**2. Hemodynamic effects of Impella® support**

Impella® hemodynamic support exhibits effects on intracardiac volumes and pressures as well as on systemic circulation, leading to augmentation of blood flow independent from heart rhythm. However, blood flow is dependent on after and preload.

During systole, the pressure gradient between aorta and LV is at its lowest, accounting for the highest pump flow and motor current. Vice versa, the increased pressure gradient during diastole between LV and aorta leads to diminished motor current and transvalvular blood flow. These periodic changes result in a sinus-like curve of motor current and blood flow on the AIC. This information is integrated and used by the AIC to control the pumps position. Accordingly, decreased preload may therefore result in reduced Impella® output.

Hemodynamic changes in patients on Impella® support are most profound in patients with CS. In CS, a decreased cardiac index leads to volume overload of the left ventricle resulting in a dilating left ventricular chamber accompanied by increased left ventricular end-diastolic pressure (LVEDP). Concomitantly, increased wall tension of the LV causes increased myocardial oxygen consumption. The increased LVEDP may also result in heart failure with lung edema, further decreasing overall oxygen supply. The positive effects of LV unloading by Impella® support are best explained using pressure-volume (PV) loops. Impella® support leads to a left shift of the PV loop resulting in a reduction of LVEDP and a reduction of area under the PV loop curve. This resembles reduced cardiac work, overall consistent with decreased cardiac oxygen consumption.

In a study by Schiller et al., cardiac index improved from 2.1 l/min/m2 to 3.8 l/min/m<sup>2</sup> [2]. Additionally, mixed venous saturation increased from 56 to 68% and diuresis increased from 69 ml/h at device insertion to 105 ml/h on support indicating improved systemic perfusion. Central venous pressure, lactate levels, and inotropic support, all consequently decreased.

Apart from patients in CS, a case study by Arain and O'Meallie demonstrated an increase in coronary artery circulation on Impella® support in a patient undergoing protected PCI. Fractional-flow reserve (FFR) and coronary flow reserve (CFR) were measured in a hemodynamically significant stenotic left anterior descending (LAD) coronary artery using a pressure wire. While FFR remained the same comparing on- and off Impella® support time points, CFR significantly increased. This demonstrates beneficial effects of Impella® support on coronary perfusion during protected PCI.
