Transcatheter aortic valve implantation: current and future approaches. he first human transcatheter aortic valve implantation (TAVI) in 2002, and several subsequent single-center series, showed the feasibility of this new approach for the treatment of patients with severe aortic stenosis who were considered to be at very high or prohibitive surgical risk. More-recent multicenter registries have confirmed the safety and efficacy of this procedure, despite a very-high-risk patient profile. Moreover, the randomized, controlled PARTNER trial has confirmed both the superiority of TAVI over medical treatment in patients not considered to be candidates for standard surgical aortic valve replacement and the noninferiority of TAVI compared with surgical aortic valve replacement in high-risk patients. The hemodynamics of transcatheter valves are usually excellent, although residual paravalvular aortic regurgitation (usually trivial or mild) is frequent. Stroke, major vascular complications, and conduction disturbances leading to permanent pacemaker implantation remain among the most-concerning periprocedural complications of TAVI. Nevertheless, promising preliminary data exist for long-term outcomes following TAVI, ‘valve-in-valve’ TAVI for surgical prosthesis dysfunction, and for the treatment of lower-risk patients. Improvements in transcatheter valve technology, optimization of procedural and midterm results, and confirmation of long-term durability of transcatheter valve prostheses will determine the expansion of TAVI towards the treatment of a broader spectrum of patients
Quebec Heart and Lung Institute, Laval University, 2725 Chemin Ste-Foy, G1V 4G5 Quebec City, QC, Canada josep.rodes@ criucpq.ulaval.ca
Transcatheter aortic valve implantation: current and future approachesJosep Rodés-Cabau
Abstract | The first human transcatheter aortic valve implantation (TAVI) in 2002, and several subsequent single-center series, showed the feasibility of this new approach for the treatment of patients with severe aortic stenosis who were considered to be at very high or prohibitive surgical risk. More-recent multicenter registries have confirmed the safety and efficacy of this procedure, despite a very-high-risk patient profile. Moreover, the randomized, controlled PARTNER trial has confirmed both the superiority of TAVI over medical treatment in patients not considered to be candidates for standard surgical aortic valve replacement and the noninferiority of TAVI compared with surgical aortic valve replacement in high-risk patients. The hemodynamics of transcatheter valves are usually excellent, although residual paravalvular aortic regurgitation (usually trivial or mild) is frequent. Stroke, major vascular complications, and conduction disturbances leading to permanent pacemaker implantation remain among the most-concerning periprocedural complications of TAVI. Nevertheless, promising preliminary data exist for long-term outcomes following TAVI, ‘valve-in-valve’ TAVI for surgical prosthesis dysfunction, and for the treatment of lower-risk patients. Improvements in transcatheter valve technology, optimization of procedural and midterm results, and confirmation of long-term durability of transcatheter valve prostheses will determine the expansion of TAVI towards the treatment of a broader spectrum of patients.
Rodés-Cabau, J. Nat. Rev. Cardiol. 9, 15–29 (2012); published online 15 November 2011; doi:10.1038/nrcardio.2011.164
IntroductionFollowing experimental work in the transcatheter valve field in the 1990s,1,2 the first-in-human transcatheter aortic valve implantation (TAVI) was performed by Cribier and colleagues in 2002.3 This case was followed by several single-center and small multicenter registries and series that included nonoperable or very-high-risk patients, which were associated with promising results that confirmed the feasibility of TAVI.4–18 In more-recent years, the technology has developed very rapidly and, to date, more than 40,000 transcatheter valves have been implanted worldwide. The results of several large multi-center registries,19–26 and the prospective, randomized Placement of Aortic Transcatheter Valves (PARTNER) trial,27,28 have provided definitive data confirming this treatment as an alternative to standard surgical aortic valve replacement (SAVR) in nonoperable and high-risk surgical candidates. The objectives of this article are to review the main characteristics of transcatheter valves and TAVI procedures, and to evaluate the acute and late outcomes associated with TAVI.
Transcatheter prosthetic valvesTo date, two types of transcatheter aortic valves have been widely used in the clinical setting: the balloon-expandable Edwards valve—the first-generation
Cribier-Edwards, second-generation Edwards SAPIEN®, and third-generation Edwards SAPIEN XT® (Edwards Lifesciences Corporation, Irvine, CA, USA) versions —and the self-expandable CoreValve® (Medtronic CV Luxembourg S.a.r.l., Luxembourg) system.
Balloon-expandable Edwards valveThe first two generations of the Edwards valve (Cribier-Edwards and Edwards SAPIEN®) comprised three leaf-lets of bovine pericardium mounted in a stainless steel frame. The valves were implanted using 22 French and 24 French delivery catheters. The Edwards SAPIEN XT® (Figure 1a,b) is the third generation of the balloon-expandable Edwards valve, which consists of a trileaflet pericardial bovine valve mounted in a cobalt chromium frame. The frame design of the Edwards SAPIEN XT® also has fewer rows, columns, and vertical struts between com-missure posts than the SAPIEN® design. These changes have led to a reduction in the valve size, with no loss of radial strength. In addition, the scallop shape of the SAPIEN XT® leaflets reduces leaflet volume and improves valve profile. The SAPIEN XT® valve is available in 20 mm, 23 mm, 26 mm, and 29 mm sizes, and is implanted using 18 French (for the 20 mm and 23 mm valves), 19 French (for the 26 mm valve), or 22 French (for the 29 mm valve) delivery catheter and sheath systems. Smaller 16 French (for the 20 mm and 23 mm valves), 18 French (for the 26 mm valve), and 20 French (for the 29 mm valve) expandable sheaths (eSHEATH®, Edwards Lifesciences Corporation) are also available in Europe and Canada.
Competing interestsThe author declares associations with the following companies: Edwards Lifesciences and St Jude Medical. See the article online for full details of the relationships.
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Self-expandable CoreValve® systemThe first generation of the CoreValve® system consisted of a self-expanding nitinol frame with a bovine pericardial heart valve, and was implanted using a 25 French delivery catheter. The second generation of the CoreValve® system consisted of three leaflets of porcine pericardium seated higher in the nitinol frame to provide true supra-annular placement. The nitinol frame had been redesigned to
Key points
■ Transcatheter aortic valve implantation (TAVI) represents a less-invasive strategy than surgical aortic valve replacement (SAVR) for the treatment of severe symptomatic aortic stenosis
■ The transfemoral approach is usually the first option for TAVI; transapical, subclavian, axillary, and transaortic routes are alternative approaches
■ TAVI is currently the treatment of choice for patients not considered to be candidates for SAVR, and a proven alternative for those considered to be at high surgical risk
■ Transcatheter valves are associated with excellent hemodynamic results, usually with concomitant improvements in the patient’s functional status and quality of life; however, minor residual aortic regurgitation occurs in many patients
■ Periprocedural stroke, vascular and conduction disturbance complications, occurrence of moderate or severe paravalvular aortic regurgitation, relatively high midterm mortality, and valve durability beyond 3-year follow-up are unresolved issues in TAVI
■ The ‘valve-in-valve’ treatment of surgical prosthesis dysfunction and the treatment of intermediate-risk patients are two of the most-important fields for the development of TAVI in the near future
increase radial force in the inflow portion and expand the outflow diameter for a better anatomical fit. The valve was implanted using a 21 French delivery catheter. Finally, the current, third generation of the CoreValve® aortic system (Figure 1c,d) differs slightly from the previous version in the sealing skirt (fabricated from three separate pieces instead of one), to facilitate uniform tissue thickness and improve the valve profile. The valve is available in 26 mm, 29 mm, and 31 mm sizes, and is implanted using an 18 French delivery catheter and sheath system.
Pre-TAVI work-upThe work-up before TAVI using the Edwards or CoreValve® prostheses is summarized in Figure 2. Evaluation of the size (by CT angiography or iliofemoral angiography), tortu-osity, and degree of calcification (assessed by CT) of iliofe-moral arteries is mandatory to determine the suitability of the transfemoral approach.
The size of the aortic annulus is usually measured by transthoracic echocardiography, transesophageal echocardiography, CT angiography, or a combination of these imaging techniques. Accurate measurement of the aortic annulus is critical to determine the trans-catheter valve size, which is systematically oversized (by 2–5 mm) with respect to the diameter of the aortic annulus. Although sizing the aortic annulus with trans-esophageal echo cardiography has been associated with good clinical results in most cases, some studies have suggested a tendency towards an underestimation of the aortic annulus by echocardiography as compared with CT angio graphy.29–33 CT studies have clearly shown the oval shape of the aortic annulus in most patients, further highlighting the complexity of aortic annulus measure-ment. Indeed, CT angiography studies with 3D-imaging reconstruction also provide very accurate spatial and tem-poral resolution for the evaluation of the aortic annulus.33 Importantly, annulus measurements and valve oversizing have been mostly based on industry recommendations rather than on scientific evidence. Future studies will have to further evaluate the most-appropriate imaging modal-ity to measure the aortic annulus and determine the gold standard for aortic-annulus measure ments before TAVI as well as the most-appropriate degree of valve oversizing.
Coronary angiography is performed before the proce -dure to evaluate the presence and severity of coronary artery disease. In cases of severe stenoses in the main coro-nary vessels, complete or partial coronary revasculariza-tion is often performed before TAVI, although no data showing the superiority of this strategy compared with no revascularization exist.
Approaches used for TAVITransfemoral approachThe transfemoral route (Figure 3a) is the first choice of approach in the vast majority of centers performing TAVI procedures. As stated above, an accurate evalua-tion of the iliofemoral anatomy is of major importance in determining the appropriateness of this approach for each individual patient. The procedure is performed in a catheterization laboratory or a hybrid operating room.
a
c d
b
Figure 1 | Photographs of the transcatheter prosthetic valves currently used for transcatheter aortic valve implantation. a,b | The Edwards SAPIEN XT® (Edwards Lifesciences Corporation, Irvine, CA, USA) valve. c,d | The third generation of the CoreValve® (Medtronic CV Luxembourg S.a.r.l., Luxembourg) system (courtesy of Marc Ruel, Ottawa Heart Institute, Ottawa, ON, Canada).
Although surgical cut-down was the technique used for the transfemoral approach at the beginning of the TAVI experience, most centers are now using a fully percutane-ous technique for this approach. This strategy makes it possible to avoid the use of general anesthesia, especially if the procedure is performed without transesophageal echocardiographic guidance.
Transapical approachThe transapical approach (Figure 3b) was first reported as an alternative to the transfemoral approach in 2006 by Litchenstein and colleagues,7 who used the Cribier-Edwards valve system. The approach requires a small left lateral thoracotomy and a direct puncture of the left ventricular apex. A 24 French (for the 23 mm and 26 mm valves) or 26 French (for the 29 mm valve) sheath is used to advance the Edwards SAPIEN XT® valve, and implanta-tion is performed in a similar way to that used with the transfemoral approach (see the next section on valve placement). In the era when larger catheters (≥22 French) were used for the transfemoral approach, about half of the TAVI procedures with the Cribier-Edwards and Edwards SAPIEN® valves were performed using the transapical approach;19,20 this percentage is expected to decrease with the use of smaller (18 French) catheters. First-in-human CoreValve® implantation by the trans apical approach has been reported,34 but this approach has not been further developed for this valve system.
Potential advantages of the transapical approach include the avoidance of using large catheters though the iliofemoral system, aortic arch, ascending aorta, and aortic valve; improved coaxility of the valve pros-thesis within the aortic annulus, which can be especially helpful in cases of horizontal aorta;35 and the possibility of obtaining very accurate transesophageal echocardio-graphic images for valve positioning, which might lead to a reduction in the amount of contrast used during the procedures.35 The main disadvantages are the need for a thoracotomy; a greater degree of myocardial injury, owing to the apical perforation of the left ventricle;36 and the potentially life-threatening bleeding complications associated with the surgical repair of the apex.
Transaortic approachIn 2009 and 2010, the use of the transaortic approach through a small right or mid sternotomy (Figure 3c) was proposed as an alternative approach with the Corevalve® and Edwards systems.37–39 Although requiring sterno tomy, this approach avoids the use of large catheters through the iliofemoral system and aortic arch, and avoids puncture of the ventricular apex.
Subclavian approachThe left subclavian approach (Figure 3d) has emerged as an alternative to the transfemoral approach with the CoreValve® system.40,41 A surgical cut-down is needed to isolate the subclavian artery (usually the left vessel). The very short distance between the vascular access and the native aortic valve might be associated with better control of the CoreValve® prosthesis during positioning
and deployment. However, any injury of the subclavian artery would translate into a major intrathoracic bleed-ing that might be difficult to control. Tamburino et al.22 reported the use of the subclavian approach in up to 20% of the patients included in the Italian registry.
Transaxillary approachFirst-in-human CoreValve® implantation by the trans-axillary approach (Figure 3e) has been reported.42 Like the subclavian approach, a surgical cut-down is per-formed to isolate the left axillary artery, and the sheath and delivery catheters are advanced through the axillary artery. The potential advantage of this approach versus the subclavian approach is that any injury to the axillary artery could be easily repaired with no major clinical consequences, as compared with the potentially life-threatening consequences of a subclavian-artery injury. Indeed, and unlike in iliofemoral vessels, occlusion of the axillary artery would be compensated by the col-lateral circulation between the thyrocervical trunk of the subclavian artery and the subscapular artery.
Valve placementBalloon aortic valvuloplasty is systematically performed before valve implantation for both types of prosthetic valves currently used in TAVI, although Grube et al. have
Patients considered at very high risk or nonsurgical candidates
Evaluation by a TAVI multidisciplinary team(interventional cardiologists and cardiac surgeons)
Iliofemoral axis >6 mm (Edwards SAPIEN XT® 20 mm, 23 mm or CoreValve® 26 mm, 29 mm, 31 mm)Iliofemoral axis >6.5 mm (Edwards SAPIEN XT® 26 mm)Iliofemoral axis >7 mm (Edwards SAPIEN XT® 29 mm)Absence of signi�cant peripheral vascular diseaseAbsense of severe iliofemoral calci�cation
Surgical aorticvalve replacement
Medical treatment
Transfemoral approach using theEdwards SAPIEN XT® or CoreValve® systems
Transapical approach using theEdwards SAPIEN XT® system
Transaortic approach using theEdwards SAPIEN XT® or CoreValve® systems
Subclavian-axillary approach using theCoreValve® system with
axilo-subclavian axis >6 mmand/or >7 mm with patent LIMA graft
Patients eligble for TAVI
Yes No
or
or
Figure 2 | Pre-procedural work-up in patients with severe aortic stenosis who are candidates for a TAVI procedure with the Edwards SAPIEN XT® (Edwards Lifesciences Corporation, Irvine, CA, USA) valve or CoreValve® (Medtronic CV Luxembourg S.a.r.l., Luxembourg) systems. Abbreviations: CT, computed tomography; LIMA, left internal mammary artery; TAVI, transcatheter aortic valve implantation.
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suggested direct implantation of the CoreValve® system with no prior balloon valvuloplasty.43 The Edwards valve is positioned using fluoroscopy, angiography, and trans-esophageal echocardiography, and valve expansion is achieved by balloon inflation under rapid pacing (180–220 bpm) to minimize cardiac output and avoid valve embolization during valve implantation (Figure 4a,b). CoreValve® positioning is usually performed by fluoro-scopy and angiography, and the valve is deployed without rapid pacing, by retracting the outer sheath of the delivery catheter (Figure 4c–e).
Outcomes of the procedureFindings from the eight largest multicenter registries and series of TAVI published in the past few years are sum-marized in Table 1. The patients included in the multi-center registries were considered nonoperable or at very high surgical risk, with mean logistic EuroSCORE >20% and Society of Thoracic Surgeons (STS) score >8%.19–26 Most patients were octogenarians, about half of them had prior coronary artery disease, about one-third had chronic kidney disease, and about a quarter had chronic obstructive pulmonary disease or peripheral vascular disease. Overall, the procedural success rate was >90% in all studies. Valve embolization or conversion to open heart surgery occurred in ~1% of the patients (0.3–3.0% for valve embolization; 0.5–2.3% for conversion to open heart surgery).
The PARTNER trial is, to date, the only prospective, randomized trial on TAVI. The findings are summarized in Table 1. PARTNER included two differentiated cohorts of patients—those considered to be nonoperable (that is, comorbidities leading to a predicted risk of ≥50% of death by 30 days after surgery or a serious irreversible condi-tion; patients with comorbidities leading to a life expec-tancy <1 year were excluded)27 and those considered to be at high surgical risk (that is, predicted risk of opera-tive mortal ity ≥15% as determined by site surgeon and cardiologist; guideline of STS score ≥10).28 The Edwards SAPIEN® valve was used in all cases. The primary end point was all-cause mortality at 1-year follow-up, and the trial was powered to demonstrate the superiority of TAVI versus medical treatment (including balloon valvulo-plasty) for the nonoperable cohort and the noninferiority of TAVI versus SAVR for the high-surgical-risk cohort.
MortalityIn the aforementioned multicenter registries and series, mortality was systematically <10% in patients treated using the transfemoral approach and ranged from 11.3% to 16.9% in patients treated using the transapi-cal approach, probably owing to the higher risk profile of the patients treated via the latter route.19–26 At 1-year follow-up, the survival rates were ~80% (75–85%) for the transfemoral approach and ~70% (63–78%) for the transapical approach.
a c
d e
b
Figure 3 | Approaches used for transcatheter aortic valve implantation. a | The transfemoral approach. The delivery catheter for implantation of the valve prosthesis is advanced through the right or left femoral arteries. b | The transapical approach. After left lateral minithoracotomy (usually between the fifth and sixth intercostal spaces), the delivery catheter for implantation of the valve prosthesis is advanced through the left ventricular apex. c | The transaortic approach. After right or mid ministernotomy, the delivery catheter for implantation of the valve prosthesis is advanced directly through the ascending aorta. d | The subclavian approach. The delivery catheter for implantation of the valve prosthesis is advanced through the subclavian artery (usually the left vessel). e | The transaxillary approach. The delivery catheter for implantation of the valve prosthesis is advanced through the axillary artery (usually the left vessel).
In the nonoperable cohort of the PARTNER trial,27 the 30-day mortality was 5.0% in the TAVI group (trans-femoral approach in all patients) and 2.8% in the medical treatment group (P = 0.41). Importantly, up to 84% of the patients in the medical treatment group had at least one procedure of balloon aortic valvuloplasty during the study period. At 1-year follow-up, mortality was 30.7% in the TAVI group, compared with 50.7% in the medical treatment group (P <0.0001).
In the high-risk PARTNER trial cohort,28 30-day mortal-ity was 3.4% in the TAVI group, compared with 6.5% in the SAVR group (P = 0.07). Mortality at the 1-year follow-up was 24.2% and 26.8% in the TAVI and SAVR groups, respectively (P = 0.44). In patients eligible for the trans-femoral approach, mortality at the 30-day and 1-year follow-ups in the TAVI group were 3.3% and 22.2%, respec-tively, and 6.2% and 26.4% in the SAVR group (P = 0.13 for 30-day mortality, P = 0.29 for 1-year mortality). In patients ineligible for the transfemoral approach, mortality at the 30-day and 1-year follow-ups was 3.8% and 29%, respec-tively, in the TAVI group (using the transapical approach) and 7.0% and 27.9% in the SAVR group (P = 0.32 for 30-day mortality, P = 0.85 for 1-year mortality).
Very few data on the long-term results associated with TAVI procedures exist. Gurvitch et al. reported a survival rate of 51% at 3-year follow-up in 88 patients who had undergone TAVI with the balloon-expandable Cribier-Edwards or Edwards SAPIEN® valves.44 Among the patients who survived the TAVI procedure, the sur-vival rates were 74% and 61% at the 2-year and 3-year follow-ups, respectively. Buellesfeld et al. reported a survival rate of 72% at 2-year follow-up after TAVI with the CoreValve® system.45 The patients included in these studies represent the initial TAVI experience and the use of very early versions of the transcatheter valve and delivery catheter systems, which, together with the learning-curve phenome non, has probably had a negative influence on the results. Indeed, in the past few years, 1-year survival rates from some registries have been reported to be ≥80%,19–26 and we can expect better survival rates at the 2-year and 3-year follow-ups in the coming years. Importantly, no structural failures of the transcatheter valves have been seen in studies with a follow-up of more than 1 year.44,45
The baseline and procedural factors associated with poorer outcomes after TAVI are shown in Table 2. In summary, baseline cardiovascular factors (low left ventricular ejection fraction [LVEF], pulmonary hypertension, and severe mitral regurgitation) and peri-procedural complications (low cardiac output, major vascular complications, cardiac tamponade, conversion to open heart surgery, acute kidney injury, stroke, and moderate-to-severe residual aortic regurgitation) seem to have a major role in acute mortality and in mortality occurring during the 1-year follow-up period.19,22,26,46–51 Generally, noncardiac comorbidities, such as chronic obstructive pulmonary disease, chronic kidney disease, and liver disease, are important predictors of mortality during the follow-up period, rather than of acute mortal-ity.19,22,26,46–51 Indeed, studies have shown that most deaths occurring late after TAVI are of noncardiac origin,19,48,52
highlighting the importance of patient selection in the results of TAVI at midterm follow-up.
Surgical risk scores, such as logistic EuroSCORE and STS score, have been used to estimate the mortality risk of the patients undergoing SAVR and TAVI. Although the logistic EuroSCORE has been shown to be a predic-tor of 30-day and 1-year mortality in some studies of TAVI,48,53 this risk score seems to overestimate the risk of mortality in most cases.54–56 By contrast, the mortality risk as determined by the STS score seems to be close to the observed mortality in patients undergoing SAVR and TAVI,19,27,28,55 although no studies to date have found this score to be an accurate predictor of acute and midterm mortality after TAVI. In addition to baseline and proce-dural factors, the learning-curve phenomenon and the improvements in valve prosthesis and delivery catheters have also been associated with a substantial improvement in the results obtained with TAVI.57–59
Major periprocedural complicationsThe most-important complications associated with TAVI are summarized in Table 1. Notably, the defini-tion of major complications associated with TAVI has not been standardized, which might explain at least
a
c d e
b
Figure 4 | Valve implantation of balloon-expandable and self-expandable transcatheter valves. a | Deployment of a balloon-expandable Edwards SAPIEN XT® (Edwards Lifesciences Corporation, Irvine, CA, USA) valve. The white arrow indicates the balloon during maximal expansion. b | Fluoroscopic image of an Edwards SAPIEN XT® valve (white arrow) after valve implantation. c,d | Deployment of a self-expandable CoreValve® (Medtronic CV Luxembourg S.a.r.l., Luxembourg) system (courtesy of Marc Ruel, Ottawa Heart Institute, Ottawa, ON, Canada). The white arrows indicate the outer sheath that is being retracted to allow the expansion of the valve. e | Fluoroscopic image of a third-generation CoreValve® system (white arrow) after valve implantation (courtesy of Marc Ruel, Ottawa Heart Institute, Ottawa, ON, Canada).
Edwards Lifesciences Corporation (Irvine, CA, USA) is the manufacturer and registered trademark owner of the Cribier-Edwards, SAPIEN®, and SAPIEN XT® valves. Medtronic Inc. (Minnesota, MN, USA) manufactures the CoreValve®, which is a registered trademark of Medtronic CV Luxembourg S.a.r.l., Luxembourg. Abbreviations: IQR, interquartile range; N/A, data not available; SC, subclavian; TA, transapical; TAo, transaortic; TAVI, transcatheter aortic valve implantation; TF, transfemoral.
some of the variation in the complication rates observed among TAVI studies and preclude any meaningful com-parison between them. In early 2011, the Valve Academic
Research Consortium (VARC) proposed standardized consensus definitions for important clinical end points, including major complications in TAVI.60 This consensus
Table 2 | Factors predictive of 30-day and 1-year mortality after trancatheter aortic valve implantation
Predictive factor Study, n Mortality period OR or HR for mortality
95% CI
Baseline noncardiac variables
Chronic obstructive pulmonary disease Rodés-Cabau et al.,19 n = 339 Sinning et al.,47 n = 77 Moat et al.,26 n = 870
1 year 1 year 1 year
1.75 2.9 1.41
1.09–2.83 1.2–7.1 1.00–1.98
Chronic kidney disease Rodés-Cabau et al.,19 n = 339 Thomas et al.,48 n = 463 for TF Thomas et al.,48 n = 575 for TA Sinning et al.,47 n = 77 Tamburino et al.,22 n = 663
1 year 1 year 1 year 30 days 1 year 30 days to 1 year
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document represents an important step forward in provid ing consistency across studies and in contributing to a more-appropriate evaluation of TAVI technology. Another important consideration when reviewing the findings of TAVI studies is that, in all published multi-center TAVI registries and series, except SOURCE,20 data was captured without source verification, and no data-monitoring or event-adjudication committee was established for the validation of clinical events.
Major vascular complicationsThe use of large sheaths (18–24 French) in a very old (usually octogenarian) population has led to a high rate (>5% to 10% in most series) of major vascular complica-tions during TAVI procedures.4–28 Accurate evaluation of the iliofemoral arteries before the procedure (see Figure 2), and the use of alternatives to the transfemoral approach in borderline cases, seem to have a major role in avoiding such complications.61,62 The use of smaller catheters might also have a substantial impact on the rate of vascular complications (complication rate for the CoreValve® system: <5% with 18 French sheaths versus >20% with 24 French sheaths).16–18,21,22 Finally, appropriate vascular access with true anterior entry in a disease-free segment of the common femoral artery is also important. This access can be achieved using echocardio graphically guided Seldinger puncture, although this puncture tech-nique is used in only a few centers. Alternatively, puncture can be guided by advancing a catheter into the femoral artery via the contralateral site—a widespread practice, but one that does not appropriately depict a disease-free area of the femoral artery or guarantee a true anterior entry during the puncture of the artery.
Importantly, the occurrence of major vascular complica-tions has been shown to be an independent predictor of 30-day mortality.22,61 The TAVI team should be able to treat these complications rapidly and appropriately or have some back-up with experienced peripheral interventionalists or vascular surgeons.
In the past, surgical cut-down and vascular repair were used in most transfemoral TAVI cases performed with ≥22 French catheters, but most centers are now using percu taneous closure devices such as Prostar® or Perclose® (both Abbott Vascular Inc, Red City, CA, USA) in trans-femoral cases performed with 18 French catheters.63–66 Despite the promising preliminary results obtained with the use of these percutaneous closure devices, more data are needed to determine the safety and efficacy of these devices in patients undergoing TAVI procedures.
StrokeThe occurrence of cerebrovascular events is one of the most-worrisome complications of TAVI. The 30-day stroke rate was ~3.5% (ranging from 1.2% to 6.7%) in the multicenter registries and series and the PARTNER trial.19–28 In the high-risk cohort of the PARTNER trial, the stroke rate tended to be higher in the TAVI group than in the SAVR group at 30 days (4.6% versus 2.4%, P = 0.12) and at the 1-year follow-up (6.0% versus 3.2%, P = 0.08).28 The nonoperable cohort of the PARTNER trial also
showed a higher rate of stroke or transient ische mic attack at 30 days (6.7% versus 1.7%, P = 0.03) and at the 1-year follow-up (10.6% versus 4.5%, P = 0.04) among patients who underwent TAVI compared with those managed conservatively (including balloon aortic valvulo plasty in 84% of the patients).27 Also, MRI studies have shown an incidence of silent cerebral ischemic defects as high as 66–84% following TAVI, irrespective of the valve type and approach.67–69
Although transcranial Doppler studies have shown that cerebral emboli can occur at any time during the TAVI procedure, most occur during positioning and implantation of the valve prosthesis,70,71 indicating that the embolization of valve particles from the native calcified aortic valve leaflets might be an important mechanism for cerebral emboli associated with TAVI. This hypothesis could partially explain why clinical and MRI studies have failed to demonstrate any dif-ference in stroke rate between transfemoral and trans-apical procedures, despite the use of large catheters in the aortic arch and ascending aorta, and the retrograde crossing of the native aortic valve, being avoided in the transapical approach.
Nietlispach et al. showed the feasibility of using an embolic protection device (Embrella embolic deflec-tor system®, Edwards Lifesciences, Irvine, CA, USA) during TAVI,72 and future studies will have to evaluate the useful ness of this and other such devices, including those from SMT Medical Technologies (Herzliya, Israel) and Claret Medical (Santa-Rosa, CA, USA), in reducing cerebral embolic events during TAVI procedures.
However, data from the PARTNER trial27 showed that as much as half of the postprocedural (30-day) cerebro-vascular events occurred more than 24 h after the proce-dure, indicating that embolic mechanisms other than the use of catheters and native valve stretching might have a role in a substantial proportion of cases. A substudy of the PARTNER trial73 indicated that periprocedural cerebro-vascular events early after TAVI were associated with a smaller native aortic valve area, whereas those occurring late after the procedure were mostly related to a higher atherosclerotic burden. This finding supports the lack of correlation between TAVI and late neurologic events. The combination of clopidogrel and aspirin has been empiri-cally recommended as treatment after TAVI,19–28 but future studies will have to determine the optimal antithrombotic regimen after these procedures.
Coronary obstructionCoronary ostia obstruction (especially of the left main coronary artery) can occur following TAVI,74–79 but the global incidence of this life-threatening complica-tion is very low (<1%).5–28 This complication is related to the displacement of the native aortic leaflet towards the coronary ostia during valve prosthesis implantation, and the risk seems to be higher in patients with heavily calcified leaflets, especially in those with some degree of aortic sinus effacement, low aortic implantation of the coronary ostia, and long aortic valve leaflets. However, the low number of cases reported to date has precluded a
specific recommendation on the cut-off for the distance between the aortic annulus and the coronary ostia, size of the sinus of Valsalva, or amount of leaflet calcification that should contraindicate TAVI because of a prohibitive risk of coronary occlusion. In patients considered at risk for this complication (as evaluated by CT angio graphy during the work-up before TAVI), the use of aortic angio graphy during balloon valvuloplasty before valve implanta tion might be helpful in determining whether valve leaflet displacement would compromise the coronary flow after valve prosthesis implantation. Notably, several case reports have already shown the feasibility of perform-ing a coronary angioplasty through the struts of the transcatheter valve.74–79
Myocardial infarctionTAVI has been associated with a variable rate of myo-cardial infarction, ranging from 0% to 16.3%.4–28 This vari-ability is probably related to the lack of uniformity in the definition of periprocedural myocardial infarction among the various TAVI studies. The VARC definition for peri-procedural myocardial infarction is the occurrence of new symptoms or signs of ischemia associated with an eleva-tion of cardiac biomarkers (preferably creatine kinase MB) at least 10 times the upper normal limit or at least 5 times the upper normal limit with new pathological Q waves.60 However, one study has shown that some degree of myo-cardial injury occurs in most TAVI procedures, and a higher degree of myocardial injury was associated with a reduced LVEF recovery and increased cardiac mortality at midterm follow-up.36
Acute kidney injuryThe incidence of acute kidney injury, and the need for hemodialysis, after TAVI has ranged from 11.7% to 28%, and from 1.4% to 15.7%, respectively.46,47,53,80–82 In the high-risk cohort of the PARTNER trial,28 the need for renal replacement therapy was similar in the TAVI and SAVR groups at 30 days (2.9% and 3.0%, respectively) and at the 1-year follow-up (5.4% and 6.5%, respectively). Chronic kidney disease is a common comorbidity (preva-lence 30–50%) in patients undergoing TAVI,18–27 and increasing degrees of preprocedural renal dysfunction are associated with an increasing rate of postprocedural acute kidney injury.81,82 In addition, periprocedural blood trans-fusion has been recognized as a major predictive factor
of post-TAVI acute kidney injury,46,53,80,82 highlighting the need to avoid unnecessary transfusions in such cases. Importantly, the occurrence of acute kidney injury has been associated with worse acute and midterm outcomes after TAVI.46,47,53,80–82
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0 –
– 2.4
– 2.0
– 1.6
– 1.2
– 0.8
– 0.4
– 0.0
Baseline
47 ± 17 1.61 ± 0.40*1.50 ± 0.36*
* P <0.05 versus baseline
10 ± 4* 10 ± 4*
0.60 ± 0.14
Discharge
Mea
n gr
adie
nt (m
mH
g)
Aortic valve area (cm2)
1-year follow-up
P = 0.007(TAVI vs SAVR-ST and SAVR-SL) P = NS
60 –
50 –
40 –
30 –
20 –
10 –
0 –
16–18(n = 18)
0
33
50
9
32
27
6
46
26
2212
38
42
8
13
31
6
0 0 0
19–20(n = 66)
Patie
nts
with
sev
ere
PPM
(%
)
100 –
80 –
60 –
40 –
20 –
0 –
At discharge At 1-year follow-up
Patie
nts
with
aor
tic r
egur
gita
tion
(%)
21–22(n = 48)
Annulus size (mm)
23–25(n = 18)
TAVI
SAVR-ST
SAVR-SL
Moderate
Mild
Trivial
None
a
c
b
NSFigure 5 | Valve hemodynamics following TAVI with the balloon-expandable Cribier–Edwards and Edwards SAPIEN® (Edwards Lifesciences Corporation, Irvine, CA, USA) valve (on the basis of the work of Clavel et al.95). a | Mean gradient and aortic valve area after TAVI (at hospital discharge and at 1-year follow-up). b | Incidence of severe PPM according to aortic annulus size following TAVI, SAVR-ST, and SAVR-SL. c | Residual aortic regurgitation following TAVI (at hospital discharge and at 1-year follow-up). Abbreviations: NS, not significant; PPM, prosthesis–patient mismatch; SAVR-SL, surgical aortic valve replacement with stentless surgical valves; SAVR-ST, surgical aortic valve replacement with stented surgical valves; TAVI, transcatheter aortic valve implantation.
24 | JANUARY 2012 | VOLUME 9 www.nature.com/nrcardio
Intraventricular conduction abnormalitiesNew-onset intraventricular conduction disturbances, parti cularly new left bundle branch block, occur frequently after TAVI (7–18% with the balloon- expandable Edwards valves, 30–83% with the self- expandable CoreValve®).83–91 Direct mechanical injury of the left bundle branch and inflammation created by the stent containing the valve prosthesis are potential mechanisms for these conduc-tion disturbances. Interestingly, Nuis et al. have reported that about half of these conduction disturbances occur during balloon valvuloplasty before valve implanta-tion.89 Unsurprisingly, the presence of a prior right bundle branch block seems to be an important predictor of complete atrioventricular block and need for pace-maker implantation after TAVI.88,91–94 Among proce-dural variables, the use of the CoreValve® system and a deeper (ventricular) implantation of the valve prosthe-sis are the two most-important factors determining the occurrence of conduction disturbances and the need for pacemaker implantation.23,25,26,84,86,88,90,91 CoreValve® implantation is associated with a need for permanent pacemaker in ~20% of patients (systematically >9% to 10%, but up to ~40% in some series) compared with in ~5% of patients implanted with the Edwards valves (almost systematically <7%).19–28,84–94 The nitinol frame of the CoreValve® might produce a higher pressure on the ventricular septum as compared to the stainless steel or cobalt chromium frame of the Edwards valves, leading to an increased risk of damag ing the left bundle branch. Also, a higher rate of deeper implantation of the CoreValve® system (>5 mm from aortic annulus) might partially explain the differences between the two devices. In the PARTNER trial,27,28 the rate of permanent pacemaker implantation after TAVI with the balloon- expandable Edwards SAPIEN® valve was 3.4% and 3.8% in the non-operable and high-risk cohorts, respectively, with no dif-ferences compared with the medical treatment (5.0%) and SAVR (3.6%) groups. Further studies are needed to better determine the predictive factors of complete
50 –
45 –
40 –
35 –
30 –
0 –
Baseline
∆ = 14 ± 15%
∆ = 7 ± 11%
TAVI (n = 41)
SAVR (n = 120)
*‡§
‡*‡
Discharge
LVEF
(%
)
At 1-year follow-up
Figure 6 | Changes in LVEF after TAVI and SAVR in patients with severe aortic stenosis and low LVEF (on the basis of the work of Clavel et al.101). *Different from SAVR (P <0.05). ‡Different from baseline (P <0.05). §Different from discharge (P <0.05). Abbreviations: LVEF, left ventricular ejection fraction; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation.
atrioventricular block and pacemaker implantation following TAVI. These studies should lead to the implemen tation of preventive measures of this frequent and important post-TAVI complication.
Hemodynamics of transcatheter valvesDespite transcatheter valves being expanded within severely calcified native aortic valves that are left in place, the hemodynamic results after TAVI are excel-lent, with mean residual gradients <15 mmHg and aortic valve areas >1.5 cm2.3–28 Importantly, these hemodynamic results seem to be maintained at midterm follow-up. Also, Clavel et al. demonstrated that the hemodynamic results associated with TAVI (using the Cribier-Edwards and Edwards SAPIEN® valves) were superior to those obtained with stented and stentless surgical biopros-theses, especially in patients with small (<20 mm) aortic annulus95 (Figure 5). In accordance with these results, Smith et al. showed the superior hemodynamics of trans-catheter valves compared with surgical valves in the high-risk cohort of the prospective, randomized PARTNER trial.28 These good hemodynamic results might parti-ally be explained by the systematic oversizing of the trans catheter valves with respect to the aortic annulus, although some experi mental and CT studies have sug-gested that the frame of the transcatheter valve adapts to the dimension of the aortic annulus,96,97 and the final aortic valve area after TAVI has been shown to be mainly determined by the size of the aortic annulus as evaluated by echocardiography.98 Also—and possibly most relevant for patients with small aortic annulus—the stent of trans-catheter valves is much thinner than that of the stented valves used for SAVR, which results in minimal obstruc-tion to blood flow. In 2011, Kalavrouziotis et al. con-firmed the outstanding results of TAVI with the 23 mm balloon-expandable Edwards SAPIEN® valve in a series of 34 consecutive patients with small (<20 mm, mean 18.5 mm) aortic annulus, with a mean residual gradient of <12 mmHg and an incidence of severe prosthesis–patient mismatch as low as 5.9%.99 The improvement in valve hemo dynamics associated with TAVI translates into a significant improvement in LVEF, especially in patients with low LVEF.6,95,100,101 Indeed, Clavel et al. showed that the ventricular function of most patients with low (<50%) LVEF undergoing TAVI had normalized at 1-year follow-up;101 this finding compared favorably with those patients with low LVEF undergoing SAVR (Figure 6).
However, although trivial or mild in most cases and moderate or moderate-to-severe in ~10% (5–17%) of patients, the incidence of TAVI-associated prosthetic regurgitation (mostly paravalvular) is very high (65–89%).3–28,51,95 In the high-risk cohort of the PARTNER trial,28 some degree of paravalvular aortic regurgitation occurred in 77% (12% moderate or severe) of patients in the TAVI group compared with 26% (0.9% moder-ate or severe) in the SAVR group (P <0.001). Several studies have shown that the degree of paravalvular and transvalvular residual aortic regurgitation remains stable at midterm (1-year) follow-up,14,27,28,95 but studies with a longer follow-up are needed to further evaluate
the progression and potential clinical impact of these residual leaks. Notably, the presence of moderate or severe residual aortic regurgitation has been identified as an independent predictor of acute and late mortality following TAVI.22,26,51
Several factors have been associated with the occur-rence of moderate or severe aortic regurgitation. Valve malpositioning (too aortic or too ventricular) might be the reason for moderate-to-severe residual paravalvular aortic regurgitation, and this can be treated with the implanta-tion of a second valve (valve-in-valve procedure).102,103 Also, CoreValve® malpositioning (low implantation) can sometimes be corrected by snaring and repositioning the valve.104 A high degree of calcification of the native aortic valve, a large aortic annulus, a small valve area, and a high angle between the ascending aorta and the left ventri-cular outflow tract, have also been associated with an increased rate of moderate-to-severe paravalvular aortic regurgitation.51,105–107 Some studies have also suggested that echocardiography might undersize aortic-annulus measure ments, as compared with CT, and this undersiz-ing could be associated with an increased degree of para-valvular leak because of the selection of an undersized valve prosthesis.29–32,51 In addition to providing more infor-mation about the predictive factors of significant residual aortic regurgitation, further research is needed to improve transcatheter valve technology to further reduce the incidence and severity of paravalvular leaks.
Functional class and quality of lifeImprovements in the NYHA functional class follow-ing TAVI have systematically been reported.3–28 Most patients are in NYHA class III before the procedure and
improve to NYHA class I or II at midterm follow-up. Exercise capacity, as evaluated by the 6-min walk test, has also been shown to increase after TAVI.108,109 Several studies have determined the effect of TAVI on quality of life using the Short Form (SF)-12, SF-36, Kansas City Cardiomyopathy, EuroQuol-5D, and Duke Activity Status Index questionnaires, and all showed TAVI-associated improvement in quality of life at 6–12 months after implantation.110–116 However, some studies have indicated a lack of improvement in quality of life, func-tional status, or both in a substantial proportion of patients (20–30%) after TAVI,13,112,117 in part related to comorbidities such as severe mitral regurgitation and chronic kidney disease.112,117 Future studies will have to continue evaluating the benefits of TAVI for both func-tional status and quality of life and further identifying the patients with aortic stenosis who might not benefit from this treatment (‘survival without improvement’) owing to an excessive comorbidity burden.
Looking to the futureLower-risk patientsThe rapid and substantial improvements in TAVI techno logy and the increasing treatment-center experi-ence in the past few years, the results obtained in multi-center registries and, more importantly, the results from the high-risk cohort of the PARTNER trial have provided the basis for evaluating whether TAVI should be used for the treatment of a lower-risk population with aortic stenosis. Indeed, some preliminary results of TAVI in intermediate- risk patients with severe aortic stenosis have been promising.118 Two TAVI studies on intermediate- risk patients are planned in the near future.
Table 3 | Main characteristics of emerging transcatheter valves
Valve type Valve material
Stent material
Valve size (mm)
Delivery catheter size (French)
Approach Mechanism of expansion
Reposition-able?
Year of first-in-human study
Direct Flow Medical® (Direct Flow Medical, Santa Rosa, CA, USA)126,127
Bovine pericardium
No stent (polyester fabric cuff)
23, 25 18 Transfemoral or subclavian
Inflation of ring balloons by a polymer
Yes 2006
Heart Leaflet Technologies (Heart Leaflet Technologies, Maple Grove, MN, USA)
Porcine pericardium
Nitinol 21, 23 18 Transfemoral Self-expandable
Yes 2009
Innovare (Braile Biomedical, São José do Rio Preto, Brazil)128,129
Bovine pericardium
Stainless steel
20, 22, 24, 26, 28
20 (for 20, 22, & 24 mm valves); 22 (for 26 & 28 mm valves)
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For cohort A of the PARTNER II trial,119 investigators will randomly assign patients with aortic stenosis and STS score of 4–8% (that is, intermediate risk), or specific qualifying intermediate risk criteria requiring formal petition to the executive committee heart-valve team (which will include cardiac surgeons and interventional cardiologists), to TAVI or SAVR. Patients with con-comitant coronary artery disease will be substratified to percutaneous coronary intervention plus TAVI versus CABG surgery plus SAVR. The estimated sample size is 1,500–2,000 patients, and ~50 US centers are expected to participate. The Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial120 will include elderly (≥70 years) patients with aortic stenosis and an STS score of 3–8%. Approximately 1,200 patients will be randomly assigned to TAVI or SAVR, and ~40 European centers are expected to participate. In addi-tion, a randomized study comparing TAVI and SAVR in Danish patients ≥70 years of age, irrespective of their expected surgical risk, is presently ongoing.121 The results of these randomized trials should determine the exact role of TAVI for the treatment of intermediate-risk patients with severe aortic stenosis.
Treatment of surgical prosthesis dysfunctionA high number of patients undergoing SAVR require reintervention as a result of the limited durability of surgical bioprosthesis. Several reports have shown the feasibility of TAVI for the treatment of surgical biopros-thesis dysfunction, including of stented and stentless
valves, which opens up a new avenue for the treatment of this challenging group of patients.122–125 However, larger studies are needed to prove the safety and good clinical outcomes associated with this ‘valve-in-valve’ strategy in all of the different types of surgical valve prostheses.
Emerging transcatheter valve technologyVarious transcatheter valves are being developed. The main characteristics of the new transcatheter valves with first-in-human data are summarized in Table 3 and Figure 7.
ConclusionsTAVI represents a less-invasive strategy than SAVR for the treatment of severe symptomatic aortic stenosis. TAVI is currently the treatment of choice for patients considered not to be candidates for SAVR and is a proven alternative for those considered to be at high surgical risk. Despite the good acute and midterm clinical results obtained in large multicenter series and registries and the random-ized, controlled PARTNER trial, efforts should be made to improve patient selection and reduce peri procedural complications such as stroke, major vascular complica-tions, and the need for permanent pacemaker implanta-tion. Importantly, TAVI should be performed in centers with highly experienced interventional and surgical teams. Also, a close collaboration between inter ventional cardiologists and cardiac surgeons (the so-called ‘heart team’) as well as careful training of the team seem to have a major role in achieving a successful TAVI program.
Transcatheter valve hemo dynamics are excellent, and even superior to those achieved with surgically implanted valves, but residual paravalvular aortic regurgita tion (moderate in 5–17% of cases) remains an issue that should be addressed in the near future. Preliminary data on long-term outcomes, valve-in-valve procedures for the treatment of surgical valve dysfunction, and the treatment of lower-risk patients have been promising, but further studies are needed to confirm these results. These studies might result in the expansion of TAVI to the treat-ment of a much broader spectrum of patients with severe aortic stenosis.
Review criteria
The MEDLINE and PubMed databases were searched for primary research articles focusing on transcatheter aortic valve implantation published between 1990 and 2011. The search terms used were “transcatheter aortic valve implantation/replacement”, “percutaneous aortic valve implantation/replacement”, “transfemoral aortic valve implantation/replacement”, “transapical aortic valve implantation/replacement”, alone and in combination. All papers identified were English-language full-text papers. We also searched the reference lists of identified articles for further relevant papers.
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AcknowledgmentsThe author wishes to thank Mélanie Côté, MSc, (Quebec Heart and Lung Institute, Quebec City, QC, Canada) for her outstanding work in the preparation of tables and figures.
