**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, 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 factor 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:

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

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-

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

Moreover, many publications have disclosed a dramatic burden of complications using percutaneous VA-ECMO leading to higher costs and ethical discussions on the right clinical set-

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

Percutaneous VA-ECMO appears fitted to restore peripheral flows when the patient experiences 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

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

Contemporary registries and center reports support the ultimate finality of therapy for acute decompensated heart failure being myocardial recovery [26]. When pathology is reversible,

**2. Incidence of complications and ECMO configuration**

change and is still ranging between 50 and 70% [17].

authors as a good goal to direct VA-ECMO perfusion [21].

tings for its clinical adoption [9, 18–20].

pulmonary edema [23–25].

wide spectrum of configurations.

**3. Destination of VA-ECMO**

biatrial VA-ECMO is also possible.

186 Advances in Extra-corporeal Perfusion Therapies

ing and after VA-ECMO support.


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 phenomena. 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 detrimental by increasing the complexity of management and when is indeed indicated the transition 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 support with the combination of Impella 5.0 and RP or percutaneous biatrial ECMO is also possible 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 various parameters of LV performance [33–35] and, in extreme situations, the aortic valve can remain closed even during systole.

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 warranting 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.

Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO

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

189

Placed in the setting of hypotension and cardiogenic shock, the increase in MAP after initiation of VA-ECMO is associated with a significant increase in PCWP and decrease in LV SV,

Careful management of patients on VA-ECMO should include monitoring of intravascular

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 manipulation 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 perfusion 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

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 coronary 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 hemodynamic 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,

counteracting the emptying of the ventricle and its work.

which MAP is controlled while maintaining a minimal LV SV.

volume status, MAP, and PCWP.

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 ventricle. 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 reduction 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 pulmonary capillary occlusion pressure. The presence of severe mitral regurgitation may worsen left atrial hypertension congesting the pulmonary bed leading to pulmonary edema and even hemorrhage. 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 physiopathologic and/or eventual simulation models do not already suggest the need of an unloading. 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 formation. 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 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 warranting 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.

various parameters of LV performance [33–35] and, in extreme situations, the aortic valve can

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

The presence of a pulse pressure depends (without IABP) on the stroke volume of the left ventricle. 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 reduction 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 pulmonary capillary occlusion pressure. The presence of severe mitral regurgitation may worsen left atrial hypertension congesting the pulmonary bed leading to pulmonary edema and even hemorrhage. 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 physiopathologic and/or eventual simulation models do not already suggest the need of an unloading. 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 formation. 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

remain closed even during systole.

188 Advances in Extra-corporeal Perfusion Therapies

LV is relatively afterload insensitive.

Placed in the setting of hypotension and cardiogenic shock, the increase in MAP after initiation 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 manipulation 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 perfusion 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 coronary 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 hemodynamic 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,

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 adoption 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.

Flow Optimization, Management, and Prevention of LV Distention during VA-ECMO

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191

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 synchronized with cardiac cycle: the deflation just before systolic ejection aims to decrease afterload and improve LV ejection, while the inflation during diastole warrants increased diastolic

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 mechanical 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 pumping 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

perfusion aiming at improve coronary, cerebral, and visceral blood flow.

**4. IABP during ECMO**

**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 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 adoption 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.
