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REVIEW TOPIC OF THE WEEK

Aortic Bioprosthetic Valve DurabilityIncidence, Mechanisms, Predictors, and Management ofSurgical and Transcatheter Valve Degeneration

Tania Rodriguez-Gabella, MD, Pierre Voisine, MD, Rishi Puri, MBBS, PHD, Philippe Pibarot, DVM, PHD,Josep Rodés-Cabau, MD

ABSTRACT

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rec

da

fro

ten

Ma

In recent times, there has been a considerable increase in the use of aortic bioprostheses (vs. mechanical prostheses)

for treating aortic valve disease, and this tendency is likely to continue in the near future. However, the occurrence of

structural valve degeneration, limiting valve durability, remains an important drawback of surgical and transcatheter

bioprostheses. In this paper, we provide an overview of bioprosthetic valve durability, focusing on the definition,

incidence, mechanisms, predictive factors, and management of structural degeneration of aortic bioprostheses.

(J Am Coll Cardiol 2017;70:1013–28) © 2017 by the American College of Cardiology Foundation.

M ore than 200,000 surgical aortic valvereplacements (SAVRs) are performedyearly worldwide (1,2). This treatment

has significantly evolved over the last 15 years, witha considerable increase in the use of aortic bio-prostheses relative to mechanical prostheses (1).This trend may be explained by the aging targetpopulation, the quest to avoid systemic anticoagula-tion treatment post-valve replacement, and theimproved hemodynamic performance of aortic bio-prostheses. According to the 2017 focused update ofthe American College of Cardiology (ACC)/AmericanHeart Association (AHA) guidelines, it is reasonable(Class IIa): 1) to select a bioprosthesis in patients>70 years of age; and 2) to individualize the choiceof either a bioprosthesis or a mechanical valve onthe basis of patient age (50 to 70 years) or otherpatient-related factors and preferences (3). In paral-lel, transcatheter aortic valve replacement (TAVR)has emerged as a valid option for patients with

m the Department of Cardiology and Cardiac Surgery, Québec Heart & Lu

nada. Dr. Tania Rodriguez-Gabella has been supported by a grant from the

eived research grants from Edwards Lifesciences and Medtronic. Dr. Rod

tion Famille Jacques Larivière” for the Development of Structural Heart Dis

m Edwards Lifesciences and Medtronic. All other authors have reported

ts of this paper to disclose. Patrick T. O’Gara, MD, served as Guest Edito

nuscript received June 5, 2017; revised manuscript received June 25, 201

severe aortic stenosis who are at intermediate tohigh/prohibitive surgical risk (4–6), and multipletrials are currently evaluating TAVR for treatingpatients who are at low surgical risk. All transcathetervalves are bioprosthetic valves, and the arrival ofTAVR, coupled with the growing field of valve-in-valve procedures in the case of valve dysfunction(7), has further stimulated the increased use of surgi-cal aortic bioprostheses in younger patients. How-ever, the treatment of younger patients with longerlife expectancies has raised questions regarding valvedurability. The overriding aim of aortic valve replace-ment therapy is to offer an effective and durablesolution for aortic valve disease, and valve durabilityshould ideally be longer than the patient’s life expec-tancy. The biological tissue from both surgical andtranscatheter bioprostheses is prone to structuralvalve degeneration (SVD), a multifactorial processmediated by calcification of the connective tissue,leading to valve dysfunction (stenosis and/or wear

ng Institute, Laval University, Québec City, Québec,

Fundacion Alfonso Martin Escudero. Dr. Pibarot has

és-Cabau holds the Canadian Research Chair “Fon-

ease Interventions; and has received research grants

that they have no relationships relevant to the con-

r for this paper.

7, accepted July 6, 2017.

ABBR EV I A T I ON S

AND ACRONYMS

AR = aortic regurgitation

EOA = effective orifice area

SAVR = surgical aortic valve

replacement

SVD = structural valve

degeneration

TAVR = transcatheter aortic

valve replacement

TEE = transesophageal

echocardiography

TTE = transthoracic

echocardiography

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and tear) that mitigates valve durability.Valve durability has therefore emerged as afundamental issue in the current era of aorticvalve replacement. The objectives of thisreview are to summarize the available dataon the durability of aortic bioprostheses(surgical and transcatheter); review the defi-nitions, incidence, timing, and mechanismsof SVD; and evaluate the current treatmentoptions for valve failure due to SVD.

BIOPROSTHETIC VALVES

Biological surgical valves include homo-grafts, pulmonary autografts, and porcine

(assembled aortic valve leaflets or complete aorticvalves) or pericardial bovine bioprostheses. Bio-prosthetic valves can be divided into stented orstentless types. Stented valves are composed ofvalve leaflets reinforced with a stent frame, whichis composed of polymeric material or alloys, and acircular or scallop-shaped external sewing ringlocated outside of the stent frame (7). The sewing ringis placed at the bottom of the stent frame in supra-annular designs, or 3 to 5 mm above the bottom ofthe stent frame in intra-annular designs (8). Stentlessvalves have neither a stent frame that supportsvalve leaflets nor a base ring. They are sutured usingdifferent surgical techniques, such as the sub-coronary technique, full-root replacement, or mini-root replacement. Stentless valves are designed toprovide a larger orifice area to achieve a more physi-ological flow pattern and improve hemodynamicperformance (9). However, some studies have ques-tioned their theoretical hemodynamic advantage, andthe expected longevity benefit remains controversial(10–12). More recently, sutureless and rapid deploy-ment valves have emerged as an option to reducecardiopulmonary bypass times and facilitate mini-mally invasive approaches (13). These valves seemalso especially suitable for patients with small aorticannuli to optimize hemodynamic results. Suturelessand rapid-deployment aortic valves are biological,non–hand-sewn, pericardial prostheses that anchorwithin the aortic annulus with no more than 3sutures. Finally, transcatheter valves represent asignificant proportion of the aortic bioprosthesescurrently implanted.

The most common transcatheter aortic valvesimplanted to date have been the balloon-expandableEdwards valves (Sapien, Sapien XT, and Sapien 3;Edwards Lifesciences, Irvine, California), and theself-expandable CoreValve system (CoreValve,Evolut R, and Evolut Pro; Medtronic, Minneapolis,

Minnesota). The Sapien XT and Sapien 3 valvesconsist of 3 bovine pericardial leaflets sutured to acobalt chromium stent frame, and the CoreValve/Evolut R/Evolut Pro systems are made of 3 leafletsof porcine pericardium sutured, in a supra-annularposition, within a self-expanding nitinol stentframe. Multiple new self-expanding valve systemsmade from bovine pericardial or porcine leafletshave recently emerged in the TAVR arena. Figure 1shows the main surgical and transcatheter aorticbioprostheses.

DIAGNOSIS AND DEFINITION OF SVD

SVD is a gradual process ultimately leading to valvedysfunction secondary to stenosis (40%), regurgita-tion (30%), or a combination of stenosis and regurgi-tation (30%) (14). Historically, most surgical studieshave associated SVD with the need for reoperation,but did not provide any specific criteria to define SVDand/or the indication for reoperation. Given thatreoperation does not necessary imply SVD, and viceversa, one would expect a systematic underestima-tion of the true incidence of SVD if it is solely definedon the basis of reoperation. This is especially true inelderly patients with SVD, who often are refused redosurgery because of their high or prohibitive surgicalrisk profile (15). Hence, a systematic assessment ofprosthetic valve morphology and function by Dopplerechocardiography may more accurately portray thereal prevalence of SVD.

Despite the considerable experience reportedwith different types of surgical bioprostheses, there isno unified definition of SVD to date. In the surgicalfield, Sénage et al. (15) were among the first to pro-pose a definition for bioprosthetic SVD according toechocardiographic criteria. This included a progres-sion of the transprosthetic aortic gradient, leading toa mean gradient $30 mm Hg associated with aneffective orifice area (EOA) reduced to #1 cm2, orintraprosthetic aortic regurgitation (AR) grade $3.Similarly, Bourguignon et al. (16) defined SVD ofsurgical aortic bioprostheses as severe aortic stenosis(mean transvalvular gradient >40 mm Hg) or severeAR (effective regurgitant orifice area >0.30 cm2, venacontracta >0.60 cm). Mahjoub et al. (17) proposed toidentify SVD based on an increase in mean trans-prosthetic gradient $20 mm Hg with a concomitantdecrease in EOA and/or a progression of intra-prosthetic regurgitation by at least 1 grade.

In the TAVR field, Dvir (18) defined SVD as at leastmoderate regurgitation and/or mean transvalvulargradient $20 mm Hg that was not present in the first30 days post-intervention and was not related to

FIGURE 1 Main Surgical and Transcatheter Aortic Bioprostheses

AllograftsCadaveric aortic valve

Stented

PorcineCE SAV

Medtronic Hancock IIMedtronic Mosaic

Abbott BiocorAbbott Epic

Stentless Sutureless

Transcatheter heart valves

First generationiterations

Edwards SAPIENEdwards SAPIEN XTMedtronic CoreValve

Newer generationDevices

Edwards SAPIEN 3Medtronic CoreValve Evolut R

Medtronic CoreValve Evolut ProBoston Scientific Lotus

Abbott PorticoBoston Scientific ACURATE neo

Edwards CenteraJenaValve

PericardialCE PERIMOUNT lineSorin Mitroflow PRT

Abbott TrifectaAvalus Medtronic

PorcineAbbott Toronto SPVMedtronic Freestyle

PericardialSorin Solo Smart

SuturelessEdwards INTUITY Elite

Sorin Perceval S

Bioprosthetic heartvalves

AutograftsRoss procedure

XenograftsHuman tissue valves

B

A

(A) The general classification of bioprosthetic valves. (B) The various types of surgical and transcatheter heart valves. Adapted with

permission from Puri et al. (31).

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TABLE 1 Definitions for Structural Valve Degeneration

Definitions Used for SVD

Reoperation for structural valve failure

Mean transvalvular gradient $30 mm Hg associated with a reducedEOA #1 cm2 or intraprosthetic aortic regurgitation grade $3.

Mean transvalvular gradient>40mm Hg or severe aortic regurgitation(effective regurgitant orifice area >0.30 cm2, vena contracta>0.60 cm)

Mean transvalvular gradient $20 mm Hg not present in the first30 days post-intervention, and/or moderate/severe aorticregurgitation

Increase in the mean gradient $10 mm Hg during follow-up, leadingto a mean transvalvular gradient >20 mm Hg and/or aorticregurgitation grade $3 not present at the 30-day echocardiogram

Proposed Definition

Possible SVD: Increase in the mean transvalvular gradient by>10 mm Hg with concomitant decrease in EOA by >0.3 cm2

(and/or decrease in Doppler velocity index >0.08) not leading tosevere aortic stenosis according to current guidelines, and/or newonset of at least mild intraprosthetic regurgitation or increase by atleast 1 grade of pre-existent intraprosthetic regurgitationcompared with baseline echocardiographic assessment performed1–3 months post-intervention, resulting in a regurgitationgrade # moderate.

Clinically-relevant SVD: Increase in mean transvalvular gradient by>20 mm Hg with concomitant decrease in EOA by >0.6 cm2

(and/or decrease in Doppler velocity index >0.15) duringfollow-up, leading to severe aortic stenosis according to currentguidelines, and/or new onset of or increase by at least 1 gradeof intraprosthetic regurgitation leading to moderate-to-severeor severe aortic regurgitation.

EOA ¼ effective orifice area.

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endocarditis. According to this definition, approx-imatively 50% of transcatheter valves had SVD within8 years after implantation. This definition generatedcontroversy, raising several questions regarding itsaccuracy and validation. Of note, this definitiondid not account for the dynamic process of SVD andfailed to address hemodynamic changes over time.Eltchaninoff (19) defined SVD by taking into accounthemodynamic changes over time, and suggested amean transvalvular gradient >20 mm Hg in combi-nation with an increase of at least 10 mm Hg from the30-day echocardiography and/or AR grade $3(moderately severe/severe) that was not present atthe 30-day follow-up. The Valve Academic ResearchConsortium-2 (20) recommendations suggest consid-eration of valve dysfunction at follow-up if there is anincrease in the mean gradient >10 mm Hg, a decreasein the EOA >0.3 to 0.4 cm2, or a reduction in thedimensionless velocity index >0.1 to 0.13 from theechocardiography performed within 30 days post-TAVR.

The recent European Association of CardiovascularImaging guidelines suggest defining SVD usingthe following criteria: 1) an increase in meangradient $10 mm Hg (possible SVD) or $20 mm Hg

(significant SVD) during follow-up, with a concomi-tant decrease in EOA and abnormal valve leafletmorphology and mobility; and/or 2) new onset orworsening of transprosthetic regurgitation (21).

The list of definitions proposed for SVD to dateis summarized in Table 1. As previously described,there is an important variability in the definition ofSVD, with a universal definition for SVD still lacking.Considering that SVD is usually a progressive processwith gradual changes in hemodynamic valve perfor-mance and severity of SVD over time, we suggestan alternative definition for: 1) possible SVD that isoften subclinical; and 2) clinically-relevant SVD.Subclinical changes at echocardiography should alertclinicians of possible structural changes within thebioprosthesis warranting additional imaging testsand closer follow-up. This approach is particularlyimportant, considering that the time period betweensubclinical and clinically-relevant SVD remainslargely unknown. The definition for possible (sub-clinical) SVD would be based on echocardiographycriteria as follows: 1) an increase in mean trans-valvular gradient of >10 mm Hg with a concomitantdecrease in EOA >0.3 cm2 (and/or decrease in Dopplervelocity index >0.08), and/or new onset of at leastmild intraprosthetic regurgitation or increase by atleast 1 grade of pre-existent intraprosthetic regurgi-tation compared with baseline echocardiographicassessment performed 1 to 3 months post-intervention, with the resulting regurgitationgrade # moderate; and 2) changes in morphology(thickening, calcification, flail, pannus) and/ormobility (reduced, avulsed) of the bioprosthetic valveleaflets when compared with the baseline assessmentobtained in the echocardiography performed at 1 to3 months post-intervention. Clinically-relevant SVDwould be defined as an increase in mean trans-valvular gradient >20 mm Hg with a concomitantdecrease in the EOA >0.6 cm2 (and/or decrease inDoppler velocity index >0.15), leading to severe aorticstenosis according to current guidelines (22,23),and/or new occurrence or increase of at least 1 gradeof intraprosthetic AR leading to moderate-to-severeor severe AR. The diagnosis of clinically relevantSVD may be individualized in borderline cases and inpatients with other specific hemodynamic conditions,such as severe prosthesis-patient mismatch or low-flow, low-gradient aortic stenosis. In these situa-tions, the identification of abnormalities of valveleaflet morphology and motion becomes crucial fordifferential diagnosis and confirmation of SVD. Also,the need for a post-operative baseline echocardiog-raphy to define SVD underlies the limitation of thepotential difficulties in obtaining baseline

FIGURE 2 Examples of Bioprosthetic Degeneration

(A) Bioprosthetic porcine valve. Bulky calcifications nodules on the leaflets surface leading to severe aortic stenosis. (B) Bioprosthetic

pericardial valve. Excessive pannus overgrowth, with a fibrotic reaction encasing the sewing ring sutures. Adapted with permission from

Thoracic Key (89).

J A C C V O L . 7 0 , N O . 8 , 2 0 1 7 Rodriguez-Gabella et al.A U G U S T 2 2 , 2 0 1 7 : 1 0 1 3 – 2 8 Bioprosthetic Valve Durability

1017

echocardiographic data. In such cases, clinical judg-ment and case-by-case evaluation with an accurateassessment of valve leaflet morphology and motionare key to confirm SVD.

With respect to the diagnosis of SVD, transthoracicechocardiography (TTE) is the standard examinationto evaluate prosthetic valve structure and function.The AHA/ACC guidelines recommend an initialTTE study for evaluation of valve hemodynamicsfollowing prosthetic valve implantation (23), and theEuropean Society of Cardiology guidelines recom-mend a baseline assessment at 6 to 12 weeks post-surgery (22). At follow-up, the guidelines suggestTTE in the present of a change in clinical symptoms orsigns suggesting valve dysfunction, whereas annualTTE is only recommend after the first 5 or 10 years inthe European Society of Cardiology and AHA/ACCguidelines, respectively. Following these recommen-dations, subclinical changes in hemodynamic valveperformance may go largely unnoticed. RegardingTAVR, recommendations are much more stringentand suggest an echocardiogram during the first30 days post-TAVR, followed by a second assessmentat the 1-year follow-up and annually thereafter (24).It could therefore be deduced that, with currentguideline recommendations, the sensitivity fordetecting changes in valve hemodynamics overtime would be higher for TAVR than for SAVR,particularly with regard to subclinical changes asso-ciated with early SVD. Efforts should be made tostandardize guideline recommendations for all types(surgical and transcatheter) of bioprostheses. We

suggest that at least 1 TTE examination shouldbe repeated between the 1- and 5-year follow-ups(e.g., at the 3-year follow-up), and then yearlythereafter.

Its higher resolution makes transesophageal echo-cardiography (TEE) a helpful imaging technique whenTTE has technical limitations. The role of TEEremains essential for assessing aortic insufficiencyand distinguishing between transvalvular and para-valvular regurgitation. The 3-dimensional echocar-diographic en face surgical view of the valve isextremely useful for determining the presence,origin, direction, and extension of regurgitant jets(21). However, poor echocardiographic windows,artifacts, and acoustic shadowing are well-knownlimitations of both TTE and TEE. The use of multi-detector computed tomography avoids these tech-nical limitations, and enables the visualization ofvalve morphology and bioprosthetic leaflet motion(25). Cardiovascular magnetic resonance is also auseful tool that provides a precise evaluation ofAR, given that echocardiographic quantification maybe difficult and less reliable following bioprosthesisimplantation (26).

MECHANISMS OF SVD

SVD is a multifactorial process with 2 main conse-quences: calcification and leaflet degradation leadingto valve stenosis or leaflet tear with ensuing valveregurgitation. Bovine pericardial valves have agreater propensity to develop stenosis as the mode of

TABLE 2 Studies on Surgical Bioprosthesis Durability

First Author, Year (Ref. #) Valve Type NMean Follow-Up

(yrs)SVD Requiring

Reintervention, n (%)Freedom From

SVD (%)

Jamieson et al., 2005 (37) Carpentier-Edwards SAV 1,823 8 � 5 132 (7.2) 15 yrs: 74.9 � 2.318 yrs: 64.0 � 3.6

David et al., 2007 (38) St Jude Medical Toronto 357 8 � 3 49 (13.7),4 were inoperable

10 yrs: 86 � 312 yrs: 69 � 4

Yankah et al., 2008 (39) Mitroflow 1,513 4 � 0.12 64 (4.2) 20 yrs: 62.3 � 5.0

Mykén and Bech-Hansen,2009 (40)

St Jude Medical Biocor 1,518 6 � 5 77 (5) 20 yrs: 61.1 � 8.5

David et al., 2010 (41) Hancock II 1,134 12 87 (7.6),13 were inoperable

5 yrs: 99.7 � 0.210 yrs: 97.6 � 0.615 yrs: 86.6 � 1.820 yrs: 63.4 � 4.2

Forcillo et al., 2013 (42) Carpentier-Edwards 2,405 6 � 9 91 (3.7); 2 refusedredo surgery

5 yrs: 98.0 � 0.210 yrs: 96 � 120 yrs: 67 � 4

Bach and Kon, 2014 (43) Freestyle 725 8 34 (4.6) 10 yrs: 96.4 � 1.415 yrs: 85.1 � 4.9

Bourguignon et al., 2015 (16) Carpentier- Edwards Perimount 373 9 � 6 78 (20) 10 yrs: 86.8 � 2.515 yrs: 66.8 � 4.220 yrs: 37.2 � 5.4

Guenzinger et al., 2015 (44) St Jude Medical Biocor 455 8 � 6 37 (8.1); 13 were inoperableor refused surgery

5 yrs: 97.9 � 0.810 yrs: 92.1 � 1.715 yrs: 84.8 � 3.020 yrs: 67.0 � 7.3

Johnston et al., 2015 (45) Carpentier Edwards Perimount 12,569 6 155 reoperated; 268 SVDwithout reoperation (3.3)

NR

Christ et al., 2015 (11) St. Jude Medical Toronto 50 14 � 6 24 (48) 5 yrs: 97.7 � 2.210 yrs: 76.0 � 6.715 yrs: 44.1 � 8.9

Repossini et al., 2016 (46) Freedom Solo 565 7 � 4 23 (4) 10 yrs: 90.8

NR ¼ not reported; SAV ¼ supra-annular valve; SVD ¼ structural valve deterioration.

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SVD, whereas porcine valves have a tendency todevelop leaflet tear with regurgitation (27). Also,stented valves tend to develop stenosis, whereas ARappears to be the main mechanism of valve failure inthe stentless valves (7). Some examples of SVD areshown in Figure 2.

Several mechanisms have been identified in thepathogenesis of SVD. Bioprosthetic leaflet tissue isfixed in glutaraldehyde to cross-link and mask anti-gens, avoiding immune system rejection of thexenograft and making the bioprosthesis

TABLE 3 Studies on Transcatheter Valve Durability

First Author (Ref. #) Valve Type

Mack et al. (48) Edwards SAPIEN

Kapadia et al. (49) Edwards SAPIEN

Toggweiler et al. (51) Cribier-Edwards/Edwards SAPIEN

Barbanti et al. (52) CoreValve

Dvir et al. (18) Cribier-Edwards/Edwards SAPIEN/Edwards SAPIEN

Eltchaninoff et al. (19) Cribier-Edwards/Edwards SAPIEN/Edwards SAPIEN

TAVR ¼ transcatheter aortic valve replacement; other abbreviations as in Table 2.

“immunologically inert.” Free aldehyde groupsresulting from this treatment, along with phospho-lipids and calcium ions in the circulation, result in apassive process of calcification (28). Hypercalcemia,hyperphosphatemia, and increased leaflet mechanicalstress are among the main mechanisms leading tomineralization, thickening, and disruption of valveleaflet tissues. Hence, diseases or conditions lead-ing to dysregulation of phosphocalcic metabolism(renal failure, hyperparathyroidism) or to increasedmechanical stress on valve leaflets (arterial

N Follow-Up (Yrs)SVD Requiring

Reintervention (n) SVD (%)

179 5 0 0

348 5 0 0

88 5 0 3.4

343 5 2 (redo TAVR) 1.4

XT 378 6–10 NR w50

XT 239 5–9 1 (redo TAVR) 1.67

FIGURE 3 PARTNER 5-Year Echocardiographic Prosthetic Performance

0 1 2 3 4 5

304294

TAVR groupSAVR group

Numberat risk

211154

151121

p = 0.3464

p = 0.0019 p = 0.10 p = 0.06

p < 0.0001

p < 0.0001

p = 0.66 p = 0.29

TAVR Group SAVR Group

10684

7960

5346

Mea

n Va

lve

Area

(cm

2 )

2.5

2.0

1.5

0.5

1.0

0

A

0 1 2 3 4 5

310299

TAVR groupSAVR group

Numberat risk

219158

156123

p = 0.80

p = 0.0023p = 0.19 p = 0.51 p = 0.29 p = 0.92

10686

7961

5648

Mea

n Gr

adie

nt (m

m H

g)

70.0

60.0

50.0

40.0

20.0

10.0

30.0

0

B

(A) Aortic valve area. (B) Mean transvalvular gradient. Points are mean, bars are SDs.

PARTNER ¼ Placement of Aortic Transcatheter Valves; SAVR ¼ surgical aortic valve

replacement; TAVR ¼ transcatheter aortic valve replacement. Reprinted with permission

from Mack et al. (48).

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hypertension, prosthesis-patient mismatch) mayaccelerate SVD.

In addition to this passive degenerative process,several studies have suggested active mechanismsthat trigger inflammatory responses that are fol-lowed by calcification. It appears that glutaralde-hyde fixation decreases, but does not entirelyeliminate the antigenicity of bioprosthetic tissueinducing immune responses and accelerating tissuemineralization (29). Animal model studies showedthat glutaraldehyde treatment caused humoral andcellular responses, including infiltration of xeno-grafts by macrophages, T cells, and eosinophils (30).These mechanisms provide a potential explanationfor the higher likelihood of younger patients,who are more immunologically active, to developSVD.

Valve thrombosis may occur during the early post-procedural phase in up to 15% of patients undergoingbiological aortic valve replacement (AVR) (31–34). It isalso possible that the occurrence of valve thrombosis,even if subclinical and/or treated successfully withanticoagulant agents, might trigger inflammation andsubsequent fibrocalcific remodeling of valve leaflets.Further studies are thus needed to determine if valvethrombosis in the early post-AVR phase might sub-sequently accelerate SVD.

Numerous treatments have been tested in aneffort to prevent valve calcification. As previouslymentioned, glutaraldehyde is 1 of the leading causesof calcification, and indeed, tissue crosslinking andstabilization without the use of glutaraldehyde ap-pears to prevent the process of tissue calcification(35). Alternative crosslinking agents (dye-mediatedphotofixation, carbodiimide-based fixation) exhibi-ted good anticalcification preventive properties, butnone of these methods are clinically used. Further-more, most cells and matrix components present intissues used for bioprosthetic fabrication arevulnerable to calcification. In this sense, several at-tempts were made to remove devitalized cells, sta-bilized collagen, and elastin, and to add naturalcalcification inhibitors like glycosaminoglycans (35).

In vitro tests have been developed to asses SVDand valve durability. Currently, valve prostheseshave specific durability requirements to achieve theInternational Organization for Standardization certi-fication before valve commercialization. Each valvewill be subjected to a recommended number of ster-ilization cycles, a minimum of 200 million cycles(equivalent to 5 years durability) (36), chemical pro-cessing, aging effects, and catheter loading anddeployment steps.

INCIDENCE AND TIMING OF SVD

SURGICAL BIOPROSTHESES. Durability stands as 1of the main limitations of surgical bioprosthesescompared with their mechanical counterparts. Bio-prosthesis durability is usually reported at 5, 10, 15,and even 20 years, and most reports refer to a specificbioprosthesis model. The data of the studies thatanalyzed valve durability following SAVR are sum-marized in Table 2 (11,16,37–46).

Studies on valve performance during the firstdecade following valve implantation have reported

FIGURE 4 CoreValve 5-Year Follow-Up

Pre-TA

VI (n = 353)

Discharg

e (n = 335)

1 yea

r (n = 274

)

2 years

(n = 24

6)

3 years

(n = 211)

4 years

(n = 17

5)

5 years

(n = 10

8)

Mea

n Ao

rtic

Gra

dien

t (m

m H

g)

100

60

80

20

40

0

Echocardiography evaluation of the CoreValve system performance over 5 years of

follow-up. Lack of any significant increase in transvalvular mean gradient over 5 years of

follow-up. Reprinted with permission from Barbanti et al. (52). TAVI ¼ transcatheter

aortic valve implantation.

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encouraging data, with most of these showing rates offreedom from SVD at 10 years >85% (11,38,43,46). Astudy conducted by David et al. (41) stands out, with apopulation of 1,134 patients (>50% of whom were <70years of age) who received a Hancock II bioprosthesis.The proportion of patients free from SVD at 10 yearswas as high as 97.6%. Also, only 87 patients (7.6%)had an echocardiographic diagnosis of SVD; 74 ofthem had reoperations and the remaining 13 weredeemed inoperable.

Limited and heterogeneous data exist on thedurability of surgical bioprostheses at 20 years offollow-up. For example, the 20-year experience withthe Carpentier-Edwards Perimount pericardial bio-prosthesis (Edwards Lifesciences) was reportedseparately by 2 studies. Forcillo et al. (42) showed a67% rate of freedom from reoperation, whereasBourguignon et al. (16) (with an echocardiography-based SVD definition) found a rate of freedom fromSVD as low as 37%. This large variability in the rate ofSVD between studies reflects the importance of thedefinition used for SVD, with those studies focusingonly on reoperation rates systematically under-estimating the real incidence of SVD. Furthermore,many studies have provided data on valve durabilitywith variable follow-up times among the patientsincluded. In fact, some studies have quoted “20-yearexperience” with different surgical valve platforms

when the real median follow-up in all of themwas <10 years (39,40,42,44).

In summary, SVD is not usual (#15%) during thefirst decade post-SAVR, but its incidence progres-sively increases thereafter. Nevertheless, comparisonbetween studies remains challenging due to themultiplicity of definitions and times used to evaluateSVD post-SAVR. There is therefore an urgent need fora universal consensus with standard definitions toprovide accurate data on SVD, enabling reliablecomparisons between studies and valve platforms.

TRANSCATHETER BIOPROSTHESES. Several limita-tions should be taken into account concerning trans-catheter valve durability. First, following the very firstTAVR procedure in 2002 (47), its wider adoption star-ted with the CE mark and U.S. Food and Drug Admin-istration approval in 2007 and 2011, respectively,representing a relatively young technology that pre-cludes valve durability analysis beyond 10 years. Sec-ond, current data on long-term outcomes ($5 years)post-TAVR refers to the first-generation transcathetervalves that were implanted by relatively inexperi-enced operators, with much higher rates of valvemalpositioning and issues concerning valve sizing.Finally, and more importantly, the TAVR populationcurrently consists of elderly patients with multiplecomorbidities and high-risk profiles leading to alimited life expectancy, with a subsequent paucity ofpatients (usually <50% of the initial population)available for long-term follow-up studies. Studies onvalve durability post-TAVR are summarized in Table 3.

The results of several TAVR studies with $5-yearfollow-up were recently reported. The 5-year resultsof the PARTNER-1 (Placement of Aortic TranscatheterValves) trial showed no evidence of SVD (48,49). Also,in PARTNER-1A, valve performance, as evaluated byechocardiography at the 5-year follow-up, was similarin both the TAVR and SAVR groups. Thus, the meantransvalvular gradient was 10.7 and 10.6 mm Hg andaortic valve area was 1.6 and 1.5 cm2 in the TAVRand SAVR groups, respectively (48), confirming thesatisfactory hemodynamics profiles of transcathetervalves up to 5 years post-implantation (Figure 3).These results have also been confirmed in a PARTNERI echocardiographic substudy including paired echo-cardiographic data for up to 5 years from 86 patientswho underwent TAVR and 48 who underwent SAVR(50). However, moderate or severe AR caused byparavalvular (but not intraprosthetic) regurgitationwas more common in the TAVR group. This hemo-dynamic dysfunction was, however, already presentat the outset of valve implantation and does notrepresent SVD.

TABLE 4 Predictors of SVD (Aortic Bioprosthesis)

Patient-related factors

Age HR: 0.97; 95% CI: 0.96–0.98; p < 0.01 (54)

Cardiovascular risk and comorbid factors

Smoking HR: 2.58; 95% CI: 1.85–3.60; p < 0.001 (54)

BMI (per m2) HR: 1.84; 95% CI: 1.08–3.16; p ¼ 0.026 (54)

Diabetes mellitus p ¼ 0.020 (56)

Dyslipidemia OR: 3.9; p ¼ 0.011 (56)

Renal insufficiency HR: 1.1; 95% CI: 1.03–1.16; p ¼ 0.047 (55)

Valve-related factors

Persistent LVH HR: 2.38; 95% CI: 1.61–3.51; p < 0.001 (54)

Prosthesis size HR: 0.82; 95% CI: 0.70–0.98; p ¼ 0.010 (54)

PPM HR: 1.79; 95% CI: 1.11–2.87; p ¼ 0.017 (54)

BMI ¼ body mass index; CI ¼ confidence interval; DM ¼ diabetes mellitus; HR ¼ hazard ratio; LVH ¼ left ven-tricular hypertrophy; OR ¼ odds ratio; PPM ¼ prosthesis patient mismatch; SVD ¼ structural valve deterioration.

TABLE 5 Cumulative Risk of Reoperation Due to SVD by Age Group: Competing

Risk Estimates

Probability (%) 20-Yr 25-Yr 30-Yr 35-Yr 40-Yr 45-Yr 50-Yr 55-Yr 60-Yr

5 6.9 6.9 7.0 7.5 7.8 8.3 8.7 9.1 9.2

10 7.8 8.4 9.0 9.2 9.6 9.9 10.3 11.1 11.6

15 9.1 9.2 9.9 10.0 10.7 11.4 13.1 14.0 14.8

20 9.9 10.0 10.7 11.4 13.1 14.0 14.8 15.1 16.3

25 10.4 11.1 12.5 13.9 14.2 14.9 15.5 16.7 17.8

30 11.2 13.1 14.0 14.8 15.1 16.3 16.9 17.9 18.6

35 13.1 14.0 14.8 15.3 16.3 17.3 18.0 18.6 21.2

40 14.0 14.8 15.3 16.3 17.3 18.0 18.6 21.2 23.4

45 14.8 15.3 16.3 17.3 18.0 18.6 21.2 23.4 —

50 15.1 16.3 16.9 17.9 18.6 21.0 23.4 — —

Values are the number of years a patient could expect to be free from reoperation for structural valve deteri-oration (SVD), depending on age at implantation. Adapted with permission from Bourguignon et al. (16).

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Toggweiler et al. (51) showed a 3.4% incidence ofSVD at 5-year follow-up in a cohort of 88 patients whohad received a balloon-expandable Edwards Sapienvalve. Moderate AR, stenosis, or combined AR andstenosis occurred in 1 patient each, and no patientrequired reintervention. Barbanti et al. (52) reported a5-year experience with the CoreValve system andfound 5 cases (1.4%) of SVD, with 2 patients requiringreintervention (valve-in-valve) because of symptom-atic aortic stenosis at 4 and 4.6 years post-TAVR. Inaddition, 10 patients (2.8%) showed late mild steno-sis, with a mean transaortic gradient ranging from 20to 40 mm Hg (Figure 4).

Ten-year follow-up data on TAVR are scarce. Dvir(18) reported a study totaling 378 patients followedfor up to 10 years. The valves included were Cribier-Edwards (14%), Edwards Sapien (50%), and EdwardsSapien XT (36%). A total of 35 cases of SVD wereidentified: approximately two-thirds presented withintraprosthetic AR and one-third with valvular ste-nosis or mixed disease. Based on these findings, theestimated SVD rate at 8 years was approximately50%. However, the definition of SVD in this studyused a fixed cutoff value of a mean transaorticgradient >20 mm Hg and did not take hemodynamicchanges over time into account, which may haveoverestimated the real incidence of SVD. Also, theevaluation of intraprosthetic versus paravalvularleaks (very frequent in the TAVR population, partic-ularly with first-generation devices) may be chal-lenging with TTE and cannot exclude the inclusion ofparavalvular leak cases interpreted as SVD. Further-more, with the first generations of transcathetervalves, a significant proportion (>50%) of patientsdemonstrated at least mild AR on the dischargeechocardiogram. Finally, it must be considered thatonly <10% of the initial study group was available foranalysis beyond 5 years. Eltchaninoff (19) presentedthe results of 239 patients with a follow-up beyond 5years. SVD was defined as a mean transvalvulargradient >20 mm Hg, in combination with an increaseof at least 10 mm Hg from the 30-day echocardiogra-phy or AR grade 3 or 4. Only 4 patients (1.67%) metthese criteria for SVD. Once again, the variability incriteria to define SVD highlight the importance ofstandardized definitions. More recently, Testa (53)presented the results from 2,343 patients treated in13 Italian centers with up to 9 years of follow-up. Theinvestigators found 3 patients with severe SVD thatled to death, and 12 patients with prosthesis-relatedclinical events leading to a new hospitalization forheart failure (treated with valve-in-valve procedures[n ¼ 8 patients], SAVR [n ¼ 2], and medical treatment[n ¼ 2]).

FACTORS ASSOCIATED WITH

BIOPROSTHESIS DETERIORATION

SURGICAL BIOPROSTHESES. The main factors asso-ciated with SVD following SAVR can be divided into3 groups: factors directly related to the patient, car-diovascular risk/comorbid conditions, and factorsrelated to the valve (Table 4) (54–56). Among thefactors directly related to the patient, age at the timeof valve implantation has been 1 of the most impor-tant factors determining bioprosthesis durabilityacross most studies. The rate of SVD at 10-year follow-up is usually <10% in elderly patients, whereas itrises to 20% to 30% in patients <40 years of age(42,45,57). The cumulative risk of reoperation sec-ondary to SVD according to age is shown in Table 5.Larger body surface area has been associated withaccelerated SVD, potentially explained by greaterhemodynamic stress and a lower tolerance to theeffects of stenosis or regurgitation (55). Male sex was

TABLE 6 Selected Series of Reoperative, Isolated SAVR

First Author, Year (Ref. #) NNYHA FunctionalClass III to IV (%)

Time From InitialSurgery (yrs)

MeanAge (yrs)

In-HospitalMortality (%)

Blanche et al., 1999 (69) 35 91 NR 83 � 3 9

Jones et al., 2001 (70) 187 NR NR 55 6.4

Maganti et al., 2009 (71) 40 56 NR 78 � 2 5

Balsam et al., 2010 (68) 211 49 9.5 � 6.5 81 � 4 12.8

Leontyev et al., 2011 (72) 86 42 6.7 � 7.9 58 � 16 5.8

Onorati et al., 2014 (73) <80 yrs of age: 437>80 yrs of age: 84

<80 yrs of age: 9.6>80 yrs of age: 13

NR 6583

5.53.6

NR ¼ not reported; NYHA ¼ New York Heart Association; SAVR ¼ surgical aortic valve replacement.

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associated with accelerated SVD in some studies(37,55), whereas other studies found that female sexis a risk factor for SVD (46,57).

Cardiovascular risk factors, such as smoking, hy-pertension, metabolic syndrome, diabetes mellitus,and dyslipidemia, were identified as predictors ofSVD in some studies (55,57,58). The fact that valvedegeneration and atherosclerosis share similar pre-dictors supports the idea of a potential lipid-mediatedmechanism accelerating SVD. However, there arediscordant data about the beneficial effect of statintherapy on the evolution of SVD (59).

Several comorbid conditions are also linked to SVD.A more rapid progression of valve degeneration isexpected in patients with renal insufficiency (56).Secondary hyperparathyroidism and the underlyingalteration of calcium metabolism could be the mech-anisms that increase the risk of SVD in such patients(60).

There are also several factors in SVD related tovalve type and hemodynamics. Some studies sug-gested that pericardial valves display improved

FIGURE 5 Examples of Valve-In-Valve Procedures

(A) Valve-in-valve with the CoreValve Evolut R system. (B) Valve-in-va

hemodynamic performance compared with porcinevalves (61). However, whether this hemodynamicimprovement associates with lower rates of SVDremains controversial (62). Small prosthesis size andprosthesis-patient mismatch (PPM) cause an abnor-mally high gradient across the valve due to increasedmechanical stress, which may contribute to anincreased incidence of SVD (29,55,63). The persis-tence of left ventricular hypertrophy has been asso-ciated with valve deterioration, which has beenexplained by the coexistence of left ventricularhypertrophy and prosthesis-patient mismatch orsystemic hypertension (55).

TRANSCATHETER BIOPROSTHESES. The evaluationof the factors associated with SVD post-TAVR ispresently limited by the small number of patientswith long-term follow-up data, linked to the smallnumber of SVD events. This explains the lack of dataon the predictors of SVD among TAVR candidates.Taking into account that transcatheter valves areessentially bioprosthetic valves, we may expect

lve with the Edwards Sapien S3 valve.

TABLE 7 Studies on ViV TAVR Procedures

First Author,Year (Ref. #) N THV

Age(Yrs)

STSScore

LogisticEuroSCORE

ProceduralSuccess (%)

Mean GradientPost-ViV (mm Hg)

AR >

Moderate30-Day

Mortality (%)1-Yr

Mortality (%)

Kempfert et al., 2010 (74) 11 SAPIEN 78 7.2 31.7 100 11 0 0 0

Webb et al., 2010 (75) 10 SAPIEN 82.1 10 30.4 100 12.8 0 0 NR

Pasic et al., 2011 (76) 14 SAPIEN 73.3 21.9 45.3 100 13.1 0 0 14.3

Eggebrecht et al., 2011 (77) 47 SAPIEN/CoreValve 79.8 11.6 35 98 17 2 17 NR

Bedogni et al., 2011 (78) 25 CoreValve 82.4 8.2 31.5 100 13.8 0 12 16

Bapat et al., 2012 (79) 23 SAPIEN 76.9 7.6 31.8 100 9.1 0 0 12.5

Seiffert et al., 2012 (80) 11 SAPIEN 79.3 12.5 31.8 100 17.9 0 NR 16.6

Latib et al., 2012 (81) 18 SAPIEN 75 8.2 37.4 94 12.4 0 0 5.6

Linke et al., 2012 (82) 27 CoreValve 74.8 NR 31.3 100 18 7.4 7.4 12

Gaia et al., 2012 (83) 14 Braile Inovare 69.8 38.6 42.9 100 12.8 NR 14.3 NR

Dvir et al., 2014 (84) 459 CoreValve/SAPIEN 77.6 9.8 31.1 93.1 15.8 5.4 7.6 16.8

Ihlberg et al., 2013 (85) 45 CoreValve/SAPIEN 80.6 14.6 NR 95.6 16.4 2 4.4 11.9

Subban et al., 2014 (86) 12 SAPIEN/CoreValve 78.5 7.4 NR 100 15 8.3 0 0

Camboni et al., 2015 (87) 31 SAPIEN/CoreValve/others 77.8 20.9 NR 88 16.1 NR 22.5 NR

Adapted with permission from Paradis et al. (7).

AR ¼ aortic regurgitation; AS ¼ aortic stenosis; LVEF ¼ left ventricular ejection fraction; STS ¼ Society of Thoracic Surgeons; TA ¼ transapical; TAO ¼ transaortic; Tax ¼ transaxillary; TF ¼ transfemoral;THV ¼ transcatheter heart valve; TS ¼ transseptal; ViV ¼ valve-in-valve; other abbreviations as in Tables 2 and 4.

TABLE 8 Main Complications Associated With Aortic ViV

Procedures and Conventional TAVR

Complications ViV Conventional TAVR

Elevated post-procedural gradients þþþ þCoronary obstruction þþþ þMalpositioning þþ þVascular complications þþ þþPermanent pacemaker þ þþParavalvular leak - þþAnnulus rupture - þ

Adapted with permission from Paradis et al. (7).

Abbreviations as in Tables 3 and 7.

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similar risk factors (as surgical bioprostheses) toassociate with bioprosthetic deterioration post-TAVR.However, some considerations specific to the TAVRfield need to be considered. The valve implantationtechnique differs from that used during SAVR, andconcerns have been raised regarding the possibility ofspecific TAVR-related procedural aspects potentiallytriggering and accelerating SVD. The potential leafletdamage during the crimping process, the asymmetricexpansion with suboptimal leaflet coaptation, andincomplete frame expansion leading to leaflet-frameinteraction and increasing the mechanical stressmay associate with an accelerated SVD process(64–66). The development of lower-profile sheathsizes and delivery catheters for TAVR may requirethinner leaflet material, along with further crimpingof valve leaflets that could potentially reduce valvedurability (67). Also, the occurrence of subclinicalvalve thrombosis early after TAVR has been detectedby 4-dimensional multidetector computed tomogra-phy in 10% to 15% of patients (31). Future studies willneed to evaluate the potential effect of these episodesof subclinical valve thrombosis on mid- to long-termSVD.

MANAGEMENT OF BIOPROSTHETIC

VALVE DEGENERATION

The treatment for dysfunctional surgical heart valveshas conventionally been redo surgery. However, redosurgery has been associated with increased morbidityand mortality, and a significant proportion of patientsare refused for reoperation (68). The data reported on

redo valve surgery frequently include a heterogeneouscohort of patients with differing indications for bothreoperation (prosthetic valve dysfunction, para-prosthetic leak, endocarditis, or thrombosed valves)and types of reoperation (single or double valvereplacement, isolated paraprosthetic leak repair, valverepair, or replacement with a different valve than forthe first operation). Overall, the operative mortalityassociated with repeated aortic valve surgery hasranged between 5.8% and 12.8% (Table 6) (68–73).Several risk factors have been identified for perioper-ative mortality in these patients, including pre-operative New York Heart Association functionalclass III/IV or reduced left ventricular ejection fraction,and noncardiac comorbidities, such as renal failure/dialysis, chronic obstructive pulmonary disease, orneurological disorders (69,73). These data may help torefine the future selection of patients for reoperation.

FIGURE 6 Valve-in-Valve Procedures: 1-Year Follow-Up Mortality Rates

Mortality rate following aortic valve-in-valve procedures, according to: (A) themainmechanism

of structural valve dysfunction; (B) surgical valve size; and (C) type of transcatheter valve.

From Dvir et al. (84) and Paradis et al. (7). Reprinted with permission from Paradis et al. (7).

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Valve-in-valve procedures have been identified asa feasible, less-invasive treatment option for pa-tients with degenerated surgically implanted bio-prostheses, and the ACC/AHA guidelines currentlyrecommend this approach in high-risk patients withaortic bioprosthesis dysfunction (Figure 5) (3). Inthese patients, valve-in-valve procedures have beenassociated with a high rate (95%) of successful valveimplantation and a mean 30-day mortality of 8%(7). The periprocedural outcomes of valve-in-valveprocedures are summarized in Table 7 (74–87). Ofnote, some aspects of valve-in-valve proceduresdiffer from conventional TAVR procedures (Table 8)(7,84). Among others, there is an increased risk forhigh residual gradients and coronary obstruction,but lower risk for paravalvular leaks and permanentpacemaker implantation. To date, there are scarcedata on late outcomes following valve-in-valveprocedures. A mortality rate of w15% has been re-ported at 1-year follow-up, and the factors associ-ated with increased mortality were the implantationof smaller surgical valves, stenosis as the mainmechanism of valve dysfunction, and the use of thetransapical approach (Figure 6) (7,84). These factorsmay be considered when determining the optimaltreatment strategy (redo surgery vs. valve-in-valveTAVR) in patients with bioprosthesis dysfunction.Two valves (Sapien 3, CoreValve) have alreadyreceived U.S. Food and Drug Administrationapproval to be used for TAVR valve-in-valveprocedures.

Silaschi et al. (88) recently compared redo surgeryand valve-in-valve TAVR for treating bioprosthesisfailure. Although valve-in-valve patients were olderand had higher-risk profiles, there were no differ-ences in 30-day mortality between the groups (4.2%and 5.1% in the valve-in-valve and redo surgerygroups, respectively). Redo surgery was associatedwith a higher rate of life-threatening bleeding, acutekidney injury, and permanent pacemaker implanta-tion, whereas residual transvalvular gradients weresignificantly higher in patients who underwent valve-in-valve TAVR. However, the validity of the studyresults was limited by the retrospective, non-randomized nature of the study and the lack ofappropriate adjustment for the comparison betweenthe TAVR and SAVR groups.

Although the limitations of valve-in-valve proced-ures need to be recognized, the growth of this tech-nology in the coming years is inevitable. This mayinfluence the selection of valve type (favoring bio-prostheses) and procedural technique (e.g., annularenlargement to obtain the largest possible EOA) at thetime of index valve surgery.

CENTRAL ILLUSTRATION Structural Valve Degeneration Following Surgical or Transcatheter AorticBioprosthesis Implantation

Rodriguez-Gabella, T. et al. J Am Coll Cardiol. 2017;70(8):1013–28.

SAVR ¼ surgical aortic valve replacement; TAVR ¼ transcatheter aortic valve replacement.

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In addition to redo surgery and valve-in-valveTAVR, it would be important to consider the possi-bility of valve thrombosis as a potential cause ofincreasing transvalvular gradients, particularlywithin the months following bioprosthetic valveimplantation (31). In these cases, anticoagulationtherapy should be the preferred treatment, and redosurgery or valve-in-valve TAVR should be consideredonly if anticoagulation treatment fails.

CONCLUSIONS

The avoidance of chronic anticoagulation therapy andthe possibility of less invasive therapies (valve-in-valve TAVR) for treating valve failure have drivenmajor increases in the use of aortic bioprostheses inrecent times. However, SVD limiting valve durabilitycontinues to be one of the main limitations of bio-logical (vs. mechanical) valves (Central Illustration).Valve leaflet calcification has been recognized as theprimary mechanism responsible for SVD, and thefactors associated with an increased risk are related topatient characteristics (younger age, larger body massindex), cardiovascular risk factors, and variablespertaining to bioprosthetic valves per se (increased

transvalvular gradient, prosthesis-patient mismatch).Although the reported durability of surgical aorticbioprosthesis is >85% at 10 years, most studies todate have used reoperation instead of valve perfor-mance parameters to define valve durability, leadingto a likely underestimation of the real incidence ofSVD. In fact, the large variety of definitions used inpublished reports highlights the urgent need for auniversal definition of SVD using echocardiographicparameters that consider the changes in valve per-formance over time. It would thus be important tostandardize follow-up echocardiographic recommen-dations following TAVR and SAVR, and the frequencyof echocardiographic examinations at follow-up willprobably need to increase with respect to currentguideline recommendations. Further research shoulddetermine whether yearly echocardiograms afterSAVR or TAVR are warranted (vs. some less-frequentinterval). Data on transcatheter valve durabilityremain scarce, and are mainly limited to 5-yearfollow-up. To date, the rate of clinically-relevantSVD post-TAVR has been very low and similar tothat reported for surgical bioprostheses. However,longer-term follow-up data are needed before claim-ing transcatheter valve durability comparable to that

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of their surgical counterparts. Redo surgery remainsthe gold standard for treating aortic bioprostheticfailure, but valve-in-valve TAVR has become a validalternative that will likely expand within the next fewyears. However, the limitations of valve-in-valveprocedures, particularly suboptimal valve perfor-mance in patients with small and stenotic surgicalvalves, should be acknowledged when determiningthe optimal treatment strategy (redo surgery vs.valve-in-valve TAVR) in this challenging group ofpatients. The significant increase in the use of aorticbioprostheses in recent times will inevitably lead torising numbers of patients diagnosed with SVD in thenext decade. This should stimulate further research

efforts in the prevention and treatment of this entity,particularly if we embrace the possibility of treatingyounger patients with biological (instead of mechan-ical) valves.

ACKNOWLEDGMENTS The authors thank MelanieCôté, MSc, Claire Gibrat, PhD, and Emilie Pelletier,MSc, from the Quebec Heart & Lung Institute, fortheir help in the preparation of figures.

ADDRESS FORCORRESPONDENCE:Dr. Josep Rodés-Cabau,Quebec Heart & Lung Institute, Laval University, 2725,Chemin Sainte-Foy G1V 4G5, Quebec, Canada. E-mail:josep.rodes@criucpq.ulaval.ca.

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KEY WORDS aortic valve insufficiency,aortic valve stenosis, bioprosthesis, heartvalve prosthesis, transcatheter aortic valveimplantation, transcatheter aortic valvereplacement