- It's my pleasure to speak with you this morning. My name is Dr James Gammie and I am system chief of cardiac surgery at Johns Hopkins. And I presented at this weekend at the American Heart Association, on behalf of my colleagues in the International Cardiothoracic Surgery Trials Network, the results of our trial, which was entitled: "Evaluating the Benefit of Concomitant Tricuspid Repair During Mitral Valve Surgery".
Reasoning for this Study
Well, this is a very common question or dilemma that faces us as heart surgeons. One of the most common operations we do is for mitral regurgitation, degenerative mitral regurgitation, and it is frequent that there is some degree of tricuspid valve regurgitation that accompanies the mitral regurgitation. And we have a clear acceptance amongst our community that we should fix the tricuspid regurgitation when it is severe. However, there is a lot of controversy over to whether or not to fix less than severe, so, in other words, moderate or even less than moderate, tricuspid regurgitation at the time of mitral valve surgery. And, in fact, this is reflected in the current guidelines; both the US guidelines, as well as the European guidelines, have a class 2A recommendation for repairing the tricuspid valve at the time of mitral valve surgery, under certain circumstances. But those guidelines are not supported by prospective randomised data.
Study Design and Patient Population
So it was on that background that we made the decision, a number of years ago, to conduct a prospective randomised trial to try and answer that question. And it was a fairly straightforward design. You were eligible to be in the trial if you had severe mitral regurgitation, degenerative MR and were going for surgery, and you were included in the trial if you had either moderate tricuspid regurgitation or less than moderate tricuspid regurgitation and dilation of the tricuspid annulus, which, if you're interested in details, was absolute value about 40 millimetres or an index value above 21 to body surface area. So those were the patients that were enrolled and we did a one-to-one allocation to either isolated mitral valve surgery or mitral valve surgery with tricuspid valve repair. And one of the interesting and unique aspects of this trial is that we standardised the operative approach. One of the challenges with surgical trials is that there is significant variation from surgeon to surgeon. So what was specified in this trial was that all patients were repaired within an undersized rigid non-planar annuloplasty device. And by "undersized" we meant a size 26 through 30. And, as you may know, the devices typically come between size 26 and 40. So we were on the lower end. We undersized with the rationale that the key mechanism in a functional tricuspid regurgitation is annular dilation. So by placing this annuloplasty device, we could downsize the annulus and fix it and in so doing fix the tricuspid regurgitation. So that was the general outline of the trial. Our primary endpoint was a combined endpoint, which included three components: death, re-operation or progression of leakage, tricuspid leakage, which was defined as either severe TR, which was almost always the case when we found it, or progression by two grades. So that was the primary endpoint and we assess this at two years of follow-up after surgery. So, a total of 401 patients were enrolled. The patient population was quite similar to those patients that would typically be in an operating room for degenerative MR; they were in their late 60s. They had preserved ejection fraction. They almost all had severe mitral regurgitation. About a third of our patients, 37%, met the criteria for moderate TR, whereas the other two thirds had less than moderate and annular dilation to get into the trial. About 44% percent of our patients had atrial fibrillation. And we found that the amount of time on the heart lung machine was extended by 34 minutes, amongst those undergoing tricuspid repair. We found that the overall mitral repair rate was about 90% and about half of the patients had a concomitant procedure, such as coronary bypass surgery, or, most commonly, atrial fibrillation ablation.
The primary endpoint, which you will recall is death, re-operation or progression of TR, was substantially more common in those patients that just had mitral valve surgery. And in fact, we found that 10.2% of patients in the mitral alone group
reached the endpoint, whereas only 3.9% did in the tricuspid annuloplasty plus mitral repair group. And this was driven, there were no re-operations in either group. The mortality rate was low and about 4% at two years in both groups. And this was really driven by a difference in progression of TR which was almost a never event in the tricuspid annuloplasty group, but which was substantially more common. And in fact, 5.6% of patients that were not treated, with an annuloplasty ring on the tricuspid side, progressed to severe tricuspid regurgitation. And we did a post-hoc analysis of our two subgroups. Remember, one was the moderate TR group and the other was less than moderate TR with annular dilation. And we found that there really wasn't a significant difference in the endpoint in the less than moderate group with tricuspid dilation, whereas we saw a big difference in the moderate TR group. So, the moderate TR group, 14.5% of that group progressed to severe TR and zero did in the tricuspid annuloplasty group. And in fact, if we looked at the degree of TR out to two years, the presence of moderate or severe TR was 25% in the untreated group and it was only 3.4% in the treated group. We did find one key aspect of this was, and as we anticipated, that there would be a higher rate of need for permanent pacemaker implantation amongst those patients that had the tricuspid valve repair. And in fact, those numbers were 14.1% of patients in the tricuspid repair group needed a pacemaker, whereas only 2.5% in the non-tricuspid group.
To sort of synthesise that, the take-away is that the undersized non-planar rings were highly effective at preventing progression of tricuspid regurgitation, over the two-year study time period. However, the placement of these came at a slightly increased cost and that was an increased risk of permanent pacemaker implantation. And in post-hoc analyses, which were not pre-specified and were underpowered but were done to inform our primary outcome, it certainly appeared as though the risk of progression was essentially limited to those patients with moderate TR. So I think the take-aways from this are that our guidelines currently are based on annular dilation as a really key decision-making or data point to make a
decision about whether or not to do a tricuspid annuloplasty and I think these results call into question the basis of those recommendations. And in fact, our experience was that the annular dilation was not related to tricuspid progression. On the other hand, we found a significant rate of progression in the untreated group that had moderate preoperative TR. So, in that group, I think surgeons and their patients and cardiologists in particular will want to think very carefully about fixing those patients.
And I also think we are looking forward to doing further analyses to try and understand better why it is that we had a high
pacemaker implantation rate, and it may well be related to technique, technical aspects. It also may be related to management of those patients and timing of pacemaker implantation and whether or not we waited long enough for a native rhythm to come back in those patients. So I think some of those questions remain and, most importantly, these patients are relatively young. They have a normal, long life expectancy and so the impact of this decision will be played out in the coming years. And we plan to follow these patients on a regular basis and I think we look forward to presenting data out to five years, that will further inform this decision. We didn't really see a difference in our two patient populations
in clinical outcomes at two years and so, again, following them for five years or more will be helpful in informing that. This trial took place in three countries: the United States, Canada, and Germany. And I just like to thank our patients for participating as well as to all the investigators and the coordinators and the research teams and the Cardiothoracic Surgery Trials Network, who put forth a spectacular effort here. Our funding sources from the NHLBI and the German Heart Group and finally the Data Coordinating Centre at Mount Sinai, which just did a spectacular job in leading this trial.