ECPella: Concept, Physiology and Clinical Applications

Addition of Impella on top of venoarterial extracorporeal membrane oxygenation (VA-ECMO) has gained wide interest as it might portend improved outcomes in patients with cardiogenic shock. This has been consistently reported in retrospective propensity-matched studies, case series, and meta-analyses.The pathophysiologic background is based on the mitigation of ECMO-related side effects and the additive benefit of myocardial unloading. In this perspective, thorough knowledge of these mechanisms is required to optimize the management of mechanical circulatory support with this approach and introduce best practices, as the interplay between the two devices and the implantation-explantation strategies are key for success. Addition of Impella on top of venoarterial extracorporeal membrane oxygenation (VA-ECMO) has gained wide interest as it might portend improved outcomes in patients with cardiogenic shock. This has been consistently reported in retrospective propensity-matched studies, case series, and meta-analyses. The pathophysiologic background is based on the mitigation of ECMO-related side effects and the additive benefit of myocardial unloading. In this perspective, thorough knowledge of these mechanisms is required to optimize the management of mechanical circulatory support with this approach and introduce best practices, as the interplay between the two devices and the implantation-explantation strategies are key for success. VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION (VA-ECMO) commonly is used to support patients with refractory cardiac arrest or cardiogenic shock,1Szabo G. Veres G. Radovits T. et al.The novel synthetic serine protease inhibitor CU-2010 dose-dependently reduces postoperative blood loss and improves postischemic recovery after cardiac surgery in a canine model.J Thorac Cardiovasc Surg. 2010; 139: 732-740Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 2Schwarz B. Mair P. Margreiter J. et al.Experience with percutaneous venoarterial cardiopulmonary bypass for emergency circulatory support.Crit Care Med. 2003; 31: 758-764Crossref PubMed Scopus (122) Google Scholar, 3Stulak J.M. Dearani J.A. Burkhart H.M. et al.ECMO cannulation controversies and complications.Semin Cardiothorac Vasc Anesth. 2009; 13: 176-182Crossref PubMed Scopus (58) Google Scholar mainly via percutaneous cannulation.4Zornoff L.A. Skali H. Pfeffer M.A. et al.Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction.J Am Coll Cardiol. 2002; 39: 1450-1455Crossref PubMed Scopus (359) Google Scholar This strategy may cause left ventricle (LV) distention that compromises myocardial recovery.5Kawashima D. Gojo S. Nishimura T. et al.Left ventricular mechanical support with Impella provides more ventricular unloading in heart failure than extracorporeal membrane oxygenation.ASAIO J. 2011; 57: 169-176Crossref PubMed Scopus (109) Google Scholar Direct LV unloading provided by Impella was associated with lower mortality in patients with cardiogenic shock supported with VA-ECMO in a recent international multicenter study.6Schrage B. Becher P.M. Bernhardt A. et al.Left ventricular unloading is associated with lower mortality in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation: Results from an international, multicenter cohort study.Circulation. 2020; 142: 2095-2106Crossref PubMed Scopus (87) Google Scholar The present paper has a specific purpose to provide a complete overview of this strategy, starting from a solid pathophysiologic approach. Then, the rationale for unloading the LV and the related available techniques is discussed. Finally, the combined configuration of VA-ECMO and Impella (ECPella) is fully treated, providing its significant clinical applications. The mechanical and hemodynamic properties of the heart are shown by the ventricular pressure-volume loop (PVL). The PVL describes the four phases of the cardiac cycle, respectively: (1) isovolumic contraction, (2) ejection, (3) isovolumic relaxation, and (4) filling. Typically, the PVL is characterized by the intrinsic (ventricular) properties of the myocardium and by the influence of the extrinsic vascular conditions. The ventricular intrinsic properties are represented by two lines that inscribe the PVL shape. The end-systolic pressure-volume relationship is linear.7Burkhoff D. Sayer G. Doshi D. et al.Hemodynamics of mechanical circulatory support.J Am Coll Cardiol. 2015; 66: 2663-2674Crossref PubMed Scopus (261) Google Scholar On the contrary, the end-diastolic pressure- volume line is a nonlinear relationship and reflects the diastolic properties.8Burkhoff D. Mirsky I. Suga H. Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: A guide for clinical, translational, and basic researchers.Am J Physiol Hearty Circ Physiol. 2005; 289: H501-H512Crossref PubMed Scopus (505) Google Scholar Differently, the extrinsic conditions mainly are defined by the concepts of preload and afterload. The end-diastolic volume (and, therefore, pressure) indicate the preload, which is a surrogate of the sarcomere length. Differently, the afterload can be depicted on the pressure-volume plane by the “effective arterial elastance” line, influenced by the systemic vascular resistances, the heart rate, and, finally, the preload 9Sunagawa K. Maughan W.L. Burkhoff D. et al.Left ventricular interaction with arterial load studied in isolated canine ventricle.Am J Physiol. 1983; 245: H773-H780PubMed Google Scholar (see Table 1 and Figure 1).Table 1Main Pressure-Volume Loop Features Related to Figure 1.Intrinsic PropertiesESPVRThe linear relationship is defined by 2 main features7Burkhoff D. Sayer G. Doshi D. et al.Hemodynamics of mechanical circulatory support.J Am Coll Cardiol. 2015; 66: 2663-2674Crossref PubMed Scopus (261) Google Scholar:- the slope is the end-systolic elastance (Ees), a load-independent LV contractility parameter. Therefore, different loading conditions lead to distinct PVLs which move along the same ESPVR line defined by identical Ees.- the volume–axis intercept VoEDPVRThe nonlinear relationship defines only the passive diastolic properties of the ventricle and represents diastolic stiffness. These properties are influenced by pressure and required sophisticated engineering assumptions. Consequentially, diastolic properties are difficult to apply in practice.8Burkhoff D. Mirsky I. Suga H. Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: A guide for clinical, translational, and basic researchers.Am J Physiol Hearty Circ Physiol. 2005; 289: H501-H512Crossref PubMed Scopus (505) Google ScholarExtrinsic PropertiesVedThe end diastolic volume (Ved) defines the pre-load which is strongly determined by the venous return.9Sunagawa K. Maughan W.L. Burkhoff D. et al.Left ventricular interaction with arterial load studied in isolated canine ventricle.Am J Physiol. 1983; 245: H773-H780PubMed Google ScholarEaThe arterial elastance (Ea) connects the Ved with the end systolic pressure volume. The Ea line slope is defined by the ratio between systemic vascular resistance (SVR) and the duration of the heartbeat. Therefore, Ea is influenced by the SVR, the heart rate and the preload (Ved).9Sunagawa K. Maughan W.L. Burkhoff D. et al.Left ventricular interaction with arterial load studied in isolated canine ventricle.Am J Physiol. 1983; 245: H773-H780PubMed Google ScholarOthersSVThe stroke volume (SV) is the width of the loop. The product between SV and heart rate is the cardiac output.PesThe Pes (ventricular end-systolic pressure) represents the height of the loop Open table in a new tab Finally, the PVL defines the determinants of myocardial oxygen consumption.8Burkhoff D. Mirsky I. Suga H. Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: A guide for clinical, translational, and basic researchers.Am J Physiol Hearty Circ Physiol. 2005; 289: H501-H512Crossref PubMed Scopus (505) Google Scholar The most important determinant is the pressure-volume area (PVA). The PVA is the sum of the external stroke work and the potential energy, which represents the residual energy stored in the myofilaments at the end of systole. Myocardial oxygen consumption (MVO2) is linearly related to ventricular PVA; therefore, any increase in PVA corresponds to a linear increase in MVO2 10Suga H. Ventricular energetics.Physiol Rev. 1990; 70: 247-277Crossref PubMed Scopus (638) Google Scholar (see Figure 2). During cardiogenic shock, VA-ECMO primarily alleviates the hemometabolic shock associated with low-output state, supporting the cardiopulmonary system and secondarily reducing the heart's preload, by drawing blood from the right atrium. However, a direct hemodynamic consequence after peripheral VA-ECMO implantation is the increase of LV afterload, moving the arterial elastance line to the right. In this condition, only the LV volume increase allows overcoming the high generated afterload the a the LV distention to LV end-diastolic left pressure and pressure that may cause this is LV volume may cause in end-diastolic The is the of PVL and along the end-diastolic pressure-volume and (see Figure these in hemodynamic PVA the volume Therefore, the blood to and the myocardial oxygen might the LV D. Sayer G. Doshi D. et al.Hemodynamics of mechanical circulatory support.J Am Coll Cardiol. 2015; 66: 2663-2674Crossref PubMed Scopus (261) Google Scholar LV by peripheral VA-ECMO is a for LV The of in the that might lead to LV left and is it ventricular in the of myocardial In case of and LV the may blood in the LV and the risk of P. S. et and effects of left ventricle unloading on extracorporeal A of the J PubMed Scopus Google Scholar the LV the of LV contractility and systemic vascular resistance is mechanical strategies be to the left The was which the LV by afterload T. A. J. et effects on and in cardiogenic shock patients supported by venoarterial extracorporeal membrane Care Med. PubMed Scopus Google Scholar more sophisticated are required in to significant ventricular These techniques or percutaneous A paper an of percutaneous the to for left ventricular venoarterial extracorporeal membrane oxygenation A Cardiothorac Vasc Anesth. 2020; Full Text Full Text PDF PubMed Scopus Google Scholar The percutaneous approach might of a in the or in the left side the or approach. different percutaneous as Impella or may be for or reducing the LV P. S. et and effects of left ventricle unloading on extracorporeal A of the J PubMed Scopus Google Scholar The most of unloading the left by the and P. S. et and effects of left ventricle unloading on extracorporeal A of the J PubMed Scopus Google Scholar a of the and the benefit from are percutaneous Impella represents the most The Impella is a of drawing from of blood from the LV the the The of Impella and VA-ECMO is and is an to the B. Becher P.M. Bernhardt A. et al.Left ventricular unloading is associated with lower mortality in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation: Results from an international, multicenter cohort study.Circulation. 2020; 142: 2095-2106Crossref PubMed Scopus (87) Google Scholar VA-ECMO support in cardiogenic shock to a significant afterload which the PVL and The effects of end-diastolic stroke work and MVO2 This might be by left and and B. of left ventricular peripheral extracorporeal membrane oxygenation for cardiogenic PubMed Scopus Google Scholar The hemodynamic effects generated by Impella may be in main concepts the of this (1) cardiac (2) oxygen and (3) oxygen of the in the provides an that on the support and the pressure The between and pressure as a consequence of VA-ECMO support and afterload, in a that is by et provides more cardiac unloading and circulatory support left heart failure than Full Text Full Text PDF PubMed Scopus Google P. G. et al.Left ventricular unloading and cardiac increase by the of percutaneous Impella Cardiovasc 2005; PubMed Scopus Google Scholar Impella is to oxygen The the is influenced by the pressure the and vascular the venous pressure and the resistance as the on the resistance and In to the the unloading of the reducing end-diastolic pressure and of and to D. Sayer G. Doshi D. et al.Hemodynamics of mechanical circulatory support.J Am Coll Cardiol. 2015; 66: 2663-2674Crossref PubMed Scopus (261) Google Scholar These are supported by different et reported a increase in with Impella in K. et Impella and support to ventricular unloading and blood for myocardial 31: PubMed Scopus Google Scholar and et reported this in et of left ventricular unloading by Impella on Cardiovasc 70: PubMed Scopus Google Scholar The effects studied by et a this the of myocardial with Impella by the of the blood the Finally, the of the between these to the myocardial oxygen of myocardial with a left ventricular Cardiol. 2010; PubMed Scopus (13) Google Scholar the reduces ventricular end-diastolic volume and left and drawing blood from the et provides more cardiac unloading and circulatory support left heart failure than Full Text Full Text PDF PubMed Scopus Google Scholar et a significant from in mechanical work and end-diastolic pressure-volume with K. et Impella and support to ventricular unloading and blood for myocardial 31: PubMed Scopus Google Scholar in an by et et of left ventricular unloading by Impella on Cardiovasc 70: PubMed Scopus Google Scholar a consequence of reducing mechanical work and myocardial the myocardial oxygen is H. 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Bernhardt A. et al.Left ventricular unloading is associated with lower mortality in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation: Results from an international, multicenter cohort study.Circulation. 2020; 142: 2095-2106Crossref PubMed Scopus (87) Google Scholar In clinical patients VA-ECMO support and a LV in the of left ventricular be at a high risk for significant LV the ventricular interaction is of as right ventricular contractility may to mechanical which on the left ventricular D. et al.Left ventricular unloading A J. PubMed Scopus Google Scholar In this right ventricular it may be to blood via the left the LV that is an afterload as by the extracorporeal in the the Therefore, right ventricular is a risk for a LV VA-ECMO Impella may at the in case of LV unloading. 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