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Hospital Healthcare Europe

Mechanical support for the fragile heart: The Impella system

Annemarie E Engstr
27 July, 2012  
Annemarie E Engström MD
José PS Henriques MD PhD
Department of Cardiology,
Academic Medical Centre ,
Amsterdam,
The Netherlands
The concept of developing a mechanical device capable of assisting, or even replacing, the cardiac pump function has been an appealing and heavily researched area for many decades. Ever since the development of the first total artificial heart, a wide variety of cardiac support systems has emerged, ranging from minimally invasive heart pumps through total artificial heart systems. In the 1960s, the intra-aortic balloon pump (IABP) was developed as the first minimally invasive mechanical circulatory support device. Since then, it has been the most widely used device in the catheterisation laboratory. In both American and European treatment guidelines, IABP support was strongly recommended in patients with acute myocardial infarction complicated by cardiogenic shock. In addition, IABP support has been common practice for the past decades when performing percutaneous coronary intervention (PCI) in patients at high risk for haemodynamic compromise. Nevertheless, two recently conducted meta-analyses showed no beneficial effect of IABP treatment both in ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock(1) and STEMI patients with high-risk characteristics.(2) 
In addition, a recently conducted randomised trial of IABP versus no IABP in high-risk PCI did not show any benefit either,(3) nor did a randomised trial of IABP versus no IABP in patients without cardiogenic shock after acute myocardial infarction.(4) In a report from the national cardiovascular data registry in the US, the hospital variation in IABP use in the setting of high-risk PCI, and its association with mortality, was investigated. Proportional IABP use were categorised into quartiles. No differences were demonstrated between mortality across quartiles; therefore, IABP use was not associated with a difference in mortality.(5) In this article, we discuss a new minimally invasive cardiac support device: the Impella system. This pump is not designed for total replacement of cardiac pump function. Instead, it entails temporary circulatory support and unloading of the heart, to potentially enable the recovery of damaged heart muscle.  
Principles of the Impella system
The Impella system (Figure 1) is a miniaturised catheter-mounted cardiac assist device, which can be inserted via a standard catheterisation procedure. It is introduced through the femoral artery and placed across the aortic valve, with its inlet located in the left ventricle and its outlet in the ascending aorta. Alternatively, the device may also be introduced through the axillary artery, to enable better patient mobility.(6) The system is purged with fluid containing dextrose and heparin, which is delivered to the motor housing through the catheter; this is to prevent aspirated blood from entering the motor housing and clotting. The Impella system is designed for short-term mechanical circulatory support and left ventricular unloading. By actively expelling blood from the left ventricle into the aorta, the device reduces myocardial workload and oxygen consumption, in addition to increasing cardiac output and improving coronary perfusion.(7) Therefore, in addition to providing temporary circulatory support, the device may have a beneficial effect on the recovery of damaged heart muscle cells.  
Currently, two versions of the Impella system are available for clinical use: the Impella 2.5 and the Impella 5.0. Whereas the Impella 2.5 device provides a maximum flow of 2.5 l/min of blood, the 5.0 device is capable of providing twice the support. The Impella 2.5 device has been CE-approved for use up to five days, whereas the Impella 5.0 device is CE-approved for use up to 10 days. Both devices have received 510 (k) clearances by the US Food and Drug Administration (FDA) for circulatory support up to six hours. A recently announced intermediate version called Impella cVAD will be capable of producing at least 3.7 l/min (Tables 1 and 2). This device should be available under CE mark approval in 2012. 
European insurance companies have started to cover Impella over the past few years. A recent cost-effectiveness analysis has shown that the Impella 2.5 is a cost-effective option against both IABP and extra-corporal membrane oxygenation (ECMO). From a 10-year time horizon, Impella dominates ECMO (Impella provides improved clinical outcomes at lower cost) and achieves an incremental cost-effectiveness ratio (ICER) of €27,852 per quality adjusted life year (QALY) gained against IABP – and is, therefore, well below the threshold of €50,000/QALY generally accepted in Europe (Table 3). Impella treatment will be reimbursed in the Netherlands from 2012 onwards. During Impella support, patients are treated with heparin to ensure adequate anticoagulation. Reported complications with the device are low(8,9) but may include vascular access site complications, limb ischaemia and stroke. To further reduce the risk of stroke, echocardiography before device placement is mandatory.
Indications for Impella support 
Mechanical support with a minimally invasive cardiac support device such as the Impella system can be beneficial in several patient categories. The first category comprises patients undergoing elective treatment of coronary artery lesions, who are at high risk for developing peri-procedural haemodynamic compromise. Basically, these patients have complex coronary artery disease, often including complex left main or last remaining vessel lesions, combined with an often severely reduced cardiac pump function. In those patients, who are often too fragile to undergo coronary artery bypass grafting, percutaneous treatment of their complex coronary lesion is a last resort treatment. The high risk associated with such a percutaneous procedure can be attenuated by prophylactically inserting a mechanical circulatory support device. The second category concerns patients with acute myocardial infarction complicated by cardiogenic shock. In these patients, cardiac pump function is severely diminished as a result of a large area of damaged myocardial muscle due to an acute ischaemic insult. The rationale for Impella treatment in this category of patients is twofold; on the one hand, the Impella device may reduce myocardial workload and oxygen consumption, and thus promote recovery of damaged myocardium. 
On the other hand, it is capable of providing circulatory support, thus replacing cardiac pump function to maintain adequate perfusion of vital organs. As a third and final category, patients with cardiogenic shock after undergoing cardiac surgery may benefit from Impella support. In those patients, cardiac pump function is severely diminished as well, which is often due to myocardial stunning following the perioperative-induced ischaemia. Due to the severe reduction in cardiac pump function, those patients cannot be weaned from cardiopulmonary bypass (CPB) or experience some haemodynamic compromise post-weaning from CPB. The role for Impella treatment in this category of patients is comparable to that in cardiogenic shock after acute myocardial infarction. Other indications have been becoming of increased interest, such as myocarditis, resuscitation, circulatory support during high-risk general surgery, balloon aortic valvuloplasty, and high-risk electrophysiology procedures. Also, the Impella can be used during percutaneous aortic valve procedures and more generally as a bridge to bridge in any circulatory poor condition (Table 1).
Impella 2.5
The Impella 2.5 device plays an especially important role in the field of supported elective high-risk PCI. Safety and feasibility of this approach have been demonstrated in a multitude of previously conducted studies, including a multi-centre European registry of Impella-supported high-risk PCI.(10) In all of these previous studies, prophylactic Impella placement during high-risk PCI was easy to perform. Importantly, complication rate was low. As IABP-support during high-risk PCI was demonstrated not to have any clinical benefit, as discussed above, a very interesting question would be whether the Impella device would be a suitable alternative. This question was largely answered by the PROTECT II trial, which is the first large randomised study, designed under FDA guidance, to compare patient outcomes between Impella 2.5 and IABP in high-risk patients undergoing non-emergent PCI (n=448). Compared with IABP, the 30-day rate of major adverse events (MAE) appeared to be lower in the Impella arm, although the difference did not reach statistical significance. At 90 days, the difference between the two arms was magnified, yielding a relative risk reduction in MAE of 18% and 22% in favour of Impella as compared with IABP in the intent-to-treat and per-protocol populations, respectively (p=0.06 and 0.023, respectively; presented at TCT2011). These results support that the Impella system might actually be superior to IABP for elective high-risk PCI. Further analyses of the PROTECT II data and other future studies should identify patients that might benefit most from this technology.
In the setting of cardiogenic shock, no clear picture arises from previously conducted studies. A small, randomised trial of IABP versus Impella 2.5 was performed in patients with STEMI complicated by CS, the ISAR-SHOCK study.(11) In this study, a significant increase in cardiac index at 30 minutes after the initiation of support was demonstrated in Impella-supported patients, when compared to patients supported with an IABP. In a registry of Impella 2.5 usage in cardiogenic shock from the US (USpella registry; presented at TCT 2010), there was a beneficial effect of Impella 2.5 treatment on haemodynamics and metabolic conditions. In addition, the survival rate to discharge was higher in patients who received the device before undergoing PCI for acute myocardial infarction when compared with those receiving the device post-PCI. (Figure 2) Cardiogenic shock is a highly complex clinical entity, and rather a continuum ranging from mild degrees of haemodynamic compromise to severe treatment-refractory cardiogenic shock. For those patients in treatment-refractory shock, non-responsive to Impella 2.5 support, an upgrade to the 5.0 device might further improve clinical outcome.(12) 
Cost-effectiveness
For both high-risk PCI and cardiogenic shock, a cost-effectiveness analysis of Impella 2.5 versus two other minimally invasive cardiac support devices (IABP and extracorporeal membrane oxygenation) was performed. For this analysis, data from both the multicentre European registry (Europella) and the multicentre US registry (USpella) were used. For the European data analysed on a 10-year time horizon, the Impella 2.5 generated an incremental QALY of 0.2 compared with IABP, and 1.2 compared with ECMO. Impella 2.5 dominated ECMO (as ECMO was associated with a higher cost), and provided 1 QALY at an incremental cost of €27,852 against IABP. For the US figures, the incremental costs against IABP were €22.889 per QALY gained. In summary, both data sources showed long-term cost-effectiveness of Impella 2.5 against IABP by producing an incremental cost-effectiveness ratio significantly below the conventional threshold of €50,000/QALY.
Impella 5.0
The applicability of the Impella 5.0 device is limited by the fact that it requires a surgical cut-down of the femoral or axillary artery. Once introduced, however, its placement and working is similar to that of the smaller devices. The primary indication for this device is severe haemodynamic compromise, either post-myocardial infarction or post-cardiac surgery. In cardiogenic shock post-cardiac surgery in particular, the Impella 5.0 is a relatively easily applicable device that provides powerful mechanical circulatory support. Importantly, in such a setting, a surgical cut-down of the femoral or axillary artery is not a significant limitation. Previous studies are limited, although several small studies have been published on this pump and the predecessor of the current Impella systems, which was more similar to the 5.0 device than to the 2.5 device. In general, outcomes are comparable to those in patients supported with larger assist devices, with 30-day mortality rates of approximately 40–60%. More recently, an FDA prospective multicentre study (RECOVER I) investigated the use of the Impella 5.0 in patients experiencing low cardiac output syndrome or cardiogenic shock despite receiving a high dose of inotropic support after weaning from cardiopulmonary bypass post-cardiac surgery (n=16). The study showed that Impella enabled immediate restoration of haemodynamics with a gradual reduction in the need of inotropic support. Overall, 94% of patients survived to 30 days. Survival to three months and one year was 81% and 75%, respectively.(13) 
It is likely that the early restoration of the haemodynamics prevented the irreversible end organ dysfunction, which led to a higher survival rate in this multicentre study. These results suggest that the less invasive nature and ease of insertion of the Impella 5.0 could position it as an attractive and feasible alternative to more extensive and invasive surgically implanted circulatory support systems. Eligible patients might include those who do not respond to conventional therapy, consisting of IABP support and high-dose inotropes. Cardiogenic shock after acute myocardial infarction, however, is a more complex situation. Although, from our preliminary experience, the 5.0-device seems to be associated with a more favourable outcome,(12) its immediate insertion can be challenging, owing to the mandatory surgical cut-down. Thus, close collaboration with a surgical team is of key importance, as the goal should be to establish full support as quickly as possible. Potentially, patients could be bridged to 5.0-implantation through the temporary placement of a 2.5 device. Despite the potential favourable effect of 5.0-support, cardiogenic shock remains an important clinical challenge. In general, about 30% of patients may be bridged to full recovery after temporary support. Another 30% of patients is fully treatment-refractory and succumbs to multi-organ failure. The remaining 30% of patients is also a challenging group, because partial recovery of cardiac function might have occurred but not sufficiently to be weaned from Impella support. These patients would be potential candidates for more permanent solutions, such as surgically implantable ventricular assist devices.
Conclusions
The Impella system is a valuable new minimally invasive mechanical circulatory support system. Currently available data suggest it can be an attractive alternative to the IABP, especially in the setting of high-risk PCI. Not only has it been demonstrated to be safe and cost-effective, but it could also lead to lower rates of major adverse events compared with the IABP. Additionally, the system could be of potential benefit in patients with cardiogenic shock. Nevertheless, only preliminary data are available to support this assumption. Further research remains paramount, to greater define the patients that can benefit most from the device in both prophylactic and emergent settings. 
References
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  13. Griffith B et al. The RECOVER I: A multicenter prospective study of Impella 5.0/LD for postcardiotomy circulatory support. Submitted.