TEER Evaluated in MATTERHORN, RESHAPE-HF2, and Tri.fr Trials

September 16, 2024—The European Society of Cardiology (ESC) announced the presentation of three studies evaluating transcatheter edge-to-edge repair (TEER): MATTERHORN, RESHAPE-HF2, and Tri.fr.

ESC stated that the MATTERHORN trial found that TEER is noninferior to surgery in patients with secondary mitral regurgitation (MR). The RESHAPE-HF2 trial showed TEER was better than optimal medical therapy (OMT) alone in patients with heart failure (HF) and MR. In the Tri.fr trial, new evidence showed benefits of TEER in secondary tricuspid regurgitation (TR).

The studies were presented in Hot Line sessions at the ESC Congress 2024 held August 30 to September 2 in London, United Kingdom.

MATTERHORN
According to ESC, the investigator-initiated MATTERHORN randomized controlled trial recruited patients with secondary MR, left ventricular ejection fraction (LVEF) ≥ 20%, with symptoms of HF (New York Heart Association [NYHA] class ≥ 2) despite guideline-directed OMT, who were considered at high surgical risk by the local heart team. Professor Volker Rudolph, MD, of the Heart and Diabetes Center NRW in Bad Oeynhausen, Germany, presented the MATTERHORN study at ESC.

The study enrolled 210 patients (average age, 70.5 years; female, 40%) at 16 centers in Germany. Patients’ mean LVEF was 43%. HF was NYHA class III or IV in 86% of patients. The median EuroSCORE II score was 3%.

Patients were randomized 1:1 to mitral TEER or surgical mitral valve therapy (mitral valve repair or replacement at the surgeon’s discretion). In the surgical group, 72% of patients underwent mitral valve repair and 28% underwent mitral valve replacement.

The ESC press release stated that the primary efficacy endpoint was the composite of death, hospitalization for HF, mitral reintervention, assist device implantation, and stroke at 1 year. The key secondary endpoint was the recurrence of MR grade ≥ 3 at 1 year.

The primary composite safety endpoint, assessed at 30 days, included death, myocardial infarction, major bleeding, stroke or transient ischemic attack, rehospitalization, all reinterventions, nonelective cardiovascular surgery, renal failure, deep wound infection, mechanical ventilation > 48 hours, gastrointestinal complications requiring surgery, new-onset atrial fibrillation (AF), septicemia, and endocarditis.

As summarized in the ESC press release, for patients in the TEER group versus patients in the surgical group at 1 year, investigators reported the following:

• No significant difference in the primary composite endpoint (16.7% vs 22.5%; odds ratio [OR], 0.69; 95% CI, 0.33-1.44; P = .32), with noninferiority confirmed (P < .01 for noninferiority).
• No significant difference in the recurrence of MR grade ≥ 3 in the TEER group versus the surgical group (8.9% vs 1.5%; OR, 6.22; 95% CI, 0.75-51.95; P = .091).
• MR grade ≤ 1 was achieved (73.2% vs 87.3%), highlighting the efficacy of both therapies.

The primary safety endpoint occurred in significantly more patients in the surgical group than in the TEER group (54.8% vs 14.9%; P < .001), which was largely driven by more major bleeding (29% vs 3%, respectively), all reinterventions (19% vs 8%), and new-onset AF (33% vs 9%).

MATTERHORN’s Principal Investigator, Professor Stephan Baldus, MD, from the University of Cologne in Cologne, Germany, commented in the ESC press release, “The MATTERHORN trial is the first randomized trial to demonstrate the noninferiority of TEER and surgery in patients with secondary MR. These new data may become important to guide decision-making as European guidelines currently recommend TEER may be considered in patients who are judged inoperable or at high surgical risk by the heart team.”

RESHAPE-HF2
The investigator-initiated RESHAPE-HF2 randomized controlled trial found that mitral TEER (M-TEER) reduced cardiovascular death and HF-related hospitalizations with improved health status in patients with HF and moderate-to-severe functional MR (FMR). The new data provide conclusive evidence for the benefits of M-TEER in patients who currently have limited treatment options, noted the ESC press release.

In the study, M-TEER was shown to be more effective than OMT alone in patients with HF and moderate to severe MR ineligible for surgery. Also, M-TEER was associated with improved health status and no safety concerns.

“Patients with FMR who are ineligible for surgery have limited treatment options,” commented RESHAPE-HF2’s Principal Investigator Professor Stefan Anker, MD, from the Charite University Hospital in Berlin, Germany, in the ESC press release. “When M-TEER was studied previously, mainly in patients with severe FMR, one trial [Stone et al. N Engl J Med. 2018;379:2307-2318] showed positive effects while the other [Obadia et al. N Engl J Med. 2018;379:2297-2306] was neutral. RESHAPE-HF2 now provides additional compelling evidence for using M-TEER over OMT alone, which will help to guide medical decision-making.”

RESHAPE-HF2 recruited patients with symptoms of HF (NYHA class ≥ 2) despite guideline-directed OMT, who had LVEF ≥ 20% and ≤ 50%, MR grade 3+ or 4+, and had a recent hospitalization for HF or elevated plasma natriuretic peptide concentrations within the last 90 days. Patients for whom mitral valve surgery was recommended were not eligible.

Patients were randomized 1:1 to M-TEER plus OMT or OMT alone.

The three primary endpoints were: the composite rate of total (first and recurrent) HF hospitalizations and cardiovascular death within 24 months; the rate of total HF hospitalizations within 24 months; and the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score assessing the impact of HF on quality of life (QoL).

In total, the study randomized 505 patients (mean age, 70 years; female, 20%) from 30 centers in nine countries. The patients’ mean LVEF was 31% and HF was NYHA class III or IV in approximately three quarters of patients. The mean KCCQ overall summary score was 46, indicating significant symptoms and limitations caused by HF.

According to the ESC press release, the investigators reported the following findings at 24 months for the M-TEER group versus the control group:

• The rate of total hospitalizations for HF and cardiovascular death was significantly lower (37 per 100 patient-years vs 58.9 per 100 patient-years; rate ratio, 0.64; 95% CI, 0.48-0.85; P = .002).
• The rate of total hospitalizations for HF was significantly reduced by 41% (26.9 per 100 patient-years vs 57.8 per 100 patient-years; rate ratio, 0.59; 95% CI, 0.42-0.82; P = .002).

In addition, the mean (standard deviation) change from baseline to 12 months in the KCCQ overall summary score was greater (improved) in the M-TEER group (+21.6 [26.9]) than in the control group (+8.0 [24.5]), resulting in a mean difference of +10.9 points (95% CI, 6.8-15.0; P < .001).

During the total follow-up of 38.1 (18.1) months, there was no difference between the M-TEER group and the control group for all-cause mortality (17.0% vs 18.5%; hazard ratio, 0.90; 95% CI, 0.71-1.13). Periprocedural adverse events were reported in four patients (1.6%) in the M-TEER group.

Tri.fr
In the Tri.fr trial, the tricuspid TEER (T-TEER) plus OMT resulted in reduced severity of secondary TR including significant improvement of the primary endpoint of death, cardiovascular hospitalization, functional class, and patient-reported outcomes. Additionally, T-TEER plus OMT was associated with major QoL improvements, noted the ESC press release.

“Patients with severe secondary TR often have reduced QoL and a poor prognosis, with many ineligible for surgery due to the associated risks,” commented Principal Investigator Professor Erwan Donal, who is with the Hospital of Rennes, France, in the ESC press release. “In common with others, we were interested in exploring T-TEER as a new treatment option and we conducted the investigator-led Tri.fr trial to test this approach on top of OMT. The benefits of T-TEER plus strict medical therapy and management in terms of reducing the impact of TR on patients’ daily lives are highly encouraging.”

According to ESC, the Tri.fr trial was an open-label randomized trial conducted in patients who had symptomatic, severe secondary TR despite medical management, were stable for at least 30 days, and were ineligible for surgical correction. The patients in the trial were randomized in a 1:1 ratio to receive either T-TEER in addition to OMT or OMT alone.

The investigators recruited 300 patients (mean age, 78 years; female, 54%) from 24 centers in France and Belgium. In total, 40% of patients had been hospitalized for HF within 1 year before enrollment and 15% had a cardiac implantable electronic device.

The primary endpoint was the Packer composite score (combining NYHA class, patient global assessment [PGA], and major cardiovascular events: all-cause mortality, cardiovascular mortality, tricuspid valve surgery, HF hospitalizations, and cardiovascular and noncardiovascular hospitalizations). Secondary endpoints included components of the primary composite, severity of TR assessment, and QoL improvement using the KCCQ score.

As summarized in the ESC press release, rates of clinical composite endpoint improvement were higher in the T-TEER group than in the OMT alone control group of (74.1% vs 40.6%; P < .0001). After 1 year, the severity of TR significantly improved in the T-TEER group versus the control group—the probability of a better TR grade (ordinal variable < 4+, 4+, or 5+) was 0.73 (95% CI, 0.68-0.78; P < .0001). Lower rates of hospitalization and death were observed in the T-TEER group, although the trial was not designed to detect statistically significant differences in these outcomes.

Additionally, QoL significantly improved in the T-TEER group versus the control group. At 1 year, the overall KCCQ score was 69.9 (standard deviation [SD] 25.5) with the T-TEER group compared with 55.4 (SD 28.8) in the control group (P < .0001). Patient-reported outcomes were considerably better in the T-TEER group and consistently improved over time. In the T-TEER group, 74.6% of patients had an improved PGA versus 39.5% in the control group.

“We clearly showed the benefits of T-TEER, as seen in the TRILUMINATE trial [Sorraja et al. N Engl J Med. 2023;388:1833-1842], but using T-TEER as part of a global approach and treating heart failure with guideline-directed medical management and follow-up,” stated Prof. Donal in the ESC press release. “A key message of the Tri.fr trial is that implementing rigorous multidisciplinary medical management resulted in a low event rate, even in very ill patients with secondary TR. Using T-TEER with optimal medical management also led to important QoL improvements.”

Prof. Donal concluded, “It remains to be seen if patients with a particular phenotype of severe TR derive more benefit from T-TEER than others. We expect to provide more insightful outcomes data in the coming years as we continue to follow-up the trial participants.”