The growing number of patients undergoing transcatheter aortic valve implantation (TAVI) underscores the need for more data on managing dysfunctional percutaneous prostheses, including repeat “valve-in-valve” procedures. This study aimed to evaluate the safety and effectiveness of percutaneous valve-in-valve implants in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) national registry. The study included all consecutive patients recorded from November 9, 2011, to December 30, 2022, who underwent TAVI with balloon-expandable valves, either for dysfunctional transcatheter prostheses (redo-TAVI) or native aortic valves (native-TAVI). Procedural, echocardiographic, and clinical outcomes were compared between redo-TAVI and native-TAVI cohorts using propensity score matching.

Among 350,591 patients (1,320 redo-TAVI; 349,271 native-TAVI), 1,320 propensity-matched pairs undergoing redo-TAVI and native-TAVI were analyzed (redo-TAVI cohort: mean age 78 years, 57.7% male, average predicted 30-day mortality risk 8.1%). Procedural complication rates for redo-TAVI were low (coronary compression or obstruction: four [0.3%]; intraprocedural death: eight [0.6%]; conversion to open-heart surgery: six [0.5%]) and similar to those of native-TAVI. There was no significant difference between redo-TAVI and native-TAVI populations in 30-day mortality (4.7% vs. 4.0%, p = 0.36) or one-year mortality (17.5% vs. 19.0%, p = 0.57), nor in stroke at 30 days (2.0% vs. 1.9%, p = 0.84) or one year (3.2% vs. 3.5%, p = 0.80). Redo-TAVI effectively reduced aortic valve gradients at one year, although they remained higher in the redo-TAVI group compared to the native-TAVI group (15 mmHg vs. 12 mmHg; p < 0.0001). Rates of moderate or severe aortic insufficiency were similar between redo-TAVI and native-TAVI groups at one year (1.8% vs. 3.3%, p = 0.18). Mortality or stroke after redo-TAVI were not significantly affected by the timing of redo-TAVI (before or after one year from TAVI) nor by the type of transcatheter valve (balloon-expandable or non-balloon-expandable). Redo-TAVI with balloon-expandable valves effectively addressed previous dysfunctional percutaneous prostheses, with low rates of procedural complications and mortality and stroke rates comparable to patients with a similar clinical profile undergoing TAVI for native aortic valve stenosis.

COMMENTARY:

Before delving into the analysis of this article, it is essential to provide historical context for the world of TAVI. Over the years, clinical trials involving Edwards® Sapien® and Medtronic® CoreValve®/Evolut® prostheses with patients of progressively lower surgical risk have evolved. Today, age has become the key factor in the decision between TAVI and SAVR according to current clinical guidelines. This decision is based on five-year follow-up in high- and intermediate-risk patients, as observed in trials such as PARTNER IA, CoreValve US, PARTNER 2A, and SURTAVI. These studies have shown no significant differences in mortality, although consistently yielding slightly better results in the surgical cohort.

For low-risk surgical patients, the five-year follow-up of the PARTNER 3 study and the four-year follow-up of Evolut-Low Risk, recently published and discussed in this blog, show no significant differences in mortality or stroke (which is, incidentally, worse than data for conventional SAVR in the low-risk cohort of the STS registry). Initially, poorer performance was observed in the surgical arm in both studies, but it balanced out in PARTNER 3 starting from the fourth year. Additionally, the similarity in the incidence of endocarditis, gradients, and quality of life suggests that both procedures have comparable outcomes at 4-5 years. Although the studies do not explore deficiencies in data and poorer outcomes in the TAVI group, such as paravalvular leakage, prosthetic thrombosis, or pacemaker implantation, the key question remains: will these results persist in the long term? The durability of percutaneous prostheses in trials has been demonstrated with only five years of follow-up, an insufficient time to justify reducing age as a criterion for TAVI. The increased use of TAVI in younger patients suggests that the lifespan of the bioprosthesis may be exceeded by the patient’s life expectancy, increasing the likelihood of percutaneous valve dysfunction and, therefore, the need for reintervention.

The STS/ACC TVT registry analysis, published in The Lancet by Makkar et al., is notable for three main reasons: (1) it is the largest study to date on patients undergoing redo-TAVI with balloon-expandable valves for dysfunctional bioprostheses, (2) it confirms the safety and efficacy of TAVI reimplantation in this clinical context, and (3) it shows a mortality rate up to three times lower than surgical reintervention studies for TAVI.

Comparing redo-TAVI and native-TAVI groups yielded notably similar outcomes in critical clinical endpoints, including 30-day and one-year mortality and stroke rates. These findings are of great significance, as 30-day mortality in redo-TAVI (4.7% in this study) is consistently lower compared to mortality following surgical reintervention after TAVI, which some studies place close to 15%, as we have previously analyzed in blog articles.

Redo-TAVI accounted for only 0.4% of all TAVI cases (1,320 of the 350,591 TAVI patients in the study). This low number is unsurprising, as TAVI was initially indicated only for elderly patients with high or prohibitive surgical risk, in whom it was expected that the transcatheter valve would “outlive” the recipient.

The STS/ACC TVT registry still leaves important questions unanswered. For instance, data were not collected on the timing or mechanism of transcatheter bioprosthetic dysfunction. The etiology of bioprosthetic dysfunction can include endocarditis, thrombosis, or structural versus non-structural valve degeneration. Non-structural valve degeneration is mainly caused by paravalvular leakage (more common in TAVI) or patient-prosthesis mismatch (more common in surgically implanted bioprostheses). It could be argued that non-structural valve degeneration manifests early, requiring reintervention in the first years after the initial procedure. Structural deterioration, however, involves intrinsic degeneration of the bioprosthetic leaflets due to chronic inflammatory processes (e.g., pannus formation and degenerative calcification) or wear, thus taking more time to develop and typically occurring later, usually after five years from the initial procedure. Numerous historical publications demonstrate the long-term durability of conventional bioprostheses, often based on reoperation or mortality rates over long periods. However, the historical lack of rigorous durability studies and the recent emergence of consensus documents that define structural deterioration and bioprosthetic dysfunction with a unified terminology partly invalidate past evidence based on studies that did not employ these definitions. From this perspective, many cardiologists argue that there are no contemporary studies with mean echocardiographic follow-ups of 5-8 years that show less structural degeneration in conventional bioprostheses compared to percutaneous ones.

The study by Makkar et al. suggests that redo-TAVI may be the preferred therapeutic option in cases of transcatheter prosthesis dysfunction, provided it is technically feasible. However, it is essential to note that this analysis contains significant selection bias. Moreover, redo-TAVI was exclusively performed with balloon-expandable stents and low-profile stents, a relevant choice to ensure coronary access and avoid obstruction of coronary arteries. On the other hand, certain specific anatomical conditions, such as a high proportion of bioprostheses with paravalvular leaks, low coronary implantation, or prosthetic endocarditis, can only be adequately addressed through surgical extraction rather than redo-TAVR. This critical aspect was not considered in the STS/ACC TVT registry.

Younger and lower-risk patients often choose an aortic bioprosthesis over a mechanical valve. These patients are likely to need multiple procedures on their valve throughout their lives. At the time of the initial procedure, it is essential to design a personalized management plan that considers both initial and future strategies (whether transcatheter or surgical), adapting them to the patient’s risk and specific anatomy.

As a surgeon, and by conviction, I advocate for the SAVR-TAVI-TAVI strategy as the preferred choice to maximize the durability of the bioprosthesis in young, low-risk patients. Here are my reasons:

Starting with the implantation of a surgical bioprosthesis offers clear advantages:

• It facilitates better support for subsequent percutaneous procedures, with specially designed supports such as the Edwards® Inspiris® or the possibility of performing aortic root/ring enlargement techniques to prevent mismatch with the surgical prosthesis or future valve-in-valve implants.
• The long-term durability of surgical bioprostheses is known and reliable, while that of percutaneous ones remains uncertain.
• It has a significantly lower incidence of paravalvular leaks compared to TAVI, which has prognostic implications.
• It is associated with a lower incidence of pacemaker requirements.
• It also has a lower incidence of prosthetic thrombosis.

It makes sense for the second procedure to be a TAVI, provided that certain technical criteria are met, as suggested by the results of this study. Opting for surgical reintervention in TAVI seems to imply a greater risk of complications and mortality. In fact, if reintervention is required due to endocarditis or patient-prosthesis mismatch after repeated valve-in-valve procedures, the technical aspects and risks of explanting the surgical prosthesis (with or without a TAVI bioprosthesis inside) are more predictable than those needed for explanting a first TAVI implanted over the native aortic valve. In this “biological pathway,” reintervention at the third stage (SAVR-TAVI-SAVR) opens the possibility for an eventual fourth implant (TAVI), minimizing the risk of patient-prosthesis mismatch.

REFERENCE:
Makkar RR, Kapadia S, Chakravarty T, Cubeddu RJ, Kaneko T, et al. Outcomes of repeat transcatheter aortic valve replacement with balloon-expandable valves: a registry study. Lancet. 2023 Oct 28;402(10412):1529-1540. doi: 10.1016/S0140-6736(23)01636-7.