Temporary Mechanical Circulatory Support
There are no uniform definitions for temporary mechanical circulatory support (tMCS), which is often contrasted with permanent mechanical circulatory support.
The former, in my opinion, pertains to those in-patient approaches to MCS that are designed to help support the left ventricle (LV) of patients through acute or sub-acute episodes with the expectation that native heart function will recover sufficiently to wean them off the device and ultimately discharge them with no permanent implant.
The latter typically pertains to surgical left ventricular assist devices (LVADs), which are implanted invasively through a surgical procedure, often requiring a sternotomy, and are designed to provide mechanical support for the failed LV of ambulating patients for many months and even years.
Our discussion here is focused on tMCS.
Types of Temporary Mechanical Circulatory Support
The are many ways to segment tMCS, but a fundamental differentiator between technologies is whether blood is drawn by the pump from inside or outside the heart. While the main goal of tMCS is to provide circulatory support, and thus augment or replace the heart as a pump, it is also important to create the hemodynamic milieu to allow the heart to rest and recover, i.e., to effect mechanical unloading of the LV.
Research over the years has shown that the oxygen consumption of the LV is directly tied to LV wall stress, which in turn is proportional to both the pressure and the radius (volume) of the LV (Laplace’s law).
Thus, effective mechanical unloading of the LV has been shown to be achievable only by pumps that extract the blood directly from the LV and expel it downstream into the aorta. Although intra-aortic balloon pumps (IABPs) and extra-corporeal membrane oxygenation (ECMO) have demonstrable physiological benefits and clinical utility, mechanical unloading and recovery of the LV are not among them.
A Brief History of Temporary Mechanical Circulatory Support
The first clinically available pump to extract blood from the LV was the HEMOPUMP. This device was quite large and required a surgical cutdown to be inserted into the arterial vasculature and then advanced in a retrograde fashion into the LV through the aortic valve. Once activated, the pump delivered flow from the LV to the aorta and supported a variety of indications, including post-cardiotomy cardiogenic shock (PCCS) and acute myocardial infarction cardiogenic shock (AMI-CS).
The hemodynamics and the physiology were very promising, as was the novel approach to tMCS. However, for a variety of business and engineering reasons, it did not ultimately make it to market.
The second device to utilize the trans-valvular approach was also the first attempt at a self-expanding tMCS device – the HeartMate PHP. This pump was commercially available for a time in Europe, but, following several technical failures during the pivotal study in the US (SHIELD II), the device was pulled from the market and the program was eventually shut down.
The Impella pumps are, so far, the only and most successful devices to implement the LV-to-aorta flow approach to tMCS. Following Impella’s acquisition by Abiomed, several Impella devices have been gradually introduced into the market, starting with Impella 2.5 (the smallest pump offering the least flow), followed by Impella CP, Impella 5.0 and Impella 5.5 (the largest pump offering the most flow).
The Impella devices comprise rigid impellers and internal electrical motors, which, together, dictate the overall diameter of the pumps and their level of invasiveness, as well as the flows that they provide.
Impella devices, depending on the model, are currently FDA approved for two indications: high-risk percutaneous coronary interventions (HR-PCI) and cardiogenic shock (CS). Abiomed, now a Johnson & Johnson company, is actively enrolling patients for the Door-to-Unload (DTU) clinical study, with the goal of expanding the labelling of tMCS devices to a third indication: ST-segment Elevation Myocardial Infarction (STEMI).
Unmet Needs in Temporary Mechanical Circulatory Support
When examining currently available tMCS devices through the clinical lens, there are three important limitations and unmet needs:
- Size. Current devices are at least 14Fr and are associated with meaningful vascular access complications, bleeding events, and episodes of limb ischemia.
- Flow. The most popular tMCS devices are unable to reach even 4 L/min of mean flow, limiting the ability to provide optimal flow in patients with significant LV dysfunction.
- Waste of resources. If a patient receives a smaller tMCS device, which is later found to be inadequate in terms of flow, therapy is escalated to a larger tMCS device. Such a decision requires significant hospital resources (another pump, more cath-lab time and the involvement of a surgeon to place an Impella 5.0 or 5.5), but also subjects the patient to another procedure, more radiation, and further potential complications.
Next-Generation Temporary Mechanical Circulatory Support
Next generation tMCS devices must reduce the insertion profile, provide a broad range of flows (up to > 5 L/min, which is the full cardiac output of a grown adult), and eliminate the need to escalate therapy to a larger/higher flow device.
Several tMCS programs are currently under development, and most have chosen to externalize the electrical motor to eliminate one of the two size-determining components of such devices.
In addition, several next-generation devices feature a non-rigid impeller to help reduce their size. The engineering strategies to achieve this vary dramatically between programs and indeed achieve variable success in miniaturizing the technology.
Self-Expanding vs. Compressible Pumps
When evaluating new technology in the tMCS space, it is important to make the non-semantic distinction between compressible impellers and true self-expanding impellers.
The former are much more common and cover those monolithic impellers that are molded from compressible materials, such as polyurethane. These impellers allow for the pump to be inserted into the vasculature at a diameter that is about half that of the fully deployed device inside the heart. Thus, a 9-10Fr device upon insertion may become a 20-22Fr device inside the heart. The flow physics inside a 20-22Fr cannula are well understood, and it is not reasonably expected from such pumps to deliver mean flows that surpass 4 or 4.5 L/min. Two examples of devices under development utilizing compressible impellers are the Impella ECP and Supira Medical.
Magenta Medical’s Elevate™ System features a true self-expanding impeller, where the skeleton is made from a memory shape alloy and the body of the impeller (i.e., the blades) is made from a biocompatible elastomer.
This technology truly breaks the glass ceiling of size and flow, since Elevate™ is crimped into a 9Fr delivery system and self-expands inside the heart to 30Fr. The ramifications are profound: on the one hand, the insertion profile is the smallest known in the category, carrying with it the expected benefits of reduced vascular access complications and minimizing the risk of limb ischemia; on the other hand, the 30Fr diameter of the deployed pump permits the highest flow in the category (well over 5 L/min of mean flow) at the lowest RPM, which is important for blood compatibility considerations.
Conclusion
With a single percutaneous device, which obviously does not require any surgical cutdown, one can treat the full spectrum of tMCS patients, ranging from a relatively low-flow indication like HR-PCI to high-flow indications like CS and, in the future, STEMI. The future of heart care is with temporary mechanical circulatory support.
