Using a MitraClip as a bridge to heart transplantation is safe and may even lead to functional improvements that permit patients to be removed from the transplant list, results of a retrospective, multinational registry suggest.
The findings fly in the face of prevailing notions about the degree of left ventricular degeneration relative to mitral regurgitation that can be modulated by the use of a clip.
“MitraBridge demonstrated that in well-selected patients, the use of MitraClip as a bridge strategy to heart transplantation . . . can be safe in 87% of procedures with no deaths at 30 days and was also effective, with two-thirds of patients free from the composite of adverse events, 15.5% becoming eligible for transplantation, and near to one-quarter of patients being removed from the transplant list,” said Cosmo Godino, MD (San Raffaele Hospital, Milan, Italy).
Godino, reporting the results during today’s late-breaking clinical science session at TCT Connect 2020, noted that patients with severe/end-stage heart failure comprise up to 10% of the heart failure population and this number is growing. Moreover, the marked imbalance between clinical demand and the supply of donor hearts means that wait times often extend 12 months, proving lethal for many patients. According to 2019 European numbers, approximately 13% of patients on the Eurotransplant waiting list died within a year, a figure that rose to nearly 20% by 3 years.
Commenting on the study for TCTMD, Shelley Zieroth, MD (St. Boniface Hospital, Winnipeg, Canada), called the findings “intriguing,” noting that many heart failure centers around the world have likely tried using the MitraClip in this particular setting, outside of current indications, in the hopes of offering something—anything—to these very sick patients when a transplant is not in the offing.
“It’s a strategy that many centers are exploring, and I was impressed by the number of patients, here, that were delisted and had functional improvement,” Zieroth said. “That’s a feat in itself.”
There are likely “a lot of other patients out there” that could be added to this pool, Zieroth added, saying that getting these numbers would help clarify clip performance across an even more diverse range of hospitals.
The MitraBridge results were simultaneously published in the Journal of Heart and Lung Transplantation.
A (Tiny) Bridge to Transplant
The MitraBridge registry, launched in June 2018, includes 17 centers from Europe and Canada, enrolling advanced/end-stage heart failure patients with 3+ or 4+ mitral regurgitation. In all, 119 patients were included in this analysis and spanned across patients deemed to be “pure bridge” candidates who were actively waiting transplant but who had a low likelihood of a match due to body weight or blood type; “bridge to decision” (BTD) patients waiting for a clinical decision on eligibility; and a “bridge to candidacy” (BTC) group who, due to other clinical conditions that were potentially reversible, were currently contraindicated for transplant.
When all three groups were combined, the median age of the patients was 58 years, 77% were men, median LVEF was 26%, and 95% of patients were NYHA class III-IV. Nearly 44% of patients were in INTERMACS category 5-6 and 16% were INTERMACS 7. Of note, left ventricular end diastolic volume index (LVEDVI), reflecting ventricle size, was a mean of 122.5 mL/m2.
In all, 104 patients (87.5%) were successfully implanted with a clip and survived the periprocedural period (30 days) and two-thirds remained free of adverse events at 1 year. At a median follow-up of 532 days, 13 out of the 116 patients with available data (11%) had died, including nine cardiac deaths, primarily due to heart failure. Seven patients underwent urgent heart transplantation, and 21 required implantation of a left ventricular assist device (LVAD) due to failed MitraClip bridge therapy. Another 19 patients got an LVAD as bridge during follow-up.
Elective transplantation was ultimately performed in 17 patients (15%) after a median delay of 477 days, but 27 patients (23.5%) no longer had an indication for transplant due to significant clinical improvement, including five in the “pure bridge” group, 22 in the BTD group, and 10 in the BTC group. Eight patients previously on the BTD and BTC lists were able to move onto the active transplant list. All showed improvements in MR grade and significant reductions in NYHA functional class, with 89% of patients experiencing an improvement of at least one grade, leaving none in NYHA IV.
“Of course, these results should be considered exploratory and hypothesis-generating,” Godino cautioned.
Strikingly, four out of five patients in this registry would have been ineligible for the COAPT trial, where the mean LVEDVI was 101 mL/m2 as compared to 135 mL/m2 in MITRA-FR, a factor often cited as the reason for why these trials differed so starkly, with COAPT—but not MITRA-FR—demonstrating a benefit of the clip. COAPT investigators and others have speculated that patients with mitral regurgitation that is “disproportionate” to the left ventricular geometry are less likely to benefit from the MitraClip.
Asked by TCTMD how to explain this apparent contradiction, Godino acknowledged the results were a surprise, even to investigators. Their best guess relates to the age of the patients who were roughly 20 years younger than the patients enrolled in MTRA-FR and 15 years younger than those in COAPT. “From a pathophysiological point of view, we can suppose—[although] we need more data also with cardiac MRI, maybe in the future—that the correction of the mitral regurgitation independently from that ‘proportional/disproportional’ grade, from the grade of the left ventricular dilatation, can induce a benefit in younger patients.”
David Cohen, MD (Kansas City, MO), a COAPT investigator, speaking during a press conference, pointed out that a similar observation was made in the COAPT trial where nine patients in the optimal medical therapy group ultimately required transplantation as compared to four in the MitraClip group.
“I think one of the things this highlights is that there’s a lot we don’t understand about which LVs are going to benefit, the LV mechanics, and there’s a lot of variability,” said Susheel Kodali, MD (NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY), also speaking to the press. “I think one of the biggest things from this trial, and this is a very sick population, is that the procedure was safe. So outside of cost, you didn’t lose a lot. . . . The fact that 25% came off the transplant list, to me, is probably one of the key numbers.”
Making Sense of the Data
Zieroth pointed out that the quality of medical therapy among the registry patients was excellent—captured by the fact that a high proportion of patients in the study had defibrillators implanted, well above what has been seen in contemporary clinical trials—reflecting the expertise of the centers involved. This is a factor to consider if MitraClip therapy is being used in heart transplant patients at less-experienced institutions, where the outcomes might not look so rosy. She also noted that the survival rates at 1 year in MitraBridge may in part reflect the fact that nearly 60% of patients here were INTERMACS 5, 6, or 7, so the results might not apply to the sickest patients.
She would like to see a randomized controlled trial of clip therapy and said that such a trial would still be appropriate and ethical, despite the promising findings of MitraBridge. “It’s great to be hopeful that we’re doing the right thing, but it doesn’t absolutely prove it,” Zieroth noted, “and there’s lots of potential confounders as well.”
Following Godino’s late-breaking presentation, panelists also struggled with the mix of patients included in the registry analysis.
“You’ve got patients on the waiting list, patients waiting for a decision, and you’ve got patients who are not candidates for that and I’m not sure what patient I can discern from this [who] would benefit from this,” said Michael Mack, MD (The Heart Hospital Baylor, Plano, TX), who also pointed out that some patients actually went in wrong opposite direction, needing urgent transplant or an LVAD. “So we don’t know that this is safe and that we didn’t actually accelerate the need for a VAD or transplant with that.”
Vinod Thourani, MD (Piedmont Heart Institute, Atlanta, GA), agreed. “I’m having a hard time discerning which kind of patient population I’d want to use this in,” he said, pointing out that information on right ventricular (RV) failure was not presented. “A lot of these patients who are getting transplant also have concomitant RV failure and tricuspid regurgitation . . . and that becomes a component of who gets a clip and who doesn’t get a clip. So there are too many different types of patients that we’re talking about and I’m unable to tell you who should get [a MitraClip] and who’s going to get worse with this therapy.”