Transcatheter aortic valve replacement (TAVR) has been shown to improve mortality and quality of life in patients with severe aortic stenosis who are designated inoperable or high risk for surgical aortic valve replacement (SAVR).^1-5 The first implantation of a transcatheter heart valve (THV) in the aortic position was performed by Cribier et al⁶ to treat an inoperable patient with severe symptomatic aortic stenosis. From the development of the porcine model to the first clinical implantation in the aortic position, the makeup of a THV was a foldable biological cardiac valve sewn inside an expandable stent frame. This device would be crimped onto a balloon in order to deploy the THV via inflation. With this concept, the technology has emerged as one of the most transformative in the field of interventional cardiology. Given the initial focus on development of a balloon-expandable THV to facilitate TAVR, the largest experiences with TAVR are with balloon-expandable THVs. The main objectives of this chapter are to review the available devices, methods of implantation, clinical outcomes, valve hemodynamics, and durability associated with these systems.

The initial large-scale clinical experience with the balloon-expandable THV was with the Cribier-Edwards balloon-expandable aortic stent valve (Edwards Lifesciences, Irvine, CA). This consisted of a trileaflet tissue valve composed of equine pericardium mounted on a stainless steel frame.⁶

Subsequent improvements to this system led to the development of the second-generation Edwards SAPIEN THV (Edwards Lifesciences). Major differences between the first- and second-generation devices were the incorporation of pretreated bovine pericardium as the material for the valve leaflets, which had been demonstrated to decrease valve calcification, in addition to a polyethylene terephthalate skirt, which extended to a larger expanse of the stent frame, thus improving sealing and potentially reducing paravalvular regurgitation (PVR).⁷ The 2 sizes of this device, the 23- and 26-mm diameter THVs, could be inserted via 22- and 24-Fr delivery systems for transfemoral (TF) TAVR and through a 29-Fr sheath via transapical access for patients without vascular adequate for the TF approach.

The third-generation of the balloon-expandable Edwards THVs is the SAPIEN XT THV (Edwards Lifesciences). This also consists of a trileaflet pericardial bovine valve, but the leaflets have a scallop shape to improved leaflet durability and the valve is mounted on a cobalt chromium stent frame.⁷ The latter decreases the profile of the THV, given the thinner struts and fewer rows between commissures. The SAPIEN XT THV is available in 23-, 26-, and 29-mm sizes in the United States, with a 20-mm size available internationally. The sheath sizes are smaller than those of the previous generation Edwards THVs because of the lower profile characteristics, as described earlier. The NovaFlex+ delivery system replaced the original RetroFlex3 sheath used for the previous generation device (Edwards Lifesciences). Through this system, the 20- and 23-, 26-, and 29-mm SAPIEN XT can be advanced through 16-, 18-, and 20-Fr expandable TF delivery sheaths, respectively. The clinical manifestations of these reduced catheter profiles are discussed later.

The latest generation of Edwards THVs is the SAPIEN 3 THV, recently approved by the US Food and Drug Administration (FDA); it improves upon the previous generation by the addition of an outer skirt, which is used to further fill paravalvular gaps and reduce paravalvular leak.⁸ The crimped cobalt chromium stent frame shortens significantly (up to 8 mm depending on valve size used) when deployed. This foreshortening is a critical component of the sleek delivery profile. Through the latest generation TF delivery system, the Commander (Edwards Lifesciences), 20- and 23-mm and 26- and 29-mm THVs can be deployed through 14- and 16-Fr expandable sheath systems, respectively. The Commander system also has increased flex properties and a fine-tuning dial, which may facilitate less traumatic and more precise valve deployments. The SAPIEN 3 THV is currently in use internationally and has recently been approved based on data from the Placement of Aortic Transcatheter Valves (PARTNER) II Trial, as described later.

After the first 4 TAVR cases, Cribier and colleagues petitioned the French government to start a feasibility trial, which was restricted to compassionate use.⁹ The first study was the Initial Registry of Endovascular Implantation of Valves in Europe (I-REVIVE) trial, which involved 7 patients receiving antegrade or retrograde approach for implantation.¹⁰ Twenty additional patients were recruited into the Registry of Endovascular Critical Aortic Stenosis Treatment (RECAST) trial, involving only antegrade access.¹¹ There was an 80% procedural success rate in these initial small studies, and although many of these critically ill patients died of their comorbidities, some survived years, and all had no prosthesis dysfunction. Future feasibility analyses supported the use of TAVR in at least inoperable patients, with demonstrated survival extending well beyond that of patients without TAVR.

The PARTNER trial was the world’s first prospective randomized TAVR trial and analyzed inoperable patients (cohort B), who had an estimated mortality or major morbidity from SAVR of >50%. This trial demonstrated that TF TAVR is superior compared to standard medical therapy and resulted in a 20% absolute reduction in mortality at 12 months.¹ This trial also included a high-risk operable arm (cohort A) that included patients with estimated mortality from SAVR of at least 15%.⁵ The results from this analysis showed that transapical (TA) and TF TAVR have similar 1-year survival compared to SAVR. As a result of these impressive results, the FDA approved TF TAVR using the Edwards SAPIEN THV in November 2011 for treatment of aortic stenosis in inoperable patients. In 2012, this approval was extended for the TF and TA access routes to high-risk patients who are eligible for surgery but face high risk of serious complications or death.

Long-term data for balloon-expandable THVs are currently limited and will become available with further follow-up of existing trials and registries. Toggweiler et al¹² published the first 5-year outcome data, following 88 patients who received the second-generation Edwards SAPIEN THV. Survival rates at 1, 2, 3, 4, and 5 years were 83%, 74%, 53%, 42%, and 35%, respectively. Interpretation of mortality per year is limited by the small patient numbers and also from the learning curve given the early experience of the center. However, no patient developed severe transvalvular regurgitation or prosthetic stenosis. Recently presented data for PARTNER I cohort B showed 5-year mortality of 93.6% in the standard therapy arm versus 71.8% in the TF TAVR arm (P < .01). Longer term follow-up of the surgical arm (cohort A) demonstrated equivalent survival between TAVR and SAVR at 5 years with high mortalities in both arms (~70%).¹³ Importantly, valve durability was demonstrated with no increase in transvalvular gradient or significant attrition of valve area during the 5-year follow-up of both arms.^13,14

The second randomized PARTNER trial (PARTNER II) has also completed recruitment. Cohort B of this trial was designed to investigate the performance and outcomes with the third-generation SAPIEN XT THV and the NovaFlex+ delivery catheter in patients deemed inoperable. In comparison to the Edwards SAPIEN THV, the SAPIEN XT demonstrated similar survival at 30 days but lower rates of important complications including bleeding and vascular complications. The surgical arm of the trial (cohort A) was designed to investigate outcomes related to TAVR versus SAVR in patients at intermediate surgical risk. Enrollment has been completed in this arm, and results will be forthcoming in 2016.

The PARTNER II trial also incorporated the use of the latest generation SAPIEN 3 THV in an attached registry of high-risk and intermediate-risk patients, completed in 2014. The results of the SAPIEN 3 registry showed excellent early results. All-cause and cardiovascular mortality rates at 30 days were 2.2% and 1.4% for the high-risk/inoperable registry and only 1.1% and 0.9% for the intermediate-risk registry, respectively. The frequencies of stroke and disabling stroke were 1.5% and 0.9% for the high-risk/inoperable registry and 2.6% and 1.0% for the intermediate-risk registry, respectively. Finally, rates of moderate or severe PVR were 2.9% and 4.2% in the high-risk/inoperable and intermediate-risk registries, respectively.¹⁵ These outcomes will markedly influence TAVR indications as well as the landscape of available balloon-expandable THV technologies.

Hallmarks of planning prior to performing TAVR with a balloon-expandable THV include assessments of the aortic valve annulus and vascular access. Multimodality imaging is essential for patient screening and procedural guidance during TAVR and has been incorporated into consensus statements, reviews, and guidelines.^16,17 Correct valve sizing for a balloon-expandable THV requires meticulous attention to 3-dimensional imaging, including multislice computed tomography (CT) and transesophageal echocardiography (TEE). A multislice CT is also a gold standard assessment in determining the adequacy of peripheral access, in addition to evaluating anatomy relevant to the alternative access options discussed in the following section. Optimal TAVR implantation requires: (1) determining anatomic features that would preclude or make advantageous the use of a particular access route; (2) valve sizing based on established criteria for measuring the annulus dimensions matched to the specific valve type; and (3) accurate valve positioning (axial height and alignment) within the annular valve plane. The challenge of valve sizing and positioning cannot be underestimated and requires an intimate understanding of the anatomy of the aortic valvar complex. Correct sizing and placement of transcatheter aortic valves will result in excellent valve hemodynamics, no or trace PVR, low requirements for new pacemakers due to conduction abnormalities, and no evidence of coronary obstruction or annulus injury.

The first TAVR with a balloon-expandable THV was performed via an antegrade approach through the femoral vein, incorporating a transseptal puncture through which the THV crossed the mitral valve and led to final positioning in the aortic valve annulus.⁶ Because of the difficulty and complexity inherent in these approaches, the contemporary TF and TA approaches were developed after improvements in valve design and delivery systems as mentioned earlier.

Factors that may determine preferred TAVR vascular access include peripheral arterial disease (inadequate vessel diameter, severe calcification, or extreme tortuosity of the iliofemoral vessels), the presence of extensive calcification of the ascending aorta (ie, porcelain aorta), hostile chest wall anatomy (due to either orthovoltage radiation exposure or chest wall deformities), previous coronary bypass graft surgery with mammary conduits adherent to the chest wall, and severe lung disease. The 4 most common techniques for TAVR access with the balloon-expandable THV are the retrograde TF, antegrade TA, and the more recently developed direct or transaortic (TAo) approach. In the PARTNER trial, using the larger profile SAPIEN RetroFlex3 introducer sheath (outer sheath diameter of 9.2 mm for the 26-mm valve), there were frequent major vascular complications associated with TF TAVR procedures.¹ In the PARTNER II trial, the previous-generation SAPIEN system was compared to the lower profile SAPIEN XT system and its NovaFlex+ introducer sheath (33% lower cross-sectional area), and major vascular complications were reduced from 15.5% to 9.6% (P = .04).¹⁸ This highlights the importance of lower profile delivery systems in maximally using safe fully percutaneous TF TAVR as a primary default access strategy. The SAPIEN XT system was approved by the FDA in 2014 for commercial use in high-risk and inoperable patients and uses the NovaFlex+ introducer sheath replacing the larger profile SAPIEN RetroFlex3 introducer sheath.

The TA approach has also become lower profile with the SAPIEN 3 THV, which uses the Certitude delivery system (Edwards Lifesciences), an 18-Fr system. This is much lower in profile than the previous generation Edwards SAPIEN and SAPIEN XT systems, requiring at least 24-Fr, and therefore potentially reduces the occurrence of bleeding due to myocardial tears and the incidence of myocardial injury.¹⁹ The TA approach avoids peripheral access issues, but also has limitations, including increased length of hospitalization and increased risk of 30-day and 1-year all-cause mortality.^20,21 These adverse TA outcomes may have been influenced by differences in underlying baseline comorbidities between the 2 populations, given the “TF first” approach often adopted by clinicians, which relegated only patients with significant peripheral vascular disease to TA TAVR. Recently, a propensity matched analysis from the PARTNER I trial comparing TF and TA approaches demonstrated higher 30-day mortality and increased length of stay with the TA approach.²² Other adverse outcomes associated with the TA approach include a higher likelihood of periprocedural bleeding, increased risk of hemodynamic instability, and greater patient discomfort, due to pain related to the anterolateral thoracotomy.^23,24 In an analysis of PARTNER cohort A health-related quality of life (HRQoL) outcomes, Reynolds et al⁴ showed short-term differences in favor of TF TAVR when compared to SAVR. However, in patients deemed unsuitable for a TF approach and thus meriting TA TAVR, HRQoL was not significantly different from that of SAVR across all studied follow-up time points. This was further validated in an analysis of the PARTNER TA TAVR nonrandomized continued access registry.²⁵

The TAo access site for balloon-expandable TAVR has been introduced more recently. In the largest series of TAo cases,²⁶ when compared with a contemporary group of TA patients, there was a lower combined bleeding and vascular event rate (27% vs 46%; P = .05), shorter median intensive care unit length of stay (3 vs 6 days; P = .01), and a favorable learning curve. Transcarotid access and antegrade transseptal access via the femoral vein have also been described,^27,28 but like TAo, these approaches have not been studied in a randomized controlled trial. Access alternatives present themselves as individual to each patient, taking into account several variables such as caliber, atherosclerotic disease, and calcification of the vasculature, in addition to various patient comorbidities. While the TF approach is currently preferred, there remains a somewhat undefined niche for each access method, given the lack of data comparing TAVR access alternatives.

Balloon aortic valvuloplasty (BAV) has traditionally been performed before balloon-expandable THV deployment. This provides better transition of the valve through the annulus and potentially avoids mechanical complications related to the force and contour of the delivery system. However, BAV carries independent risks of atrioventricular block requiring permanent pacemaker (PPM), aortic insufficiency, and cerebrovascular accident (CVA). Garcia et al²⁹ more recently studied forgoing pre-TAVR BAV with the SAPIEN XT THV. In this small study, 10 patients with moderate calcification, homogenous distribution of calcium, symmetric opening of the valve, and some degree of aortic insufficiency as defined by TEE underwent SAPIEN XT valve placement without antecedent BAV. No patients were found to merit need for postdilation, and PVR was classified as none or trivial in all patients.²⁹ TAVR without predilation thus appears to be a feasible technique with potential benefits but has not yet been investigated comprehensively.

Undersizing of the valve, which may be unavoidable given limited size availability of current platforms, or valve underexpansion can result in PVR or device migration. The impetus to avoid PVR after valve deployment needs to be balanced with the risk of annular rupture with postdilation. Barbanti et al³⁰ studied 31 patients receiving balloon-expandable valves who experienced rupture and compared them to a group of matched controls to define predictors of rupture. These included subannular/left ventricular outflow tract calcification, annular area oversizing ≥20%, and balloon postdilation. Figure 43-1, adapted from Barbanti et al,³⁰ shows case examples of 2 patients demonstrating the interplay of these variables on clinical outcome. As a potential modification, a routine strategy of initial underexpansion of the valve and subsequent postdilation when deemed necessary showed potential in reducing the risk of annular injury and PVR in selected patients.³¹