Accepted Manuscript

Mitral valve stenosis after transcatheter aortic valve replacement:

Case report and review of the literature

Francesco Cannata, Damiano Regazzoli, Giancarlo Barberis,

Mauro Chiarito, Pier Pasquale Leone, Vincenzo Lavanco, Giulio
G. Stefanini, Giuseppe Ferrante, Paolo Pagnotta, Renato Bragato,
Elena Corrada, Lucia Torracca, Gianluigi Condorelli, Bernhard
Reimers

PII: S1553-8389(19)30156-3
DOI: https://doi.org/10.1016/j.carrev.2019.02.023
Reference: CARREV 1529
To appear in: Cardiovascular Revascularization Medicine
Received date: 2 January 2019
Revised date: 5 February 2019
Accepted date: 19 February 2019

Please cite this article as: F. Cannata, D. Regazzoli, G. Barberis, et al., Mitral valve
stenosis after transcatheter aortic valve replacement: Case report and review of the
literature, Cardiovascular Revascularization Medicine, https://doi.org/10.1016/
j.carrev.2019.02.023

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 ACCEPTED MANUSCRIPT

Mitral valve stenosis after transcatheter aortic valve replacement:

case report and review of the literature

Francesco Cannata MD1*, Damiano Regazzoli MD1*, Giancarlo Barberis MD1, Mauro Chiarito MD1, Pier
Pasquale Leone MD1, Vincenzo Lavanco MD2, Giulio G. Stefanini MD1, Giuseppe Ferrante MD1, Paolo
Pagnotta MD1, Renato Bragato MD2, Elena Corrada MD2, Lucia Torracca MD3, Gianluigi Condorelli MD1,
Bernhard Reimers MD1

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1.Interventional Cardiology Unit, Cardio Center, Humanitas Research Hospital, Rozzano-Milano, Italy.

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2.Non-invasive Cardiology Unit, Cardio Center, Humanitas Research Hospital, Rozzano-Milano, Italy

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3.Cardiac Surgery, Cardio Center, Humanitas Research Hospital, Rozzano-Milano, Italy.

*Dr. Cannata and Dr. Regazzoli contributed equally to this manuscript and are joint first authors
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Corresponding author:
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Damiano Regazzoli MD

Interventional Cardiology Unit, Cardio Center, Humanitas Research Hospital

Via Manzoni 56, 20089 Rozzano-Milano, Italy

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damiano.regazzolilancini@humanitas.it
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+390282244610
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Word count: 2329 (abstract excluded)

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Figures: 5

Tables: 1
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Key Words: transcatheter aortic valve replacement; mitral stenosis; multimodality imaging.

Declarations of interest: none.

Funding: this research did not receive any specific grant from funding agencies in the public, commercial, or
not-for-profit sectors.
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Abstract

Mitral stenosis is a rare and potentially severe complication of transcatheter aortic valve replacement
(TAVR). Given the anatomic coupling and interdependence of the aortic and mitral valves, it comes by itself
that procedures (either surgical or percutaneous) involving the aortic valve imply the risk of altering mitral
valve function. Indeed, transcatheter aortic prostheses may impair adequate anterior mitral leaflet (AML)
opening, especially when implanted in a “low” position, thus resulting in high transvalvular gradients.

Hereby, we report the case of a 71-year-old male with symptomatic severe aortic stenosis and a history of
previous surgical mitral valve repair who underwent TAVR with a self-expandable prosthesis.
Notwithstanding an acceptable angiographic position, the prosthetic frame was shown to interfere with the
AML, as evidenced by augmented transmitral gradients; nonetheless, pulmonary artery pressures remained

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unchanged, and the patient experienced symptomatic improvement. Therefore, a conservative approach
was chosen and the patient was discharged home after medical therapy optimization.

Moreover, we provide a review of the available literature regarding the incidence, predictors and possible

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management of this infrequent complication.

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Abbreviations
AML: anterior mitral leaflet
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AV: aortic valve
eGFR: estimated glomerular filtration rate
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LVEF: left ventricular ejection fraction

LVOT: left ventricular outflow tract
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MAC: mitral annular calcification

MDCT: multidetector computed tomography
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MS: mitral stenosis

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MV: mitral valve

NYHA: New York Heart Association
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sPAP: systolic pulmonary artery pressure

TAVR: transcatheter aortic valve replacement
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TEE: trans-esophageal echocardiogram

TTE: trans-thoracic echocardiogram
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Introduction

Mitral (MV) and aortic valves (AV) are coupled and interdependent, as the anterior mitral annulus is
anatomically linked to both the left and non-coronary aortic cusps through a shared fibrous rim. [1]

This close anatomical and functional relationship has been studied in vitro and, recently, even more so with
advanced imaging techniques such as computed tomography scan and echocardiography, both in the
physiological setting and in patients with AV stenosis. When AV becomes fibrotic and calcific, and
eventually develops high transvalvular gradients, MV is in turn affected, as inter-commissural diameter,
valvular area, annular height and motion are all reduced. [1] While these parameters seem to remain
unchanged after transcatheter aortic valve replacement (TAVR), there is an additional reduction of the
antero-posterior diameter due to the prosthetic metallic frame, with consequent distortion of the MV

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annular saddle shape. [1 - 3]

MV area is usually large enough to compensate some amount of impairment in leaflet motion; indeed,
hemodynamically relevant mitral stenosis (MS) is rarely reported after TAVR.

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Case description

We report the case of a 71-year-old male patient with coronary artery and valvular disease, who was
referred to our institution for severe aortic valve stenosis symptomatic for dyspnea (NYHA III) leading to
three hospitalizations for congestive heart failure.

He had an history of hypertension, diabetes mellitus, smoke, paroxysmal atrial fibrillation and chronic
kidney disease (stage IV; eGFR 25 ml/min/1,73 m2).

He was diagnosed in 2004 with ischemic heart disease due to significant two-vessel coronary stenosis, left
ventricular dysfunction (LVEF 35%), severe mitral regurgitation due to a mixed degenerative-functional
mechanism (P2 prolapse and annular dilatation) and moderate tricuspid regurgitation. He subsequently
underwent heart surgery: mitral valve repair with quadrangular resection of the posterior leaflet and

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undersized annuloplasty (incomplete 26 mm Cosgrove Band; Edwards Lifesciences, Irvine, USA), tricuspid
valve repair and coronary artery bypass grafting (left internal mammary artery to left anterior descending
artery and saphenous vein graft to marginal branch).

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Trans-thoracic echocardiogram (TTE) performed at admission showed severely dilated left ventricle with
diffuse hypokinesia and a significant reduction of systolic function (LVEF 27%); AV was calcific with severe

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low flow-low gradient stenosis (mean gradient 32 mmHg; aortic area 0.8 cm 2) and moderate regurgitation;
transmitral gradients were slightly high (mean gradient 5 mmHg) due to reduced motion of the posterior
leaflet and due to the restrictive annuloplasty (Fig. 1); systolic pulmonary artery pressure (sPAP) was
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increased (65 mmHg).

After Heart Team discussion, the patient was deemed inoperable due to prohibitive surgical risk (STS score
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17.4%; Euroscore II: 39.8%), and was therefore referred for TAVR.

Computed tomography scan showed sufficient femoral accesses, while coronary angiography excluded
coronary artery stenosis requiring treatment, and showed patent grafts.
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The patient underwent TAVR with a 34-mm CoreValve Evolut R (Medtronic, Minneapolis, USA): the
procedure was performed under local anaesthesia and conscious sedation through right femoral access.
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Final angiogram showed a “low” position of the valve, which was deemed acceptable, with mild
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paravalvular leak, also confirmed by TTE (Fig. 2).

The following hospitalization was clinically uncomplicated, but the echocardiographic examination
performed before discharge showed a significant increase of the transmitral gradients (mean gradient = 12
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mmHg, peak gradient = 24 mmHg); subsequent trans-esophageal echocardiogram (TEE) confirmed a

reduced mitral valve area (planimetric MV area = 1.5 cm²), mainly due to the interference of the aortic
prosthesis with the anterior mitral leaflet (AML) (Fig. 3).
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As the patient experienced a significant improvement of functional capacity (NYHA II) after TAVR, and as
pulmonary pressures and NT-proBNP remained unchanged, a conservative approach was chosen: rate
control therapy was titrated, and the patient was discharged with a strict follow-up schedule. The 1-month
and 3-month follow-up TTE confirmed the stability of transmitral gradients, while quality of life improved
and functional capacity remained unchanged (NYHA II).

Discussion

Aortic stenosis (AS) is the most prevalent valvular heart disease of advanced age, and its incidence will
continue to rise [4], as will its healthcare burden. In recent years, TAVR emerged as an alternative to open
heart surgery, allowing an effective and safer treatment of AS in patients deemed inoperable or at
intermediate-high surgical risk. [5 - 7]
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While several complications can occur after this procedure (such as vascular or aortic damages, rhythm
disturbances, stroke), only few are the reported cases of increased transmitral gradients following aortic
valve implantation. Furthermore, clinical relevance of this event is unknown, as a wide range of clinical
presentations varying between asymptomatic increase of mitral gradients to severe MS needing urgent
intervention may occur.

In the following sections, the main aspects of this rare complication will be analysed.

A. Incidence

It is difficult to correctly estimate the incidence of MS after transcatheter aortic procedures.

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The prevalence of MS in developed countries has recently been reported around 0.1% [4]. Nonetheless, the
coexistence of MS and AS has been frequently identified in patients undergoing both surgical and
transcatheter aortic valve replacement, reaching peaks of 15-17% [8].

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On the other hand, no data is available regarding the actual share of patients that develop elevated

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transmitral gradients after TAVR. As of today, it is a complication rarely reported (Table 1) [9 - 13], although
its true incidence may exceed that currently described due to under-reporting.

Further studies and registries are needed to evaluate the incidence of this issue.
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B. Predictors
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Because of the strict relationship and interdependence between aortic and mitral valve, predictive factors
of MS after TAVR should be searched for taking into account this interaction. Possible predictors identified
from literature and pathophysiology are the following:
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 Mitral calcifications: severe annular calcification, defined as calcific degeneration of more than half
of the mitral annulus circumference, may play a role in developing transvalvular gradients after
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TAVR [14 - 16]. In fact, patients with at least moderate mitral annular calcification have significantly
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smaller MV areas compared with those with mild or no calcification, resulting in a reduction in MV
height and motion as well. [1] Moreover, severe mitral annular calcifications are a strong
independent predictor of all-cause and cardiovascular mortality after TAVR [6].
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 Transcatheter valve implantation model and depth: among reported cases of MS after TAVR, 80%
occurred with a self-expandable valve, either Corevalve or Portico (Abbott, Santa Clara, USA). [9 -
12] Balloon expandable valves are usually implanted with minimal protrusion (2 to 4 mm) below
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the aortic annulus; the only reported case of MS after Edwards implantation (Edwards Lifesciences,
Irvine, USA) was actually related to underestimation of baseline transmitral gradients in a valve
with significant degenerative alterations involving both annulus and leaflets. [13] On the other
hand, self-expanding devices are usually positioned slightly lower (3 to 5 mm) into left ventricular
outflow tract (LVOT), and may sometimes be implanted even deeper (in a so called “low” position).
The high profile of these valves, associated with ventricular protrusion, may lead to impingement
on the anterior mitral leaflet and limit its diastolic opening.
 Altered transmitral gradients at baseline: impaired transmitral flow before TAVR may be hidden by
the elevated left-ventricular diastolic pressure related to the severe aortic stenosis. Thus, after
TAVR, the sudden change in left heart haemodynamics may unveil the already hampered
transmitral flow. [13, 17, 18] The finding of high or slightly altered transmitral gradients at baseline
must prompt a careful evaluation of MV anatomy and area before TAVR.
 Previous MV surgery: caution is warranted when it comes to TAVR in patients who have already
undergone MV surgical repair. MV surgery predisposes to MS, either due to distortion of the
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fibrous curtain between aortic and mitral valves, even when this is minimal, or due to considerable
reduction of MV area (i.e. MV repair with undersized annuloplasty). When MV is replaced with a
prosthesis, a mitro-aortic space of 4 mm is required in order to permit secure deployment of the
inflow portion of the aortic prosthesis frame. Indeed, two registries showed that sPAP increases
after TAVR in patients with previous MV surgery, likely due to the above-mentioned mechanisms.
[19, 20]

C. Diagnostic work-up

TTE is the main diagnostic tool to assess such complication. (Fig. 4) The echocardiographic evaluation
begins with visual inspection, focusing on the position of the TAVR stent and its relationship with the AML,

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which may be impinged in case of a low TAVR implant. [18] A careful evaluation of mitral valve leaflets is
mandatory in order to examine their morphology and motion, while colour Doppler highlights any
suspicious accelerations of transmitral flow. Continuous-wave Doppler assesses mean transmitral

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gradients, which are rather suggestive of any impediment to ventricular filling, even though highly rate and
flow dependent. Provided favourable and stable haemodynamics and rhythm, if mean transmitral gradients

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are higher than 5 mmHg and, above all, are far increased after TAVR, MS must be suspected. MV area is the
reference measurement of MS severity, whereas mean transvalvular gradients reflect its haemodynamic
consequences. [21] MV area is independent of flow and rate, and should be measured using planimetry,
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which is a more reliable method than pressure half-time. Of note, MS does not usually have clinical
consequences at rest when valve area is larger than 1.5 cm². Eventually, a comprehensive
echocardiographic evaluation should assess the sPAP and the right heart, which would be altered in
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presence of hampered transmitral flow.

However, when poor acoustic windows significantly impact the accuracy of trans-thoracic
echocardiographic studies, alternative imaging methods are needed. First of all, TEE permits an optimal
view of MV anatomy and function, with an accurate focus on the interaction between MV and TAVR device.
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Planimetric MV area can be reliably measured via trans-gastric position or through three dimensional tools.
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Cardiac magnetic resonance may play a role in this setting since it can precisely assess valve anatomy and
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motion, turbulences and velocities of blood flow and volumes. [22] The main limitations are related to its
availability, costs and the necessity to perform it in a clinically stable setting, while echocardiography (both
TTE and TEE) can be effectively performed at bedside.
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Heart catheterization represents a valuable technique when imaging studies are equivocal, as it allows
direct haemodynamic assessment of MS and its consequence on pulmonary circulation. Its invasive nature
and the necessity to cross the prosthetic aortic valve limit its use.
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While multidetector CT scan (MDCT) does not allow evaluation of mitral valve function, it is fundamental in
order to verify feasibility of transcatheter procedures such as valve-in-ring or implantation of a
percutaneous valve in severely calcific annuli (valve-in-MAC) [23].

D. Management

Several factors should be taken into account when determining the optimal management strategy, such as
symptoms, haemodynamic repercussions, procedural risk and available treatment options (Fig. 5). [24]

At first, focus should be emphasized on implementation and titration of rate-control therapy (ideally short
acting beta-blockers), optimization of volume load and blood pressure control and correction of anaemia
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and thyroid disease, if present. Indeed, these factors represent possible confounders that may lead to
overestimation of transvalvular gradients, to worsening of symptoms and haemodynamics and, eventually,
to inappropriate decision-making.

Second, symptoms and haemodynamic repercussions should be taken into account. In fact, elevated
transmitral gradients may have no symptomatic correlates, especially if associated with a decrease of
valvular area other than severe. In such cases, a conservative approach with strict echocardiographic and
clinical follow-up may be suggested, especially if sPAP and heart failure markers such as NT-proBNP remain
unchanged. On the other hand, if MS either reduces functional capacity or compromises the clinical result
after TAVR causing dyspnoea at rest, additional treatment should be pursued. Patients abruptly developing
severe symptoms such as pulmonary oedema and haemodynamic instability may need immediate
evaluation and treatment.

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Third, surgical risk must be carefully evaluated, since patients being referred for TAVR are usually at high-
risk, due to comorbidities and frailty. If an intervention is needed in order to improve symptoms or

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haemodynamic stability, the case should be promptly discussed in a multidisciplinary Heart Team in order
to choose the best option. If surgical risk is not prohibitive, heart surgery may be opted for: surgical aortic
valve replacement may be associated with mitral valve replacement or repair in case of irreversible damage

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or if the MV is highly calcific and degenerated. In case of inoperable patients, imaging assessment of the
underlying mechanism of MS should guide the choice of the percutaneous approach. A too lowly implanted
TAVR causing a restricted diastolic opening of AML may be corrected with the “snare” technique, that is a
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loop-equipped catheter may be used to capture and pull the bioprosthesis slightly towards the ascending
aorta, often with the aid of a partially inflated valvuloplasty balloon. If the bioprosthesis is not stable in the
new position, a second valve may be implanted. [25, 26] When the TAVR is correctly positioned and the MS
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is due to distortion of a highly-calcific MV or due to an already impaired transmitral flow unveiled after
TAVR, trans-catheter mitral valve replacement could be taken into consideration. Provided some
anatomical features, such as circumferential heavy calcification of the MV ring and adequate valve sizing, a
balloon-expandable bioprosthesis may be positioned and deployed into the calcific native MV through a
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trans-septal or trans-apical access. [27, 28]

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Conclusions:

Mitral stenosis is a rare and potentially severe complication of TAVR. Possible risk factors may be extensive
calcifications of the mitral annulus, previous mitral valve repair (especially in the case of an undersized
annuloplasty) and pre-existing impaired transmitral flow. Implant height is of paramount importance, since
low implant of the prosthetic aortic valve may interfere with anterior mitral leaflet and increase transmitral
gradients; similarly, careful evaluation of mitral flow before and after the procedure is to be considered. If
mitral valve stenosis occurs after TAVR, therapeutic options include medical therapy, aortic prosthesis
snaring, implant of a transcatheter valve in mitral position and urgent or elective surgery.

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Figures

Fig.1: Baseline echocardiographic evaluation: mitral leaflets are thickened with impaired diastolic motion
(mainly of the posterior leaflet) as a result of previous mitral repair. Colour Doppler shows an acceleration
of transmitral flow, that reflects on continuous wave Doppler (mean gradient 5 mmHg).

Fig. 2: Echocardiographic (Panel A and B) and angiographic (Panel C) evaluation of the prosthetic valve
position, that appears to be lowly positioned into the left ventricular outflow tract.

Fig. 3: At transesophageal evaluation, restricted diastolic opening of the anterior mitral leaflet can be noted
(Panel A and B) due to the impingement of the aortic prosthesis. This resulted in significant transmitral
acceleration (Panel C) and elevated mean gradients of 12 mmHg (Panel D).

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Fig. 4: Diagnostic evaluation of increased mitral gradients after transcatheter aortic valve replacement. TTE:
trans-thoracic echocardiogram; TEE: trans-esophageal echocardiogram; CMR: cardiac magnetic resonance;
MDCT: multi-detector CT scan; CAT: heart catheterism; CW: continuous wave; PSAX: parasternal short axis;

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TAVR: trans-catheter aortic valve replacement; AML: anterior mitral leaflet; MV: mitral valve; MAC: mitral
annular calcification.

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Fig. 5: Possible therapeutic flow-chart. SAVR: surgical aortic valve replacement; TAVR: trans-catheter valve
replacement; MV: mitral valve; MAC: mitral annular calcification.
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Tables:

Table 1. Cases of post-TAVR mitral valve stenosis in patients with native mitral valves.
Title Authors Journal Ref. Prosthesis Patient and Mitral Valve post- Mechanism of Mitral Intervention Discharge
Indication TAVR Stenosis outcome
Transcatheter aortic valve Balghith M. et al J Saudi Heart Assoc [9] CoreValve 29 mm 90-y female Area = 2.04 cm² Impingement of anterior None Alive

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implantation (CoreValve) 2012;24:149–150 Symptomatic Mean gradient = 6 mmHg mitral valve leaflet by the
prosthesis complicated by severe aortic inflow portion of CoreValve

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mitral stenosis stenosis prosthesis

Acute mitral stenosis

after transcatheter aortic
Franco E. et al J Am Coll Cardiol.
2012;60(20):e35.
[10] Valve in Valve with
two CoreValve 26
78-y female
Symptomatic
Mean gradient = 13
mmHg
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Restricted diastolic opening
of the anterior mitral leaflet
Acute heart failure
Urgent aortic valve replacement
Alive

C
valve implantation mm severe aortic caused by the surgery in which both CoreValves
stenosis low-placed CoreValve were extracted and a 23-mm

Iatrogenic mitral stenosis

following transcatheter
Harries I. et al Indian Heart J.
2015;67(1): 60–61.
[11] CoreValve 29 mm 57-y female
Symptomatic
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Mean gradient = 7 mmHg
At 12-month mean
S Impingement of the
anterior leaflet of the mitral
Mitroflow bioprosthesis was
implanted
None Alive
At 12-month
aortic valve replacement

Acute severe mitral

stenosis immediately
Auer J. et al J Invasive Cardiol
2017;29(10):E154
[12] Portico 25 mm
severe aortic
stenosis
86-y female
Symptomatic
A N
gradient = 12 mmHg

Mean gradient = 11
mmHg
valve

Restricted diastolic opening

of the anterior mitral leaflet
Acute heart failure
Urgent aortic valve replacement
follow-up NYHA III

Alive

after transcatheter aortic

valve implantation
severe aortic
stenosis
M because of the migration of
the Portico valve into LVOT
surgery with removal of the Portico
valve and replacement with a 21

D
mm Perimount Magna
bioprosthesis

Increased mitral gradient Essandoh M. et J Cardiothorac Vasc [13]

T
Sapien3 23 mm E
81-y female Area = 2.2 cm² The mitral stenosis was None Alive

P
after transcatheter aortic al Anesth. Mean gradient = 7 mmHg presumably pre-existing but
valve replacement: is it 2018;32(1):598-599 was underestimated on the

E
anatomic mitral valve baseline TEE most likely
obstruction or related to because of conditions that

C
hemodynamic? increase left ventricular
diastolic pressure and

C
reduce mitral blood flow
rate: severe aortic stenosis

A and mild aortic

regurgitation.
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Highlights
 transcatheter aortic valve replacement is an effective and safer alternative to open heart surgery,
but still bears risk for dangerous complications
 increased transmitral gradients after transcatheter aortic valve replacement is a worrying finding,
whose clinical relevance and management are not well established
 risk factors are to be searched into the complex interaction and coupling between mitral and aortic
valves
 a multi-modality imaging approach is fundamental to detect this complication, to evaluate its
hemodynamic consequences and to drive the therapeutic strategy

PT
 the optimal management strategy choice should be based on the patient symptoms, hemodynamic
conditions and feasibility of the surgical and percutaneous techniques

RI
SC
NU
MA
E D
PT
CE
AC
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