Expert Review of Medical Devices

ISSN: 1743-4440 (Print) 1745-2422 (Online) Journal homepage: http://www.tandfonline.com/loi/ierd20

Evaluation of the Edwards Lifesciences SAPIEN transcatheter heart valve Sa’ar Minha & Ron Waksman To cite this article: Sa’ar Minha & Ron Waksman (2014) Evaluation of the Edwards Lifesciences SAPIEN transcatheter heart valve, Expert Review of Medical Devices, 11:6, 553-562, DOI: 10.1586/17434440.2014.947272 To link to this article: http://dx.doi.org/10.1586/17434440.2014.947272

Published online: 09 Aug 2014.

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Date: 02 December 2016, At: 05:48

Device Profile

Evaluation of the Edwards Lifesciences SAPIEN transcatheter heart valve Expert Rev. Med. Devices 11(6), 553–562 (2014)

Sa’ar Minha and Ron Waksman* Interventional Cardiology, MedStar Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010, USA *Author for correspondence: Tel.: +1 202 877 2812 Fax: [email protected]

Severe aortic stenosis is a common valvular disease and is associated with both morbidity and mortality. Surgical aortic valve replacement was the only available therapeutic option until technological advances allowed for the development of a transcatheter heart valve system. The first available THV was the Edwards SAPIEN. The merits of this system in terms of safety and efficacy were explored in the pivotal Placement of AoRTic TraNscathetER (PARTNER) randomized trial whose results then led to the approval of this device for commercial use in the US. The valve is now indicated for inoperable patients and may be considered an alternative for surgery for high-risk patients. Two successive models, the XT and more recently the S3, were developed with the intent to improve procedural outcomes. In this article, the SAPIEN transcatheter heart valve family is described in terms of technology, scientific data and future directions. KEYWORDS: aortic stenosis • SAPIEN • transcatheter aortic valve replacement

Therapy for severe symptomatic aortic stenosis; the unmet need

Aortic stenosis (AS) is the most common valvular disease. It is estimated that 2–7% of patients aged >65 years have severe AS [1,2]. AS is manifested clinically as syncope, angina or congestive heart failure. It is the result of a continuous degenerative process that leads to calcification of the valve leaflets that leads to restriction in valve leaflet opening. Until recently, surgical aortic valve replacement (SAVR) was the only available therapeutic alternative for patients with severe, symptomatic AS. SAVR is associated with both symptom relief and improved survival; thus, a class I recommendation for SAVR was given in the practice guidelines [3]. Unfortunately, not all patients are eligible for surgery and the outcomes of patients treated with medical therapy are reported to be poor, with only 50% of patients surviving at 1-year follow-up [4]. This motivated the research and development of less-invasive means for treating AS. Transcatheter heart valve: technology & evolution

The first-in-human transcatheter valve was developed by Bonhoeffer et al. A bovine

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10.1586/17434440.2014.947272

jugular vein valve was mounted onto a stent to be used in children with stenosed conduits between the right ventricle and pulmonic valve [5]. The first-in-human, balloon-expandable transcatheter heart valve (THV) for AS was developed and deployed by Alan Cribier et al. in 2002 [6]. This was a three-leaflet equine valve that was crimped and mounted on a steel, balloon-expandable stent. A special delivery system carrying the crimped valve enabled the successful deployment via a transseptal antegrade approach. The inferior vena cava was accessed and a transseptal puncture performed. The delivery system was then advanced over a stiff wire from the inferior vena cava to the right atrium, left atrium, left ventricle and finally across the aortic valve. This initial model led to the research and development of the first commercial THV for treating AS, – the Edwards SAPIEN valve. The two essential components of the SAPIEN THV system are the prosthetic valve and its delivery system. The valve is composed of a three-leaflet bovine pericardial tissue sewed onto a stainless steel frame and is available in 23 mm and 26 mm sizes. Two valve delivery catheters are available: Retroflex for transfemoral (TF) access (22/24F) and Ascendra (26F)


2014 Informa UK Ltd

ISSN 1743-4440

553

Device Profile

Minha & Waksman

Table 1. SAPIEN transcatheter heart valve systems. SAPIEN

SAPIEN XT

SAPIEN 3

Available sizes

23 mm, 26 mm

23 mm, 26 mm, 29 mm

23 mm, 26 mm, 29 mm

Valve design

Stainless steel Bovine pericardium

Cobalt–chromium Bovine pericardium

Cobalt–chromium Bovine pericardial larger cells Inner and outer skirt (polyethylene terephthalate)

Transfemoral delivery system

RetroFlex

NovaFlex

Commander

RetroFlex 3 delivery system 18 Fr profile

Sheath sizes

22/24F Outer diameter (8.4/9.2 mm)

for the transapical (TA)/direct aortic access. After the initial antegrade experience with the Cribier valve, two alternatives for access and deployment were developed. In the TF access, after the introducer sheath is secured in the common femoral artery, the delivery system is advanced retrogradely through the aorta to the left ventricle. The TA access utilized a small thoracotomy and puncture of the left ventricle apex to deploy the valve. Opposed to coronary stents, which are crimped and mounted over a balloon during production, the SAPIEN prosthetic valve is stored within the stent in its neutral, open position and is then crimped on the balloon at the tip of the delivery system adjacent to the actual deployment. The delivery system uses a 22F sheath for the 23-mm valve and a 24F sheath for the 26-mm valve; thus, adequate caliber ilio-femoral arteries are needed to accommodate this relatively large system (7.0 and 8.0 mm, respectively) (TABLE 1). The Edwards SAPIEN THV system was succeeded by the SAPIEN XT system. SAPIEN XT uses a new delivery system (NovaFlex for TF and Ascendra II for TA), and 20- and 29-mm sized valves were added to the previously available 23 mm and 26 mm sizes. Several technical differences exist between the original SAPIEN and the XT. The stent on the XT system is not crimped and mounted onto the balloon as it is with the original SAPIEN. The stent is crimped upstream from the balloon at the tip of the delivery system and the actual mounting is performed in vivo after access is achieved. This allows smaller caliber sheaths to be used, which allows more patients to be eligible for TF access. Further, the TF sheaths for the XT system are 16F (outer diameter 6.7 mm 554

16/18/20F eSheath Outer diameter (6.6/7.2/7.8 mm)

unexpanded/8.9 mm expanded) and 18F (outer diameter 7.2 mm unexpanded/8.9 mm expanded) expandable sheaths. The sheath design includes an embedded fold in the sheath which allows a transient expansion of the sheath during valve passage and recoiling afterward. The use of these expandable sheaths allows the delivery of the valve system through vessels with diameters as low as 6.0 mm. The XT valve is made of cobalt–chromium and the leaflets are partially closed. Recently, a new member of the SAPIEN family was introduced, the S3, which is available in 23, 26 and 29 mm sizes. Technological advances have allowed the introduction of a new delivery system (Commander for TF and Certitude for TA) to fit into 14F and 16F sheaths (14F outer diameter 6 mm unexpanded/8 mm expanded; 16F outer diameter 6.7 mm unexpanded/8.9 mm expanded; minimal lumen diameters of 5.5 and 6.0 mm, respectively). The valve design has also changed. The THV is currently taller than the XT and SAPIEN models, but also includes a polyethylene terephthalate skirt, which aims at decreasing the degree of aortic regurgitation. Clinical trials Initial clinical experience

The Cribier valve was explored in the initial registry of endovascular implantation of valve in Europe both in TF and transvenous access [7], while the TRAVERCE registry (TRAns apical surgical deliVEry of the Cribier Edwards aortic bioprosthesis) explored the feasibility of TA access [8]. TRanscatheter EndoVascular Implantation of VALves (REVIVAL) I and II were prospective, non-randomized Expert Rev. Med. Devices 11(6), (2014)

Evaluation of the Edwards Lifesciences SAPIEN THV

Device Profile

Table 2. The main inclusion and exclusion criteria of PARTNER trial. Main inclusion criteria

Main exclusion criteria

• Symptomatic patient with degenerate aortic valve that meets the following echocardiographic criteria: AVA 4 m/s

• Acute myocardial infarction within a month from the planned procedure or significant coronary disease requiring revascularization • Bicuspid, unicuspid or non-calcified valve • Mixed aortic disease (aortic stenosis with aortic regurgitation >3+) • Any pre-existing prosthetic valve • Blood dyscrasias • Hemodynamic instability • Active or past gastrointestinal bleeding (£3 months) • Recent (£6 months) cerebrovascular accident • Renal insufficiency (creatinine >3.0 mg/dl or chronic dialysis) • Life expectancy 50%, as determined by two cardiac surgeons OR • High (cohort A) – defined as at least 15% chance for death at 30 days, as determined by two cardiac surgeons

AVA: Aortic valve area.

feasibility trials [9,10]. REVIVAL I was a feasibility trial with the original Cribier–Edwards valve that led to redesign of the device (to include bovine instead of equine valve leaflets) and to the decision to abandon the antegrade (transvenous) access. REVIVAL II and REVIVE-II (Registry of EndoVascular Implantation of Valves in Europe II) were both multicenter registries set up in the US, Europe and Canada. The data collected in these trials led to European CE Mark for the SAPIEN valve given in 2007. These data, alongside data from the European Placement of AoRTic traNscathetER (PARTNER) (single arm; n = 130) and Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registries paved the way for the PARTNER pivotal trial, the largest randomized, controlled trial performed thus far in the Transcatheter Aortic Valve Replacement (TAVR) arena.

over standard therapy in inoperable patients, these patients (n = 560) were randomized in PARTNER II to either SAPIEN or SAPIEN XT valves. In order to establish the merits of TAVR in patients with intermediate surgical risk (STS ‡ 4), the second arm randomized operable patients (n = 2000) at intermediate risk (STS ‡ 4) to either SAPIEN XT (via TF/TA or direct aortic) or SAVR. Data are currently available for the inoperable cohort only. Patients randomized to the original SAPIEN valve had numerically higher rates of 30-day mortality (5.1 vs 3.5%; p = 0.36) and similar rates of stroke (4.1 vs 4.3%; p = 0.88). Major vascular complication rate was significantly lower in the patients who underwent TAVR with the XT system (9.6 vs 15.5%; p = 0.04). These differences stemmed from lower rates of perforation and dissection documented in the XT cohort (0.4 vs 4.8%; p = 0.003 and 4.3 vs 9.2%; p = 0.03, respectively) [13].

Main outcomes of the PARTNER pivotal trial

The PARTNER trial was the first and most rigorous effort to establish the merits of a THV in a randomized, clinical trial. This multicenter trial comprised two arms: PARTNER cohort A randomized high-risk patients (Society of Thoracic Surgeons [STS] score >8) to either TAVR or SAVR (n = 699), while in cohort B, which included high-risk patients deemed inoperable by cardiac surgeons (TABLE 2), patients were randomized to either TAVR or standard therapy (n = 358). PARTNER A demonstrated non-inferiority of TAVR to SAVR for the primary endpoint of all-cause mortality at 1 year (24.2 vs 26.8%; p = 0.44; p for non-inferiority with 7.5 percentage point margin = 0.001) [11]. These results were sustained after 2 years of follow-up (33.9 vs 35.0%; p = 0.78) [11]. In PARTNER B, lower mortality rates were recorded when TAVR was compared with standard therapy (30.7 vs 50.7%; p < 0.001) and once again, sustainability of the result was retained at 2 years (43.3 vs 68.0%; p < 0.01) (TABLE 3) [12]. PARTNER II is ongoing, but the trial’s design and initial results were recently presented. Similar to PARTNER, this study has two arms: After establishing the merits of TAVR informahealthcare.com

Main outcomes of large-scale registries

The European PARTNER registry was a single-arm, prospective trial to establish the feasibility and outcome of patients undergoing TF and TA TAVR in several European centers. Mortality rates at 30 days and at 1 year were 13.8 and 36.9%, respectively [14]. Since this trial included centers that carried out their first TAVR cases as part of this registry, the results do not necessarily reflect true, ‘real-world’ results. PARTNER EU was succeeded by the SOURCE registry, one of the largest SAPIEN ‘real-world’ registries [15,16]. The mortality rate at 30 days was 6.3% (TF) and 10.3% (TA) [15]. The mortality rate at 1 year was 23.9% for this large cohort consisting of 1038 patients from 32 European centers. More recent data including a total of 2307 patients demonstrated similar results (all-cause mortality rate at 1 year, 23.6%). SOURCE-XT was the European post-approval arm of the SAPIEN XT valve. Enrollment started in 2010 and the 1-year follow-up data from 93 centers (17 countries) demonstrated the most current ‘reallife’ SAPIEN data. These data included 2688 patients who underwent TAVR with the SAPIEN XT. All-cause mortality 555

Device Profile

Minha & Waksman

Table 3. Comparison of major SAPIEN/SAPIEN XT clinical trials. Ref.

Study (year)

Type

N

Included valves

Success 30-day rate (%) mortality (%)

30-day 1-year mortality stroke rate (%) (%)

30-day aortic 30-day regurgitation vascular events (%) (%)

PARTNER A Smith (2011)

RCT

348

SAPIEN TA/TF

–

3.4

24.2

4.7

17.0

12.3

[25]

PARTNER B Leon (2011)

RCT

358

SAPIEN TF

–

5.0

30.7

6.7

30.7

13.2

[4]

SOURCE ANZ

Registry

129

SAPIEN TF/TA

92.4 TF 87.1 TA

7.8

18.3

3.8

10.1

1.6

SOURCE Thomas (2010, 2011)

Registry

1038

SAPIEN TF/TA

93.8

8.5

23.9

2.5

12.8

1.9

PARTNER EU Lefevre (2011)

Registry

130

SAPIEN TF/TA

96.4 TF 95.4 TA

13.8

36.9

2.3

15.3

Canadian Registry Rode´s-Cabau (2010)

Registry

345

SAPIEN/XT TF/TA

93.3

10.4

24.0

2.3

13.0

6

[26]

PRAGMATIC Chieffo (2013)

Registry

204

SAPIEN/XT TA/TF

96.6

6.4

12.3

1.5

12.3

1.0

[51]

PARTNER II-B Leon (2013)

RCT

560

TF

–

5.1 SAPIEN 3.5 XT

4.1 SAPIEN 4.3 XT

22.9 SAPIEN 14.6 XT

21.3 SAPIEN 24.8 XT

[13]

PREVAIL-TA

Registry

150

TA/SAPIEN XT 98.7

8.7

2.7

SOURCE-XT (2013)

Registry

2.688 TF/TA/SC/TAO 92.7

2.3

2.2

11.0

5.7

[17]

Transcatheter valve therapy registry Mack (2013)

Registry

7710

TA/TA/ alternative

92

7.6

2.8

6.4

TCVT Europe Registry Di Mario (2013)

2604

TF/TA/ alternative

96.8

7.9

1.7

3.3

19.5

[15,16]

[14]

[18]

0.6

[49]

RCT: Randomized control trial; SC: Trans-subclavian; TA: Transapical; TAO: Transaortic; TF: Transfemoral.

rates at 30 days and at 1 year were 6.3 and 19.5%, respectively, but it should be noted that the patients included in this cohort were from lower-risk strata compared to the original SOURCE registry (TABLE 3) [17]. The US FDA’s approval of the SAPIEN valve in November 2011 led to the initiation of a mandatory post-approval US registry. Participation in the transcatheter valve therapy registry initiated by the STS and the American College of Cardiology is necessary for reimbursement purposes. The first report from this registry included 8075 patients with the majority (80%) considered as high-risk, operable. The mortality rate at 30 days was 7.6% [18]. Clinical merits & cost–effectiveness Quality of life & symptom relief

Beyond increased survival rates, the goal of TAVR is to alleviate symptoms and improve a patient’s quality of life. This is especially challenging in light of the fact that many of the patients 556

referred to TAVR are frail, elderly patients with multiple comorbidities. The improvement in quality of life after TAVR was demonstrated in a subanalysis of patients from PARTNER cohort A at 2 years of follow-up. After TAVR, patients had sustained improvement of symptoms with 83.9% of them reported to be in New York Heart Association class I–II [11]. This was also demonstrated in the European PARTNER registry [14]. More recent data from the SAPIEN XT valve registry reported that at 1-year follow-up, the rate of angina symptoms decreased (from 45% at baseline to 20.6%; p < 0.001), New York Heart Association heart failure class improved (73.5% had New York Heart Association class III–IV at baseline vs 9.7% at 1-year follow-up) and quality of life, as reflected by various questionnaires, demonstrated significant improvement as well. It is now suggested that a poor outcome after TAVR will be determined by combining the two aforementioned indices, mortality and quality of life, and the outcome will be judged as poor if the patient died after the procedure, had poor quality of life postExpert Rev. Med. Devices 11(6), (2014)

Evaluation of the Edwards Lifesciences SAPIEN THV

TAVR, or a sustained decline in quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire [19]. Although most patients demonstrate improvement in quality of life, it is clear that a subset of patients do not benefit from TAVR. Since the procedure demands the utilization of significant resources, it signifies the importance of predicting ‘futility’ parameters. For example, Beohar et al. have, by utilizing PARTNER data, demonstrated that low body mass index at baseline, liver disease, kidney disease, decreased mini-mental state test score and complications during the procedure are all independent predictors for short-term survival [20]. It was further demonstrated that patients who underwent TAVR as part of the PARTNER IB trial with STS score ‡15 had similar mortality rates at 2 years compared to patients who had standard therapy [12]. Thus, beyond efforts to expand the use of TAVR for intermediate-risk AS patients, efforts are made to better define patients who unfortunately will not benefit from the procedure in ‘cohort C’. Adverse events Vascular complications

Most TAVR procedures are performed via TF access. Although considered as a less invasive procedure compared with open heart surgery, the introduction of large bore sheaths (22/24F with SAPIEN and 16/18/20F with SAPIEN XT) is still associated with significant vascular complication rates. These complications include, among others, access vessel perforation/dissection, retroperitoneal bleeding, aortic dissection and limb ischemia. The exact complication rate is unknown since different definitions were used by different authors. This has led to the publication from Valve Academic Research Consortium [21], which is now considered as the standard for reporting adverse events. In PARTNER (SAPIEN valve), the reported rate of major vascular complications was 13.7–17.5%. These events were associated with increased risk for bleeding, need for transfusion and a twofold increase in mortality risk. Of note, a decrease in the rate of these complications to 5.5% was recorded in non-randomized patients included later in the trial. This could be attributed to several factors, such as better patient selection and technical proficiency gained during the enrollment period, the fact that the delivery device had improved during the trial and the gradual transition to a fully percutaneous TAVR. Similar results (6.4%) were reported in the large ‘real-life’ transcatheter valve therapy registry and with the use of smaller caliber sheaths with the XT valve [13,18]. Intuitively, the ratio between the outer diameter of the sheath used and the vessel’s smallest diameter is an important determinant [22], but patient characteristics, such as vessel degree of calcification and female gender, were also associated with these complications [21], Along the years, a gradual transition from surgical cut-down for access to fully percutaneous access and closure has evolved as the preferred access strategy. This fully percutaneous access mandates pre-closure of the artery with either the Perclose-Proglide suture mediated closure system (Abbott Vascular, Abbott Park, IL, USA) or the Prostar-XL vascular surgical system (Abbott Vascular). This approach was associated with a informahealthcare.com

Device Profile

decrease in vascular complication rate (1% in one series of 137 patients [23]), though it should be noted that other authors reported similar rates of vascular complications when the percutaneous approach was compared to the surgical cut-down [24]. Thus, it is expected that by improving patient screening process, using lower sheaths with smaller diameter, alongside the experience gained over performing hundreds of cases, a decrease in the vascular complication rate will be observed. Stroke

Stroke and transient ischemic attacks are significant, sometimes debilitating, events after TAVR. The reported stroke rates after TAVR vary and are definition dependent (0.9–6.7% at 30 days). In cohort A of the PARTNER trial, higher rates of stroke were observed at 1 year in patients who underwent TAVR compared to those who had SAVR, but this did not reach statistical significance (5.1 vs 2.4%; p = 0.07). Postprocedural stroke is associated with a 3.5-fold increase in the risk for mortality [15,25–27]. Beyond the overt clinical events, magnetic resonance imaging and other imaging modalities demonstrated multiple cerebral infarcts after TAVR, with most of these events being clinically silent [28–30]. As opposed to overt strokes, the long-term impact of these seemingly clinically silent events is currently unknown. From an etiological standpoint, the imaging of multiple bilateral foci suggests embolic events as a causative etiology. These embolic events may be explained by several technical aspects of TAVR: first, wire and relatively bulky devices delivered through the aorta promote scraping and embolization of atherosclerotic material; second, multiple engagement of the native, heavily calcified valve with the prosthesis and valvuloplasty balloons is associated with embolization; and finally, an inherent increased risk for thromboembolism due to atrial fibrillation exists in a large proportion of patients referred to TAVR, with reports indicating a 4.4-fold increase in the stroke risk for patients who demonstrate atrial fibrillation post-procedure [31,32]. Since most of the clinical events were recorded during the procedure or within 24 h of the procedure, it is assumed that the mechanical manipulation is the governing etiology [33]. Several embolic protection devices were developed to mitigate the increased embolic risk and are currently being studied [34,35]. These devices are deployed from either radial or femoral access and placed in the brachiocephalic and left carotid arteries, thereby filtering debris from reaching the cerebral circulation. Another associated controversial issue is the ability to decrease the stroke rate by prescribing either antithrombotic or anticoagulant therapy. At present, due to paucity of data to support one specific regimen, no uniform evidencebased recommendation can be made and most operators prescribe dual antiplatelet therapy for periods of 1–6 months based on data from coronary stents [36]. Recent encouraging data demonstrating a 2.0% stroke rate came from the ‘real-life’ post-approval US registry. These results may be related to the completion of the initial curve and increased proficiency of operators [18]. 557

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Minha & Waksman

Aortic regurgitation

As opposed to a surgical valve sewn to the aorta after the native valve is extracted, the SAPIEN stent-based prosthesis is deployed by balloon inflation. Since the valve leaflets are severely calcified in most AS patients and the aortic valve itself lacks a round shape in most cases, the ability to completely seal the annulus is limited and some degree of perivalvular leak (PVL) often exists [37]. Although PVL is a common phenomenon, as described by a meta-analysis, including 7279 patients who underwent SAPIEN implantation, the incidence of moderate-severe PVL was 9.1% (95% CI: 6.2–13.1%; I2 = 93.6; Q = 313.7) [38]. Interestingly, accumulating evidence indicates that PVL degree remains unchanged or improved over time in most of the patients [11,39]. Thus, although these data should be interpreted cautiously since only patients who survived to follow-up were included, the timing of the PVL may be important in determining the actual association between PVL and outcome. The association between PVL and outcome has clinical implications; when significant PVL is diagnosed immediately post-TAVR, post-dilatation of the valve is possible which may decrease the degree of PVL. Controversy exists regarding the impact of PVL on outcome. While the association between post-procedural PVL >2+ and poor outcome is well established [38,40], the association between mild degree of PVL and outcome is still under debate. Kodali et al. described the association between mild degree of PVL and increased mortality [11], but other reports including meta-analysis challenged this conclusion [38]. Since PVL grading is both operator dependent and a semi-quantitative measurement, it is plausible to assume that the different definitions used for grading PVL in the different trials may have influenced the population explored and, thus, the associated outcome. Several patient and procedural parameters are associated with PVL. Among them are the degree of valvular calcification, implantation depth and valve undersizing. Appropriate sizing became a significant issue in TAVR, which was driven mainly by the association between PVL and mortality. While transthoracic echocardiography was the standard imaging modality used to determine the valve size, more recent data indicate that multidetector computed tomography is better equipped to evaluate the shape and size of the valve and to predict PVL [23]. Since the prosthetic valve sizes are limited, the chosen size can be either oversized (i.e., deploying a prosthesis with larger nominal area in relation to the native valve area) or undersized (i.e., deploying a relatively smaller area prosthesis in relation to the native valve area) in relation to the native valve. Based on current data, significant PVL rates are associated with undersizing >10% of the native annular valve area [23]. On the other hand, oversizing >20% is associated with annular rupture [41]. Thus, a relatively small margin for sizing exists. These data had led to a shift in the pre-procedural size decision-making from TEEbased diameter only to a thorough multidetector computed tomography–based analysis in which valve area, and not diameter, is used for guidance of valve size selection. If after careful 558

sizing and implantation of the valve PVL >2+ is noted, re-ballooning should be considered and in extreme cases in which sever PVL remains, another valve should be deployed within the prosthesis (valve-in-valve). Other adverse events

The fact the TAVR is being performed in elderly patients with multiple co-morbidities exposes these patients to other adverse events. Coronary artery occlusion after deployment of the valve may result from the displacement of the calcified native valve leaflets toward the coronary ostia. Although the incidence of this adverse event is low (10 mm is usually sufficient) and the potential space between the implanted prosthesis and the sinuses of Valsalva. In borderline cases, an interventional guiding catheter can be positioned in the aorta with the undeployed stent placed in the coronary artery at risk. If obstruction had occurred after valve deployment, the stent is positioned and deployed in order to restore flow. Conduction disturbances were also reported as adverse events after TAVR. This is probably related to the radial forces applied by the prosthesis on the myocardium, thereby compressing the fibers of the conducting system. While new leftbundle block is the most common disturbance, other abnormalities may occur and lead to the need for permanent pacemaker. In a meta-analysis by Erkapic et al., the incidence of the need for permanent pacemaker after SAPIEN TAVR was 4–6% [43]. Right-bundle block at baseline was noted in several studies as being associated with the need for pacemaker. It is thus suggested that TAVR patients be monitored for at least 72 h post-procedure. Acute kidney injury is yet another complication of TAVR that is associated with a fourfold increase in mortality risk [44]. Depending on the definition used, the rate of acute kidney injury after TAVR ranges from 0 to 12% [4,44] and the rate of hemodialysis is as high as 7% [15]. Hypertension, blood transfusion, previous myocardial infarction, previous renal disease and EuroSCORE risk were all associated with this complication. Patient–prosthesis mismatch (PPM), an effective valve orifice area too small in relation to the patient’s body size, is another well-reported issue with any bioprosthetic valve. In PARTNER A cohort, the rate of moderate/severe PPM of patients who underwent TAVR was lower than the rate observed in patients randomized to surgery (47 vs 60%; p = 0.002). Further, patients with moderate/severe PPM after TAVR had similar rates of mortality at 2 years compared with patients without PPM [45]. Expert Rev. Med. Devices 11(6), (2014)

Evaluation of the Edwards Lifesciences SAPIEN THV

Cost–effectiveness

The cost–effectiveness of TAVR with the SAPIEN valve was studied on data from the two PARTNER trials. In the inoperable cohort of patients in whom the therapeutic alternative was medical therapy and balloon valvuloplasty, TAVR increased the quality-adjusted life expectancy from 1.19 to 1.93 years. The incremental cost–effectiveness was reported to be 116,500 per quality-adjusted life-year gained [46]. On the other hand, in the cohort of patients randomized to TAVR versus SAVR, the costs and the adjusted life expectancy at 1 year were similar [47]. When the data was broken down according to the TAVR access (TA or TF), the authors reported slightly lower costs and slightly higher quality of life in patients who underwent TF TAVR compared to SAVR [47]. Alternative access

TF access is the used as the default access site for most TAVR procedures. A non-neglectable percentage of patients referred to TAVR have severe peripheral vascular disease or otherwise small diameter arteries that exclude them from the TF access. The next most common access used is TA. Conflicting results were reported when the short- and the long-term mortality rates of TA patients were compared to those of TF patients [16,26]. Poor outcome was noted in TA patients in both registries and in one large-scale meta-analysis including over 6500 patients [48,49]. These results should be interpreted cautiously since the default access in the vast majority of the trials was ‘femoral-first’ and only patients ineligible for TF were steered toward TA, which represented a higher-risk group of patients. More recently, different access routes were used to deliver TAVR. Direct aortic, trans-subclavian and even carotids were used as alternative access sites. SAPIEN in failed bioprosthetic valves

Attention was given to the use of TAVR in inoperable patients with failed bioprosthetic valves. At present, the SAPIEN valve has been implanted in failed aortic valves, mitral valves, tricuspid valves and even after failed mitral annuloplasty. These procedures pose a technical challenge in both sizing and positioning of the valve, especially in supra-annular prostheses. The caveats of these valve-in-valve (VIV) procedures are PPM, increased risk for coronary artery obstruction and device embolization. Dvir et al. presented the outcomes of 202 patients included in the global VIV registry [50]. Success rate was 93.1% in these procedures. Although no differences were noted in the outcome at 30 days, mean post-procedural gradients were higher in the SAPIEN group when VIV was performed in small bioprosthetic valves (