Promising First Dips Into a Bigger Pool of MitraClip Candidates

CHICAGO -- Emerging real-world data supported benefits of MitraClip therapy in patients with secondary mitral regurgitation (MR) who didn't fit the COAPT profile, the EXPAND study showed.

MR was often reduced to mild or better (MR 1+) after placement of the MitraClip third-generation NTR and XTR systems, and this was maintained at 1 year in:

• 86.5% of those who fit COAPT enrollment criteria (n=125)
• 97.2% of patients with moderate MR who would not fit COAPT criteria (n=128)
• 81.3% of patients with advanced heart failure (HF) who were not COAPT-eligible (n=32)

The evidence "confirms" the clinical benefit of MitraClip therapy in COAPT-like people and hints at favorable MR reduction and functional class improvement in moderate MR and advanced HF, said Gilbert Tang, MD, a cardiac surgeon at Mount Sinai Health System in New York City, in presenting the results at the Transcatheter Valve Therapeutics (TVT) conference hosted by the Cardiovascular Research Foundation (CRF).

Rates of survival and HF hospitalization at 1 year were no different among COAPT-like and non-COAPT-like patients in EXPAND, and were comparable to what was observed in the pivotal randomized trial. Nevertheless, "we know the curves may diverge with time," Tang cautioned.

"It's good data, but we need to consider it hypothesis-generating," commented Robert Bonow, MD, a cardiologist at Northwestern Medicine in Chicago. Speaking on a panel at TVT, he stressed the importance of comparing MitraClip recipients against a well-treated medical group.

Ran Kornowski, MD, of Rabin Medical Center in Petah Tikva, Israel, questioned the external validity of this cohort and suggested that there was likely something about the moderate MR patients that led them to a referral for the MitraClip procedure.

COAPT was the landmark trial that established transcatheter edge-to-edge repair of the mitral valve as beneficial in secondary MR patients who remained symptomatic despite guideline-directed medical therapy. On the basis of the COAPT report from 2018, FDA officially expanded MitraClip's indication to this group in 2019. CMS widened its coverage accordingly in 2021.

Notably, the MitraClip arm of COAPT had achieved MR 1+ at 1 year in just 69.o% of cases.

Yet this trial is now considered a somewhat outdated historical control in light of recent improvements related to patient selection and operator experience and the greater uptake of sacubitril/valsartan (Entresto) and SGLT2 inhibitors.

The EXPAND study spanned 57 sites across seven countries. Enrollment was determined based on site interpretation of MR severity.

Out of more than 1,000 people with secondary MR who got the MitraClip, 413 had sufficient echocardiographic core lab assessment and were selected for the present analysis. They were divided into three groups:

• COAPT-like: severe MR (3+/4+) and left ventricular ejection fraction (LVEF) 20-50% at baseline
• Moderate MR: not COAPT-eligible due to moderate MR (2+) and LVEF at least 20% or fairly normal left ventricles or systolic pulmonary artery pressure (PAP)
• Advanced HF group: not COAPT-eligible due to severe MR and LVEF under 20% or left ventricles that were too big or systolic PAPs that were too high

Average age was 75 years in the entire study population, and men represented 60% of patients. Baseline use of heart failure medications was similar across groups.

Tang reported that the three cohorts had sustained improvements in New York Heart Association symptoms. Quality of life assessed by Kansas City Cardiomyopathy Questionnaire scores showed significant improvements in the COAPT-like and moderate MR groups, whereas the advanced HF group trended toward gains without reaching statistical significance.

A limitation of the EXPAND data was the difficulty investigators had following up with patients due to the COVID-19 pandemic. There was some heterogeneity within each group, and limited information was available on guideline-directed medical therapy optimization, Tang acknowledged.

He said more analysis is needed in patients with atrial secondary MR, which tends to occur in atrial fibrillation and heart failure with preserved ejection fraction, and those in more contemporary practice who got the newer G4 MitraClip.

Comment