The history of percutaneous treatment of aortic valve disease began with the work of Danish researcher, H.R. Andersen, who in the late 1980s experimented in an animal lab with a balloon-expandable stented valve.¹ The technology was later acquired by PVT Company, further developed, and later sold to Edwards. Additional early work was done by Alain Cribier^2,3 and subsequently the valve was adopted in the United States and further modified. The initial approach taken by Cribier was to insert the valve via the femoral vein, then snaking the catheter through the mitral valve and into the aortic annulus via transeptal puncture. This turned out to be a fairly cumbersome and difficult procedure with a fairly high mortality rate and an 8.1% stroke rate. At the same time, animal experiments were carried out by Michael Mack, Todd Dewey, and Lars Svensson,^4,5 using the transapical (TA) approach to insert the aortic valve. Concurrently, John Webb et al^6,7 were also developing a TA aortic valve method, and subsequently they introduced the retrograde transfemoral (TF) artery approach. This latter technique became feasible once Edwards developed a catheter that could be flexed to get around the aortic arch to access the aortic valve. At the same time the Edwards balloon-expandable valve was being developed, Medtronic introduced a nitinol-based, self-expanding percutaneous valve system, the CoreValve. Following feasibility studies,^5,8 the safety and effectiveness of both valves were established through the Placement of Aortic Transcatheter Valves (PARTNER) trial and the US CoreValve pivotal trial and both valves are currently approved by US Food and Drug Administration (FDA) for use in patients who are at extreme or high risk (owing to comorbidities or anatomical considerations) for conventional surgery in the United States.^9-11

At present in the United States, there are only two transcatheter valves approved for use in patients who are at extreme or high risk (owing to comorbidities or anatomical considerations) for conventional surgery.

The balloon-expandable Edwards valves consist of bovine pericardium fashioned into a trileaflet valve within a short cylindrical stent, available in sizes 23, 26, and 29 to treat annular sizes from 18 to 27 mm. There are three generations of SAPIEN valves (SAPIEN, SAPIEN XT, and SAPIEN 3) that differ by stent material and construction (Fig. 33-1) as well delivery device size (Table 33-1) and other delivery device characteristics. At the time of publication, the commercially available generation is the SAPIEN XT in the United States with the SAPIEN 3 commercially available only in Europe. However, this generation is almost certain to replace the SAPIEN XT in the United States in the coming years. The SAPIEN valves can be delivered via retrograde (eg, TF, transaortic, transcarotid, transaxillary/subclavian) and antegrade (TA) approaches. The self-expanding Medtronic CoreValve is constructed of porcine pericardium mounted in a nitinol stent that anchors within the aortic annulus and extends superiorly to anchor in the ascending aorta. It is available in sizes 23, 26, 29, and 31 to fit annulus sizes 18 to 29 mm (Fig. 33-2, Table 33-1). The CoreValve can only be delivered using retrograde approaches.

The major landmark trials in the percutaneous treatment of aortic valve disease are the PARTNER and the CoreValve Pivotal Trials. In prospective randomized fashion, the PARTNER Trial compared balloon-expandable (SAPIEN generation) transcatheter aortic valve replacement (TAVR) with valve and medical management in inoperable (combined risk of serious morbidity or mortality exceeding at least 50% and two surgeons agreeing the patient was inoperable) patients in its IB cohort and with surgical valve replacement in high risk (Society of Thoracic Surgeons (STS) >10%) patients in its IA cohort. Likewise, the CoreValve Pivotal Trials compared self-expandable TAVR with medical and surgical treatments in similar cohorts.

Transcatheter Aortic Valve Replacement Versus Medical Therapy

In the PARTNER IB cohort, inoperable patients were randomly assigned to SAPIEN TAVR or medical management. TAVR was associated with improved 1- and 2-year mortality (30.7% 1 year, 43.4% 2 year) compared with medical (including the use of balloon valvuloplasty) management (50.7% 1 year, 68% 2 year). The rate of the composite end point of death or repeat hospitalization was also reduced with TAVR (42.5 vs 71.6%). The stroke rate was significantly higher in the TAVR group than that in the medical therapy group at 30 days (6.7 vs 1.7%) and at 2 years (13.8 vs 5.5%).^10,12 It should be noted that TAVR improved survival in patients with an STS score of <15% but not in those with an STS score of ≥15%.⁹

These very convincing results with the balloon-expandable valve led to the conclusion that a randomized trial comparing self-expanding (CoreValve) TAVR and medical therapy could not ethically be performed. Instead, a prospective single-arm study, the CoreValve Extreme Risk US Pivotal Trial, was used to compare CoreValve TAVR to a prespecified estimate of 12-month mortality or major stroke with medical therapy (43%).¹³ Nearly 500 patients underwent attempted treatment with CoreValve. In those patients, the rate of all-cause mortality or major stroke at 1 year was significantly lower than the prespecified expected rate (26 vs 43%), echoing the results of the PARTNER Trial.¹³

Given the known dismal prognosis of nonsurgically managed severe symptomatic aortic stenosis,^14-16 it was perhaps not surprising that aortic valve replacement was found to be associated with obviously increased survival in inoperable patients. With regard to comparison of TAVR and high-risk aortic valve replacement, the differences are subtler.

Transcatheter Aortic Valve Replacement Versus Surgery

The PARTNER Trial found similar 30-day (3.4 and 6.5%, p = .07), 1-year (24.3 and 26.8%), and 2-year (33.9 and 35.0%) mortality rates between SAPIEN TAVR and surgical valve replacement in patients at high risk for surgery randomized to either SAPIEN TAVR or surgery.

The combined stroke and transient ischemic attack rate was more frequent in the patients assigned to TAVR at 30 days (5.5% TAVR vs 2.4% surgery, p = .04) and at 1 year (8.7% TAVR vs 4.3% surgery, p = .04). The difference was of borderline significance at 2 years (11.2 vs 6.5%, p = .05). More patients undergoing TAVR reported symptom improvement at 30 days, but at 1 year, symptom improvement was similar in the two groups. At 30 days, TAVR was associated with more frequent major vascular complications (11.0 vs 3.2%) and surgery was associated with more frequent major bleeding episodes (19.5 vs 9.3%) and new-onset atrial fibrillation (16.0 vs 8.6%). The rate of new pacemaker requirement at 30 days was similar between the TAVR and surgical groups (3.8 vs 3.6%). Moderate or severe paravalvular aortic regurgitation was more common after TAVR than surgery at 30 days, 1 year, and 2 years and, importantly, was associated with increased late mortality.^10,12

As in PARTNER, the US CoreValve High Risk Study found no difference in 30-day mortality in patients at high risk for surgery randomized to CoreValve TAVR or surgery (3.3 and 4.5%). However, unlike PARTNER, the 1-year mortality rate was lower in the CoreValve TAVR group than that in the surgical group (14.2 vs 19.1%, p < .0001 for noninferiority, p = .04 for superiority).^13,17 It is to be noted, that diabetes was more common in the surgery group compared with the TAVR cohort (45.4 vs 34.9%; p = .003), and this among other factors has led to questions about conclusions regarding the true survival benefit to TAVR over surgery in this trial.¹⁸