CARMAT Total Artificial Heart and the Quest to Improve Biventricular Mechanical Support (2021)

The last several decades of advancement in mechanical circulatory support have focused on durable, rotary flow left ventricular assist devices (LVAD). The Heartmate (HM) 3 LVAD demonstrates a number of important advances including reduced pump thrombosis, reduced stroke, and impressive durability.1 One important adverse event; however, which has not been eliminated or diminished, is right heart failure or dysfunction (RVD).1 There was no improvement in RVD in MOMENTUM and in fact there was a trend toward greater RVD with HM3 versus HMII support.1 This is particularly concerning when one considers that exclusion criteria for the trial were designed to specifically remove potential subjects who were at higher risk for post-LVAD RVD. Furthermore, one of the most important causes for readmission after durable LVAD is RVD, and ventricular arrhythmias associated with RVD, are also an important cause of both readmission and death (see Figure 1). These observations emphasize that among patients with advanced heart failure, a significant fraction could benefit from biventricular mechanical replacement.Figure 1.: Typical echocardiographic appearance of LVAD supported patients with right heart failure. The LV is completely decompressed (sucked down), whereas the RV remains dilated with functional tricuspid insufficiency. LVAD, left ventricular assist devices.So why do not we employ more biventricular mechanical support? Even for cases that feature ventricular arrhythmias and restrictive myopathy, durable biventricular support in the form of Total Artificial Heart (TAH) have been clinically tested for years but has not been strongly embraced by surgeons in heart failure community. Unfortunately, adverse event rates for BIVAD and TAH patients have exceeded those of patients who are supported with LVAD alone.3,4 Perhaps the single most important event is thromboembolism and stroke; Runyan et al describe a stroke rate with the current FDA-approved TAH product which far exceeds the reported stroke rate seen with HM3 LVAD support.3 Furthermore, TAH support requires that the right and left heart circulations be properly balanced; specifically, right-sided mechanical support can result in pulmonary over circulation and lung injury, manifested as edema or hemorrhage. Our group has supported a number of patients with two durable centrifugal VADs but improper speed settings or obstruction of inflow for the left-sided device has been experienced, resulting in severe lung injury. CARMAT is the new kid on the TAH block. The device features biocompatible blood-contacting surface comprised of bovine pericardium including four bioprosthetic valves. In addition, an electro-hydraulic pumping mechanism achieves pulsatile flow which simulates natural ventricular contraction and avoids high shear and potential damage to Von Willebrand’s multimers. Relative to the current FDA-approved TAH product, CARMAT is electrically driven with a single percutaneous lead. Finally, in the current article by Netuka et al, the auto mode of operation is highlighted.4 In this mode, ventricular in flow pressure (filling pressure) is measured and set. Filling pressures above the set threshold trigger an increased beat rate. This feature has been used in clinical implants in Europe and Asia. The auto mode required minimal change in settings and achieved balanced right and left circulations as well as exercise responsive changes in output. The first US implant at our center similarly required no manipulation after switching to auto mode. Furthermore, there was no evidence for pulmonary over-circulation or imbalance of the right and left circulations, a problem which we have struggled with when using two centrifugal VADS as a TAH system. Although the initial experience would suggest that CARMAT has provided a safer TAH product, clinical trial has just begun and important questions will need to be addressed. The cases described by Netuka et al are INTERMACS level 3 patients, substantially less ill compared with the earlier TAH trials which approached patients in cardiogenic shock, often already on temporary MCS.5 The US application will certainly challenge the CARMAT TAH with a much sicker cohort. Furthermore, the durability of CARMAT TAH is unknown and many of us still equate pulsatile flow and bio-prosthetic valves with the old Thoratec Heartmate XVE which displayed awful durability. Finally, the size constraints of this initial device will enable use in only a small fraction of the biventricular failure population. Nevertheless, CARMAT TAH seeks to address the unmet need to support larger patients with severe biventricular failure. Patients who are too big to be rapidly transplanted and for whom current biventricular MCS strategies fall short with very high adverse event rates. We are excited to trial new technology and hold great hope that CARMAT will represent an advance in the challenging, TAH space.