (28,29). Optimal alignment with the MV plane and therefore more precise THV deployment is better achieved through the apical access since the LV apex is closer to the MV and the THV deployment sheath is inserted coaxially to the valve plane without the need of steering. This might be related to a lower incidence of valve malposition and LVOT obstruction since the proximity allows the operator to fine tune the position and deployment. In particular, in case of increased risk of LVOT obstruction a slightly more atrial deployment of the valve might be helpful. However, gated MV cardiac CT remains as a mainstay in pre-procedural planning in order to minimize the risk of this potentially deathly complication. In our series the incidence of LVOT obstruction was low, 4.5% and only haemodynamically significant in 3% of cases. Our findings are consistent with those reported in literature where the incidence of significant LVOF obstruction causing hemodynamic impairment is reported between 2.2% to 6.9% (8,12,30) and lower than those reported for Valve-in-Ring and Valve-in-MAC procedures (5,8,13). Unfortunately, we did not observe any difference between TA and TS cases in support of our hypothesis and in literature the incidence of THV embolization or LVOT obstruction after TMVIV is similar between these two groups (31).

Conclusions

In conclusion, our fourteen-year institutional experience with TMVIV confirms the safety and effectiveness of the procedure, and should be offered as an alternative to redo surgery in high-risk or inoperable patients. Percutaneous TS access has consistently demonstrated excellent periprocedural and clinical results since the introduction of smaller and fully steerable THV systems as showed by our case series. Nevertheless, the superior control on valve alignment and deployment provided by TA access should be carefully considered when approaching patients with complex anatomy, high risk of LVOT or those requiring combined TMVIV and TAVR.

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: Dr. Webb is consultant for Edwards Lifesciences. The other authors have no conflicts of interest to declare.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Bourguignon T, Bouquiaux-Stablo AL, Loardi C, et al. Very late outcomes for mitral valve replacement with the Carpentier-Edwards pericardial bioprosthesis: 25-year follow-up of 450 implantations. J Thorac Cardiovasc Surg 2014;148:2004-2011.e1. [Crossref] [PubMed]
2. Vohra HA, Whistance RN, Roubelakis A, et al. Outcome after redo-mitral valve replacement in adult patients: a 10-year single-centre experience. Interact Cardiovasc Thorac Surg 2012;14:575-9. [Crossref] [PubMed]
3. Mehaffey HJ, Hawkins RB, Schubert S, et al. Contemporary outcomes in reoperative mitral valve surgery. Heart 2018;104:652-6. [Crossref] [PubMed]
4. Maganti M, Rao V, Armstrong S, et al. Redo valvular surgery in elderly patients. Ann Thorac Surg 2009;87:521-5. [Crossref] [PubMed]
5. Simonato M, Whisenant B, Ribeiro HB, et al. Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry. Circulation 2021;143:104-16. [Crossref] [PubMed]
6. Cheung A, Webb JG, Barbanti M, et al. 5-year experience with transcatheter transapical mitral valve-in-valve implantation for bioprosthetic valve dysfunction. J Am Coll Cardiol 2013;61:1759-66. [Crossref] [PubMed]
7. Ye J, Cheung A, Yamashita M, et al. Transcatheter Aortic and Mitral Valve-in-Valve Implantation for Failed Surgical Bioprosthetic Valves: An 8-Year Single-Center Experience. JACC Cardiovasc Interv 2015;8:1735-44. [Crossref] [PubMed]
8. Yoon SH, Whisenant BK, Bleiziffer S, et al. Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification. Eur Heart J 2019;40:441-51. [Crossref] [PubMed]
9. Sengupta A, Yazdchi F, Alexis SL, et al. Reoperative Mitral Surgery Versus Transcatheter Mitral Valve Replacement: A Systematic Review. J Am Heart Assoc 2021;10:e019854 [Crossref] [PubMed]
10. Walther T, Falk V, Dewey T, et al. Valve-in-a-valve concept for transcatheter minimally invasive repeat xenograft implantation. J Am Coll Cardiol 2007;50:56-60. [Crossref] [PubMed]
11. Cheung A, Webb JG, Wong DR, et al. Transapical transcatheter mitral valve-in-valve implantation in a human. Ann Thorac Surg 2009;87:e18-20. [Crossref] [PubMed]
12. Guerrero M, Pursnani A, Narang A, et al. Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes. JACC Cardiovasc Interv 2021;14:859-72. [Crossref] [PubMed]
13. Eleid MF, Cabalka AK, Williams MR, et al. Percutaneous Transvenous Transseptal Transcatheter Valve Implantation in Failed Bioprosthetic Mitral Valves, Ring Annuloplasty, and Severe Mitral Annular Calcification. JACC Cardiovasc Interv 2016;9:1161-74. [Crossref] [PubMed]
14. Blanke P, Naoum C, Dvir D, et al. Predicting LVOT Obstruction in Transcatheter Mitral Valve Implantation: Concept of the Neo-LVOT. JACC Cardiovasc Imaging 2017;10:482-5. [Crossref] [PubMed]
15. Reid A, Ben Zekry S, Turaga M, et al. Neo-LVOT and Transcatheter Mitral Valve Replacement: Expert Recommendations. JACC Cardiovasc Imaging 2021;14:854-66. [Crossref] [PubMed]
16. 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 2019;380:1706-15. [Crossref] [PubMed]
17. 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 2019;380:1695-705. [Crossref] [PubMed]
18. Dvir D, Webb JG, Bleiziffer S, et al. Transcatheter aortic valve implantation in failed bioprosthetic surgical valves. JAMA 2014;312:162-70. [Crossref] [PubMed]
19. Gurvitch R, Cheung A, Ye J, et al. Transcatheter valve-in-valve implantation for failed surgical bioprosthetic valves. J Am Coll Cardiol 2011;58:2196-209. [Crossref] [PubMed]
20. Whisenant B, Kapadia SR, Eleid MF, et al. One-Year Outcomes of Mitral Valve-in-Valve Using the SAPIEN 3 Transcatheter Heart Valve. JAMA Cardiol 2020;5:1245-52. [Crossref] [PubMed]
21. Gada H, Kirtane AJ, Wang K, et al. Temporal Trends in Quality of Life Outcomes After Transapical Transcatheter Aortic Valve Replacement: A Placement of AoRTic TraNscathetER Valve (PARTNER) Trial Substudy. Circ Cardiovasc Qual Outcomes 2015;8:338-46. [Crossref] [PubMed]
22. Blackstone EH, Suri RM, Rajeswaran J, et al. Propensity-matched comparisons of clinical outcomes after transapical or transfemoral transcatheter aortic valve replacement: a placement of aortic transcatheter valves (PARTNER)-I trial substudy. Circulation 2015;131:1989-2000. [Crossref] [PubMed]
23. Biancari F, Rosato S, D'Errigo P, et al. Immediate and Intermediate Outcome After Transapical Versus Transfemoral Transcatheter Aortic Valve Replacement. Am J Cardiol 2016;117:245-51. [Crossref] [PubMed]
24. Suri RM, Minha S, Alli O, et al. Learning curves for transapical transcatheter aortic valve replacement in the PARTNER-I trial: Technical performance, success, and safety. J Thorac Cardiovasc Surg 2016;152:773-780.e14. [Crossref] [PubMed]
25. Tabata M. Transapical approach in transcatheter cardiovascular interventions. Gen Thorac Cardiovasc Surg 2018;66:185-91. [Crossref] [PubMed]
26. Higgins J, Ye J, Toggweiler S, et al. Transapical aortic valve implantation: The Vancouver experience. Ann Cardiothorac Surg 2012;1:138-44. [PubMed]
27. Elmariah S, Fearon WF, Inglessis I, et al. Transapical Transcatheter Aortic Valve Replacement Is Associated With Increased Cardiac Mortality in Patients With Left Ventricular Dysfunction: Insights From the PARTNER I Trial. JACC Cardiovasc Interv 2017;10:2414-22. [Crossref] [PubMed]
28. D'Onofrio A, Besola L, Rizzoli G, et al. Impact of Changes in Left Ventricular Ejection Fraction on Survival After Transapical Aortic Valve Implantation. Ann Thorac Surg 2017;103:559-66. [Crossref] [PubMed]
29. D'Onofrio A, Salizzoni S, Filippini C, et al. Transapical aortic valve replacement is a safe option in patients with poor left ventricular ejection fraction: results from the Italian Transcatheter Balloon-Expandable Registry (ITER). Eur J Cardiothorac Surg 2017;52:874-80. [Crossref] [PubMed]
30. Yoon SH, Whisenant BK, Bleiziffer S, et al. Transcatheter Mitral Valve Replacement for Degenerated Bioprosthetic Valves and Failed Annuloplasty Rings. J Am Coll Cardiol 2017;70:1121-31. [Crossref] [PubMed]
31. Regueiro A, Granada JF, Dagenais F, et al. Transcatheter Mitral Valve Replacement: Insights From Early Clinical Experience and Future Challenges. J Am Coll Cardiol 2017;69:2175-92. [Crossref] [PubMed]