A Novel Morphological Classification to Guide Transcatheter Mitral Valve Edge-to-Edge Repair for Commissural Mitral Regurgitation

Abstract

Background

Mitral commissural prolapse poses significant anatomical challenges that can hinder the effectiveness of transcatheter edge-to-edge repair (TEER).

Objectives

The aim of this study was to estimate the safety and effectiveness of applying a novel morphological classification to guide TEER in patients with commissural degenerative mitral regurgitation (DMR).

Methods

In this prospective, multicenter study across 18 centers in China, we classified patients with severe commissural DMR into 4 morphological types through detailed echocardiographic analysis. Customized TEER strategies were applied accordingly. Procedural success, clinical outcomes, echocardiographic parameters, and quality of life were assessed over a follow-up period, with a median follow-up of 18 months (Q1-Q3: 15-21 months).

Results

Among 540 patients screened, 126 (23.3%) exhibited commissural involvement. Tailored TEER strategies were successfully applied to 68 patients, achieving a technical success rate of 100% (n = 68 of 68; 95% CI: 0.933-1.000) and a device success rate of 97.1% (n = 66 of 68, 95% CI: 0.888-0.992). The 1-year follow-up revealed that 94.1% (n = 64 of 68; 95% CI: 0.849-0.981) of patients had residual mitral regurgitation of grade ≤2+, with 82.4% (n = 56 of 68; 95% CI: 0.708-0.902) at grade ≤1+, and no major complications. Additionally, significant improvements were noted in left ventricular dimensions and functional status.

Conclusions

Our results highlight the value of the morphological classification system in enhancing TEER for commissural DMR. By addressing specific anatomical challenges, this system promotes tailored interventions that optimize procedural success and improve patient outcomes.

Central Illustration

Patients with severe mitral regurgitation (MR) may develop heart failure (HF), which has traditionally been regarded as the final stage of MR progression and is associated with poor outcomes. Transcatheter edge-to-edge repair (TEER) has become a pivotal therapeutic option for patients with MR and concomitant HF who are considered at high or prohibitive risk for surgery.^1,2 The landmark EVEREST II (Endovascular Valve Edge-to-Edge Repair Study)³ initially focused on patients with central MR and favorable valve anatomy using the first-generation TEER devices. Subsequent large international registries have expanded applications to more complex cases, demonstrating high procedural success and significant reductions in MR severity. These advancements underscore the benefits of increased operator experience, improved device technology, and enhanced imaging techniques, enabling effective treatment of a broader range of anatomical challenges. However, mitral commissural prolapse or flail remains a particularly challenging subtype for contemporary TEER because its intricate and diverse anatomical characteristics are under-recognized, resulting in gaps in the established echocardiographic techniques that guide procedural planning and predict outcomes.

Recently, Seo et al⁴ made a preliminary exploration into TEER for isolated commissure prolapse, proposing a systemic approach that includes various techniques, such as the “stitch artifact technique” to optimize clip placement and identify appropriate grasping targets. They categorized possible grasping strategies into 3 patterns for posteromedial commissure (PC) prolapse (A3-PC, medial A3-P3, and PC-P3) and anterolateral commissure (AC) prolapse (A1-AC, lateral A1-P1, and AC-P1), respectively.⁵ Although these strategies offer valuable insights, they lack a comprehensive approach to restore the physiological coaptation of the commissure with the corresponding anterior and posterior leaflets. This principle is crucial for successful TEER in commissural lesions, especially in complex anatomical scenarios. Moreover, the methods of Seo et al^4,5 focus primarily on isolated commissure prolapse and do not address the broader clinical context where commissural lesions often coexist with other segments or involve complex pathological mechanisms. In such cases, a more nuanced approach is required to accurately assess the extent of the lesion, the length of the target leaflets, and the underlying pathophysiological mechanisms.

To address these limitations, we introduce a novel morphological classification for commissural degenerative mitral regurgitation (DMR) based on detailed echocardiographic core laboratory (ECL) analysis from a multicenter registry. Our classification system categorized commissural DMR into 4 distinct types, each with specific anatomical features and corresponding TEER strategies. This comprehensive approach not only incorporated the anatomical considerations highlighted by Seo et al^4,5 but also integrates clinical parameters to enhance procedural decision-making and improve long-term outcomes.

The primary objective of this study is to evaluate the feasibility and effectiveness of our morphological classification system in guiding TEER procedures for commissural DMR. We hypothesize that this system will enhance procedural success rates, reduce residual MR, and improve patients’ quality of life. By providing a structured framework for preprocedural planning and intraprocedural guidance, our classification system aims to bridge the gap in the management of this challenge’s subtype of MR.

Methods

Study design

This study is an exploratory analysis nested within the China-DVD2 (China Degenerative Valve Disease II Cohort Study; NCT05044338), a prospective, multicenter, observational registry dedicated to understanding the distribution, characteristics, and treatment paradigms of valvular heart disease in the elderly Chinese population. Our research aimed to assess the feasibility and efficacy of a novel morphological classification system for guiding TEER procedures in patients with commissural DMR. The design of our exploratory study is inherently prospective, because it involves the application of a predefined morphological classification to inform clinical decision-making and procedural strategies before the TEER intervention. Patients enrolled in this study were classified according to the newly proposed anatomical classification, and the corresponding interventional strategies were developed based on this classification before the procedure was undertaken. Postprocedural outcomes were collected and evaluated on a prospective basis, ensuring that data analysis was conducted in accordance with a prespecified plan. We have established a systemic Standard Operating Procedure for this classification system and demonstrated in Figure 1.

Figure 1.

TEER Strategy SOP for Commissural DMR

This figure outlines the Standard Operating Procedure (SOP) for guiding transcatheter edge-to-edge repair (TEER) in patients with commissural degenerative mitral regurgitation (DMR). The SOP includes detailed steps for patient selection, echocardiographic assessment, and predefined procedural strategies tailored to different morphological types of commissural DMR, ensuring standardized and effective interventions. A = anterior leaflet; C = commissural leaflet; China-DVD2 = China Degenerative Valve Disease II Cohort; ECL = echocardiographic core laboratory; MR = mitral regurgitation; P = posterior leaflet.

It is important to note that although this exploratory study was not registered separately on ClinicalTrials.gov, it was conducted in compliance with the ethical standards of the China-DVD2 Study, which does have a registration. The study was approved by the Institutional Review Boards and ethics committees of each participating centers. All patients provided written informed consent, and the study protocol conformed to the principles of the Declaration of Helsinki and Good Clinical Practice.

Patient selection

The study included patients at 65 years of age or older diagnosed as symptomatic severe (4+) commissural DMR by an independent ECL using standardized echocardiographic protocols;deemed at high or prohibitive surgical risk by a multidisciplinary heart team (Supplemental Table 1); and with mitral valve anatomy suitable for TEER adjudicated by the central screening committee (CSC). Exclusion criteria were: patients with DMR not involving the commissural regions or with MR from causes other than degenerative changes, such as functional MR or rheumatic heart disease; patients with active endocarditis, intracardiac thrombus, or mitral stenosis; patients with anatomy unsuitable for septal puncture, device steering, or device placement; and participants who are unwilling or unable to provide informed consent (Supplemental Table 2). Treatment was administered using the MitraClip NTR/XTR system, the only device approved in China during the study period. Each participating center was required to have performed at least 50 TEER procedures before enrollment. Safety, echocardiographic, clinical, functional, and quality of life outcomes were assessed at baseline, during hospital stay, at discharge, or 7 days postprocedure with follow-up visits at 30 days, 6 months, 1 year, and annually to 5 years. Major adverse events through 30 days were adjudicated by the Clinical Events Committee. Adverse events through 1 year were reported by individual sites.

Echocardiographic core laboratory

The classification of mitral MR lesions in our study was conducted by an independent ECL. The ECL conducted a standardized assessment of MR severity at baseline and follow-up using both transesophageal echocardiography (TEE) and transthoracic echocardiography. This assessment was based on a comprehensive analysis of quantitative and semiquantitative criteria as recommended by the American Society of Echocardiography (ASE).⁶ Echocardiographic images were evaluated by a team of experienced echocardiographers who were blinded to the patients' clinical outcomes and procedural details. The ECL utilized a comprehensive echocardiographic protocol that included 2-dimensional (2D), 3-dimensional (3D), and Doppler echocardiography to assess the mitral valve's anatomy and function. Multiplanar reconstruction (MPR) based on 3D imaging was employed to confirm the anatomical characteristics of leaflet length and mitral annulus, which are critical for the classification of MR lesions. Quality control measures were strictly adhered to within the ECL. The ECL's findings were centralized and served as the reference standard for the classification of commissural DMR in our study.

Imaging protocol

Determination of mitral commissures

The anterior and posterior mitral leaflets are separated by 2 commissures (AC and PC). The AC is proximal to the left fibrous trigone and the left atrial appendage, while the PC is adjacent to the right fibrous trigone and the interatrial septum. The commissures define distinct areas where anterior and posterior leaflets appose each other during systole. The amount of tissue in the commissure varies from several millimeters of leaflet tissue to distinct leaflet segments. The typical commissure entity presents a functional Y-shape morphology upon 3-edge coaptation, including A1-AC-P1 segments or A3-PC-P3 segments, which are identified anatomically by the characteristic chordae where input from anterolateral and posteromedial papillary muscles merged into a fanlike appearance attachment.⁷ Given the challenge of discerning individual chordae tendineae attachments via TEE, we utilized the cleavage segment separating the anterior leaflet from the posterior leaflet as a 3D TEE imaging approximation of true anatomic commissures⁸ (Figure 2A).

Figure 2.

Definition of Mitral Valve Commissures and Commissural Degenerative Mitral Regurgitation

(A) Commissures, where anterior and posterior mitral leaflets converge during systole, typically form a Y-shaped structure by joining 3 segments (eg, A1-anterolateral commissure-P1 or A3-posteromedial commissure-P3), distinguished by fanlike chordae tendineae stemming from anterolateral and posteromedial papillary muscles. Given the difficulty in distinguishing individual chordae on transesophageal echocardiography, the cleavage segment that separates the anterior leaflet from the posterior leaflet is used as imaging anterolateral and posteromedial commissure approximation of true anatomic commissures. (B) The protrusion of the commissural segment into the left atrium during systole or (C) the rupture of commissural chordae tendineae characterizes commissural prolapse or flail. AV = aortic valve.

Definition of commissural DMR

The morphological abnormalities defining commissural DMR include prolapse or flail. The crucial evidence for the diagnosis of commissural degenerative disease is the abnormal protrusion of the commissural segment into the left atrium during systole, caused by elongation or rupture of the commissural chordae tendineae, as observed in 2D and 3D echocardiographic imaging (Figures 2B and 2C). Prolapse occurs when the commissures bulge into the left atrium during systole without chordae tendineae rupture, whereas flail involves a completely detached leaflet edge caused by chordae rupture, leading to independent movement.

Determination of commissural DMR

A standardized TEE protocol was implemented at each participating site and monitored by the ECL. Initial imaging was conducted at the midesophageal level to assess the mitral valve. If high-quality images were not obtained, imaging was conducted at the transgastric level. The protocol included 2D single-plane and simultaneous multiplane imaging, as well as 3D imaging with MPR mode to comprehensively delineate the pathology of MR (Figure 3).⁹ This integrated approach ensured detailed visualization of the mitral valve anatomy and function, which is essential for accurate classification of commissural DMR (Table 1).

Figure 3.

Imaging Protocol for Mitral Valve Commissural Disease

(A) Illustration of the mitral valve, surgeon’s view in the “clock-face plane” with the aortic valve (AV) at the 12 o’clock. utilizing transesophageal echocardiography (TEE) to identify optimal mitral valve planes: (B) Bicommissural view at ∼50° to 70° and long axis (LAX) view at ∼120° to 150° for central segments. (C, E) Biplane imaging with (D, F) color Doppler showcases the posteromedial and anterolateral commissural lesions. (G) A 3-dimensional (3D) rendered en face view with multiplanar reconstruction is used to determine the mechanism of mitral regurgitation (MR). 3D = 3-dimensional; AC = anterolateral commissure; Ant = anterior; AV = aortic valve; Lat = lateral; LAX = long axis; MC = mitral commissure; ME = midesophageal; Med = medial; MR = mitral regurgitation; Post = posterior; SAX = short axis.

Table 1.

Echocardiographic Imaging Protocol for Evaluating MV Commissural Lesions

Optimized bicommissural view	Adjust the TEE to achieve an anatomically optimized MV plane at an angle of approximately 50°-70°, essential for a detailed assessment of the mitral commissures
LAX view for coaptation plane	Utilize the LAX view to delineate the MV coaptation plane, adjusting the angle to ∼120°-150° for central segments, >∼150° for lateral segments and anterolateral commissure, and <∼130° for medial segments and posteromedial commissure. The typical commissure entity presents 3-edge coaptation, including A1-AC-P1 segments or A3-PC-P3 segments.
Biplane imaging	Employ simultaneous biplane imaging to display 2 real-time 2-dimensional images on a dual screen, using the primary MV commissure view as a reference and rotating the second view (LAX) from 0° to 180° for comprehensive interrogation of MV coaptation
3D rendered en face view	Apply 3D rendered en face view with MPR to ascertain the exact mechanism of MR and to characterize the morphological features of the MV
Stitch artifact techniquea	When using the echocardiography system without 3D live MPR mode, the stitch artifact technique can serve as a confirmation method to visualize the stitch line on a wide-angle 3D image. This technique helps to clearly identify the target site on a conventional 2D imaging during leaflet grasping, especially in commissural lesions or other complex anatomical scenarios

AC = anterolateral commissure; LAX = long axis; MR = mitral regurgitation; MV = mitral valve; PC = posteromedial commissure; TEE = transesophageal echocardiography.

^aStitch artifact technique: This technique leverages the intentional creation of a stitch artifact line on a 3-dimensional (3D) image by acquiring a 2-beat image without stopping ventilation. Unlike conventional multiplanar reconstruction (MPR) or live MPR modes, which may have limitations in spatial and temporal resolution, the stitch artifact technique provides higher resolution and is widely applicable across various 3D echocardiography machines. It is particularly useful for identifying the exact position, angle, and leaflets of the visualized 2-dimensional (2D) image, ensuring precise leaflet grasping during transcatheter edge-to-edge repair (TEER) procedures, even in complex anatomical scenarios.

TEER-specific morphological classification for commissural DMR

Our study introduces a novel morphological classification system designed to categorize commissural DMR into distinct types to guide TEER strategies. The classification is based on a detailed echocardiographic analysis and is defined as follows (Central Illustration A):

• •Type I (pseudo-commissural prolapse): Characterized by excessive motion of the commissural leaflet driven by adjacent leaflet prolapse or flail without an intrinsic commissural lesion. The commissural leaflet body may extend beyond the mitral valve annulus in systole, but coaptation lines with adjacent leaflets remain under the mitral valve annulus (Figures 4A to 4C, Videos 1 and 2).
• •Type II (combined commissural prolapse/flail): Involves the commissural segment and adjacent scallops, often presenting with severe symptoms of heart failure and requiring complex grasping strategies for effective repair. The most common form of Type II is associated with Barlow's disease, where the lesion responsible for commissural prolapse can vary and may involve the extensive leaflet tissue, chordae, or papillary muscle (Figures 4D to 4F, Videos 3 and 4).
• •Type IIIa (isolated commissural prolapse/flail with sufficient adjacent leaflet length [≥7 mm]): Characterized by an isolated commissural prolapse where the adjacent leaflet length is sufficient for clip grasping (≥7 mm). The involvement of the first-order chordae tendineae,or a separate commissural head of a subdivided papillary muscle, is usually short and supports a confined part of the valve producing less severe regurgitation, with slower hemodynamic deterioration and less pronounced left ventricular (LV) enlargement (Figures 4G to 4I, Videos 5 and 6).
• •Type IIIb (isolated commissural prolapse/flail with short adjacent leaflet length [<7 mm]): Defined by an isolated commissural prolapse/flail with an adjacent leaflet length <7 mm, which is insufficient for standard clip grasping. Type IIIb is associated with elongation or rupture of the commissural chord emerging from a single papillary muscle located deep into the ventricle produces more severe MR a larger prolapse or flail lesions, faster hemodynamic deterioration, and more rapid LV enlargement. Papillary muscle displacement and posterior leaflet tethering are more commonly seen in this subtype (Figures 4J and 4K, Videos 7 and 8).

Central Illustration.

A Commissural Degenerative Mitral Regurgitation Imaging Classification for TEER

(A) A novel morphological classification scheme for commissural degenerative diseases, distinguishing between pseudo-commissural prolapse (Type I), and combined commissural prolapse/flail (Type II) and isolated commissural prolapse/flail (Type III). (B) Dedicated transcatheter edge-to-edge repair (TEER) procedural strategies tailored to each type, emphasizing restrictive clipping for Type I, zipping clipping for Type II, simultaneous clipping for Type IIIa and staged clipping for Type IIIb. (C) Procedural outcomes highlight mitral regurgitation (MR) reduction and improvements in NYHA functional class across types. Each line represents a patient, and line colors indicate different morphological classifications. Abbreviations: The P values were calculated by Wilcoxon signed rank test. AC = anterolateral commissure.

Figure 4.

TEE Examples of Commissural DMR Classification

(A to C) Type I features pseudo-commissural prolapse driven by adjacent P1 prolapse without regurgitant jets. (D to F) Type II presents combined anterolateral commissure (AC) flail and P1 prolapse causing severe mitral regurgitation (MR). (G to I) Type IIIa shows isolated commissural prolapse with sufficient leaflet length for grasping, (J to L), while Type IIIb has insufficient leaflet length, requiring tailored clipping. 3-dimensional multiplanar reconstruction is crucial for precise anatomical assessment. Prolapse and flail regions are indicated by arrows. MV = mitral valve; PC = posteromedial commissural; TEE = transesophageal echocardiography.

The morphological and pathophysiological differences between Types IIIa and IIIb are further detailed in Table 2, which provides a comprehensive comparison of these subtypes and their implications for TEER strategies.

Table 2.

Morphological Characteristics and Pathology of Type IIIa and IIIb

	Type IIIa	Type IIIb
Involved chordae	First-order chordae tendineae, or a separate commissural head of a subdivided papillary muscle	Elongation or rupture of the commissural chord emerging from a single papillary muscle located deep into the ventricle
Mitral regurgitation severity	Less severe	Severe
Hemodynamic deterioration	Slow	Rapid
Left ventricular enlargement	Slow progression	Rapid progression
Papillary muscle displacement	Less common	More common
Posterior leaflet tethering	Less common	More Common
Tethering-related leaflet shortening	Less common	More Common

Morphological Classification-Directed TEER Strategies for Commissural DMR

Utilizing the proposed morphological classification system for commissural prolapse, we developed tailored procedural strategies for each specific subgroup (Central Illustration B). In patients classified as Type I, the "restrictive clipping strategy" aims to address the true prolapse lesions adjacent to the commissural area, thereby limiting the motion of the commissural leaflet (Figures 5A and 5B, Video 9). For Type II patients, we employ a “zipping clipping strategy” which often involves the use of multiple clips to address extensive lesions (Figures 5C and 5D, Video 10). Type IIIa patients are treated with a “simultaneous clipping strategy” where a single clip is used to directly oppose the A1-AC-P1 or A3-PC-P3 segments (Figures 5E and 5F, Video 11). In contrast, Type IIIb patients require a “staged clipping strategy,” which typically involves an initial clip to fuse A1-AC or A3-PC, followed by a second clip to achieve edge-to-edge repair with the adjacent posterior leaflet. This staged approach is particularly important for managing the complex anatomy present in Type IIIb cases (Figures 5G and 5H, Video 12). The differences in TEER procedural strategies for Type IIIa and Type IIIb patients, based on their distinct morphological characteristics, are further detailed in Table 3.

Figure 5.

TEE Examples of TEER Strategies for Commissural DMR

TEE-guided procedural strategies for commissural DMR. (A, B) Restrictive clipping strategy was used in Type I patients in which 1 clip to grasp true P1 prolapse with corresponding A1 scallop, and subsequently restricted the motion of billowing anterolateral commissure leaflet with trivial residual mitral regurgitation. (C, D) Treatments of combined commissural prolapse with “zipping” strategies in Type II patients. (E, F) Type IIIa patients were successfully treated using a single clip simultaneous engaged the A3-PC-P3 segments. (G, H) A Type IIIb patient was effectively managed with the staged clipping strategy; the initial XTR clip unified the A1 to AC leaflets, followed by a second XTR clip applying edge-to-edge repair to the consolidated A1 to AC tissue and the adjacent P1 scallop. AC = anterolateral commissural; AO = aortic outflow; DMR = degenerative mitral regurgitation; TEE = transesophageal echocardiography.

Table 3.

TEER Procedural Strategies for Type IIIa and IIIb

	Type IIIa	Type IIIb
Mobile leaflet length	≥7 mm (sufficient for grasping)	<7 mm (insufficient for standard clip grasping)
Initial clipping strategy	Simultaneous Clipping Strategy: Direct apposition of A1-AC-P1 or A3-PC-P3 with a single clip	Staged clipping strategy: initial clip fuses A1-AC or A3-PC, followed by a second clip in the adjacent posterior leaflet to achieve edge-to-edge repair
Additional clip usage	Often 1 clip is sufficient, additional clip if the prolapse is wide	Often requires 2 or more clips caused by complexity of the lesion
Procedural consideration	Easier to achieve apposition and satisfied MR reduction, lower risk of SLDA	A higher risk of SLDA and recurrent MR, potentially caused by the gap formed between the first clip, the second clip, and the short posterior leaflet, necessitates meticulous clip placement and a staged edge-to-edge repair strategy

TEER = transcatheter edge-to-edge repair; other abbreviations as in Table 1.

Study outcomes

The study endpoints followed the definitions of the Mitral Valve Academic Research Consortium criteria.¹⁰ The primary endpoints were technical success assessed at the end of the procedure and device success assessed 30 days after device implantation. Technical success was defined as absence of procedural mortality; successful access, delivery, and retrieval of the device delivery system; successful deployment and correct positioning of the first intended implant; and freedom from surgical conversion or reintervention related to the device or the vascular access. Device success at 30 days was defined as successful device implantation, MR grade ≤2+, and the absence of mitral stenosis (defined as a transvalvular gradient ≥5 mm Hg or an effective regurgitant orifice area <1.5 cm²), absence of mortality and stroke, freedom from unplanned surgical or interventional procedures, and absence of device-related failure or complications. Secondary efficacy endpoints encompassed: 1) the proportion of patients achieving MR reduction to ≤2+ upon discharge, and at 30 days, 6 months, and 1 year; 2) changes in LV ejection fraction, left atrial and ventricular dimensions and volumes, and pulmonary arterial systolic pressure across these time points; and 3) variations in NYHA functional classification, 6-minute walk distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at discharge, 30 days, 6 months, and 1 year. Secondary safety outcomes included a composite of major adverse events such as all-cause and cardiovascular mortality, myocardial infarction, cerebrovascular incidents, complications at the access site and vascular complications, bleeding incidents, renal failure requiring dialysis, rehospitalization caused by heart failure, and the need for reintervention for MR.

Statistical analysis

Statistical analyses were conducted using SPSS software (version 27.0). Continuous variables are presented as the mean ± SD or median with IQR and were compared using Student’s t-test, analysis of variance, or Kruskal-Wallis test, as appropriate. For multiple group comparisons, analysis of variance was followed by Bonferroni post hoc testing for pairwise differences. For non-normally distributed data, the Kruskal-Wallis test was used, with Dunn’s post hoc test for pairwise comparisons. Categorical variables are reported as numbers with relative percentages (%) and were compared using Pearson’s chi-square test or Fisher exact test, as appropriate. Bonferroni correction was applied for multiple comparisons to adjust P values. A P value <0.05 was considered statistically significant.

Results

Between September 2021 and September 2022, 126 commissural DMR patients (23.3%) were identified in 540 severe DMR cases referred to TEE examination by ECL. Among them, types I, II, IIIa, and IIIb diseases were found in 23 (18.3%), 47 (37.3%), 31 (24.6%), and 25 (19.8%) patients, respectively. The proposed morphological classification was used to guide interventional strategy in 68 patients (age 74.1 ± 6.0 years, 61.8% men) who subsequently underwent TEER in 6 experienced centers. The median follow-up time for all included participants was 18 months (Q1-Q3: 15-21 months). The flowchart of this study is shown in Figure 6. Details on the reasons for patients being excluded from the study and not undergoing TEER are described in Supplemental Figure 1.

Figure 6.

Patient Disposition and Flow

This figure shows the patient disposition and flow in our study of commissural DMR from September 2021 to September 2022. Of 540 patients with severe MR (≥4+) confirmed by ECL, 126 (23.3%) had commissural involvement. Patients were classified into 4 morphological types (I to IIIb). A total of 68 patients underwent TEER, with follow-up at 1 year. TEE = transesophageal echocardiography; TTE = transthoracic echocardiography; other abbreviations as in Figure 1.

Baseline Clinical Characteristics

The baseline clinical characteristics of TEER-treated patients with commissural DMR were summarized in Table 4. The Society of Thoracic Surgeons (STS) risk scores averaged 6.3% ± 0.9% for mitral valve repair and 8.8 ± 0.8% for replacement, respectively. Hypertension was the predominant comorbidity, affecting 63.2% (n = 43 of 68) of patients, followed by hyperlipidemia (57.4%, n = 39 of 68) and atrial fibrillation (50.0%, n = 34 of 68). Notably, 48.5% (n = 33 of 68) of the cases had coronary artery disease, with 8.8% (n = 6 of 68) reporting a prior myocardial infarction. Chronic lung disease and renal impairment were present in 20.6% (n = 14 of 68) and 7.4% (n = 5 of 68) of the patients, respectively. Additionally, 7.4% (n = 5 of 68) had experienced a stroke or transient ischemic attack, while 22.1% (n = 15 of 68) had undergone percutaneous coronary intervention. A solitary case (1.5%, n = 1 of 68) reported a previous surgical intervention on the aortic valve. The majority of the cohort (80.9%, n = 55 of 68) was classified within NYHA functional classes III or IV. In terms of medical therapy before TEER, 60.3% (n = 41 of 68) of patients were treated with ACE inhibitors or angiotensin II receptor blockers, 51.5% (n = 35 of 68) with sacubitril, 76.5% (n = 82 of 68) with beta-blockers, and 50.0% (n = 34 of 68) with aldosterone antagonists. Demographic and comorbid conditions did not significantly vary across the morphological subgroups (Supplemental Table 3).

Table 4.

Baseline Clinical Characteristics of TEER-Treated Commissural DMR Patients (N = 68)

Overall
Age, y	74.1 ± 6.0
Male	42 (61.8)
BMI, kg/m2	24.5 ± 3.4
STS score for mitral valve repair, %	6.3 ± 0.9
STS score for mitral valve replacement, %	8.8 ± 0.8
Comorbidities
Diabetes mellitus	12 (17.6)
Hypertension	43 (63.2)
Hyperlipidemia	39 (57.4)
Atrial fibrillation	34 (50.0)
Coronary artery disease (>50% stenosis)	33 (48.5)
Previous myocardial infarction	6 (8.8)
Chronic lung disease	14 (20.6)
Chronic renal failure (eGFR <60 mL/min)	5 (7.4)
Stroke/TIA	10 (14.7)
Previous cardiac intervention
Previous PCI	15 (22.1)
Previous CABG	4 (5.9)
SAVR	1 (1.5)
TAVR	0 (0)
Previous permanent pacemaker placement	3 (4.4)
Cardiac function
NYHA functional class
II	13 (19.1)
III	51 (75.0)
IV	4 (5.9)
III or IV	55 (80.9)
6MWD, m	239.1 ± 73.9
Medical treatments
ACE inhibitor/angiotensin II blocker	41 (60.3)
Sacubitril (LCZ696)	35 (51.5)
Beta-blocker	82 (76.5)
Aldosterone antagonist	34 (50.0)

Values are mean ± SD or n (%).

6MWD = 6-minute walk distance; BMI = body mass index; CABG = coronary artery bypass graft; DMR = degenerative mitral regurgitation; eGFR = estimated glomerular filtration rate; PCI = percutaneous coronary intervention; SAVR = surgical aortic valve replacement; STS = Society of Thoracic Surgeons Score; TEER = transcatheter edge-to-edge repair; TIA = transient ischemic attack.

Echocardiographic characteristics

Baseline echocardiographic analyses showed 44.1% (n = 30 of 68) patients present AC involvement, 51.5% (n = 35 of 68) patients showed PC involvement, and 4.4% (n = 3 of 68) patients had bicommissural involvement. The presence of commissural flail was noted in 27.9% (n = 19 of 68) of cases and there were no significant differences in the distribution of commissural flail and prolapse across the various subtypes (P > 0.05). Baseline echocardiographic assessments, including measurements of LV dimensions, volume, systolic function, pulmonary artery systolic pressure, and MR grades, did not significantly differ among the subtypes (P > 0.05). Type II patients had the widest prolapse/flail widths (14.9 ± 4.9 mm) and the largest flail gaps (8.1 mm [4.9-11.5 mm]), with both parameters showing statistical significance after Bonferroni post hoc testing compared to Type IIIa (P < 0.05). Type IIIb patients were distinguished by wide commissural prolapse (14.6 ± 3.2 mm) and the shortest adjacent posterior leaflet lengths (6.3 [6.0-6.8] mm), with the latter significantly different from other groups (P < 0.001) based on Bonferroni post hoc testing, as shown in Table 5.

Table 5.

Baseline Echocardiographic Characteristics of TEER-Treated Commissural Patients

	Overall (N = 68)	Type I (n = 19)	Type II (n = 21)	Type IIIa (n = 17)	Type IIIb (n = 11)	P Value
Commissure involved						0.603
Anterolateral	30 (44.1)	7 (36.8)	8 (38.1)	8 (47.1)	7 (63.6)
Posteromedial	35 (51.5)	11 (57.9)	11 (52.4)	9 (52.9)	4 (36.4)
Both	3 (4.4)	1 (5.3)	2 (9.5)	0 (0)	0 (0)
Basic echocardiographic parameters
Left ventricular ejection fraction, %	60.2 ± 8.5	60.6 ± 7.2	59.4 ± 9.3	58.2 ± 9.6	63.9 ± 7	0.366
Left ventricular end-diastolic dimension, mm	52.2 ± 5.8	51.4 ± 5.0	51.8 ± 6.6	52.2 ± 4.7	54.5 ± 6.9	0.862
Left ventricular end-systolic dimension, mm	34.7 ± 5.8	34.3 ± 5.9	33.7 ± 4.9	36.6 ± 6.2	34.6 ± 7.0	0.799
Left ventricular end-diastolic volume, mL	123.4 ± 34.2	124.7 ± 34.7	117.1 ± 38.8	123.6 ± 26.6	132.6 ± 36.6	0.681
Left ventricular end-systolic volume, mL	48.4 ± 22.5	49.1 ± 22.8	44 ± 17.6	55.1 ± 28.8	44.9 ± 19.4	0.466
Left atrial volume, cm3	130.8 ± 55	121.4 ± 38.3	133.6 ± 59.1	125.0 ± 39.7	151.0 ± 86.2	0.526
Pulmonary artery systolic pressure, mm Hg	41.6 ± 15.7	37.5 ± 10.2	45.7 ± 15	41.0 ± 23.2	41.5 ± 9.4	0.442
MR severity parameters
Effective regurgitant orifice area, mm2	77.4 ± 26.6	76.8 ± 24.5	83.9 ± 34	69.1 ± 20.5	79.1 ± 21.4	0.404
Regurgitant volume, mL	105.8 ± 31.9	100.2 ± 27.4	118.8 ± 38.9	100.7 ± 25.8	98.5 ± 29.4	0.168
Mitral valve area, cm2	6.0 ± 1.2	6.0 ± 0.9	6.1 ± 1.6	6.0 ± 1.1	6.0 ± 1.2	0.996
Mean transmitral pressure gradient, mm Hg	2.6 ± 1.0	2.9 ± 1.0	2.3 ± 1.0	2.4 ± 0.8	3.1 ± 1.0	0.053
MV anatomic characteristic
Flail disease	19 (27.9)	8 (42.1)	5 (23.8)	2 (11.8)	4 (36.4)	0.198
Prolapse/flail width, mm	13.2 ± 4.3	12.5 ± 4.9	14.9 ± 4.9a	11.0 ± 2.3	14.6 ± 3.2a	0.027
Prolapse/flail gap, mm	5.3	5.2	8.1a	4.1	5.5	0.049
	(4.0-7.7)	(3.6-6.7)	(4.9-11.5)	(3.4-6.0)	(4.3-7.2)
Anteroposterior diameter of mitral valve annulus, mm	31.3 ± 3.9	32.3 ± 3.6	30.4 ± 3.7	30.7 ± 4.5	32.5 ± 3.2	0.286
Medial-lateral diameter of mitral valve annulus, mm	34.9 ± 4.7	35.7 ± 5.1	34.4 ± 4.6	35.1 ± 4.8	34.4 ± 4.5	0.822
Adjacent anterior leaflet length, mm	18.4 ± 4.1	18.0 ± 3.3	19.7 ± 4.2	16.8 ± 4.8	18.8 ± 3.8	0.191
Adjacent posterior leaflet length, mm	10.4	12.2	11.3	10.3	6.4b	< 0.001
	(8.3-12.4)	(9.5-13.8)	(10.1-12.7)	(8.7-11.2)	(6.3-6.8)
Others
Barlow disease	2 (2.9)	0 (0)	2 (9.5)	0 (0)	0 (0)	0.203
Calcification of mitral valve	4 (5.9)	0 (0)	2 (9.5)	1 (5.9)	1 (9.1)	0.594
Severity of tricuspid regurgitation						0.634
0	16 (23.5)	6 (31.6)	4 (19.0)	4 (23.5)	2 (18.2)
1+	36 (52.9)	10 (52.6)	9 (42.9)	10 (58.8)	7 (63.6)
2+	8 (11.8)	1 (5.3)	4 (19.0)	1 (5.9)	2 (18.2)
3+	2 (2.9)	0 (0)	2 (9.5)	0 (0)	0 (0)
4+	6 (8.8)	2 (10.5)	2 (9.5)	2 (11.8)	0 (0)

Values are n (%), mean ± SD, or median (Q1-Q3).

Abbreviations as in Table 1.

^aStatistical significance was found compared with Type IIIa (P < 0.05 for all tests, using Bonferroni or Dunn’s post hoc test).

^bBonferroni post hoc testing showed Type IIIa was significantly different from the other groups (P < 0.001 for all comparisons).

Procedural outcomes

Procedural outcomes and major adverse events were summarized in Table 6. The morphological classification-directed procedural strategy achieved a total technical success rate of 100% (n = 68 of 68; 95% CI: 0.933-1.000) and a device success rate of 97.1% (n = 66 of 68; 95% CI: 0.888-0.992). The mean overall procedure time was 123.3 ± 25.8 minutes, and the mean device time was 71.0 ± 31.9 minutes. Type II patients required the longest procedure and device times (148.3 ± 20.8 minutes and 99.3 ± 29.8 minutes, respectively), followed by Type IIIb patients (129.5 ± 14.3 minutes and 90.5 ± 15.3 minutes, respectively). Procedure time in Type II patients was significantly longer than in all other types (P < 0.05) after Bonferroni post hoc testing. Although no significant difference was observed between Type II and Type IIIb device times, both Type II and Type IIIb had significantly longer device times compared with Type I and Type IIIa (P < 0.05). Additionally, fluoroscopy duration was significantly longer in Type II patients than in all other types (P < 0.05). The use of 2 clips was significantly more prevalent in Type II and IIIb patients (P < 0.001). For Type II patients, 66.7% (n = 14 of 21; 95% CI: 0.431-0.845) utilized a “zipping strategy,” 19.0% (n = 4 of 21; 95% CI: 0.063-0.426) an “anchoring strategy,” and 14.3% (n = 3 of 21; 95% CI: 0.038-0.374) an “integrating strategy.” Most Type IIIb patients (90.9%, n = 9 of 11; 95% CI: 0.478-0.968) employed NTR and XTR clips for stabilizing commissural lesions, with 1 patient (9.1%, n = 1 of 11; 95% CI: 0.005-0.429) requiring 2 XTR clips caused by extensive commissural prolapse. Leaflet injury occurred in 1 Type II and 1 Type IIIb patient because of multiple grasping attempts.

Table 6.

Procedural Characteristics and Major Adverse Events

	Overall (N = 68)	Type I (n = 19)	Type II (n = 21)	Type IIIa (n = 17)	Type IIIb (n = 11)	P Value
Procedure time, min	123.3 ± 25.8	103.8 ± 16.9	148.3 ± 20.8a	110.2 ± 17.8	129.5 ± 14.3a	<0.001
Device time, min	71.0 ± 31.9	44.8 ± 11.4	99.3 ± 29.8b	52.8 ± 19.2	90.5 ± 15.3b	<0.001
Fluoroscopy duration, min	25.3 ± 6.7	20.1 ± 5.1	30.9 ± 5.1a	24.5 ± 6.1	25.3 ± 4.9	<0.001
Number of implanted clips						<0.001
1	38 (55.9)	17 (89.5)	5 (23.8)	16 (94.1)	0 (0)
2	30 (44.1)	2 (10.5)	16 (76.2)	1 (5.9)	11 (100)
Devices types						<0.001
NTR only	18 (26.5)	5 (26.3)	1 (4.8)	12 (70.6)	0 (0)
XTR only	20 (29.4)	12 (63.2)	4 (19.0)	4 (23.5)	0 (0)
NTR+XTR	23 (33.8)	1 (5.3)	13 (61.9)	0 (0)	9 (81.8)
XTR+XTR	5 (7.4)	1 (5.3)	3 (14.3)	0 (0)	1 (9.1)
NTR+NTR	2 (2.9)	0 (0)	0 (0)	1 (5.9)	1 (9.1)
Adverse clinical outcomes during procedure
Totalc	6 (8.8)	1 (5.3)	3 (14.3)	0 (0)	2 (18.2)	0.270
Mitral leaflet injury	2 (2.9)	0 (0)	1 (4.8)	0 (0)	1 (9.1)	0.425
Single-leaflet device attachment	1 (1.5)	0 (0)	0 (0)	0 (0)	1 (9.1)	0.154
Clip entanglement	2 (2.9)	0 (0)	1 (4.8)	0 (0)	1 (9.1)	0.425
Vascular complication	2 (2.9)	1 (5.3)	1 (4.8)	0 (0)	0 (0)	0.707
30-d major adverse events
Stroke/transient ischemic attack	1 (1.5)	0 (0)	0 (0)	1 (5.9)	0 (0)	0.385
1-y major adverse events
All complicationsd	6 (8.8)	0 (0)	2 (9.5)	2 (11.8)	2 (18.2)	0.344
Stroke/transient ischemic attack	1 (1.5)	0 (0)	0 (0)	1 (5.9)	0 (0)	0.385
Rehospitalizations for heart failure	5 (7.4)	0 (0)	2 (9.5)	1 (5.9)	2 (18.2)	0.308
New onset atrial fibrillation	1 (1.5)	0 (0)	1 (4.8)	0 (0)	0 (0)	0.518

Values are mean ± SD or n (%). Procedure time: from procedure start (femoral vein puncture/skin incision) to femoral vein access closure. Device time: from delivery system insertion into left atrium to guide sheath or steerable guide removal.

^aThe P value was statistically significant when compared with the other types (P < 0.05, Bonferroni post hoc test).

^bThe P value was statistically significant when compared with Type I and Type IIIa (P < 0.05, Bonferroni post hoc test).

^cOne patient in Type IIIb experienced leaflet injury caused by transient clip entanglement and multiple grasping, thus recorded as the 1 patient in total.

^dOne patient in Type II experienced rehospitalization caused by rapid atrial fibrillation, thus recorded as the one patient in total.

Two patients developed femoral arteriovenous fistulae at the access site, despite the use of ultrasound-guided vascular access, but were effectively managed with local compression.

Clinical outcomes during follow-up

A transient ischemic attack in 1 patient at 30 days. Rehospitalizations because of heart failure in 5 patients, including new onset of fast atrial fibrillation in a Type II patient, novel coronavirus pneumonia in a Type IIIb patient, and decompensated heart failure in 3 patients. Remarkably, no deaths were reported during the follow-up period.

Echocardiographic, functional, and quality-of-life outcomes

Our study introducing morphological classification-guided TEER procedures for commissural DMR showed a high rate of MR reduction, with 97.1% (n = 66 of 68; 95% CI: 0.888-0.992) of patients achieving an MR grade ≤2+ at 30 days, and this rate was maintained at 94.1% (n = 64 of 68; 95% CI: 0.849-0.981) at the 1-year follow-up. Similarly, 86.7% (n = 59 of 68; 95% CI: 0.759-0.934) of patients had an MR grade of ≤1+ at 30 days, which was consistent with the 82.4% (n = 56 of 68; 95% CI:0.708-0.902) rate at 1 year (Central Illustration C). When compared with previous studies, the sustained efficacy of MR reduction in the present study is particularly noteworthy. For instance, the study by Rodrigo Estévez-Loureiro et al,¹¹ using the initial generation of TEER devices, demonstrated a 30-day MR grade ≤2+ rate of 96.6% for noncentral DMR, but data was not available beyond this point.¹¹ The EVEREST II High Risk study reported an 83.6% rate for MR ≤2+ at 1 year, but a considerably lower 36.9% for MR ≤1+.¹² The EXPAND (A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices) with the third-generation TEER devices showed a slight decrease in efficacy from 96.3% at 30 days to 93.8% at 1 year for MR ≤ 2+.¹³ The EXPAND G4 (A Post-Market Study Assessment of the Safety and Performance of the MitraClip G4 System; NCT04177394) study, utilizing the fourth-generation TEER devices, exhibited the highest rates of MR reduction at 1 year with 97.7% for MR ≤2+ and 88.8% for MR ≤1+.¹⁴ CLASP IID registry, within the Edwards PASCAL Transcatheter Valve Repair System Pivotal Clinical Trial (CLASP IID; NCT03706833), in contrast, showed lower rates of MR reduction with 94.9% for MR ≤2+ at 30 days, decreasing to 93.2% at 1 year.¹⁵ These comparative results underscore the effectiveness of the third-generation TEER devices in the present study and suggest a positive trend with newer device technology, as seen in the EXPAND G4 study, toward achieving and maintaining higher rates of MR reduction post-TEER (Table 7).

Table 7.

Comparison With Previous Studies

Trial Name /First Author	Device		MR Grade, %
			30 Days		6 Months		1 Year
			≤2+	≤1+	≤2+	≤1+	≤2+	≤1+
Present study	Third-generation TEER devices	Commissural DMR	97.0	86.7	95.5	82.3	94.1	82.4
Rodrigo Estévez-Loureiro et al	First-generation TEER devices	Central DMR	96.0	63.3	95.2	33.4	NA	NA
		Noncentral DMR	96.6	65.5	91.7	66.7	NA	NA
EVEREST II High Risk	First-generation TEER devices	Central DMR	NA	NA	NA	NA	83.6	36.9
EXPAND	Third-generation TEER devices	Complex DMR	96.3	82.4	NA	NA	93.8	79.2
EXPAND G4	Fourth-generation TEER devices	Complex DMR	97.3	90.1	NA	NA	97.7	88.8
PASCAL IID	PASCAL	Complex DMR	94.9	59.4	93.2	54.3	93.2	57.6

MR = mitral regurgitation; NA = not available; other abbreviations as in Table 4.

For all commissural DMR patients, LV end-diastolic volume significantly reduced from 123.4 ± 34.2 mL to 96.5 ± 20.3 mL after 1 year (P < 0.001), and pulmonary arterial systolic pressure decreased from 41.6 ± 15.7 mm Hg to 36.5 ± 10.2 mm Hg at 30 days, stabilizing at 34.4 ± 10.9 mm Hg at 1 year (P < 0.001). NYHA functional class III/IV dropped from 80.9% (n = 55 of 68; 95% CI: 0.692-0.890) to 14.7% (n = 10 of 68; 95% CI: 0.077-0.259) (P < 0.001) (Central Illustration C), KCCQ scores improved from 52.2 ± 13.7 to 78.1 ± 7.1 (P < 0.001), and 6MWD increased from 239.1 ± 73.9 m to 303.8 ± 86.6 m (P < 0.001) over 1 year. These echocardiographic, functional, and quality of life outcomes improvements were shown in Figure 7.

Figure 7.

Echocardiographic, Functional, and Quality-of-Life Outcomes

Changes in echocardiographic, functional, and quality-of-life outcomes for patients with commissural DMR post-TEER, measured at 30 days, 6 months, and 1 year. (A-D) MR reduction in subtypes of commissural DMR patients; (E-H) changes in echocardiographic parameters (LVEDV and PASP), NYHA functional class, and KCCQ scores in overall commissural DMR patients receiving TEER therapy. 6MWD = 6-minute walk distance; KCCQ = Kansas City Cardiomyopathy Questionnaire; DMR = degenerative mitral regurgitation; LVEDV = left ventricular end-diastolic volume; PASP = pulmonary artery systolic pressure; TEER = transcatheter edge-to-edge repair.

In subgroup analysis, 100% (n = 19 of 19; 95% CI: 0.791-1.000) of Type I patients maintained an MR grade of ≤1+ after 1 year. For Type II patients, 95.2% (n = 20 of 21; 95% CI: 0.741-0.998) achieved MR grade ≤2+ and 76.2% (n = 16 of 21; 95% CI: 0.525-0.909) achieved MR grade ≤1+ at 30 days; at 1 year, 90.5% (n = 19 of 21; 95% CI: 0.682-0.983) maintained MR grade ≤2+ and 66.7% (n = 14 of 21, 95% CI: 0.431-0.845) maintained MR grade ≤1+. Two patients with Barlow’s disease progressed from grade 1+ to 2+. In Type IIIa, 100% (n = 17 of 17; 95% CI: 0.771-1.000) maintained MR grade ≤2+ and 94.1% (n = 16 of 17; 95% CI: 0.692-0.997) achieved MR grade ≤1+ over 1 year. Type IIIb patients showed 90.9% (n = 10 of 11; 95% CI: 0.571-0.995) achieving MR grade ≤2+ and 72.7% (n = 8 of 11; 95% CI: 0.393-0.927) achieving MR grade ≤1+ at 30 days; at 1 year, 81.8% (n = 9 of 11; 95% CI: 0.478-0.968) maintained MR grade ≤2+ and 63.6% (n = 7 of 11; 95% CI: 0.312-0.876) maintained MR grade ≤1+. These echocardiographic, functional and quality of life outcomes improvements were consistent across subgroups, although not all changes achieved statistical significance (Table 8, Figure 7).

Table 8.

Echocardiographic and Functional Outcomes During Follow-Up

	Baseline	30 Days	6 Months	1 Year	P Valuea	P Valueb	P Valuec
Type I (n = 19)
MR grade ≤2+	0 (0)	19 (100)	19 (100)	19 (100)	<0.001	<0.001	<0.001
MR grade ≤1+	0 (0)	19 (100)	19 (100)	19 (100)	<0.001	<0.001	<0.001
Left ventricular end-diastolic volume, mL	124.7 ± 34.7	106.9 ± 19.3	99.1 ± 15.2	97.5 ± 14.5	0.003	0.001	< 0.001
Left ventricular end-systolic volume, mL	49.1 ± 22.8	45.8 ± 20.9	43.8 ± 18.9	47.2 ± 17.3	0.158	0.081	0.508
Pulmonary artery systolic pressure, mm Hg	37.5 ± 10.2	32.8 ± 5.8	31.4 ± 4.5	30.9 ± 4.8	0.009	0.005	0.002
NYHA functional class III to IV	14 (73.7)	0 (0)	1 (5.3)	2 (10.5)	<0.001	<0.001	0.002
6MWD, m	233.2 ± 85.7	288.2 ± 74.7	303.4 ± 63.7	310.5 ± 78.1	<0.001	<0.001	0.003
KCCQ score, points	52.7 ± 18.6	75.1 ± 7.3	78.8 ± 5.8	79.8 ± 7.3	<0.001	<0.001	<0.001
Type II (n = 21)
MR grade ≤2+	0 (100.0)	20 (95.2)	19 (90.5)	19 (90.5)	<0.001	<0.001	0.001
MR grade ≤1+	0 (0)	16 (76.2)	14 (66.7)	14 (66.7)	<0.001	<0.001	0.001
Left ventricular end-diastolic volume, mL	117.1 ± 38.8	98.2 ± 32.0	94.1 ± 23.6	90.0 ± 23.0	<0.001	<0.001	<0.001
Left ventricular end-systolic volume, mL	44.0 ± 17.6	43.5 ± 16.1	42.5 ± 15.9	41.8 ± 15.9	0.862	0.612	0.494
Pulmonary artery systolic pressure, mm Hg	45.7 ± 15.0	39.9 ± 10.8	37.3 ± 11.2	37.8 ± 10.2	0.013	<0.001	0.020
NYHA functional class III to IV	19 (90.5)	2 (9.5)	3 (14.3)	5 (23.8)	<0.001	<0.001	<0.001
6MWD, m	217.1 ± 57.7	249.8 ± 34.7	266.0 ± 59.8	280.5 ± 89.3	<0.001	0.003	0.015
KCCQ score, points	50.4 ± 8.9	75.0 ± 9.4	76.8 ± 6.5	77.7 ± 7.9	<0.001	<0.001	<0.001
Type IIIa (n = 17)
MR grade ≤2+	0 (0)	17 (100)	17 (100)	17 (100)	<0.001	<0.001	<0.001
MR grade ≤1+	0 (0)	16 (94.1)	16 (94.1)	16 (94.1)	<0.001	<0.001	<0.001
Left ventricular end-diastolic volume, mL	123.6 ± 26.6	105.3 ± 21.4	99.4 ± 15.6	96.0 ± 15.7	0.006	<0.001	<0.001
Left ventricular end-systolic volume, mL	55.1 ± 28.8	55.5 ± 24.6	50.9 ± 22.1	50.6 ± 21.5	0.877	0.153	0.118
Pulmonary artery systolic pressure, mm Hg	41.0 ± 23.2	35.4 ± 12.7	31.6 ± 11.1	32.8 ± 13.5	0.158	0.050	0.063
NYHA functional class III to IV	13 (76.5)	0 (0)	1 (5.9)	0 (0)	<0.001	<0.001	<0.001
6MWD, m	273.1 ± 86.2	299.4 ± 65.2	317.5 ± 71.3	317.7 ± 94.1	0.028	0.008	0.019
KCCQ score, points	53.1 ± 13.9	76.3 ± 8.2	77.9 ± 7.9	78.9 ± 5.6	<0.001	<0.001	<0.001
Type IIIb (n = 11)
MR grade ≤2+	0 (0)	10 (90.9)	10 (90.9)	9 (81.8)	0.002	0.002	0.004
MR grade ≤1+	0 (0)	8 (72.7)	7 (63.6)	7 (63.6)	0.008	0.016	0.016
Left ventricular end-diastolic volume, mL	132.6 ± 36.6	113.1 ± 28.5	105.5 ± 27.3	107.6 ± 14.1	<0.001	0.028	0.011
Left ventricular end-systolic volume, mL	44.9 ± 19.4	42.1 ± 15.1	42.7 ± 14.2	44.2 ± 14.0	0.176	0.445	0.802
Pulmonary artery systolic pressure, mm Hg	41.5 ± 9.4	37.9 ± 9.4	35.9 ± 18.7	36.6 ± 14.2	0.425	0.435	0.386
NYHA functional class III to IV	9 (81.8)	1 (9.1)	1 (9.1)	3 (27.3)	0.008	0.008	0.031
6MWD, m	239.7 ± 38.6	298.2 ± 63.9	314.3 ± 66.7	315.8 ± 87.5	0.015	0.009	0.012
KCCQ score, points	53.7 ± 12.7	74.1 ± 11.0	75.4 ± 8.6	75.1 ± 6.9	<0.001	<0.001	<0.001

Values are mean ± SD, n (%).

6MWD = 6-min walk distance; KCCQ = Kansas City Cardiomyopathy Questionnaire; MR = mitral regurgitation.

^a,b,cThe P-value of baseline echocardiographic data versus 30-days, 6 months and 1-year post-procedure, respectively.

Discussion

This study is the first to report 1-year outcomes in patients with commissural DMR with ECL adjudication in the contemporary TEER era. Unlike previous multicenter registries that have predominantly focused on noncentral or broadly complex primary MRs, our analysis distinctly targets a significant yet challenging subgroup—commissural DMR, noted for its complex anatomy. We introduce a novel morphological classification system for commissural DMR and demonstrated its feasibility and effectiveness in guiding TEER procedures. Furthermore, our findings uniquely demonstrate that an imaging-centric approach to TEER not only achieves substantial MR reduction but also ensures low mortality rates and persistent improvements in LV remodeling, cardiac function, and quality of life in patients with commissural DMR.

Our study highlights the significant prevalence of commissural DMR among the elderly, accounting for 23.3% of cases. Notably, posteromedial prolapse occurs 1.5 times more frequently. This finding contrasts with earlier research indicating variability in commissural prolapse distribution across different ethnic groups. For example, in a Korean study by Kim et al,⁷ isolated commissural prolapse was more frequent (25% of cases) and PC was approximately twice as common as AC prolapse. PC was 3 times more common than AC prolapse in a large Japanese study,¹⁶ and similar results were obtained in a German study,¹⁷ suggesting an ethnic influence on anatomical presentation, pointing toward the necessity for personalized therapeutic approaches based on anatomical and epidemiological insights.

TEE is crucial for detailed anatomical assessment but has limitations in visualizing complex structures and variability in image quality. Our study incorporates advanced imaging techniques, including 3D imaging with MPR, to enhance visualization. Centers without these technologies may benefit from alternative methods such as the “Stitch Artifact Technique.”⁴ Future work should focus on developing more robust imaging protocols to improve the applicability of our classification system.

The implementation of this classification guided TEER strategies has led to high technical and device success rates, highlighting its potential to enhance procedural precision and outcomes in TEER. By providing a detailed framework for understanding and addressing the anatomical complexities of commissural DMR, our approach significantly contributes to minimizing procedural risks and optimizing device placement.

Moreover, the study reveals notable variations in procedural times and MR severity outcomes across different commissural DMR subtypes, underscoring the impact of detailed preprocedural imaging on procedural efficiency and effectiveness. Type I lesions, driven by less complex prolapses, typically show shorter procedural times and more favorable MR severity reductions. In contrast, Type II and Type IIIb lesions, because of their complex and extensive nature, require longer times and exhibit varied MR outcomes, emphasizing the critical role of tailored imaging and intervention strategies.

Our study, focusing on TEER for commissural DMR, has demonstrated superior outcomes in MR reduction, illustrating distinct advantages compared with the first-generation TEER devices.⁶ However, our study noted a lower percentage of patients achieving an MR grade of ≤1+ at 1 year compared with the results from the EXPAND G4 study, possibly caused by the low proportion of complex lesions in their cohort and the improvements of newer-generation TEER devices. This highlights the evolving efficacy of advanced TEER technologies, which are known for its versatility with varying arm lengths and widths and are particularly beneficial in managing complex lesions such as those categorized as Type II and Type IIIb.

Significant reductions in LV volume and pulmonary arterial systolic pressure and improvements in NYHA functional class, KCCQ scores, and 6MWD further underscore the positive outcomes of TEER on patient-reported measures, corroborating the efficacy of our classification system in directing interventions that enhance cardiac function and patient quality of life.

Study limitations

This investigation, while pioneering in its approach to commissural DMR through TEER, has several limitations. Primarily, the study's findings are based on a relatively small sample size within a predominantly Chinese population, and its applicability to diverse patient demographics remains to be validated. Moreover, the procedural success and complication rates reported here are reflective of highly specialized centers with considerable expertise in TEER; outcomes in less experienced settings might differ. Therefore, we are conducting a prospective, multicenter, single-arm study in Asia to further evaluate the safety and effectiveness of TEER in patients with commissural DMR.

Conclusions

Our study provides preliminary evidence supporting the utility of a morphological classification system in guiding TEER for commissural DMR. Although the results are promising, the sample size limits the generalizability of our findings. Future research with larger cohorts is necessary to confirm the effectiveness of this classification system and to explore its impact on patient outcomes more broadly. Our findings suggest potential directions for such research and underscore the need for continued exploration into the anatomical complexities of commissural DMR and their implications for TEER.

Data Sharing

The data will be available based on reasonable requests to the corresponding author.

Funding Support and Author Disclosures

This study is part of the China Degenerative Valve Disease II Cohort Study (China-DVD2 Study, NCT05044338), which is support by National Key R&D Program of China (2020YFC200801100). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Video 1

Three-Dimensional Image of Type I Patients

Video 2

Three-Dimensional Image With Color Doppler of Type I Patients

Video 3

Three-Dimensional Image of Type Ⅱ Patients

Video 4

Three-Dimensional Image With Color Doppler of Type Ⅱ Patients

Video 5

Three-Dimensional Image of Type IIIa Patients

Video 6

Three-Dimensional Image With Color Doppler of Type IIIa Patients

Video 7

Three-Dimensional Image of Type IIIb Patients

Video 8

Three-Dimensional Image With Color Doppler of Type IIIb Patients

Video 9

Three-Dimensional Image of Restrictive Clipping Strategy for Type I

Video 10

Three-Dimensional Image of Zipping Clipping Strategy for Type II

Video 11

Three-Dimensional Image of Simultaneous Clipping Strategy for Type IIIa

Video 12

Three-Dimensional Image of Staged Clipping Strategy for Type IIIb