**5.2. Cardiogenic shock**

Mortality of patients suffering from acute myocardial infarction (AMI) complicated by CS remains high. Given the potential benefits of pVADs in this specific scenario, short-term circulatory support seems to be a promising therapeutic option. Hypoperfusion caused by cardiogenic shock triggers the so called "shock spiral" by systemic hypoxemia leading to dismal systemic regulatory efforts. The implantation of a pVAD may halt this downward spiral by increasing cardiac output, decreasing LVEDP by unloading of the left ventricle, and therefore reducing oxygen consumption of the myocardium. As appealing as this approach may sound, there is currently no randomized, controlled trial available that may prove the benefit of pVADs in this scenario. The IMPRESS (IMPella versus IABP REduces mortality in STEMI patients treated with primary PCI IN SEVERE and deep cardiogenic SHOCK) trial, a recent controlled, randomized, multi-center study by Ouweneel et al. has found no difference in short-term and 6-month mortality in patients undergoing pVAD support through the Impella® CP in cardiogenic shock compared to Intra-aortic balloon pump (IABP) [18]. Furthermore, a recent meta-analysis from the same authors evaluating the three available randomized trials of Impella® usage in CS patients and comparing it to IABP also revealed no survival benefit at 30 days and 6 months [19].

Interestingly, there seems to be differences in survival in-between men and women. Data from the cVAD registry (catheter-based ventricular assist device registry), a database retrospectively enrolling patients that underwent pVAD support with Impella®, showed that early initiation of hemodynamic support in patients with AMI complicated by CS was associated with a greater survival benefit in women compared to men [20]. These data are encouraging, as women usually suffer higher unadjusted mortality rates and experience the use of guideline-recommended therapies to a lesser extent.

Although the concept of pVADs in CS seems convincing and there is ample data showing improved hemodynamic parameters, there is still no evidence from RCTs that pVADs improve survival in these patients. One issue is certainly identifying patients that might profit from pVAD implantation and selecting the appropriate pVAD. Future trials should therefore focus on identifying the "right" patient and the "right" time for Impella® implantation in CS.

#### **5.3. Right ventricular failure**

The Impella® RP received FDA approval in 2015 upon completion of the RECOVER RIGHT (The Use of Impella RP Support System in Patients with Right Heart Failure: A Clinical and Probable Benefit Study) trial, resembling the first percutaneous right ventricular assist device [21]. This prospective, multi-center, single-arm study included 32 patients from 15 institutions in the USA. Of these patients, 18 were included with right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation and 12 patients presented with RVF after cardiotomy or myocardial infarction. All patients included exhibited life-threatening RVF with three vasopressors/inotrops installed and a mean cardiac index of 1.8 l/min/m<sup>2</sup> .

Cardiac index increased to 3.3 l/min/m2 and central venous pressure decreased from 19.2 to 12.6 mmHg under Impella® RP support. In total, 73.3% of patients survived more than 30 days after an average hemodynamic support of only 3.0 days. RECOVER RIGHT was not designed to compare Impella® RP to standard medical treatment; however, the safety and hemodynamic efficacy of the device were shown. The device is approved for a period of 14 days, warranting more durable solutions in patients that do not recover.

Besides above-mentioned causes of RVF included in the RECOVER RIGHT study, further indications for temporary right ventricular support seem appealing. Hansen et al. presented a case of a patient with sepsis induced RVF on grounds of pulmonary hypertension that initially recovered after Impella® RP implantation [22]. Again, markedly improved hemodynamic parameters were reported after initiation of hemodynamic support.

The Impella® RP therefore may serve as a valuable therapeutic option in patients presenting with life-threatening RVF of a variety of causes and under already applied standard of care. Again, patient selection plays a crucial role for the success of the treatment.

#### **5.4. Impella® as a bridge to decision or bridge to next therapy**

A growing number of patients with a severely reduced LV require temporary mechanical support to bridge time to multidisciplinary assessment of best therapeutic strategy or bridge to next therapy. Lima et al. reported their single-center experience with Impella® 5.0 for either bridge to heart transplant or bridge to durable left ventricular assist device in 40 patients [4]. The primary endpoint survival to next therapy was reached in 75.0% of patients. Compared to the predominant bridging strategy employing Extracorporeal membrane oxygenation (ECMO), this reveals a significantly higher likelihood of survival. Furthermore, critical complications are significantly lower in patients undergoing Impella® support compared to ECMO. In summary, Impella® may serve as a valuable therapeutic alternative in patients being bridged to next therapy overcoming some of ECMOs limitations.
