MR Improves in Half of Low-Flow/Low-Gradient AS Patients Undergoing TAVR

Most patients with low-flow/low-gradient aortic stenosis (AS) have some form of mitral regurgitation (MR), but transcatheter aortic valve replacement improves MR in roughly half of this group, according to a new analysis of the TOPAS-TAVI registry.

For those who do not see an improvement in MR following TAVR, however, there is a significantly increased risk of all-cause and cardiac mortality, as well as rehospitalization for cardiac causes, at 1 year when compared with patients who had an improvement in MR.

“It’s a complex population,” said senior investigator Josep Rodés-Cabau, MD (Quebec Heart & Lung Institute/Laval University, Quebec City, Canada), referring to patients with low-flow/low-gradient AS and MR. “But once you establish [the diagnosis], you can move forward with treatment. When you make a decision, you have to understand that in some cases, treating only the aortic valve isn’t going to be enough. In many cases, yes, it will be enough, but there are still a significant proportion where a second intervention may be necessary.”

To TCTMD, Rodés-Cabau said low-flow/low-gradient AS represents roughly 5% to 10% of the population with severe AS, and they have worse long-term outcomes compared with patients with high-gradient AS and/or preserved LVEF. Many of those with low-flow/low-gradient AS also have moderate-to-severe MR. “The reason is that [low-flow/low-gradient AS] patients have low ejection fractions and dilated left ventricles, which is associated with functional MR,” said Rodés-Cabau. “It means the prevalence of MR in this group of patients is higher than in the typical TAVR population.”

In the general population with severe AS and mitral valve disease, MR improves in roughly half of patients who undergo TAVR, but the rate of improvement is higher if patients have functional MR. For patients with moderate-or-severe functional MR, approximately two-thirds will see an improvement in the degree of MR following TAVR, which is attributable to positive ventricular remodeling associated with the treatment of AS with TAVR, said Rodés-Cabau.

TOPAS-TAVI and the MR Impact

The new study, published February 12, 2020, in JACC: Cardiovascular Interventions, is a substudy of the TOPAS-TAVI multicenter registry and focuses exclusively on the incidence of MR and its clinical impact in patients with low-flow/low-gradient AS, defined as an aortic valve area < 1 cm² (or an indexed aortic valve area ≤ 0.6 cm²/m²), a mean transvalvular gradient < 35 mm Hg, and LVEF ≤ 40%. Of the 308 patients, mild and moderate-to-severe MR was present in 118 and 115 patients, respectively. For those with mitral valve disease, 77.3% had functional MR and 22.7% had a mixed etiology (functional and organic MR).

More than 44% of patients died after a median follow-up of 2 years; 68 of those 138 individuals died from cardiovascular causes. There were no significant differences in all-cause mortality, cardiovascular mortality, or heart failure hospitalizations among patients with mild MR and those with moderate-to-severe MR.

At 1-year follow-up, echocardiographic data was available in 131 patients with baseline MR. In the overall cohort, MR improved by at least 1 grade in 44.3% of patients and remained unchanged or worsened in 55.7% of patients. For the patients with functional etiology, MR improved by 1 grade in 44 of 105 patients. For those with a mixed etiology, MR improved in 12 of 26 patients. Among the 53 patients with moderate-to-severe MR at baseline, there was an improvement in MR by at least 1 grade in 62.3% post-TAVR.   

Importantly, the patients who showed no evidence of an improvement in MR following TAVR were at a significantly increased risk of adverse events compared with those who improved. Lack of improvement from baseline to 1 year was associated with a higher risk of all-cause mortality (HR 2.02; 95% CI 1.29-3.17), cardiac mortality (HR 3.03; 95% CI 1.27-7.23), rehospitalization (HR 1.50; 95% CI 1.01-2.22), and cardiac rehospitalization (HR 1.50; 95% CI 1.04-2.15).

Christopher Meduri, MD (Piedmont Heart Institute, Atlanta, GA), who wasn’t involved in the study, said that for patients with low-flow/low-gradient AS, the presence of MR “complicates, but doesn’t preclude” treatment with TAVR. “We realize these patients benefit from some type of treatment so we don’t deny them treatment even if they do have significant MR,” he told TCTMD. “The challenge right now is that we don’t have an effective way to determine if it is going to help the MR or not.”

For Meduri, the most interesting aspect of the TOPAS-TAVI analysis is that the study identified no baseline clinical or echocardiographic variables in the univariate analysis that predicted clinical improvements in MR. Instead, postprocedure changes in LVEF and changes in left ventricular end-diastolic diameter were both associated with a change in MR grade at 1 year. “It was how they improved after we did an intervention that predicted how they did,” he said. “We really only have a better understanding of prognosis after we have done the TAVR intervention.”

COAPT-Like Patient After TAVR 

One of the remaining questions is whether or not treating residual MR after TAVR would translate into improved clinical outcomes. The present study provides little insight into that question, said Meduri, noting that only three of the 115 patients with moderate-or-greater MR underwent mitral valve repair following TAVR and only one patient had an improvement in MR.

“We will need a larger study to see if these patients will benefit from a mitral valve intervention,” he said. “But as a clinician, it reminds me that we need to be more aggressive in our post-TAVR screening and flagging these patients that have a lot of MR afterwards to look at them closely. We need to have a long, hard conversation about whether they need a mitral-valve intervention or not.”  

To TCTMD, Rodés-Cabau said that many of the patients with low-flow/low-gradient AS treated with TAVR resembled COAPT patients after the intervention because they still had low LVEFs.  

“If you solve the problem of aortic stenosis, many of them recover the ejection fraction, but a lot of them recover only partially,” he said. “If MR persists, even if we have no proof, I think you could consider these patients as having functional MR. If you have optimized their heart-failure treatment, and they are still symptomatic, then I think these patients could benefit from an intervention at the level of the mitral valve, which means MitraClip.”

In an editorial, Martin Swaans, MD, PhD, and Livia Gheorghe, MD (St. Antonius Hospital, Nieuwegein, the Netherlands), state that the combination of AS, MR, and impaired LVEF is associated with high mortality if left untreated and requires careful consideration from the heart team about the best course of treatment. For patients with low-flow/low-gradient AS, TAVR has been shown to be a safe alternative to SAVR (which is associated with high perioperative risk because of the diminished LVEF in these patients), with a 30-day mortality rate of 3.8%.

As for people with residual MR after TAVR, the editorialists also highlight the COAPT trial as bringing “hope” to patients, although there are some issues still to work out. “It is questionable when (during follow-up) we can be certain the mitral valve changes after TAVR have fully evolved and find the proper moment for mitral valve therapy, if needed,” they write.

They also point out that a degeneration of the mitral valve related to calcification is not negligible in patients with low-flow/low-gradient AS, and there is no solid therapy yet for those patients, although mitral valve replacement might be an option.