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Dort2019 Article HaemodynamicEfficacyOfMicroaxi
Dort2019 Article HaemodynamicEfficacyOfMicroaxi
Neth Heart J
https://doi.org/10.1007/s12471-019-01351-7
Abstract The Impella percutaneous mechanical cir- ysis showed an increase of 0.39 W [95% confidence in-
culatory support device is designed to augment car- terval (CI): 0.24, 0.54], (p = 0.01) and 0.22 W/m2 (95%
diac output and reduce left ventricular wall stress and CI: 0.18, 0.26), (p < 0.01) for the CP and CPI, respec-
aims to improve survival in cases of cardiogenic shock. tively. The overall survival rate was 56% (95% CI: 0.50,
In this meta-analysis we investigated the haemody- 0.62), (p = 0.09). The quality of the studies was moder-
namic effects of the Impella device in a clinical setting. ate, mostly due to the presence of confounders. Our
We systematically searched all articles in PubMed/ study suggests that in patients with cardiogenic shock,
Medline and Embase up to July 2019. The primary Impella support seems effective in augmenting CP(I).
outcomes were cardiac power (CP) and cardiac power This study merely investigates the haemodynamic ef-
index (CPI). Survival rates and other haemodynamic fectiveness of the Impella device and does not reflect
data were included as secondary outcomes. For the the complete clinical impact for the patient.
critical appraisal, we used a modified version of the
U.S. Department of Health and Human Services qual- Keywords Impella · Haemodynamic monitoring ·
ity assessment form. The systematic review included Cardiogenic shock · Heart failure · Left ventricular
12 studies with a total of 596 patients. In 258 patients assist device
the CP and/or CPI could be extracted. Our meta-anal-
Introduction
D.I.M. van Dort and K.R.A.H. Peij contributed equally to this The Impella (Abiomed, Danvers, MA, USA) is a percu-
manuscript. taneous mechanical circulatory support (MCS) device
Electronic supplementary material The online version of consisting of a non-pulsatile microaxial flow pump
this article (https://doi.org/10.1007/s12471-019-01351-7) based on the Archimedes screw principle that propels
contains supplementary material, which is available to blood from the left ventricle into the ascending aorta.
authorized users. Aside from increasing blood flow, the Impella device
D. I. M. van Dort () · K. R. A. H. Peij · W. J. Morshuis · aims to reduce ventricular wall stress, thereby unload-
G. S. C. Geuzebroek ing the left ventricle, reducing oxygen consumption
Department of Cardiothoracic Surgery, Radboud University and decreasing infarct size [1]. A series of Impella de-
Medical Centre, Nijmegen, The Netherlands vices are available for left ventricular support. The
d.vandort@radboudumc.nl
Impella 2.5 and Impella CP can provide haemody-
O. C. Manintveld namic support up to 2.5 and 3.7 l/min, respectively.
Department of Cardiology, Thoraxcenter, Erasmus MC, The strongest Impella, the Impella 5.0, can deliver up
Rotterdam, The Netherlands to 5 l/min of haemodynamic support. However, this
S. E. Hoeks includes the use of a 21 Fr pump motor, making the
Department of Anaesthesiology, Erasmus MC, Rotterdam, implantation in the acute setting more challenging [2,
The Netherlands 3].
N. van Royen · T. Ten Cate MCS devices have been increasingly used as a key
Department of Cardiology, Radboud University Medical element in the management of patients with cardio-
Centre, Nijmegen, The Netherlands genic shock (CS) [4]. Based on the results of the US-
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
pella Registry, which showed a significant increase manuscripts to determine whether they met the in-
of cardiac output (CO) [5], the Impella received FDA clusion criteria. Disagreement between reviewers (K.P.
approval in 2016 for the treatment of CS. Increased and D.D.) was resolved by consensus. Reference lists
flow is beneficial in CS, since low CO and reduced from eligible studies were checked to identify addi-
perfusion pressure are the bases of CS syndrome [6]. tional studies and citations. For the critical appraisal,
However, these two factors are intertwined, and a de- we used an adapted version of the U.S. Department of
creased output does not necessarily indicate a de- Health and Human Services quality assessment form
creased perfusion pressure and vice versa. The prod- (see Fig. 6; [10]).
uct of these combined parameters is the cardiac power Both reviewers independently extracted the data
(CP), and is the strongest haemodynamic predictor of from all the selected manuscripts. For haemodynamic
mortality in the SHOCK trial registry [7]. This find- parameters the CO, cardiac index (CI), mean arte-
ing was confirmed in a more recent study, where the rial pressure (MAP), CP, CPI and pulmonary wedge
cardiac power index (CPI) was found to be the best pressure (PWP) were obtained. For non-haemody-
haemodynamic predictor of survival in a CS popula- namic parameters, type and duration of MCS, me-
tion [8]. chanical ventilation, cardiopulmonary resuscitation,
As CP and CPI are the best predictors for survival, gender and survival were also extracted from the in-
we focused specifically on the effects of Impella on dividual studies.
CP(I).
Outcomes
Methods Primary outcomes were CP and CPI. The CP is calcu-
lated as: CO × MAP/451 [7]. The CPI was computed by
We performed a systematic review and meta-analysis substituting CO with CI in the respective formula.
on the haemodynamic effects of the Impella during Secondary outcomes included survival, type and
CS. Survival rate was a secondary outcome. duration of MCS, mechanical ventilation, cardiopul-
monary resuscitation, gender and other haemody-
Search strategy namic data (CO, CI, MAP, PWP).
Medical literature databases PubMed/Medline and
Embase were searched using the following keywords: Statistical analysis
(((Impella[tiab] OR (microaxial[tiab] OR axial[tiab]) All data were analysed using Review Manager 5.3.5
AND flow[tiab] AND (pump*[tiab] OR catheter*[tiab]) and Rstudio. Categorical variables were presented as
OR percutaneous left ventricular assist device*[tiab])) percentages. Continuous variables were presented as
AND (((cardiogenic shock[tiab] OR cardiac shock[tiab] range or mean ± standard deviation (SD). For continu-
OR cardiovascular shock[tiab] OR heart shock[tiab] ous variables reported as median ± interquartile range,
OR acute cardiac failure[tiab] OR acute decom- the mean and SD were estimated by using the formula
pensated heart failure[tiab] OR acute heart insuf- as proposed by Hozo et al. [11]. Not all studies men-
ficiency[tiab] OR acutely decompensated heart fail- tioned the CP or CPI directly; therefore the missing CP
ure[tiab] OR ADHF[tiab] OR forward heart failure[tiab] or CPI and accessory SD were calculated according to
OR low cardiac output[tiab] OR low output syn- the appropriate formulas [11].
drome[tiab] OR systolic dysfunction[tiab])) OR Heterogeneity defined as variation among the re-
(((Shock, Cardiogenic[Mesh] OR Heart Failure[Mesh: sults of the individual studies was assessed with
noexp] OR Heart Failure, Systolic[Mesh])) OR “My- Cochrane’s Q-statistic (pchance and I2 statistic). Ran-
ocardial Infarction”[Mesh]))). A methodological filter dom effects models were used to calculate mean
was used to limit the results to adult humans. The pooled differences of haemodynamic data between
search was last updated on 9 July 2019. baseline and Impella support for CP and CPI. A sub-
group analysis of the Impella 2.5 and 5.0 was made.
Inclusion and exclusion criteria For survival rates, the overall proportion from studies
This article is in accordance with the PRISMA guide- reporting a single proportion was calculated. Note
lines (see Electronic Supplementary Material for that since not all variables were measured in all pa-
checklist, online Table 1) [9]. Studies eligible for tients and all studies, the number of patients and
inclusion were original articles that met the follow- studies per meta-analysis is different.
ing criteria: retrospective, prospective cohort studies
and randomised controlled trials in CS patients, with Results
a reported CS. We excluded letters, case reports and
studies that focused on high-risk percutaneous coro- Study characteristics
nary intervention (PCI). No further restrictions on Our systematic literature search in PubMed/Medline
publication date, status or language were imposed. and Embase resulted in 946 records (Fig. 1). After ex-
The search was then loaded into Endnote X8 and clusion, 12 articles (including 1 via cross-reference) re-
possible duplicates were deleted. The two review- mained for qualitative and quantitative synthesis and
ers independently reviewed all titles, abstracts and meta-analysis [5, 12–22]. Nine of the 12 studies were
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
Idenficaon
Percutaneous coronary in- Records idenfied through Records idenfied through Embase
tervention PubMed/Medline (n=682)
(n=328)
(n=66) (n=55)
Studies included in
quantave synthesis
(meta-analysis)
(n=12)
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
with a mean pooled difference of –8.30 mm Hg (95% pella support. This meta-analysis, including 258 pa-
CI: –10.63, –6.06), (p < 0.01). See Tab. 2, Figs. 4 and 5 tients from 12 studies, showed that the use of the Im-
and Electronic Supplementary Material. pella device significantly increases the CP by 0.39 W
(+67%) and CPI by 0.22 W/m2 (+76%). When compar-
Critical appraisal ing the different Impella devices, the Impella 2.5 in
One study was considered of sufficiently good quality general achieves a lower performance relative to the
to show that Impella support results in increased CP Impella 5.0 in both CP (+48% vs +82%) and CPI (+58%
and CPI [14]. Overall studies were considered to be vs +102%).
of moderate quality, mostly due to lack of description The observed increase in CP(I) during Impella sup-
of confounders and data acquisition protocol. On the port, which has been shown to be a strong haemody-
other hand, all studies were comparable in terms of namic predictor of survival in CS [7, 8], should theo-
outcomes, study design, study population and type of retically lead to a reduction in mortality. Extrapolating
support, which allowed us to conduct a meta-analysis from the survival graph of Fincke et al., the increase of
(see Fig. 6). CP from 0.5 W to 0.9 W should decrease mortality from
approximately 50% to 20% [7]. The overall percent-
Discussion age survival in our meta-analysis, 56%, is in line with
two small randomised controlled trials [14, 23] and
To our knowledge, this is the first meta-analysis that a propensity-matched analysis [24], which all com-
has focused on the increase in CP and CPI during Im- pared the Impella CP to passive unloading with the
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
Fig. 2 Forest plot of a cardiac power (CP) and b cardiac power index
intra-aortic balloon pump. This indicates that the re- as surgically implantable ventricular assist devices
lationship between (mechanical) haemodynamic im- [26]. Therefore, patient selection in terms of cause
provement and survival is less evident than suggested. and reversibility of cause is an important determinant
In our study we focused mainly on CS after AMI of survival in CS.
(64% in our analysis). However, CS has a broad scope Within the CS-AMI group, patient selection might
of aetiology. In some very specific indications, such be an explanation for the lack of a clear survival bene-
as a biopsy-proven myocarditis, there is growing evi- fit with improved haemodynamics. Patients with a rel-
dence of improved survival with Impella support [25]. atively preserved cardiac function seem to have the
In other indications for Impella support, such as the best chance of survival and show a better haemody-
post-cardiotomy population (5% in our study), evi- namic improvement [27]. In patients who have no car-
dence is still limited and in need of further research. diac reserve, the intrinsic CP is unchanged and thus
However, small registries show survival rates compa- remains the Achilles’ heel of survival. Only when the
rable with those of more invasive assist devices, such
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
affected myocardium is able to recover can the intrin- and better haemodynamic performance [33]. A recent
sic CP increase and thereby improve outcome. clinical trial also showed promising results when the
To achieve recovery of the myocardium Impella Impella support was initiated before emergency PCI
provides unloading, represented by a significant de- [34]. This is in contrast to our meta-analysis, in which
crease of the PWP by 8 mm Hg in our meta-analysis. support was given after almost 3 days after the onset
This clearly distinguishes mechanical support with of CS. The late initiation of support might preclude the
the Impella device from medical therapy (inotropic potential benefit to survival rates. On the other hand,
or vasoactive agents), which increases the workload real-world data are refractory. In the 12-year experi-
of the heart in order to improve the CPI [28]. Un- ence of the Amsterdam Medical Centre there was no
loading of the left ventricle leads to reduced oxygen significant improvement of survival when support was
consumption and should thereby reduce infarct size initiated before PCI [35].
in patients with CS-AMI. Animal studies have shown
that unloading does reduce infarct size [1, 29], espe- Clinical and future perspectives
cially when support is started at an early stage. How-
ever, the clinical trial which investigated if unloading In the critical setting of CS, the Impella device im-
with Impella support would reduce the infarct size proves the haemodynamic state and relieves conges-
(MINI-AMI, Minimizing Infarct Size with Impella 2.5 tion. However, in order to significantly improve out-
Following PCI for Acute Myocardial Infarction, Clini- comes, more research is needed. Patient selection and
calTrials.gov identifier NCT01319760) was terminated timing of Impella support may well be the crucial de-
due to a ‘change in company priority’. This raises nominator that decides its effectiveness. To further
questions as to whether the study was able to show optimise patient selection and to overcome hetero-
positive results. genic outcomes in future studies on MCS, we suggest
In terms of the timing of support, several studies a standard data set of core outcomes and measure-
suggest that early implantation of a mechanical as- ments.
sist device would improve survival [30–32]. Recent
extensive animal studies showed that mechanical un- Limitations
loading of the left ventricle before coronary reper-
fusion limits the expression of proteolytic enzymes. Eight of the 12 included studies were registries, which
This resulted in less cell decay, reduced infarction size in general have a heterogeneous patient population,
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
Meyns [12]
Dens [13]
Seyfarth[14]
Bresson [15]
Griffith [16]
O’Neill [5]
Casassus
[17]
Lima [18]
Schiller [19]
Joseph [20]
Mastroianni
[21]
Hall [22]
Fig. 6 Adapted quality assessment for individual studies according to the U.S. Department of Health and Human Services.
National Heart, Lung and Blood Institute
treatment and outcome. Additionally, 3 out of 12 stud- acceptable heterogeneity score for the overall study
ies are from the cVAD (catheter-based ventricular as- group.
sist devices) registry, owned by Abiomed. Possible Furthermore, although the intrinsic CP(I) may be
overlap cannot be excluded. When taking these stud- a strong predictor in CS-AMI, this relationship might
ies out of the calculation, the overall results remain be less strong for the CP(I) added by MCS. This dis-
the same. tinction is crucial for adequate interpretation of our
The key hindrance to providing an in-depth meta- results. In addition, this meta-analysis focuses on the
regression analysis at the study level is the great haemodynamic efficacy in the clinical setting, and
disparity in the available data reported. Possible merely reflects whether the pump is effective in in-
confounding factors are not always reported, includ- creasing output. Procedure- and device-related com-
ing the use of vasoactive medication, clinical patient plications (stroke, access bleeding, infection) are not
characteristics and the timing and completeness of included in this study, hampering the true reflection
measurements. Although the overall quality of the of clinical benefit for the patient.
studies was considered moderate, all studies showed
a uniform increase in CP(I). This was reflected by an
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .
Review Article
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mortality for postcardiotomy failure: a three-center experi- again! J Interv Cardiol. 2017;30:584–5.
ence. J Thorac Cardiovasc Surg. 2004;127:812–22. 33. Esposito ML, Zhang Y, Qiao X, et al. Left ventricular
28. Nativi-Nicolau J, Selzman CH, Fang JC, Stehlik J. Pharma- unloading before reperfusion promotes functional recov-
cologic therapies for acute cardiogenic shock. Curr Opin ery after acute myocardial infarction. J Am Coll Cardiol.
Cardiol. 2014;29:250–7. 2018;72:501–14.
29. Yoshitake I, Hata M, Sezai A, et al. The effect of com- 34. Basir MB, Schreiber T, Dixon S, et al. Feasibility of early
bined treatment with Impella((R)) and landiolol in a swine mechanical circulatory support in acute myocardial in-
model of acute myocardial infarction. J Artif Organs. farction complicated by cardiogenic shock: the Detroit
2012;15:231–9. cardiogenic shock initiative. Catheter Cardiovasc Interv.
30. Basir MB, Schreiber TL, Grines CL, et al. Effect of early 2018;91:454–61.
initiation of mechanical circulatory support on survival in 35. Ouweneel DM, de Brabander J, Karami M, et al. Real-life
cardiogenic shock. Am J Cardiol. 2017;119:845–51. use of left ventricular circulatory support with Impella in
31. Lazkani M, Murarka S, Kobayashi A, et al. A retrospective cardiogenic shock after acute myocardial infarction: 12
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Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review. . .