Overview and outcomes of large Impella with a focus on the transition to pMCS/HTX.
Large microaxial pump systems (Impella 5.0, or Impella 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) have gained increasing levels of attendance as valuable tools of mechanical circulatory support (MCS). Patients undergoing heart transplantation (HTX) often need temporary MCS in the perioperative course, either as a preoperative bridge or occasionally in the early post-transplant period. Here we present our experience using Impella 5+ support for patients designated to undergo HTX, describe technical aspects of implantation and removal, and further analyze factors influencing the overall patient outcome. Significant factors are discussed in front of the background of contemporary international literature, and current scientific questions are highlighted.
- cardiogenic shock
- heart failure
- heart transplantation
- bridge to transplant
- temporary mechanical circulatory support
Impella (Abiomed Inc., Danvers, MA, USA) is a microaxial pump catheter inserted retrogradely into the left ventricle (LV) via the aortic valve to support antegrade blood flow from LV to the ascending aorta by the lifting force of rotation. Due to less invasive closed-chest application and convenient profile, Impella 5+ has attracted an increasing level of attention and widespread use to stabilize CS patients and to provide temporary mechanical circulatory support (MCS) combined with LV unloading.
Patients undergoing heart transplantation (HTX) often need large Impella 5+ as part of temporary mechanical circulatory support (tMCS) in the perioperative course, either as a preoperative bridge or occasionally in the early post-transplant period. However, despite some observational studies the evidence supporting this is yet limited, particularly in the specific cohort of patients awaiting HTX . Therefore, we summarize the reported articles that focused on large Impella for a bridge to transplantation (BTT). Further, we present our experience using Impella 5+ support for patients undergoing HTX and further analyze factors influencing the overall patient outcome.
2. ECMELLA strategy for a bridge to candidacy
Impella 5+ plays a significant role as part of tMCS in patients considered eligible for a bridge to candidacy. In crash and burn patients suffering from acute cardiogenic shock or refractory decompensated heart failure, physicians are faced with four clinical therapy choices: (1) conservative therapy with adequate inotrope support, (2) tMCS using va-ECMO implantation, (3) tMCS by Impella implantation, and (4) the combination of the latter two represented by so-called ECMELLA concept.
Traditionally, va-ECMO is preferred as the first choice of tMCS for acute or sustained CS, e.g., in the setting of cardiopulmonary resuscitation (CPR), because of its convenience, rapid initiation effect, and stable mode of action. Moreover, patients can be not only supported hemodynamically but also regarding the respiratory situation. However, va-ECMO does not unload the left ventricle (LV), and by increasing the afterload, it may lead to LV congestion, pulmonary edema, and secondary right ventricular (RV) failure. To compensate for these limitations of va-ECMO, a large microaxial pump catheter, i.e., Impella 5+, maybe additionally administrated to obtain the concept of “ECMELLA” support. Herein, Impella enables to provide antegrade flow and unload LV to reduce myocardial oxygen consumption and increase coronary perfusion, which leads to improving pulmonary congestion . Simultaneous use of Impella with va-ECMO contributes to a shift of LV pressure-volume loops to the left, which is particularly effective when a larger microaxial pump is used. This is supported by a simulation study, in which a 23% decrease in end-diastolic LV volume and a 41% decrease in pulmonary capillary wedge pressure has been demonstrated .
Regarding the superiority of clinical outcomes of ECMELLA over va-ECMO, a recent meta-analysis sheds new light on patient outcomes . A total of 425 patients (only va-ECMO (n = 312 (73.4%)) and ECMELLA (n = 113 (26.6%)) arising from five retrospective observational comparative studies were selected for this analysis [5, 6, 7, 8, 9]. Although most of ECMELLA cohorts received “small” Impella, i.e., (Impella CP or Impella 2.5; n = 95 (84.1%), Impella 5.0; n = 18 (15.9%)), study results prompted the authors to suggest that ECMELLA strategy might contribute to lower mortality with a reasonable potential to improve the hemodynamic status and promote bridge to recovery or to the next therapy, i.e., pMCS or HTX. Further observational/meta-analysis studies support this hypothesis [10, 11, 12]. Further, the multicenter cohort study “STOP-SHOCK” shows a 21% reduction in 30-day mortality in propensity-score matched patients with LV unloading by Impella (thereof n = 14 with Impella 5.0; (5.5%)) despite a higher rate of bleeding or ischemic complications
3. Role for a bridge to pMCS/HTX strategy
In fact, how many Impella 5+ patients could be successfully bridged to pMCS/HTX? A comprehensive search of the database “Pubmed” up to September 20, 2021 in English has been conducted. Studies that focused on clinical outcomes inclusive transition to pMCS/HTX in consecutive series of adult patients (>18 years) with CS utilizing a large Impella system, i.e., Impella 5+, were included. Case reports were excluded. In the interest of comparable results, studies that did not mention the size of applied Impella were also excluded. Some studies contained patients with various sizes of Impella or with other LV unloading systems. These were also excluded because of a small cohort of large Impella systems and mixed effects. Finally, a total of 6 observational studies were signed up (Table 1) [15, 16, 17, 18, 19, 20].
|Author||Year||Impella||Total||ECMELLA||Deceased at discharge||Successfully weaned||Transition to pMCS|
|Chung ||2020||5.0||100||10 (10.0)||38 (38.0)||14 (14.0)||51 (51.0)||14 (14.0)||11 (78.6)||37 (37.0)||37 (100)|
|Tarabichi ||2020||5.0||40||9 (22.5)||21 (52.5)||11 (27.5)||8 (20.0)||6 (15.0)||N/A||2 (5.0)||N/A|
|Seese ||2020||5.0||236||14 (5.8)||N/A||31 (13.1)||144 (61.0)||87 (37.0)||N/A||57 (24.1)||55 (96.5)|
|Nelson ||2021||5.0||34||4 (11.8)||8 (23.5)*||13 (38.2)*||10 (29.4)||8 (23.5)||8 (100)||2 (5.9)||2 (100)|
|Bernhardt ||2021||5.5||46||14 (30.4)||13 (28.3)||16 (34.8)||20 (43.5)||19 (41.3)||17 (89.5)**||1 (2.2)||1 (100)|
|Sugimura ||2021||5+||50||38 (74.0)||25 (50.0)||17 (34.0)||8 (16.0)||6 (12.0)||6 (100)||2 (4.0)||2 (100)|
Because the patient cohort of each study was heterogeneous, e.g., proportion of ECMELLA patients varying between 10 and 74%, the mortality rate of each study also differed (23.5–50%). However, patients who were successfully weaned from Impella 5+ were 13.1–38.2% of total patients. On the other hand, 16–61% of patients were successfully bridged to pMCS/HTX. Of note, patients who were successfully bridged to pMCS/HTX obtained favorable clinical outcomes. Strikingly, almost all patients who underwent HTX survived until discharge. Seese
As a study for the superior function of preconditioning of Impella 5+ for direct bridging to HTX, Nordan
In summary, although there are no randomized comparative studies about clinical outcomes between groups with and without Impella 5+ in CS patients and we cannot make definitive statements in this field yet, we suppose that large Impella systems most likely offer a valuable contribution to preconditioning of CS patients and to bridging strategies to pMCS/HTX, and furthermore, these strategies are associated with excellent postoperative clinical outcome.
4. Expected role for a bridge to recovery in post-transplant phase
After HTX, comprehensive therapy is required for recovery. We sometimes encounter life-threatening complications. Primary graft dysfunction (PGD) is one of the critical complications and might occur in 2-28% of patients in the acute phase after HTX . In PGD, mortality is reported to be as high as up to 85% . The primary clinical manifestation of PGD is LV failure, which is affected by various factors, e.g., age and ischemic time of donor, acute rejection [23, 24]. Thus, most patients require MCS, e.g., va-ECMO support or temporary ventricular assist device (VAD) in PGD. A recent study has indicated that va-ECMO initiation due to “early graft failure,” defined as the need of va-ECMO within the first 24-hours post-HTX, might be associated with a worse survival rate at 1 year (36%) and 5 years (28%) when compared to outcome in patients without early graft failure . On the other hand, as far as temporary extracorporeal centrifugal VAD, i.e., CentriMag (Levitronix, LLC, Waltham, MA, USA) is concerned, a retrospective study of CentriMag utilization in the setting of PGD in 34 post-HTX patients reported that CentriMag support contributed to the salvage of 32% patients with severe PGD (survival rate at 30 days; 50%, at 1 year; 32%) .
The efficacy of Impella is theoretically comparable to that of CentriMag when used as a temporary VAD. Because of its convenient use, Impella will be the preferred system for the management of PGD. However, no studies have been yet reported, to the best of our knowledge. We suppose that Impella certainly must have been used as a bridge to recovery tool in the early post-HTX phase in clinical practice. Due to limited cases of PGD, no robust data have been published so far. More studies are warranted to evaluate the role of standard and primary utilization of Impella for PGD.
5. Our experience
At our institute, Impella 5+ has been utilized since November 2018. We reported our initial experience with the first 50 consecutive cases treated with Impella 5+, in which patients were enrolled in the observation period between November 2018 and August 2020 . However, meanwhile more patients have been treated with Impella 5+ at our institution. In front of this background, we would like to discuss the clinical role and the clinical outcomes of Impella 5+ in the setting of a bridge to HTX. As described, reports on the role of Impella 5+ in the context of the bridge to HTX are still scarce. Thus, we designed a single-center observational retrospective study to identify the clinical outcome of large Impella-bridged HTX and to elucidate the usefulness of the large Impella system as a temporary MCS in a larger patient cohort.
5.2 Study population
At our institute from November 2018 up to September 2021, a total of 102 Impella 5+ were utilized for MCS in 89 patients. Finally, pMCS implantation or HTX were performed in 12 of them (13.5%), in whom 11 patients were directly bridged to pMCS/HTX under Impella 5+ support, whereas 1 patient underwent HTX after successfully weaning of Impella 5 at the current admission.
LVAD implantation as primary pMCS was performed in 8 patients whose therapy concept was “BTT” for 7 patients and “destination therapy (DT)” for 1 patient because of his advanced age (76 years old).
Direct HTX were performed in 4 patients (primary HTX; n = 3, secondly HTX; n = 1). Further, HTX following LVAD after Impella 5+ support was also performed in 5 patients, who build up 62.5% of patients who underwent LVAD implantation as primary tMCS after Impella 5+ support. Thus, a total of 9 patients (10.1%) underwent HTX after Impella 5+ support (Figure 1).
5.3 Patients characteristics
Table 2 shows baseline clinical characteristics of 11 patients (BTT n = 7, direct HTX n = 4), without 1 DT patient. The most common underlying disease for Impella implantation was ischemic cardiomyopathy (ICM) (n = 7, 63.6%), followed by dilated cardiomyopathy (DCM; n = 2, 18.2%). Three patients were post-CPR, and a combination of va-ECMO plus Impella, referred to as ‘ECMELLA’ was administrated in 7 patients (63.6%). In all eleven cases, implantation of Impella 5 was performed via the right subclavian artery.
|Patients (n = 11)|
|Age (y)||52.4 ± 9.8|
|Male, n (%)||10 (90.9)|
|Arterial hypertension, n (%)||5 (45.5)|
|Hyperlipidemia, n (%)||5 (45.5)|
|Diabetes, n (%)||4 (36.4)|
|Peripheral vascular disease, n (%)||1 (9.1)|
|Arrhythmia, n (%)||3 (27.3)|
|COPD, n (%)||0 (0.0)|
|Nicotine abuses, n (%)||5 (45.5)|
|Drug abuses, n (%)||0 (0.0)|
|Dialysis, n (%)||0 (0.0)|
|History of PCI, n (%)||3 (27.3)|
|post CPR, n (%)||3 (27.3)|
|Biventricular failure, n (%)||7 (63.6)|
|ICM, n (%)||7 (63.6)|
|DCM, n (%)||2 (18.2)|
|Myocarditis, n (%)||1 (9.1)|
|Heart transplant rejection, n (%)||1 (9.1)|
|va-ECMO implantation, n (%)||7 (63.6)|
|Upgrade from Impella CP, n (%)||4 (36.4)|
5.4 Clinical outcomes
Table 3 shows the clinical course of MCS in 11 patients successfully bridged to pMCS/HTX. Impella 5+ support time was 17.4 ± 15.6 days (median 12 days) for bridge to pMCS/HTX in 11 patients. It means that patients underwent either LVAD implantation or HTX on average after 17.4 days following Impella 5+ initiation.
|ECMELLA||va-ECMO ex?||Impella ex?||tRVAD?|
In 5 of 7 ECMELLA patients, va-ECMO explanation was performed before pMCS/HTX, of whom 1 patient required a temporary right ventricular assist device (tRVAD). As described, 1 patient underwent HTX after successful weaning of Impella 5 at the same admission (patient 4).
Among LVAD patients (n = 7), simultaneous tRVAD was required in 4 patients for postoperative management.
All 11 patients survived the first 30 days after pMCS/HTX operations. However, 2 patients (patients 9, 11) died of septic shock (after 129 days, 122 days, respectively) after HTX. The latter patient was after secondly HTX due to heart transplant rejection.
As far as complications of Impella 5+, a re-implantation of Impella 5+ was necessary total in 3 patients due to (1) Impella thrombosis (n = 2), and (2) Impella dislocation (n = 1). Additionally, Impella dislocation occurred in one more patient. The patient (Patient 10. in Table 3) was directly implanted LVAD.
Our experience shows (1) successful transition to pMCS/HTX of 13.5% (n = 12/89), (2) 30 days survival after bridging to pMCS/HTX of 100%, (3) HTX of 10.1% (n = 9/89), and (4) 30 days survival rate of 100% and in-hospital mortality of 22.2% (n = 2/9) after HTX.
According to already published articles, a large Impella system seems to contribute to preconditioning of CS patients not only for a bridge to pMCS/HTX but also for the excellent postoperative clinical outcome. This hypothesis is supported by 100% post-transplant 30 days survival rate in patients who underwent HTX on Impella 5+ in our study. Using Impella 5+ the majority of patients with ECMELLA due to CS could be successfully weaned from va-ECMO before pMCS/HTX installation. This fact also indicates favorable clinical outcomes of Impella 5+ in CS patients awaiting HTX. However, patient selection and choice of size and timing of Impella support remain the subject of future studies for bridging strategies to pMCS/HTX. As a caution, Impella dysfunction due to thrombosis or dislocation of the pump could occur with the long-term utilization of Impella 5+ for bridge to pMCS/HTX.
We gratefully acknowledge the work of the members of the heart failure team at the University Hospital Duesseldorf.
Conflict of interest
The authors declare no conflict of interest.
Wernly B, Bhatt DL, Thiele H, Jung C. Impella in cardiogenic shock: Is it time to hit the break? Shock. 2021; 55(5):693-694
Donker DW, Brodie D, Henriques JPS, Broome M. Left ventricular unloading during veno-arterial ECMO: A review of percutaneous and surgical unloading interventions. Perfusion. 2019; 34(2):98-105
Donker DW, Brodie D, Henriques JPS, Broome M. Left ventricular unloading during veno-arterial ECMO: A simulation study. ASAIO Journal. 2019; 65(1):11-20
Vallabhajosyula S, O’Horo JC, Antharam P, Ananthaneni S, Vallabhajosyula S, Stulak JM, et al. Venoarterial extracorporeal membrane oxygenation with concomitant impella versus venoarterial extracorporeal membrane oxygenation for cardiogenic shock. ASAIO Journal. 2020; 66(5):497-503
Patel SM, Lipinski J, Al-Kindi SG, Patel T, Saric P, Li J, et al. Simultaneous venoarterial extracorporeal membrane oxygenation and percutaneous left ventricular decompression therapy with impella is associated with improved outcomes in refractory cardiogenic shock. ASAIO Journal. 2019; 65(1):21-28
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. 2019; 65(3):219-226
Mourad M, Gaudard P, De La Arena P, Eliet J, Zeroual N, Rouviere P, et al. Circulatory support with extracorporeal membrane oxygenation and/or impella for cardiogenic shock during myocardial infarction. ASAIO Journal. 2018; 64(6):708-714
Tepper S, Masood MF, Baltazar Garcia M, Pisani M, Ewald GA, Lasala JM, et al. Left ventricular unloading by impella device versus surgical vent during extracorporeal life support. The Annals of Thoracic Surgery. 2017; 104(3):861-867
Pappalardo F, Schulte C, Pieri M, Schrage B, Contri R, Soeffker G, et al. Concomitant implantation of Impella((R)) 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
Grajeda Silvestri ER, Pino JE, Donath E, Torres P, Chait R, Ghumman W. Impella to unload the left ventricle in patients undergoing venoarterial extracorporeal membrane oxygenation for cardiogenic shock: A systematic review and meta-analysis. Journal of Cardiac Surgery. 2020; 35(6):1237-1242
Russo JJ, Aleksova N, Pitcher I, Couture E, Parlow S, Faraz M, et al. Left ventricular unloading during extracorporeal membrane oxygenation in patients with cardiogenic shock. Journal of the American College of Cardiology. 2019; 73(6):654-662
Schrage B, Burkhoff D, Rubsamen N, Becher PM, Schwarzl M, Bernhardt A, et al. Unloading of the left ventricle during venoarterial extracorporeal membrane oxygenation therapy in cardiogenic shock. JACC Heart Failure. 2018; 6(12):1035-1043
Schrage B, Becher PM, Bernhardt A, Bezerra H, Blankenberg S, Brunner S, 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(22):2095-2106
Tongers J, Sieweke JT, Kuhn C, Napp LC, Flierl U, Rontgen P, et al. Early escalation of mechanical circulatory support stabilizes and potentially rescues patients in refractory cardiogenic shock. Circulation. Heart Failure. 2020; 13(3):e005853
Sugimura Y, Katahira S, Immohr MB, Sipahi NF, Mehdiani A, Assmann A, et al. Initial experience covering 50 consecutive cases of large Impella implantation at a single heart centre. ESC Heart Fail. 2021. DOI:10.1002/ehf2.13594
Nelson DW, Sundararajan S, Klein E, Joyce LD, Durham LA, Joyce DL, et al. Sustained use of the impella 5.0 heart pump enables bridge to clinical decisions in 34 patients. Texas Heart Institute Journal. 2021; 48(3):e207260
Bernhardt AM, Potapov E, Schibilsky D, Ruhparwar A, Tschope C, Spillmann F, et al. First in man evaluation of a novel circulatory support device: Early experience with the Impella 5.5 after CE mark approval in Germany. The Journal of Heart and Lung Transplantation. 2021; 40(8):850-855
Tarabichi S, Ikegami H, Russo MJ, Lee LY, Lemaire A. The role of the axillary Impella 5.0 device on patients with acute cardiogenic shock. Journal of Cardiothoracic Surgery. 2020; 15(1):218
Seese L, Hickey G, Keebler ME, Mathier MA, Sultan I, Gleason TG, et al. Direct bridging to cardiac transplantation with the surgically implanted Impella 5.0 device. Clinical Transplantation. 2020; 34(3):e13818
Chung JS, Emerson D, Ramzy D, Akhmerov A, Megna D, Esmailian F, et al. A new paradigm in mechanical circulatory support: 100-patient experience. The Annals of Thoracic Surgery. 2020; 109(5):1370-1377
Lima B, Kale P, Gonzalez-Stawinski GV, Kuiper JJ, Carey S, Hall SA. Effectiveness and safety of the impella 5.0 as a bridge to cardiac transplantation or durable left ventricular assist device. The American Journal of Cardiology. 2016; 117(10):1622-1628
Kobashigawa J, Zuckermann A, Macdonald P, Leprince P, Esmailian F, Luu M, et al. Report from a consensus conference on primary graft dysfunction after cardiac transplantation. The Journal of Heart and Lung Transplantation. 2014; 33(4):327-340
Russo MJ, Chen JM, Sorabella RA, Martens TP, Garrido M, Davies RR, et al. The effect of ischemic time on survival after heart transplantation varies by donor age: an analysis of the United Network for organ sharing database. The Journal of Thoracic and Cardiovascular Surgery. 2007; 133(2):554-559
Del Rizzo DF, Menkis AH, Pflugfelder PW, Novick RJ, McKenzie FN, Boyd WD, et al. The role of donor age and ischemic time on survival following orthotopic heart transplantation. The Journal of Heart and Lung Transplantation. 1999; 18(4):310-319
Loforte A, Fiorentino M, Murana G, Gliozzi G, Cavalli GG, Mariani C, et al. Mechanically supported early graft failure after heart transplantation. Transplantation Proceedings. 2021; 53(1):311-317
Thomas HL, Dronavalli VB, Parameshwar J, Bonser RS, Banner NR. Steering group of the UKCTA. Incidence and outcome of Levitronix CentriMag support as rescue therapy for early cardiac allograft failure: A United Kingdom national study. European Journal of Cardio-Thoracic Surgery. 2011; 40(6):1348-1354