Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of
aortic stenosis and is the treatment of choice for patients at prohibitive and high
surgical risk. Extension of indications into intermediate surgical risk has begun,
and recently 2 large randomized trials demonstrated that TAVR may be superior to surgery
in patients at low surgical risk and can potentially offer better results at initial
follow‐up.1, 2, 3 TAVR practice has evolved continuously with concomitant simplification
of the procedure. If one disregards the financial considerations, predictability of
the procedural outcome and certainty regarding the durability of TAVR prostheses are
2 of the main remaining restrictions to universal implementation.
Transfemoral access is the preferred approach, as it has a 20% relative reduction
in mortality compared with surgical aortic valve replacement (SAVR) (hazard ratio
HR, 0.80; 95% CI, 0.69–0.93; P=0.024).3 Understanding the mechanisms that underlie
complications during transfemoral TAVR is essential, and familiarity with the techniques
for their prevention and treatment is mandatory. In this review, we provide a state‐of‐the‐art
overview on the avoidable procedural complications of contemporary transfemoral TAVR
practice, with a specific focus on strategies for their prevention and management.
Vascular Access Complications
Prevention, early identification and effective management of vascular access complications
remain an important aspect of managing patients undergoing TAVR. The incidence of
vascular complications has varied according to the definition that has been applied.
In patients receiving first‐generation valves, ≈12% of patients experienced a major
vascular complication and 16% a life‐threatening bleed, as defined by the Valve Academic
Research Consortium criteria.4 Over time, there has been a significant reduction in
major vascular complications, with an incidence of 6% to 8% in recent TAVR trials.5,
6, 7 This reduction has been driven by a combination of smaller sheath sizes, flexible
delivery systems, multidetector computed tomography (MDCT) assessment of the peripheral
vasculature, and operator experience.8, 9 However, vascular complications and hemorrhage
remain a significant challenge in contemporary practice and are associated with increased
length of stay and higher mortality at 1 year (HR, 2.31; 95% CI, 1.20–4.43; P=0.012).6,
10, 11
The contemporary Valve Academic Research Consortium‐2 criteria include aortic and
peripheral access complications within the category of major vascular complications.12
This category comprises aortic/annular dissection or rupture, ventricular perforation,
and pseudoaneurysm or aneurysm. Major access complications include vascular injury
(dissection, stenosis, perforation, rupture, fistula, pseudoaneurysm, hematoma, irreversible
nerve injury, compartment syndrome, closure device failure), or a requirement for
unplanned surgical/endovascular intervention leading to death, life‐threatening or
major bleeding, visceral ischemia, or neurological impairment. The Valve Academic
Research Consortium‐2 also includes distal embolization resulting in amputation or
irreversible end‐organ damage, and any significant ipsilateral lower extremity ischemia
or access‐site nerve injury (Table S1).
Vascular complications most commonly occur at the access site, and bleeding and/or
hematoma formation occurs most frequently. Interestingly, studies consistently show
that failure of a closure device (adopted to prevent vascular access complication)
is the most common cause of a major vascular complication.13, 14
A number of patient‐ and procedural‐related risk factors have been identified. Patient‐related
factors include vascular calcification (especially when circumferential), preexisting
peripheral vascular disease, and female sex.11, 13 Procedural‐related risk factors
include larger sheath sizes, increased sheath:femoral artery ratio, and operator inexperience.14,
15
Complications involving the femoral segment are more common than those involving the
iliac segment, with dissection being more frequent than rupture.13 In larger series
of patients undergoing TAVR, ileofemoral dissection has been reported in ≈6.5% of
patients and rupture in ≈3% to 5%.16, 17 Pseudoaneurysm, embolization, occlusion,
and access site infection are uncommon.
How to Avoid
Avoidance of vascular complications begins with meticulous MDCT assessment of the
peripheral vessels (Figure 1). The role of MDCT is to assess the minimal luminal diameter
and identify heavy (>270°) calcification or calcification at the site of probable
puncture, the position of the femoral bifurcation relative to the femoral head, and
any significant vascular pathology.18 In patients with significant anterior calcification
or deep femoral arteries, surgical cutdown may be preferable to percutaneous access
to avoid the increased risk of vascular closure device failure. When transfemoral
access is not feasible, MDCT is the modality of choice to assess suitability for subclavian
access or to determine the location of “calcium‐free windows” in the descending aortic
wall if transcaval access is being considered.
Figure 1
Checklist of avoidable procedural complications as part of the procedural planning
for TAVR. AGU indicates angiographic, guidewire, and ultrasound; CEPD, cerebral embolic
protection device; LMS, left main stem; LV, left ventricular; LVOT, left ventricular
outflow tract; MDCT, multidetector computed tomography; PPM, permanent pacemaker;
RBBB, right bundle branch block; TAVR, transcatheter aortic valve replacement; TPW,
temporary pacing wire.
Several intraprocedural techniques have emerged to reduce vascular access complications.
The use of real‐time ultrasound guidance to puncture the common femoral artery has
become commonplace. Ultrasound reduces the incidence of vascular complications during
cardiac catheterization19 and was associated with reduced vascular complications in
patients undergoing TAVR in a single‐center retrospective cohort.20 Fluoroscopy can
be used to facilitate femoral puncture, using a radiopaque marker to “label” the position
of the femoral head or digital subtraction angiography to puncture the vessel in real
time. An alternative approach is to “road‐map” the common femoral artery after performing
an angiogram from the contralateral access site. Use of a micropuncture kit (Cook
Medical, Bloomington, IN) to confirm the position of the puncture prior to upsizing
the sheath is an intuitive strategy to minimize trauma before passage of a large catheter
at an unfavorable common femoral artery site.
Recently, an integrated technique involving (1) angiographic assessment of the iliac‐femoral
axis via secondary access, (2) a J‐tip 0.035‐inch guidewire placed as reference in
the ideal femoral artery spot (above the bifurcation), and (3) ultrasound imaging
to identify the J‐tip of the 0.035‐inch guidewire and guide the femoral puncture has
been proposed21 (Figure 2). Another novel technique in heavily calcified iliofemoral
vessels is the use of intravascular lithotripsy to facilitate transfemoral access
by disrupting intimal and medial calcification and increasing vascular compliance
via controlled microfractures and microdissections. This technology has been tested
in patients with calcific femoropopliteal vascular lesions in the DISRUPT‐PAD (Shockwave
Medical Peripheral Lithoplasty System Study for Peripheral Artery Disease) I and DISRUPT‐PAD
II studies.22, 23 Interestingly, the incidence of vascular complications was low in
these studies, with only 1 (1.7%) wire‐related dissection requiring stent placement.
Notably, no embolic debris was present when distal embolic filters were used, suggesting
a low risk of distal embolization.23
Figure 2
The angiographic, guidewire, and ultrasound (AGU) technique for vascular management.
The J tip of the 0.035‐inch guidewire is placed, under fluoroscopic guidance, in the
ideal femoral artery spot (above the bifurcation) (A). The J tip of the 0.035‐inch
is identified using ultrasound imaging (B). The femoral artery puncture is performed
under ultrasound guidance. The asterisk indicates the needle penetrating the anterior
wall of the femoral artery (C). Site of sheath insertion (D).
Recently, in a registry of 42 patients with iliofemoral vascular disease considered
prohibitive for transfemoral access undergoing TAVR, intravascular lithotripsy allowed
femoral access and safe delivery system passage in >90% of the cases.24, 25 In this
experience, no iliofemoral perforation or dissection requiring stent implantation
was observed, and only 1 (2.4%) patient developed pseudoaneurysm and 1 (2.4%) required
endarterectomy.25
Novel vascular closure devices, such as the MANTA (Teleflex, Wayne, PA) collagen‐plug
device, may reduce the rate of closure failure but await evaluation in head‐to‐head
studies against current suture‐based closure devices (eg, ProStarXL and Perclose ProGlide;
Abbott Vascular, Abbott Park, IL).26
How to Manage
Optimal management of vascular complications relies on early recognition. Routine
crossover angiography to assess for aortic/iliofemoral dissection or perforation after
sheath removal is current standard practice, and placement of a crossover wire from
the contralateral femoral artery allows rapid vascular access if required. Transradial
secondary access has recently been demonstrated to be suitable for the management
of peripheral vascular complications during TAVR and may reduce the rate of secondary
femoral access site complications.27, 28
Limited dissection or perforation may be successfully managed by prolonged occlusive
balloon inflation. Percutaneous deployment of a covered stent or surgical repair is
indicated for more extensive dissection or bleeding (especially if there is associated
cardiovascular instability or threatened/actual limb compromise) and is associated
with good long‐term outcome.29 Stenting is usually preferred to surgical repair when
the injury is above the inguinal ligament.
Device Landing Zone Rupture
Device landing zone rupture is a rare but feared complication of TAVR, with an overall
mortality up to 48% and can be as high as 75% in cases of uncontained rupture.30 Overall,
landing zone ruptures account for 7% of all the cases of emergent conversion to surgery
during TAVR.31 The reported incidence of landing zone rupture is up to 0.5% to 1%
of all TAVR procedures,5, 30, 32, 33, 34 although the real incidence might be higher
when cases with delayed presentation are accounted for.35
The most frequent anatomic site of rupture is the aortic annulus (involved in two
thirds of cases), although left ventricular outflow tract (LVOT, 10%), sinus of Valsalva
(16%), and sinotubular junction (6%) rupture have also been described.30 Self‐expanding
systems have rarely been associated with aortic root rupture (unless valve balloon
postdilatation is performed) and landing zone rupture is usually related to use of
a balloon‐expandable device.36
How to Avoid
Meticulous procedural planning using preprocedural imaging with MDCT and 3‐dimensional
reconstruction is essential to minimize the risk of landing zone rupture. Both anatomic
and procedural variables are associated, but a high burden of LVOT/subannular calcification
is recognized as the most important predictor. Notably, in a large multicenter TAVR
cohort, the calcium score was significantly increased in patients who experienced
landing zone rupture compared with other patients (181±211 versus 22±37; P<0.001).30
Perhaps more important than the calcific burden is the distribution of calcium. In
particular, a higher calcium volume in the upper LVOT (but not in the aortic valve
region) has been associated with the risk of landing zone rupture.37 Notably, Barbanti
et al30 reported no significant difference in annular size or degree of aortic cusp
calcification between patients with landing zone rupture and those with uncomplicated
TAVR. Advanced MDCT analysis may provide useful parameters to predict the risk of
landing zone complications, including (1) quantitative measurement of annular calcification
(>550 Hounsfield units), (2) leaflet asymmetry, defined as:
(
NC leaflet area
−
RC leaflet area
)
2
+
(
RC leaflet area
−
LC leaflet area
)
2
and (3) annular cover index (calculated as prosthesis nominal area − annular area/prosthesis
nominal area×100). Notably, the multivariate MDCT‐based risk model provides incremental
predictive value compared with single anatomic features.
Condado et al38 reported that focal calcification extending from the annular plane
to at least 4 mm into the LVOT was present in 4 of 7 patients who experienced annular
rupture. Similarly, Hayashida et al39 suggested that significant calcification located
in a particular vulnerable area, as revealed by MDCT, might be the possible mechanism
for some cases of annular rupture. The vulnerable area was identified as the spot
in the pericardial fat area of the annulus—an area uncovered by any cardiac structure
and therefore at risk of mechanical stress at the time of forceful deployment of a
balloon‐expandable valve over a calcified nodule. Other authors reported the association
between LVOT perforation and severe subannular calcification adjacent to the vulnerable
muscular region of the LVOT (between the left fibrous trigone and the left/right aortic
cusp commissure),40 suggesting the critical importance of careful anatomic MDCT assessment
and procedural planning.
The choice of valve prosthesis is also critical, and a self‐expandable valve is preferable
in cases with a high‐risk LVOT calcification pattern and shallow sinuses of Valsalva
(Figure 1). Additionally, it must always be noted when optimizing TAVR results that
postdilatation significantly increases the risk of landing zone rupture, especially
with >20% area oversizing (Figure 3).
Figure 3
Procedural and anatomical risk factors for device landing zone rupture. Heavy calcification
in the annular and left ventricular outflow tract region are important risk factors
for device landing zone complications. Careful assessment of the baseline multidetector
computed tomography provides important information on the presence of high‐risk calcium
distribution (A). Among the procedural variables, >20% area oversizing (B) and postdilatation
(C) increase the risk of device landing zone rupture.
How to Treat
In cases of uncontained rupture, conversion to emergency surgery is the only possible
solution. Maintenance of hemodynamic stability is essential in the acute setting,
and circulatory support should be immediately considered alongside a rapid search
for the cause of hemodynamic instability using angiography and/or transthoracic/transesophageal
echocardiography. In some cases, the correct diagnosis is established only by direct
surgical exploration.35
Percutaneous coil embolization to seal the point of landing zone rupture has been
described and may be a bailout option in cases of rapid deterioration.41
Contained rupture producing a periaortic hematoma has a less dramatic presentation.
Pericardial drainage and/or observation may be initially considered in cases with
limited injury and noncatastrophic clinical presentation. Nevertheless, close surveillance
and repeated MDCT assessment remain important because adverse evolution is possible
up to several hours or days from the rupture event.35
Device Embolization
Valve embolization is an infrequent yet important TAVR complication (Table 1) and
accounts for ≈45% of emergency cardiac surgery in patients treated with TAVR.42, 43,
44, 45, 46, 47 Its occurrence imparts a 9‐fold increase in mortality compared with
uncomplicated cases.31 Embolization usually happens acutely and intraprocedurally,
though late device migration (up to 1 year after TAVR) has also been described.48,
49, 50 Notably, the incidence of valve embolization has decreased over the years attributable
to increasing institutional and operator experience and the availability of preplanning
MDCT and newer‐generation valves.8, 44, 45, 51
Table 1
Incidence of Valve Embolization in TAVR
Study
Year(s)
Rate
References
Hamm et al
2011
0.5%
42
Gaede et al
2014–2016
0.2%
43
Ludman et al
2008–2015
0.2%–1.7%
44
Ludman et al
2016–2017
0.3%
45
Auffret et al
2010–2015
1.2%
46
Holmes et al
2012–2014
0.9%
47
TAVR indicates transcatheter aortic valve replacement.
John Wiley & Sons, Ltd
Valve dislocations are either cranial toward the aorta or caudal into the LVOT/left
ventricle. Aortic embolization is commonly the result of deployment in a high position
and/or poor coaxial alignment of the device to the valve plane during implantation.
Rarely, delivery system failure can lead to misalignment of the balloon and stent
frame of balloon expandable systems or failed valve release in self‐ and mechanically
expanding systems.52
Caudal migration toward the LVOT or left ventricle usually occurs because of low implantation
depth, eccentric and asymmetric calcification, and more rarely because of device undersizing.53
How to Avoid
Avoidance of stored tension in the delivery system is important to prevent the risk
of valve dislocation. During general anesthesia, a “breath hold” maneuver may be useful
during valve deployment.
TAVR device migration can also arise during equipment retrieval after valve deployment.
Inaccurate maneuvering of the pigtail catheter can hook the stent frame and snare
the device during withdrawal. Use of a conventional 0.035‐inch wire to straighten
the pigtail facilitates safe removal.
How to Treat
Treatment options are strictly related to operator experience, clinical and anatomic
factors, and the mechanics of device migration.
Hemodynamics determine initial management in the case of acute valve embolization.
Where necessary, general anesthesia and femoral‐femoral cardiopulmonary bypass can
be considered before conventional cardiac surgery. Fortunately, hemodynamics are usually
not catastrophic, and the dislocated valve can be snared and secured in a suitable
position. Permanent fixation of the embolized valve may be achieved using an aortic
stent (Figure 4), and a second valve can then be deployed in standard fashion. When
caudal embolization occurs toward the LVOT/left ventricle, the choice is either to
implant a second device to secure the embolized valve in a suitable subannular position
or surgical removal of the embolized valve followed by transapical deployment of a
second device or conventional surgical aortic valve replacement.52, 53, 54, 55, 56
Figure 4
A case of aortic TAVR device embolization. In this case, a balloon‐expandable Sapien
XT valve was deployed in a standard fashion under rapid pacing (A). However, the device
was dislocated into the aortic root during delivery system retrieval (B). The Sapien
XT was snared and secured in a suitable position in the descending aorta (C and D).
A second Sapien XT was deployed in the standard position (E) and an aortic stent used
to secure the embolized valve position (F).
If surgery is not an option because of prohibitive risk, the embolized valve can be
dragged into a subannular position using a partially inflated valvuloplasty balloon
under rapid ventricular pacing. Maintaining coaxial wire positioning is essential
during this maneuver. A partially overlapping second valve can then be implanted to
anchor the dislocated valve and prevent distal migration. Tiroch et al55 described
a successful case in which an Amplatz GooseNeck Snare (ev3; Endovascular Inc, Plymouth,
MN) was used to retrieve a Sapien 3 valve from the left ventricle after unsuccessful
attempts using standard valvuloplasty balloons.
Coronary Occlusion
Coronary artery obstruction by leaflet material during TAVR is a relatively infrequent
complication but has potentially catastrophic clinical consequences, with an associated
mortality of up to 50%. Coronary occlusion occurs in <1% of native valve interventions
and tends to involve the left main stem more frequently than the right coronary artery.4
Occlusion is typically caused by displacement of the calcified leaflets of the native
aortic valve toward the coronary ostia valve implantation. Coronary flow obstruction
can thus be related either to coverage of the coronary ostia or sealing of the sinus
of Valsalva at the sinotubular junction. Identification of patients at high risk of
coronary occlusion is therefore a key component of procedural planning. Anatomic features
that predispose to coronary occlusion are low coronary height (<12 mm) and narrow
sinus of Valsalva diameter (<30 mm).57
Intraprocedural coronary occlusion is more common during valve‐in‐valve procedures
(TAVR within a failed surgical bioprosthesis) as a consequence of reduced distance
between the valve leaflets and coronary ostia (attributable to the supra‐annular design
of surgical prostheses) and the narrower sinus of Valsalva (attributable to surgical
bioprosthesis suturing). In particular, bioprosthetic valves with leaflets mounting
outside an internal stent (eg, Mitraflow Sorin and Triflecta, St. Jude Medical Inc.,
St Paul, MN) or stentless bioprosthetic valves are at higher risk because the leaflets
of these bioprostheses may extent outward beyond the surgical device implantation
after TAVR.58
Coronary occlusion causes rapidly worsening severe hypotension with dynamic ST‐segment
changes in 50% and ventricular arrhythmias in 25% of cases.57 Immediate angiographic
assessment of coronary patency is required in patients in whom coronary occlusion
is suspected.
How to Avoid
Preprocedural cardiac MDCT is critical to identify patients at risk of coronary occlusion
by measurement of the height of the coronary ostia in relation to the aortic annulus,
the width and height of the sinus of Valsalva, and the width of the sinotubular junction.
In patients who are deemed at high risk, coronary protection with a standard 0.014‐inch
guidewire is advisable to help prevent and treat potential occlusion. In some cases,
a preemptive coronary balloon or stent can be mounted on a guidewire and advanced
in the left anterior descending artery and/or right coronary artery during valve deployment.
If coronary occlusion occurs, the stent can be pulled back and deployed in a “chimney”
fashion to maintain coronary patency59 (Figure 5).
Figure 5
Preventive strategies to avoid coronary occlusion in a high risk valve‐in‐valve procedure.
This case shows the wire and jailed stent protection technique in a patient with a
degenerated Sorin Freedom stentless 23 mm valve (A through C). Baseline multidetector
computed tomography and angiography showed the low bilateral coronary takeoff. An
undeployed stent was prophylactically positioned in the left main stem (LMS) before
advancing a Sapien XT 20‐mm valve (C and D). Immediately after valve deployment, the
patient's hemodynamics crashed and the coronary stent was inflated at high pressure
in the LMS at the ostial position (E). The final aortogram showed the Sapien‐XT valve
in correct position and widely patent coronary arteries (F). Reprinted from Maggio
et al59 with permission. Copyright ©2017, Oxford University Press.
Although there are no prospective data, a repositionable TAVR valve is preferred in
patients at high risk of coronary occlusion.
How to Manage
In patients in whom coronary occlusion occurs without a protective guidewire in situ,
immediate cannulation of the affected coronary artery with a guiding catheter is required
to allow balloon angioplasty. Coronary stent deployment with high‐pressure postdilatation
is often needed to avoid ostial deformation.
Engaging the coronary ostia with a TAVR device in situ may be difficult and requires
dedicated strategies. Balloon‐expandable valves are deployed in the subcoronary position
and interact with the coronary arteries in <10% of cases—even then, coronary access
through the valve struts is generally straightforward.60 However, sudden coronary
occlusion is more frequently observed with balloon expandable valves, especially following
high implantation in an aortic root with shallow sinuses and low coronary ostia. The
CoreValve Evolut self‐expandable valve (Medtronic, Minneapolis, MN) is deployed in
the supra‐annular position, and coronary access can be difficult through the alternating
diamond‐shaped valve cells. Conversely, the ACURATE neo valve (Boston Scientific,
Natick, MA), despite its self‐expanding surpra‐annular design, allows easy access
to the coronary ostia thanks to the high commissure posts and a low sealing skirt
profile. Moreover, the ACURATE neo is designed to minimally protrude into the LVOT,
minimizing the risk of coronary occlusion.
The catheter of choice for the left coronary artery should be the Judkins left catheter
with preference for a smaller size (3.5 instead of 4.0), or the Extra‐Back‐up catheter
3.5, maintaining the diagnostic 0.035‐inch J‐wire within the catheter to facilitate
orientation of the catheter tip to engage the coronary ostia through the valve struts.
The basic technique is to curl the J‐wire against the valve leaflet and slide the
catheter over to open the primary curve. At this point, the tip of the catheter usually
passes through the valve strut to engage the left main ostium. Further catheter manipulation
may be required to obtain the best coaxial engagement. The Judkins right catheter
is effective for the right coronary artery in most cases.60
Coronary occlusion after self‐expandable device deployment can be resolved by snaring
the TAVR valve frame and lifting the deployed valve above the sinotubular junction.
This option is not available after deployment of a balloon‐expandable valve.
Recently, the BASILICA (Bioprosthetic or Native Aortic Scallop Intentional Laceration
to Prevent Iatrogenic Coronary Artery Obstruction) trial assessed the safety and feasibility
of transcatheter electrosurgery to lacerate the native aortic valve leaflets in patients
with a high risk of coronary occlusion.61 This is a modification of the LAMPOON procedure
in which an electrified guidewire (Astato XS 20, Asahi Intecc USA, Santa Ana, CA)
is used to lacerate the anterior mitral leaflet to prevent LVOT obstruction in patients
undergoing transcatheter mitral valve replacement.62 In the first experience on 30
high‐risk patients, the procedure was successful in 95%, and there was 100% freedom
from coronary occlusion during TAVR. This new transcatheter technique may thus prove
useful in elective high‐risk patients and as a bailout option for coronary occlusion.
However, the safety of the procedure needs to be confirmed in larger studies because
adverse cardiovascular events were observed in 30% of the cases, including 1 (3%)
disabling stroke and 2 (7%) nondisabling strokes.61
Stroke
Recent trials in low‐risk patients have demonstrated a low incidence of disabling
stroke (0.6% and 0.5% at 30 days in the PARTNER 3 [Safety and Effectiveness of the
SAPIEN 3 Transcatheter Heart Valve in Low‐Risk Patients With Aortic Stenosis] and
Evolut Low Risk trials, respectively) and noninferiority of TAVR compared with surgery
with respect to stroke‐free survival (HR, 0.25; 95% CI; 0.07–0.88; P=0.02 in PARTNER
3).1, 2 Nevertheless, stroke remains one of the most feared complications of TAVR,
with a high risk of 30‐day mortality (odds ratio [OR], 6.45; 95% CI, 3.9–10.6).1,
2, 63 Contemporary data including different TAVR technologies in high‐ and intermediate‐risk
patients show a 30‐day stroke rate ranging from 1.4% to 1.9%.64, 65, 66, 67 Subclinical
new cerebral ischemic lesions are much more common and can be identified using diffusion‐weighted
magnetic resonance imaging in up to 80% of patients undergoing TAVR.68
The occurrence of TAVR‐related stroke demonstrates a bimodal pattern of distribution,
with up to 50% of events occurring within the first 24 hours after TAVR (dependent
on clinical and procedural factors) and a late phase >10 days after TAVR (dependent
on clinical characteristics—specifically, the atherosclerotic and overall frailty
profile).69 Among early (0–10 days) patient‐related predictors, those associated with
stroke in multivariate models in the CoreValve trials were peripheral vascular disease
(HR, 1.44; 95% CI, 1.03–2.00), prior transient ischemic attack (HR, 2.48; 95% CI,
1.67–3.67), angina (HR, 1.63; 95% CI, 1.15–2.33), body mass index <21 kg/m2 (HR, 2.14;
95% CI, 1.37–3.34) and a previous fall (HR, 1.72; 95% CI, 1.20–2.47), while the absence
of previous coronary artery bypass grafts was protective (HR, 0.58; 95% CI, 0.39–0.86).
Among the procedural variables, total time in the catheterization laboratory (HR,
1.003; 95% CI, 1.000–1.005), total time of delivery system in the body (HR, 1.01;
95% CI, 1.004–1.02), and rapid pacing during valvuloplasty (HR, 9.86; 95% CI, 1.37–70.7)
were associated with early stroke.70
Histopathology of debris collected by cerebral embolic protection devices (CEPDs)
used during TAVR demonstrates that embolized tissue particles can originate from the
aortic valve, the aorta, and the left ventricle and often involve a thrombus. The
embolized material can cause cerebral ischemia itself or can trigger further thrombus
development, thus explaining why the clinical manifestation (and consequent diagnosis)
of early TAVR‐related stroke can be delayed for up to 10 days.
How to Avoid
Optimal anticoagulation throughout the procedure is essential to minimize thrombus
formation. The BRAVO (Effect of Bivalirudin on Aortic Valve Intervention Outcome)
trial has shown that bivalirudin and heparin yield similar rates of major bleeding
and ischemic cardiovascular events 30 days after TAVR.71 Unfractionated heparin therefore
remains the standard during TAVR, with a parenteral bolus followed by additional doses
until an activated clotting time of 250 to 300 seconds is achieved.
CEPDs positioned across the origins of the supra‐aortic vessels capture or deflect
embolic debris away from the cerebral vasculature and potentially reduce the burden
of ischemic strokes during TAVR. However, their use in current clinical practice remains
limited, with <2% of CEPD‐assisted TAVR in the Evolut Low Risk trial and even less
in routine clinical practice.2
Use of CEPD has been associated with a smaller volume of silent ischemic lesions,
although a recent meta‐analysis failed to demonstrate a reduction in the number of
single or multiple ischemic lesions.72, 73 Despite a significant reduction in 30‐day
stroke rate (OR, 0.55; 95% CI, 0.31–0.98), CEPDs have no impact on 30‐day mortality
(OR, 0.43; 95% CI, 0.18–1.05).72
A significant number of thromboembolic cerebral insults relate to territories supplied
by the vertebral arteries (a segment of the cerebral circulation unprotected by most
currently available CEPDs; Figure 6) and extended coverage across all the supra‐aortic
vessels (including the left subclavian artery) is preferable. However, most currently
available devices (including the Sentinel CPS [Claret Medical Inc, Santa Rosa, CA]
and Embrella [Edwards Lifesciences, Irvine, CA]) protect only the brachiocephalic
and left common carotid arteries, which supply only 9 of 28 brain regions as a consequence
of the dual posterior circulation blood supply.
Figure 6
Cerebral embolic protection device. The upper panel shows the degree of cerebral protection
provided by currently available embolic protection devices. Devices that cover the
brachiocephalic trunk and left common carotid arteries protect only 9 of 28 brain
regions, considering the dual blood supply of the posterior cerebral circulation.
TAVR indicates transcatheter aortic valve replacement.
The TriGuard device (Keystone Heart Ltd., Herzliya, Israel) is the only commercially
available CEPD that allows complete coverage of the supra‐aortic vessels. In the DEFLECT
III (Prospective, Randomized Evaluation of the TriGuard HDH Embolic Deflection Device
During Transcatheter Aortic Valve Implantation) trial, this device was successfully
positioned in 89% of cases and appeared to mitigate new neurological deficits and
cognitive impairment after transcatheter aortic valve implantation yielding a numeric
greater freedom from new cerebral ischemic lesions (26.9% versus 11.5%) and smaller
lesion volume (19.6 mm3 versus 34.8 mm3; P=0.07) and improved cognitive function compared
with the control arm (P=0.028).74
Several new CEPDs that provide full coverage of the aortic arch are under evaluation
for clinical use,75 including the Emblock Embolic Protection System (Innovative Cardiovascular
Solutions, LLC, Grand Rapids, MI) and the Emboliner Embolic Protection Catheter (Emboline
Inc, Santa Cruz, CA). The Emblock device incorporates a 4F pigtail catheter to facilitate
TAVR device positioning, while the Emboliner captures both cerebral and noncerebral
emboli to provide full‐body embolic protection.
The optimal combination (single versus double) and duration of antiplatelet therapy
to mitigate the risk of thrombosis after TAVR has not been established,76 and dual
antiplatelet therapy (aspirin and clopidogrel) for 3 to 6 months is the most commonly
used regime.
How to Manage
Diagnosis of periprocedural stroke is often delayed because patients are often under
general anesthesia or conscious sedation. When stroke is considered, prompt access
to computed tomography of the brain, computed tomography cerebral angiography, and
specialist care by a dedicated stroke team are essential. Anectodal experiences suggest
that mechanical thrombectomy may have a role in acute and late‐presenting stroke following
TAVR.77
Periprocedural Conduction Abnormalities
Conduction abnormalities requiring permanent pacemaker (PPM) implantation and development
of new left bundle branch block (LBBB) remain the most common TAVR complications.78
Many patients with aortic stenosis have some conduction disease already, but the close
proximity of the atrioventricular conduction system to the aortic valve apparatus
makes it especially susceptible to injury during TAVR.79
Perioperative conduction abnormalities result from mechanical compression of the conduction
tissue as a result of pre‐ or postdilatation, deep implant depth, or the use of self‐expanding
devices and those with longer stent frames.80
High‐Grade Atrioventricular Block and PPM
The development of high grade atrioventricular block usually occurs within 24 hours
of the procedure independent of the valve used.81 However, 2% to 7% of patients can
develop high‐grade atrioventricular block beyond 48 hours and 85% to 90% of PPM implants
are required within 7 days of the procedure (median 3 days).81, 82 Late‐onset high‐degree
atrioventricular block is uncommon, and in one recent study no patients with a normal
ECG 2 days after TAVR developed delayed high‐degree atrioventricular block.81 Similarly,
99.6% of patients without LBBB remained PPM free after 1 year.83
New LBBB
New‐onset LBBB after SAVR is a predictor of syncope, atrioventricular block, and sudden
cardiac death.80
After TAVR, the incidence of new periprocedural LBBB varies widely and is higher with
self‐expanding (18%–65%, Medtronic CoreValve) compared with balloon‐expandable valves
(4%–30%, Edwards Sapien/Sapien XT).79, 84 Studies of LBBB with new‐generation valves
are limited: 12% to 22% for Sapien 3 valve,85, 86 34% for Evolut R,87 and 55% to 77%
for Boston Lotus valve.1, 2, 88, 89
In PARTNER 3, the incidence of new LBBB at 1 year was 23.7% in the TAVR cohort compared
with 8.0% in the SAVR cohort (HR, 3.43; 95% CI, 2.32–5.08).1 LBBB usually develops
within 24 hours of TAVR (85%–94%) and may resolve within 30 days, but 55% of patients
have persistent LBBB.78 The main predictors are use of a self‐expandable valve (OR,
2.5–8.5),90, 91, 92 depth of prosthesis within the LVOT (OR, 1.15–1.4/1 mm),93, 94,
95 overexpansion of the native aortic annulus (OR, 5.3 if >15%),93, 96 and larger
valve size.83, 84
There are limited studies evaluating the association of new LBBB and need for PPM
implantation, but 2 recent meta‐analyses97, 98 suggested a 2‐fold higher risk of PPM
implant in patients with new LBBB after TAVR. Approximately 8% to 19% of patients
with new LBBB require a PPM, the most frequent indication being progression to atrioventricular
nodal block.83, 99, 100, 101 New LBBB is also associated with higher cardiovascular
mortality (OR, 1.39; CI, 1.04–1.86),97 especially in patients with QRS >160 ms (HR,
4.78; CI, 1.56–14.53).102
How to Prevent
Conduction disturbances in patients undergoing TAVR are largely dependent on unmodifiable
patient‐related risk factors, including electrical and anatomic variables. Baseline
right bundle branch block is the strongest and most consistent risk factor for PPM
regardless of valve type (OR, 2.8–46.7).78, 79, 96 First‐degree atrioventricular block
is also strongly associated (OR, 4.0–11.4).103, 104, 105 Among anatomic predictors,
the presence of calcification below the aortic annulus and in the LVOT increases the
risk for PPM (OR, 1.03–4.7).103, 106
Procedural variables are also important. In a recent systematic review,107 the rate
of PPM varied considerably depending on the type of valve deployed—self‐ and mechanically
expanding valves (CoreValve/Evolut/Lotus) have a consistently higher risk of PPM107
(Medtronic CoreValve versus Edwards Sapien/Sapien XT; OR, 2.6–25.7)79 (Table 2). In
PARTNER 3 (using the Sapien 3 valve) there was no difference in PPM rate between TAVR
and surgery (6.6% versus 4.1%; HR, 1.65; 95% CI, 0.92–2.95), while the Evolut Low
Risk study showed a higher rate of PPM in the TAVR group (17.4% versus 6.1%).
Table 2
Rate of Permanent Pacemaker Implantation
Valve
Permanent Pacemaker Implantation Rate (%)
Sapien/Sapien XT
2.3–28.2
Sapien 3
4–24
CoreValve
16.3–37.7
Evolut R
14.7–26.7
Lotus
27.9–36.1
Direct flow medical
17
Portico
13.5
JenaValve
14.4
Accurate Neo
2.3–10.2
Reprinted from van Rosendael et al107 with permission. Copyright ©2018, Oxford University
Press.
John Wiley & Sons, Ltd
Depth of implantation is also strongly associated with increased risk of PPM regardless
of the type of prosthesis (OR, 1.1–1.5/1 mm of LVOT).84, 89, 106, 108, 109, 110 (Table 3).
Another factor is oversizing/stretching of aortic annulus by 10% to 15%, which increases
the risk of PPM with first‐generation devices.84
Table 3
Risk of Conduction Disturbances According to the Depth of Implantation
Valve Prosthesis
Proposed Cutoff Values
References
Edwards Sapien XT
6.3 mm
108
Edwards Sapien 3
7 mm or 25% of stent frame
106, 108
Medtronic CoreValve
6–7.8 mm
109, 110
Lotus
5–6.7 mm
89, 108
John Wiley & Sons, Ltd
The baseline risk of developing conduction abnormalities may also influence the strategy
of pacing support during the TAVR procedure. Rapid ventricular pacing is indeed often
required during balloon aortic valvuloplasty or valve deployment and use of pacing
via the left ventricular guidewire is an established technique to simplify the procedure
and reduce the risk of vascular complications and pericardial effusion.111 However,
left ventricular guidewire pacing could expose the patient to a period of hemodynamic
instability if the left ventricular guidewire was removed prematurely. Thus, a right
ventricular temporary pacing wire may be preferable in patients at high risk of periprocedural
conduction disturbances. Prophylactic PPM implantation may also be considered in patients
with preexisting high‐grade conduction abnormalities (Figure 1).
How to Manage
The prognostic implications of PPM after TAVR are currently unclear, with conflicting
data. Registry data from the United States99 showed increased mortality in patients
requiring PPM (HR, 1.31; CI, 1.09–1.58), whereas other studies observed mortality
reduction (HR, 0.31; CI, 0.11–0.85).108 Furthermore, a recent systematic review107
and meta‐analysis112 have shown no association between PPM and all‐cause mortality.
The European Society of Cardiology guidelines113 suggest 7 days of observation for
stable high‐degree atrioventricular block before PPM implant, in contrast with current
routine clinical practice, where 50% of patients receive a PPM within 3 days of TAVR.97
Recovery of intrinsic rhythm has been observed in up to 50% of paced patients at the
time of TAVR follow‐up.114, 115
Clear indications are crucial, as PPM implantation exposes patients to prolonged hospital
stay, risk of infection, thromboembolism, and suboptimal functional recovery. While
immediate PPM implant can be considered in stable patients with preexisting conduction
disease (right bundle branch block and first‐degree atrioventricular block) who develop
high‐grade atrioventricular block during valve deployment, spontaneous recovery of
atrioventricular node function might occur within 24 hours of observation in cases
without preexisting conduction disorder.
Management of new LBBB following TAVR remains controversial. The general consensus
is for a period (48–72 hours) of inpatient monitoring to detect possible progression
to atrioventricular nodal block and need for PPM implant. Persistent LBBB with QRS
>160 ms and associated first‐degree heart block may require prophylactic PPM. An implantable
loop recorder may be an option when LBBB persists and further studies are required
to define optimal management.
General Considerations and Conclusion
The PARTNER 3 trial has shown superiority of TAVR for the composite end point of mortality,
stroke, and hospital readmission at 1 year (HR, 0.38; 95% CI, 0.15–1.00) compared
with SAVR. Similarly, the Evolut Low Risk trial demonstrated the noninferiority of
TAVR versus SAVR regarding the composite primary end point of death and stroke (5.3%
versus 6.7%) with a longer follow‐up of 2 years.1, 2 If confirmed at long‐term follow
up, these favorable results in low‐risk patients will drive expanded indications for
TAVR. Focus on the prevention and treatment of procedural complications is therefore
essential.
Before any TAVR procedure, it is essential for the heart team to discuss bailout options,
including whether conversion to open heart surgery is appropriate. Procedural planning
is key to prevent potentially catastrophic complications, including landing zone rupture,
device embolization, or coronary occlusion. Preprocedural imaging is essential to
plan vascular access, and intravascular lithotripsy may have a role in high‐risk cases.
Further studies are warranted to define the place of CEPDs in reducing the risk of
stroke during TAVR and the indications for their use. Ultimately, all members of the
heart team need to understand strategies for the prevention and management of procedural
complications during TAVR. This will produce a more predictable procedure with better
long‐term outcomes for more of our patients with aortic stenosis.
Disclosures
Dr Scarsini received an education and training grant from European Association of
Percutaneous Cardiovascular Interventions and served on the advisory board for Abbott.
Dr Prendergast received unrestricted education and research grants from Edwards Lifesciences
and speaker fees from Edwards Lifesciences. Dr Ribichini received an institutional
research grant from Philips‐Volcano and Edwards Lifesciences. Dr Banning received
institutional funding for an interventional fellowship from Boston Scientific. The
remaining authors have no disclosures to report.
Supporting information
Table S1. VARC‐2 Vascular Access Site and Access‐Related Complication
Click here for additional data file.