Effectiveness and safety of edge-to-edge MItral vaLve repair in patients with significant mitraL rEgurgitatioN aNd cardIac ATTR amyloidosis: design and rationale of the MILLENNIAL trial
Bibliographic record
Abstract
Abstract Background Transcatheter edge-to-edge mitral valve repair (M-TEER) has emerged as an effective treatment option for patients at elevated risk for cardiac surgery, but patients with transthyretin cardiomyopathy (ATTR-CM) were explicitly excluded from large M-TEER trials. From a pathophysiological perspective, effective treatment of significant regurgitant volume and consecutive improvement of forward volume appears highly desirable in a condition with intrinsically low output. However, whether this translates into improved clinical outcomes and better quality of life compared to conservative heart failure management alone remains to be investigated. The MILLENNIAL trial is designed to investigate the effectiveness of M-TEER in patients with ATTR-CM and concomitant significant MR. Methods and Study Design The MILLENNIAL trial is an investigator-driven, multi-center, prospective, parallel-group, open-label, randomized, controlled trial. For enrolment the local heart team must have excluded mitral valve surgery as a treatment option and deemed patient anatomy feasible for M-TEER (Figure 1). In total, 100 participants will be randomized 1:1 to receive either a) M-TEER alongside optimal medical therapy (OMT) or b) OMT alone (Figure 2). Randomization is stratified according to baseline treatment with ATTR-specific medication and concomitant TEER for the tricuspid valve. The primary endpoint is a hierarchical combination of (i) all-cause mortality, (ii) cumulative frequency of cardiovascular-related hospitalizations, (iii) change from baseline in six-minute walk distance, and (iv) change from baseline in NT-proBNP serum levels through 48 months, as analysed with the Finkelstein-Schoenfeld method. Power calculations are based on an anticipated win ratio of 2:1 in favour of the treatment arm. The change from baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) will be assessed as a secondary endpoint. Technical, device and procedural success, intraprocedural change in haemodynamics before and after device deployment, and change in echocardiographic parameters serve as exploratory endpoints. On-site follow-up is at 6, 12, and 48 months. Cross-over from control to treatment is allowed after 48 months. Conclusion The MILLENNIAL trial will determine if minimally invasive treatment of significant MR can improve outcome and quality of life in patients with ATTR-CM. If positive, these findings could reshape treatment paradigms and establish M-TEER as a standard therapeutic approach in this high-risk population with currently limited treatment options.Figure 1:Study Population Figure 2:Study Design
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.020 | 0.015 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".