Technologies in minimally invasive treatment of severe mitral regurgitation

Abstract

Mitral valve regurgitation is the second most common valve defect in Europe among adults. Primary mitral regurgitation (MR) results from structural abnormalities of the valve apparatus (e.g., leaflet prolapse, chordae rupture), often due to myxomatous degeneration or congenital defects. Secondary MR arises from left ventricular remodeling (e.g., after myocardial infarction or heart failure), leading to functional valve incompetence despite normal valve structure. The choice of treatment depends on the degree of valve regurgitation and the severity of the patient‘s clinical symptoms. The focus herein is on discussing the anatomy of the mitral valve, the pathophysiology of regurgitation, and diagnostic methods. The qualification process is then outlined for invasive treatment and various methods of mitral valve repair, including new minimally invasive techniques. Transcatheter mitral valve repair methods are discussed, among other methods, “edge-to-edge” repair and transcatheter mitral valve replacement. Publicly available data confirms that the latter is a widely available and safe treatment method, that represents a promising alternative to surgical treatment.

Introduction

Mitral regurgitation (MR) is the second most common (after aortic valve stenosis) valvular disease in Europe. Worldwide, it affects 24 million people. Untreated mitral regurgitation may cause ventricular dilatation, arrhythmias, and heart failure. Prognosis depends on severity and cause — primary MR responds better to early surgery, while secondary MR has a poorer outcome due to ventricular dysfunction. Recently, new approaches for mitral valve repair have been developed [1–3].

The aim of the study is to evaluate new techniques for minimally invasive mitral valve repair.

Anatomy of the mitral valve

Primary mitral regurgitation (MR) results from structural abnormalities of the valve apparatus (e.g., leaflet prolapse, chordae rupture), often due to myxomatous degeneration or congenital defects. Secondary MR arises from left ventricular remodeling (e.g., after myocardial infarction or heart failure), leading to functional valve incompetence despite normal valve structure.

The mitral valve apparatus consists of anterior and posterior leaflets, annulus, and subvalvular structures. The shape of the valve is based on the aortic annulus and the aorto-mitral curtain from the front, and the muscular attachments of the left atrium at the atrioventricular (A–V) junction from the rear. The front leaflet has a larger diameter anterior-posterior (AP) and occupies one-third of the annulus circumference, and the posterior leaflet, the remaining part of the ring, has a smaller diameter and is more rectangular in shape. Each leaflet has three serrated segments which are defined as A1, A2, A3 for the anterior leaflet and P1, P2, P3 for the posterior one. These segments are formed by adipose tissue. Subvalvular structures include tendinous fibers and papillary muscles that connect the mitral valve leaflets to papillary muscles of the left ventricle [4–6].

Carpentier classification for mitral valve regurgitation

A Carpentier classification for mitral valve regurgitation categorizes it into three types based on leaflet motion. Type I involves normal leaflet motion with annular dilatation or leaflet perforation. Type II is characterized by excessive leaflet motion (prolapse), often due to chordal or papillary muscle rupture. Type III involves restricted leaflet motion, with Type IIIa affecting both systole and diastole (e.g., rheumatic disease), and Type IIIb restricting systolic motion due to altered ventricular geometry (e.g., post-myocardial infarction) [7].

Pathophysiology of mitral valve regurgitation

Primary

Primary mitral regurgitation may involve one or more components of the valve apparatus. It manifests as leaflet prolapse (according to Carpentier classification: Type II) or its perforation (Type I), rupture of the papillary muscle or tendinous cords (Type II). One of the most common causes is myxomatous degeneration (Type II). Other causes include congenital anomalies such as double orifice mitral valve (Type I), parachute mitral valve (Type IIIa), and isolated cleft valve (Type I). Connective tissue diseases also can lead to primary regurgitation (Type IIIa). Advanced age is considered a factor intensifying the progression of the disease [4, 8, 9].

Secondary

Secondary MR, often referred to as functional MR, occurs when the chordae and leaflets are structurally normal. Still, regurgitation arises due to an imbalance of forces on the valve, secondary to altered LV geometry. According to the Carpentier classification, it is categorized as Type IIIb, where leaflet motion is restricted during systole. Causes include ischemic MR following myocardial infarction, congestive heart failure, and hypertrophic cardiomyopathy. In the early stages, LV walls stretch due to volume overload, maintaining normal ejection fraction. However, as MR progresses, LV dilatation alters geometry, worsening MR severity. This leads to increased left atrial pressure, pulmonary hypertension, and eventually, LV failure. Early intervention is crucial to prevent irreversible LV damage and optimize outcomes [8–10].

Atrial functional mitral regurgitation

Atrial functional mitral regurgitation (AFMR) results from annular dilation due to atrial enlargement, often from atrial fibrillation or chronic volume overload, rather than LV dysfunction. In AFMR, structurally normal valve leaflets fail to coapt due to mitral annulus dilation, exacerbated left atrial enlargement and regurgitation. Unlike ventricular MR, AFMR is driven by atrial factors, requiring different therapeutic approaches, often targeting atrial rhythm or structural correction [11].

Timely intervention, guided by advanced imaging, is crucial to prevent irreversible damage and optimize long-term outcomes [10–13].

Diagnosis of mitral regurgitation and qualification for invasive treatment

Echocardiography is the key and most important diagnostic tool for detecting and evaluating mitral regurgitation. The role of transthoracic echocardiogram includes: 1) identifying the cause of mitral regurgitation (MR); 2) measuring the severity of the regurgitation; 3) evaluating how the left ventricle responds to the volume overload; and 4) determining whether long-term repair is feasible. Whenever transthoracic ultrasound with doppler imaging is not sufficient to evaluate the severity of regurgitation, transesophageal echocardiography, cardiac magnetic resonance imaging (CMR) and CT are performed [9, 10].

Cardiac MRI precisely quantifies MR severity and assesses ventricular function, especially when echocardiography is inconclusive, while also evaluating myocardial viability. Cardiac CT offers detailed visualization of valve anatomy and is key for planning transcatheter interventions. Both modalities support accurate diagnosis and treatment selection in complex MR cases [10, 14].

The treatment of mitral regurgitation depends on the severity of the condition and the patient’s clinical characteristics. For acute mitral regurgitation, immediate medical attention is necessary as this is a life-threatening condition. The surgical intervention cannot be postponed [10, 12].

In mild cases of chronic MR, close monitoring may be all that is necessary, with regular follow-up. Lifestyle modifications such as regular exercise, a heart-healthy diet, and avoiding smoking and excessive alcohol consumption can also be helpful [10, 12, 15].

In moderate to severe cases of chronic MR with symptoms, medications are used to reduce symptoms and improve heart function. These medications include diuretics, ACE inhibitors or ARBs, and beta-blockers [10, 12, 15]. In primary mitral regurgitation, surgery is recommended in asymptomatic patients with LV dysfunction (LVESD ≥ 40 mm and/or LVEF ≤ 60%), and should be considered in asymptomatic patients with preserved LV function (LVESD < 40 mm and LVEF > 60%) and atrial fibrillation (AF) secondary to mitral regurgitation or pulmonary hypertension, as well as in low-risk asymptomatic patients with LVEF > 60%, LVESD < 40 mm and significant LA dilatation (volume index ≥ 60 mL/m² or diameter ≥ 55 mm). The valve should be repaired whenever possible [16].

The edge to edge repair may be considered in symptomatic patients who fulfil the echocardiographic criteria of eligibility, are judged inoperable or at high surgical risk [17].

In secondary mitral regurgitation, valve surgery/intervention is recommended only in patients with severe regurgitation who remain symptomatic despite optimal medical treatment (including cardiac resynchronization if indicated) and has to be decided by a structured collaborative Heart Team. Valve surgery is also recommended in patients undergoing coronary artery bypass grafting (CABG) or other cardiac surgery. In high-risk symptomatic patients not eligible for surgery and not fulfilling the criteria suggesting an increased chance of responding to transcatheter edge-to-edge repair (TEER), the Heart Team may consider in selected cases a TEER procedure or other transcatheter valve therapy if applicable, after careful evaluation for ventricular assist device or heart transplant [17].

Approaches for mitral valve repair

Mitral valve repair is a medical procedure involving fixing an impaired mitral valve, one of the valves regulating blood flow through the heart [17, 18].

Surgical mitral valve repair involves open-heart surgery, where a surgeon makes a chest incision to gain access (sternotomy or right minithoracotomy), uses extracorporeal circulation and arrests the heart [17, 18].

Regardless of the approach used, cardiopulmonary bypass with arterial cannulation and bicaval venous cannulation is used. The repair techniques may include artificial chordae implantation, partial posterior leaflet resection, chordae translocation, cleft closure etc. (Central illustration). The surgical repair should always be completed with an artificial ring implantation, shaping the annulus adequately and ensuring long-term effect [19, 20].

Central illustration.

Percutaneous mitral valve repair methods

Transcatheter mitral valve regurgitation repair comes with some benefits — reduced morbidity, faster recovery and shorter hospitalization. It may reduce symptoms and improve the quality of life for patients with mitral valve insufficiency, but the choice of procedure depends on the mechanism and severity of the valve damage, the patient’s overall health, and the experience and preference of the treating physician [16, 17].

Options for percutaneous mitral valve intervention

Edge-to-edge repair

MitraClip

In 2003, the first human MitraClip implant in Venezuela marked the beginning of percutaneous mitral valve repair. The introduction through a catheter allows it to be placed on the leaflets of the mitral valve, causing their permanent approximation and the formation of a “double-orifice” mitral valve. As standard procedure transseptal puncture is performed by an interventional cardiologist. The transseptal puncture is guided by transesophageal echocardiography. The puncture site needs to be roughly 5 cm above the mitral annulus to allow sufficient catheter and clip maneuvering. Next, the MitraClip is positioned into the LV below the mitral leaflets and open the clip to 180 degrees. After another check of the perpendicular position to the coaptation line, the implant is placed withdrawn towards the left atrium to “capture” the leaflets of the mitral valve and it is closed to above 60 degrees (Fig. 1). This procedure is performed after heparin administration. After the intervention, patients are treated with ASA 325mg daily for 6–12 months and clopidogrel 75 daily for 30 days [21].

Figure 1.

MitraClip positioning and implantation in fluoroscopy (A, B), 2D transesophageal echocardiography (TEE) (C) and 3D TEE (D)

The Endovascular Valve Edge-to-Edge Repair Study (EVEREST) II study demonstrated the effectiveness of MitraClip therapy as a viable option for patients with severe functional or degenerative MR, compared to traditional surgery. In 2016, the upgraded MitraClip NT system was introduced. The steerable sleeve was improved, allowing for more precise steering of the clip, resulting in less anterior movement while turning the M knob. Additionally, the gripper material was changed from Elgiloy to Nickel, enabling a more efficient and active leaflet capture through an increase in gripper drop angle [21].

The MitraClip NTR/XTR system was introduced in 2018 and brought several improvements. Firstly, the clip delivery shaft is now a multi-lumen extrusion with a reinforced braid and Pebax jacket and a stiffer shaft system that reduces rotation during clip advancement into the LV. Secondly, the clip delivery shaft was lengthened by 1.5 cm, allowing for a higher transseptal puncture without impacting reach on the mitral valve. Additionally, the increased height system increased maneuvering within the left atrium. Thirdly, opening and closing the clip arms did not require locking the device, minimizing inadvertent medial and lateral movements. Lastly, the XTR system has 3 mm longer clip arms for better reach and grasp to handle more complex anatomies. The MitraClip G4, launched in 2019, came with wider clips with an additional 2 mm grasping area, maximizing horizontal coaptation. With the NTR, XTR, NTW, and XTW systems, there are now four different clip options available to tackle various leaflet pathologies. The G4 also features Controlled Gripper Actuation, allowing for independent gripper movement for optimized leaflet grasping, and an integrated pressure monitor in the MitraClip catheter to observe atrial pressure during implantation [21].

In 2018, the French MITRA-FR study was presented, which focused on patients with functional mitral regurgitation (FMR) and moderate-severe MR receiving optimal medical treatment as determined by the heart team. The study included patients with severe secondary MR, who received either medical therapy alone or combined with the MitraClip procedure. At the time of hospital discharge, the severity of mitral regurgitation was evaluated, and 95.1% of patients showed an improvement of at least one grade. The findings suggest that combining MitraClip with standard medical treatment did not lead to a meaningful reduction in mortality or heart failure-related hospitalizations over a two-year period when compared to medical therapy by itself. The rates of ischemic or hemorrhagic stroke, renal replacement therapy, and severe hemorrhage were higher in the intervention group (Tab. 1) [18, 21, 22].

Table 1.

Emerging transcatheter mitral valve (MV) repair technologies for mitral regurgitation (MR) with data in humans

Device	Access	Design	Mechanism	Clinical experience
Edge-to-edge repair
MitraClip	Femoral vein	Approximate the anterior and posterior leaflets Clip arms and grippers Longitudinal frictional elements with an active closure	Clip-based edge-to-edge repair involves creating a double-orifice MV to minimize regurgitation	MITRA-FR 152 patients in interventional group 96% procedural success 14.6% procedural complications 54.6% rate of the primary composite endpoint 48.7% rate of unplanned HR hospitalization at 1 year 24.3% rate of mortality at 1 year
				COAPT 302 patients in interventional group 95% procedural success 8.5% procedural complications 96,6% the primary safety endpoint of freedom from device-related complications at 12 months 35.8% annualized rate of all hospitalizations for HR 29.1% the rate of mortality 177 patients
PASCAL Transcatheter MV	Femoral vein	Approximate the anterior and posterior leaflets Paddles and clasps Central spacer to fill the regurgitant orifice area Retainer elements in a horizontal fashion with a passive closure		96.5% effectiveness 3.4% major adverse event rate 27.7% mortality rate at 2-year 77.5% freedom from HF hospitalizations 95% MR reduction
Indirect annuloplasty
CARILLON Mitral Contour System	Internal jugular	System joins two nitinol stents through a curvilinear segment By modulating the tissue near the MV annulus, posterior and anterior leaflets are brought closer, resulting in mitral annular dilation as well as MR To determine the device’s size, both CS’ diameter and length are taken into account	Reduction of MR can be achieved by decreasing the size of the MV annulus through the CS	AMADEUS 30 implanted devices Reduction in the mitral annulus diameter and an average reduction of 23% 88% were in NYHA class I or II at the 6-month follow-up Improvement in the quality of life score and 6-minute walk testing at the 6-month follow-up
				TITAN 36 implanted Devices No control group 68% successful implantation procedure 50% decrease in regurgitation Mortality rate 1.9% at 30 days and 22.6% at 12 months
				TITAN II 30 implanted devices No control group Procedural success 83% Mortality rate 20% at 12 months
				REDUCE-FMR 87 implanted devices Control group 13,7% mortality rate 67,9% Improvement of at least one class in NYHA
ARTO device: The MVRx ARTO	Internal jugular + femoral vein	Comprised of two anchors deployed over the lateral wall of the left atrium via the CS and in the atrial septum, connected by a tether that traverses the left atrial chamber		45 patients Adverse events reported in 24% patients Mortality rate 11% at 12 months and 18% at 24 months 80% significant improvement in symptoms MR grade had been reduced to ≤ 1 in 68%
Mitral Loop Cerclage Catheter System	Subclavian vein + femoral vein	Consists of a stainless-steel tension element delivered using a multistep procedure to form a continuous loop from the CS to a basal septal perforator coronary vein and right ventricular outflow trac		4 patients Reduction in regurgitant volume Reduction in left atrial and LV systolic and diastolic size
Direct annuloplasty
Cardioband	Femoral vein	Utilizes sutureless anchors to attach the annuloplasty device directly to the mitral annulus By enabling adjustable compression of the septolateral diameter, it reduces the size of the MV annulus and mitigates the severity of MR	Direct attachment to the MV annulus and subsequent reduction of its size can help decrease MR	60 patients 97% successful implantation 87% the overall survival rate at one 66% of the survival rate free of hospital readmission for HR
The Millipede IRIS ring	Femoral vein	Closed, semirigid ring made of nitinol, a nickel-titanium alloy that has been laser-cut and heat-set The base of the ring in a “zigzag” shape features eight helical stainless-steel anchors, each of which can be independently rotated and attached directly to the mitral annulus Anchors can be unscrewed, moved, and redeployed to achieve optimal placement Sliders that can reduce the size of the annulus Allows for targeted annuloplasty at the most dilated parts of the annulus by carefully tightening individual collars. The upper part of the device contains eight sliding collars, each collar draws the two adjacent helical anchors closer together, enabling operators to customize the final circumference and diameter of the annulus by shortening the linked portion of the ring		7 patients 31.8% reduced mitral septolateral diameter at 30 days 36.8% decreased diastolic LV volume 22.6% reduction LV volume
The AccuCinch system	Femoral artery	Nitinol cable placed Beneath the MV annulus A retrograde arterial mechanism- this involves placing adjustable anchors within the wall of the LV, connected by a nitinol cable beneath the MV annulus		Studies are ongoing
Artificial chordae
The Neochord	Transapical off-pump	Transcatheter surgical off-pump mitral repair procedure which implants artificial cords into the MV	Attachment of artificial chordae to the mitral leaflets in cases of leaflet prolapse or flail helps reduce MR	169 implanted devices 87.6% successful implantation 98% survival at 1 year 57.6% freedom from recurrent MR 78.9 freedom from reoperation Improvement in clinical status based on NYHA functional class
Harpoon MV Repair System	LV	The system anchors artificial cords on the flaps to take the place of the natural cords via transapical off-pump surgical technique using transcatheter technology		TRACER 11 patients 100% successful implantation 85% MR was mild or less after procedure Significant reduction in LV end-diastolic volumes and filling pressures 98% of patients who underwent the procedure were in NYHA I or II after 1 year 52% showing no or trace MR after 1 year 23% showing mild MR after 1 year 23% showing moderate MR after 1 year 2% showing severe MR after 1 year
Transcatheter valve replacement
The SAPIEN-XT	Femoral vein	Cobalt-chromium alloy stent-mounted bovine pericardial tissue valve with three leaflets	Transcatheter placement of a bioprosthetic MV, either within a previously implanted valve (valve-in-valve), within a surgical ring (valve-in-ring), or directly in the native mitral annulus, is performed to reduce MR	65 patients 95% successful implantation 3% died 13% reoperations 52% none/trace MR after surgery
Intrepid	LV	Circular valve shape Nitinol, double stent, self-expandable frame Radial force and subannular cleats anchoring mechanism Trileaflet, bovine pericardium The outer frame features cleats that engage the mitral leaflets and the symmetric design allows for placement without the need for orientation to the D-shaped mitral annulus Valve size 27 mm with 3 outer stent sizes: 43, 46, and 50 mm Delivery sheath size 35F with a self-expanding nitinol system		98% success rate 74% of patients had zero MR after surgery 14% mortality rate 26% had mild MR Improvement in NYHA class and quality of life during follow-up
The CardiaAQ	Femoral vei	Circular valve shape Porcine pericardium leaflets, nitino, double stent, self-expandable frame The valve available in two systems, one with a transapical and another with a transseptal access Mitral annulus capture with native leaflet engagement anchoring mechanism Trileaflet, Bovine pericardium Delivery sheath size 33F Valve sizes 30 mm		15 patients with implants 82% successful implantation
Tiara	Transapical off-pump	Saddle- or D-shaped annulus Nitinol, self-expandable frame Fibrous trigonum capture with native leaflet engagement Trileaflet, Bovine pericardium Delivery sheath size 32F Valve sizes 35 mm and 40 mm		50 patients 95% implant success rates 8.5% the 30-day mortality
Caisson	Femoral vein	D-shaped annulus 4 sub-annular anchoring feet and three atrial holding features, and is constructed from porcine pericardium with a self-expandable nitinol frame		Studies are ongoing
Tendyne system	Transapical off-pump	Outer frame contoured to mitral annulus Circular inner frame Nickel titanium alloy, double stent, self-expandable frame Apical tether anchoring mechanism Trileaflet, Porcine pericardium Outer frame in 8 standard and 5 low profile, 2 inner frame sizes Delivery sheath size 36F		319 patients 96.9% technical success 24.8% died

CS — coronary sinus; HF — heart failure; LV — left ventricle; NYHA — New York Heart Association

On the other hand, in a COAPT trial, where patients similarly received either intervention or medical treatment, the authors concluded that among patients with heart failure and ≥ moderate-to-severe secondary MR who remained symptomatic despite the use of optimal guideline-directed medical therapy (GDMT), the MitraClip procedure reduced the rates of hospitalization for heart failure and all-cause mortality within 2-years of follow-up than did medical therapy alone. (Tab. 1) [21, 23].

The differences between the results of those two trials have been widely discussed. However, the cohorts for each trial differed significantly, which may explain the results. First, there was no independent committee overseeing patient selection. Patients could be included as long as the heart team believed they were receiving optimal medical treatment. Additionally, MITRA-FR did not require follow-up echocardiograms or 6-minute walk tests, resulting in a considerable amount of missing data on echocardiographic outcomes and patient functional status after 12 months. Investigators could participate in the study if they had previously performed at least five MitraClip procedures. [18, 21, 22]. Compared with patients in the COAPT trial, those enrolled in the MITRA-FR trial had larger LV end-diastolic volumes (MITRA-FR: 135 ± 35 mL/m² vs. COAPT: 101 ± 34 mL/m²) suggesting a more advanced stage of LV disease. COAPT excluded patients with very severe LV dilation. Secondly, the inclusion criteria for LVEF in COAPT were 20–50% vs. 15–40% in MITRA-FR. Further, MITRA-FR patients also had less severe MR (EROA: 31 ± 10 mm²) as compared with COAPT (41 ± 15 mm²). In contrast to MITRA-FR, COAPT imposed a more demanding criteria for inclusion of patients: that is the use of maximal tolerated doses of GDMT, and treatment with cardiac resynchronization therapy, defibrillators, and revascularization. Finally, a more aggressive strategy for correction of MR was applied in COAPT, as suggested by the larger number of clips implanted per patient in COAPT vs. in MITRA-FR. All those factors might have greatly influenced the results and explain their differences [24].

The RESHAPE-HF2 trial (2024), an international randomized controlled study, evaluated the effectiveness of transcatheter mitral valve repair (M-TEER) using the MitraClip device in patients with symptomatic heart failure and moderate-to-severe functional mitral regurgitation. The results showed that M-TEER, when combined with guideline-directed medical therapy, significantly reduced the risk of heart failure hospitalizations and cardiovascular death compared to medical therapy alone. The treatment effects were more consistent with the COAPT trial than with MITRA-FR. However, direct comparisons are difficult due to differences in patient characteristics - patients in RESHAPE-HF2 had less severe regurgitation but more advanced symptoms. While the study provides valuable clinical insights, selecting appropriate candidates for M-TEER remains a key challenge [25].

Consequently, the findings from these studies should be interpreted with care. However, it can be concluded that MitraClip is an effective treatment for a “specific group” of patients with FMR and heart failure, highlighting the need to refine patient selection criteria moving forward [18, 21, 22].

PASCAL transcatheter MV

In February 2019, the PASCAL device received CE Mark approval for treating MR [21]. Similar to the MitraClip system, the PASCAL device approximates the anterior and posterior leaflets, but it uses paddles and clasps instead of clip arms and grippers [26]. In contrast to MitraClip, which has longitudinal frictional elements with an active closure, the PASCAL device has retainer elements in a horizontal fashion with a passive closure. A central spacer that fills the regurgitant orifice area and reduces the need to pull the mitral valve leaflets together, thus minimizing stress on the leaflets (Fig. 2) [27].

Figure 2.

The PASCAL transcatheter valve repair system

The PASCAL system was evaluated in the CLASP study with the FMR cohort. Studies have shown that the PASCAL system improves symptoms, quality of life, and severity of MR, as well as providing evidence for LV reverse remodeling for high-risk patients with FMR (Tab. 1) [17, 21].

Indirect annuloplasty

CARILLON mitral contour system

The Mitral Contour System, developed by Cardiac Dimensions, Inc. in Kirkland, Washington is a treatment option for functional MR that incorporates a proprietary, implantable device percutaneously through transjugular access. It was first launched in Europe in 2012. By leveraging the anatomical relationship of the coronary sinus and the mitral annulus, the Carillon device achieves an “indirect” annuloplasty [22]. Although pre-procedural CT scans may provide some information about the connection between LCx and the aforementioned vein, procedural imaging is currently the established standard. Because of its close proximity to the left circumflex artery, a known complication is the risk of compressing the coronary artery. Coronary angiography is done to see if the device being placed causes any squeezing in the left circumflex-obtuse marginal arterial system. The current technology allows the device to be recaptured and repositioned during the same procedure or removed and replaced with a new device if necessary, thanks to its benign design and availability in multiple sizes [27–29].

The Carillon underwent clinical trials, including the AMADEUS, TITAN, and TITAN II, to determine its safety and effectiveness. In the AMADEUS trial, the device was implanted successfully in patients with FMR and LV systolic dysfunction. The study revealed a significant reduction in the mitral annulus diameter and an average reduction in MR across five quantitative echocardiographic measures. Furthermore, 80% of patients were in NYHA class III or IV at baseline, while 88% were in NYHA class I or II at the 6-month follow-up. There was also an improvement in the quality of life score and 6-minute walk test at the 6-month follow-up (Tab. 1) [28, 30].

In the TITAN study, patients that underwent a successful implantation procedure (68% of the population) displayed a 50% decrease in regurgitation when compared to non-implanted patients who had stable volume. Additionally, the implanted group had a significant reduction in both systolic and diastolic LV volumes, whereas non-implanted patients showed an opposite effect. A decrease in classification from NYHA class III to II that lasted up to two years was observed in the implanted group (Tab. 1) [28, 31].

In the TITAN II trial, 36 patients were treated with the modified CARILLON mXE2 device, after device fractures observed during the TITAN trial. The reduction achieved in mitral annular dimension during the acute phase was sustained over the following year, with no changes observed. TITAN II demonstrated similar clinical and echocardiographic benefits as TITAN, including a reduction in mitral regurgitation, improvement in NYHA functional class, and a trend towards reverse remodeling indicated by a reduction in ventricular size [27, 28].

The REDUCE-FMR trial randomly assigned 120 patients, with 87 receiving treatment and 33 being the control group. Patients implanted with the Carillon device experienced an improvement of at least one class in NYHA, sustained in the majority at 12-month follow-up. The trial also reported a low 30-day all-cause mortality rate (Tab. 1) [32].

ARTO device: The MVRx ARTO transcatheter annular reduction therapy

MVRx ARTO is a transcatheter annular reduction therapy that utilizes an indirect annuloplasty system. The system works by reducing the anteroposterior diameter of the mitral annulus. The device received FDA approval in 2013 [27].

The procedure is done under general anesthesia with transesophageal echocardiography guiding placement of the implant. Two large tubes (16 Fr) are needed to insert the system. One tube goes into the coronary sinus through the right jugular vein, while the other goes across the atrial septum through a puncture in the femoral vein, near the front part of the skull. These tubes are connected inside the back part of the left atrium near the mitral valve using a miniscule wire. Regular tube changes are done to put in support for the coronary sinus (T-bar) and also support for the atrial septum. These supports are connected by an adjustable string to decrease the mitral valve and reduce leaking. Finally, the delivery system can be removed through the right internal jugular and femoral veins.

Patterson et al. [29] reported a significant improvement in MR grade as well as a significant reduction in the left atrial volume indexed to body surface area post-implantation of the ARTO system at the 2-year follow-up compared to baseline. Similarly, significant reductions in regurgitant volume, vena contracta, and the effective regurgitant orifice area, as measured by the proximal isovelocity surface area method were observed. The ARTO system implantation resulted in immediate improvements in LV dimensions, mitral regurgitant volume, grade, and AP diameter, which were sustained or even continued to improve over time up to 2 years. These changes translated into an improvement in NYHA class and a reduction in hospitalizations due to heart failure, which have been linked to increased morbidity and mortality (Tab. 1) [29, 33, 34].

Mitral loop cerclage catheter system

The innovative procedure developed by Tau-PNU Medical Co. Ltd., in Pusan, Korea in 2015, for mitral loop cerclage involves intricate maneuvers through both the femoral vein and left subclavian vein. By threading a wire into the coronary sinus and great cardiac vein, the cerclage is achieved by traversing the interventricular septum first from the anterior interventricular vein and afterwards into the right ventricle. The wire is then deftly looped around the mitral annular plane, having been taken from the right ventricular outflow tract. Following this delicate process, a tension device with an integrated coronary artery protection element is carefully applied to simultaneously promote mitral annulus compression and leaflet coaptation. The locking mechanism for this tension device is discreetly implanted within the left subclavicular pocket, completing the sophisticated surgical procedure [27].

The mitral loop cerclage procedure was found to reduce mitral valve regurgitation immediately and progressively for up to 6 months and resulted in favorable remodeling of the left atrial and left ventricular chamber volumes. It also appeared to induce electrical remodeling of the atria, which was observed as spontaneous reversion to sinus rhythm in patients with paroxysmal, persistent, and permanent atrial fibrillation. Device-related complications may include coronary artery occlusion, new bundle branch block, and the need for a repositioning procedure (Tab. 1) [29, 35].

Direct annuloplasty

Cardioband

The Cardioband system was manufactured by Edwards Lifesciences based in Irvine, CA. It received CE mark approval in 2015. The system is created to manage high-risk MR patients who are not suitable for open mitral surgery. Unlike a complete ring, Cardioband is implanted with the assistance of echocardiographic and fluoroscopic guidance using either a trans-femoral or a trans-septal approach. Its purpose is to attain posterior annuloplasty by placing a suture-less prosthetic band on the beating heart. The Dacron band is then anchored from the anterolateral to posteromedial commissures using stainless steel anchors to effectively decrease annular diameter and alleviate functional MR (Fig. 3). However, in challenging anatomic presentations, moderate to severe functional MR may persist even after Cardioband implantation, affecting up to 45.4% of patients at 6-month follow-up (Tab. 1) [26, 36–39].

Figure 3.

Edwards cardioband valve reconstruction system

The results of the Cardioband procedure are less effective than those achievable with a surgical undersized ring, as one-third of patients still had more than mild MR one year after device implantation [38, 40].

The millipede IRIS ring

The Millipede IRIS annuloplasty ring, developed by Millipede, Inc. of Santa Rosa, CA in 2017. This device is the pioneer in delivering a complete semi-rigid annuloplasty ring through a percutaneous, transfemoral, and transseptal route [27]. The IRIS procedure involves three primary steps: placement, anchoring, and actuation. The design of the device allows for targeted annuloplasty at the most dilated parts of the annulus and permits repositioning and retrieval until the IRIS ring has been fully released from the delivery system. In some cases, specific devices may be positioned within the left ventricular wall for decreasing mitral regurgitation [41, 42].

In a study conducted by Rogers et al. [41, 42], the transthoracic echocardiography (TTE) indicated a reduction in diameter from a baseline after 30 days. Every patient in the study showed an improvement in NYHA class and a reduction in mitral regurgitation. The mechanism of action involves complete and circumferential annuloplasty, resulting in a reduction in the mitral SL diameter, MR, LV volumes, and an improvement in NYHA Class (Tab. 1) [41, 42].

The AccuCinch system

The AccuCinch was created in 2013. This system functions by employing a retrograde arterial mechanism. This involves placing adjustable anchors within the wall of the left ventricle, connected by a nitinol cable beneath the mitral valve annulus. By tightening the cable, the left ventricular wall contracts, reducing both ventricular size and the mitral annulus. Consequently, the regurgitant volume is significantly decreased. Unlike other similar systems, the AccuCinch system focuses more on ventriculoplasty as compared to direct annuloplasty, as it provides direct support in the left ventricular myocardium. As a result, this device is currently undergoing testing in heart failure patients with dilated left ventricles but no significant valvular lesions [27].

Although the system is still undergoing feasibility trials, it is intended for use in patients with HFrEF or moderate to severe FMR who continue to experience NYHA class III–IV symptoms despite receiving optimal medical therapy (Tab. 1) [43].

Artificial chordae

The neochord

The NeoChord DS1000, developed by NeoChord Inc. in St. Louis Park, MN in 2010, is a safe and effective method for transventricular, off-pump mitral valve repair (MVRe) with neochord implantation. In anatomically suitable cases, the NeoChord procedure may be an alternative and persuasive strategy for mitral valve repair rather than replacement when standard redo surgery is not feasible or when proposing a minimally invasive alternative. In reoperative cases, the NeoChord procedure offers a significant advantage over other catheter-based mitral repair techniques, as it is generally not limited by the presence of an annuloplasty ring. The main goal of the NeoChord procedure is to provide a minimally invasive but patient-tailored intervention to address the specific underlying mechanism of recurrent MR [27, 44].

Under general anesthesia, the procedure is carried out with the aid of real-time 2D/3D transesophageal echocardiography (TEE) guidance, employing selective lung intubation. Starting with an anterolateral mini-thoracotomy in the fifth intercostal space, the pericardium is first opened and then suspended, and the left lung is isolated to expose the LV apex. Approximately 2–4 cm postero-lateral from the actual apex, the ideal entry point is established through palpation utilizing 2D-TEE imaging. Suturing two round purse-strings around the marked entry point, a trans-wall ventriculotomy is created by scalpel incision with a no. 11 blade. Navigating the device cautiously through the LV to prevent harm to the papillary muscles and subvalvular apparatus of the anterior mitral leaflet (AML), real-time guidance is provided using TEE X-plane view. After successfully navigating the valve, a comprehensive 3D imaging assessment is employed to precisely align the tip with the intended scallop. Subsequently, the device’s jaws close around the targeted scallop, with feedback provided via a fiberoptic display to ensure secure leaflet capture before closure. The grasped leaflet is then punctured at its edge to facilitate the deployment of a single pair of chords. Carefully withdrawn from the ventricle, the device exits outside the chordal loop. The two ends of the suture are threaded through the loop, forming a girth hitch knot that progresses towards the free edge of the scallop. This sequence repeats for each pair of chords deployed, typically ranging from 3 to 4 pairs to evenly distribute tension. Ultimately, under the guidance of 2D and 3D TEE, the chords are tensioned until optimal leaflet coaptation is attained, and all chordal free ends are attached to the LV wall using Teflon felt [44, 45].

The NeoChord repair procedure has a high surgical success rate and a low complication rate, making it a viable option for treating patients with posterior leaflet prolapse/flail (Type A and B anatomies) and anterior leaflet disease with adequate MV tissue over-riding. However, it is not recommended for cases of paracommissural disease and/or calcifications of the annulus/leaflets (Tab. 1) [39, 45, 46].

Harpoon MV repair system

This system was designed in 2015. The HARPOON procedure involves puncturing the left ventricle with a low-profile valved introducer and precisely navigating the HARPOON device towards the target to anchor artificial cords on the flaps via transapical off-pump surgical technique using transcatheter technology (Fig. 4) [27]. High-quality echocardiography is critical at every stage of the HARPOON procedure, from pre-screening and pre-procedural planning to the final evaluation and follow-up [47].

Figure 4.

The harpoon mitral valve repair system

Under general anesthesia with solitary lumen intubation, transesophageal 2D/3D echocardiography provides procedural guidance. A mini-thoracotomy is conducted in the fifth intercostal space to ascertain the optimal entry point on the LV apex. Two petite purse-string sutures are subsequently placed, validated by manual examination under 2D TEE. Equipped with an internal hemostatic valve, a 14 Fr introducer facilitates navigation through the LV with minimal loss of blood, puncturing the LV at the specified site. Guided by TEE X-plane view and 3D imaging assessment, the delivery system tip is positioned in the targeted scallop’s dome. The leaflet tissue is traversed by the needle, liberating the suture and retracting automatically, cinching the ePTFE coil and as a result, a double-helix knot on the atrial surface of the leaflet is created. Device retrieval and ferrying the artificial chord free-end via the introducer follows. This is reiterated until the desired results are met, employing a distinct delivery system, one per chord. Guided by 2D/3D TEE, the chords are tightened to attain the best reduction in mitral regurgitation before being secured to the LV wall [44].

The HARPOON System demonstrated excellent safety, high technical success, and effective reduction of mitral regurgitation confirmed by core laboratory analysis at the time of hospital discharge. The study also reported positive outcomes in terms of cardiac remodeling after 1 year (Tab. 1) [44, 48].

Transcatheter valve replacement

The SAPIEN-XT

The SAPIEN XT was commercialized in Europe in 2009. There is a cobalt-chromium alloy stent-mounted bovine pericardial tissue valve with three leaflets [48].

According to Halapas et al., when used in carefully selected patients, the SAPIEN XT and S3 valves offer better clinical outcomes and are more user-friendly. Compared to the self-expandable CoreValve, the latest SAPIEN valves have advantages such as a lower need for PPI, a decreased incidence of residual PVR, and lower-profile introducer sheaths. They may also be used for other cardiac valve diseases with a proper supporting structure. However, a potential drawback of the SAPIEN balloon-expandable valves is that they cannot be re-sheathed or repositioned, and there is a risk of annular rupture (Tab. 1) [48].

Intrepid

The Intrepid™ Transcatheter Mitral Valve Replacement System is among the new solutions being developed in 2021 to address mitral valve replacement. This device has a unique dual design that involves engaging the outer mitral annular anatomy using an outer frame and an inner stent, which houses the valve and replicates the original valve’s hemodynamic function [49].

The Intrepid valve system employs a trileaflet bovine pericardial valve, which has a flexible atrial portion that conforms to the native mitral annulus and atrial wall, while the ventricular portion is wider and stiffer than the native annulus. This unique design enables the valve to be properly seated and prevents perivalvular leaks. Mitral annular perimeter, intracommissure diameter, septal-lateral diameter, and potential for LV outflow tract obstruction are all factors considered in determining the proper size of the prosthesis using contrast-enhanced cardiac CT scan. The procedure is performed under general anesthesia with guidance by fluoroscopy, 2D and 3D transesophageal echocardiography, and preprocedure CT scan to locate a small left thoracotomy for LV apex access, typically to the left of the distal left anterior descending artery [50].

In contrast, Koh et al. [49] reported a significant reduction in echocardiographic evidence of MR and symptoms. Additionally, there was no evidence of valve thrombosis and patients showed improvements in NYHA class (Tab. 1).

Overall, the Intrepid device represents a promising solution for patients in need of MVRe who are at moderate to prohibitive risk for surgery [50].

The CardiaAQ

The CardiaAQ valve, developed by CardiAQ ValveTechnologies, Inc. located in Winchester, MA in 2015, is composed of a nitinol self-expanding stent, giving it a circular shape [27]. The anchoring mechanism relies on capturing the mitral annulus while engaging the native leaflets [51]. The frame design includes two sets of opposing left ventricular anchors to allow for annular attachment without radial force. Additionally, the frame retains the native subvalvular apparatus, containing a 40 mm anchoring region and a 30 mm inflow region (Tab. 1) [52].

Tiara

The TIARA transcatheter mitral valve replacement (TMVR) system from Neovasc Inc., based in Richmond, BC, Canada in 2014, is designed to address mitral regurgitation through a transapical access approach. Coaptation is facilitated by three bovine pericardial leaflets, while a generous atrial skirt is crafted to isolate the mitral inflow and in turn reduce paravalvular leaks. Securing the valve in position involves radial expansion of the TIARA frame and anchoring using ventricular tabs. Two frontal tabs fasten the valve onto the fibrous aorto-mitral curtain, while a sole rear tab lodges behind the posterior mitral leaflet onto the muscular rear shelf of the mitral annulus. Mitral annular dimensions are assessed using CT scans with contrast enhancement to ensure proper sizing. Using a sheathless system, TIARA valves for the 35 mm and larger valves are delivered into the LV with a 36-French (Fr) system and a 40 Fr system, respectively. This delivery technique facilitates the implantation process and ensures proper placement of the valves. An easy-to-use turning knob mechanism controls valve delivery, deployment, and resheathing, while entry into the LV is eased by a gentle and self-expanding tip (Tab. 1) [51, 53].

Caisson

The Caisson transcatheter mitral valve (TMV) is a percutaneous transseptal device successful human implants in 2016 (Tab. 1). During the procedure, intensive imaging is required to align the anchor when crossing the mitral valve, without interfering with the sub-chordal structures. The device is fully repositionable and retrievable, and employs a two-stage implant process for delivery of the anchor and valve. A systolic anterior motion (SAM) management feature is deployed in the final stage to capture leaflet A2 and prevent neo-left ventricular outflow tract obstruction. The Caisson TMV was designed to address both degenerative and functional mitral regurgitation and was found to have significantly lower pressure gradients compared to other techniques [54].

Tendyne system

The TendyneTM valve, developed by Abbott Vascular in California, USA and received European CE Mark approval in 2020. This is considered to be one of the most extensively researched systems for replacing the mitral valve using a transcatheter approach. This valve, designed for TMVR, is unique in that it can expand on its own, be fully retrieved, and can be repositioned as needed. It consists of two parts: an inner circular stent frame and an outer D-shaped stent frame (Tab. 1). The inner frame is fixed in size and contains three leaflets, while the outer frame comes in various sizes and includes a fabric cuff positioned at the annulus. To secure the valve to the left ventricular apex, a tethered locking pad is employed, guided by transesophageal echocardiography and fluoroscopy. This procedure is performed under general anesthesia using the transapical approach through a left minithoracotomy [55, 56].

Research indicates that using the Tendyne system for TMVR is harmless and effectively eliminates MR. This approach shows promise in addressing the needs of patients with suboptimal mitral valve anatomy for TEER. Furthermore, because it completely eliminates MR, the Tendyne system may offer significant benefits for both clinical outcomes and the reversal of left ventricular remodeling [56].

Complications of the techniques and worse prognosis factors

Percutaneous mitral interventions may lead to several complications, such as access site bleeding, device embolization, clip detachment from a single leaflet, cardiac chamber perforation, and even the development of mitral stenosis [27, 28].

Several factors have been identified as being associated with worse outcomes, including the development of heart failure symptoms (with survival worse in NYHA functional class III/IV), the onset of new atrial fibrillation, right ventricular dysfunction, severe tricuspid regurgitation, and functional etiology. Furthermore, echocardiographic parameters play a crucial role in determining patient suitability for percutaneous mitral interventions, such as an effective regurgitant orifice area greater than or equal to 40 mm² for primary MR or greater than or equal to 20 mm² for secondary MR, as well as LV systolic dysfunction with an LV ejection fraction of less than 60% [27, 28].

Conclusions

Minimally invasive strategies, including percutaneous and transapical transcatheter valve repair and replacement, have emerged as effective treatments for MR, especially in patients ineligible for surgery or unresponsive to medical therapy. Percutaneous approaches, such as MitraClip and PASCAL, have shown a strong safety profile and are associated with reduced heart failure hospitalizations and mortality. Advances in transcatheter technologies, artificial intelligence, and imaging modalities are improving patient selection and procedural planning. Future directions focus on personalized and combined therapies, with clinical trials shaping best practices and long-term outcomes.