Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation (RESHAPE-HF2)
Authors, Journal, Affiliations, Type, DOI
- Authors: Stefan D. Anker, Tim Friede, Ralph-Stephan von Bardeleben, Javed Butler, Muhammad-Shahzeb Khan, et al., for the RESHAPE-HF2 Investigators
- Journal: New England Journal of Medicine, Volume 391, Issue 19, Pages 1799–1809
- Lead affiliations: Charité Universitätsmedizin Berlin (Anker); University Medical Center Göttingen (Friede, legal sponsor); 30 sites in 9 countries
- Type: Multicenter, investigator-initiated randomized controlled trial
- DOI: 10.1056/NEJMoa2314328
- Funded by: Unrestricted grant from Abbott Laboratories to University Medical Center Göttingen (legal/academic sponsor)
- Published: August 31, 2024 (online); November 14, 2024 (updated print); ClinicalTrials.gov NCT02444338
Overview
RESHAPE-HF2 is the third landmark TEER RCT, uniquely enrolling patients with moderate-to-severe (not exclusively severe) functional SMR (median EROA 0.23 cm²) — a population representing approximately 44% of real-world TEER recipients but excluded from COAPT (EROA 0.40 cm²) and MITRA-FR (EROA 0.31 cm²). All three co-primary endpoints were met: composite HF hospitalization or CV death rate ratio 0.64 (P=0.002), HF hospitalization alone RR 0.59 (P=0.002), and KCCQ-OS improvement +10.9 points (P<0.001) vs medical therapy. All-cause mortality was not reduced (HR 0.90; NS), consistent with less advanced underlying disease than COAPT (control 2-year mortality 29.6% vs 46.1%). The NNT of 5.1 to prevent one HF hospitalization, combined with COAPT 5-year data, provided the evidentiary base for ESC 2025 upgrading TEER to Class I A for symptomatic ventricular SMR.
Keywords
Transcatheter edge-to-edge repair, MitraClip, functional mitral regurgitation, moderate-to-severe mitral regurgitation, heart failure, KCCQ, hospitalization, guideline-directed medical therapy, RESHAPE-HF2
Key Takeaways
Background and Context
- Functional (secondary) MR is common in HF and associated with poor prognosis
- COAPT showed TEER benefit in severe SMR; MITRA-FR was neutral; conflicting results left uncertainty
- ~44% of patients in real-world TEER registries have only moderate MR (EROA <0.40 cm²) — RESHAPE-HF2 specifically addresses this population
- MITRA-FR vs COAPT discordance hypothesised to reflect differences in EROA:LV relationship ("proportionate" vs "disproportionate" MR)
Study Design
- Multicenter, investigator-initiated, randomized, controlled, open-label trial
- 30 sites in 9 countries (Germany, US, Italy, Switzerland, Spain, UK, Greece, Denmark, France, Slovenia, Poland, Portugal)
- Enrollment: March 2015 – October 2023; n=505 (250 device, 255 control)
- Device group: MitraClip TEER (within 14 days of randomization) + guideline-recommended medical therapy
- Control group: Medical therapy alone
- Randomization 1:1, stratified by site and etiology (ischemic vs nonischemic)
- COVID-19 curtailed recruitment from planned 650 to 505; primary endpoint reverted to 24-month composite
Eligibility Criteria
- Symptomatic HF (NYHA II–IV) despite guideline-recommended therapy
- Functional MR grade 3+ or 4+ (EAE criteria)
- LVEF 20–50% (initially LVEF 15–35% for NYHA II; 15–45% for NYHA III/IV)
- HF hospitalization within 90 days before enrollment OR elevated NP (BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL)
- Heart team evaluation (HF specialist + interventional cardiologist + echocardiographer + cardiac surgeon) required
- Exclusion: Degenerative MR; MV surgery recommended; PCI/CV surgery/AF ablation within 90 days; isolated MV surgery recommended
Baseline Characteristics
| Parameter |
Value |
| Mean age |
70 ± 10 years |
| Women |
20% |
| Nonischemic etiology |
35% |
| CRT devices |
29% |
| Median LVEF |
31% (IQR 25–37%) |
| Median LV end-diastolic volume |
205 mL (IQR 157–250) |
| Median EROA |
0.23 cm² (IQR 0.20–0.29) |
| Median regurgitant volume |
36 mL (IQR 29–43) |
| Median KCCQ-OS score |
43 points (IQR 26–63) |
Procedure
- TEER attempted in 248/250 (99.2%); MitraClip deployed in 244/248 (98.4%)
- MR severity at end of procedure (n=243): MR ≤1+ in 74.5%; 2+ in 17.7%; 3+ in 4.1%; 4+ in 3.7%
- Median procedure time: 117 min; median fluoroscopy time: 22 min
- Procedures within 14 days of randomization: 220/248 patients
Primary Efficacy Results (24 Months)
| Endpoint |
Device |
Control |
Rate Ratio (95% CI) |
P value |
| HF hosp or CV death (events/100 pt-yr) |
37.0 |
58.9 |
0.64 (0.48–0.85) |
0.002 |
| HF hospitalization (events/100 pt-yr) |
26.9 |
46.6 |
0.59 (0.42–0.82) |
0.002 |
| KCCQ-OS change at 12 months |
+21.6 pts |
+8.0 pts |
+10.9 pts (6.8–15.0) |
<0.001 |
- Total events (HF hosp/CV death): 151 device vs 225 control
- Total HF hospitalizations: 110 device vs 178 control
- NNT = 5.1 to prevent one HF hospitalization event per 100 patient-years
Secondary Results
| Endpoint |
Device |
Control |
Effect |
| All-cause mortality (full follow-up) |
17.0%/yr |
18.6%/yr |
HR 0.90 (0.71–1.13) — NS |
| NYHA I/II at 12 months |
74.5% (140/188) |
58.5% (96/164) |
P<0.001 |
| MR ≤2+ at 12 months |
90.4% (132/146) |
36.1% (43/119) |
P<0.001 |
| 6-minute walk distance change (12m) |
+34.0 m |
+5.1 m |
+20.5 m (0.3–40.7); P=0.047 — NS per Hochberg |
| All-cause hosp rate (24m) |
199 events |
233 events |
RR 0.82 (0.63–1.07) — NS |
- Among control group with MR ≤2+ at 12 months: 35% (15/43) had undergone MV procedure
- Mean follow-up: 18.8 ± 8.2 months (planned 24 months; full follow-up: 38.1 ± 18.1 months)
Safety
- Device-specific adverse events: 4 patients (1.6%)
- 2 hematomas; 1 pericardial effusion; 1 right atrial perforation requiring thoracotomy (after successful clip implantation)
- Unplanned MitraClip in control group: 8 by 12 months; 38 total (35 by 12 months)
Comparison with COAPT and MITRA-FR
| Parameter |
COAPT |
MITRA-FR |
RESHAPE-HF2 |
| Median EROA |
0.40 cm² |
0.31 cm² |
0.23 cm² |
| Median RVol |
~41 mL |
~45 mL |
36 mL |
| Control 2yr mortality |
46.1% |
~34% |
29.6% |
| GDMT enforcement |
Strict |
Less strict |
Strict |
| HF hosp benefit |
Yes (HR 0.53) |
No |
Yes (RR 0.59) |
| Mortality benefit |
Yes (HR 0.72 at 5yr) |
No |
No (HR 0.90) |
- RESHAPE-HF2 has less severe MR and less advanced HF than COAPT; mortality benefit absent is consistent with lower disease burden
- Confirms TEER benefit extends below traditional "severe MR" thresholds
Subgroup Analyses
- Treatment effect on first primary endpoint consistent across 13 prespecified subgroups
- No apparent heterogeneity by EROA, LVEF, etiology, sex, age, NYHA class, or presence of CRT
Limitations
- Open-label: Participants, investigators, and echocardiographers unblinded — QoL outcomes (KCCQ) susceptible to placebo effect/expectation bias
- Underpowered for mortality: Not designed to detect mortality difference; 142 deaths each arm is numerically identical
- COVID-19 curtailed enrollment: 505 vs planned 650; primary endpoint design modified in blinded manner
- Control crossover: 38 unplanned TEER procedures in control group by 24 months dilute between-group differences
- SGLT2i era: Modern GDMT including SGLT2i may further reduce HF hospitalization in both arms
- Industry financial support: Abbott funded via unrestricted grant; trial independence maintained through academic legal sponsor
Key Concepts Mentioned
Key Entities Mentioned
Wiki Pages Updated
wiki/sources/mvteer-reshapehf2-nejm-2024.md — createdwiki/sourceindex.md — updatedwiki/wikiindex.md — updatedwiki/concepts/Secondary-Mitral-Regurgitation.md — updated with RESHAPE-HF2 data