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\begin{document}

\title{Valvular Complications Following the Impella Device Implantation}



\author[1]{Davorin Sef}%
\author[2]{Tito Kabir}%
\author[1]{Nicholas Lees}%
\author[1]{Ulrich Stock}%
\affil[1]{Royal Brompton and Harefield NHS Foundation Trust}%
\affil[2]{Royal Brompton and Harefield NHS Trust}%


\vspace{-1em}



  
  \date{June 10, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: Despite clear clinical benefits, there is limited evidence
regarding possible complications of the novel mechanical support device
Impella. Aortic and mitral valve regurgitation or injury are rare but
potential complications following implantation of the Impella device.
Methods: To evaluate valvular complications after the Impella device
implantation, we have performed a comprehensive search of literature on
multiple sites on this topic. Results and Conclusion: Ten case reports
and one observational retrospective study were identified, with a total
number of 19 patients identified. This article aims to draw attention to
potential periprocedural complications relating to the Impella, in
particular iatrogenic aortic and mitral valve injuries. Moreover, we
have summarized our recommendations emphasizing the need for careful
management and meticulous follow-up of these patients to avoid such
potentially devastating complications.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

Despite clear clinical benefits, there is limited evidence regarding
possible complications relating to the Impella (Abiomed Inc., Danvers,
Massachusetts) mechanical support device. The Impella device is being
increasingly used as an alternative to the intra-aortic balloon pump
(IABP) and veno-arterial extracorporeal membrane oxygenation (VA ECMO)
for haemodynamic support in patients with cardiogenic shock and
high-risk percutaneous coronary intervention {[}1{]}. It can also
effectively vent the left ventricle, especially in the setting of
incomplete unloading of the left ventricle during VA ECMO support
{[}2-5{]}. Furthermore, several percutaneous mechanical circulatory
support devices (VA ECMO, CentriMag, TandemHeart) including Impella have
been introduced into clinical practice for bridging patients with
end-stage heart failure to recovery, durable left ventricular assist
device support or orthotopic heart transplantation {[}6, 7{]}. Placement
and use of the Impella device bear potential risks. To date,
complications that have been reported are device-related, peripheral
vascular, distal thrombus formation with subsequent strokes, and
valvular injuries. The objective of this article is to draw specific
attention to valvular injuries as potential periprocedural complications
during Impella device support.

\textbf{METHODS}

Using MEDLINE/PubMed, Scopus and the Cochrane Library, we performed
searches of case reports and clinical studies published until 30 October
2020. Eligible studies were identified using various combinations of
Medical Subject Headings and keywords in the abstract or title: Impella,
aortic regurgitation, mitral regurgitation, aortic valve injury, mitral
valve injury, and mechanical circulatory support. Ethics Committee
approval was not required as this is a review manuscript.

\textbf{RESULTS}

As recent evidence still remains scarce due to the novelty of the device
and potential underreporting, we have reviewed literature in order to
highlight potentially life-threatening valvular complications. Ten case
reports and one observational retrospective study were identified, with
a total number of 19 patients identified, reporting periprocedural
complications of either aortic or mitral regurgitation related to the
Impella device. The characteristics of included studies and case reports
are presented in Table 1.

\textbf{DISCUSSION}

\textbf{Utilisation of Impella}

The Impella can provide haemodynamic support similar to ventricular
assist devices with the advantages of unloading the left ventricle and
being miniaturised and able to be placed percutaneously (2.5, CP)
{[}8{]}. By continuously aspirating blood from the left ventricle, the
Impella has a beneficial effect on LV unloading, coronary flow, and
overall cardiac output {[}9{]}. A recent study has demonstrated that in
acute myocardial infarction complicated by cardiogenic shock, treatment
with Impella, as compared with IABP, can improve shock severity
parameters due to superior haemodynamic support, although with no
significant effect on 30-day mortality {[}10, 11{]}. In addition, it has
been demonstrated that Impella can provide effective haemodynamic
support in several other indications such as high-risk percutaneous
coronary interventions (PCI) , bridge to destination or transplant {[}3,
9, 12{]}.

\textbf{Contraindications and complications}

As with other mechanical support devices, severe peripheral vascular
disease is a relative contraindication for femoral access due to the
risk of limb ischaemia. The presence of a mechanical aortic valve is
considered an absolute contraindication, while severe aortic stenosis as
a relative contraindication {[}8{]}.

Potential complications related to the use of Impella are
device-related, peripheral vascular and distal thrombus formation with
subsequent strokes. According to a recent report, the most common
complications reported were bleeding requiring transfusion (17.5\%),
vascular access complications (15.2\%), infection (12.9\%), haemolysis
(10.3\%), vascular complications with a need of surgical repair (9.7\%),
limb ischaemia (3.9\%) and bleeding requiring surgical intervention
(2.6\%) {[}8, 13{]}. Valvular complications included aortic and mitral
valve injury or regurgitation.

\textbf{Aortic valve regurgitation or injury}

Iatrogenic injury of the aortic valve (AV) is a potential complication
related to the Impella resulting in significant aortic valve
regurgitation (AR) (Figure 1). There are various contributing factors
that can be considered that may lead to AR (Table 1.). Recent studies
have described several mechanisms that can cause injury of the AV during
the implantation, repositioning, and removal of the Impella device
{[}14-16{]}. The aortic valve might be damaged by the stiff guidewire
during the insertion or with the Impella device itself following the
guidewire going through the leaflet. Alternatively, improper handling of
the device such as insertion across the aortic valve without the
guidewire or without echocardiographic guidance might be one of the
mechanisms. In addition, direct contact of the inlet during
repositioning or removal of the Impella might damage the valve due to
the effect of suction if the flow is not reduced as per guidelines.
Severe AR caused by aortic valve injury may necessitate further
treatment such as aortic valve replacement or transcatheter aortic valve
intervention. It is important to distinguish AR caused by commissural
malcoaptation of the two leaflets related to the device, which might
improve after its removal {[}17{]}. AR can be challenging to detect with
echocardiography because of the artefacts generated by the device
{[}15{]}. Importantly, a recent observational study has demonstrated
that even after short-term Impella support, a significant proportion of
patients may develop progression of AR {[}18{]}. The authors have
observed this complication in 9 patients despite an extremely short
support duration in their cohort (median less than 1 day) {[}18{]}.
However, the causality of AR and follow-up of these patients were not
investigated.

\textbf{Mitral valve regurgitation or injury}

There have been several reports of acute severe mitral regurgitation
(MR) caused by iatrogenic injury of the mitral valve apparatus related
to the Impella, in particular due to chordal rupture {[}19-22{]}. A
possible mechanism of chordae tendineae injury during the initial
positioning of the Impella across the aortic valve is from mechanical
damage from either guidewire, or the Impella device {[}21{]}. If not
diagnosed, acute severe MR may lead to rapid decompensation after
Impella removal, therefore, prompt diagnosis is of paramount importance
{[}19{]}. If there is extensive damage of the mitral valve apparatus,
mitral valve repair or replacement may be required. However, surgical
treatment might not be successful despite supportive measures, due to
the severity of complications in combination with the underlying
clinical condition {[}22{]}.

There are several limitations to this study. Firstly, available
literature about complications related to Impella remains limited. Data
are derived from case reports and observational retrospective studies.
Furthermore, there is a lack of follow-up and detailed description of
mechanisms of valve injury in some of the reports.

\textbf{CONCLUSION}

This present study contributes to the emerging evidence about rare but
potentially life-threatening complications related to the Impella
device, emphasising the need for careful management and meticulous
follow-up of these patients so as to recognise complications early and
prevent potentially devastating complications. In order to reduce the
risk of these complications, our recommendation would be to use
continuous echocardiographic and/or fluoroscopy guidance during Impella
implantation. Furthermore, device repositioning or removal should be
always performed under echocardiographic guidance. Optimal placement of
the Impella device should be accomplished by positioning the inlet
approximately 3.5cm from the aortic valve annulus (in a normal
ventricular cavity) and avoiding displacement towards the mitral valve
leaflets {[}23{]}. Special care must be taken that the Impella catheter
is properly fixed and secured to avoid any dislodgment. This includes
documentation of the exact position. In our opinion, it is very
important that the flow is either stopped or nearly completely reduced
before either repositioning or removal of the Impella to avoid any
leaflet damage related to the effect of suction. Further prospective
studies with long-term follow-up are still needed.

\textbf{Author contributions: DS} : Conceptualization; Formal analysis;
Investigation; Methodology; Writing - Original Draft; Writing - Review
\& Editing. \textbf{TK, NJL, US} , Conceptualization, Investigation;
Methodology; Writing - Review \& Editing.

\textbf{Data Availability Statement}

The data that support the findings of this study are available on
request from the corresponding author. The data are not publicly
available due to privacy or ethical restrictions.

\textbf{Table 1. Characteristics of included studies.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllllll@{}}
\toprule
\textbf{Study name} & \textbf{Year} & \textbf{Country} & \textbf{Study
design} & \textbf{Device} & \textbf{Type of valve complication} &
\textbf{n} & \textbf{Age (yrs)} & \textbf{Possible mechanism} &
\textbf{Outcome} & \textbf{Follow-up}\tabularnewline
\midrule
\endhead
Toggweiler{[}24{]} & 2008 & Switzerland & CR & Impella 2.5 & Functional
mitral stenosis & 1 & 70 & Device displacement & Mitral stenosis
resolved, mild regurgitation & Until discharge\tabularnewline
Chandola{[}14{]} & 2012 & Canada & CR & Impella 2.5 & Aortic valve
injury & 1 & 45 & Device removal & TAVI for AR & Until
discharge\tabularnewline
Elhussein{[}22{]} & 2014 & Canada & CR & Impella 5.0 & Acute MR & 1 & 75
& Chordal rupture due to the device displacement & MOF; Died &
N/A\tabularnewline
Sharma{[}17{]} & 2014 & USA & CR & Impella 2.5 & AR & 1 & 18 &
Commissural malcoaptation & Medical treatment & 6 months\tabularnewline
Bhatia{[}19{]} & 2017 & USA & CR & Impella CP & Acute MR & 1 & 52 &
Chordal rupture due to the device insertion or removal & MVR+CABG; Died
postoperatively & N/A\tabularnewline
Hong{[}15{]} & 2019 & USA & CR & Impella 5.0 & Aortic valve injury & 1 &
50 & Device upgrade or frequent manipulation & AVR for AR and upgrade to
CentriMag; Heart and kidney transplant & Until discharge\tabularnewline
Khalid{[}20{]} & 2020 & USA & CR & Impella 5.0 & Acute severe MR & 1 &
47 & Chordal rupture due to the device displacement & MVR+CABG & Until
discharge\tabularnewline
Pivato{[}21{]} & 2020 & Italy & CR & Impella CP & Acute severe MR & 1 &
85 & Chordal rupture due to the device displacement & Mitraclip & 1
month\tabularnewline
Butala{[}18{]} & 2020 & USA & RO & Impella & Increase in AR & 9 & 64\selectlanguage{ngerman}±5.5
& Not investigated & Not investigated & No follow-up\tabularnewline
Vila{[}16{]} & 2020 & UK & CR & Impella CP & Aortic valve injury & 1 &
34 & Device repositioning & AVR & Until discharge\tabularnewline
\bottomrule
\end{longtable}

Abbreviations: AR, aortic regurgitation; AVR, aortic valve replacement;
CABG, coronary artery bypass graft; CR, case report; MOF, multiorgan
failure; MR, mitral regurgitation; MVR, mitral valve replacement; N/A,
not applicable; RO, retrospective observational study; TAVI,
transcatheter aortic valve intervention

\textbf{FIGURE LEGENDS}

\textbf{FIGURE 1.} Intraoperative transoesophageal echocardiogram: A -
immediately after removal of the Impella CP, midesophageal aortic valve
long axis view, and B - midesophageal aortic valve short axis view.
Figure 1A shows the same view with severe aortic regurgitation despite
removal of the Impella device. Nearly complete right coronary cusp
injury is visualized in the Figure 1B. Written informed consent to
publication was provided by the patient.

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2008;9(3):412-3.\selectlanguage{english}
\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/Figure-1-AR-post-Impella/Figure-1-AR-post-Impella}

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