Mechanical circulatory support has evolved markedly over the recent years. In particular, the use of venoarterial membrane oxygenation (VA-ECMO) and Impella (Abiomed, Danvers, MA) has become a widely accepted therapy option for patients in cardiogenic shock.1 The application of Impella or VA-ECMO for immediate resuscitation and patient stabilization with the potential of end-organ function recovery is a useful strategy to improve survival of this otherwise extremely sick patient population. The availability of these systems was initially limited to only few specialized centers. However, this has changed during the recent years and the accessibility of these system in almost all cath laboratories led to explosion in the number of implanted systems worldwide. This positive trend was possibly associated with saving lives of many patients. However, the “uncontrolled” application of these systems on the other hand was not necessarily accompanied by improving survival.2 As a matter of fact, some centers started implanting these systems without knowing the detailed ”know-hows” of dealing with these complex patient population.
The article of Vallabhajosyula et al.3 shed light on one of the important aspects in the management of these complex patient population namely the necessity of left ventricular (LV) venting in patients with VA-ECMO by adding additional circulatory support in the form of Impella (so-called ECPELLA strategy). The study was determined to compare early mortality in patients with cardiogenic shock treated with ECPELLA in comparison to VA-ECMO alone. All published literature from 2000 to 2018 was reviewed. Five retrospective observational studies, representing 425 patients, were included. There were no randomized studies included. The main findings of this study can be summarized as ECPELLA is being increasingly used during the recent years and ECPELLA strategy was associated with higher weaning from VA-ECMO and bridging to permanent ventricular assist device or cardiac transplant in some studies. However, both strategies were associated with a high rate of complications, including major bleeding, transfusions, limb ischemia, and acute kidney injury.
One of main limiting factor in this article includes the heterogeneity of the included studies. This fact limits the clinical significance of the study findings to a great extent. For instance, in one of the included studies, Akanni et al.4 evaluated 29 patients with unselected cardiogenic shock who were converted to ECPELLA from either VA-ECMO (n = 14) or Impella (n = 15) monotherapy and compared them with patients receiving VA-ECMO during the same time period.4 Impella patients were post acute myocardial infarction (AMI) patients, while VA-ECMO patients were predominantly postcardiotomy patients. Meanwhile, in another included study by Mourad et al.,5 42 AMI patients with cardiogenic shock were treated with VA-ECMO (n = 23) and Impella (n = 19) monotherapy initially with a subsequent conversion to ECPELLA strategy. Different kinds of Impella were used including seven patients supported with Impella 5.0. No differences in the outcome between the groups were observed. However, in the study of Pappalardo et al.,6 which may be in my opinion, the most representative study included 34 cardiogenic shock patients with ECPELLA (only Impella 2.5 and Impella CP were used) were evaluated. These patients were compared with propensity-matched controls on VA-ECMO. A better outcome in ECPELLA group was documented. Notably, patients in the control group of that study had higher rates of cardiac arrest and preimplantation cardiopulmonary resuscitation as compared with the ECPELLA cohort.
We assume that all of VA-ECMO included in these studies were supported later with Impella to unload the LV. Therefore, one of the interesting finding of Vallabhajosyula et al.3 study is that use of ECPELLA strategy was associated with improvements in systolic and diastolic pulmonary arterial pressures, improvements in central venous pressures, decrease in liver enzymes, decreased total vasoactive medication requirements, higher-VA-ECMO weaning, and greater bridging to recovery or bridge to permanent therapies such as durable assist devices and cardiac transplant.3 Considering the mortality, diverging results were documented. The overall mortality was high in both cohorts. As expected, mortality among the individual studies varied between 32% and 78% for ECPELLA and 43–80% for VA-ECMO patients. Two studies reported a lower mortality in the ECPELLA cohort as compared with the VA-ECMO cohort. Meanwhile, in one study, early mortality was higher in the ECPELLA cohort. The remaining two studies reported no difference in early mortality between the two treatment groups.3
There are many factors determining the outcome in cardiogenic shock patients. These factors include type of shock (postcardiotomy, post-AMI or acute on chronic heart failure), predominantly affected cardiac site (right ventricle, LV, or biventricular), and severity of the shock (stage A versus stage E).7 As mentioned earlier, the study of Vallabhajosyula et al.3 included different kinds of cardiogenic shock patients, which per default offer different outcome regardless of the strategy used. Another important factor determining the outcome is the “know-how” how to manage these patients. The management of these patients is very complex and require huge amount of resources. There are many critical points to consider while managing these patients. One of the most important factor that was underestimated until recent years is the so-called “venting” of the LV. It is important to understand the major differences in these two forms of circulatory support systems. Impella has the advantage of being easier to implant, provide physiologic flow but provide no pulmonary support and the flow is limited. Meanwhile, VA-ECMO provides adequate amount of flow and simultaneous pulmonary support. However, VA-ECMO is not physiologic, increase the LV afterload, and the LV is not adequately unloaded unless vented. It is very crucial to prevent lung edema on VA-ECMO and not to wait for it. There are many clinical clues that can assist the clinician in decision making regarding the need of venting. These include observing the arterial pulse pressure (with pulse pressure <20 mm Hg being a risk factor) and measuring the pulmonary artery wedge pressure using pulmonary catheter while on ECMO. Off course, the above-mentioned parameters need to be combined with the finding of the echocardiography (severe mitral regurgitation, observing smoke phenomena in LV, and closed aortic valve being major risk factors). Once potential patient is detected, quick actions are mandatory to avoid pulmonary congestion. There are many ways recommended to overcome this issue. One of the easiest and fastest way, which we use very often at our center, is the use of inotropic agents (epinephrine or dobutamine) to facilitate ejection through the aortic valve. This option is, however, only applicable for patients with rest LV ejection. Other options include use of intra-aortic balloon pump (IABP), surgical vent, catheter vent in pulmonary artery, or use of Impella. The importance of LV venting has been postulated in many recent publications.6,8 Russo et al.8 recently reported the outcome of a meta-analysis summarizing 2,221 publications including 17 observational studies and 3,997 patients. Various forms of venting were used; the majority of these patients were vented using IABP (91.7%), Impella in 5.5%, and left atrium/pulmonary artery cannulation in 2.8%. The main finding of this study was that venting the LV was associated with decreasing mortality.
Each of the above-mentioned venting options has its own advantage and limitations. Traditionally, the IABP has been used, but multiple studies did not show convincing evidence of improved outcomes of concomitant IABP use.9 However, the Paris group conducted multiple studies on this topic showing promising results.10 Meanwhile, other centers published promising results with atrial septostostomy only.11 The use of “surgical” venting has been advocated from some centers. However, these surgical vents have been associated with higher bleeding and complication rates and therefore not frequently used.12 Another strategy that has been advocated by some clinicians is the use of central ECMO instead of peripheral ECMO.13–16 This strategy has the theoretical advantage that using axillary artery or aorta may generate lower LV afterload compared with peripheral ECMO due to the presence of physiologic blood flow. However, there are no data supporting this finding with particular focus on LV unloading. In the setting of postcardiotomy cardiogenic shock, a multicenter trial including our group failed to demonstrate a survival advantage in central ECMO group.14 Notably, this was mainly caused by increased bleeding rate in the central ECMO group of that study. Meanwhile, our group failed to demonstrate any advantage of central versus peripheral ECMO in cardiogenic shock and cardiac transplant patients in two different studies.15,16 Therefore, is it yet to be investigated if central or peripheral ECMO offers any advantage considering LV unloading.
One of the promising venting options which is the subject of Vallabhajosyula et al.3 publication is the use of Impella.3 It is important to mention that due to the expected increase in the complication rates (particularly hemolysis and limb ischemia) many centers avoid using these two mechanical support options simultaneously. The usual scenario is either Impella which is not providing enough support (cardiac or pulmonary), therefore need additional VA-ECMO support or VA-ECMO patient, who develop lung edema and need Impella for mechanical venting. Importantly, as already mentioned, the indication for the placement of a secondary device (usually an Impella for patients on VA-ECMO) should be defined by objective criteria, such as elevated wedge pressures, persistent pulmonary edema, or objective echocardiographic criteria of LV distention.10 Needless to say, despite the described potential benefits of LV venting with Impella, the role of ECPELLA strategy needs to be balanced against the risks of blood transfusions for hemorrhage, hemolysis, and vascular complications with lack of conclusive information on mortality benefit. Notably, to minimize vascular complications in patients with ECPELLA, some centers use distal leg perfusion for the impella site. Another attractive option is to add Impella 5.0 through the right axillary artery in VA-ECMO patients. This option has the advantages of avoiding limb ischemia and enables better evaluation of the right ventricular function (LVAD candidacy) and mobilization after ECMO explanation at later stage.
In summary, as the authors already stated, due to high baseline confounding and inadequate adjustment for severity of illness, this study is unable to directly compare the early mortality in the two cohorts and incapable to give the clinician convincing data to push for ECPELLA strategy in the presence of the above-mentioned less invasive venting strategies. The results of the Prospective Randomised Trial of Early LV Venting Using Impella CP for Recovery in Patients With Cardiogenic Shock Managed With VA ECMO Trial, which is initiated from the University of Pennsylvania group may provide a more representative insight to the usefulness of this controversial ECPELLA strategy.
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