There are a couple of critical points I would like to make regarding this study. First is the trial design. Traditionally, the FDA has mandated that one needs to define the intended use of the LVAD clearly as destination therapy or bridge to transplantation when we’ve been doing randomized trials in mechanical support. The adaptive design in this trial is a landmark that opens the door for further device trials that do not require investigators to label the patient with an intended use. The distinction becomes irrelevant as the pump becomes indicated for HF. The only agency that needs to catch up with this is CMS, which needs to look at the results of this trial and determine whether they are comfortable defining use of chronic implantable LVADs for the indication of HF failing medical therapy as opposed to the artificial labels of destination therapy and bridge to transplantation. The investigators of the MOMENTUM 3 trial are to be congratulated for coming up with such a design, which was suggested 4 years ago by an expert panel to the FDA.

The second major takeaway from these results is that the investigators achieved what they set out to do, which is to demonstrate that the HeartMate 3 was noninferior to the HeartMate II with respect to the primary composite endpoint of 6-month survival free from device failure or disabling stroke. There is a complex secondary analysis that demonstrates benefit with the HeartMate 3.

The question that remains is whether we have significantly reduced what cardiologists are most concerned about, which are the adverse events that accompany the utilization of these mechanical circulatory support devices. That’s a question that I’m not sure this study will be able to answer clearly, as the results represent only approximately 7% of the total numbers of patients that will be enrolled over the two years of follow-up and enrollment in this trial. We must also understand that there are no INTERMACS Category 1 patients in this trial. It is a less-sick population right off the bat. The HeartMate II patients reached 77% success in the composite endpoint at 6 months; this was characterized by a 14% pump thrombosis rate. The question is why. In my mind, the trial is a success, but the real information is going to come later as there is more widespread use in a much larger population of patients.

It was interesting to see that the gastrointestinal bleeding rates were approximately 15% in both populations. At 6 months, that is not inconsequential. We need a deeper dive into why that occurred. Also of interest was that the driveline infection rate was approximately 11% in the HeartMate 3 population vs. 6% in HeartMate II. It’s not significantly different, but it shows that even in the best hands with the latest technology, there are adverse events that need to be addressed. There is always a tradeoff between death and adverse events; for patients with advanced HF, for whom the only other option is death, the only option to offer may the LVAD, especially if the patient is not a transplant candidate. Thus this may be the tradeoff we have to live with. We have to determine how to cope with GI bleeding and driveline infections, and develop engineering and therapeutic strategies to eliminate them.

I was pleased and surprised by right atrial pressures and the creatinine levels. What this tells me is that the cardiologists are choosing to offer LVAD therapy before it’s too late and are more comfortable offering this option at an earlier stage in the congestive HF timeline. There is a shift in the field toward a more intelligent adoption of the technology, not just as rescue from death, but as a true alternative for end-stage HF for which medical therapy is failing.

This is a well-designed device that has set the bar high for future devices. No pump thromboses in 6 months is an important achievement. But we need to understand that this technology is not just about the pump. What also fails in this technology are the batteries, controllers and drivelines, and all the things that attach to the pump. It will be interesting to see how robust the technology is to withstand the rigors of what people put it through in real-life situations. Ultimately, we must not lose sight of the need to develop a truly implantable device where there are no more peripherals. In the meantime, we need to design better tissue-engineered driveline interfaces with the skin, so they withstand accidental trauma. Battery technology is slow to evolve for long-term medical products. The technology needs to last longer for medical uses. The technologic ability is there, but there may not be enough motivation behind it from those that need to prioritize its development.

Also, it is important that we better understand the HF state from the perspective of it being an inflammatory process. The implantation of an LVAD probably magnifies the inflammatory response that may lead to some of the complications we see such as right heart failure and GI bleeding. We need to recognize and address this inflammatory signal throughout the various stages of congestive HF through more focused research.