Real-world Primary MR TEER Outcomes Carry a Reminder: Do Better

NEW ORLEANS, LA—A snapshot covering nearly a decade of transcatheter edge-to-edge repair (TEER) for primary mitral regurgitation (MR) suggests operators have been getting better at these procedures as time goes on, but also that a sizeable proportion of patients have been left with residual MR levels substantial enough to have an impact on survival and subsequent hospitalizations.

Presenting 9 years’ worth of MitraClip outcomes from the STS/ACC TVT Registry at the American College of Cardiology/World Congress of Cardiology (ACC/WCC) 2023 meeting, Raj Makkar, MD (Cedars-Sinai Medical Center, Los Angeles, CA), stressed that most patients come through these procedures meeting the benchmark of “success” as defined by this analysis. What’s abundantly clear from this study, however, is that leaving behind as little MR as possible, without creating significant mitral valve stenosis, is the sweet spot that operators need to be aiming for to achieve the best for their patients.

“Successful repair, defined as reduction of MR severity to moderate or less and no severe stenosis, was achieved in 89% of the patients,” he said during a featured clinical research presentation. “Both residual MR and mitral gradients were associated with death and heart failure (HF) readmission at 1 year, with the best clinical outcomes in patients with mild or less residual MR and no mitral stenosis.”

A number of other registry studies of TEER have recently made headlines, including PRIME-MR and CLASP IID, but these have typically been focused on expert centers: the data presented by Makkar at ACC/WCC represents the largest real-world, consecutive series analyzed to date.

A Decade of Learning

It’s been nearly 10 years since the US Food and Drug Administration approved the MitraClip (Abbott) for edge-to-edge repair in degenerative MR (DMR) and in that time more than 60,000 consecutive TEER patients have been included in the STS/ACC TVT Registry. Between January 1, 2014, and June 30, 2022, 19,088 patients got one or more MitraClips for “pure” primary MR, defined as originating from abnormal leaflets and/or chordae as a result of prolapse or flail, and were included in this analysis, jointly led by Makkar and Joanna Chikwe, MD (Cedars-Sinai Medical Center).

The mean age of patients was 82 years, 49% were female, mean STS score was 4.6%, and patients had a range of comorbidities including chronic lung disease (32%), recent HF events (77%), atrial fibrillation/flutter (60%), and coronary artery disease (47%). In all, 82.2% had severe MR (4+) at baseline, while 17.8% had moderate-to-severe (3+); in terms of pathology, 80.2% had leaflet prolapse and 62.7% had flail leaflet.

By 30 days postprocedure, 2.7% of patients had died, 2.6% had been readmitted for HF, 1.7% had an unplanned cardiac surgery or intervention, and 1.4% had a stroke or TIA.

Echocardiographic results at 30 days, which were site reported, painted a somewhat disappointing picture. While MR severity of ≤ 2+ was part of the primary endpoint in the study—and 95.3% of patients were in this category at 1 month—only 65.7% of patients had MR severity ≤ 1+ at this time point. Meanwhile, mitral stenosis of moderate or less (mean mitral valve gradient of < 10 mm Hg), was seen in 95.6% at 30 days.

Thus, the primary endpoint of “MR success,” defined as MR ≤ 2+ and mean mitral gradient of < 10 mm Hg was seen in 89% of patients at 30 days when averaged over the 9 years of the study. Notably, said Makkar, those success rates have been creeping higher, starting at 81.5% back in 2014 and reaching 92.2% in 2022, likely as a result of “collective learning” as well as individual operator experience. Critically, he said, the advent of three-dimensional echocardiography and refinement of structural imaging protocols have also played a key role in improving procedure success.

What’s clear, however, is that passing the trial-defined benchmark of success does make a difference for patients, Makkar said. Mortality at 1 year, for example, was 14% for those successfully treated according to the study definitions, compared with 26.7% in those whose procedures did not achieve the thresholds for residual MR and mitral valve area. Both HF readmissions and mitral valve reinterventions following a similar pattern.

But that “successful” MR cutoff of ≤ 2+ is broad. In an analysis comparing patients whose procedures left them with mild or less MR and a gradient < 10 mm Hg against those with similar gradients but moderate MR, mortality rates at 1 year were significantly lower: 12.3% vs 18% (adjusted HR 0.73; 95% CI 0.66-0.82), as were HF readmissions: 7.3% vs 10.8% (adjusted HR 0.68; 95% CI 0.60 - 0.78).

Speaking with TCTMD, co-PI Chikwe observed that STS data for surgical mitral valve repair show patient mortality rates in the range of 0.3%, whereas the rate for these TEER patients in this registry was 2.7% at 30 days. “Surgery is incredibly safe, and it's been incredibly effective at delivering mild mitral regurgitation,” she said. That has implications for very careful patient selection going forward, but also makes the case for high-quality procedures that leave as little residual MR as possible.

“I think what we’ve learned here, beyond the fact that TEER can be delivered very, very safely, is that it's really important to eliminate mitral regurgitation without causing stenosis and that there's a survival benefit associated with mild mitral regurgitation compared to moderate regurgitation,” she said. “We've all assumed that moderate regurgitation wasn’t a good thing, but I don't think that we've been able to illustrate that as clearly as these data show.”

Another way to look at it, she continued, is that as many as 30% of patients in this series had residual moderate MR, and that was associated with worse survival and more HF hospitalizations. “That may be acceptable for a palliative care strategy,” she said, “but it is not acceptable in patients who may otherwise be candidates for a surgical repair.”

Real-world Reactions

Commenting on the registry findings for TCTMD, Gilbert Tang, MD (Icahn School of Medicine at Mount Sinai, New York), said he found the data somewhat “concerning,” noting that a surgeon would never deem residual MR of 2+ or less “successful,” particularly since studies have documented the clear link between residual MR and mortality, a finding affirmed in these data.

“One thing that would be interesting would be to look at the device iteration and the impact of that on MR reduction,” since the third- and fourth-generation MitraClip devices have been shown to improve upon the earlier residual MR rates, Tang said. “We also know there's a learning curve with any device, so would we see any improvement in MR reduction if we looked at this by tertile or quartile of operator experience or volumes during the study period? Because that would be an encouraging sign.”

“Another thing that I would point out is that these data are discordant with other published data such as the EXTEND G4 registry, although those were expert sites and this is real-world data,” said Tang. That raises another question, he continued: “should TEER be proliferated to other cardiac sites, or similar to mitral valve surgical repair, should it only be done at experienced sites?”

During the discussion following Makkar’s presentation, Amy E. Simone, PA-C (Piedmont Heart Institute, Atlanta, GA), pointed out that this is the first large-scale analysis in this particular population, providing “a great springboard” for future work. A key question, she said, is the choice of MR ≤ 2+ as the definition of success in this analysis.

“In this real-life registry, where often the device is used for less-than-optimal anatomy, our goal was to find a threshold that would predict some degree of impact on outcomes, so we chose 2+ or less residual mitral regurgitation as a starting point,” Makkar replied. And indeed, patients whose procedures met this definition of success did, indeed, have fewer deaths, rehospitalizations, and reinterventions, he noted. “I think retrospectively, it was not a bad definition, but I think it is important to point out that our goal was not to say that that is enough. . . . I think the message that should come out of this is that we should strive to get the least amount of residual MR that is possible without increasing gradients.

Less-invasive options, such as percutaneous transcatheter mitral valve replacement, might be better options for certain patients down the line, Makkar suggested. “And I think it is important to also point out that these thresholds may be acceptable in these high-risk patients and older patients, but when we talk about younger patients with good pathology, we expect a lot more and the definitions need to be a lot more stringent: we should expect mild residual MR and no significant stenosis.”