This translational interventional study demonstrated feasibility of three-dimensional intracardiac echocardiography with a wide azimuthal elevation of 50° to provide adequate guidance for intracardiac implantation of the Impella CP percutaneous temporary left ventricular assist device. The combination with two-dimensional intracardiac echocardiography modality further improved the quality of imaging and the precision of guidance for optimal Impella CP positioning.
The Impella CP provides a minimally invasive option for temporary left ventricular support. This potentially includes sufferers from COVID-19 cardiac injury with severe left ventricular failure in the absence of respiratory failure, unresponsive to pharmacological therapy . Early mechanical cardiac support should be considered in these patients who have a reasonable probability of recovery, to avoid multiple organ dysfunction resulting from a low cardiac output state.
The optimal choice of the extracorporeal circulatory assist device remains controversial in wide clinical practice and is not yet clear for COVID-19 sufferers. Physiological considerations suggest that in some patients with isolated cardiac complications, left ventricular assist device-based approaches may be superior to VA ECMO in unloading left ventricle while in others a modular approach by combination of both techniques (ECPELLA)  or by combination of VV ECMO and Impella  may offer the best results.
A significant subgroup of COVID 19 patients reportedly developed rapidly progressive cardiac failure during the recovery phase from acute respiratory failure . These patients remain highly contagious, while being unstable with regard to both respiratory and hemodynamic parameters. Transfer of these patients to the catheterisation laboratory for fluoroscopic-guided implantation of the Impella would represent a high risk for these patients, hospital staff and other patients. High oxygen requirements, tachypnea and non-invasive ventilatory support can often be prohibitive for adequate TTE image acquisition . TEE in these patients would require general anaesthesia, reintubation and return to invasive ventilation. This also presents a risk of disease transmission to attending physicians. All the above could be prohibitive for the provision of mechanical cardiac support to otherwise suitable patients. Point of care ICE is the most invasive echocardiographic modality but it could provide an alternative approach to guide awake implantation of the Impella CP under local anaesthesia in this subgroup of patients and avoid undesirable intrahospital transfers and the need for invasive ventilation.
Although it would be of interest to compare ICE to TTE and TEE, such a comparison was beyond the scope of this study for the following reasons. Our ovine model was thoracotomized for a parallel study making TTE impossible at the time of Impella implantation. The proximity of the right atrium to the aortic root is similar in sheep and humans but the sheep left ventricular apex is midline and the main chamber of the left atrium is lateral to the midline. Previous investigations suggested limited anatomical feasibility of TEE in ovine models . We therefore do not believe that a comparison between intracardiac echo and either TEE or TTE in sheep would be directly applicable to humans. Thus, the study was not designed to compare different echocardiographic techniques but aimed to explore the hypothesis that ICE can be used as a feasible alternative to TTE and TEE when those techniques are clinically unsuitable.
Two-dimensional ICE has been reported in six patients during percutaneous coronary interventions supported by the Impella Recover LP 2.5 . ICE was used to assess aortic root and aortic valve, left ventricular outflow tract, left ventricle and mitral apparatus prior to the implantation of the Impella. The ICE probe was inserted via the femoral vein to obtain views from the right atrium. As the ICE was performed in the catheterisation laboratory, standard fluoroscopic guidance may have been used to assist in implantation of the pumps in these patients. 2D ICE was further reported to be used in one patient during percutaneous coronary intervention supported by the Impella Recover LP 2.5. 2D ICE was used in that case for dynamic assessment of short axis left ventricular area from the right ventricular window .
Femoral venous access is normally used for intracardiac echocardiography. Jugular two-dimensional ICE catheter access for guiding intracardiac device implantation has been described  in a patient undergoing transcatheter aortic valve replacement. The authors sited two major benefits – good imaging planes for the anatomical structures of interest (ascending aorta, long-axis aortic valve and long-axis left ventricle) and an absence of interference with the operator inserting the prosthetic valve. Our experimental findings support this report. Percutaneous implantation of the Impella CP is routinely performed via femoral arterial approach. The use of jugular access for the ICE has the benefit of eliminating physical interference with the operators inserting the Impella but might not be preferred in awake COVID patients who have their heads enclosed in a protective barrier.
Transthoracic, transesophageal  and epicardial  echocardiography has been used to navigate implantation of various Impella devices. We did not find any animal or human reports that have described implantation of the Impella with guidance purely by ICE, nor any reports of wide-angle three-dimensional echocardiography used to guide and to optimally position the Impella.
Our intracardiac imaging was adequate in all cases. It required a short learning curve for the sonographer with expertise in 2D and 3D TTE and TEE. Jugular access presented unfamiliar views, but cardiovascular structures relevant to the implantation of the Impella were clearly identifiable. Standard factory scanning settings had to be adjusted for grey scale and Colour Doppler modalities to optimise image quality. We did not use fluoroscopy in any of the cases except to demonstrate the favourable three-dimensional spatial relationship between the implanted pump and ICE probe tip on completion of the insertion and running of the Impella (Figure 14). Adequate ICE imaging of the ovine aortic arch can be obtained from the superior vena cava to identify a guide wire in the arch (Figure 15, Movie 11) but such views have not been reported in humans.
Human clinical implantation of Impella CP usually utilize percutaneous femoral or axillary arterial access , with fluoroscopically guided guidewire advancement to the left ventricle. We used a cut-down approach for the left common carotid artery. This approach was selected based on the anatomical specifics of the ovine model and intraoperative convenience and did not imply any recommendations to change traditional human vascular access. The inability of ICE to image the descending aorta has been accepted from the outset as an inherent limitation of this imaging technique where blind guidewire advancement would be required through that portion of the aorta. A similar limitation would apply for TTE, while most of the abdominal aorta would not be imaged with TEE. Guide wires are often inserted into the descending aorta from the femoral artery without any form of imaging as is the case of intra-aortic balloon counter-pulsation. The use of a curved guide wire or sheath dedicated to successful transit of the aortic arch into the ascending aorta will allow blind insertion of the guide wire into the ascending aorta in the majority of patients and can likely be assisted by ICE imaging of the arch. COVID-19 patients potentially selected for the mechanical cardiac support are likely to be younger and without underlying serious vascular pathology, which would minimize the risk of aortic complications during blind introduction of the guidewire through parts of the aorta which are not suitable for imaging with ICE. Careful ultrasound-guided placement of the femoral arterial introducer sheath and high level of postprocedural vigilance in monitoring for potential aortic complications would be justified in cases of “blind” aortic instrumentation. This limitation of ICE constitutes additional risk for the patient and needs to be considered in making clinical decision to select ICE among other imaging techniques.
Two complications with tangled soft guidewire after implantation of the Impella CP across the aortic valve demonstrated important shortcoming of ICE related to the limitations in spatial resolution. In contrast with fluoroscopy, ICE did not clearly identify excessive length of the thin soft guidewire within left ventricle and intravascular trajectory of this guidewire outside Impella between the catheter outflow port and vascular introducer. This led to the unrecognized by echocardiography entanglements and life-threatening complications. Because the guide wire exits the Impella through the pump outflow port, excessive tension on the guide wire is likely to cause bowstringing of the drive sheath resulting in vascular perforation at the point of maximum kinking of the sheath. Accordingly, excessive traction should not be applied to the guidewire. In cases of difficulty during guidewire withdrawal, the whole implanted device together with the Impella CP should be removed as a block.
Limited visualization of the plastic pigtail tip due to the strong reverberation artifact arising from the apex tear-drop part of the Impella CP made it difficult to use this portion of the pump as a guide in one third of experiments. Detection of the tear-drop of the Impella CP impacted into the left ventricular apex suggests a potential danger for left ventricular perforation by the rigid portion of the catheter. Slowing insertion of the device after transiting the aortic valve with ongoing careful dynamic imaging of the tear-drop position instead of the plastic pigtail within left ventricular cavity may help to avoid excessive propagation into the apex and minimize the risk. Vascular perforation occurred in two of the 25 implantations and both were associated with quite forceful traction on the guidewire. The guidewires used were generic rather than those supplied by Abiomed.
The strengths of the study include a pre-specified protocol, high data integrity and simple explorative analysis plan. The study was conducted over a very short inception period of one week considering utmost emergency to develop alternative approaches for COVID 19 patients suffering from acute severe heart failure and the world-wide pandemic closure of most research facilities, including our laboratory.
The limitations of the study include a relatively small sample size. Confounding bias was mitigated by standardising investigative techniques and operator-dependent errors using echocardiography experts for image acquisition and analysis. The translational nature of the study involves utilization of the ovine model thus human application remain speculative.
There have been no previous studies investigating implantation of the Impella CP left ventricular assist device with both two and three-dimensional intracardiac echocardiography.
Our study demonstrates potential to expand the use of the Impella CP for subgroups of patients where other types of imaging to guide implantation are clinically problematic.