We are IntechOpen,

the world’s leading publisher of

Open Access books
Built by scientists, for scientists

6,300
Open access books available
170,000
International authors and editors
190M Downloads

Our authors are among the

154
Countries delivered to
TOP 1%
most cited scientists
12.2%
Contributors from top 500 universities

Selection of our books indexed in the Book Citation Index

in Web of Science™ Core Collection (BKCI)

Interested in publishing with us?

Contact [email protected]
Numbers displayed above are based on latest data collected.
For more information visit www.intechopen.com
 Chapter 13

Flow Optimization, Management, and Prevention of LV

Distention during VA-ECMO

Cristiano Amarelli,
Cristiano Amarelli, Francesco
Francesco Musumeci,
Musumeci,
Antonio Loforte, Andrea Montalto, Sveva Di Franco
Sveva
and Di Franco
Jaime and Jaime Hernandez-Montfort
Hernandez-Montfort

Additional
Additional information is available
information is available at
at the
the end
end of
of the
the chapter
chapter

http://dx.doi.org/10.5772/intechopen.80265

Abstract

Cardiogenic shock (CS) still carries an unacceptably high mortality (30–60%), despite
several therapeutic approaches; the SHOCK II trial questioned the benefit of intra-aortic
balloon pump (IABP), while IMPRESS and CULPRIT-SHOCK trials confirmed hetero-
geneity in disease spectrum and patient selection for acute myocardial infarction-related
CS requiring acute mechanical circulatory support (AMCS). The heterogeneity of devices
employed as AMCS, including temporary micro-axial flow pumps (Impella), percutane-
ous bypass (TandemHeart), and extracorporeal life support (VA-ECMO), contributed to
the actual dramatic scenario, where CS is defined clinically rather than hemodynami-
cally. To date, the role of VA-ECMO is emerging as rapid strategy to mitigate mortality
rates of severe refractory states, despite the lack of data regarding the best practices of
management and flows control. VA-ECMO’s flow represents the “dose” of treatment and
higher flows are less tolerated percutaneously requiring, to prevent deleterious pulmonary
edema and ventricular distention, additional approaches such as pulmonary, left atrial, or
left ventricular unloading. Any efforts have to be directed to (1) determine adequate man-
agement of patients on VA-ECMO, (2) define the safer duration of VA-ECMO support, and
(3) establish algorithms and techniques to predict and obtain stable weaning from ECMO
or ensure fast transition to durable VAD and/or heart transplant.

Keywords: ECMO, myocardial recovery, cardiogenic shock, ventricular unloading,

VA-ECMO, Impella, ECLS, ECPELLA, ECMO dose retrieval

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative
Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
distribution, and reproduction in any medium, provided the original work is properly cited.
184 Advances in Extra-corporeal Perfusion Therapies

1. Introduction

Cardiogenic shock (CS) continues to exhibit a high mortality rate (30–60%), despite several
therapeutic approaches; recent data derived from the SHOCK II trial [1] questioned the benefit
of intra-aortic balloon pump (IABP) in the treatment of the CS. Subsequently, IMPRESS [2] and
CULPRIT-SHOCK [3] confirmed heterogeneity in disease spectrum (using a non-hemodynamic
clinical definition for CS) and patient selection for AMI-related cardiogenic shock requiring
acute mechanical circulatory support (AMCS) with alternative strategies to counterpulsation
such as temporary micro-axial flow pumps (Impella), percutaneous left atrium-aortic bypass
(TandemHeart) and venoarterial extracorporeal membrane support (VA-ECMO) [4]. In this dra-
matic clinical scenario, VA-ECMO is emerging as an alternative strategy to mitigate such elevated
mortality. Although a beneficial effect on peripheral perfusion/circulation has been demonstrated
with VA-ECMO implantation in patients affected by CS, there is a potential for increasing load-
ing conditions into the left ventricle potentially compromising transition to myocardial recovery.
Contemporary VA-ECMO systems are now widely used with a broad spectrum of configura-
tions. Due to case mix and implantation timing differences (from report to report and depending
on the institutions), outcomes have wide variability and are limited by its retrospective nature
and lack of granular profiling prior and after support. The timing of the implantation potentially
accounts for further differences in outcomes between different institutions. Central cannula-
tion, when feasible, warrants the best peripheral flows, the best cardiac perfusion, and unloads
adequately both ventricles but is still complicated by a high incidence of bleeding and need of
multiple re-sternotomy. Moreover, central VA-ECMO is not always bedside available. Despite
the growing experience in the use of VA-ECMO, the target flow has still not been identified, and
in literature, there is a lack of data regarding best practices with management. Indeed, VA-ECMO
flow represents the “dose” of the treatment: the lower dose corresponding to lower flow may be
readily achieved through percutaneous cannulation, while the higher the dose or higher flow can
be obtained through larger cannulas (Figure 1) and may require modifying VA-ECMO configu-
ration during support aiming to prevent the common complications due to overflow. However,
a higher flow warrants optimal peripheral organ perfusion, lower venous pressure, and higher
mean pressure. The decongestion of the venous side appears a critical factor in recovery end-
organ function and is pivotal both for renal and liver function recovery. The building of the circuit
should always aim at the lowest venous pressure to restore a normal perfusion pressure despite
low continuous flow pressure. On the other hand, high flow not only induces highly turbulent
flows, increasing shear stress, and damaging platelets but also increase the quota of shunt and
the left ventricular afterload. The latter mechanism may explain the increased risk of pulmonary
edema and moreover the reduced hazard of myocardial recovery [5].

Preventing pulmonary edema is one of the principal targets to reduce the biologic impact of
VA-ECMO and possibly to maintain the patients extubated and even ambulatory. A large
number of possible approaches have been described to aim through a small-incision pul-
monary, left atrial, or left ventricular unloading, thus preventing pulmonary edema. The
implantation of a double ECLS (extracorporeal life support) circuit (surgical with CentriMag
or percutaneous with TandemHeart) thus aiming to reduce all the possible complications due
to the need of an oxygenator [6–8] represents one of the possible solutions.
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 185
http://dx.doi.org/10.5772/intechopen.80265

Figure 1. ECMO configuration tailored on needed flow. Representation of the existing relation from type of cannula, site
and technique of insertion and flow rates. The figure defines that according to the needed flow the operator may utilize
different approaches starting from lower flows provided with a femoral percutaneous small nonocclusive cannula (blue
dot) reaching the higher flows with a large cannula in central ECMO or BiVAD.

Today, the first indication of treatment is myocardial recovery as clearly shown both from
data coming from leading centers in the VA-ECMO implantation and ELSO registries [9, 10].
This target is more frequently achieved in myocarditis or potentially reversible diseases [11]
and stresses the importance of etiological diagnosis at the moment of implantation to define
the strategy of implantation. To warrant optimal outcomes, many efforts have to be directed
to:

1. Determine adequate management of patients on VA-ECMO.

2. Minimize the time the patient is on VA-ECMO.

3. Establish algorithms and techniques to predict and obtain stable weaning from VA-ECMO.

When pathology is reversible, probably, the quality of myocardial unloading can potentially
make an essential difference in the platform for transition (recovery vs. VAD and/or heart
transplant). Recent data support the need to reason about a transition to a midterm platform
as soon as a stable organ perfusion and function have been warranted, possibly between day 7
[12] and before day 14 [13]. Data emerging on the beneficial effect of early myocardial unload-
ing on the acutely failing hearts with temporary micro-axial flow pumps continue to arise
[14–16]; however, there is no clear consensus or longitudinal hemodynamic data to support
a specific combination or transition strategy for severe refractory, hemometabolic, and/or
biventricular cardiogenic shock, and although it appears that the most commonly described
combination is VA-ECMO with LV unloading via an Impella device, the emerging alternative
186 Advances in Extra-corporeal Perfusion Therapies

of high-profile biventricular support with combination of Impella 5.0 and RP or percutaneous

biatrial VA-ECMO is also possible.
This chapter aims to evaluate best practices and strategies that can be implemented to prevent
and reduce ventricular distention and to increase the likelihood of recovery and survival dur-
ing and after VA-ECMO support.

2. Incidence of complications and ECMO configuration

VA-ECMO currently represents the most effective minimally invasive circulatory support
system. VA-ECMO has evolved and can now be placed quickly at the bedside, in the medical
unit, or in the cardiac intensive care unit. It provides oxygenation, it is the best option in the
setting of associated lung injury, it can be placed peripherally (without thoracotomy), and it
is the only percutaneous option for biventricular support. It may provide sufficient support
to enable adequate tissue perfusion even in cardiac arrest, and it is a suitable device for acute
resuscitation of a patient in shock, even if mortality for cardiogenic shock did not significantly
change and is still ranging between 50 and 70% [17].

Moreover, many publications have disclosed a dramatic burden of complications using per-
cutaneous VA-ECMO leading to higher costs and ethical discussions on the right clinical set-
tings for its clinical adoption [9, 18–20].
Looking critically at the landscape of effects and complications of different configurations
of mechanical circulatory support and specifically of VA-ECMO emerges the importance to
select the right device and the right VA-ECMO’s configuration to warrant the best outcome.
The crucial factor in selecting the device and the VA-ECMO’s configuration is the amount of
flow needed to restore organ function. Venous oxygen saturation has been indicated by many
authors as a good goal to direct VA-ECMO perfusion [21].

Percutaneous VA-ECMO appears fitted to restore peripheral flows when the patient experi-
ences a moderate reduction of cardiac output. When the patient needs higher flows, the risk
of pulmonary edema and left ventricular distention increases [22], and additional cares may
be necessary to unload the left ventricle and eventually to restore pulmonary function after
pulmonary edema [23–25].
Although a beneficial effect on peripheral perfusion/circulation has been demonstrated with
VA-ECMO implantation in patients affected by cardiogenic shock, there is a potential for
increasing loading conditions into the left ventricle potentially compromising transition to
myocardial recovery. Contemporary VA-ECMO systems are increasingly being used with a
wide spectrum of configurations.

3. Destination of VA-ECMO

Contemporary registries and center reports support the ultimate finality of therapy for acute
decompensated heart failure being myocardial recovery [26]. When pathology is reversible,
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 187
http://dx.doi.org/10.5772/intechopen.80265

the time to recovery on the basis of the etiopathology of the disease plays a pivotal role
together with the modality of support aiming to help myocardial healing [27].

Therefore, if during the acute phase of VA-ECMO implantation the “dose” is a critical fac-
tor to recovery the end-organ function, the complementary goal is to reduce the biologic
impact of support and favor myocardial healing. Many data are emerging in support of a
role of myocardial unloading to reach this aim [28]. Data coming out from experimental
data on animal and computer simulations seem to support the hypothesis that ventricular
unloading is more effective than atrial unloading. Data emerging on the beneficial effect of
early myocardial unloading on the acutely failing hearts with temporary micro-axial flow
pumps continue to arise; however, there is no clear consensus or data to support a specific
combination or transition strategy for severe refractory, hemometabolic, and/or biventricular
cardiogenic shock.

VA-ECMO has multiple effects on the left ventricular myocardium:

• The decrease of venous return and the volume work may reduce the wall tension of the
heart and subsequently the LVEDV and LVEDP.
• The increase of arterial pressure (MAP) and reduction of venous pressure improve the
pressure gradient and then the myocardial perfusion.
• The increase of blood pressure increases afterload and the pressure work of myocardium
affecting the Frank-Starling law.

The overall effect of the decrease in volume work and the increase in pressure work depends
on the “dose” of VA-ECMO as well as myocardial function and its response to these phenom-
ena. Peripheral ECMO with a high flow may further increase afterload due to the reversal of
flow in the most of the aorta [29, 30].
The real question remains if myocardial unloading is always beneficial or potentially detri-
mental by increasing the complexity of management and when is indeed indicated the transi-
tion from ECMO support to ECMO + LV unloading.

Although it appears that the most commonly described combination is VA-ECMO with LV
unloading via an Impella device, the emerging alternative of high-profile biventricular sup-
port with the combination of Impella 5.0 and RP or percutaneous biatrial ECMO is also pos-
sible valuable solutions [31].

Many contradictory data are emerging regarding the effect of VA-ECMO on LV contractile
function. LV afterload before ECMO is related to systemic arterial pressure, and the Starling
curve generated before initiation of ECMO flow predicts the filling pressure associated with
any target SV at that systemic pressure. The addition of ECMO flow or alterations solely
in SVR does not alter the relationship between filling pressure and native LV SV, and then
the abrupt increase of afterload due to the ECMO flow may be useful to predict ventricular
distension during ECMO support [32].

In the presence of severe LV dysfunction, the left ventricle is unable to eject a sufficient volume
of blood against the increased afterload caused by the ECMO flow, resulting in impairment of
188 Advances in Extra-corporeal Perfusion Therapies

various parameters of LV performance [33–35] and, in extreme situations, the aortic valve can
remain closed even during systole.
When VA-ECMO is established due to ongoing cardiogenic shock, it is possible to measure
PCWP and LV SV directly. The additional systemic flow conferred by ECMO may be offset by
volume reduction of venous return that may cause a reduction in PCWP. When VA-ECMO is
established for cardiogenic shock due to right ventricle failure, PCWP is typically low, and the
LV is relatively afterload insensitive.

The presence of a pulse pressure depends (without IABP) on the stroke volume of the left ven-
tricle. The absence of arterial pulsatility may prove an appropriate level of support (60–80%
of the predicted cardiac output allowing for the remaining 20–40% to pass through the lungs
and heart). However, on the other end, it indicates also the inability of the myocardium to
overcome the superimposed afterload worsened by a decreased preload and volume work.

When mitral regurgitation is absent, and a significant amount of blood returns in the LV, blood
may stagnate within the left ventricle and at the aortic root. The persistent closure of the aortic
valve may increase the risk of thrombus formation and subsequent embolic. Besides, the reduc-
tion of the stroke volume and of the transmitral flow due to VA-ECMO, the increase of the
PCWP, the persistent venous return from thebesian and bronchial veins lead to overdistension
of the LV. The distention of the LV measured in terms of LVEDV leads to an LVEDP; impairing
coronary perfusion pressure may further worsen the ischemic subendocardial injury to the
myocardium. In some instance, left ventricular distension may cause tethering of a previously
competent mitral valve causing functional mitral insufficiency due to annular dilation. In this
scenario, a pulmonary artery catheter may demonstrate an increase in the telediastolic pulmo-
nary capillary occlusion pressure. The presence of severe mitral regurgitation may worsen left
atrial hypertension congesting the pulmonary bed leading to pulmonary edema and even hem-
orrhage. Functional assessment of the heart in a partially bypassed state can be challenging, but
transesophageal echocardiography may aid in confirming aortic valve opening as well as by
providing an assessment of the variations of the left ventricular end-diastolic dimension after
VA-ECMO institution. The serial evaluation of LVED and of the PCWP should be routinely
used during VA-ECMO to give a prompt indication to LV unloading when the simple physio-
pathologic and/or eventual simulation models do not already suggest the need of an unload-
ing. Recently, the option to first unload and then evaluate the need of VA-ECMO has been
prompted. The increase in systemic pressure, in this scenario, is slight, and a modest increase
in PCWP would accompany the increase in LV afterload without a significant change in LV SV.

When VA-ECMO is established for cardiogenic shock due to acute LV failure, the magnitude
in afterload change depends on the increase of systemic pressure. In this scenario, if PCWP is
already high and without a substantial improvement in LV contractility, a dramatic rise in PCWP
with LV distension is expected. LV and pulmonary venous distension lead shortly to a massive
acute pulmonary edema and blood stasis in the left heart with a serious risk of thrombus forma-
tion. Prompt diagnosis and a high suspicion have to be kept in this situation as it is imperative
to both unload the central circulation while maintaining a minimal LV SV. The effectiveness of
oxygenation and drainage is a vital factor for the diagnosis as if the patient is well drained and
perfused; the diagnosis of pulmonary edema may be masked by ECMO. VA-ECMO differs from
the standard cardiopulmonary bypass circuit due to the absence of a venous reservoir halting
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 189
http://dx.doi.org/10.5772/intechopen.80265

the possibility to control the amount of venous return to the left heart during VA-ECMO; the
blood volume bypassing the venous cannula due to incomplete drainage or coursing through
the bronchial circulation returns to the left heart; this represents the additional LV output to
VA-ECMO flow in the systemic circulation. While this additional flow may be altered by changes
in circulating blood volume (e.g., diuresis), the LV will require a preset inflow pressure warrant-
ing to deliver a target SV (to prevent blood stasis) depending on the Starling relations. The risk
of ventricular distention after initiation of VA-ECMO is related to the preinitiation EF in a setting
of high afterload sensitivity as contractile strength is reduced. Even a moderate reduction in pre-
ECMO EF (less than 50%) may predict high PCWP after VA-ECMO institution, due to the abrupt
increase of systemic pressure and afterload when peripheral cannulation is accomplished.
Placed in the setting of hypotension and cardiogenic shock, the increase in MAP after initia-
tion of VA-ECMO is associated with a significant increase in PCWP and decrease in LV SV,
counteracting the emptying of the ventricle and its work.
Careful management of patients on VA-ECMO should include monitoring of intravascular
volume status, MAP, and PCWP.
Volume status should be managed in a way to warrant a minimally acceptable LV SV, while
the MAP should be kept down acting on VA-ECMO flow rates and by pharmacologic manip-
ulation of SVR. VA-ECMO flows can be reduced in an attempt to reduce afterload. However,
this maneuver may not be possible if it compromises oxygen delivery and end-organ perfu-
sion due to the inability of the heart to produce a compensatory increase in native cardiac
output. The value of PCWP depends on LV contractility and MAP but not on the method by
which MAP is controlled while maintaining a minimal LV SV.
LV overload and distension except for pulmonary edema may induce increased wall stress and
myocardial oxygen consumption [36]. During acute decompensation of chronic heart failure
leading to cardiogenic shock, the left ventricle is compliant, and the mitral valve is frequently
incompetent as a result of chronic annular dilation and mitral valve leaflet tethering. Mitral
regurgitation in this setting decompresses the left ventricle to some extent but may result in
elevation of left atrial pressure and pulmonary edema [21, 37]. In contrast, acute myocarditis
or myocardial infarction is associated with a noncompliant left ventricle and competent mitral
valve. LV distension in this setting will result in a significant rise in intraventricular pressure
and wall tension, which could be detrimental to the damaged myocardium, and reduced coro-
nary blood flow, causing subendocardial myocardial ischemia [38]. Aortic regurgitation should
always be kept into account in ECMO patients due to its potentially detrimental effects [39].

Commonly, myocardial recovery on VA-ECMO support is suggested by an increase in pulse

pressure and by improved contractility on echocardiography, but the appearance of pulsatility
on the arterial waveform may also reflect a worsening volume overload. Tracking PCWP or
repeat echocardiographic assessment may help to ascertain to manage the patient at the best.
The ultimate test of myocardial recovery, however, is accomplished by assessing hemo-
dynamic stability on minimal or no support. Under adequate heparinization, the “dose”
of VA-ECMO can be decreased to achieve ~1 L/min of flow or the cannulas can be briefly
clamped to ascertain the ability of the native ventricle to handle the full cardiac output.
When the myocardium has recovered, during the weaning phases or temporary withdrawal,
190 Advances in Extra-corporeal Perfusion Therapies

Figure 2. Flow-chart for ECMO management.

Figure 3. Flow-chart describing the suggested therapeutical strategy according to patient’s clinical conditions and needs.

acceptable contractility on echocardiography and stable hemodynamics (MAP, CVP and

heart rate) has to be checked. We provide a schematic view of the Flow-chart for ECMO
management form step 1 to step 4 and complete weaning (Figure 2). Hypotension, a rising
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 191
http://dx.doi.org/10.5772/intechopen.80265

CVP, atrial fibrillation, and a poorly contractile myocardium on echocardiography suggest

weak recovery and a high risk of need of support [40, 41]. Recently, the group of Esposito
and Kapur [42] has suggested a facilitating effect in withdrawal when the patients have
an Impella in place to sustain left ventricular function. This knowledge, merged with the
knowledge of the need of a short period of ECMO support and to the capability of Impella to
interrupt the vicious cycle leading the patient to biventricular failure, may suggest the adop-
tion of Impella when cardiac power output falls under 0.6 and IABP is judged not enough
to maintain adequate end-organ perfusion [43], in this case ECMO need has to be evaluated.
In Figure 3, it has been represented a scheme of the associations between patients’ clinical
conditions and the suggested therapeutical strategy to face patients’ hemodynamic needs.

4. IABP during ECMO

Intra-aortic balloon pump (IABP) has long been clinically applied to augment pulsatility,
decrease afterload, and improve blood flow in native coronary arteries and bypass grafts [44, 45].
The inflations and deflations of the 30–50 ml balloon delivered by the IABP device are syn-
chronized with cardiac cycle: the deflation just before systolic ejection aims to decrease after-
load and improve LV ejection, while the inflation during diastole warrants increased diastolic
perfusion aiming at improve coronary, cerebral, and visceral blood flow.
Despite the controversial data from the Intra-Aortic Balloon Pump in cardiogenic SHOCK
(IABP-SHOCK) II trial [1], IABP currently remains one of the most commonly used mechani-
cal circulatory support devices in the treatment of acute heart failure. When administered
promptly, it can play a critical role in the rescue of patients with acute myocardial damage,
reversing the ongoing vicious cycle leading to death. It has been shown in animal models that
IABP may improve several parameters of LV performance during VA-ECMO support [46].
Currently, several centers use IABP during VA-ECMO therapy to reduce LV afterload and
warrant pulsatility in the end-organ capillary bed [47]. In a group of 219 patients treated with
VA-ECMO after cardiac surgery, Doll et al. [18] found that the use of IABP during ECMO
support was associated with a significantly higher survival rate. Ma et al. [48] reported 54
adult patients with acute heart failure who received combined ECMO and IABP support, all
of whom showed improvements in terms of overall circulation. Thirty-four of the patients
were successfully weaned from mechanical circulatory support, and 21 (39%) survived to
hospital discharge. Petroni et al. [49] showed that adding an IABP to peripheral VA-ECMO
was associated with improved LV function, and discontinuation of intra-aortic balloon pump-
ing was associated with higher pulmonary artery wedge pressure, increased LV end-, and
end-diastolic diameters, while decreasing pulse pressure (15 ± 13 versus 29 ± 22 mmHg;
P = 0.02) [49]. Park et al. [50] did not find any mortality or morbidity benefit with IABP in
the group of 96 VA-ECMO-treated patients with cardiogenic shock due to acute myocardial
infarction. Recent data coming out from the Shock trial suggest that cardiac power output
(CPO = cardiac output × MAP × 0.022) may be the best predictor of the effectiveness of IABP
during impending cardiogenic shock [51]. Impella or VA-ECMO is needed when CPO is very
low or upgrading of the MCS is necessary. Eventually the upgrade to ECMO or ECPELLA
192 Advances in Extra-corporeal Perfusion Therapies

(VA-ECMO + IMPELLA) may portend both optimal perfusion and ventricular unloading aim-
ing to myocardial recovery. Etiologic definition and eventual correction of the cause should
be mandatory to increase the chance of recovery.
A marked increase in systemic blood pressure caused by VA-ECMO and retrograde aortic
ECMO flow may increase cardiac afterload, together with severe systolic dysfunction, result-
ing in LV overload with a subsequent increase in left atrial pressure, severe pulmonary edema,
myocardial ischemia, elevated pulmonary pressures, blood stasis, and potential thrombus
formation, jeopardizing ventricular recovery.

Echocardiographic monitoring should be strictly recommended to detect a fluid overload

early, and a Swan-Ganz catheter should be inserted to measure the pulmonary capillary
wedge pressure to detect high left ventricular filling pressures as an indicator for left ven-
tricular distension. Ventilation with low tidal volumes and positive end-expiratory pressure
(PEEP) has been suggested to keep the lung open. A higher PEEP is advisable in patients with
ongoing pulmonary edema. Early extubation is feasible and desired when the patient has a
low risk of pulmonary edema because optimal unloading.
To date, there are several possibilities to decrease the likelihood of left ventricular distension
on ECMO, but the cohort of patients who benefit from left ventricular venting is unclear.
Decreasing afterload leads to a decrease in workload and O2 consumption. In case of an
extremely poor left ventricular function, it is advisable to administer inotropes with a suf-
ficient mean arterial pressure of 50–60 mmHg. Physiologic lactate levels, normal pH levels,
and regular central venous saturations as a guide and flow rates of 2.5–4 L/min are probably
sufficient in most cases. Even if sometimes lower pump flow rates also reduce the perfusion-
related afterload [21].
Intra-aortic balloon pumping (IABP) concomitant to retrograde aortal perfusion is seen con-
troversial as the inflated balloon in the descending aorta might hinder proper perfusion. IABP
counterpulsation is a device that inflates and deflates a 30–50 cm balloon in the descending
aorta. The balloon inflations and deflations are synchronized with cardiac cycle, and, therefore,
deflation just before systolic ejection may decrease afterload and improve LV ejection. Moreover,
increased diastolic pressure on IABP could also improve coronary blood flow [52, 53].
Despite the general expectations that IABP is useful during VA-ECMO for a supposed “perfu-
sion benefit” which indeed is overcome by ECMO blood flow, our belief is that the rationale of
the combined use of VA-ECMO and IABP is to provide a pressure unloading to the left ven-
tricle especially when a certain amount of residual SV is provided by the native circulation.
Although in a very unstable patient ECMO can stabilize end organs and restore their func-
tion, the lack of left ventricular unloading and reduced ventricular work threaten the myocar-
dium worsening the already impaired myocardial performance superimposing an extremely
high afterload further compromising wall tension and myocardial oxygen demand. Multiple
studies have shown that coronary perfusion worsens, especially if the patient is cannulated
peripherally. Because relative cerebral or coronary hypoxia occurs in many situations due to
a “watershed” effect, it is imperative to check blood saturations at multiple sites to determine
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 193
http://dx.doi.org/10.5772/intechopen.80265

if perfusion is adequate everywhere to avoid to misdiagnose the “Harlequin syndrome” due

to inadequate mixing of the two parallel circulations (ECMO and native heart) [23, 54, 55].

As a matter of fact, IABP should be already in place at the time of VA-ECMO implantation,
as stated by ELSO Guidelines 2017 [www.elso.org]. For those patients who do not have one,
it should be placed via the contralateral femoral artery, associating earlier the hemodynamic
effects of IABP to those of VA-ECMO; from a mechanistic point of view IABP could neutralize
some of the unwanted effects of VA-ECMO [56].

The role of IABP in patients suffering from cardiogenic shock should be highlighted as (I)
it is rapidly deployable at any hospital and therefore reduces the duration of “uncontrolled
shock”; (II) it allows, thereafter, safe transport to MCS units; (III) it does allow foe exploiting
the same vascular access for Impella implant; and (IV) it has a major role in weaning from
VA-ECMO and therefore reduces the burden of the complications related to ECLS.

Despite the controversial data from the intra-aortic balloon pump in cardiogenic SHOCK
(IABP-SHOCK) II trial, which could not demonstrate a survival benefit for the IABP applica-
tion, IABP currently remains one of the most commonly used mechanical circulatory sup-
port devices in the treatment of acute heart failure. The bad news is that for none of the
percutaneous devices, used in LV venting, a survival benefit has yet been documented in
adequately sized randomized clinical trials (RCTs). A meta-analysis, by Cheng et al., includ-
ing a total of 100 patients in three small RCTs with the TandemHeart and the Impella PL2.5
pump did not see a survival benefit in comparison to the IABP, despite better hemodynamic
effects [57].

When administered in a timely manner, IABP can play a critical role in the rescue of patients
with acute myocardial damage. It has been shown in animal models that insertion of IABP
during VA-ECMO support may improve several parameters of LV performance and can
reduce mean arterial pressure as well as oxygen saturation in the coronary sinus [24].

The combination of IABP and VA-ECMO can be found in the nationwide Japanese Diagnosis
Procedure Combination national inpatient database; IABP combined with VA-ECMO was
associated with reduced mortality and successful weaning from VA-ECMO. They also con-
cluded, of course, that randomized controlled studies are required to confirm the mortality-
reducing effect of the combination of IABP and VA-ECMO [57].

Despite the lack of clarity, in a systematic literature search, the use of concomitant IABP with
ECMO is widespread. IABP was present in approximately 55% of all ECMO cases reviewed,
stretching across all etiologies of cardiac failure beyond acute myocardial infarction (AMI).

The rationale for concomitant IABP use is primarily for LV venting [58]. The incremental ben-
efit of IABP support for afterload reduction and increasing organ perfusion in the presence of
ECMO support is relatively minimal. Regarding improved diastolic pressures and coronary
flow, despite the previously held belief of an estimated 11% survival benefit from pooled
analyses of retrospective studies of IABP use in AMI, it is now known from the prospective
and randomized IABP-SHOCK II study that the use of IABP in this cohort had no survival
benefit [59].
194 Advances in Extra-corporeal Perfusion Therapies

Early IABP, or, when CPO is very low and Impella offering the adequate flow, would sig-
nificantly impact the management of cardiogenic shock as it would avoid the administra-
tion of “toxic doses” of inotropes, allowing for smoother transition to VA-ECMO and routine
unloading of the LV [44–60].
Even though, the combined use of IABP and VA-ECMO or Impella and VA-ECMO is well
described to improve the hemodynamic facilitating and supporting conditions for recovery
or ventricular assist device implantation [61, 62].

Recently, a simulation published on the ASAIO Journal [63] has supported the relevance of opti-
mal medical management, fluid removal while minimizing VA-ECMO flow, reducing blood
pressure, and eventually adding inotropes to reduce PCWP and prevent pulmonary edema
[64]. Recent clinical data support this notion for different clinical settings and do not advocate
a routine combination of VA-ECMO and IABP. Clinical studies have shown a slight reduction
in PCWP, LV dimensions, and pulmonary edema in-line with the computer simulation [65].
Patients showing PCWP above 25 mmHg or a virtually non-ejecting LV will require interven-
tional or surgical adjunct measures, which theoretically reduce PCWP by more than 5 mmHg.
It has to be kept in mind that sometimes when you think of adding an unloading is too late
for the patient, a proactive management reasoning on the patient characteristics and hemo-
dynamics is pivotal.
In a recent computer simulation, this combined approach showed only limited LV unloading,
although pulsatility and increased stroke volume were noted. The CPO before VA-ECMO
implantation and the native heart stroke volume after VA-ECMO implantation could be rel-
evant determinants of the effectiveness of IABP also during VA-ECMO perfusion (Figure 3),
while a low PAPi may push toward biventricular support with Impella or TandemHeart.

5. Differences between atrial and ventricular unloading

When echocardiographic monitoring discloses surrogates of low contractility, LV distention

or high filling pressure (PCWP) of the left ventricle, inotropic support should be considered or
up titrated to increase contractility of the myocardium, and volume load should be assessed
and eventually treated. Other conditions to be considered as drivers for unloading need have
been represented in (Figure 4).
There are different drivers for atrial or ventricular unloading (Figure 5).
The kind of left side’s chamber decompression is strictly related to the mechanism of pulmo-
nary congestion and left ventricular distension. The variables that need to be kept in mind are:

• Adequacy of venous drainage: if the venous drainage may be considered poor, placement
of pulmonary artery or left atrial drainage (comprised septostomy) may be sufficient.
• Mitral regurgitation: atrial drainage may be sufficient to unload the ventricle if a significant
mitral regurgitation impedes the distension of the left ventricle.
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 195
http://dx.doi.org/10.5772/intechopen.80265

• Reversibility of left ventricle damage: ventricular unloading is pivotal to increase the

chance of recovery.

• Aortic regurgitation: addressing aortic valve may be needed to avoid blood recirculation
and stagnation.

Figure 6 shows the decisional process of management of conditions that may require unload-
ing if not properly treated, the only condition where unloading seems to be mandatory is
smoking effect or slow flow through the MV. Figure 7 shows the possible surgical invasive,
minimally invasive and percutaneous approaches aiming at ventricle unloading. When atrial
unloading may be sufficient, a percutaneous left atrial septostomy may be accomplished,
which allows blood from the LA to drain down its pressure gradient into the right atrium
(RA) to then be drained via the venous cannula. This procedure is quite common in many
hemodynamic lab especially used to treat pediatric patients. A cannula may also be placed
into the LA through a transseptal puncture to facilitate drainage [66]. In addition, the left
atrium or left ventricle can be directly cannulated allowing blood to be vented into the venous
arm of the ECMO circuit. The transition to a BiVAD (TandemHeart or Centrimag or Rotaflow)
could be considered if the oxygenator is no longer needed [67]. Finally, the use of a left ven-
tricular assist device such as the Impella (Abiomed, Danvers, MA) or BiPella (left and right
Impella RP) [68] to provide left ventricular decompression as well as forward flow has been
described and is gaining success due to its ease also bedside.

Figure 4. Factors driving unloading need in crash and burn patients. It has to be considered the possibility of unloading
LV if signs of fluid overload (high pulsatility and LV distension at Echo and hemodynamic data) are not effectively
treated with diuretics. Unloading is needed when there is low or absent LVEF, absent pulsatility without vasodilatation,
smoking effect or slow flow through the MV.
196 Advances in Extra-corporeal Perfusion Therapies

Figure 5. Atrial or ventricular unloading, decision making graph. In the graph, the pathological conditions in the blue
dots are drivers of ventricular unloading while that ones in the red dots are drivers for atrial decompression. In green
the first step therapy according to etiology.

Figure 6. Management of conditions that may require unloading if not properly treated.
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 197
http://dx.doi.org/10.5772/intechopen.80265

Figure 7. Surgical invasive, minimally invasive and percutaneous approaches to ventricle unloading.

Left-to-right shunt can achieve effective decompression of the left ventricle in the setting of
VA-ECMO at the presence of atrial communication (atrial septal defect or patent foramen
ovale); atrial shunt can be, however, created also artificially with a percutaneous blade or
balloon septostomy [69]. The procedure may be fruitful to induce pulmonary decongestion
reducing atrial pressure and pulmonary edema but led to a suboptimal LV decompression.
An alternative way to perform atrial unloading, under guidance by bedside transoesophageal
echocardiography, is by transseptal puncture and placement of a drain (8 Fr to 15 Fr). The
percutaneous atrial transseptal cannula can then be placed and connected to the inflow part
of the ECMO circuit, thus, decompressing the pulmonary circulation [70].

The left ventricle can be vented directly by placing a transaortic vent through the axillary
artery or by echocardiography-guided insertion of a pigtail catheter into the left ventricle
through the aortic valve and connected to the inflow part of the ECMO circuit [71]. Fumagalli
et al. [72] achieved the decompression with a catheter placed percutaneously through the
aortic valve into the left ventricle. The blood drained from the left ventricle was pumped into
the femoral artery through the VA-ECMO circuit. The normalization of left heart filling pres-
sures led to the resolution of pulmonary edema, and the patient underwent successful heart
transplantation. Barbone et al. [73] claimed LV unloading with a 7 Fr pigtail catheter inserted
into the left ventricle via the femoral artery contralateral to the arterial outflow cannula. Using
this approach in three different patients, the authors described resolution of LV distension
and prevention of lung congestion without major complications. However, a so long and tight
198 Advances in Extra-corporeal Perfusion Therapies

Figure 8. Techniques to unload the heart during ECMO. (1) Pathophysiology of LV distension during ECMO and (2)
Impella on top of ECMO (ECPELLA): pathophysiology.
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 199
http://dx.doi.org/10.5772/intechopen.80265

Figure 9. Optimal Arterial Pressure on VA-ECMO (Copyright from ASAIO).

line may be argued ineffective to warrant a large amount of drainage as it is generally needed.
Indeed, a recent paper indicates an algorithm to select the right dimension of the pig aiming
to reach the right unloading flow [74].

An alternative approach to LV decompression is the percutaneous insertion of a venous can-

nula into the pulmonary artery and connection of this cannula to the inflow part of the ECMO
circuit [75]. A small (15 Fr) venous cannula may be placed percutaneously to the pulmonary
artery and connected to the ECMO circuit to decompress the left heart and to facilitate LV
function. Surgical minimal invasive access to directly drain the pulmonary artery has been
also suggested.
Impella (Abiomed Inc., USA) is a catheter-based transaortic axial flow pump that can be intro-
duced through a percutaneous femoral approach. The device is placed across the aortic valve
and pumps up (2.5–5 L/min) of blood on the basis of the model (2.5, CP or 5 L) from the left
ventricle to the ascending aorta. The 2.5 and the CP are placed in the groin percutaneously
while the 5.0 is generally placed surgically in the right axillary artery to warrant to the patient
the possibility to be extubated and ambulatory.
Koeckert et al. [75] reported the use of Impella LP 2.5 for left ventricle decompression in a
70-year-old man with acutely decompensated heart failure who was placed on VA-ECMO for
cardiogenic shock with severe pulmonary edema and respiratory failure. Both devices were
successfully weaned on day 5 after myocardial recovery. Narain et al. [76] described a case
involving 31-year-old man with fulminant myocarditis treated with the Impella device and
200 Advances in Extra-corporeal Perfusion Therapies

Figure 10. Patient survival from end-organ function to myocardial recovery.

VA-ECMO. On full mechanical circulatory support, the hemodynamic status improved, and
both systems were explanted after 48 h. Many centers are now moving toward the adoption
of Impella as bailout for weaning and to unload the ventricle during VA-ECMO even if many
warnings have been expressed regarding the risks to add more complexity to the management
of an already complex patient [77, 78]. Figure 8 shows the pathophisiology of Left Ventricle dis-
tention due to ECMO (Figure 8-1) and the effects of adding Impella during ECMO (Figure 8-2).
Figure 9 shows all the possible surgical and percutaneous solutions to unload the left cir-
culation, preventing pulmonary edema and, possibly, facilitating the myocardial recovery
when the underlying disease is potentially reversible. According to what said before, to reach
patient survival, from end-organ function to myocardial recovery, we should balance arterial
pressure, flow rate and unloading passing through IABP if necessary. The delicate balance of
this therapeutical strategy is described in Figure 10.

6. Arterial pressure management during ECMO

While maintenance of flows is crucial to the care of the patient on VA-ECMO, attention must
also be paid to the mean arterial pressure, as the end organs require both a cardiac output and
a perfusion pressure for optimal function and a low venous pressure. A goal MAP >65 mmHg
may be used as a starting point but can be adjusted either lower or higher given individual
circumstances keeping in mind that the differential pressure between MAP and LAP is the
driving force of organ perfusion and function. On the other side, MAP should never exceed
90 mmHg to limit afterload and to promote forward flow, especially when peripheral
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 201
http://dx.doi.org/10.5772/intechopen.80265

cannulation limits the adequacy of drainage and leaves a remarkable amount of blood stag-
nating in the lung bed. A recent paper on the ASAIO Journal showed an inverse relation-
ship between mortality and MAP in VA-ECMO but not in VV-ECMO (Figure 10) [79]. In the
hypotensive patient, MAP may be increased by manipulating either CO or SVR. The total
cardiac output of the body is composed of native cardiac output and VA-ECMO flows. Thus,
hypotension may potentially be corrected by increasing VA-ECMO flows and its contribution
to total CO. Assuming a centrifugal pump, this may be achieved by administering volume
or by increasing the RPMs of the pump. If the problem is related to SVR, such as with septic
shock, a vasoconstrictor may be needed to increase MAP, although this must be weighed
against the effect of increased afterload and the increase in pressure work of the left ventricle.
Many different policies exist on the management of arterial pressure during VA-ECMO: one
concern is about the equivalence of MAP in patients with or without pulsatility. Physiologic
autoregulation is pivotal for end-organ perfusion and particularly for the brain and kidney.
Many studies dealt with ideal MAP value in the ICU patient, the most identify a cutoff of
65 mmHg, as a value usually sufficient also if the study [80] suggested a MAP of 75–85 as
protective for acute kidney injury in patients with a previous history of hypertension. To our
knowledge, however, there has been only few studies examining optimal MAP for patients on
ECMO and evidences in support of every practice are still weak.
Clearly, the physiology of VA-ECMO patients is considerably different from other critically ill
patients. Several studies identified to determine the optimal pressure on cardiopulmonary bypass
(CPB) during cardiac surgery [81–83] and the majority supports a MAP higher than 70 mm Hg
on CPB. VA-ECMO is quite different from CPB: CPB is usually initiated electively for patients on
stable patients, while VA-ECMO intervenes on an unstable circulatory condition. Moreover, the
circuit is not open as in the CPB, the heart is not arrested, and there is not a reservoir to avoid pul-
monary fluid overload. The heart is in a dynamic parallel circulation with ECMO aiming to reach
an equilibrium to eject against incoming blood flow from the ECMO circuit. The amount of work-
load may often be incompatible with the failing heart performance of most VA-ECMO patients.
VA-ECMO could induce increased afterload and further worsen myocardial dysfunction. If a lower
MAP could have the rationale to permit the heart to eject against a lower resistance decreasing the
myocardial oxygen demand, the clinical impact of hypotension on the patient in cardiogenic shock
has to be carefully judged. Furthermore, it may not be suitable to compare the MAP of patients
with and without pulsatility because patients without pulsatility may require a higher MAP for
end-organ perfusion. It may not be suitable to compare the MAP of patients with and without
pulsatility because patients without pulsatility may require a higher MAP for end-organ perfusion.

Pulsatility is a dynamic property due to the interaction between the two concurrent parallel circu-
lations; indeed a loss of pulsatility may signal worsening myocardial function, while the appear-
ance of pulsatility or an improvement in pulse pressure may signal recovery. However, the loss of
pulsatility may also suggest that VA-ECMO flows are too high, so reducing the amount of blood
managed from the impaired native circulation. The higher the ECMO flows, the more blood that
drains into the circuit causing a more significant decrease in LV preload, stroke volume, and
pulse pressure. Total bypass, where the ECMO circuit takes over 100% of the cardiac output,
creates a flat, non-pulsatile arterial tracing and signifies the lack of ejection of blood from the left
202 Advances in Extra-corporeal Perfusion Therapies

ventricle. A recent study from Sakir Akin and the Erasmus group has shown how the peripheral
recovery of pulsatility is a predictor of recovery that should push to weaning of ECMO [84].

Reduced pulsatility may also reflect a decrease in intravascular volume or a mechanical cause
of decreased venous return (i.e., atrial tamponade) that may cause a decrease in LV preload
leading decreased stroke volume and pulse pressure.

VA-ECMO reduces the volume work of the right ventricle through the decreased RV pre-
load, while pulmonary edema may cause hypoxic pulmonary vasoconstriction worsening
pulmonary hypertension and increasing RV pressure work. If this setting, the right ventricle
may be unable to pump to the left side of the heart, flattening arterial pressure waveform and
decreasing the stroke volume. Nitric oxide with inodilators such as milrinone and dobuta-
mine (which will also provide inotropic assistance) are needed. If systemic pressures allow,
nitroglycerin or nitroprusside may also be utilized.

7. Conclusions

Today, the first indication of treatment is weaning from ECMO and myocardial recovery.
This target is more frequently achieved in myocarditis or potentially reversible diseases and
stresses the importance of etiological diagnosis at the moment of implantation to define the
strategy of implantation. In Figure 11 there is a flow chart that clarifies how VA-ECMO should
be managed, according to the etiology, to reach the weaning from ECMO goal and myocardial
recovery, analysing the phases of the hemodynamic support and detecting unloading need
at the right time.

Figure 11. Flow chart on VA-ECMO management according to etiology.

 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 203
http://dx.doi.org/10.5772/intechopen.80265

VA-ECMO has to be deemed as temporary short-term support, and the risks related to the
permanence of an oxygenator must focus on a rapid transition to further MCS systems. The
assessment of left atrial pressure (direct or indirect) should be a mandatory tool in patients
with VA-ECMO to increase the chance of recovery or transition to next support or treatment.
When left atrial pressure is deemed increased in surgical unloading, or percutaneous unload-
ing has to be considered preferring whenever possible ventricular unloading especially when
mitral regurgitation is absent.

Randomized trials and registries will have to answer some of the open questions the clinician
has to solve daily, dealing with the patient on VA-ECMO:

• Which goal directs the “dose” of VA-ECMO?

• Does one VA-ECMO configuration fit all?

• When unload before and when after VA-ECMO institution?

• Which clinical and hemodynamic profiles favor upfront VA-ECMO with LV venting?

• To vent or not to vent?

• When is vent mandatory?

• How vent without harm the patient?

• Should we transition to durable LVAD or BiVAD as soon as the end organs recovers?

• What are the granular aspects of management that should be included in trial design for
VA-ECMO and LV venting?

Acknowledgements

Cristiano Amarelli acknowledges the Abiomed for the figures freely provided on the associa-
tion between ECMO and Impella.

This section of your manuscript may also include funding information.

Conflict of interest

No conflict of interest to declare.

Notes/thanks/other declarations

Thanks to IntechOpen for trusting and awaiting for the work to be finished.
204 Advances in Extra-corporeal Perfusion Therapies

Author details

Cristiano Amarelli1*, Francesco Musumeci2, Antonio Loforte3, Andrea Montalto2,

Sveva Di Franco4 and Jaime Hernandez-Montfort5

*Address all correspondence to: [email protected]

1 Department of Cardiac Surgery and Transplants, Monaldi Azienda dei Colli, Napoli, Italy
2 Department of Heart and Vessels, Cardiac Surgery Unit and Heart Transplantation Center,
S. Camillo-Forlanini Hospital, Rome, Italy

3 Department of Cardiovascular Surgery and Transplantation, S. Orsola-Malpighi Hospital,

Bologna University, Bologna, Italy

4 Department of Anaesthesiology and Critical Care Medicine, L. Vanvitelli University,

Naples, Italy

5 Department of Cardiology, University of Texas Medical Branch, Galveston, USA

References

[1] Thiele H, Zeymer U, Neumann F-J, Ferenc M, Olbrich H-G, Hausleiter J, et al. Intraaortic
balloon support for myocardial infarction with cardiogenic shock. New England Journal
of Medicine. 2012;367(14):1287-1296. DOI: 10.1056/NEJMoa1208410

[2] Ouweneel DM, Eriksen E, Sjauw KD, van Dongen IM, Hirsch A, Packer EJS, et al. Impella CP
versus intra-aortic balloon pump in acute myocardial infarction complicated by cardiogenic
shock: The IMPRESS trial. Journal of the American College of Cardiology. 2017;69(3):278-
287. DOI: 10.1016/j.jacc.2016.10.022. [Epub 2016 Oct 31]

[3] Thiele H, Akin I, Sandri M, Fuernau G, de Waha S, Meyer-Saraei R, et al. PCI strategies in
patients with acute myocardial infarction and cardiogenic shock. New England Journal
of Medicine. 2017;377(25):2419-2432. DOI: 10.1056/NEJMoa1710261

[4] Csepe TA, Kilic A. Advancements in mechanical circulatory support for patients in acute
and chronic heart failure. Journal of Thoracic Disease. 2017;9(10). Retrieved from: http://
jtd.amegroups.com/article/view/16372
[5] Kawashima D, Gojo S, Nishimura T, Itoda Y, Kitahori K, Motomura N, et al. Left ven-
tricular mechanical support with impella provides more ventricular unloading in heart fail-
ure than extracorporeal membrane oxygenation. ASAIO Journal. 2011;57(3):169-176. DOI:
10.1097/MAT.0b013e31820e121c. Retrieved from: https://journals.lww.com/asaiojournal/
Fulltext/2011/05000/Left_Ventricular_Mechanical_Support_with_Impella.5.aspx
[6] Amarelli C, Mastroianni C, Brechot N. Prompt diagnosis of a new clinical entity: Mem-
brane oxygenator infection during ECMO. ASAIO Journal. 2013;59(4):367. DOI: 10.1097/
MAT.0b013e31829c5d21
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 205
http://dx.doi.org/10.5772/intechopen.80265

[7] Beely BM, Campbell JE, Meyer A, Langer T, Negaard K, Chung KK, et al. Electron
microscopy as a tool for assessment of anticoagulation strategies during extracorporeal
life support: The proof is on the membrane. ASAIO Journal. 2016;62(5):525-532. DOI:
10.1097/MAT.0000000000000394. Retrieved from: https://journals.lww.com/asaiojournal/
Fulltext/2016/09000/Electron_Microscopy_as_a_Tool_for_Assessment_of.5.aspx

[8] Wilm J, Philipp A, Müller T, Bredthauer A, Gleich O, Schmid C, et al. Leukocyte adhe-
sion as an indicator of oxygenator thrombosis during extracorporeal membrane oxygen-
ation therapy? ASAIO Journal. 2018;64(1):24-30. DOI: 10.1097/MAT.0000000000000586.
Retrieved from https://journals.lww.com/asaiojournal/Fulltext/2018/01000/Leukocyte_
Adhesion_as_an_Indicator_of_Oxygenator.4.aspx

[9] Karagiannidis C, Brodie D, Strassmann S, et al. Extracorporeal membrane oxygenation:

Evolving epidemiology and mortality. Intensive Care Medicine. 2016;42:889-896

[10] Smith M, Vukomanovic A, Brodie D, Thiagarajan R, Rycus P, Buscher H. Duration of

veno-arterial extracorporeal life support (VA ECMO) and outcome: An analysis of the
extracorporeal life support organization (ELSO) registry. Critical Care. 2017;21(1):45.
DOI: 10.1186/s13054-017-1633-1

[11] Nakamura T, Ishida K, Taniguchi Y, Nakagawa T, Seguchi M, Wada H. Prognosis of

patients with fulminant myocarditis managed by peripheral venoarterial extracorpo-
real membranous oxygenation support: A retrospective single-center study. Journal of
Intensive Care. 2015;3(1). DOI: 10.1186/s40560-014-0069-9

[12] Rousse N, Juthier F, Pinçon C, Hysi I, Banfi C, Robin E, et al. ECMO as a bridge to
decision: Recovery, VAD, or heart transplantation? International Journal of Cardiology.
2015;187(1):620-627. DOI: 10.1016/j.ijcard.2015.03.283

[13] Durinka JB, Bogar LJ, Hirose H, Brehm C, Koerner MM, Pae WE, et al. End-organ recov-
ery is key to success for extracorporeal membrane oxygenation as a bridge to implant-
able left ventricular assist device. ASAIO Journal (American Society for Artificial Internal
Organs: 1992). 2014;60(2):189-192. DOI: 10.1097/MAT.0000000000000043

[14] Cheng A, Swartz MF, Massey HT. Impella to unload the left ventricle during periph-
eral extracorporeal membrane oxygenation. ASAIO Journal. 2013;59(5):533-536. DOI:
10.1097/MAT.0b013e31829f0e52

[15] Pappalardo F, Schulte C, Pieri M, Schrage B, Contri R, Soeffker G, et al. Concomitant

implantation of Impella® on top of veno-arterial extracorporeal membrane oxygenation
may improve survival of patients with cardiogenic shock. European Journal of Heart
Failure. 2017;19(3):404-412. DOI: 10.1002/ejhf.668

[16] Patel SM, Lipinski J, Al-Kindi SG, Patel T, Saric P, Li J, et al. Simultaneous venoarterial
extracorporeal membrane oxygenation and percutaneous left ventricular decompres-
sion therapy with impella is associated with improved outcomes in refractory cardio-
genic shock. ASAIO Journal. 2018:1. DOI: 10.1097/MAT.0000000000000767. [Epub ahead
of print]
206 Advances in Extra-corporeal Perfusion Therapies

[17] Goldberg RJ, Spencer FA, Gore JM, Lessard D, Yarzebski J. Thirty-year trends (1975 to
2005) in the magnitude of, management of, and hospital death rates associated with
cardiogenic shock in patients with acute myocardial infarction a population-based
perspective. Circulation. 2009;119(9):1211-1219. DOI: 10.1161/CIRCULATIONAHA.
108.814947
[18] Doll N, Kiaii B, Borger M, et al. Five-year results of 219 consecutive patients treated with
extracorporeal membrane oxygenation for refractory postoperative cardiogenic shock.
The Annals of Thoracic Surgery. 2004;77:151-157
[19] Sauer CM, Yuh DD, Bonde P. Extracorporeal membrane oxygenation use has increased
by 433% in adults in the United States from 2006 to 2011. ASAIO Journal. 2015;61(1):31-
36. DOI: 10.1097/MAT.0000000000000160

[20] Han JJ, Swain JBD. The perfect ECMO candidate. Journal of the American College of
Cardiology. 2018;71(10):1178-1182. DOI: 10.1016/j.jacc.2018.02.001

[21] Chung M, Shiloh AL, Carlese A. Monitoring of the adult patient on venoarterial extra-
corporeal membrane oxygenation. The Scientific World Journal. 2014;2014:393258. DOI:
10.1155/2014/393258
[22] Truby LK, Takeda K, Mauro C, Yuzefpolskaya M, Garan AR, Kirtane AJ, et al. Incidence
and implications of left ventricular distention during venoarterial extracorporeal
membrane oxygenation support. ASAIO Journal. 2017;63(3):257-265. DOI: 10.1097/
MAT.0000000000000553

[23] Rupprecht L, Flörchinger B, Schopka S, et al. Cardiac decompression on extracorporeal

life support: A review and discussion of the literature. ASAIO Journal. 2013;59(6):547-
553. DOI: 10.1097/MAT.0b013e3182a4b2f6
[24] Strunina S, Ostadal P. Left ventricle unloading during veno-arterial extracorporeal
membrane oxygenation. Current Research: Cardiology. 2016;3(1):5-8
[25] Bernhardt AM, Hillebrand M, Yildirim Y, Hakmi S, Wagner FM, Blankenberg S, et al.
Percutaneous left atrial unloading to prevent pulmonary oedema and to facilitate ven-
tricular recovery under extracorporeal membrane oxygenation therapy. Interactive
Cardiovascular and Thoracic Surgery. 2018;26(1):4-7. DOI: 10.1093/icvts/ivx266

[26] Flecher E, Anselmi A, Corbineau H, Langanay T, Verhoye J-P, Felix C, et al. Current aspects
of extracorporeal membrane oxygenation in a tertiary referral Centre: Determinants of
survival at follow-up. European Journal of Cardio-Thoracic Surgery. 2014;46(4):665-671.
DOI: 10.1093/ejcts/ezu029

[27] Meani P, Pappalardo F. The step forward for VA ECMO: Left ventricular unloading!
Journal of Thoracic Disease. 2017;9(11):4149-4151. http://doi.org/10.21037/jtd.2017.10.14

[28] Hireche-Chikaoui H, Grübler MR, Bloch A, Windecker S, Bloechlinger S, Hunziker L.

Nonejecting hearts on femoral veno-arterial extracorporeal membrane oxygenation.
Critical Care Medicine. 2018;1:e459-e464. DOI: 10.1097/CCM.0000000000002966
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 207
http://dx.doi.org/10.5772/intechopen.80265

[29] Hékimian G, Jovanovic T, Bréchot N, Lebreton G, Leprince P, Trouillet J, et al. When the
heart gets the flu. Journal of Critical Care. 2018;47:61-64

[30] Stevens MC, Callaghan FM, Forrest P, Bannon PG, Grieve SM. Flow mixing during
peripheral veno-arterial extra corporeal membrane oxygenation—A simulation study.
Journal of Biomechanics. 2017;55:64-70. DOI: 10.1016/j.jbiomech.2017.02.009

[31] Meani P, Gelsomino S, Natour E, Johnson DM, Rocca HPBL, Pappalardo F, et al.
Modalities and effects of left ventricle unloading on extracorporeal life support: A
review of the current literature. European Journal of Heart Failure. 2017;19:84-91. DOI:
10.1002/ejhf.850

[32] Dickstein ML. The starling relationship and veno-arterial ECMO. ASAIO Journal.
2018;64(4):497-501. DOI: 10.1097/MAT.0000000000000660

[33] Ostadal P, Mlcek M, Kruger A, et al. Increasing venoarterial extracorporeal membrane

oxygenation flow negatively affects left ventricular performance in a porcine model of
cardiogenic shock. Journal of Translational Medicine. 2015;13:266

[34] Aissaoui N, Guerot E, Combes A, et al. Two-dimensional strain rate and Doppler tissue
myocardial velocities: Analysis by echocardiography of hemodynamic and functional
changes of the failed left ventricle during different degrees of extracorporeal life sup-
port. Journal of the American Society of Echocardiography. 2012;25:632-640

[35] Soleimani B, Pae WE. Management of left ventricular distension during peripheral
extracorporeal membrane oxygenation for cardiogenic shock. Perfusion. 2012;27:326-331

[36] Fuhrman BP, Hernan LJ, Rotta AT, Heard CMB, Rosenkranz ER. Pathophysiology of
cardiac extracorporeal membrane oxygenation. Artificial Organs. 1999;23:966-969

[37] Burkhoff D, Sayer G, Doshi D, Uriel N. Hemodynamics of mechanical circulatory

support. Journal of the American College of Cardiology. 2015;66(23):2663-2674. DOI:
10.1016/j.jacc.2015.10.017

[38] Doufle G, Ferguson ND. Monitoring during extracorporeal membrane oxygenation.

Current Opinion in Critical Care. 2016;22(3):230-8. DOI: 10.1097/MCC.0000000000000309

[39] Sidebotham D, Allen S, McGeorge A, Beca J. Catastrophic left heart distension following
initiation of venoarterial extracorporeal membrane oxygenation in a patient with mild
aortic regurgitation. Anaesthesia and Intensive Care. 2012;40:568-569

[40] Douflé G, Roscoe A, Billia F, Fan E. Echocardiography for adult patients supported
with extracorporeal membrane oxygenation. Critical Care. 2015;19:326. DOI: 10.1186/
s13054-015-1042-2

[41] Donker DW, Meuwese CL, Braithwaite SA, Broomé M, van der Heijden JJ, Hermens
JA, et al. Echocardiography in extracorporeal life support: A key player in procedural
guidance, tailoring and monitoring. Perfusion (United Kingdom). 2018;33(1_suppl):31-
41. DOI: 10.1177/0267659118766438
208 Advances in Extra-corporeal Perfusion Therapies

[42] Esposito ML, Kapur NK. Acute mechanical circulatory support for cardiogenic shock: The
“door to support” time. F1000Research. 2017;6:737. DOI: 10.12688/f1000research.11150.1
[43] Truesdell AG, Tehrani B, Singh R, Desai S, Saulino P, Barnett S, et al. “Combat” approach
to cardiogenic shock. Interventional Cardiology Review. 2018;13(2):81-86. http://doi.
org/10.15420/icr.2017:35:3

[44] Williams DO, Korr KS, Gewirtz H, Most AS. The effect of intraaortic balloon counter-
pulsation on regional myocardial blood flow and oxygen consumption in the presence
of coronary artery stenosis in patients with unstable angina. Circulation. 1982;66(3):593-
597. DOI: 10.1161/01.CIR.66.3.593

[45] Marra C, De Santo LS, Amarelli C, Della Corte A, Onorati F, Torella M, et al. Coronary
artery bypass grafting in patients with severe left ventricular dysfunction: A prospec-
tive randomized study on the timing of perioperative intraaortic balloon pump support.
International Journal of Artificial Organs. 2002;25(2):141-146
[46] Zobel G, Dacar D, Kuttnig M, Rodl S, Rigler B. Mechanical support of the left ventricle
in ischemia induced left ventricular failure: An experimental study. The International
Journal of Artificial Organs. 1992;15(2):114-119

[47] Werdan K, Gielen S, Ebelt H, Hochman JS. Mechanical circulatory support in cardio-
genic shock. European Heart Journal. 2014;35(3):156-167. DOI: 10.1093/eurheartj/eht248.
[Epub 2013 Sep 7]
[48] Ma P, Zhang Z, Song T, Yang Y, Meng G, Zhao J, et al. Combining ECMO with IABP for
the treatment of critically ill adult heart failure patients. Heart Lung and Circulation.
2014;23(4):363-368. DOI: 10.1016/j.hlc.2013.10.081

[49] Petroni T, Harrois A, Amour J, et al. Intra-aortic balloon pump effects on macrocircula-
tion and microcirculation in cardiogenic shock patients supported by venoarterial extra-
corporeal membrane oxygenation. Critical Care Medicine. 2014;42:2075-2082

[50] Park TK, Yang JH, Choi SH, et al. Clinical impact of intra-aortic balloon pump during
extracorporeal life support in patients with acute myocardial infarction complicated by
cardiogenic shock. BMC Anesthesiology. 2014;14:27
[51] Fincke R, Hochman JS, Lowe AM, Menon V, Slater JN, Webb JG, et al. Cardiac power is
the strongest hemodynamic correlate of mortality in cardiogenic shock: A report from
the SHOCK trial registry. Journal of the American College of Cardiology. 2004;44(2):340-
348. DOI: 10.1016/j.jacc.2004.03.060
[52] De Silva K, Lumley M, Kailey B, Alastruey J, Guilcher A, Asrress KN, et al. Coronary
and microvascular physiology during intra-aortic balloon counterpulsation. JACC:
Cardiovascular Interventions. 2014;7(6):631-640. DOI: 10.1016/j.jcin.2013.11.023

[53] Scandroglio AM, Pieri M, Pappalardo F, Landoni G. Intra-aortic balloon pump dur-
ing venoarterial extracorporeal membrane oxygenation: Still a matter of debate?
Contemporary multi-device approach to cardiogenic shock. Journal of Thoracic Disease.
2017;9(5):E522-E524
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 209
http://dx.doi.org/10.5772/intechopen.80265

[54] Shishehbor MH, Moazami N, Tong MZY, Unai S, Tang WHW, Soltesz EG. Cardiogenic
shock: From ECMO to Impella and beyond. Cleveland Clinic Journal of Medicine.
2017;84(4):287-295. DOI: 10.3949/ccjm.84gr.17002

[55] Hoeper MM, Tudorache I, Kühn C, Marsch G, Hartung D, Wiesner O, et al. Extra-
corporeal membrane oxygenation watershed. Circulation. 2014;130(10):864-865. DOI:
10.1161/CIRCULATIONAHA.114.011677

[56] Lin LY, Liao CW, Wang CH, Chi NH, Yu HY, Chou NK, et al. Effects of additional intra-
aortic balloon counter-pulsation therapy to cardiogenic shock patients supported by
extra-corporeal membranous oxygenation. Scientific Reports. 2016;6:23838 DOI: 10.1038/
srep23838

[57] Cheng JM, den Uil CA, Hoeks SE, et al. Percutaneous left ventricular assist devices vs.
intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: A meta-
analysis of controlled trials. European Heart Journal. 2009;30:2102-2108
[58] Nuding S, Werdan K. IABP plus ECMO—Is one and one more than two? Journal of
Thoracic Disease. 2017;9(4):961-964
[59] Sauren LDC, Accord RE, Hamzeh K, De Jong M, Van Der Nagel T, Van Der Veen FH,
et al. Combined Impella and intra-aortic balloon pump support to improve both ven-
tricular unloading and coronary blood flow for myocardial recovery: An experimental
study. Artificial Organs. 2007;31(11):839-842. DOI: 10.1111/j.1525-1594.2007.00477.x

[60] O’Connor CM, Rogers JG. Evidence for overturning the guidelines in cardiogenic shock.
New England Journal of Medicine. 2012;367(14):1349-1350. DOI: 10.1056/NEJMe1209601

[61] Gaudard P, Mourad M, Eliet J, Zeroual N, Culas G, Rouvière P, et al. Management and
outcome of patients supported with Impella 5.0 for refractory cardiogenic shock. Critical
Care. 2015;19(1). DOI: 10.1186/s13054-015-1073-8
[62] Pieri M, Contri R, Winterton D, Montorfano M, Colombo A, Zangrillo A, et al. The con-
temporary role of Impella in a comprehensive mechanical circulatory support program:
A single institutional experience. BMC Cardiovascular Disorders. 2015;15(1):126. DOI:
10.1186/s12872-015-0119-9
[63] Donker DW, Brodie D, Henriques JPS, Broomé M. Left ventricular unloading during
veno-arterial ECMO. ASAIO Journal. 2018. DOI: 10.1097/MAT.0000000000000755. [Epub
ahead of print]

[64] Bréchot N, Demondion P, Santi F, Lebreton G, Pham T, Dalakidis A, et al. Intra-aortic

balloon pump protects against hydrostatic pulmonary oedema during peripheral
venoarterial-extracorporeal membrane oxygenation. European Heart Journal: Acute
Cardiovascular Care. 2018;7(1):62-69. DOI: 10.1177/2048872617711169. [Epub 2017 Jun 2]

[65] Cheng R, Hachamovitch R, Makkar R, Ramzy D, Moriguchi JD, Arabia FA, et al. Lack of
survival benefit found with use of intraaortic balloon pump in extracorporeal membrane
oxygenation: A pooled experience of 1517 patients. Journal of Invasive Cardiology.
2015;27(10):453-458
210 Advances in Extra-corporeal Perfusion Therapies

[66] Baruteau A-E, Barnetche T, Morin L, Jalal Z, Boscamp NS, Le Bret E, et al. Percutaneous
balloon atrial septostomy on top of venoarterial extracorporeal membrane oxygenation
results in safe and effective left heart decompression. European Heart Journal: Acute
Cardiovascular Care. 2018;7(1):70-79. DOI: 10.1177/2048872616675485. [Epub 2016 Oct 14]

[67] Saffarzadeh A, Bonde P. Options for temporary mechanical circulatory support. Journal
of Thoracic Disease. 2015;7(12):2102-2111. DOI: 10.3978/j.issn.2072-1439.2015.09.14

[68] Kuchibhotla S, Esposito ML, Breton C, Pedicini R, Mullin A, O’Kelly R, et al. Acute biven-
tricular mechanical circulatory support for cardiogenic shock. Journal of the American
Heart Association. 2017;6(10). pii:e006670. DOI: 10.1161/JAHA.117.006670
[69] Seib PM, Faulkner SC, Erickson CC, Van Devanter SH, Harrell JE, Fasules JW,
et al. Blade and balloon atrial septostomy for left heart decompression in patients
with severe ventricular dysfunction on extracorporeal membrane oxygenation.
Catheterization and Cardiovascular Interventions. 1999;46(2):179-186. DOI: 10.1002/
(SICI)1522-726X(199902)46:2<179::AID-CCD13>3.0.CO;2-W

[70] Aiyagari RM, Rocchini AP, Remenapp RT, Graziano JN. Decompression of the left
atrium during extracorporeal membrane oxygenation using a transseptal cannula incor-
porated into the circuit. Critical Care Medicine. 2006;34(10):2603-2606. DOI: 10.1097/01.
CCM.0000239113.02836.F1
[71] Avalli L, Maggioni E, Sangalli F, Favini G, Formica F, Fumagalli R. Percutaneous left-
heart decompression during extracorporeal membrane oxygenation: An alternative to
surgical and transeptal venting in adult patients. ASAIO Journal. 2011;57(1):38-40. DOI:
10.1097/MAT.0b013e3181fe5d0b
[72] Fumagalli R, Bombino M, Borelli M, Rossi F, Colombo V, Osculati G, et al. Percutaneous
bridge to heart transplantation by venoarterial ECMO and transaortic left ven-
tricular venting. International Journal of Artificial Organs. 2004;27(5):410-413. DOI:
10.1177/039139880402700510

[73] Barbone A, Malvindi PG, Ferrara P, Tarelli G. Left ventricle unloading by percutaneous
pigtail during extracorporeal membrane oxygenation. Interactive Cardiovascular and
Thoracic Surgery. 2011;13(3):293-295. DOI: 10.1510/icvts.2011.269795
[74] Kim WH, Hong TH, Byun JH, Kim JW, Kim SH, Moon SH, et al. Flow rate through
pigtail catheter used for left heart decompression in an artificial model of extracorpo-
real membrane oxygenation circuit. ASAIO Journal. 2017;63(3):346-350. DOI: 10.1097/
MAT.0000000000000472
[75] Koeckert MS, Jorde UP, Naka Y, Moses JW, Takayama H. Impella LP 2.5 for left ven-
tricular unloading during venoarterial extracorporeal membrane oxygenation support.
Journal of Cardiac Surgery. 2011;26:666-668

[76] Narain S, Paparcuri G, Fuhrman TM, Silverman RB, Peruzzi WT. Novel combination of
Impella and extra corporeal membrane oxygenation as a bridge to full recovery in fulmi-
nant myocarditis. Case Reports in Critical Care. 2012;2012:1-3. DOI: 10.1155/2012/459296
 Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO 211
http://dx.doi.org/10.5772/intechopen.80265

[77] Camboni D, Schmid C. To vent or not on veno-arterial extracorporeal membrane

oxygenation, does it improve myocardial recovery and outcome? Journal of Thoracic
Disease. 2017;9(12):4915-4918. https://doi.org/10.21037/jtd.2017.11.98
[78] Akanni OJ, Takeda K, Truby LK, Kurlansky PA, Chiuzan C, Han J, et al. EC-VAD: Combined
use of extracorporeal membrane oxygenation and percutaneous microaxial pump left
ventricular assist device. ASAIO Journal. 2018. DOI: 10.1097/MAT.0000000000000804
[Epub ahead of print]. Retrieved from: https://journals.lww.com/asaiojournal/Fulltext/
onlinefirst/EC_VAD_Combined_Use_of_Extracorporeal_Membrane.98870.aspx

[79] Tanaka D, Shimada S, Mullin M, Kreitler K, Cavarocchi N, Hirose H. What is the optimal
blood pressure on Veno-arterial extracorporeal membrane oxygenation? Impact of mean
arterial pressure on survival. ASAIO Journal. 2018. DOI: 10.1097/MAT.0000000000000824.
[Epub ahead of print]. Retrieved from: https://journals.lww.com/asaiojournal/Fulltext/
onlinefirst/What_Is_the_Optimal_Blood_Pressure_on.98853.aspx

[80] Leone M, Asfar P, Radermacher P, Vincent JL, Martin C. Optimizing mean arterial pres-
sure in septic shock: A critical reappraisal of the literature. Critical Care. 2015;19:101.
DOI: 10.1186/s13054-015-0794-z
[81] Gold JP, Charlson ME, Williams-Russo P, Szatrowski TP, Peterson JC, Pirraglia PA, et al.
Improvement of outcomes after coronary artery bypass: A randomized trial compar-
ing intraoperative high versus low mean arterial pressure. The Journal of Thoracic and
Cardiovascular Surgery. 1995;110(5):1302-1314. DOI: 10.1016/S0022-5223(95)70053-6

[82] Murphy GS, Hessel EA, Groom RC. Optimal perfusion during cardiopulmonary bypass:
An evidence-based approach. Anesthesia and Analgesia. 2009;108(5):1394-1417. DOI:
10.1213/ane.0b013e3181875e2e
[83] Levin MA, Lin HM, Castillo JG, Adams DH, Reich DL, Fischer GW. Early on-cardio-
pulmonary bypass hypotension and other factors associated with vasoplegic syndrome.
Circulation. 2009;120(17):1664-1671. DOI: 10.1161/CIRCULATIONAHA.108.814533

[84] Akin S, dos Reis Miranda D, Caliskan K, Soliman OI, Guven G, Struijs A, et al. Functional
evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO
in cardiogenic shock. Critical Care. 2017;21(1):265. DOI: 10.1186/s13054-017-1855-2