Mitral regurgitation (MR) is commonly classified as primary (degenerative) or secondary (functional), depending on whether the primary abnormality involves the mitral valve apparatus itself or results from left ventricular remodeling and dysfunction. This distinction is clinically relevant, as underlying mechanisms, therapeutic strategies, and expected outcomes differ substantially between these entities.

Mitral valve repair surgery has traditionally been considered the first-line treatment for both primary and secondary MR, with high efficacy rates particularly in patients at low surgical risk [1, 2]. In recent years, mitral transcatheter edge-to-edge repair (M-TEER) has evolved from an emerging procedure to the therapeutic strategy of choice for patients with severe secondary MR and high surgical risk. The American Heart Association/American College of Cardiology guidelines assign M-TEER a class IIa indication for symptomatic patients with primary or secondary MR who are at high surgical risk or deemed inoperable [3], whereas the ESC guidelines provide a class I recommendation for patients with symptomatic secondary (ventricular) MR persisting despite guideline-directed medical therapy, and a class IIa recommendation for patients with primary MR who are symptomatic, have suitable anatomy, and are at high surgical risk [4]. This recommendation is supported by robust evidence showing that, compared with surgery, the percutaneous approach is associated with lower periprocedural morbidity, significant improvements in quality of life, and reductions in both heart failure (HF)–related hospitalizations and all-cause mortality [5].

Beyond established indications, M-TEER is increasingly being adopted across a broader range of clinical scenarios, reflecting expanding experience and encouraging outcomes in real-world practice. The purpose of this review is to investigate the various clinical scenarios in which the use of M-TEER has allowed for an expansion beyond established indications. These include settings in which M-TEER has been applied based on real-world experience and emerging evidence, such as acute ischemic MR, papillary muscle rupture (PMR), functional MR following myocardial infarction, moderate secondary MR, hypertrophic obstructive cardiomyopathy (HOCM), advanced HF, concomitant transcatheter interventions, and mitral annulus calcification.

Acute MR is a serious complication of acute myocardial infarction (AMI) associated with high morbidity and mortality [6, 7] (Fig. 1). A recent large study found that most patients had mild MR (76%), followed by moderate (21%) and severe MR (3%) [8]. In the CADILLAC trial, which evaluated patients with AMI treated with primary percutaneous coronary intervention, MR was found in approximately 13% of patients at baseline ventriculography [9]. Even though most cases were mild, the presence and severity of MR were closely associated with older age, female sex, higher Killip class, multivessel coronary disease, and reduced left ventricular function. Importantly, MR of any grade emerged as an independent predictor of mortality at both 30 days and one year, with a stepwise increase in risk from mild to severe MR. These findings underscore that ischemic MR, even when mild, is not a benign finding in the context of AMI and continues to carry adverse prognostic significance despite timely mechanical reperfusion.

Fig. 1.

M-TEER in acute ischemic mitral regurgitation. (A) 3D multiplanar view of TEE showing chordal rupture and P3 scallop prolapse. (B) 2D TEE using orthogonal views: severe mitral regurgitation. (C) TEE: transseptal puncture at 37 mm height. (D) PASCAL Ace implantation: the first device was implanted in the medial commissural position and the second device in A3-P3 in close relation to the first one. (E) Fluoroscopy image of the implantation of two PASCAL Ace devices. (F) Mild mitral regurgitation post M-TEER. (G,H) Zoom-3D w/o colour: final result. M-TEER, mitral transcatheter edge-to-edge repair; TEE, transesophageal echocardiogram; W/o, with and without.

While PMR is the classical presentation described in the literature, MR may also manifest in a more “functional” phenotype, leading to marked clinical deterioration. Distinguishing between these mechanisms is critical for understanding the clinical presentation and guiding therapy. Mitral valve replacement surgery in this setting carries a high surgical risk, especially when compared to percutaneous repair in terms of morbidity and mortality 30 days post-intervention. A systematic review reported an aggregate 30-day mortality rate of 19%, with some studies describing rates approaching 40% during the acute phase [10]. In the current era of transcatheter mitral valve interventions, M-TEER has emerged as a percutaneous option for post-infarction acute MR. It should be noted that no randomized controlled trials have evaluated M-TEER in this setting; available evidence is limited to observational studies and case series. Some reports suggest that the procedure may improve survival in selected patients [11].

2.2 Secondary MR Phenotype

The European Registry of MitraClip (Abbott) in Acute Mitral Regurgitation following Acute Myocardial Infarction (EREMMI) prospectively enrolled 44 patients with severe MR developing shortly after transmural MI who were deemed at prohibitive surgical risk [14]. Median EuroSCORE II was 15.1%, reflecting extreme risk. MitraClip implantation achieved technical success in 86.6%, with significant MR reduction and rapid clinical improvement. Thirty-day mortality was 9.1%, and at six months 72.5% of survivors had MR $\le$2+ and 75.9% were in New York Heart Association (NYHA) class I–II. Despite the small sample size, this registry suggests the feasibility, safety, and meaningful clinical benefit of transcatheter edge-to-edge repair in acute post-MI MR.

The International Registry of MitraClip in Acute Mitral Regurgitation following Acute Myocardial Infarction (IREMMI) suggests the feasibility of M-TEER in this high-risk population, showing better outcomes compared with conservative management in post-AMI functional MR and supporting M-TEER as a viable alternative to surgery in selected patients [15]. Building on this, the registry recently reported outcomes from 471 patients across 21 centers. All had at least moderate-to-severe MR with HF symptoms within 90 days of MI and were treated with surgical mitral valve repair/replacement (SMVR), M-TEER (MitraClip or PASCAL [Edwards Lifesciences]) or conservative therapy. Of these, 205 underwent intervention (106 surgery, 99 TEER). Surgery was performed earlier than M-TEER (median 12 vs. 19 days post-AMI; p = 0.01). Despite worse baseline status, patients who underwent intervention had better outcomes than those managed conservatively (in-hospital mortality 11% vs. 27%; 1-year mortality 16% vs. 35%). Although procedural success was similar between surgery and M-TEER, the lower mortality with M-TEER suggests it may offer a safer alternative for high-risk post-AMI patients with significant MR.

Another subanalysis from the IREMMI Registry evaluated 93 patients with acute MR after AMI treated with MitraClip across 18 centers, of whom 54% presented with cardiogenic shock [16]. Procedural success was high and comparable between cardiogenic and non-cardiogenic shock patients (90% vs. 93%), with no excess in major complications. At 30 days, mortality was numerically higher in cardiogenic shock (10% vs. 2.3%), but not statistically significant, and after a median 7-month follow-up, combined death or HF rehospitalization did not differ between groups (28% vs. 26%). Multivariable analysis confirmed that cardiogenic shock was not independently associated with adverse outcomes, whereas procedural success strongly predicted survival. These findings support the feasibility of MitraClip in acute post-AMI MR even in patients presenting with CS, provided initial stabilization is achieved (Fig. 2).

Fig. 2.

Management algorithm for acute severe mitral regurgitation after myocardial infarction. AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; GDMT, guideline-directed medical therapy; MR, mitral regurgitation; M-TEER, mitral transcatheter edge-to-edge repair; MV, mitral valve; TEE, transesophageal echocardiogram; LVAD, left ventricular assist device; IABP, intra-aortic balloon pump; ECMO, extracorporeal membrane oxygenation.

Over the past decade, evidence supporting M-TEER has expanded considerably. Yet, two landmark trials—MITRA-FR and COAPT—reported strikingly different outcomes despite enrolling seemingly similar patient populations [5, 17]. In MITRA-FR, patients had symptomatic HF with left ventricular ejection fraction (LVEF) 15–40%, larger LV volumes (mean LVEDV 135 mL/m²), and only moderate-to-severe MR (effective regurgitant orifice area [EROA] $\ge$20 mm²; regurgitant volume $\ge$30 mL). The trial failed to demonstrate a benefit of MitraClip over optimal medical therapy. In contrast, COAPT enrolled patients with symptomatic HF and more severe MR (EROA $\ge$30 mm², regurgitant volume $>$45 mL), smaller ventricles (LVEDV 101 mL/m²), and optimized medical and device therapy prior to enrollment. In this more “disproportionate” MR phenotype—where MR severity exceeded the degree of LV dilation—M-TEER significantly reduced both HF hospitalizations and all-cause mortality. These divergent results gave rise to the concept of proportionate versus disproportionate MR, which links regurgitation severity to LV remodeling [18, 19]. Patients with disproportionate MR (severe MR relative to LV size) appear most likely to benefit from M-TEER, whereas those with proportionate MR (moderate MR appropriate to severe LV dilation) derive limited hemodynamic improvement.

A subsequent randomized trial, RESHAPE-HF2, further expanded the evidence for M-TEER by including patients with HF and moderate-to-severe secondary MR across a broader range of LV systolic function, thereby extending the target population beyond the classical paradigm of secondary MR associated with severe LV dysfunction [20]. The study enrolled 505 patients with symptomatic HF, LVEF 20–50%, recent HF hospitalizations, and EROA $>$20 mm², all on guideline-directed medical therapy. At 24 months, the addition of MitraClip to medical therapy significantly reduced the composite of first or recurrent HF hospitalizations or cardiovascular death (rate ratio 0.64, 95% CI 0.48–0.85; p = 0.002), as well as the rate of HF hospitalizations alone (rate ratio 0.59, 95% CI 0.42–0.82). Procedural success was high, with durable MR reduction in ~90% of patients, and health status markedly improved at 12 months compared with controls. Collectively, RESHAPE-HF2 confirmed the results of COAPT and extended the benefit of M-TEER to a broader population with moderate MR and less advanced LV dysfunction, reinforcing its role in reducing HF events and improving quality of life. This has prompted a reevaluation of conventional severity thresholds (e.g., EROA $\ge$40 mm²) and generated debate about earlier intervention in selected patients with less severe MR but persistent symptoms and inadequate left ventricular remodeling.

Asgar et al. [21] confirmed the importance of M-TEER in moderate secondary MR in a real-world population. The safety and effectiveness were evaluated in both moderate (335 patients) and severe MR (525 patients). There were no differences in baseline characteristics, and patients with moderate MR experienced significant 1-year improvements in NYHA functional class and quality of life ($>$20 points on the Kansas City Cardiomyopathy Questionnaire–Overall Summary). Additionally, significant LV reverse remodeling was observed, reflected by a $>$20 mL decrease in LV end-diastolic and end-systolic volumes in the moderate MR cohort. Rates of major adverse events were low in both groups, and the occurrence of death and HF hospitalizations was similar between the two subgroups.

Taken together, these data suggest that patients with symptomatic HF, clearly quantifiable moderate-to-severe MR, optimized medical and device therapy, and LV volumes that are not excessively remodeled represent the phenotype most likely to benefit from M-TEER.

Hypertrophic cardiomyopathy (HCM) has an estimated prevalence of 1:200 to 1:500 in the general population [22]. Approximately 25% to 70% of patients develop dynamic left ventricular outflow tract (LVOT) obstruction, both at rest (25% to 30%) and when induced by Valsalva maneuvers (up to 70%). This is determined by the systolic anterior motion (SAM) of the mitral valve leaflets, which is responsible for LVOT obstruction and MR.

Pharmacological therapy remains the first-line treatment. Beta-blockers, non-dihydropyridine calcium channel blockers, and disopyramide have been traditionally used. However, recent studies have positioned cardiac myosin inhibitors (mavacamten or aficamten) as effective options in obstructive forms of HCM (EXPLORER-HCM and SEQUOIA-HCM) [23, 24]. They are also included in the latest ESC clinical practice guidelines with a class IIa recommendation [25]. In patients with a persistent LVOT gradient $\ge$50 mmHg, severe symptoms (NYHA class III–IV) and a history of syncope despite medical treatment, septal reduction strategies or surgical myectomy should be considered. Alcohol septal ablation is now the main option for septal reduction therapy [26]. The most common non-fatal complication is atrioventricular block, seen in about 7–20% of patients [27]. The procedure, however, can only be done when the septal anatomy is suitable.

In patients who are not candidates for septal reduction therapies, M-TEER has been explored as a potential alternative to reduce SAM-related LVOT obstruction and MR. Evidence supporting this approach is extremely limited. Sorajja et al. [28] conducted a study to evaluate the efficacy of percutaneous mitral valve plication as a therapeutic option for patients with symptomatic HOCM who were not candidates for septal ablation or myectomy. Their report consisted of a small case series including six elderly patients (mean age 83 years, predominantly female), each treated with a single MitraClip device implanted at the A2–P2 scallops. The procedure was technically successful in five patients; the sixth developed cardiac tamponade during the intervention. Significant hemodynamic improvements were observed, including a reduction in LVOT gradient (from 91 $\pm$ 44 mmHg to 12 $\pm$ 6 mmHg, p = 0.007), a decrease in left atrial pressure (from 29 $\pm$ 11 mmHg to 20 $\pm$ 8 mmHg, p = 0.06), a reduction in MR severity (from grade 3.0 to 0.8, p = 0.0002), and an increase in cardiac output in four patients (from 3.0 $\pm$ 0.6 L/min to 4.3 $\pm$ 1.2 L/min, p = 0.03). At 1.5 years of follow-up, all patients showed improvement to NYHA functional class $\le$II. While early results of percutaneous mitral valve repair were encouraging in this limited population, robust evidence supporting M-TEER in patients with HOCM is still lacking. All available data originate from isolated case reports and very small case series [29, 30], so additional large-scale studies are needed to validate these preliminary results. Therefore, while M-TEER therapy may offer symptomatic improvement in highly selected, elderly, or anatomically unsuitable patients who cannot undergo septal reduction therapy, it should be viewed as an exploratory, off-label strategy rather than a validated alternative to guideline-supported therapies. Fig. 3 (Ref. [31]) shows a patient treated with M-TEER for SAM secondary to HCM.

Fig. 3.

M-TEER in systolic anterior motion-related mitral regurgitation secondary to HOCM. (A) Continuous-wave Doppler: LVOT gradient at a rest of 159 mmHg. (B) 2D TEE using orthogonal views: severe mitral regurgitation. (C) Device implantation (MitraClip System) in A3-P3 position. (D) Mild mitral regurgitation post M-TEER. (E) Zoom-3D: final result. (F) Continuous-wave Doppler without LVOT gradient. HOCM, hypertrophic obstructive cardiomyopathy; LVOT, left ventricular outflow tract; TEE, transesophageal echocardiogram; M-TEER, mitral transcatheter edge-to-edge repair. Panels A and F are adapted from our previous work [31] and combined with new data (Panels B–E) generated in this review.

Advanced HF is associated with a poor prognosis, with annual mortality approaching 20% in de novo HF and a substantial proportion of patients progressing to stage D disease [32]. Secondary MR is common in this population, exacerbating symptoms and outcomes.

Several registries have examined outcomes of M-TEER in patients with advanced HF. The German TRAMI registry included 777 patients and reported on 256 with severely reduced LVEF (30%) and elevated NT-proBNP. In this subgroup, in-hospital mortality was relatively low (3.1%), one-year mortality reached 24.2%, and nearly 70% of patients improved by at least one NYHA class [33]. Similarly, the EXPAND study, the largest real-world evaluation of the MitraClip NTR/XTR, enrolled over 1000 patients worldwide, including 118 with NYHA IV symptoms [34]. Procedural success was high (92.4%), with sustained MR reduction at 30 days (90.7%) and 12 months (92.9%). Even though mortality and rehospitalizations were more frequent in the NYHA IV group (29.2% vs. 17.7%), functional class and quality of life improved, with more than 70% of patients transitioning to NYHA I/II at one year.

Data from the Italian GIOTTO registry further highlights the prognostic implications of HF severity. Among 984 patients with SMR treated with M-TEER, those fulfilling criteria for advanced HF (NYHA III–IV, LVEF $\le$30%, and recent HF hospitalization) had significantly higher two-year mortality (47% vs. 29%). Importantly, achieving an optimal procedural result (MR $\le$1+) was associated with a survival benefit in both advanced and non-advanced HF groups, underscoring the critical importance of procedural success [35]. Conversely, hospitalizations for HF remained more frequent in advanced HF despite intervention, illustrating the intrinsic disease progression.

MitraBridge provided complementary evidence in the transplant population. In this multicenter registry, 119 patients with advanced HF and significant MR underwent MitraClip as bridging therapy [36]. Procedural success was 87.5%, 30-day survival was 100%, and one-year survival was 64%. Notably, nearly one-quarter of patients no longer met criteria for listing due to clinical improvement. These findings suggest that M-TEER may provide meaningful stabilization in select patients, delaying or even obviating the need for advanced therapies. However, small retrospective studies evaluating M-TEER prior to left ventricular assist device (LVAD) implantation, including series by Dogan et al. [37] and Kreusser et al. [38], suggest that although MR reduction is generally achieved, pre-LVAD TEER does not appear to improve survival or halt heart failure progression. These findings highlight the limited impact of M-TEER on long-term outcomes in this population and underscore the complexity of therapy sequencing in patients with advanced HF.

Overall, while patients with advanced HF undergoing M-TEER have worse outcomes compared with less advanced cohorts, available evidence demonstrates that the procedure is safe and can provide symptomatic and hemodynamic benefit, particularly when an optimal reduction in MR is achieved. In carefully selected patients, especially those unsuitable for transplant or LVAD, or those requiring stabilization as a bridge to candidacy, M-TEER represents a reasonable therapeutic consideration. Its role should be determined by a multidisciplinary heart team, weighing baseline and anatomical characteristics that predict procedural success, with the understanding that durable advanced therapies continue to offer superior long-term survival (Fig. 4).

Fig. 4.

M-TEER for secondary mitral regurgitation as a bridge to left ventricular assist device in a patient with stage D heart failure. (A,B) TTE + TEE: secondary severe mitral regurgitation. (C) Zoom-3D with colour: confirms the diagnosis. (D) Device implantation (DragonFly™ System): the first device was implanted in centro-medial position with moderate residual lateral jet. (E) Second device was implanted in a central-lateral position, in close relation to the first one. (F) Mild mitral regurgitation post procedure. (G) Zoom-3D: final result. (H) Fluoroscopy image showed ICD, two DragonFly™ devices and pump housing HM3. M-TEER, mitral transcatheter edge-to-edge repair; TTE, transthoracic echocardiogram; TEE, transesophageal echocardiogram; LVAD, left ventricular assist device; ICD, implantable cardioverter-defibrillator; HM3, HeartMate 3.

Advances in percutaneous therapies have supported the extension of M-TEER toward combined procedures, including concomitant mitral–tricuspid repair, M-TEER performed after or alongside transcatheter aortic valve implantation (TAVI), and integrated strategies with left atrial appendage closure (LAAC). While these approaches appear technically feasible, it is important to acknowledge that the available evidence remains extremely limited and is derived predominantly from observational studies. Available data derive almost entirely from observational series, with inherent risks of selection bias, center effect, and unmeasured confounding. To date, no randomized controlled trials have compared concomitant, staged, or isolated strategies, and therefore no conclusions can be drawn regarding long-term outcomes, patient selection, or comparative benefit. As such, enthusiasm for these techniques should be balanced by the recognition that their role remains exploratory and confined to carefully selected high-risk patients in experienced centers.

6.1 Mitral and Tricuspid Valve Repair

In recent years, transcatheter edge-to-edge repair of the tricuspid valve has become the most widely adopted percutaneous treatment for severe tricuspid regurgitation (TR), with procedural success rates consistently $>$85% and a favorable safety profile [39, 40, 41]. TR is associated with left-sided heart disease in 50% of cases, raising the question of whether combined or staged mitral and tricuspid repair (TMTVR) may improve outcomes compared with isolated intervention [42].

In the comparative analysis of the TRAMI (M-TEER) and TriValve (tricuspid therapies) registries, Mehr et al. [43] included 228 patients with severe MR and TR: 106 underwent isolated M-TEER, while 122 received combined mitral + tricuspid repair. At one-year, all-cause mortality was 34% in the mitral-only group versus 16% in the combined group (p = 0.035), with multivariable analysis confirming TMTVR therapy as an independent predictor of survival. However, these findings derive from observational registries, and substantial residual confounding cannot be excluded. Causal inference cannot be established.

Further confirmation comes from smaller recent series. Papadopoulos et al. [44] reported data in a cohort of 42 patients (median age 77 years, 64% female) undergoing combined M-TEER and T-TEER. Implantation success was 100%, with mean device and procedure times of 39 and 71 minutes, respectively. No major adverse events occurred in-hospital or at 30 days, aside from two cases of tricuspid single leaflet device attachment (4.8%) and one atrial septal defect closure (2.4%). During a median follow-up of 11 months, three patients (7.1%) required hospitalization for HF, but no deaths were reported. At one year, all patients were in NYHA class II or better, MR was $\le$2+ in every case, and 81% had only trivial or mild TR.

Future prospective studies are needed to define the optimal timing and patient selection, including survival, rehospitalizations, right ventricular function, and durability of repair. Until then, concomitant or staged M-TEER and T-TEER (Fig. 5) should be considered on an individual basis, particularly in high-risk surgical candidates with favorable anatomy.

Fig. 5.

Concomitant M-TEER and T-TEER. (A) TEE: central severe mitral regurgitation. (B) Implantation device: Single device (PASCAL P10) in A2-P2 position. (C,D) 2D TEE using orthogonal views (intercommissural and left ventricular outflow tract) and zoom-3D view showing mild mitral regurgitation post procedure. (E) TEE: severe tricuspid regurgitation. (F,G) Implantation devices (PASCAL Ace): the first device was implanted in anteroseptal position and the second device in central anteroseptal position in close relation to the first one. (H) Fluoroscopy image showing all the devices. M-TEER, mitral transcatheter edge-to-edge repair; T-TEER, tricuspid transcatheter edge-to-edge repair; TEE, transesophageal echocardiogram.

Mitral annulus calcification (MAC) is a chronic, degenerative process characterized by calcium deposition within the fibrous support ring of the mitral valve. It may range from focal, mild calcification to extensive circumferential involvement extending into the leaflets, subvalvular apparatus, or ventricular myocardium. MAC is frequent among older patients with MR and is associated with increased procedural complexity and higher baseline risk. Contemporary series show that M-TEER is feasible and generally safe in carefully selected MAC anatomies, but outcomes depend heavily on detailed multimodality imaging.

Favorable anatomy typically includes:

- calcium confined to the annulus without extension into the coaptation zone;

Conversely, “no-go” features for M-TEER include:

- extensive leaflet calcification limiting grasping;

In the multicenter study by Fernández-Peregrina et al. [57] (61 MAC vs 791 no/mild MAC), procedural success was similar (91.8% vs 95.1%; p = 0.268) with low complication rates. At 1 year, MR $\le$2+ was achieved in 90.6% (MAC) and 79.5% (no/mild MAC), and ~80% in both groups were NYHA $\le$II [57]. There was a trend toward higher all-cause mortality in MAC (19.7% vs 11.3%; p = 0.050), while cardiovascular mortality did not differ significantly, underscoring that excess risk in MAC may relate to overall substrate rather than valve failure per se.

Larger multicenter cohorts and meta-analyses align with these findings. Hatab et al. [58] reported that M-TEER in significant MAC achieved similar 1-year MR reduction compared with none/mild MAC, but moderate/severe MAC carried higher 1-year mortality and less symptomatic improvement, reinforcing the prognostic weight of the underlying disease. A recent meta-analysis likewise found durable MR reduction and functional gains after M-TEER in MAC, yet higher 1-year mortality persisted, pointing to patient risk rather than procedural futility [59].

Interestingly, Condos et al. [60] reported the feasibility of M-TEER in 13 patients with MAC and large mitral annuli as a preparatory step before transcatheter mitral valve replacement. The rationale was to shorten the intercommisural distance using M-TEER. Commissural M-TEER was successful in all patients, with no leaflet detachment, and NTW devices were the most frequently employed. Following TMVR, paravalvular leak was absent or limited to trace in all cases. Overall, M-TEER can be a reasonable option in patients with MAC when the anatomy suggests that a durable repair is achievable—meaning adequate leaflet coaptation and acceptable transmitral gradients. The decision, however, has to be made in the context of the patient’s overall risk profile and expected benefit. Careful imaging, using echocardiography and CT when necessary, together with discussion in a multidisciplinary heart team, is key to weighing the potential gains of the procedure against the challenges and risks imposed by MAC.

Mitral transcatheter edge-to-edge repair has evolved into a versatile and increasingly adopted therapy across a broadening spectrum of clinical scenarios beyond current guideline indications. Evidence consistently supports its safety and effectiveness in high-risk patients with acute post-myocardial infarction MR, moderate secondary MR, advanced heart failure, HOCM, mitral annulus calcification, and in carefully selected candidates for combined structural interventions. Across these settings, successful MR reduction is associated with meaningful symptomatic improvement and, in several scenarios, with improved survival compared with conservative therapy. Nevertheless, patient selection remains the cornerstone of optimal outcomes, and the balance between anatomical feasibility, procedural success, and long-term benefit must be individualized within a multidisciplinary heart team. Future progress will rely on randomized trials clarifying the role of M-TEER in high-risk patients, establishing its utility in advanced HF as bridge or destination strategy, and evaluating combined transcatheter approaches and interventions in MAC. Such studies are essential to refine patient selection, determine long-term durability, and delineate the true boundaries of expanding indications for M-TEER.

HF, heart failure; HOCM, hypertrophic obstructive cardiomyopathy; LV, left ventricle; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; M-TEER, mitral transcatheter edge-to-edge repair; AMI, acute myocardial infarction; NYHA, New York Heart Association; PMR, papillary muscle rupture; GDMT, guideline-directed medical therapy; LAAC, left atrial appendage closure; TAVI, transcatheter aortic valve implantation; MAC, mitral annulus calcification; LVAD, left ventricular assist device.

Writing—original draft preparation, CIO and JEM; writing—review and editing, CIO, JEM, DGF and REL; visualization, CIO, JEM, and DGF; validation, AÍR; supervision, REL. All authors contributed to the conception and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Not applicable.

The authors gratefully acknowledge Dr. Manuel Barreiro Perez for his clinical expertise and meaningful contributions to the development of this study.

This research received no external funding.

The authors declare no conflict of interest.