Contemporary Review on Multi-Modality Imaging Evaluation and Management of Functional Mitral Regurgitation

Functional mitral regurgitation (FMR), or secondary mitral regurgitation, has traditionally been defined as valvular incompetence occurring in the setting of structurally normal mitral leaflets and chordae, where regurgitation results from adverse geometric remodeling of the left ventricle (LV) rather than from primary leaflet pathology [1]. In this classic, LV-centric paradigm, FMR is distinguished from primary (organic) mitral regurgitation by its etiology: global or regional LV remodeling displaces the papillary muscles and tethers the leaflets, thereby impairing systolic coaptation [1]. More recently, this concept has been refined, and FMR is now recognized to encompass at least two distinct pathophysiological phenotypes: ventricular FMR (VFMR) and atrial FMR (AFMR) [1]. VFMR represents the traditional LV-driven mechanism, whereas AFMR arises from left atrial (LA) enlargement with resultant annular dilatation, typically in the context of atrial fibrillation (AF) or heart failure with preserved ejection fraction (HFpEF) where left atrial pressure is chronically elevated, and this can occur despite preserved LV systolic function [1,2,3,4,5,6,7,8].

Irrespective of the underlying mechanism, FMR is a clinically important entity because of its rising prevalence, close association with heart failure symptoms, and adverse impact on prognosis [2,4,9,10,11]. Recognition of the distinct ventricular and atrial phenotypes is critical, as they differ in anatomy, clinical course, and response to therapy and may thus require tailored diagnostic and interventional strategies [1,2,3,4,5,6,7,8]. Multimodality imaging, including transthoracic and transesophageal echocardiography, cardiac magnetic resonance, and computed tomography, has become indispensable not only for accurate quantification of MR severity but also for distinguishing between AFMR and VFMR and for procedural planning [3,9,10]. In parallel, management has evolved from a foundation of guideline-directed medical therapy (GDMT) to a broad spectrum of surgical and, increasingly, transcatheter interventions targeted to the specific mechanism of regurgitation [10,12,13,14,15,16]. This review synthesizes contemporary understanding of FMR, emphasizing the pivotal role of multimodality imaging and outlining current and emerging management strategies across the spectrum of ventricular and atrial phenotypes.

FMR is one of the most prevalent forms of moderate-to-severe mitral regurgitation in adults, accounting for approximately 65% of cases in a community-based cohort [17]. The estimated prevalence of moderate-to-severe mitral regurgitation in the general adult population ranges from 0.46% to 2.3% [2,17,18], with FMR occurring more frequently among older individuals and those with comorbid conditions, such as heart failure or atrial fibrillation [2,19,20,21].

The clinical burden of FMR is significant. Compared to the general population and to patients with primary mitral regurgitation of similar severity, individuals with FMR experience markedly increased morbidity and mortality [2,4,9,10,11]. The five-year heart failure incidence can be as high as 80% in VFMR and 59% in AFMR [22]. All-cause mortality is significantly elevated, with reported risk ratios ranging from 1.88 to 3.45 across FMR subtypes [17,23,24,25]. Notably, severe FMR confers a graded increase in mortality across all heart failure phenotypes, with hazard ratios reaching as high as 7.5 in the most advanced cases [24,25,26]. Despite its high prevalence and adverse prognosis, FMR remains a challenge to diagnose and treat. Fewer than 10% of affected patients undergo surgical or transcatheter mitral interventions [15], underscoring the need for improved recognition and management of this condition.

The mitral valve sits on a saddle-shaped annulus. There are 2 mitral valve leaflets, the anterior and posterior leaflets. There are chordae tendineae attached to each leaflet, which allow the mitral valve to perform its function during systole and diastole. FMR arises from perturbations in cardiac geometry of the saddle-shaped annulus and/or LV function that impair mitral valve competence despite structurally normal leaflets and sub-valvular apparatus [9]. On this basis, FMR can be further classified into three distinct phenotypes: VFMR, AFMR, and dual FMR [2,4,7,27,28,29]. VFMR is more common in males and is associated with left ventricular systolic dysfunction and ischemic heart disease [2,17,30,31,32], while AFMR is predominantly linked to AF and left atrial enlargement [19,27,33,34,35,36]. Dual FMR reflects the coexistence of atrial and ventricular mechanisms, in which both annular dilatation and leaflet tethering contribute to regurgitation, and may be encountered in advanced or long-standing cardiomyopathic and atrial remodeling [2,4,7,27,28,29]. Although their initiating mechanisms differ, all three phenotypes converge on a final common pathway: loss of effective leaflet coaptation due to an imbalance between tethering and closing forces [7,27,28,37]. Furthermore, FMR is a dynamic entity: its severity may fluctuate with loading conditions, heart rhythm, blood pressure, and ventricular synchrony [38,39,40]. Ultimately, a structurally normal mitral valve becomes incompetent due to its maladaptive mechanical environment [2], which clearly distinguishes FMR from primary (degenerative) mitral regurgitation, which is related to intrinsic issues with the mitral valve itself. The key mechanistic and clinical differences between VFMR and AFMR are detailed and summarized in Figure 1 and Table 1. Figure 2 details the differing management processes and considerations for VFMR and AFMR, which will be further elaborated in subsequent sections.

VFMR typically occurs in the context of ischemic or nonischemic cardiomyopathy and reflects the downstream consequences of LV dilation, papillary muscle displacement, and mitral annular enlargement [2,41]. These geometric alterations result in apical and lateral displacement of the papillary muscles, leading to increased leaflet tethering and preventing proper coaptation [29,41,42]. Impaired LV contractility reduces closing forces, further exacerbating regurgitation, even in the absence of structural valve abnormalities [3,43].

A contemporary conceptual framework, first articulated by Grayburn et al., categorizes VFMR into proportionate and disproportionate subtypes, depending on the relationship between the effective regurgitant orifice area (EROA) and the extent of LV remodeling [44]. In proportionate VFMR, MR severity aligns with the degree of LV dilation and dysfunction, implying that regurgitation is primarily a reflection of advanced myocardial disease [44]. Management in these patients should focus on reversing or stabilizing LV remodeling through GDMT, cardiac resynchronization therapy (CRT), or mechanical circulatory support, as valve intervention alone is unlikely to significantly alter outcomes [45,46,47]. Disproportionate VFMR is characterized by MR severity that is excessive relative to the degree of LV dilation, a scenario where the EROA is much larger than would be expected based on the LV end-diastolic volume (LVEDV) [44]. Mechanistically, this often results from regional wall motion abnormalities, desynchrony, or asymmetric leaflet tethering [44]. Here, MR itself is thought to drive symptoms and adverse events, so directly addressing the valve lesion surgically or via transcatheter edge-to-edge repair (TEER), offers substantial prognostic benefit [48,49]. This dichotomy has substantial clinical implications; it provides a potential explanation for divergent results in landmark trials: MITRA-FR (dominated by proportionate MR and large ventricles) found no benefit from TEER [16], whereas COAPT (which selected for those with disproportionate MR and smaller LV volumes) demonstrated significant improvements in heart failure hospitalization and mortality [49].

However, this framework has sparked considerable debate, and emerging evidence raises questions about its clinical utility. Hagendorff et al. provide a pointed critique, questioning the physiological validity of “disproportionate” MR and arguing that regurgitant flow cannot meaningfully exceed the limits set by ventricular remodeling [50]. They advocate for a comprehensive echocardiographic assessment over reliance on EROA/LVEDV ratios [50]. Similarly, Ooms et al., in a multicenter registry, observed that although patients classified as having disproportionate FMR initially experienced more robust MR reduction after TEER, this benefit was not sustained and did not translate into better long-term outcomes compared to those with proportionate MR [51]. Furthermore, Kałmucki et al. recently demonstrated that mitral annuloplasty with the Carillon device resulted in MR reduction and LV reverse remodeling, irrespective of “proportionality”, with outcomes not dependent on the EROA/LVEDV relationship [52]. These findings undermine the predictive value of the framework for durable clinical benefit [53].

Rather than viewing these perspectives as mutually exclusive, a more integrative interpretation is that proportionality may serve as a heuristic to frame competing ventricular versus valvular drivers of disease, but not as a binary determinant of treatment eligibility. When EROA and LVEDV appear discordant, a stepwise, physiology-informed approach may be more clinically useful as listed in Figure 3 which includes the following steps: (1) confirm MR severity using multiparametric echocardiographic assessment, including vena contracta width, regurgitant volume, and dynamic loading conditions; (2) interrogate mechanisms of tethering and annular deformation, with attention to regional wall motion abnormalities, dyssynchrony, and leaflet geometry; (3) assess the extent of myocardial disease and reversibility using LV volumes, strain, and cardiac magnetic resonance where available; and (4) evaluate clinical trajectory and response to optimized GDMT. In this framework, markedly dilated ventricles with only modest EROA should prompt caution that MR predominantly reflects advanced myocardial pathology, whereas severe MR in the setting of relatively preserved LV size and focal tethering may reasonably support consideration of valve intervention despite apparent “disproportionality”.

Taken together, the proportionate–disproportionate framework is best regarded as an interpretive lens rather than a prescriptive algorithm. Patient selection for surgical or transcatheter mitral intervention should ultimately rest on comprehensive multimodality imaging, longitudinal assessment of ventricular remodeling, clinical status, and heart team deliberation, rather than on simplified ratios alone. Future prospective studies integrating imaging-derived phenotypes with treatment response are needed to refine risk stratification beyond proportionality metrics and to identify patients most likely to derive sustained benefit from mitral valve intervention.

AFMR occurs in the setting of preserved LV size and systolic function and is driven primarily by LA and mitral annular enlargement [4,28,35]. The most common etiologies are chronic AF and HFpEF [19,20]. Unlike VFMR, AFMR is not associated with papillary muscle displacement or LV dilation; rather, the pathological changes are atrial and annular in origin [4,22,28,35].

Chronic AF and/or elevated LA pressures lead to progressive LA dilation, which causes mitral annular enlargement and loss of its normal saddle shape [36,54,55,56]. The annulus becomes flattened and more planar, reducing leaflet coaptation and increasing the likelihood of central regurgitation [54,55,56]. Although the mitral leaflets are structurally normal, the annular dilation exceeds the compensatory capacity of the leaflets, resulting in a leaflet-to-annulus mismatch [57,58]. AF further compromises annular contractility, diminishing systolic annular shortening and thereby exacerbating regurgitation [59,60]. In some patients, posterior annular displacement may contribute to atriogenic tethering, compounding coaptation failure [34,54,56].

Not all FMR should be treated with the same algorithm. Given that the mechanistic of AFMR is due to atrial dilation, for the cohort with AFMR, treating the driver of atrial dilatation is of great importance. A proposed framework for the management of AFMR is listed as follows.

Given that AFMR is fundamentally driven by left atrial remodeling and dysfunction, therapeutic strategies that target the reduction of continuous adverse LA remodeling need to be considered at the forefront of management. Rhythm control, most commonly via catheter ablation, has emerged as a central therapeutic pillar in AFMR, with accumulating observational evidence demonstrating meaningful reductions in MR severity, left atrial volume, and annular dimensions, alongside improvements in diastolic function, natriuretic peptide levels, and functional status [7]. Importantly, MR improvement following successful rhythm control can reduce propensity for further atrial dilatation and loss of annular contraction in AFMR, rather than irreversible leaflet or ventricular pathology.

Although randomized data are lacking, several contemporary cohorts suggest that maintenance of sinus rhythm is associated with durable MR reduction and lower progression to dual FMR, particularly when intervention occurs before advanced atrial myopathy or severe annular dilation has developed [19]. These observations underscore the importance of early rhythm control in appropriately selected patients. Consistent with this concept, the Japanese Circulation Society assigns a Class IIa recommendation for catheter ablation in symptomatic patients with persistent atrial fibrillation and severe functional MR when sinus rhythm maintenance is considered achievable, highlighting atrial-directed therapy as a disease-modifying strategy rather than purely symptomatic management.

In cases of HFpEF that contribute to elevated LA pressure, guideline-directed therapy, including diuretics for volume optimization and aggressive blood pressure control, remains an essential adjunct.

Valve intervention should be considered in patients with persistent severe MR and NHYA class III–IV symptoms despite optimized rhythm control and medical therapy. Careful consideration of MR phenotype is critical to confirm atrial-predominant MR and to exclude advanced ventricular remodeling or mixed (dual) FMR, which is associated with worse outcomes and may not respond durably to atrial-focused strategies. Multimodality imaging is essential to identify patients in whom MR has become structurally entrenched and is less likely to regress with rhythm control alone.

For patients undergoing surgical intervention, such as mitral valve surgery, surgical mitral annuloplasty, when combined with a Cox-Maze procedure, is a viable interventional consideration for AFMR [61], as it simultaneously addresses annular dilatation and the underlying arrhythmic substrate. Observational data demonstrate substantially lower rates of recurrent MR when surgical annuloplasty is paired with atrial fibrillation ablation compared with annuloplasty alone, reinforcing the concept that isolated annular correction may be insufficient in the presence of ongoing atrial myopathy [61]. However, marked annular enlargement may necessitate aggressive ring under-sizing, increasing the risks of mitral stenosis or annular dehiscence, and mitral valve replacement may be required in select cases. Concomitant repair of atrial functional tricuspid regurgitation should be strongly considered when present.

Transcatheter edge-to-edge repair (TEER) represents an effective alternative in patients at elevated surgical risk and has demonstrated high procedural success and symptomatic improvement in AFMR cohorts. TEER appears to perform more favorably in AFMR than in VFMR, likely owing to preserved LV function and minimal leaflet tethering. Nonetheless, because TEER does not directly address annular dilatation or atrial remodeling, its durability may be limited in patients with progressive atrial myopathy, emphasizing the importance of careful patient selection. It is important to have a robust heart team meeting to discuss, as the success of TEER procedures often depends on the center’s success in treating mitral valve disease with TEER devices.

Direct and indirect transcatheter annuloplasty systems offer a more mechanistically aligned approach by targeting annular geometry and, in some cases, promoting left atrial reverse remodeling. While these strategies may achieve less immediate MR reduction than TEER, they may offer advantages in selected patients in whom atrial enlargement and annular dysfunction are the dominant drivers of regurgitation. Collectively, these considerations highlight that AFMR management should not default to annular intervention alone; rather, it should integrate rhythm control, atrial substrate modification, and valve therapy in a personalized, stepwise manner.

The main symptoms of both VFMR and AFMR include exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and decreased exercise tolerance [32,42]. These symptoms reflect elevated left-sided filling pressures and pulmonary congestion resulting from both primary ventricular dysfunction and the superimposed regurgitant volume load [9,20,62]. Palpitations and light-headedness can also be present, especially when AF is the underlying rhythm [37]. On physical examination, a holosystolic murmur is often appreciated at the cardiac apex and may radiate to the axilla [2,37,63]. Additional findings typically reflect the severity of heart failure and include signs of volume overload, such as elevated jugular venous pressure, pulmonary rales, hepatomegaly, and peripheral edema [63]. Evidence of underlying left ventricular systolic dysfunction, such as a displaced apical impulse or a soft S1, may also be present [2].

FMR is associated with a high risk of heart failure hospitalization and mortality, with outcomes closely tied to MR severity [17,22,24,25]. It is essential to note that the degree of regurgitation is often dynamic, fluctuating with changes in preload, afterload, or cardiac rhythm, which underscores the importance of serial assessment under physiologic conditions [4,37]. While both FMR subtypes carry increased risk, VFMR is generally associated with higher rates of mortality and heart failure hospitalization than AFMR [17,22,64]. However, in some patients, persistent atrial overload from AFMR can lead to progressive cardiac remodeling and eventual ventricular dysfunction, resulting in a transition to a mixed or “dual FMR” phenotype [22,37].

Electrocardiography (ECG) provides valuable clues to the underlying etiology of FMR, although findings are not specific. In VFMR, ECG may reveal features of structural heart disease, including Q waves or ST-T wave abnormalities indicative of prior myocardial infarction, left bundle branch block, or nonspecific intraventricular conduction delays [31,65]. These abnormalities reflect underlying ischemic or nonischemic cardiomyopathy and may contribute to dyssynchrony that exacerbates regurgitation [65,66]. In AFMR, AF is the most common rhythm disturbance, presenting with absent P waves and an irregularly irregular rhythm [4,28,35,58]. Alternatively, patients in sinus rhythm may exhibit P-wave changes consistent with left atrial enlargement, supporting the diagnosis of AFMR driven by atrial dilation [4,28,35,58].

Laboratory testing is largely non-specific in FMR. Elevated natriuretic peptides (BNP or NT-proBNP) are frequently observed in both VFMR and AFMR, reflecting elevated intracardiac pressures and neurohormonal activation associated with heart failure [67,68]. In more advanced cases, laboratory abnormalities related to end-organ dysfunction may emerge: impaired renal function due to cardiorenal syndrome and mild transaminase elevations due to hepatic congestion from right-sided heart failure [69,70]. However, these findings are not unique to FMR and should be interpreted in the broader clinical context.

Chest radiography offers supportive evidence of cardiac chamber enlargement and pulmonary congestion. Pleural effusions may be present in cases of volume overload [37,68]. Left ventricular enlargement is typically absent in AFMR, reflecting its preserved LV geometry [8,22,54,64]. These diagnostic tools, although not definitive, play a crucial role in the initial assessment and in guiding further imaging and risk stratification.

Echocardiography serves as the cornerstone in the diagnosis and characterization of FMR, providing a direct view of the mitral valve apparatus and its interaction with surrounding cardiac structures [37,63]. A comprehensive echocardiographic examination, ideally combining 2D and 3D imaging, provides both hemodynamic grading and mechanistic insight [37,63]. Echocardiographic grading of MR severity requires a comprehensive, integrative approach, as no single parameter is definitive [37]. Figure 3 details the assessment of MR, both quantitative and semi-quantitative measures, as well as the guidelines of both ACC/AHA and ESC on MR severity thresholds.

As recommended by the ACC/AHA and ASE, this involves synthesizing qualitative parameters, such as valve morphology and color Doppler jet characteristics, with semiquantitative parameters like the vena contracta width (VCW; ≥0.7 cm for severe), pulmonary vein flow (systolic flow reversal is specific for severe MR), and a dense, triangular continuous-wave Doppler jet profile [37,63]. These are integrated with quantitative parameters, considered most specific, including regurgitant volume (RegVol; ≥60 mL for severe), regurgitant fraction (RF; ≥50% for severe), and effective regurgitant orifice area (EROA; ≥0.40 cm² for severe) [37,63].

Despite these guidelines, accurately quantifying FMR remains challenging. The regurgitant orifice in FMR is often elliptical and dynamic, making the commonly used PISA method, which assumes a circular orifice, susceptible to underestimation [71]. Contemporary professional society guidelines generally agree on the importance of integrating quantitative and qualitative parameters when assessing FMR, differ in how rigidly EROA thresholds are applied, and how they inform TEER candidacy. The ACC/AHA guidelines define severe secondary MR using an EROA ≥ 0.40 cm² (or regurgitant volume ≥ 60 mL) [37], consistent with primary MR, yet emphasize that intervention decisions, particularly TEER, should be guided by symptom burden, response to GDMT, and patient selection criteria derived from COAPT rather than by EROA alone [12]. In contrast, the ESC/EACTS guidelines adopt lower quantitative thresholds for severe FMR (EROA ≥ 0.20 cm² or regurgitant volume ≥ 30 mL) [2]. The differences in EROA thresholds reflect the challenging aspects of MR assessment, given differences in mechanistic factors and the load-dependent nature of secondary MR, but both guidelines similarly stress comprehensive assessment and clinical context over isolated cutoffs. Recent studies suggest that an intermediate value of around 0.30 cm² may better correlate with adverse outcomes and response to therapy [72,73]. The ASE/EACVI recommendations further reinforce this integrative approach, cautioning against reliance on a single parameter, such as EROA, and advocating multiparametric grading that incorporates ventricular size and function, regurgitant jet characteristics, and dynamic behavior [74]. Taken together, these documents are aligned in recognizing the limitations of rigid EROA thresholds in FMR and converge on the principle that TEER candidacy should be determined by a holistic evaluation of MR severity, ventricular remodeling, and clinical status rather than by any single quantitative metric. Figure 4 illustrates the multi-parametric transthoracic echocardiographic assessment used to grade severe AFMR, encompassing chamber enlargement, jet characteristics, and quantitative Doppler measurements.

Beyond grading, echocardiography is crucial for identifying the specific FMR mechanism [37,38]. In VFMR, the image typically shows a dilated or regionally remodeled left ventricle with apically and laterally displaced papillary muscles, leading to a tethered (Carpentier type IIIb) configuration [1,2,3,8,38]. Tenting parameters (height > 10 mm or area > 2.5 cm²) reflect this advanced distortion [1,3,38]. In contrast, AFMR is characterized by significant left atrial and annular enlargement (e.g., indexed LA volume > 34 mL/m²) in the setting of a preserved LV [7,22,28,38]. The annulus flattens and dilates, preventing the structurally normal leaflets from coapting, often creating a central regurgitant jet [4,7,41,75].

Assessment of LV and LA size, function, LV volumes, and LVEF and strain is central to this evaluation [37,38]. LA volume is a sensitive marker of chronic MR, as a normal LA size virtually excludes severe chronic MR [38,76]. Furthermore, LV global longitudinal strain (GLS) can detect early myocardial dysfunction before a decline in LVEF, while LA reservoir strain provides insight into atrial compliance; a reservoir strain below 18% indicates poor compliance, elevated pulmonary pressures, and a higher likelihood of failure with rhythm-control strategies [77,78,79,80,81,82]. This comprehensive chamber assessment is pivotal for applying the proportionate/disproportionate VFMR framework, which relies on the relationship between LVEDV and EROA to guide therapy [44,45].

Finally, specialized echocardiographic studies are used in specific clinical scenarios [44,63,83,84]. Stress echocardiography, preferably with exercise, is recommended when the severity of MR at rest does not correlate with clinical symptoms [40,63,85]. Key findings associated with adverse outcomes include a dynamic increase in MR severity (e.g., an EROA increase ≥13 mm²) or the development of pulmonary hypertension (PASP ≥ 60 mmHg) [40]. Transesophageal echocardiography (TEE) is essential when transthoracic echocardiography images are inconclusive and is mandatory for procedural planning and guidance [2,86]. TEE provides superior, high-resolution visualization of leaflet morphology, coaptation depth, and annular geometry (Figure 5) [2,86]. 3D TEE, in particular, offers a “surgical view” that is critical for assessing suitability for TEER and other transcatheter interventions [63,83,87]. During the MitraClip procedure, TEE is used for device navigation, guidance of transseptal puncture (e.g., measuring height from the annular plane), precise leaflet grasping, and assessment of the final post-deployment result [63,86]. This step-by-step guidance is critically important, as demonstrated in Figure 2.

To be clinically actionable, an echocardiographic report should document chamber dimensions, ejection fraction, annular size, leaflet tethering indices, and integrate multiple Doppler indices to estimate severity, explicitly stating which grading criteria were used. Most importantly, it should provide a mechanistic interpretation, concluding whether the regurgitation is predominantly ventricular, atrial, or mixed, as this narrative is essential for informing the management strategy.

Cardiac magnetic resonance (CMR) imaging offers a comprehensive, high-resolution, and reproducible assessment of both cardiac chambers and the mitral valve apparatus, making it an invaluable tool for evaluating FMR (Figure 6) [88,89,90,91]. As the reference standard for quantifying left ventricular and atrial volumes, systolic function, and remodeling, CMR plays an increasingly central role in the diagnosis, risk stratification, and longitudinal monitoring of patients with FMR [37,68,92,93].

One of the key advantages of CMR is its ability to quantify mitral regurgitant volume and fraction with high accuracy and low operator dependency [88,90]. This is achieved by subtracting aortic forward stroke volume, measured via phase-contrast velocity mapping, from the total left ventricular stroke volume derived from cine images [38,88,94,95]. The resulting regurgitant fraction (≥35% is often considered severe) is highly reproducible and particularly helpful when echocardiographic assessments are technically limited or yield discordant findings [78,96]. These volumetric parameters provide a robust estimate of MR severity and reflect its hemodynamic burden over time, thereby aiding in therapeutic decision-making [78,96].

Emerging 4D flow CMR techniques allow for direct visualization and quantification of complex regurgitant jets, including multiple or eccentric jets, and enable time-resolved assessment of regurgitant flow throughout systole [97]. While 4D flow offers theoretical advantages in capturing complex MR geometry, its use remains limited by longer acquisition times, post-processing complexity, and lack of standardized thresholds [98]; thus, it is currently best viewed as complementary to established indirect volumetric methods rather than a replacement in routine clinical practice.

CMR is also exceptional at defining the underlying FMR mechanism [38,90,91]. In ventricular-driven FMR, it typically reveals left ventricular dilation, impaired systolic function, and regional wall motion abnormalities [1,41,99]. It can precisely visualize apical papillary muscle displacement and leaflet tethering, correlating well with echocardiographic findings [1,99]. In contrast, atrial-driven FMR exhibits a distinctly different pattern, characterized by significant left atrial and annular enlargement, while the left ventricle remains structurally and functionally preserved [4,7,58]. CMR may also visualize subtle forms of “atriogenic” leaflet tethering, in which posterior leaflet angulation arises from posterior annular displacement, reinforcing the mechanical nature of AFMR [38,90,91].

CMR’s most notable contribution is the characterization of myocardial tissue using late gadolinium enhancement (LGE) and T1 mapping techniques [68]. LGE detects replacement fibrosis (scar), which is typically focal and associated with prior infarction or advanced remodeling [100]. In FMR, the presence and extent of LGE are independently associated with adverse outcomes, including mortality and heart failure hospitalization [101]. For example, Wang et al. demonstrated that in both ischemic (ICM) and nonischemic (NICM) cardiomyopathy, LGE (≥5% in ICM or ≥2% in NICM) predicted worse event-free survival, with the combination of high MR fraction and LGE conferring an additive risk [102]. Similarly, Badau Riebel et al. found that replacement fibrosis detected by LGE was a strong independent predictor of adverse outcomes (HR 1.83) [103].

In addition, T1 mapping and extracellular volume (ECV) quantification enable the detection of diffuse interstitial fibrosis, which often precedes overt systolic dysfunction and is not visualized by LGE [104]. Elevated native T1 and ECV values are associated with adverse remodeling and worse prognosis in MR [105,106]. Badau Riebel et al. also demonstrated that interstitial fibrosis, as identified by T1 mapping, was an independent predictor of adverse outcomes (HR 1.61) [103]. The prognostic value of this tissue characterization is substantial: both replacement and interstitial fibrosis are associated with less improvement in LV function and symptoms after intervention [103,106]. These findings can thus inform the timing and selection of therapy, identifying high-risk patients who might benefit from earlier or alternative strategies [68,107].

Taken together, the strengths of CMR lie not only in its volumetric precision and reproducibility but also in its ability to integrate structural, functional, and tissue-based assessments in a single modality. As such, CMR serves as a valuable adjunct to echocardiography, particularly when discrepancies exist or when detailed anatomical and myocardial characterization is essential for guiding therapy. Its contributions are especially critical in distinguishing phenotypes of FMR, determining chronicity, and identifying candidates for valve-directed versus rhythm- or remodeling-focused therapies.

Cardiac computed tomography (CT) has emerged as a complementary modality for the structural assessment of FMR, providing high-resolution, three-dimensional visualization of the entire mitral apparatus—including the annulus, leaflets, chordae, and papillary muscles—with submillimeter spatial accuracy (Figure 7 and Figure 8) [108]. While three-dimensional echocardiography remains central to FMR evaluation, CT is widely regarded as the reference standard for mitral annular quantification and offers unique advantages in characterizing complex mitral geometry [109]. Multiphase CT reconstructions allow precise assessment of annular area, inter-commissural and septo-lateral diameters, annular nonplanarity, leaflet length, tenting height, and papillary muscle position throughout the cardiac cycle [110,111].

Importantly, CT provides incremental value in phenotyping FMR mechanisms, particularly in differentiating ventricular from atrial functional MR. In VFMR, CT readily demonstrates LV dilation, papillary muscle displacement, leaflet tethering, and increased tenting geometry [22], whereas AFMR is characterized by marked annular dilatation, annular flattening, and preserved papillary muscle geometry in the setting of normal or near-normal LV size [4]. These distinctions are especially relevant in borderline or mixed phenotypes, where accurate mechanistic classification directly informs downstream management strategies.

CT is also indispensable for procedural planning of transcatheter mitral interventions [112,113]. In the context of transcatheter mitral valve replacement (TMVR), CT enables detailed prosthesis simulation, virtual valve deployment, and accurate calculation of the neo–left ventricular outflow tract (neo-LVOT). A projected neo-LVOT area <2.0 cm² identifies patients at high risk for LVOT obstruction and strongly influences candidacy, device selection, and the need for adjunctive techniques such as intentional laceration of the anterior mitral leaflet (LAMPOON) [114,115]. The same datasets provide critical information on leaflet anatomy, annular dimensions, and the presence, distribution, and severity of mitral annular calcification (MAC), all of which impact the feasibility and durability of both TEER and TMVR [116,117]. In selected cases, CT planimetry of the anatomic regurgitant orifice area can further refine MR severity assessment, particularly when echocardiographic grading is limited by eccentric or multiple jets.

Finally, coronary computed tomography angiography (CCTA) plays an important adjunctive role in patients with suspected ischemic VFMR, where identification of significant coronary artery disease directly informs the need for concomitant revascularization as part of a combined surgical or hybrid strategy [32,100,118,119]. In contrast, broader assessment of extracardiac aortic pathology or general redo sternotomy planning, while valuable in selected surgical cases, is typically secondary to CT’s primary role in defining FMR mechanism and guiding mitral-specific intervention.

In summary, cardiac CT offers unparalleled anatomical detail and quantitative precision for FMR evaluation, with particular strength in mechanistic phenotyping, transcatheter procedural planning, and ischemic substrate assessment. When integrated with echocardiography and cardiac magnetic resonance imaging, CT provides essential complementary information that directly informs patient selection and procedural strategy in contemporary FMR management (Table 2).

As listed above, there are many imaging modalities that prove useful for FMR assessment. Table 2 summarizes the different modalities described above, along with their strengths and limitations in FMR assessment.

FMR is inherently dynamic, with severity varying substantially according to loading conditions, heart rate, rhythm, and ventricular–atrial interactions [2]. Changes in preload, afterload, and contractility can meaningfully alter regurgitant volume and effective regurgitant orifice area over short time intervals, contributing to variability across imaging studies and potential misclassification of severity [5]. Given this marked load dependence, careful standardization of imaging conditions is essential to ensure that measured MR severity reflects the patient’s “true” clinical state rather than transient hemodynamic perturbations [38]. Whenever feasible, MR assessment should be performed under stable, near–euvolemic conditions, ideally after optimization of guideline-directed medical therapy [37]. Imaging performed during acute decompensation, excessive diuresis, dehydration, or uncontrolled hypertension may either exaggerate or underestimate regurgitation severity and should be interpreted with caution [37].

Practical steps to optimize and standardize imaging assessment include: (1) avoiding MR quantification during periods of rapid volume shifts (e.g., immediately after aggressive diuresis or intravenous fluid administration) [37]; (2) documenting blood pressure, heart rate, and rhythm at the time of imaging [37]; and (3) ensuring adequate blood pressure control, as acute elevations in afterload can disproportionately increase regurgitant severity [37]. In patients with atrial fibrillation, averaging measurements over multiple cardiac cycles is essential, and echocardiographic assessment should ideally be performed at a controlled ventricular rate [37]. Medication status should also be considered and reported. Imaging obtained before initiation or up-titration of vasodilators, diuretics, or rhythm-control therapies may not reflect steady-state conditions [32]. When serial imaging is used to guide management decisions, efforts should be made to perform studies under comparable hemodynamic and pharmacologic conditions to allow meaningful longitudinal comparison [38]. Stress echocardiography further highlights the dynamic nature of FMR by unmasking exertional increases in regurgitation severity and pulmonary pressures that may not be evident at rest [38]. However, resting MR severity used to guide interventional decisions should be grounded in standardized, clinically representative conditions rather than extreme loading states [38].

Taken together, recognition of FMR dynamism must be coupled with deliberate standardization of imaging acquisition and interpretation. Explicit documentation of loading conditions and thoughtful patient preparation reduces the risk of misclassification, improves reproducibility, and enhances the clinical relevance of imaging-based decision-making.

Treatment modalities for FMR vary significantly in patient selection, mechanism of action, supporting evidence, and clinical outcomes (Table 3). Figure 4 summarizes an imaging-guided management algorithm distinguishing VFMR from AFMR and illustrates how specific imaging phenotypes inform selection among medical therapy, TEER, surgery, and TMVR.

Medical and device-based optimization forms the foundation of management in FMR, with the overarching goals of relieving symptoms, reducing mitral regurgitant volume, and delaying or potentially avoiding invasive intervention [21,120]. Both the American College of Cardiology (ACC) and the Heart Failure Association of the European Society of Cardiology (ESC-HFA) emphasize that therapy should begin with comprehensive GDMT for heart failure, with escalation to device or interventional strategies reserved for patients who remain symptomatic despite optimal medical management [9,14,47].

In patients with FMR and reduced ejection fraction, GDMT represents the first-line approach [68]. According to joint recommendations from the ACC, American Heart Association (AHA), and Heart Failure Society of America (HFSA), all eligible patients should receive a combination of the following: a beta-blocker, a renin-angiotensin system inhibitor (ARNI preferred, or ACEi/ARB if ARNI is not tolerated), a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and a sodium-glucose cotransporter 2 inhibitor (SGLT2i) [68]. These agents not only improve survival and reduce heart failure hospitalizations but have also been shown to directly impact the severity of FMR in many cases [63]. By promoting reverse remodeling, these medications reduce left ventricular volumes and loading conditions and improve geometry, often leading to a reduction in regurgitant severity [68].

Device-based therapies are crucial adjuncts in selected patients [2]. In particular, cardiac resynchronization therapy (CRT) is indicated for individuals with an LVEF ≤ 35%, sinus rhythm, left bundle branch block, and a QRS duration of ≥150 ms [121,122,123]. CRT improves left ventricular synchrony, facilitates reverse remodeling, and has been shown to reduce the degree of FMR [2,46,124,125,126]. For patients with AFMR complicated by AF, rhythm control strategies, including antiarrhythmic medications and catheter ablation, can reduce left atrial size and improve annular function, thereby mitigating the severity of regurgitation [7,127,128].

In ischemic FMR, coronary revascularization (either PCI or CABG) plays a crucial role [74]. Many patients with moderate ischemic MR experience MR improvement after revascularization alone, especially with CABG, which is associated with better event-free survival compared to PCI [129,130]. Concomitant mitral annuloplasty with CABG further improves outcomes in selected patients [130,131]. Decision-making should be multidisciplinary, considering comorbidities, operative risk, and individual patient factors [74,132].

Surgical treatment for FMR is generally reserved for patients who remain symptomatic despite maximally optimized GDMT and, when appropriate, CRT [32,133]. According to current ACC/AHA recommendations, surgery is indicated in patients with severe FMR, whether of ventricular or atrial origin, primarily when concomitant cardiac surgery, such as coronary artery bypass grafting (CABG), is already planned [32]. Isolated mitral surgery for FMR is less commonly performed due to the lack of a proven survival benefit and the high rates of recurrence [32]. Therefore, patient selection is a nuanced process that requires a multidisciplinary approach [32,37,134].

The management of Ischemic FMR (VFMR) has been heavily influenced by two landmark randomized trials from the Cardiothoracic Surgical Trials Network (CTSN) published in The New England Journal of Medicine, which clarified the role of surgery in both moderate and severe disease (Table 4) [135,136]. For moderate ischemic MR, the trial by Smith et al. (2014) randomized 301 patients undergoing CABG to receive either CABG alone or CABG plus mitral valve repair (restrictive annuloplasty) [135]. At one year, the addition of mitral repair did not improve survival or left ventricular reverse remodeling [135]. While the combined group had less residual MR, this did not translate into improved clinical outcomes [135,136]. Furthermore, the addition of repair increased operative time, hospital length of stay, and the risk of neurologic events and arrhythmias [74,135,136]. Consequently, for patients with moderate ischemic MR, CABG alone is generally considered sufficient, as revascularization often reduces MR severity without the added morbidity of valve intervention [2,32,74,135,137]. For severe ischemic MR, the choice between repair and replacement was addressed by Acker et al. (2014) and Goldstein et al. (2016) [138,139]. This trial randomized 251 patients to either restrictive mitral annuloplasty (RMA), using a downsized rigid ring, or chordal-sparing mitral valve replacement [138]. The results highlighted a critical distinction between functional and primary MR [2]. Unlike primary MR, where repair is superior, in FMR, repair demonstrated poor durability [2,138,139]. At two years, the repair group had a significantly higher rate of recurrent moderate-to-severe MR (58.8% vs. 3.8%) and more heart failure-related adverse events compared to the replacement group [139]. However, there was no significant difference in survival between the two strategies [138,139]. These findings have shaped contemporary technical considerations. Repair remains an option for patients with mild tethering and less advanced ventricular remodeling, potentially favored in younger patients (<65 years) to avoid the risks of prosthetic valves [140]. However, because repair failure is driven by ongoing ventricular remodeling and leaflet tethering, chordal-sparing replacement is now generally preferred for patients with predictors of repair failure [2,32]. These predictors include a tenting height >10 mm, a posterior leaflet angle >45°, or significant infero-basal wall motion abnormalities [3,37]. Replacement in these high-risk anatomies provides a more durable correction of MR and fewer heart failure readmissions [2,139].

In contrast to the ventricular phenotype, AFMR requires a different surgical logic. Because the leaflets are typically structurally normal and regurgitation is driven by annular dilatation, isolated ring annuloplasty is highly effective and durable [27,141,142,143,144,145]. In the largest contemporary series, annuloplasty alone yielded a five-year survival rate of approximately 75% with low recurrence rates [141,142,144,145]. However, surgical success in AFMR often requires addressing the accompanying atrial pathology; standard practice includes concomitant Cox-Maze ablation and rhythm control strategies for atrial fibrillation, such as ablation or reducing afterload conditions that may contribute to elevated left ventricular/atrial filling pressures [111,142,143,146].

In summary, surgical management of FMR is mechanism specific. While AFMR is reliably treated with annuloplasty, moderate ischemic VFMR is often best managed with revascularization alone, and severe VFMR frequently necessitates valve replacement to ensure durability. Regardless of the technique, the decision to operate must weigh the limited survival benefit against the risks, prioritizing symptom relief and quality of life.

TEER has become a cornerstone intervention for selected patients with FMR who remain symptomatic despite maximally optimized GDMT [12,32,37]. Applicable to both VFMR and AFMR subtypes, TEER offers a less invasive alternative to surgery for patients with prohibitive operative risk [32,37].

The American College of Cardiology recommends TEER in patients with severe, symptomatic FMR and a left ventricular ejection fraction (LVEF) between 20–50%, left ventricular end-systolic dimension <7.0 cm, pulmonary artery systolic pressure <70 mmHg, and effective regurgitant orifice area (EROA) ≥0.3 cm², aligning with the inclusion criteria of the landmark COAPT trial [32,37]. These recommendations are made in the context of a multidisciplinary heart team decision, informed by comprehensive multimodality imaging to ensure anatomical suitability, specifically adequate leaflet length, coaptation depth, and a mitral valve area ≥4.0 cm², using anatomical criteria originally derived from the EVEREST trials (though notably, EVEREST II primarily studied degenerative MR) [37].

The procedure is performed under general anesthesia with continuous transesophageal echocardiography (TEE) and fluoroscopic guidance [74,147]. Devices such as the MitraClip (Abbott) are advanced transseptally across the mitral valve, where the anterior and posterior leaflets are grasped at the origin of the regurgitant jet, creating a double-orifice valve that reduces regurgitation [2,147]. Multiple clips may be deployed as needed to optimize the result [74,147]. The clinical evidence base for TEER in FMR is defined by three pivotal randomized trials, MITRA-FR, COAPT, and RESHAPE-HF2, which yielded differing results driven by distinct patient selection strategies (Table 5) [2,12,13,15,37,68,123,148].

The MITRA-FR trial randomized 304 patients with severe FMR and heart failure to MitraClip plus medical therapy versus medical therapy alone [16]. The trial found no significant difference in the composite endpoint of all-cause death or unplanned heart failure hospitalization at 1 or 2 years [16]. A critical analysis of the cohort reveals that MITRA-FR patients had larger LV volumes but less severe MR (mean EROA 0.31 cm²) relative to that ventricular size, a phenotype often described as “proportionate” MR [44,45,149]. Furthermore, the optimization of GDMT prior to enrollment was less stringent than in subsequent trials [45,150]. These factors suggest that in patients where MR is merely a biomarker of advanced ventricular disease rather than a driver, valve intervention may be futile [10,16].

In contrast, the COAPT trial enrolled 614 patients with symptomatic heart failure and moderate-to-severe or severe FMR who remained symptomatic despite a rigorous “run-in” period of maximally tolerated GDMT [48,151]. In this cohort, TEER with MitraClip led to significant reductions in heart failure hospitalizations (HR 0.53) and all-cause mortality (HR 0.62) at 24 months compared to GDMT alone, with durable benefits observed up to 36 months, along with improved quality of life [48,151]. The COAPT population differed fundamentally from MITRA-FR: patients had more severe MR (mean EROA 0.41 cm²) but less severe LV dilation [44]. This “disproportionate” MR phenotype implies that the valvular lesion contributed excessively to the pathophysiology, making it a prime target for repair [44].

Most recently, the RESHAPE-HF2 trial has expanded the evidence base. It included 505 patients with moderate-to-severe FMR (mean EROA 0.25 cm²) and symptomatic heart failure [13]. TEER significantly reduced first and recurrent heart failure hospitalizations and cardiovascular death at 24 months, with consistent benefits across subgroups [13,148,152]. Notably, the benefit was pronounced in patients with recent heart failure hospitalizations [148,152]. The results of RESHAPE-HF2 support the broader application of TEER, suggesting that clinical benefit extends to patients with MR severity that may be lower than the strict COAPT thresholds, provided they remain symptomatic despite medical therapy [13,152].

Real-world data, specifically regarding AFMR, also demonstrate encouraging outcomes. Registry data indicate procedural success rates ranging from 87% to 94%, with durable symptomatic improvement. In the Spanish Mitraclip series, 94% of AFMR patients had MR reduced to grade ≤2+, and 80% improved to a NYHA functional class I–II at 12 months [153,154]. The MITRA-TUNE registry reported mid-term MR recurrence in only 11% [155,156,157]. However, anatomical phenotype matters: patients with “hamstrung” or atriogenic tethering, characterized by massive atrial enlargement causing marked posterior leaflet angulation, often experience higher residual MR and worse outcomes, highlighting the need for careful anatomical screening [157,158].

Technological evolution continues to refine these outcomes. Beyond the MitraClip, the Edwards PASCAL system offers novel design features, including independent leaflet capture and a central spacer, which enable enhanced adaptation to complex anatomy [15,159]. In the CLASP study, PASCAL achieved MR grade ≤2+ in 96% of cases with a 92% one-year survival rate [160]. A head-to-head analysis from the CLASP IID randomized trial demonstrated non-inferiority of PASCAL compared to MitraClip in both safety (3.4% vs. 4.8% major events) and efficacy, with numerically higher rates of trace or no MR at six months (87% vs. 84%) [161,162,163].

Successful procedural planning relies heavily on 3D TEE and CT to assess jet location, leaflet length, and annular dimensions [164,165]. In VFMR, broad central jets may necessitate multiple clips, whereas AFMR often requires centrally placed devices, unless atriogenic tethering is present [164]. Residual trans-mitral gradients > 5 mmHg, severe annular calcification, and flail gaps > 10 mm remain relative contraindications [37,166]. Following TEER, particularly in AFMR, aggressive rhythm control may offer additional remodeling benefits; however, this effect diminishes in the setting of extensive atrial fibrosis [19,166]. Overall, TEER offers higher procedural success and lower morbidity than surgery, positioning it as the preferred intervention for appropriate candidates [12,15,152].

Indirect coronary sinus annuloplasty represents a minimally invasive, anatomically guided strategy for treating FMR, exploiting the proximity of the coronary sinus (CS) and the great cardiac vein to the posterior mitral annulus [167,168]. Among available technologies, the Carillon Mitral Contour System is the most extensively studied device [13,52,167,169,170,171,172]. It is deployed percutaneously via the right internal jugular or femoral vein and implanted within the coronary sinus, where it applies circumferential tension to reduce the septal-lateral annular dimension, thereby enhancing leaflet coaptation and mitigating mitral regurgitation [167,169,170].

The physiological rationale for this technique lies in the unique anatomical relationship between the coronary sinus and the adjacent mitral annulus [173,174,175]. By anchoring and “cinching” the coronary sinus, the posterior annulus can be effectively constricted without entering the left atrium or ventricle [174]. However, this anatomical relationship varies among patients, and pre-procedural imaging plays a crucial role in determining procedural feasibility [176]. Optimal outcomes are associated with a coronary sinus-to-annulus distance of less than 7.8 mm and an angle of less than 14.2°, as determined by pre-procedural cardiac CT angiography [177]. In addition, the proximity of the coronary sinus to the left circumflex artery raises the risk of coronary compression, making detailed anatomic evaluation and intraprocedural monitoring essential to avoid vascular complications [173,174,175].

Clinical trials and pooled analyses have consistently shown that the Carillon device reduces MR severity, facilitates left ventricular reverse remodeling, and improves functional capacity, particularly in patients with proportionate FMR, in which annular dilation is the dominant pathophysiologic mechanism (Table 6) [13,167,170,171,172,178]. In this subgroup, indirect annuloplasty reduces left ventricular volumes and enhances forward stroke volume, providing symptomatic relief without the need for left heart access [52]. Among patients with AFMR, the technique has also proven safe and effective, demonstrating reductions in left atrial volume and improvements in NYHA functional class; however, the degree of MR reduction may be less dramatic than with TEER [142,144,176]. Importantly, the procedural success rate is high, and major adverse events are relatively infrequent if patients are appropriately selected [169,176,179].

However, the anatomical suitability of the coronary sinus remains a major determinant of procedural efficacy [168,173,175,176]. Not all patients have favorable CS anatomy, and suboptimal alignment or excessive CS annulus separation can limit the capacity for effective annular remodeling [173,175,176,180]. As such, comprehensive multimodality imaging, including echocardiography, cardiac CT, and, where necessary, coronary angiography, is indispensable for case planning [38,83,181]. In recognition of this, both the American Society of Echocardiography and the European Association of Echocardiography recommend detailed pre-procedural evaluation to assess MR severity, annular geometry, and the spatial relationship of the coronary sinus to both the mitral annulus and coronary arteries [38,83,181].

In summary, indirect coronary sinus annuloplasty is a promising, catheter-based intervention for patients with FMR, particularly those with annular-dominant pathology, including both proportionate VFMR and atrial FMR. It offers a safe and less invasive alternative to direct mitral interventions, especially in patients with contraindications to TEER or surgery. While early results are encouraging, ongoing clinical trials and longer-term follow-up are necessary to fully define its place in the therapeutic algorithm, particularly in relation to emerging transcatheter and surgical techniques.

Direct annuloplasty techniques aim to replicate the surgical principle of annular reduction through a fully transcatheter approach [182]. This strategy directly targets annular dilatation, a central pathophysiologic driver in both atrial and select forms of ventricular FMR [182]. Among the devices currently under clinical evaluation, Cardioband (Edwards Lifesciences) and Millipede represent the most advanced platforms [182,183].

The Cardioband system is an adjustable, transcatheter direct annuloplasty device designed to mimic the effect of surgical ring annuloplasty [182,183]. Under combined fluoroscopic TEE guidance, the device is delivered transvenously and sequentially anchored along the posterior mitral annulus, from the lateral to the medial fibrous trigone [147,184,185]. Once in place, the band is cinched in the beating heart, dynamically reducing the septolateral annular dimension until optimal regurgitation reduction is achieved, while carefully monitoring trans-mitral gradient to avoid iatrogenic stenosis [184]. This real-time adjustability allows for individualized optimization of leaflet coaptation and hemodynamics [147,184,186]. Clinical studies have demonstrated that Cardioband implantation is both feasible and safe in high-risk patients, resulting in significant reductions in annular area, mitral regurgitation grade, and left ventricular volume, as well as improvements in NYHA class, exercise capacity, and quality of life at 6 to 12 months (Table 5) [184,185,187]. Device success rates across studies range from 70% to 97%, with most patients achieving moderate or less moderate MR at 1 year [185,187]. In a multicenter feasibility study involving 60 high-surgical-risk patients with moderate-to-severe secondary FMR, Cardioband achieved 87% one-year survival, 66% freedom from heart failure rehospitalization, and 78% freedom from mitral reintervention, with sustained MR reduction and symptomatic improvement [187]. Follow-up registries have confirmed durable MR ≤ 2+ at 12–24 months, with the degree of annular shrinkage correlating with the clinical response [185,187]. Ideal candidates for Cardioband therapy exhibit predominantly annular dilatation, preserved leaflet mobility, and an effective mitral valve area greater than 4.0 cm² [182,183]. Relative contraindications include heavy posterior annular calcification, inter-commissural gaps > 1 cm, and basal ventricular aneurysms, which may impair anchor seating or limit efficacy [182,183].

The Millipede annuloplasty system employs a modular approach, providing a semi-rigid, complete Nitinol ring with eight adjustable anchors, each of which can be repositioned to achieve symmetrical annular capture and reshaping [188]. The system incorporates intracardiac echo guidance, offering precise visualization during deployment [188]. In the first-in-human feasibility study involving seven patients, Millipede achieved a 31% reduction in septolateral annular diameter, with baseline MR grades of 3–4+ reduced to ≤1+ at both discharge and 30 days post-procedure, without any major periprocedural complications [188]. While large-scale data is still pending, the design allows for resheathing and resizing, offering potential advantages in anatomically complex or heterogeneous annular geometries [188]. The system is also compatible with future TMVR, positioning it as a versatile platform for staged or combined interventions [188].

As with all transcatheter mitral therapies, comprehensive pre-procedural imaging is essential for patient selection and procedural planning [37,189]. Both the American Society of Echocardiography and the European Association of Cardiovascular Imaging emphasize detailed evaluation of annular geometry, leaflet motion, and MR severity using echocardiography and cardiac CT [37,189]. Direct annuloplasty is generally most effective in patients with AFMR or milder forms of VFMR, where leaflet tethering is limited [144,166,190]. In contrast, for patients with advanced ventricular remodeling and a tenting height greater than 10 mm, edge-to-edge repair or combined strategies may be more suitable [29,37]. The hemodynamic goals of direct annuloplasty include achieving a residual trans-mitral gradient <5 mmHg and limiting residual MR to no more than mild [191]. In AFMR, where annular dilation is often atrial in origin and may be reversible, post-procedural rhythm control and hemodynamic unloading are critical adjuncts to promote sustained reverse remodeling and functional improvement [166].

In summary, direct annuloplasty with devices such as Cardioband and Millipede offers an anatomically precise, minimally invasive therapy for selected patients with FMR, particularly those with annular-dominant pathology and preserved leaflet motion. While current data support safety and early efficacy, randomized trials remain ongoing. IDE studies comparing Cardioband and Millipede with medical therapy, edge-to-edge repair, or combination strategies will be essential in defining their long-term durability, impact on remodeling, and appropriate place within the evolving treatment algorithm for FMR. As device design, imaging integration, and operator experience continue to advance, direct annuloplasty is poised to become a key tool in personalized, mechanism-driven mitral valve therapy.

TMVR is an emerging therapeutic option for patients with severe FMR who are at high or prohibitive surgical risk and are either unsuitable for transcatheter repair or have failed prior repair attempts [192,193,194]. TMVR offers a mechanistically definitive solution, replacing the native mitral valve with a bioprosthetic implant that eliminates regurgitation regardless of underlying annular or subvalvular distortion, an important advantage over repair-based strategies, whose success may be limited by complex or severely remodeled anatomy [195,196,197]. Currently available TMVR platforms include transapically delivered devices, such as the Tendyne valve (Abbott) and the Intrepid valve (Medtronic), as well as fully transseptal systems, like the Sapien M3 and Evoque valves, which are under investigation in pivotal trials [162,198,199]. These systems are designed to anchor securely within the mitral annulus and accommodate the dynamic, elliptical, and noncalcified anatomy characteristic of FMR [196].

Clinical studies of TMVR have demonstrated high procedural success rates, reaching up to 97%, with near-complete elimination of mitral regurgitation in most patients (Table 7) [191,192,194,200]. Improvements in symptoms, exercise capacity, and quality of life are typically sustained through 1 to 2 years of follow-up [191,192,194,200]. In the CTSN trial, moderate-to-severe MR recurred in 32.6% of patients who underwent surgical repair, compared to only 2.3% after valve replacement, despite similar survival rates and comparable degrees of left ventricular reverse remodeling [139,193]. These findings underscore the durability advantage of replacement, particularly in anatomies prone to recurrent tethering or annular dilation. In one prospective study of high-risk patients, TMVR reduced heart failure hospitalizations from 1.3 to 0.5 events per year, with 93% of survivors exhibiting no residual MR at two years [139,193]. However, despite these promising outcomes, early mortality remains substantial, particularly within the first 90 days, reflecting the advanced clinical status of patients typically selected for this therapy [193,194,200].

TMVR is not without challenges. Potential complications include obstruction, prosthetic thrombosis, paravalvular leak, and difficulty anchoring the device in the setting of heavy mitral annular calcification [201,202,203]. Pre-procedural planning is critical, with multimodality imaging playing a central role [204,205]. Cardiac computed tomography (CT) is used to evaluate annular dimensions, simulate device deployment, and, crucially, estimate the neo–left ventricular outflow tract (neo-LVOT) area [114,116,117,206]. A neo-LVOT <2.0 cm² is strongly associated with increased risk of LVOT obstruction [206,207]. As a result, ongoing randomized trials, most notably SUMMIT and APOLLO, are evaluating TMVR in comparison with transcatheter edge-to-edge repair to determine its relative safety, efficacy, and appropriate clinical niche [195,208].

In summary, TMVR currently remains reserved for patients with severe symptomatic FMR who are not candidates for surgery or edge-to-edge repair, and its use is predicated on a multidisciplinary heart team assessment and advanced imaging-based procedural planning. As device technology matures, imaging integration improves, and operator experience expands, the role of TMVR is expected to broaden, potentially offering a durable, anatomically agnostic treatment option for an increasing number of patients with FMR.

To assist clinicians in navigating these interventional strategies, Table 8 provides a clinical guide for selecting the most appropriate therapeutic approach based on the dominant imaging phenotype and the underlying pathophysiology of FMR.

The management of FMR has reached a critical juncture. While the success of TEER in highly selected patients has definitively demonstrated the prognostic importance of reducing MR, the conflicting results of landmark trials such as COAPT and MITRA-FR underscore a fundamental challenge: the lack of a universally applicable patient selection tool. Consequently, the future of FMR care is rapidly evolving, with a focus on enhanced, personalized risk stratification, the adoption of innovative technologies, and a deeper understanding of disease heterogeneity.

A primary research objective is to refine the timing and criteria for intervention. Recent studies, including RESHAPE-HF2 and MATTERHORN, suggest a paradigm shift toward earlier use of TEER in well-selected, symptomatic patients, moving beyond the current approach of only intervening after GDMT has failed. This emphasis on earlier, individualized intervention makes it critical to clarify whether FMR is primarily a driver or merely a marker of heart failure progression, as this distinction dictates which patients will derive the greatest benefit from valve intervention versus intensified medical therapy alone. To achieve this precision, future algorithms must move beyond traditional parameters to incorporate dynamic assessment from stress echocardiography and detailed myocardial tissue characterization from CMR, which enables the identification of viable versus scarred myocardium.

Artificial intelligence (AI) is emerging as a critical enabling technology in this effort [209,210]. AI-based tools are already being applied to automate chamber segmentation, annular geometry assessment, and volumetric analysis across echocardiography, CMR, and CT, reducing inter-operator variability and improving reproducibility of MR severity grading [211]. In echocardiography, deep learning algorithms can automatically quantify ventricular and atrial volumes, strain, and regurgitant jet parameters [212], while AI-assisted CT and CMR workflows facilitate annular sizing, neo-LVOT prediction, and myocardial scar quantification for procedural planning [213]. By harmonizing quantitative imaging across modalities, AI has the potential to address longstanding limitations in FMR phenotyping and trial generalizability.

Ultimately, future research must extend beyond procedural success to evaluate the durability of reverse remodeling, patient-centered outcomes, and cost-effectiveness. As diagnostic complexity and therapeutic options continue to expand, integrating advanced imaging, AI-assisted analytics, and clinical expertise within a multidisciplinary Heart Team framework will be essential to delivering individualized, evidence-based care for patients with functional mitral regurgitation.

FMR remains a highly prevalent and morbid condition, inextricably linked to adverse outcomes in patients with both HFrEF and preserved (HFpEF) ejection fraction. As detailed throughout this review, FMR is not a singular entity, but a spectrum defined by two mechanistically distinct subtypes: VFMR, driven by LV remodeling and leaflet tethering, and AFMR, caused by left atrial LA and annular dilation. This heterogeneity mandates a mechanism-specific approach to evaluation and management as detailed in Figure 2 (Management process of FMR).

The central clinical dilemma, determining which patients with severe secondary MR benefit from valve intervention, has been partially resolved by the landmark COAPT trial, which demonstrated that in highly selected patients, aggressive MR reduction with TEER improves prognosis. However, the discordant results with MITRA-FR underscore that the field has moved beyond simply treating all severe MR to identifying the specific mechanical and myocardial environment in which intervention is beneficial. Patient selection is paramount.

Multi-modality imaging is therefore indispensable for precision medicine in FMR. Echocardiography serves as the diagnostic cornerstone, grading severity and identifying the primary mechanism, while CMR provides the gold standard for volumetric quantification and, critically, myocardial tissue characterization via late gadolinium enhancement and T1 mapping. Furthermore, CT offers unparalleled anatomical detail, making it essential for pre-procedural planning, particularly for TMVR. These imaging data sets enable the application of advanced risk stratification tools, such as differentiating FMR phenotypes to the proportionate/disproportionate VFMR framework, which helps rationalize the divergent results observed in therapeutic trials. Effective management, as summarized in our comparative Table 1 (Mechanistic Characteristics) and Table 2 (Diagnostic Modalities), defined a carefully integrated approach.

Ultimately, FMR care is rapidly transitioning from a one-size-fits-all model to an individualized model. First-line therapy remains robust, which includes GDMT, followed by the judicious consideration of transcatheter or surgical therapies for persistent, symptomatic MR. Future efforts, guided by the multidisciplinary Heart Team, will focus on integrating artificial intelligence, next-generation devices, and refined risk stratification to target earlier, more individualized interventions that maximize myocardial recovery and substantially improve the long-term outcomes for this challenging patient population.

The authors used Google Gemini and ChatGPT 5.2 to generate ideas for visualizing and presenting the illustrations described in the paper. Grammarly was used to improve grammar and edit paragraphs in the manuscript. After using these tools, the authors reviewed and made necessary edits to the content, taking full responsibility for the final article published.

Conceptualization, T.K.M.W. and S.-W.L.; Methodology (literature search strategy), S.-W.L.; Validation (critical review of arguments), J.E.R., Y.-F.T., C.T. and T.K.M.W.; Investigation (literature collection), S.-W.L. and J.E.R.; Resources, T.K.M.W.; Writing—Original Draft Preparation, S.-W.L.; Writing—Review & Editing, S.-W.L., J.E.R., Y.-F.T., C.T. and T.K.M.W.; Visualization, S.-W.L.; Supervision, T.K.M.W.; Project Administration, T.K.M.W.; Funding Acquisition, T.K.M.W.

Not applicable. This is a review article that synthesizes and summarizes previously published literature and does not involve any new studies with human participants or animals performed by any of the authors.

Not applicable. This review article does not contain any studies with human participants performed by any of the authors.

No new data were created or analyzed in this study. Data sharing is not applicable to this article. All information discussed in this review is based on previously published studies, which are cited in the reference list.

This research received no external funding.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.