Impella device

# Overview
The Impella device is a percutaneously inserted ventricular assist device (pVAD) that is used to temporarily support left or right ventricular function in patients with cardiogenic shock complicating acute myocardial infarction who undergo high-risk percutaneous coronary intervention (PCI) or open heart surgery. Cardiogenic shock occurs in approximately 6% to 12% of patients with STEMI and 17% of patients with NSTEMI. In these patients, cardiogenic shock results in a 30% to 50% in-hospital mortality after the ischemic event. pVADs utilize a small mechanical pump to give short term support to the ventricles. pVADs aim to improve outcomes through three primary mechanisms: (1) increase the mean arterial pressure (2) reduce in ventricular diastolic pressure (3) increase in coronary perfusion.

# Structure and Function
The axial flow pumps of the Impella device are mounted on a 12Fr (Impella 2.5LP), 13Fr (Impella CP), or 21Fr (Impella 5.0) support catheter and are usually inserted through the femoral, subclavian, or axillary arteries. The micro-axial catheter is placed into the ventricle in retrograde fashion and the circulating impeller transfers oxygenated blood from the inlet in the ventricle to the outlet in the ascending aorta. This mechanism effectively and rapidly increases mean arterial pressure which increases coronary and peripheral perfusion, and unloads left ventricular volume and pressure which decreases myocardial oxygen demand.
The following video describes the function of the impella device:

# Indications

## High Risk PCI Patients
Impella is used to prevent hemodynamic compromise in high-risk patients by unloading the left ventricle and reducing end-diastolic wall stress. Additionally, the Impella device works to decrease the pulmonary capillary wedge pressure. Compared with the intra-aortic balloon pump, there is a trend toward improved 90-day outcomes among patients receiving the Impella 2.5 device. . Studies have also shown the Impella to be effective for increasing LVEF in patients undergoing high-risk PCI. 
The PROTECT II Trial was designed to assess the differences between Impella and IABP in regard to major adverse events (MAEs) at one month in patients undergoing high-risk PCI.  The study demonstrated that Impella use resulted in a trend toward significance in lower out-of-hospital MAEs compared with IABP (40.6% vs 49.3%, P=0.066) in the intent-to-treat population at 90 days, whereas the per-protocol population showed significant differences between Impella and IABP (40.0% and 51.0%, respectively, P=0.023).
In patients undergoing complex revascularization, there is a risk for periprocedural and postprocedural acute kidney injury (AKI). There is a subsequent higher risk for mortality, major bleeding, and MI in these patients.  Patients with low LVEF often require longer procedures and greater contrast use which places them at higher risk of acute kidney injury (AKI). One study examined AKI outcomes among patients with an average LVEF of 35% receiving partial Impella 2.5 hemodynamic support during high risk PCI (HRPCI).  Impella support was associated with significantly fewer AKI events than control patients not receiving the device (5.2% vs 27.8%, p < 0.001).

## Cardiogenic Shock
One of the prime indications for use of the Impella device is for cardiogenic shock, a condition in which the Impella has consistently demonstrated favorable post-interventional outcomes. In the USpella Registry, patients with cardiogenic shock (CS) complicating an acute myocardial infarction (AMI) receiving the Impella 2.5 prior to PCI demonstrated superior outcomes to patients receiving the device after PCI, showing the importance of early support in this setting.] Patients with severe refractory cardiogenic shock may also experience a beneficial short-term effect of device placement. The Impella 5.0 may also allow for more rapid weaning of inotropes in this patient population.
The IMPRESS trial, a small, exploratory study comprising a heterogeneous patient population with severe cardiogenic shock complicating acute myocardial infarction, compared patients receiving either Impella CP or IABP. Researchers found 30-day mortality was similar between Impella CP and IABP (46% vs 50%, respectively). The issue with this trial was its severely ill patient population. Since anoxic brain injury was the main cause of death, mechanical support may not even have been the most optimal treatment in this population. Additionally, the study didnt take into account timing of device placement. Early Impella support prior to initiation of PCI is considered optimal for improved outcomes  and absence of this information hinders the generalizability of the findings to clinical practice.

## Bridging to Transplantation or Durable Device Placement
Impella 5.0 may provide an effective bridge to further therapy (transplantation or durable left ventricular assist device ). A small study consisting of 40 critically ill patients with heart failure undergoing Impella 5.0 support found that 75% of patients were able to survive to next therapy with no observed events of major bleeding or stroke, There was a 68% survival rate to discharge and/or 30 days, demonstrating that hemodynamic support with the Impella device may allow for an effective and safe bridge to a definitive decision strategy in heart failure patients.

# Approved Devices
The following impella devices are approved for circulatory hemodynamic support:

## Left Ventricular Heart Failure
- Impella 2.5  The impella  2.5 delivers a maximum of 2.5L/min of blood flow from the left ventrical to the ascending aorta. Current FDA-approved indications for temporary use include:
Cardiogenic shock (4 days) that occurs <48 hours after acute myocardial infarction (MI) or open heart surgery
Protected PCI (6 hours) in elective or urgent cases of hemodynamically stable patients with depressed left ventricular ejection fraction (LVEF) and severe coronary artery disease (CAD)
- Cardiogenic shock (4 days) that occurs <48 hours after acute myocardial infarction (MI) or open heart surgery
- Protected PCI (6 hours) in elective or urgent cases of hemodynamically stable patients with depressed left ventricular ejection fraction (LVEF) and severe coronary artery disease (CAD)
- Impella CP
The Impella CP received expanded FDA approval for its use in High-Risk Percutaneous Coronary Intervention (PCI) Procedures in 2016. This device pulls blood from the left ventricle into the ascending aorta at a maximum rate of 3.5L/min. The indications for use are the same for Impella 2.5 and 5.0.
- Impella 5.0
The Impella 5.0 is an intravascular microaxial blood pump that delivers up to 5.0 L/min of forward flow blood from the left ventricle to the aorta.  The indications are the same as the Impella 2.5 and CP devices.

## Right Ventricular Heart Failure
Impella RP 
The Impella RP provides right-sided support in patients who experience right-sided heart failure after either left-sided support, a heart attack, heart transplantation, or after heart surgery. This Impella device delivers blood from the inlet area in the inferior vena cava and through the cannula to the device outlet opening in the pulmonary artery.

# Clinical Practice Guidelines

# Alternative Devices

## Left Ventricular Heart Failure
- LVAD: The Left Ventricular Assist Device is a surgically implanted device that was used as a bridge to transplantation in patients with severe heart failure. The use of LVADs has decreased significantly due to evidence of increased mortality in older high-risk patients, and due to the availability of percutaneously implantable devices.
- IABP: The intra-aortic balloon pump uses a pneumatic pump that is easily placed in the aorta at bedside and inflates a balloon in the aorta during systole and deflates during diastole. It has been widely used in clinical practice for decades until evidence from the SHOCK II trial demonstrated no increased benefit in 30 day or 12 month mortality with IABP compared to medical therapy alone.
- VA-ECMO: Venous-arterial extracorporeal membrane oxygenator extracts venous blood from the body and returns oxygenated blood to the arterial system by use of a centrifugal pump. Inflow cannulas are typically placed in the right atrium or the inferior vena cava and outflow cannulas are placed in the femoral or subclavian artery. This system provides oxygenation and circulatory support and is widely used in clinical practice despite conflicting evidence on its benefits.
- TandemHeart: The TandemHeart is an extracorporeal device that utilizes a centrifugal pump that provides a flow of 3.0 to 5.0 L/min. This system requires a transseptal puncture to bypass oxygenated blood from the inlet in the left atrium to the outlet in the femoral artery.

## Right Ventricular Heart Failure
- TandemHeart RVAD: This device uses a centrifugal pump to move blood from the inlet in the right atrium to the outlet in the main pulmonary artery. This action aims to bypass the poorly functioning right ventricle.

## Biventricular Heart Failure
- VA-ECMO: ECMO is a reasonable strategy for biventricular failure when combined with left ventricular venting to avoid distention.
- Combination strategies: Combinations of impella and TandemHeart device implantation has been described in successful procedures.
- BiPella: A procedure whereby an Impella 5.0 device is placed in the left ventricle and rapidly unloads the left ventricle and increases peripheral circulatory pressure. This also reduces the backup of blood from the left side to the right side and temporarily relieves the right ventricle but eventually leads to an increase in central venous pressure and right ventricular preload, which requires the subsequent implantation of the Impella RP device to  unload the right ventricle diastolic wall pressure.

# Randomized Clinical Trials

## PROTECT II Trial 
The trial was discontinued early due to futility.  A press release from the manufacturer Abiomed stated the following:
"Abiomed announced completion of the PROTECT II study based on a futility determination at the planned interim analysis regarding the primary end-point, which the company views as likely to be due to unanticipated confounding variables related to the use of rotational atherectomy2 in the study. The decision to end the study followed the recommendation of the Data Safety Monitoring Board. The study was designed to measure major adverse events at 30 days in high risk percutaneous coronary intervention (PCI) patients randomized to receive hemodynamic support during the procedure with the Impella versus intra-aortic balloon (IAB)."
Summary and Conclusion of Protect II:
- For the entire study population, Impella significantly reduced out of hospital major adverse events (MAE) by 52% compared to IAB for the duration of the 90 day monitoring (p=0.02, N= 302).
- There was an overall positive trend in the majority (88%, n=267) of patients in the study at the interim analysis, in which Impella reduced the major adverse event rate by 26% over the IAB (Impella 32% MAE vs. IAB 43% MAE, p=0.11).
- Impella provided a 47% reduction in major adverse events over IAB in a subgroup that represents 70% of the protocol study population (Impella 23% MAE vs. IAB 43% MAE, p=0.009). An analysis of a PROTECT score will be presented at the upcoming ACC in April.
- When using atherectomy, Impella significantly reduced repeat revascularization (p=0.02).
- The data revealed confounding variables in the treatment between the two arms with the most significant differences related to two times more frequent use (p=0.04) and two times the number of passes per use (p=0.003) of rotational atherectomy in the Impella arm compared to the IAB arm, accounting for 12% (n=38) of total PROTECT II patients at the interim. Use of atherectomy during PCI has been previously shown to increase CK-MB release (heart enzyme) following PCI, triggering an endpoint in PROTECT II.
Atherectomy was an unanticipated variable which resulted from the operators decision to do more with Impella. Our investigators had unblinded knowledge of the treatment arm after randomization, said William ONeill, M.D., University of Miami and Principal Investigator of the PROTECT II study. It is interesting that operators felt that they could do more complex interventions once randomized to Impella and this in and of itself is an important finding.