From Pages to Practice
Published February 1, 2017
When heart failure progresses despite optimal medical therapy, some patients are eligible for evaluation for heart transplant or mechanical circulatory support. LVADs can support cardiac function in this setting, either as a bridge to cardiac transplantation or as destination therapy. However, LVADs are not hazard-free: They are associated with increased risk of bleeding, thromboembolic events, infection, acquired von Willebrand disease, and hemolysis. LVADs also carry a risk of pump thrombosis that can lead to impairment in LVAD outflow and require emergency pump replacement or heart transplantation.
In this week’s issue of NEJM, the MOMENTUM3 trial and the ENDURANCE trial compared the safety and efficacy of two new centrifugal-flow LVADs to that of the existing axial-flow LVAD technology (HeartMate II). The new devices were designed and tested with the hypothesis that a centrifugal pump without bearings would reduce friction and the risk of thrombosis associated with LVADs.
The multicenter, nonblinded, randomized, noninferiority MOMENTUM 3 trial compared the new bearingless magnetically levitated centrifugal continuous-flow pump (HeartMate 3) and the existing mechanical-bearing axial continuous-flow pump (HeartMate II) in 294 patients with advanced heart failure that was not controlled by standard medical therapy who were candidates for LVADs.
The primary endpoint of survival free of disabling stroke or reoperation to replace or remove the device at 6 months was reached in significantly more patients who received the HeartMate 3 than the HeartMate II (86.2% vs. 76.8%, P<0.001 for non-inferiority, P=0.04 for superiority). This finding was largely attributed to the lower rate of reoperation due to device malfunction with the HeartMate 3 (0.7% vs. 7.7%, respectively; P=0.002). No significant differences between groups were found for rate of death, disabling stroke, functional status, or quality of life. Significantly fewer patients experienced pump thrombosis with the HeartMate 3 than with the HeartMate II (0% vs. 10.1%, P<0.001). The HeartMate 3 was associated with a nonsignificant numerical trend toward higher rates of disabling stroke and lower rates of right heart failure events.
The multicenter, noninferiority ENDURANCE trial randomized (in a 2:1 ratio) 446 patients with chronic advanced left ventricular failure who were ineligible for cardiac transplantation to receive a new bearingless small intrapericardial centrifugal-flow device (HeartWare) or the same HeartMate II device studied in the MOMENTUM 3 trial. The HeartWare device lies entirely within the pericardial space and incorporates a bearingless design with magnetic and hydrodynamic levitation of the internal rotor.
The rate of the primary endpoint of survival free from disabling stroke or need for device replacement at 2 years did not differ significantly between the HeartWare and HeartMate II groups (55.0% vs. 57.4%, P=0.67). Rates of secondary outcomes such as overall mortality, major bleeding, cardiac arrhythmias, renal dysfunction, and infections also did not differ significantly. Both devices were associated with sustained improvements in functional and quality-of-life measures at 2 years. The HeartWare device was associated with significantly higher rates of ischemic or hemorrhagic stroke (29.7% vs. 12.1%, P<0.001) as well as increased rates of right heart failure and sepsis. However, the HeartMate II control device was associated with a higher rate of the composite outcome of device replacement, device explantation, or need for urgent transplantation for device malfunction.
These two trials highlight the importance of testing new medical devices against existing ones in rigorous randomized-controlled trials. Although new technology may afford additional benefit, it may also bring unforeseen risks. In both studies, the newer devices were noninferior to the established LVAD with respect to the primary efficacy outcome. Although the intrapericardial HeartWare LVAD in the ENDURANCE trial was associated with lower rates of device replacement, explantation, and need for urgent transplantation, it was also associated with unexpected increased risks of stroke, right heart failure, and sepsis. NEJM deputy editor John Jarcho adds, “Direct comparison in randomized trials is the only way to be confident of the relative advantages and risks of a new device.”
You discuss the new LVAD options with Mr. McGillicuddy and his wife, and explain the potential benefits and risks of the centrifugal devices identified in the MOMENTUM-3 and ENDURANCE trials. Mr. McGillicuddy decides to continue milrinone for now while he evaluates his options.