The Sapien 3 Valve
`
`Current use in United States TAVR practice.
`
`BY RAMIN S. HASTINGS, MD, AND ISAAC GEORGE, MD
`
`T ranscatheter aortic valve replacement (TAVR)
`
`has become the standard for treatment of
`aortic stenosis in patients who are at high or
`prohibitive risk for conventional surgical aortic
`valve replacement,1 although its role in patients who
`are at intermediate risk for surgery is currently being
`studied. For TAVR to be considered equivalent to surgi-
`cal valve replacement, it is vital that the performance
`of transcatheter valves improve; in the past 10 years,
`the technology of transcatheter valves has advanced
`tremendously. One of the most important predictors
`of clinical outcomes in patients undergoing TAVR
`is residual paravalvular leak (PVL), and newer valve
`designs have concentrated on reducing PVL. In addi-
`tion, newer-generation valves have been designed to
`improve deliverability and safety, including reducing
`periprocedural mortality, stroke, and vascular complica-
`tions. The Sapien 3 valve (Edwards Lifesciences), which
`builds upon the Sapien platform (Edwards Lifesciences),
`has recently been approved for use in the United States.
`The valve was designed to improve on its predecessors,
`the Sapien and the Sapien XT transcatheter heart valves
`(Edward Lifesciences), in terms of vascular injury, stroke,
`positioning, and PVL. This article reviews the features of
`this device, as well as the early data that have led to its
`approval.
`
`FEATURES
`The Sapien 3 valve retains the basic structure of
`the Sapien and Sapien XT, with a cobalt chromium
`frame and bovine pericardial tissue leaflets (Figure 1A).
`The valve itself is a balloon-expandable system that is
`crimped onto a delivery catheter prior to implantation.
`Much like the Sapien XT, the Sapien 3 valve is posi-
`tioned onto the balloon in the descending aorta and
`then unsheathed after the valve is positioned across the
`aortic annulus. The frame design has been updated to
`include wider strut angles and an increase of rows and
`columns between the valve commissures. This frame has
`been designed to improve radial strength, decrease delivery
`profile, and improve access to coronary arteries after valve
`implantation. Although the frame height remains low, it
`
`42 CARDIAC INTERVENTIONS TODAY MARCH/APRIL 2016 VOL. 10, NO. 2
`
`A
`
`B
`
`C
`
`Figure 1. Sapien 3 valve design (A), dual articulation allowing
`for extreme angulation and better repositioning (B), and the
`delivery system handle (C).
`
`is slightly higher than its predecessor, the Sapien XT. As a
`result, the Sapien 3 valve will foreshorten to a greater
`extent than the Sapien XT valve upon deployment. The
`improved delivery profile has reduced the French size of
`the Sapien 3 introducer sheath. The 20-, 23-, and 26-mm
`
`A O R T I C VA LV E
`U P D AT E
`
`Page 1 of 4
`
`

`

`Figure 2. All-cause mortality at 30 days in the PARTNER trials. P1A, PARTNER IA; P1B, PARTNER IB; P2B, PARTNER IIB; P2B XT,
`PARTNER IIB XT; S3 CE HR, European CE high-risk cohort; S3 CE IR, European CE intermediate-risk cohort; S3HR, PARTNER S3
`high-risk cohort; S3i, PARTNER S3 intermediate-risk cohort; TF, transfemoral.
`
`valves are now delivered through a 14-F sheath, while
`the 29-mm valve is delivered through a 16-F sheath. This
`smaller sheath has expanded the patient population in
`which transfemoral access can now be safely utilized. The
`suggested minimal diameter of the femoral/iliac arterial
`system has been decreased to 5.5 mm with the 20- to
`26-mm valves, and 6 mm with the 29-mm valve.
`An adaptive outer skirt made of polyethylene tere-
`phthalate has been added to the ventricular aspect of
`the valve. This skirt has been designed to improve the
`rates of significant PVL (as subsequently described).
`The delivery system of the Sapien 3 valve (Sapien 3
`Commander Delivery System; Edwards Lifesciences) has
`been modified as well. There is an increased ability to
`distally retroflex the delivery system as it traverses the
`aortic arch into the ascending aorta (Figure 1B). A fine-
`control knob has been added to the handle to provide
`microcontrol of valve positioning while in the aortic
`annulus (Figure 1C). In addition, a central balloon marker
`has been added to be used as the primary landmark for
`valve positioning. These changes are designed to improve
`deliverability and allow more precise valve positioning.
`
`INITIAL DATA
`The initial feasibility data, published in 2013, were
`based on implantation in 15 patients,2 in whom all 15
`implantations were successful; there were no major com-
`plications, and one patient required a new pacemaker.
`
`These data were followed by the European CE trial of
`150 patients.3 The initial 50 patients were high risk, and
`the subsequent 100 were deemed intermediate risk.
`The average age was 84 years with an average Society of
`Thoracic Surgery (STS) score of 7.4%. Ninety-nine percent
`of the valves were implanted at the intended site, and mor-
`tality at 30 days was 2.1% in those patients in whom trans-
`femoral access was used, whereas the mortality was 11.1%
`in those who required alternative (transapical or direct
`aortic) access. The 30-day stroke rate in the transfemoral
`group was 1%, whereas the stroke rate in the alternative
`access group was 5.6%. Vascular complications were low,
`with a major complication rate of 4.2% in the transfemo-
`ral group. Pacemaker rates were higher than previously
`reported with the Sapien XT, with 13.3% of patients requir-
`ing a new pacemaker. Only 6.6% of patients had New
`York Heart Association class III/IV symptoms at 30 days.
`The average effective orifice area at 30 days was 1.5 cm2,
`and the mean gradient was reduced to 10.6 mm Hg, with
`only 3.5% of patients having more than mild PVL. This
`low rate of PVL has also been reported in several other
`small registry trials.4,5 During this early experience, it was
`evident that the valve sizing of the Sapien 3 was differ-
`ent than its predecessors. It was found that the same
`degree of oversizing for Sapien XT was not required, and
`subsequent sizing algorithms allowed up to 5% undersizing
`of the valve with no increase in PVL, which allows for easier
`and safer sizing of the Sapien 3 valve. Small comparative
`
`VOL. 10, NO. 2 MARCH/APRIL 2016 CARDIAC INTERVENTIONS TODAY 43
`
`A O R T I C VA LV E
`U P D AT E
`
`Page 2 of 4
`
`

`

`Figure 3. Percent of patients with moderate/severe paravalvular leak at 30 days across PARTNER trials. P1A, PARTNER IA; P1B,
`PARTNER IB; P2B, PARTNER IIB; P2B XT, PARTNER IIB XT; S3HR, PARTNER S3 high-risk cohort; S3i, PARTNER S3 intermediate-risk
`cohort; TF, transfemoral.
`
`registry data have found marked improvements in PVL and
`vascular complications with the Sapien 3 valve compared
`to the Sapien XT valve.6
`As explained previously, early data found that while
`the Sapien 3 valve reduced significant PVL and vascular
`complications, the rate of pacemaker implantation was
`higher than expected. Subsequent analyses of these
`patients found that lower implantation of the valve,
`which was initially suggested due to the foreshortening
`of the valve, was associated with higher pacemaker rates.
`A higher implantation seemed to be associated with
`lower pacemaker rates, similar to that of the Sapien XT,
`without affecting the rate of paravalvular leak.7 These
`early trials have found that the optimal annulus sizing
`can be anywhere from 5% undersized to 20% oversized,
`and the valve should be implanted with the bottom of
`the middle marker at the base of the annulus.
`The large PARTNER II S3 trial was designed to study the
`performance of the Sapien 3 valve in the United States. The
`trial consisted of two, single-arm, nonrandomized trials.
`One arm included patients who were deemed high risk or
`inoperable by a heart team, while the other arm contained
`patients who were deemed intermediate risk. The trial was
`designed to compare the Sapien 3 valve against historical
`controlled studies (PARTNER IA for high-risk patients and
`the PARTNER IIA for intermediate-risk patients).
`Although no published data have been presented from
`these trials, the results have been presented at national
`meetings. The initial 30-day results were presented in
`
`March 2015, at the annual meeting of the American College
`of Cardiology.8 In the high-risk cohort, the average STS score
`was 8.6%, and the average age was 83 years. The 30-day
`mortality was 2.2%, and the rate of any stroke was 1.5%. The
`1-year data were recently presented at the 2015 TCT meet-
`ing demonstrating an overall 1-year mortality rate of 14.4%
`(10.7% in high-risk patients, 15.7% in inoperable patients).9
`The Sapien 3 intermediate-risk cohort had an average STS
`of 5.3% (average age, 82 years). The 30-day mortality was
`1.1%, with a stroke rate of 2.6%. Vascular complications
`rates were low, with a major vascular complication rate of
`5% in the high-risk cohort and 5.6% in the intermediate-risk
`cohort. Coronary obstruction and annular rupture were
`very uncommon. There was a marked improvement in
`symptoms, with New York Heart Association class III/IV
`symptoms in 13% of the high-risk patients and 6% in the
`inoperable-risk patients at 30 days. Only 3.8% of patients
`had more than mild PVL at 30 days.
`
`CLINICAL IMPLICATIONS
`Although the full results of the PARTNER II and the
`PARTNER II Sapien 3 results have not been fully released,
`the collective early experience utilizing the Sapien 3
`valve suggests an excellent safety profile, with the low-
`est 30-day mortality rates seen to date with a balloon-
`expandable TAVR (Figure 2), very low rates of signifi-
`cant PVL (Figure 3), and few vascular complications.
`Pacemaker implantation appears to occur at similar rates
`as with the Sapien XT valve with proper positioning and
`
`44 CARDIAC INTERVENTIONS TODAY MARCH/APRIL 2016 VOL. 10, NO. 2
`
`A O R T I C VA LV E
`U P D AT E
`
`Page 3 of 4
`
`

`

`sizing. Based on these data, the Sapien 3 valve has been
`approved for use in patients with high-risk features for
`conventional surgical aortic valve replacement.
`Given the improvements in the Sapien 3 valve and the
`Sapien 3 valve delivery system, the Sapien 3 valve has sup-
`planted the Sapien XT as the balloon-expandable trans-
`catheter valve of choice. The improved deliverability and
`need for only a 14-F sheath (with the 20–26-mm valve)
`has also made the need for alternative access (transaortic
`or transapical) a much less common occurrence, likely fur-
`ther improving patient outcomes and recovery. Although
`some valvular anatomy may be more suitable for a self-
`expanding transcatheter valve, the Sapien 3 valve has
`proven to be reproducibly implantable in many different
`anatomies. As indications for TAVR are being broadened
`to patients at lower risk for surgical aortic valve replace-
`ment, it is imperative that newer-generation transcatheter
`valves achieve exceedingly low rates of procedural compli-
`cations and PVL. The new design iterations of the Sapien 3
`valve appear to have lowered these specific metrics to lev-
`els potentially comparable to surgical valve replacement.
`
`FURTHER AREAS OF INTEREST
`Further study of long-term, follow-up data is needed in
`the field of TAVR. It is still unclear how well these transcath-
`eter valves will perform upon later follow-up and, as we try
`to make decisions on whether to offer TAVR to younger
`patients, these clinical data will be of utmost importance.
`The original trials utilizing the Sapien valve were performed
`on patients with extreme comorbidities, with the majority
`not surviving for long-term follow-up. However, recent trials
`have enrolled lower-risk patients, and along with the advent
`of large national databases (such as the TVT registry), data
`on the longevity and durability of the new transcatheter
`valves should become available as soon as the valves have
`been used in clinical practice long enough.
`It appears that the Sapien 3 valve has an excellent safety
`profile and provides excellent early echocardiographic and
`clinical outcomes. The earlier-generation transcatheter
`valves have been shown in randomized trials to be at least
`equivalent, if not superior, to conventional aortic valve sur-
`gery. The next question will be whether the improvements
`made in the latest-generation Sapien 3 valve will lead to
`long-term improvements in clinical outcomes in patients
`who are at lower risk for surgical aortic valve replacement.
`The PARTNER IIA trial results along with the PARTNER II S3
`data will provide key information on the role of the Sapien 3
`valve in those deemed intermediate risk for surgical aortic
`valve replacement. The SURTAVI trial will provide further
`information in this key patient group. Given the marked
`improvement in the Sapien 3 valve, further studies are
`being planned in low-risk patients, including the recently
`
`approved PARTNER III study comparing TAVR to surgical
`aortic valve replacement in low-risk patients.
`
`CONCLUSIONS
`The Sapien 3 has a lower profile, improved deliverability,
`more precise positioning, and appears to improve rates of
`procedural complications. Importantly, rates of stroke, death,
`and severe PVL appear to be reduced with the Sapien 3 valve
`compared to previous Sapien valves. Given these improve-
`ments, it has become the balloon-expandable valve of choice
`for patients undergoing TAVR. Further investigation is ongo-
`ing to see if the improvements made in the valve design will
`translate into long-term clinical benefits for patients with
`aortic stenosis. As trials that will compare TAVR to conven-
`tional aortic valve replacement in low-risk patients are just
`beginning, improvements to valve design are critical to help
`achieve equivalent, and perhaps superior, outcomes. n
`
`1. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot
`undergo surgery. N Engl J Med. 2010;363:1597-1607.
`2. Binder RK, Rodes-Cabau J, Wood DA, et al. Transcatheter aortic valve replacement with the Sapien 3: a new balloon-
`expandable transcatheter heart valve. JACC Cardiovasc Interv. 2013;6:293-300.
`3. Webb J, Gerosa G, Lefevre T, et al. Multicenter evaluation of a next-generation balloon-expandable transcatheter aortic
`valve. J Am Coll Cardiol. 2014;64:2235-2243.
`4. Husser O, Pellegrini C, Kessler T, et al. Outcomes after transcatheter aortic valve replacement using a novel balloon-
`expandable transcatheter heart valve: a single-center experience. JACC Cardiovasc Interv. 2015;8:1809-1816.
`5. Wendt D, Al-Rashid F, Kahlert P, et al. Low incidence of paravalvular leakage with the balloon-expandable Sapien 3
`transcatheter heart valve. Ann Thorac Surg. 2015;100:819-826.
`6. Binder RK, Stortecky S, Heg D, et al. Procedural results and clinical outcomes of transcatheter aortic valve implantation in
`Switzerland: an observational cohort study of Sapien 3 versus Sapien XT transcatheter heart valves. Circ Cardiovasc Interv.
`2015;8:pii:e002653.
`7. Tarantini G, Mojoli M, Purita P, et al. Unravelling the (arte)fact of increased pacemaker rate with the Edwards Sapien 3
`valve. EuroIntervention. 2015;11:343-350.
`8. Kodali S. Clinical and echocardiographic outcomes at 30 days with the Sapien 3 TAVR system in inoperable, high-risk and
`intermediate-risk AS patients. Presented at: ACC 2015 meeting; March 15, 2015; San Diego, CA.
`9. Herrmann H. Sapien 3: evaluation of a balloon-expandable transcatheter aortic valve in high-risk and inoperable patients
`with aortic stenosis - one-year outcomes. Presented at: TCT 2015 meeting; October 15, 2015; San Francisco, CA.
`
`Ramin S. Hastings, MD
`Divisions of Cardiology and Cardiothoracic Surgery
`New York Presbyterian Hospital
`College of Physicians and Surgeons of Columbia
`University
`New York, New York
`raminhastings@gmail.com
`Disclosures: None.
`
`Isaac George, MD
`Divisions of Cardiology and Cardiothoracic Surgery
`New York Presbyterian Hospital
`College of Physicians and Surgeons of Columbia
`University
`New York, New York
`ig2006@cume.columbia.edu
`Disclosures: Consultant to Edwards Lifesciences and
`Medtronic, Inc.; Surgical National PI of the Direct Flow
`Medical SALUS trial.
`
`46 CARDIAC INTERVENTIONS TODAY MARCH/APRIL 2016 VOL. 10, NO. 2
`
`A O R T I C VA LV E
`U P D AT E
`
`Page 4 of 4
`
`