Review Article

Innovations

Valve-in-Valve TAVR: State-of-the- 00(0) 1–12

© The Author(s) 2019

Art Review
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DOI: 10.1177/1556984519858020
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J. James Edelman1, PhD, Jaffar M. Khan2,3, BM BCh,

Toby Rogers2,3, PhD, Christian Shults1, MD, Lowell F. Satler2 , MD, I. Itsik Ben-Dor2 ,
MD, Ron Waksman2 , MD, and Vinod H. Thourani1, MD

Abstract
An increasing number of surgically implanted bioprostheses will require re-intervention for structural valve deteri-
oration. Valve-in-valve transcatheter aortic valve replacement (ViV TAVR) has become an alternative to reoperative
surgery, currently approved for high-risk and inoperable patients. Challenges to the technique include higher rates of
prosthesis–patient mismatch and coronary obstruction, compared to native valve TAVR. Herein, we review results of
ViV TAVR and novel techniques to overcome the aforementioned challenges.

Keywords
transcatheter aortic valve replacement, valve-in-valve, aortic valve, bioprosthesis

Introduction
Bioprosthetic prostheses now represent the majority of all surgical aortic valve replacements (SAVRs) and are increas-
ingly being implanted in younger patients who can expect the need for valve re-intervention in the future.1,2 Valve-in-
valve transcatheter aortic valve replacement (ViV TAVR) was first performed in the mid 2000s and was approved by
the Food and Drug Administration in 2015 (Medtronic CoreValve) and 2017 (Edwards Sapien) for high- and extreme-
risk patients.3,4 It has become an attractive alternative to reoperative SAVR (class IIa recommendation in the 2017 ACC/
AHA Guidelines) for treatment of severe structural valve deterioration (SVD) in this group.2 The technique has a num-
ber of technical challenges, with increased potential risk of coronary obstruction in certain SAVR types, high residual
transvalvular gradients, and valve thrombosis. Herein, we review outcomes of ViV TAVR, its complications, and vari-
ous techniques designed to overcome these.

Surgical Valve Characteristics

To best understand ViV TAVR, one must first understand the types of surgical bioprosthetic valves implanted. The
characteristics of the most commonly used valves, including durability data, fracturability/expansability, leaflet mount-
ing, and true internal diameter are summarized in Table 1. Unfortunately, there remains a paucity of large, proto-
col-driven echocardiographic follow-up assessment of bioprosthetic surgical valves by an independent core-lab. In a
recent article, Rodriguez-Gabella et al. performed 10-year follow-up of an unselected population of 672 patients (mean
age 72 years) who underwent SAVR between 2002 and 2004.5 They noted that 64.3% had died (65% of these deaths
were noncardiovascular) and 7.3% underwent redo-valve intervention (either redo-SAVR or ViV TAVR). Of the survi-
vors, 6.6% had a > 20 mmHg gradient or >moderate aortic regurgitation (AR) compared to discharge and 30.1% had

1
Department of Cardiac Surgery, MedStar Heart and Vascular Institute, Georgetown University School of Medicine, Washington, DC, USA
2
Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, USA
3
Cardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD,
USA

Corresponding Author:
Vinod H. Thourani, Department of Cardiac Surgery, MedStar Heart and Vascular Institute, 110 Irving Street, Suite 6D15G, Washington, DC
20010, USA.
Email: ​vinod.​h.​thourani@​medstar.​net
2 Innovations 00(0)

Table 1.  Details of Commonly Used Surgical Bioprostheses. Internal Diameter, Minimum TAVR Size Data Obtained From Valve-
in-Valve App (Dr Vinayak Bapat and UBQO Limited). Fracturability Data From Allen et al.48 and Shahanavaz et al.51
True internal
diameter vs.
Valve Durability labeled size Minimum size for ViV Fracturable?43,44 Leaflet mounting

Edwards Perimount/ Reoperation (by age at −2 mm 19 = Evolut R 23 mm, 20 Magna: yes Inside stent frame
Magna Ease implant): mm S3 Perimount 2700: yes
(Bovine Pericardial) <60 years: 10 years 5.6%, (often stretched
15 years 20%, 20 not fractured)
years 45% Perimount 2800: yes
60-80 years: 10 years
1.5%, 15 years 5.1%,
20 years 8.1%
>80 years: 0%9
Abbott Trifecta Freedom from SVD: −2 mm 19 = Evolut R 23 mm, S3 20 No Outside stent frame
(Bovine Pericardial) 6 years: 97.3% (protocol mm
59
echocardiograms )
5 years: 84.5%
(reoperation for any
reason60)
Abbott Epic Freedom from −2 mm 19 = Evolut R 23 mm, S3 20 Yes  
(Porcine pericardium) reoperation for SVD mm
at 4 years61:
<60 years: 93.3%
61-70 years: 98.1%
>70 years: 100%
Medtronic Mosaic Freedom from 19 = −3 mm 19 = not recommended Yes Inside stent frame
(Porcine) reoperation for SVD 21/23/25 = −4 21 = Evolut R 23 mm, S2 20
at 15 years: 86.3%62 mm mm
27/29 = −5
mm
Mitroflow Freedom from 19 = −3.5 mm 19 = not recommended (this Yes Outside stent frame
reoperation for SVD 21/23/25/27 = has been performed with
at 9 years: 67.9%63 −4 mm BVF)
29 = 4.5 mm 21 = Evolut R 23 mm, S2 20
mm
Edwards Inspira Freedom from 19/21/23/25 = 19 = Evolut R 23 mm, S3 23 Yes (expansile Inside stent frame
reoperation at 2 0 mm mm segment)
years: 0.2% (0% for 27/29 = −2
SVD)64 mm
Medtronic Hancock II Freedom from SVD 21/23/25 = −4 21 = Evolut R 23 mm, S3 20 No Inside stent frame
(echocardiogram or mm mm
reoperation) 27/29 = −5
15 years: 88.4% mm
20 years: 63.4%65
Medtronic Freestyle Freedom from 19/27/29 = -−2 19 = Evolut R 23 mm, S3 20 No (would cause Porcine aortic root
Stentless porcine root) reoperation for mm mm annular injury)
SVD at 10/15 21/23/25 = −3
years: 94.6%/88.1% mm
(subcoronary
implantation)
98.9%/88.1% (aortic root
replacement)66
Edwards Intuity Freedom from re- −2 mm 19 = Evolut R 23 mm, S3 20 Unclear Inside stent frame
Sutureless intervention 1 year: mm
99.3%67

(Continued)
James Edelman et al. 3

Table 1.  Continued

True internal
diameter vs.
Valve Durability labeled size Minimum size for ViV Fracturable?43,44 Leaflet mounting

Sorin Perceval Largest trial reports S = 17.5−19 S = Evolut R 23 mm, S3 20/23 Unclear Inside stent frame
0% SVD, duration mm mm
of follow-up not M = 19.5−21
specified (>30 days); mm
1/731 patients had L = 21.5−23
pannus overgrowth68 mm
XL = 23.5−25
mm

BVF, bioprosthetic valve fracture; SVD, structural valve deterioration; TAVR, transcatheter aortic valve replacement;ViV, valve in valve.

increase >10 mmHg or >mild-moderate AR.6 Body mass index and the implantation of the Mitroflow valve (LivaNova,
Italy) were predictors of SVD. Most surgical studies have determined the durability of bioprosthetic valves based on the
rate of reoperation; this more recently has been criticized since many patients may not be candidates for reoperation or
choose not to undergo another sternotomy despite echocardiographic evidence of severe valve stenosis or regurgitation.
A standardized definition of SVD has been proposed which includes both morphological and hemodynamic character-
istics in stages of failing bioprosthetic valves.7 This may assist in uniform reporting of SVD and interpretation of dura-
bility data for not only surgical, but also transcatheter valve implantations. Indeed, the best durability data may come
from long-term follow-up of randomized trials comparing TAVR and SAVR. This information may best come from the
low-risk trials which do not have age restrictions (NCT02675114, NCT02701283), as even the intermediate-risk trials
included patients with mean ages 79.8 and 81.6 years, for self- and balloon-expandable (BE) valves, respectively.8,9 In
a recent study by Dvir and colleagues, they noted that median time from SAVR to ViV TAVR in 459 patients was 9
years (interquartile range 6 to 12 years).10
Despite robust randomized trials and prospectively collected data, the majority of younger patient are undergoing
implantation of a bioprosthetic valve in comparison to a mechanical prosthesis. It is anticipated that these younger
patients will require valve re-intervention earlier and more frequently than those in whom a bioprosthesis was placed at
older age.11,12 Consequently, it is anticipated that the number of re-interventions (either redo-SAVR or ViV TAVR) for
bioprosthetic valve failure will increase.

Safety of ViV TAVR and Reoperative SAVR

The earliest large databases to evaluate ViV TAVR have been the Valve-in-Valve International Data (VIVID) and
Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapies (TVT)
registries.10,13 Overall mortality at 30 days was 4.6% of 1,168 patients undergoing ViV TAVR that were included in the
VIVID Registry,14 2.1% in 1,150 patients in the TVT Registry,13 0.7% in the continued access patients of the Partner 2
ViV Registry,15 and 8% in a metaanalysis of 14 series (>10 patients) published prior to 2015.16
Presence of a small surgical valve (≤23 mm), and aortic stenosis, rather than regurgitation was associated with
increased mortality in the VIVID Registry.10 In a recent long-term series by de Freitas Campos Guimarães et al. with a
median follow-up of 3 years after ViV TAVR, 25.9% of patients had died (17.2% from cardiovascular causes).17 New
SVD was present in 18% of patients, but severe (>20 mmHg increase in gradient) in only 3%; in the entire cohort there
was no significant increase in the valve gradient over time. Older age, low ejection fraction (EF), renal failure, BE and
small surgical valve size were associated with late mortality risk in univariate analysis. In a matched comparison of ViV
compared with native valve TAVR from the TVT Registry, the rate of moderate-severe paravalvular leak (PVL) was
lower in ViV TAVR compared with TAVR in native valves (3.5% vs. 6.6%), but mean gradients were higher (16 mmHg
vs. 9 mmHg). Rate of stroke was 1.7% at 30 days, new pacemaker 3.0% (in-hospital); both lower than patients in whom
native valve TAVR was being performed.13
Mortality (30 days or in-hospital) after redo-AVR for previous aortic bioprosthesis was 4.7% (predicted risk of mor-
tality 5.5%) in 2,213 patients included in the STS database between 2011 and 2013.18 Stenosis was the primary indica-
tion for redo-AVR in 64.2% and 13.6% had infective endocarditis. The rate of stroke was 1.9%, need for permanent
4 Innovations 00(0)

Fig. 1.  Inclusion criteria for patients at high risk of coronary obstruction in the BASILICA trail. BAV: balloon aortic valvuloplasty;
STJ: sinotubular junction;VTC: valve-to-coronary ostia distance. Adapted from Khan et al.28 (accepted for publication; permission
pending).

pacemaker 11.5%, and renal failure 4.2%. These results are similar to other contemporary series, including one of
patients >75 years undergoing redo-AVR (90-day mortality 5%).19,20
Comparisons between redo-SAVR and ViV TAVR for failed surgical prostheses are limited; none overcome the bias
of the older patients with more comorbidities in the ViV TAVR population.21,22 One propensity score analysis reported
similar 30-day and 1-year mortality, stroke, renal failure, pacemaker insertion between redo-SAVR and ViV TAVR.
There was lower mean gradient >20 mmHg with redo-SAVR, but lower hospital length of stay with ViV TAVR.23

Coronary Obstruction
Coronary obstruction during TAVR is a rare event associated with high mortality (~50%); it occurs more frequently
during TAVR for failed bioprostheses (2.3%) than native valve TAVR (<1%).24,25 The left coronary artery is obstructed
(72%) more often than both coronaries (20%); isolated obstruction of the right coronary is less common (8%).
Obstruction usually occurs after valve implantation (58%), but can occur after initial balloon valvuloplasty (3%), after
balloon postdilatation (3%), within 24 hours following TAVR (22%) or later (14%). Obstruction can be partial (57%)
or complete (43%) and most commonly results in severe persistent hypotension (58%). The incidence of coronary
obstruction in TAVR for failed surgical prostheses is more than 7 times as likely (OR 7.67) in valves with externally
mounted leaflets (6.4%) and stentless valves (3.7%), compared with valves with internally mounted leaflets (0.7%).25
Multiple detector computed tomography (MDCT), now a standard of care in the planning of TAVR, is an important
tool for predicting coronary obstruction. The virtual transcatheter valve to coronary ostium distance (VTC) is a predic-
tor of coronary obstruction, albeit in small numbers of patients.25 At the center of the surgical valve, a virtual ring of
diameter equal to that of the planned TAVR is placed at the height of the coronary ostia. To ensure that the ring accu-
rately reflects the position of the valve to be implanted, it must be in coplanar alignment with the “virtual cylinder” that
extends from the basal ring of the surgical valve to the predicted height of the planned TAVR prosthesis. The distance
between this virtual ring and the coronary ostia is the VTC.26,27 A VTC <4 mm predicts highest risk of coronary obstruc-
tion (OR 0.22 for each millimeter increase in VTC; cutoff 4 mm – area under the curve 0.943, P < 0.0001).25 Interestingly,
coronary height did not differ between patients with and without coronary obstruction and may be less relevant in ViV
TAVR. Fig. 1 summarizes the selection criteria for inclusion as high coronary obstruction risk in the recently reported
BASILICA trial.28 The Expert Consensus Statement of the Society of Cardiovascular Computed Tomography details
CT assessment of patients undergoing TAVR, including the risk of coronary obstruction.29
Emergency percutaneous coronary intervention after TAVR is challenging and was unsuccessful in 18% in the larg-
est series.24 Mortality was 22% with successful percutaneous coronary intervention (PCI), 100% with unsuccessful PCI
and 50% when the patient was referred for emergency coronary artery bypass grafting (CABG). Identification of risk
James Edelman et al. 5

Fig. 2.  Sequence of the BASILICA procedure (a to d). An electrified guidewire is passed through the base of the left aortic cusp,
which it then lacerates, permitting coronary flow as the leaflets splay with expansion of the valve-in-valve prosthesis. Khan et al.31
(permission pending).

for coronary obstruction should prompt reevaluation of TAVR and SAVR risk by the heart team. Should a patient not
be a candidate for surgery, a strategy of coronary protection should be employed.
Placement of a coronary guidewire, through a guiding catheter, in the left anterior descending artery (a second wire
in the left circumflex offers additional support) with coronary balloon or undeployed stent in the threatened coronary is
one option for protection. Emergency left main stenting was required in 20% of patients in whom this protective strat-
egy was employed and successful in each case.30 The long-term patency of this strategy, which “chimneys” above the
TAVR prosthesis, is unclear. Mechanical deformation of the stent by the TAVR prosthesis is possible. Future access to
the coronary arteries would be very difficult and late occlusion of the chimney stent would most likely be a fatal event.
The BASILICA procedure is a promising alternative strategy that prevents obstruction in both native and prosthetic
valves undergoing TAVR (Fig. 2).31 Leaflets that threaten to occlude the coronaries are lacerated in their midline with
catheter electrosurgery, allowing them to splay laterally as they are displaced outwards by the TAVR prosthesis. The
lateral movement away from the midline of the aortic cusp prevents coronary obstruction and preserves access to the
6 Innovations 00(0)

ostia. The procedure was successful in animal models and an early feasibility trial of 7 inoperable patients with threat-
ened coronary obstruction, all of whom survived to 30 days. The BASILICA IDE trial (NCT03381989) prospectively
enrolled 30 high- and extreme-risk patients at high risk of coronary artery obstruction and reported 100% freedom from
coronary obstruction after BASILICA-TAVR, 93% procedural success, and low mortality (1 patient, day 17 from mul-
tiorgan failure); 1 patient had disabling stroke.28 This technique would improve access of ViV to patients with threat-
ened coronary obstruction.
Delayed coronary obstruction (DCO), defined as obstruction that occurs after the patient leaves the operating room
in a stable condition after TAVR, is a rare event. It occurs more frequently after ViV procedures than native valve TAVR
(0.89% vs. 0.18%, P < 0.0001) and more commonly after self-expandable than BE valves. DCO occurred within 7 days
of the procedure (63%; ≤24 hours in 47%) or ≥60 days (37%); interestingly there were no reports between 7 and 60
days. Obstruction presented as cardiac arrest in 32%.32 Potential mechanisms for early DCO include continued expan-
sion of the TAVR valve causing obstruction by the native or surgical prosthetic aortic leaflets. Less likely could be
coronary dissection or aortic root hematoma. Mechanisms for late obstruction include endothelialization of native or
surgical bioprosthetic leaflets, or embolization of thrombus that may occur in the TAVR valve or sinus of Valsalva.
There was a trend towards higher mortality with early (<= 7 days) compared to late DCO (63% vs. 29%, P = 0.09).32

Valve Thrombosis
Reduced leaflet motion caused by thrombosis has been noted in both TAVR and SAVR valves.33 The RESOLVE and
SAVOURY registries, each representing cases from a single center, were established to assess reduced leaflet motion in
greater detail and at latest report include 930 patients.34 In CT scans performed at median 83 days after AR, reduced
leaflet motion is relatively common, occurring in 12% of patients (4% of SAVR patients, 13% TAVR patients).
Subclinical leaflet thrombosis was defined as the presence of reduced leaflet motion with hypoattenuating lesions on
CT, and was associated with greater number of transient ischemic attacks (TIA) (4.18/100 person-years vs. 0.6/100
person-years, P = 0.0005), but not strokes (4.12/100 person-years vs. 1.92 person-years, P = 0.10). ViV TAVR was not
predictive of reduced leaflet motion in the RESOLVE/SAVOURY registries,34 but has been identified as a risk factor for
leaflet thrombosis in other studies.35 Computational modeling with three-dimensional flow fields suggests geometric
confinement of TAVR leaflets by failed bioprostheses may increase blood stasis in the neo-sinuses potentially leading
to leaflet thrombosis.36 Blood residence time, a measure of blood stasis on bioprostheses and higher in low-flow regions,
was increased along the fixed border of the TAVR valves where they attach to the frame. In their model, blood residence
time was increased in valves placed in the intra-annular compared to the supra-annular position as the TAVR stent is
fully, rather than partially, covered when intra-annular. In vivo data to corroborate this is active area for investigation.

Postoperative Residual Gradients

A ViV procedure may be a strong predictor for severe residual high gradients (OR 2.8, 85% CI 2.5 to 3.0) which was
associated with increased risk of mortality at 1 year. Over 30% of ViV procedures in the STS/ACC TVT and VIVID
registries resulted in severe residual gradients postoperatively.10,37 ViV TAVR was associated with hemodynamic dete-
rioration (≥10 mmHg change between consecutive echocardiograms) between discharge and 30 days in the TVT
Registry.38
A patient cohort that is even more challenging includes those patients who had severe prosthesis-patient mismatch
(PPM) with the original SAVR, who now present with SVD. Generally these patients present for SVD sooner for ViV
TAVR compared to those with moderate or no PPM as reported in the VIVID Registry (7 vs. 9 years, P < 0.001) and
other series.10,39 Severe PPM present prior to ViV procedure predicted a postprocedure gradient ≥20 mmHg, and
increased 30-day (4.3% vs. 10.3%, P = 0.01) and 1-year mortality (11.9% vs. 18.6%, P < 0.001).14
Self-expanding (SE), when compared to BE, valves were associated with lower post-ViV gradients, especially
in the presence of preexisting severe PPM (gradient ≥20 mmHg: 34% vs. 78%, P < 0.0001).10,14 In native valves,
deep positioning of SE valves may be a greater predictor of PPM than age, annulus size, left ventricular outflow
tract (LVOT) size, and valve size: a high position of the SE valve (defined for Medtronic CoreValve: proximal stent
frame 5 to 10 mm below the native aortic annulus) was associated with the lowest rate of PPM.40 However, the
optimum deployment height and size for ViV prostheses is not well understood. Lower gradients and greater effec-
tive orifice areas are achieved with higher deployment positions in in vitro testing, as leaflets in the supra-annular
position are better able to expand and coapt without the constraint of the fixed basal surgical valve ring.41–44 Lower
gradients with higher positioning need to be balanced against higher rates of regurgitation and potential for valve
James Edelman et al. 7

Fig. 3.  Various implant depths of a self-expanding valve within the Trifecta, Mitroflow, and Epic Supra valves. Reprinted from
Zenses et al.43 with permission from Europa Digital & Publishing.

embolization, which differs among various surgical valve types.42,43 Dvir and colleagues recommend an optimum
depth of 3 mm for the Medtronic Evolut SE valve and 80% aortic/20% ventricular deployment for a Edwards
Sapien 3 BE valve.45,46
A larger TAVR prosthesis is not always associated with larger effective orifice area (EOA) and varies by valve type.
For example, a when a 26-mm rather than a 23-mm SE valve was inserted into various 19 mm and 21 mm surgical
valves in vitro, a greater EOA was observed for the Trifecta and Epic Supra valves, but a smaller EOA for the Mitroflow
(Fig. 3); a greater risk of embolization observed when the larger valve was placed into an Epic Supra.43 Accelerated
degeneration of transcatheter valves has been reported with failure of full expansion.47
An in vitro study suggests that increased gradients associated with lower placement of SE valves in surgical prosthe-
ses may be attenuated by rotating the TAVR commissures (not readily controllable with current delivery systems) rela-
tive to the surgical commissures.44
The Valve-in-Valve app (Dr Vinayak Bapat and UBQO Limited) provides an excellent resource for surgical valve
details and suggested sizing for ViV TAVR.
8 Innovations 00(0)

Bioprosthetic Valve Fracture

ViV TAVR, performed in surgical valves ≤ 21 mm, yields poor results due to persistently high transvalvular gradients.10
Alternative options for replacement of a small, failing surgical valve have to date been limited to reoperative surgery,
preferably with placement of a larger valve using annular enlargement techniques. Bioprosthetic valve fracture (BVF)
has emerged as an alternative to reoperative surgery or ViV TAVR in small bioprostheses allowing placement of a ViV
TAVR. BVF is performed using a high-pressure, noncompliant balloon placed across the valve ring during rapid ven-
tricular pacing. Only the Abbott Trifecta and Medtronic Hancock II valves are not fracturable.48
In a series of 20 patients undergoing BVF (including of six 19-mm valves), there were no deaths, no root rupture,
coronary obstruction, or need for pacemaker.49 Fifteen of 20 procedures were performed after placement of the TAVR
valve. In these cases, mean transvalvular gradient decreased from 20.5 mmHg after ViV TAVR to 6.7 mmHg (P <
0.001) and EOA from 1.0 cm2 to 1.8 cm2, P < 0.001). Performance of the BVF after placement of the ViV TAVR may
allow greater expansion of the TAVR valve, lower theoretical risk of embolization of debris, and prevent hemodynamic
compromise following fracture. Assessment of the gradient after placement of the ViV TAVR allows operators to assess
gradient and determine the need for BVF. Fracture prior to ViV may allow a larger TAVR prosthesis to be placed, and
prevent potential subclinical injury to the new TAVR leaflets. BVF has been performed successfully in other series in
the aortic and pulmonary positions.50–52
We avoid BVF in patients where the annulus and LVOT are heavily calcified; there are no published reports of annu-
lar rupture using this technique. Anecdotally, BVF has led to annular rupture and ventricular septal defect; larger regis-
try data are needed to confirm safety.
A new surgical bioprosthesis (Inspiris Resilia, Edwards Lifesciences, Irvine, CA) has been designed with an expan-
sion zone in its frame specifically for ViV TAVR. Yet to be tested in clinical trials, the frame can expand with application
of radial force during ViV TAVR and allowing for hopefully larger TAVR valve implantation.
Should BVF fail to satisfactorily decrease valvular gradient, and the patient be a surgical candidate, then consider-
ation should be made for reoperative surgery to thoroughly debride the annulus and place an adequately sized prosthesis
using techniques of aortic root enlargement or replacement.53

TAVR in TAVR
Placement of a second (or third) TAVR to treat acute TAVR failure occurs in 1.4% to 6.7% (most often for acute AR),
with longer term outcomes not different to patients requiring only one valve if the procedure is successful.45–49 Incidence
of more than one valve may be higher in the larger annulus.54 Outcomes of TAVR to treat failed transcatheter valves are
available only in a small series, but appear satisfactory.55
The size of a TAVR valve (if unknown) can be estimated with MDCT using the internal diameter of the prosthesis at
the level of the leaflet insertion.29 The risk of coronary obstruction needs to be made in a similar fashion to that of a
SAVR valve with special attention to the height of the sinotubular junction (STJ), which if exceeded by the height of
the prosthesis, has the potential to become sealed.
There are no published data on sizing or valve selection TAVRs for placement inside existing TAVR prostheses. In
TAVR structural valve degeneration, we place a similar sized valve to that placed at the original procedure. Should we
choose a BE valve to be placed within a SE valve, we use the original native valve annulus measurements for selecting
a valve size. We prefer to place a SE valve within an existing BE valve as there is more likely to be a lower gradient due
to its supra-annular positioning. We choose a BE valve to sit within an existing SE valve as it offers more stability. In
our experience, a BE valve inside a SE valve can be an effective treatment strategy for moderate-severe PVL around the
original SE valve. The higher radial force of the BE valve is able to “push” the SE valve frame out and the skirt helps
seal the annulus.
Coronary intervention after placement of a TAVR prosthesis is challenging, but successful in over 90% in the largest
series.52,53 SE valves are more difficult to access as their stent post extends above the coronary arteries. Placement of a
second TAVR valve, especially if SE, has the theoretical potential to make coronary arteries significantly more difficult
to access particularly if stent cells do not perfectly overlap. To our knowledge, there are no data on coronary access after
TAVR in TAVR.
James Edelman et al. 9

For Treatment of Paravalvular Regurgitation

Late paravalvular regurgitation (PVR) in surgical prostheses is uncommon, but a difficult problem to address. Standard
treatment is reoperative surgery or use of percutaneous nitinol occluder devices to seal the leak. Percutaneous PVR
closure (to ≤mild) was achieved in 62% in one series.56 Cases have described the use of BE ViV TAVR to treat PVR.57,58
The radial force of the BE valve, with or without BVF, can be used to seal the PVR in certain patients. Identification of
the leak on MDCT and echocardiography is critical and can help guide positioning of the nitinol closure device/TAVR
valve. Intraprocedural transesophageal echocardiogram plays a key role to decipher intra- versus PVR.

The Future for ViV TAVR

Given the high rate of bioprostheses being implanted in young patients, it is likely that there will be an increase in the
number of patients requiring second, third, or more valve interventions. The improving techniques of ViV TAVR will
force questions of the optimal order of procedures. Will young patients be best served with SAVR, followed by redo-
SAVR, then ViV TAVR? Or SAVR then ViV TAVR then SAVR or another ViV TAVR? With TAVR being tested in
low-risk and younger patients, some will argue that TAVR as the initial procedure followed by ViV TAVR or SAVR
should be the optimal approach. Long-term follow-up of the low-risk randomized trials, together with large registries,
such as the STS/ACC TVT Registry, will be required to support clinical decision-making of the heart team.

Conclusion
ViV TAVR is an alternative treatment option for failed bioprosthetic surgical valves, currently approved for high- and
extreme-risk patients. In the absence of randomized data, analysis of longer term data from large multicenter registries
is required to ascertain the groups best served by ViV TAVR or reoperative SAVR in lower risk populations. Adjuncts
to ViV TAVR such as BASILICA to prevent coronary obstruction or BVF to decrease the risk of PPM may improve
safety and long-term outcomes. More work is required to better understand the mechanisms, consequences, and treat-
ment of leaflet thrombosis in the ViV population.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of
this article: Dr Thourani is an advisor for Abbott Vascular, Boston Scientific, Jenavalve, and Edwards Lifesciences. Dr Rogers
discloses a relationship with Edwards Lifesciences and Medtronic. Dr Waksman discloses a relationship with Abbott Vascular,
Amgen, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Cardioset, Cardiovascular Systems, Inc., Chiesi, MedAlliance,
Medtronic, Philips Volcano, and Pi-Cardia Ltd.

Funding
The author(s) declared no financial support for the research, authorship, and/or publication of this article.

References
1. Brown JM, O'Brien SM, Wu C, et al. Isolated aortic valve replacement in North America comprising 108,687 patients in 10
years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons national database. J Thorac Cardiovasc
Surg 2009; 137: 82–90.
2. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the manage-
ment of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task
Force on clinical practice guidelines. Circulation 2017; 135: e1159–e1195.
3. Wenaweser P, Buellesfeld L, Gerckens U, et al. Percutaneous aortic valve replacement for severe aortic regurgitation in degen-
erated bioprosthesis: the first valve in valve procedure using the CoreValve revalving system. Cathet Cardiovasc Intervent
2007; 70: 760–764.
4. Webb JG. Transcatheter valve in valve implants for failed prosthetic valves. Cathet Cardiovasc Intervent 2007; 70: 765–766.
5. Rodriguez-Gabella T, Voisine P, Dagenais F, et al. Long-term outcomes following surgical aortic bioprosthesis implantation. J
Am Coll Cardiol 2018; 71: 1401–1412.
6. Rodriguez-Gabella T, Voisine P, Puri R, et al. Aortic bioprosthetic valve durability. J Am Coll Cardiol 2017; 70: 1013–1028.
7. Dvir D, Bourguignon T, Otto CM, et al. Standardized definition of structural valve degeneration for surgical and transcatheter
bioprosthetic aortic valves. Circulation 2018; 137: 388–399.
10 Innovations 00(0)

8. Reardon MJ, Van Mieghem NM, Popma JJ, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients.
N Engl J Med Overseas Ed 2017; 376: 1321–1331.
9. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J
Med 2016; 374: 1609–1620.
10. Dvir D, Webb JG, Bleiziffer S, et  al. Transcatheter aortic valve implantation in failed bioprosthetic surgical valves. JAMA
2014; 312: 162–170.
11. Banbury MK, Cosgrove DM, White JA, et al. Age and valve size effect on the long-term durability of the Carpentier-Edwards
aortic pericardial bioprosthesis. Ann Thorac Surg 2001; 72: 753–757.
12. Johnston DR, Soltesz EG, Vakil N, et al. Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants.
Ann Thorac Surg 2015; 99: 1239–1247.
13. Tuzcu EM, Kapadia SR, Vemulapalli S, et al. Transcatheter aortic valve replacement of failed surgically implanted bioprosthe-
ses: the STS/ACC registry. J Am Coll Cardiol 2018; 72: 370–382.
14. Pibarot P, Simonato M, Barbanti M, et al. Impact of pre-existing prosthesis-patient mismatch on survival following aortic valve-
in-valve procedures. JACC Cardiovasc Interv 2018; 11: 133–141.
15. Webb JG, Mack MJ, White JM, et al. Transcatheter aortic valve implantation within degenerated aortic surgical bioprostheses:
PARTNER 2 Valve-in-Valve Registry. J Am Coll Cardiol 2017; 69: 2253–2262.
16. Paradis J-M, Del Trigo M, Puri R, et al. Transcatheter valve-in-valve and valve-in-ring for treating aortic and mitral surgical
prosthetic dysfunction. J Am Coll Cardiol 2015; 66: 2019–2037.
17. de Freitas Campos Guimarães L, Urena M, Wijeysundera HC, et al. Long-term outcomes after transcatheter aortic valve-in-
valve replacement. Circ Cardiovasc Interv 2018; 11: e007038.
18. Kaneko T, Vassileva CM, Englum B, et al. Contemporary outcomes of repeat aortic valve replacement: a benchmark for tran-
scatheter valve-in-valve procedures. Ann Thorac Surg 2015; 100: 1298–1304.
19. Maganti M, Rao V, Armstrong S, et al. Redo valvular surgery in elderly patients. Ann Thorac Surg 2009; 87: 521–525.
20. Fukunaga N, Okada Y, Konishi Y, et al. Clinical outcomes of redo valvular operations: a 20-year experience. Ann Thorac Surg
2012; 94: 2011–2016.
21. Neupane S, Singh H, Lämmer J, et al. Meta-analysis of transcatheter valve-in-valve implantation versus redo aortic valve sur-
gery for bioprosthetic aortic valve dysfunction. Am J Cardiol 2018; 121: 1593–1600.
22. Tam DY, Vo TX, Wijeysundera HC, et  al. Transcatheter valve-in-valve versus redo surgical aortic valve replacement for
the treatment of degenerated bioprosthetic aortic valve: a systematic review and meta-analysis. Catheter Cardiovasc Interv
2018; 92: 1404–1411.
23. Spaziano M, Mylotte D, Thériault-Lauzier P, et al. Transcatheter aortic valve implantation versus redo surgery for failing surgi-
cal aortic bioprostheses: a multicentre propensity score analysis. EuroIntervention 2017; 13: 1149–1156.
24. Ribeiro HB, Webb JG, Makkar RR, et  al. Predictive factors, management, and clinical outcomes of coronary obstruc-
tion following transcatheter aortic valve implantation: insights from a large multicenter registry. J Am Coll Cardiol
2013; 62: 1552–1562.
25. Ribeiro HB, Rodés-Cabau J, Blanke P, et al. Incidence, predictors, and clinical outcomes of coronary obstruction following
transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: insights from the vivid registry. Eur Heart
J 2018; 39: 687–695.
26. Blanke P, Soon J, Dvir D, et  al. Computed tomography assessment for transcatheter aortic valve in valve implantation: the
Vancouver approach to predict anatomical risk for coronary obstruction and other considerations. J Cardiovasc Comput Tomogr
2016; 10: 491–499.
27. Dvir D, Leipsic J, Blanke P, et al. Coronary obstruction in transcatheter aortic valve-in-valve implantation: preprocedural eval-
uation, device selection, protection, and treatment. Circ Cardiovasc Interv 2015; 8: e002079.
28. Khan JM, Greenbaum AB, Babaliaros VC, et al. The BASILICA trial: prospective multicenter investigation of intentional leaflet
laceration to prevent TAVR coronary obstruction. JACC Cardiovasc Interv 2019. Epub ahead of print 12 June 2019.
29. Blanke P, Weir-McCall JR, Achenbach S, et  al. Computed tomography imaging in the context of transcatheter aortic valve
implantation (TAVI) / transcatheter aortic valve replacement (TAVR): an expert consensus document of the Society of Cardio-
vascular Computed Tomography. J Cardiovasc Comput Tomogr 2019; 13: 1–20.
30. Abramowitz Y, Chakravarty T, Jilaihawi H, et al. Clinical impact of coronary protection during transcatheter aortic valve implan-
tation: first reported series of patients. EuroIntervention 2015; 11: 572–581.
31. Khan JM, Dvir D, Greenbaum AB, et al. Transcatheter laceration of aortic leaflets to prevent coronary obstruction during tran-
scatheter aortic valve replacement: concept to first-in-human. JACC Cardiovasc Interv 2018; 11: 677–689.
32. Jabbour RJ, Tanaka A, Finkelstein A, et al. Delayed coronary obstruction after transcatheter aortic valve replacement. J Am Coll
Cardiol 2018; 71: 1513–1524.
James Edelman et al. 11

33. Makkar RR, Fontana G, Jilaihawi H, et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med
2015; 373: 2015–2024.
34. Chakravarty T, Søndergaard L, Friedman J, et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic
valves: an observational study. Lancet 2017; 389: 2383–2392.
35. Jose J, Sulimov DS, El-Mawardy M, et al. Clinical bioprosthetic heart valve thrombosis after transcatheter aortic valve replace-
ment: incidence, characteristics, and treatment outcomes. JACC Cardiovasc Interv 2017; 10: 686–697.
36. Vahidkhah K, Javani S, Abbasi M, et al. Blood stasis on transcatheter valve leaflets and implications for valve-in-valve leaflet
thrombosis. Ann Thorac Surg 2017; 104: 751–759.
37. Herrmann HC, Daneshvar SA, Fonarow GC, et al. Prosthesis-patient mismatch in patients undergoing transcatheter aortic valve
replacement: from the STS/ACC TVT registry. J Am Coll Cardiol 2018; 72: 2701–2711.
38. Vemulapalli S, Holmes DR, Dai D, et al. Valve hemodynamic deterioration and cardiovascular outcomes in TAVR: a report from
the STS/ACC TVT registry. Am Heart J 2018; 195: 1–13.
39. Flameng W, Herregods M-C, Vercalsteren M, et al. Prosthesis-patient mismatch predicts structural valve degeneration in bio-
prosthetic heart valves. Circulation 2010; 121: 2123–2129.
40. Jilaihawi H, Chin D, Spyt T, et al. Prosthesis-patient mismatch after transcatheter aortic valve implantation with the Medtron-
ic-Corevalve bioprosthesis. Eur Heart J 2010; 31: 857–864.
41. Simonato M, Azadani AN, Webb J, et al. In vitro evaluation of implantation depth in valve-in-valve using different transcatheter
heart valves. EuroIntervention 2016; 12: 909–917.
42. Azadani AN, Reardon M, Simonato M, et al. Effect of transcatheter aortic valve size and position on valve-in-valve hemody-
namics: an in vitro study. J Thorac Cardiovasc Surg 2017; 153: 1303–1315.
43. Zenses A-S, Evin MA, Stanová V, et al. Effect of size and position of self-expanding transcatheter valve on haemodynamics
following valve-in-valve procedure in small surgical bioprostheses: an in vitro study. EuroIntervention 2018; 14: e282–e289.
44. Hatoum H, Dollery J, Lilly SM, et al. Implantation depth and rotational orientation effect on valve-in-valve hemodynamics and
sinus flow. Ann Thorac Surg 2018; 106: 70–78.
45. Dvir D, Khan J, Kornowski R, et al. Novel strategies in aortic valve-in-valve therapy including bioprosthetic valve fracture and
BASILICA. EuroIntervention 2018; 14(AB): AB74–AB82.
46. Seiffert M, Treede H, Schofer J, et al. Matched comparison of next- and early-generation balloon-expandable transcatheter heart
valve implantations in failed surgical aortic bioprostheses. EuroIntervention 2018; 14: e397–e404.
47. Grubitzsch H, Galloni M and Falk V. Wrinkles, folds and calcifications: reduced durability after transcatheter aortic valve-in-
valve replacement. J Thorac Cardiovasc Surg 2017; 153: 266–268.
48. Allen KB, Chhatriwalla AK, Cohen DJ, et al. Bioprosthetic valve fracture to facilitate transcatheter valve-in-valve implantation.
Ann Thorac Surg 2017; 104: 1501–1508.
49. Chhatriwalla AK, Allen KB, Saxon JT, et al. Bioprosthetic valve fracture improves the hemodynamic results of valve-in-valve
transcatheter aortic valve replacement. Circ Cardiovasc Interv 2017; 10: e005216.
50. Nielsen-Kudsk JE, Andersen A, Therkelsen CJ, et al. High-pressure balloon fracturing of small dysfunctional Mitroflow bio-
prostheses facilitates transcatheter aortic valve-in-valve implantation. EuroIntervention 2017; 13: e1020–e1025.
51. Shahanavaz S, Asnes JD, Grohmann J, et al. Intentional fracture of bioprosthetic valve frames in patients undergoing valve-in-
valve transcatheter pulmonary valve replacement. Circ Cardiovasc Interv 2018; 11: e006453.
52. Patel JS, Krishnaswamy A, White J, et  al. Optimizing hemodynamics of transcatheter aortic valve-in-valve implantation in
19-mm surgical aortic prostheses. Cathet Cardiovasc Intervent 2018; 92: 550–554.
53. Feindel CM. Aortic root enlargement in the adult. Oper Tech Thorac Cardiovasc Surg 2006; 11: 2–15.
54. Attizzani GF, Ohno Y, Latib A, et al. Acute and long-term (2-years) clinical outcomes of the CoreValve 31mm in large aortic
annuli: a multicenter study. Int J Cardiol 2017; 227: 543–549.
55. Barbanti M, Webb JG, Tamburino C, et al. Outcomes of redo transcatheter aortic valve replacement for the treatment of postproce-
dural and late occurrence of paravalvular regurgitation and transcatheter valve failure. Circ Cardiovasc Interv 2016; 9: e003930.
56. Alkhouli M, Sarraf M, Maor E, et al. Techniques and outcomes of percutaneous aortic paravalvular leak closure. JACC Cardio-
vasc Interv 2016; 9: 2416–2426.
57. Eskandari M, Roy J, Tzalamouras V, et al. Transcatheter valve-in-valve therapy using a balloon expanding valve for treatment
of aortic paravalvular leakage. Heart Lung Circ 2019; 28: e59-e63.
58. Loyalka P, Montgomery KB, Nguyen TC, et al. Valve-in-valve transcatheter aortic valve implantation: a novel approach to treat
paravalvular leak. Ann Thorac Surg 2017; 104: e325–e327.
59. Goldman S, Cheung A, Bavaria JE, et al. Midterm, multicenter clinical and hemodynamic results for the Trifecta aortic pericar-
dial valve. J Thorac Cardiovasc Surg 2017; 153: 561–569.
12 Innovations 00(0)

60. Lehmann S, Meyer A, Schroeter T, et al. Midterm durability and hemodynamic performance of a third-generation bovine peri-
cardial prosthetic aortic valve: the Leipzig experience. Ann Thorac Surg 2017; 103: 1933–1939.
61. Jamieson WRE, Lewis CTP, Sakwa MP, et al. St Jude Medical EPIC porcine bioprosthesis: results of the regulatory evaluation.
J Thorac Cardiovasc Surg 2011; 141: 1449–1454.
62. Anselmi A, Flécher E, Ruggieri VG, et al. Long-term results of the Medtronic Mosaic porcine bioprosthesis in the aortic posi-
tion. J Thorac Cardiovasc Surg 2014; 147: 1884–1891.
63. Ius F, Schulz J, Roumieh M, et al. Long-term results of the Mitroflow aortic pericardial bioprosthesis in over 800 patients: lim-
ited durability and mechanisms of dysfunction. Eur J Cardiothorac Surg 2017; 52: 264–271.
64. Puskas JD, Bavaria JE, Svensson LG, et al. The COMMENCE trial: 2-year outcomes with an aortic bioprosthesis with RESILIA
tissue. Eur J Cardiothorac Surg 2017; 52: 432–439.
65. David TE, Armstrong S and Maganti M. Hancock II bioprosthesis for aortic valve replacement: the gold standard of biopros-
thetic valves durability? Ann Thorac Surg 2010; 90: 775–781.
66. Mohammadi S, Kalavrouziotis D, Voisine P, et al. Bioprosthetic valve durability after stentless aortic valve replacement: the
effect of implantation technique. Ann Thorac Surg 2014; 97: 2011–2018.
67. Barnhart GR, Accola KD, Grossi EA, et al. TRANSFORM (Multicenter Experience with Rapid Deployment Edwards INTUITY
Valve System for Aortic Valve Replacement) US clinical trial: performance of a rapid deployment aortic valve. J Thorac Cardi-
ovasc Surg 2017; 153: 241–251.
68. Shrestha M, Fischlein T, Meuris B, et al. European multicentre experience with the sutureless Perceval valve: clinical and hae-
modynamic outcomes up to 5 years in over 700 patients. Eur J Cardiothorac Surg 2016; 49: 234–241.