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Impella unloads the left ventricle percutaneously and contributes to cardiac recovery.
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Impella improves pulmonary congestion and systemic perfusion.
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Indications of Impella range as follows: ST-elevation myocardial infarction, cardiomyopathy, fulminant myocarditis.
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Conversion to durable left ventricular assist device when patients are dependent on Impella is considered.
Abstract
Impella (Abiomed, Danvers, MA, USA) is a recently-innovated (commercially available from 2017 in Japan) percutaneous left ventricular assist device which is inserted percutaneously and transfers blood from the left ventricle to the ascending aorta, improving systemic circulation and end-organ dysfunction as well as unloading left ventricle in patients with cardiogenic shock. Impella has not yet shown a significant survival benefit in patients with cardiogenic shock compared to intra-aortic balloon pump in randomized control trials, but gives powerful circulatory support immediately with minimally invasive manner when used in appropriate patients at optimal timing with adequate management. In this review article, we will introduce and discuss optimal and practical management of Impella therapy in Japan.
Despite the shorter door-to-balloon time for patients undergoing primary percutaneous coronary intervention, in-hospital mortality in patients with ST elevation myocardial infarction (STEMI) with cardiogenic shock remains poor (approximately 28 %) [
Impella (Abiomed, Danvers, MA, USA), a percutaneous catheter-based trans-valvular left ventricular (LV) assist device, which provides continuous pumping of blood directly from the LV cavity that was commercially available from 2018 in Japan, independent of the phase of the cardiac cycle, results in loss of normal isovolumic periods. This transforms ventricular-pressure volume loop (PVL) from its normal trapezoidal shape to a triangular shape. As pump flow rate increases, the LV becomes increasingly unloaded (progressive leftward shifted PVL), peak LV pressure generation decreases, and there are marked decreases in pressure-volume area, which is the sum of the external stroke work (the area inside the PVL), and myocardial oxygen consumption. This direct unloading also results in decreased left atrium and wedge pressures, improved blood oxygenation, systemic pressures, and perfusion may improve the metabolic milieu and invoke beneficial secondary changes in LV contractility and total peripheral resistance [
Several small-scale randomized clinical trials could not demonstrate survival benefit of Impella over intra-aortic balloon pumping despite superiority in improving hemodynamics [
A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.
]. Nevertheless, Impella may be useful as a temporary mechanical circulatory device, which improves systemic circulation and end-organ dysfunction and unloading left ventricle in carefully selected patients with cardiogenic shock with optimal management. In this review, we will discuss optimal patient selection and management of Impella therapy in combination with other currently available intensive therapies in Japan, where the clinical situation is somehow unique.
Impella left ventricular support system
The Impella LV assist device family (Table 1) is inserted fluoroscopically into LV cavity via aortic valve in retrograde fashion through the femoral artery or axillary artery. As of November 2019, Impella 2.5, CP, and 5.0 have been approved and commercially available in Japan.
Table 1Types of Impella.
2.5
CP
5.0
Max flow (L/min)
2.5 L/min
3.7 L/min
5.0 L/min
Maximum rotation speed (rpm)
51,000
46,000
33,000
Pump size (Fr)
12 Fr
14 Fr
21 Fr
Placement
Perc (puncture)
Perc (puncture)
Perc (cut down)
Insertion Site
Femoral
Femoral
Axillary
Effective length of LV
7.5 cm
8.5 cm
7.0 cm
Duration of support
Hours to days
Days
Days to weeks
Fr, French; Perc, Percutaneous; LV, left ventricle.
The distal portion of the Impella is a pigtail configuration (Fig. 1A) that is meant to reside in the mid LV approximately 3.5 cm below the aortic annulus and its length varies slightly depending on the type of device (Fig. 1B). Blood is drawn from the inlet located just superior to the catheter’s pigtail in the LV cavity and delivered through the outlet, which is seated just above the aortic valve (Fig. 1A).
Fig. 1Overview of Impella (A) and the lengths that are required for insertion of the Impella pump catheter into the left ventricle (B).
A pressure barrier is formed with pressurized heparinized glucose solution (purge solution) so that blood does not enter the motor pump catheter, which is called “purge system”.
Indication, background, and complications of Impella
The Impella devices have been used in various clinical situations, including cardiogenic shock with STEMI, acute on chronic decompensated heart failure dominantly due to cardiomyopathy, fulminant myocarditis, takotsubo cardiomyopathy [
Prolonged circulatory support with an Impella assist device in the management of cardiogenic shock associated with takotsubo syndrome, severe sepsis and acute respiratory distress syndrome.
Mechanical circulatory support with Impella percutaneous ventricular assist device as a bridge to recovery in takotsubo syndrome complicated by cardiogenic shock and left ventricular outflow tract obstruction.
It has been reported that the clinical outcome was superior in 30-day mortality in patients with cardiogenic shock due to STEMI when Impella was inserted before percutaneous coronary intervention (PCI) compared with those inserted after the intervention [
]. Furthermore, it has been reported that LV unloading by Impella before PCI reduced reperfusion injury as well as infarcted myocardial size and improved cardiac function [
However, several small-scale randomized clinical trials could not demonstrate survival benefit of Impella over the intra-aortic balloon pumping despite superiority in improving hemodynamics [
A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.
]. Of note, most trials of Impella were conducted in small cohorts. Furthermore, the timing of Impella initiation was not clearly stated or defined in these clinical trials. Impella 5.0 can provide superior LV unloading and higher systemic flows compared to the conventional types of Impella, whereas it has not yet been evaluated in prospective randomized trials. A recent meta-analysis examining the outcome of Impella 5.0 among a total of 163 patients with cardiogenic shock demonstrated 74 % of survival to discharge and a high rate of myocardial recovery [
Recently, various favorable clinical outcomes of Impella or ECPELLA support have been reported particularly in patients with acute fulminant myocarditis [
Successful bridge-to-recovery treatment in a young patient with fulminant eosinophilic myocarditis: roles of a percutaneous ventricular assist device and endomyocardial biopsy.
]. A case report of cardiac recovery with prolonged LV unloading by Impella 5.0 and immunosuppressive therapy in fulminant myocarditis was reported. In particular, the sequential endocardial biopsy revealed that the reduction of cardiac immune cells infiltration was observed only during the Impella support period despite continuation of immunosuppressive therapy, which emphasized the importance of LV unloading for bridge to recovery [
], whereas delayed surgery in patients who respond to aggressive medical therapy seems to be have better outcome, minimizing the mortality rate to about 15 % [
]. The first case of Impella for VSP was reported in Italy in 2009, which suggested a reduction in left-to-right shunt and right ventricular overload in addition to increasing cardiac output [
]. The retrospective study of Impella 5.0 for very small patients with cardiogenic shock due to VSP showed the hemodynamic benefit of Imella, which provided the delay of surgery [
]. Patients with any active bleedings are not good candidates for Impella therapy, and we instead prefer other mechanical supports including central extracorporeal membrane oxygenation with LV vent.
The positive hemodynamic effect provided by the Impella might be neutralized by the higher incidence of peripheral vascular complications, severe or life-threatening bleedings, and infections, in the large-scale clinical trials [
]. Improvements in the device technology and peri-procedural management to reduce such comorbidities might clarify the actual clinical benefit of Impella therapy.
ECPELLA (ECMO plus Impella)
In cases of ventricular tachycardia/ventricular fibrillation or any other critical hemodynamic deterioration complicated with STEMI, not only LV support with Impella but also right ventricle (RV) support and oxygenation supply are required, and extracorporeal membrane oxygenation (ECMO) is concomitantly used recently together with Impella targeting synergetic effects of both devices (i.e. ECPELLA).
In cases of fulminant myocarditis with additional severe impairment of the RV, ECMO has frequently been used. However, ECMO increases systemic afterload, LV filling pressures, and pulmonary artery wedge pressures (PAWP) due to the blood return to central artery. The increased systemic afterload and cardiac filling pressure can be reduced by concomitantly used Impella [
It is reported that the survival was better when supported by ECPELLA system than ECMO support alone in 30-day mortality in patients with refractory cardiogenic shock [
Simultaneous venoarterial extracorporeal membrane oxygenation and percutaneous left ventricular decompression therapy with Impella is associated with improved outcomes in refractory cardiogenic shock.
]. In cases with advanced pulmonary congestion and pulmonary oxygenation disorders, the Veno-veno-arterial ECMO system is preferable to VA-ECMO to prevent hypoxic blood perfusion to the brain through Impella [
Veno-veno-arterial extracorporeal membrane oxygenation for acute respiratory distress syndrome with septic-induced cardiomyopathy due to severe pulmonary tuberculosis.
The Impella indwelling guidewire is inserted into the LV so that it arches at the apex, after adding a large J curve to the tip of the floppy part. The stiff part of the guidewire becomes like a rail and can guide the Impella pump catheter toward the apex (Fig. 2).
Fig. 2The method of Impella (guidewire) insertion to the left ventricle.
After Impella insertion, mean arterial pressure would increase and pulse pressure would decrease. Optimal mean arterial pressure is between 70 mmHg and 90 mmHg. There are three points to be confirmed following the initiation of Impella support: (1) The appropriate positioning of Impella pump catheter; (2) Bleeding at the puncture site and others; (3) Improvement of end-organ function and pulmonary congestion. Especially in patients with Impella inserted via femoral artery, we should confirm and adjust the position of the Impella pump catheter using echocardiography at least once a day.
At the time of Impella insertion, activated clotting time (ACT) >250 s is recommended, whereas maintenance level of ACT should not be longer than 200 s to avoid critical bleeding. The heparin concentration of the purge solution is initiated at 10–20 units/mL at first and is gradually increased to maintain ACT 160–180 s and APTT 50–70 s after confirmation of the hemostasis at the puncture site.
A suction alarm might be noticed if the inlet part contacts with the LV wall or any other structures and cannot vacuum sufficient blood. Pulmonary artery pulsatility index (PAPi) should be calculated to assess whether the suction alarm comes from right heart failure or from volume insufficiency [
]. PAPi is calculated as follows: (systolic pulmonary artery pressure - diastolic pulmonary artery pressure)/(right atrial pressure). If PAPi is low (for example, under 0.9), additional approach to manage RV failure should be considered, including administration of dobutamine, milrinone, or initiation of ECMO (Fig. 3).
Fig. 3Impella initiation and subsequent management.
A cut-off level of PAPi to consider additional intervention to RV failure has not been clearly demonstrated thus far. The level of RV function that can maintain LV output may vary in each patient and the target levels of PAPi may also differ between acute and chronic heart failure cohorts. Prospective studies are warranted to establish the optimal cut-off level of PAPi.
It is reported that the patients who achieved cardiac power output, calculated as (mean blood pressure × cardiac output) /451, >0.6 and lactate <4 mmol/L at 12–24 h after initiation of Impella support was associated with better survival [
]. In our institute, we set the target goal: (1) mean blood pressure about 70–80 mmHg and (2) mixed venous oxygen saturation (SvO2) >60 % (preferably >65 %) (Fig. 3).
If SvO2 >65 % and mean blood pressure >80 mmHg are achieved, inotropic agent is reduced and weaning from the Impella support might be considered (Fig. 3A). If SvO2 does not reach above 60 %, we will check the value of PAPi for detailed assessment of cardiac function.
If PAPi <0.9, we up-titrate the dose of intravenous inotropes for RV support (Fig. 3B). When central venous pressure >15 mmHg in addition to PAPi <0.9, we consider more intensive device support with a veno-arterial ECMO in combination with Impella (Fig. 3C).
If PAPi is preserved (>0.9), we will see the PCWP: If PCWP > 15 mmHg, we will increase the support level or upgrade the device (for example, Impella 2.5 to Impella 5.0) given these data indicate left-side heart failure rather than right-side failure.
Management of hemolysis
Hemolysis occurs when a strong share stress is added to the blood cells. For example, hemolysis may occur when the thrombus formation develops in the device, when a structure in the LV is adjacent to the inlet part, or the aortic valve or aortic wall is adjacent to the outlet part.
If the color of urine changes to red (Fig. 4), we should check urinary occult blood, serum level of lactate dehydrogenase, creatinine, and indirect bilirubin. If hemolysis is highly suspected, we should perform echocardiography to see the device position, and the optimization of device position or patients’ volume status is highly recommended [
]. In many cases, hemolysis improves by lowering the device support level or increasing the volume status as well as optimization of anticoagulant therapy (Fig. 4). If hemolysis does not improve, free hemoglobin causes renal tubular dysfunction and acute kidney injury. In some cases, the administration of haptoglobin preparation prevents the progression of renal injury [
If arterial blood pressure is maintained as well as the normalization of pulmonary artery pressure and improvement of end-organ function and cardiac function, we consider to decrease the assist level of Impella. For example, the support level is lowered by 2 steps from P8 and the hemodynamic status will be observed for 3–4 h. Finally, hemodynamics at P2 level is observed for at least 3–4 h. If hemodynamics are preserved despite a reduction in Impella support, the Impella will be explanted. In case of ECPELLA support, ECMO is weaned at first and Impella weaning follows.
Next step to Impella
If patients are completely depending on the Impella support, next strategies should be considered, including the device upgrade from Impella 2.5 to Impella 5.0 or the bridge to the durable left ventricular assist device (LVAD), or valvular intervention during the Immpella support [
In the case of bridge to durable LVAD, patients should be listed for heart transplantation beforehand. Given various tests that are required for the listing take several weeks, Impella would be converted to extracorporeal LVAD considering their durability. Of note, Impella 5.0, instead of Impella 2.5, can support approximately one month for the heart transplant listing and conversion to durable implantable LVAD.
The designed support periods of Impella are 5 days for Impella 2.5, 8 days for CP, and 10 days for 5.0, respectively. In practice, Impella 5.0 can provide hemodynamic support for approximately one month at most. Given the risk of pump thrombosis or device failure, the device exchange is required for long support over one month. In the case of the exchange of Impella 5.0, ECMO support is recommended. Therefore, long-term Impella therapy for months is not realistic given the durability of the device, the risk of critical comorbidities, and the cost. For the bridge to recovery (it takes generally over one month), Impella is considered to be converted to extracorporeal LVAD [
A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction.
Prolonged circulatory support with an Impella assist device in the management of cardiogenic shock associated with takotsubo syndrome, severe sepsis and acute respiratory distress syndrome.
Mechanical circulatory support with Impella percutaneous ventricular assist device as a bridge to recovery in takotsubo syndrome complicated by cardiogenic shock and left ventricular outflow tract obstruction.
Successful bridge-to-recovery treatment in a young patient with fulminant eosinophilic myocarditis: roles of a percutaneous ventricular assist device and endomyocardial biopsy.
Simultaneous venoarterial extracorporeal membrane oxygenation and percutaneous left ventricular decompression therapy with Impella is associated with improved outcomes in refractory cardiogenic shock.
Veno-veno-arterial extracorporeal membrane oxygenation for acute respiratory distress syndrome with septic-induced cardiomyopathy due to severe pulmonary tuberculosis.
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