EXPANDed: Atrial Secondary MR Patients Get Clinical Benefit From TEER

Patients with atrial fibrillation who also have atrial secondary mitral regurgitation (SMR) see numerous clinical improvements with MitraClip (Abbott) transcatheter edge-to-edge repair (TEER), according to postmarket data gleaned from the EXPANDed cohort.

The 1-year results showing reductions in MR severity, LV end-diastolic volume, and heart failure hospitalizations, as well as better quality of life, were presented online Monday as part of the Heart Failure Society of America (HFSA) 2024 meeting. The in-person conference had been cancelled at the last minute due to the impending Hurricane Helene.

Atrial SMR refers to the specific subset of individuals with mitral regurgitation whose mitral annular enlargement stems from left atrial dilatation, rather than LV dysfunction or remodeling.

As presenter Mark J. Ricciardi, MD (Endeavor Health, Evanston, IL), told HFSA viewers, little is known about how underlying pathology in secondary mitral regurgitation responds to edge-to-edge repair; the bulk of patients treated to date developed functional MR secondary to ischemic or nonischemic disease impacting the left ventricle. “The point here was to evaluate each SMR population and their outcomes following a MitraClip procedure from the global expanded studies,” he said.

EXPANDed combines the EXPAND and EXPAND G4 studies of the MitraClip NTR/XTR and G4 systems, respectively, providing a real-world perspective on outcomes obtained in the US, Canada, Europe, the Middle East, and Japan.

What they found, said Ricciardi, is that “1-year outcomes suggest that atrial SMR subjects in EXPANDed experienced clinical benefit when treated with the MitraClip system.”

Ricciardi, speaking with TCTMD, emphasized that the subset of SMR patients with atrial pathology represents an unmet clinical need. “We knew that there were many patients out there with this, [who] remained symptomatic and remained with severe regurgitation despite efforts at rhythm control and medical therapy.”

The uncertainty was how far, in this complex condition, addressing the MR might impact outcomes. “So much of the data out there suggests that if you reduce mitral regurgitation, independent of anything else, people do better. I mean, I know it sounds kind of obvious, but with medical science, you want to prove that point.”

Patients with atrial SMR, also referred to as atrial functional MR, are an increasing focus for investigators, Mohamad Alkhouli, MD (Mayo Clinic, Rochester, MN), agreed. He co-authored an editorial on the topic to accompany a prior analysis of the EXPAND cohort as well as data from the Cedars-Sinai Medical Center and Heart Center Bonn experiences, all published together in 2022 in JACC: Cardiovascular Interventions.

This latest study extends what was found in EXPAND, Alkhouli commented to TCTMD. Before data like these were available on the atrial SMR population, there were concerns that these patients might not fare as well as other patients with functional MR. This is “because we view left atrial enlargement and chronic A-fib, which are the hallmarks of this disease, as negative predictors of outcomes,” he explained, adding that there also was the false impression that this patient subgroup had a higher comorbidity burden.

What the totality of the data now shows, said Alkhouli, is a “win” for MitraClip, in that these patients with atrial SMR “maybe have a slightly more favorable clinical profile, and they do equally well technically, and maybe slightly better clinically, over time.”

Are the people with mitral regurgitation the same as all the other HFpEF patients? Definitely not. Mark J. Ricciardi

Among the 2,205 EXPANDed participants, 967 had SMR. Out of this group, 160 (16.5%) had atrial SMR, which was defined as a history of atrial fibrillation and LVEF ≥ 45% plus one of three left-atrial characteristics: volume index larger than 34 mL/m², diameter exceeding 4 cm in men or 3.8 cm in women, or diameter index greater than 2.3/m².

The atrial SMR patients were older than the overall SMR group (mean age 78.2 vs 75.1 years) and were more often female (50% vs 41%). They were less likely to have had a prior MI (22.3% vs 30.9%) or been treated with a cardiac resynchronization therapy device, implantable cardioverter-defibrillator, or permanent pacemaker (7.5% vs 17.4%) than SMR patients as a whole. Within the atrial subgroup, 73.8% had NYHA class III or IV symptoms at baseline and patients had enlarged left atrial volumes (mean 120.2 mL) with preserved ejection fraction (mean LVEF 56.3%). Nearly all were on some sort of heart failure medication, most commonly beta-blockers (81.3%).

Acute procedural success was 97.5% in atrial SMR and 95.8% in all SMR, with mean procedure times of 92 versus 86 minutes and a mean number of 1.4 clips implanted per patient. Nearly two-thirds received one clip. There were no procedural deaths or conversions to mitral valve surgery.

Event rates were “very low,” Ricciardi reported. Apart from two deaths before 30 days, all major adverse events occurred between 30 days and 1 year. There were no instances of embolization.

EXPANDed: 1-Year MitraClip Outcomes by Underlying Pathology

Rates of heart failure hospitalization decreased between baseline and 1 year by 56% among atrial SMR patients and 60% among all SMR patients.

Also at 1 year, 95.2% of the atrial-SMR group and 94.3% of the all-SMR group had MR grades of 1+ or lower. Most patients in these two populations—79.5% and 77.9%, respectively—were in NYHA class I/II. Kansas City Cardiomyopathy Questionnaire overall summary score rose by 19 points in both groups over the course of a year (P < 0.001 vs baseline).

Among the atrial SMR patients, LV end-diastolic volume dropped by a mean of 16 mL between baseline and 1 year (P < 0.001).

This sort of natural experiment, albeit an uncontrolled one, conducted in these patients provides really interesting clues and perhaps some optimism. Nancy Sweitzer

Nancy Sweitzer, MD, PhD (Washington University School of Medicine, St. Louis, MO), the assigned discussant for Ricciardi’s presentation, described the EXPANDed atrial SMR cohort as “a particularly interesting group of patients treated in the expanded postmarket experience.”

Essentially, said Sweitzer, these patients are presenting with heart failure with preserved ejection fraction (HFpEF). As is the case for many with HFpEF, “they have multiple contributors to the HFpEF syndrome, [here] one of which is obviously their significant mitral regurgitation,” she explained, adding that they may well also have left ventricular disease as a contributor to their condition. “And then of course everyone in the cohort also had atrial fibrillation,” Sweitzer commented.

She observed: “So, really, I think this is a chicken-egg problem, right? Is the A-fib primary, resulting in left atrial enlargement, annular dilatation, and ultimately mitral regurgitation, which was treated then with the MitraClip? Or is HFpEF primary, increasing intracardiac pressures [and] leading to left atrial enlargement resulting in A-fib, annular dilatation, and then MR?”

Given that in neither scenario is MR primary, she continued, “the question of whether treating the MR results in clinical improvement is really important, because these patients could still be left with HFpEF, persistent symptoms, and risk.”

For Sweitzer, the new EXPANDed data provide valuable insights. “Hearing the results of this sort of natural experiment, albeit an uncontrolled one, conducted in these patients provides really interesting clues and perhaps some optimism,” she said.

Future topics to be addressed are whether women and men benefit equally; if there are any differences among patients whose atrial fibrillation was paroxysmal, persistent, or permanent; and if the impact of treatment is influenced by the degree of underlying left atrial or left ventricular structural abnormality.

“HFpEF guidelines have long advised that we screen and treat etiologies and comorbidities in patients with HFpEF, because they always have multiple contributors,” Sweitzer noted. “And I think the data shown today suggests that we should add assessment and treatment of atrially mediated mitral regurgitation to our HFpEF toolbox.”

Perhaps, she suggested, treating both the arrythmia and the regurgitation could reduce the toll taken by HFpEF.

Key questions going forward, said Alkhouli, are how atrial SMR should be defined, since criteria currently vary, and how transcatheter mitral valve replacement would compare to TEER in this setting. Particular to the EXPANDed analysis, he cited a missed opportunity to compare older versus newer-generation MitraClip designs.

Some clarity will come from the upcoming TCT 2024 meeting later this month, where an analysis of the MATTERHORN trial will compare outcomes of MitraClip versus surgery in patients with atrial pathology.

As for what should come next, Ricciardi said that given the limitations of observational data, a randomized controlled trial could shed additional light on what TEER might add beyond optimal medical therapy in these patients with atrial SMR who have HFpEF. “There's evolving evidence that there are good meds besides just a diuretic for people who have preserved ejection fraction,” he noted. “And are the people with mitral regurgitation the same as all the other HFpEF patients? Definitely not.”

While some in the field might argue for such a trial, “I would actually go out on a little bit of a limb here and argue that although it would be nice, it's not mandatory,” said Ricciardi, adding that this is because it’s already possible to see firsthand how the decision-making plays out.

In daily practice when counseling patients, Ricciardi said, he checks to make sure they’re on the medical therapies thought to benefit HFpEF. His advice to them: “If you are and you remain symptomatic and your mitral regurgitation is 3+ or greater, I'm pretty darn convinced that we can safely repair that valve, reduce your MR, and make you feel better.”