This may be one of the most exciting trials presented here at TCT 2018. The reason is that this was an anticipated study to see whether or not the MitraClip procedure would be a viable procedure that can be used in patients who are symptomatic with moderate to severe or severe mitral regurgitation or leakage of the mitral valve. These are not because of an anatomical issue, but because of a functional mitral regurgitation from antecedent HF.

In the past, these patients honestly were mostly treated with medical therapy. There were some pacemaker devices and other novel devices that were used to try and help these HF patients and to perhaps reduce the leakage of the mitral valve, but aside from surgery, it was not considered necessarily that MitraClip would be a therapy that can be used with these patients.

What is encouraging and exciting is that with this large group of patients who were randomly assigned to medical therapy or to the MitraClip procedure for functional mitral regurgitation from previous or antecedent HF after being followed for 2 years with successful MitraClip therapy, those patients actually did significantly better and specifically they had less hospitalizations for HF and lower all-cause mortality at the end of 2 years compared with the medical therapy group.

This opens up MitraClip as a viable and encouraging procedure that can be used for these patients that previously were relegated to the best medical therapy they can have, but not necessarily in a way that was improving their clinical situation. It did appear that this improves these patients’ clinical situation.

It was also exciting that the device failure or complication rate was lower than expected. Again, that points to anytime you have a new therapy, particularly if it is a device, a minor surgery or what have you that regards something that is potentially invasive, that is always a concern of complications, but this had very low, several percentage complication rate and less than what they expected on the front end of the procedures.

Several of the studies that have been presented here really knocked it out of the park because it showed a new therapy for an indication for something that we have not had optimal treatments for in the past. This is a large group of patients with HF, and then with secondary mitral regurgitation that can now be treated with the MitraClip.

This trial is encouraging, and we do have to take everything in totality, but this may impact the guidelines for use of this therapy. It may not be that it is going to be a Ia guideline recommendation, but it may be a IIb or perhaps even a IIa, meaning that it is one that can be considered for use in these patients.

We have seen that MitraClip has been a successful therapy in patients who were high surgical risk before. Now this gives another group of patients that can be treated with MitraClip. That is great because that means that they have other options if they are at high surgical risk, which these HF patients are, other than medical therapy. They are going to feel better.

COAPT is an incredible trial. It is probably one of the biggest trials in our field in a really long time. There have been a lot of very important trials, but as a structural interventionalist, probably after PARTNER, this is probably the biggest trial in the field. It has been 8 to 10 years since we had another blockbuster like that. Off the bat, it suggests that transcatheter mitral valve approximation using the MitraClip is superior to medical therapy alone for selected patients with HF and moderate-to-severe or severe mitral regurgitation. The striking thing is that all the endpoints are completely concordant. The primary endpoint of HF hospitalizations was reduced, but so was mortality. The MitraClip provided a durable result at 1 year in this trial, and as a result, the left ventricles didn’t dilate further, and patients also felt better. Only CV mortality and hospitalization, and that too, the portion related to HF, got better; non-CV mortality and hospitalization rates were similar between the two arms. The overall story is thus very convincing, even though this was an open-label study.

There have been a lot of sessions and a lot of discussions at TCT about how to best reconcile COAPT with the trial at ESC, MITRA-FR, and what this means for the field in general. There are key differences between the trials as far as identifying which patients would benefit the most. For example, COAPT suggests that you have to catch patients with cardiomyopathy and severe MR that are not too far gone when their left ventricles are really dilated, which was the case for many patients in MITRA-FR. You could argue that those patients are too far gone for the MitraClip to actually help them.

Another difference is that the severity of MR was higher in COAPT. The sweet spot is thus probably patients with not very dilated ventricles, but low ejection fraction — 31% was average in the trial — and at least having moderate-to-severe to severe mitral regurgitation.

Regarding optimal medical therapy, in the MITRA-FR trial, you had to be on medical therapy, but you could have some changes made as you went through the trial on both sides. In COAPT, this was minimal (< 5%).

Everyone is asking where we go from here after MITRA-FR and COAPT. There is at least one other trial called RESHAPE-HF2 that is ongoing in Europe. My feeling is that, because the two trials enrolled different patient populations, we do not necessarily need another trial in this space. In some ways, given the results of COAPT, some may say that it would be unethical to randomize patients with the same criteria as COAPT to medical therapy alone, knowing that there is also a mortality benefit.

I do not know if there will be a tiebreaking trial ever in this space, but going forward, this is likely to be the gold standard with the caveat that it is not yet FDA-approved for that indication. That would need to come.

Probably in a good way, this complicates the field for the other devices. There are so many devices that are being tested in many different stages of development. Unless they are not MitraClip candidates, it may be unethical again for the same reason to randomly assign them to the new device vs. medical therapy. They would need to have potentially a tiered approach.

The results of this trial have been described as spectacular and breathtaking. It is an amazing trial and is extremely important because this is a difficult population of patients with a high underlying mortality and morbidity.

The implication is, for this group of patients with HF and mitral regurgitation who have hit the limit as far as medical therapy, there is another option, which this trial conclusively shows will improve their quality of life and improve their survival.

There are significant differences in COAPT and MITRA-FR. A very important part of COAPT, for which I was a principal site investigator, was the participation of HF doctors and achievement of maximum medical therapy before a patient was accepted into the trial. As a result, the patients that were in the trial had more mitral regurgitation and were sicker. From what I understand with MITRA-FR, there was no such requirement, and their HF treatment was allowed to change before and after their MitraClip.

The reason that is important is that mitral regurgitation is very sensitive to variations in medications, BP, etc. We had many patients that started out with severe mitral regurgitation, but by the time they reached their maximum medical therapy, it was no longer as severe, and they were excluded from the trial.

An important outcome of the trial was how safe the procedure is. The complication rate was only about 3% in a very sick population. That is important because if you are having an invasive intervention in a sick population, you want to know that it is safe. It has been shown to be safe.

The outcomes of COAPT were staggering. As a surgeon who deals with this in the cath lab and also in the operating room, the management of patients with severe functional mitral regurgitation has been moderately successful at best. We were anticipating some pathway that would give us better outcomes in addition to guideline-directed medical therapy.

In these high-risk patients with an ejection fraction of approximately 30%, surgical outcome has been good, but not phenomenal. Therefore, a lot of these patients have been treated with guideline medical therapy with or without CRT. What this study shows is that in addition to guideline-directed medical therapy, decreasing that mitral regurgitation is a safe procedure that significantly reduces mortality, and more importantly, decreases hospitalization and improves quality of life. This is extremely impactful for a patient. Not only the individual patient, but for health care resources for this very sick patient population. I am exceedingly encouraged and optimistic of the future management in these complex patients.

It would have been nice to have both COAPT and MITRA-FR] have positive results, but there are differences between the studies. The rigor that was performed with COAPT, especially with guideline-directed medical therapy, was like no other and has a 2-year follow-up. When I look at both studies, I am more impacted by COAPT, especially since I know the rigors of what it took to perform.

We would hope that MitraClip will become approved in the U.S. for this patient population. Going forward, it will be important to tease out which patient cohorts had a successful recovery and those who did not. This will be important from anatomic considerations and patient preoperative characteristics. We have just now gotten to the tip of the iceberg in treating patients with functional mitral regurgitation. This is a very exciting time indeed.