Circulation Journal
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Impact of the MitraClip G4 System on Routine Practice and Outcomes in Patients With Secondary Mitral Regurgitation
Taishi OkunoMasaki Izumo Noriko ShiokawaShingo KuwataYuki IshibashiYukio SatoMasashi KogaKazuaki OkuyamaNorio SuzukiKeisuke KidaYasuhiro TanabeYoshihiro J. Akashi
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JOURNAL OPEN ACCESS FULL-TEXT HTML Advance online publication

Article ID: CJ-23-0503

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Abstract

Background: The MitraClip G4 system is a new iteration of the transcatheter edge-to-edge repair system. We assessed the impact of the G4 system on routine practice and outcomes in secondary mitral regurgitation (2°MR).

Methods and Results: Consecutive patients with 2°MR treated with either the MitraClip G2 (n=89) or G4 (n=63) system between 2018 and 2021 were included. Baseline characteristics, procedures, and outcomes were compared. Inverse probability of treatment weighting and Cox regression were used to adjust for baseline differences. Baseline characteristics were similar, except for a lower surgical risk in the G4 group (Society of Thoracic Surgeons Predicted Risk of Mortality ≥8: 38.1% vs. 56.2%; P=0.03). In the G4 group, more patients had short (≤2 mm) coaptation length (83.7% vs. 54.0%; P<0.001) and fewer clips were used (17.5% vs. 36.0%; P=0.02). Acceptable MR reduction was observed in nearly all patients, with no difference between the G4 and G2 groups (100% vs. 97.8%, respectively; P=0.51). The G4 group had fewer patients with high transmitral gradients (>5mmHg; 3.3% vs. 13.6%; P=0.03). At 1 year, there was no significant difference between groups in the composite endpoint (death or heart failure rehospitalization) after baseline adjustment (10.5% vs. 20.2%; hazard ratio 0.39; 95% confidence interval 0.11–1.32; P=0.13).

Conclusions: The G4 system achieved comparable device outcomes to the early-generation G2, despite treating more challenging 2°MR with fewer clips.

Transcatheter edge-to-edge repair (TEER) has been increasingly recognized as a viable therapeutic option for the treatment of secondary mitral regurgitation (MR) in selected patients with symptomatic heart failure and moderate-to-severe or severe MR who receive optimal medical therapy.1,2 As the global adoption of the mitral TEER using MitraClip (Abbott Vascular, Abbott Park, IL, USA) has grown, the challenges and possibilities related to this device have come into focus.3

To address the technical difficulties presented by the diverse range of mitral valve anatomies, improvements have been made to both the MitraClip device and its delivery system. The MitraClip G4 system represents the most recent iteration, currently in use worldwide.4 As it stands, the safety and effectiveness of the MitraClip G4 system are being evaluated in the ongoing EXPAND G4 study (NCT04177394), a post-market, multicenter, single-arm, prospective study.

Nevertheless, the literature regarding the impact of the new G4 system on the treatment of secondary MR in routine clinical practice remains sparse. Therefore, the aim of the present study was to investigate the effects of the introduction of the MitraClip G4 system on routine clinical practice and patient outcomes up to 1 year in the treatment of secondary MR at a high-volume center.

Methods

Study Population

All patients diagnosed with MR who underwent TEER using the MitraClip system at St. Marianna University Hospital were consecutively enrolled into a prospective registry. This single-center registry is a component of a larger multicenter registry, which obtained approval from the local institutional review board (No. 4209) and is registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (Treatment and Prognosis of Heart Valve Registry; UMIN ID: 000023653). All patients provided their written informed consent to participate in the registry. The study was conducted in accordance with the ethical guidelines set forth by the Declaration of Helsinki.

For the purpose of the present study, patients with secondary MR who underwent TEER either with the MitraClip G2 or G4 between 2018 and 2021 were included and analyzed retrospectively.

Procedure

All procedures were deliberated upon by the heart team and conducted in line with the best-practice guidelines currently established.2 An echocardiography specialist performed standardized transthoracic echocardiography prior to the procedure. The procedures were performed under general anesthesia, leveraging both 2- and 3-dimensional transesophageal echocardiographic as well as fluoroscopic guidance in a hybrid operating room.

The MitraClip G4 system has been in use at St. Marianna University Hospital since October 2020. This new system offers 4 distinct clip sizes and allows for the independent grasping of the anterior and posterior mitral valve leaflets. The selection of clip size was based on a meticulous anatomical assessment of the mitral valve, using intraprocedural transesophageal echocardiography. Transthoracic echocardiography was performed on the third day or prior to hospital discharge at the latest.

Data Collection and Definitions

Clinical, echocardiographic, procedural, and follow-up data were prospectively recorded into an institutional integrated data system. Regular clinical follow-up visits were scheduled at 30 days, 1 year, and annually thereafter. Clinical follow-up data were sourced from documentation provided by referring physicians, hospital discharge summaries, and standardized telephone interviews.

Experienced cardiologists retrospectively adjudicated technical success and device success based on the Mitral Valve Academic Research Consortium (MVARC) criteria.5,6 Technical success encapsulated the following: (1) the absence of procedural mortality; (2) successful access, delivery, and retrieval of the device delivery system; (3) successful deployment and accurate positioning of the first intended device; and (4) avoidance of emergency surgery or reintervention related to the device or access procedure. Device success incorporated: (1) the absence of procedural mortality or stroke; (2) appropriate placement and positioning of the device; (3) freedom from unplanned surgical or interventional procedures related to the device or access procedure; and (4) sustained intended safety and performance of the device. The intended safety and performance of the device included: (1) no evidence of structural or functional failure; (2) the absence of specific device-related technical failure issues and complications; and (3) a reduction of MR to either optimal or acceptable levels (reduction by at least 1 class/grade from baseline and to no more than 2+ in severity) without significant mitral stenosis (post-procedure effective orifice area ≥1.5 cm2 with a transmitral gradient <5 mmHg). The effective orifice area of the mitral valve was measured using the planimetry method. MR was graded as 0, 1+, 2+, 3+, 4+ according to the MVARC criteria.5,6

Statistical Analysis

Categorical data are presented as frequencies and percentages, with differences between groups evaluated using the Chi-squared test or Fisher’s exact test. Continuous variables are presented as the median with interquartile range (IQR) and were compared between groups using the Mann-Whitney U test. Event-free survival curves were constructed using the Kaplan-Meier method, whereas Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI).

Given the small sample size of this study, an inverse probability treatment weighting (IPTW) approach was adopted to balance the baseline differences between the study groups. This IPTW analysis was executed using propensity scores derived from a multivariable logistic regression model. This model accounted for 13 baseline variables that were deemed potential confounders of the study outcomes, namely: age, sex, body mass index, Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM), New York Heart Association (NYHA) functional class III or IV, hypertension, diabetes, chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2), chronic obstructive pulmonary disease, history of coronary artery disease, atrial fibrillation/atrial flutter, previous permanent pacemaker implantation including implantable cardioverter defibrillator, and pulmonary hypertension (right ventricular systolic pressure ≥40 mmHg). Absolute standardized differences (ASD) were calculated for each baseline variable to evaluate the balance in baseline characteristics. An ASD <0.10 was deemed to indicate a good balance, and an ASD <0.20 was considered to reflect an acceptable balance. Further multivariable adjustment using Cox regression was performed to address a residual imbalance between the groups.

Throughout this study, P<0.05 was considered statistically significant. All statistical analyses were performed using EZR software (Saitama Medical Center, Jichi Medical University, Saitama, Japan) a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria).

Results

Study Population and Baseline Characteristics

Throughout the study period, 223 patients underwent TEER with the MitraClip system at St. Marianna University Hospital . Of these patients, 152 who exhibited secondary MR and met the inclusion criteria were analyzed retrospectively. Among these 152 patients, 89 were treated with the G2 system and 63 were treated with the G4 system. Baseline characteristics are presented in Table 1. No significant differences were observed in baseline clinical characteristics, except for a lower prevalence of high surgical risk (STS PROM ≥8) (38.1% vs. 56.2%; P=0.03) and a lower prevalence of coronary artery disease (15.9% vs. 33.7%; P=0.02) in the G4 compared with G2 group. Medication usage prior to the MitraClip procedure was also similar between the G4 and G2 groups (renin-angiotensin system inhibitors: 64.0% vs. 63.5%, respectively [P>0.99]; β-blockers: 84.3% vs. 76.2%, respectively [P=0.22]; mineralocorticoid receptor antagonists: 51.7% vs. 60.3%, respectively [P=0.32]).

Table 1.

Baseline Characteristics in Patients Treated With the MitraClip G2 or G4 System

  Unadjusted cohort IPTW-adjusted cohort
G2 (n=89) G4 (n=63) P value ASD G2 (n=87.2) G4 (n=66.7) ASD
Age (years) 77 [73–82] 78 [70–82] 0.97 0.097 77 [73–82] 78 [70–82] 0.097
Sex (male) 58 (65.2) 38 (60.3) 0.61 0.10 53.9 (61.9) 44.9 (68.4) 0.14
Body mass index (kg/m2) 21.4
[18.9–23.7]
22.2
[18.8–24.6]
0.55 0.15 21.4
[18.9–23.7]
22.2
[18.8–24.6]
0.15
High surgical risk (STS PROM ≥8) 50 (56.2) 24 (38.1) 0.03 0.37 41.0 (47.1) 31.6 (48.2) 0.02
NYHA Class III or IV 76 (85.4) 53 (84.1) 0.82 0.04 74.3 (85.2) 57.4 (87.3) 0.06
Hypertension 71 (79.8) 50 (79.4) >0.99 0.01 68.1 (78.2) 50.8 (77.2) 0.02
Diabetes 36 (40.4) 22 (34.9) 0.50 0.11 31.3 (35.9) 19.2 (29.2) 0.15
Chronic kidney diseaseA 69 (77.5) 54 (87.3) 0.14 0.26 70.5 (81.0) 47.2 (71.8) 0.22
Coronary artery disease 30 (33.7) 10 (15.9) 0.02 0.42 23.7 (27.2) 18.9 (28.8) 0.04
Atrial fibrillation 62 (69.7) 36 (57.1) 0.12 0.26 56.8 (65.2) 43.4 (66.1) 0.02
Permanent pacemaker/ICD/CRT 25 (28.1) 12 (19.0) 0.25 0.21 21.4 (24.6) 13.6 (20.7) 0.09
Pulmonary hypertension
(SPAP ≥40 mmHg)
40 (44.9) 20 (31.7) 0.13 0.27 34.2 (39.3) 22.2 (33.7) 0.12

Unless indicated otherwise, data are given as the median [interquartile range] or n (%). AChronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. ASD, absolute standardized difference; CRT, cardiac resynchronization therapy; ICD, implantable cardioverter defibrillator; IPTW, inverse probability of treatment weighting; NYHA, New York Heart Association; SPAP, systolic pulmonary artery pressure; STS PROM, Society of Thoracic Surgeons Predicted Risk of Mortality.

Baseline echocardiographic data are summarized in Table 2. The coaptation length was significantly shorter in the G4 than G2 group (2.0 [IQR 1.6–2.8] vs. 3.0 [IQR 2.3–4.0] mm; P<0.001). Although 83.7% of patients in the G2 group exhibited ideal coaptation length (>2 mm), only 54.0% of patients in the G4 group met this criterion (P<0.001). The remaining echocardiographic parameters, including the severity of MR, left ventricular (LV) systolic function, LV dimensions, transmitral mean pressure gradients, mitral valve areas, tricuspid annular plane systolic excursion, and systolic pulmonary artery hypertension, were comparable between the 2 groups.

Table 2.

Echocardiographic Characteristics in Patients Treated With the MitraClip G2 or G4 System

  G2 (n=89) G4 (n=63) P value
MR severity     0.11
 <3+A 37 (41.6) 16 (25.4)  
 3+ 21 (23.6) 20 (31.7)  
 4+ 31 (34.8) 27 (42.9)  
LVEF (%) 38.0 [33.0–52.0] 38.5 [30.5–52.5] 0.37
LVESV (mL) 85.0 [53.0–123.0] 89.0 [52.8–137.5] 0.51
LVEDV (mL) 150.0 [107.0–182.0] 143.5 [105.5–204.3] 0.63
Atrial MR 12/89 (13.6) 16/60 (25.4) 0.09
Coaptation length (mm) 3.0 [2.3–4.0] 2.0 [1.6–2.8] <0.01
Coaptation length >2 mm 72 (83.7) 34 (54.0) <0.01
Tenting height <11 mm 66 (74.2) 52 (82.5) 0.24
Mean pressure gradient (mmHg) 1.5 [1.0–2.1] 1.7 [1.1–2.3] 0.24
Mitral valve area (mm2) 5.0 [4.1–6.0] 5.5 [4.5–6.6] 0.13
Moderate or severe TR 30 (33.7) 17 (27.0) 0.48
TAPSE (mm) 14.2 [11.5–17.5] 16.5 [13.5–19.3] 0.06
FAC (%) 33.0 [25.0–39.0] 33.5 [24.0–39.8] 0.94
SPAP (mmHg) 38.2 [27.7–46.1] 31.8 [26.7–45.7] 0.37

Unless indicated otherwise, data are given as the median [interquartile range] or n (%). AIn patients with mitral regurgitation (MR) <3+, exercise stress echocardiography was performed to confirm the worsening of MR severity in accordance with Japanese guidelines. FAC, fractional area change; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; SPAP, systolic pulmonary artery pressure; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation.

Procedural Characteristics and Outcomes

Procedural characteristics and outcomes are summarized in Table 3. No significant differences were noted in median procedural time. Significantly fewer clips were used in a single procedure in the G4 compared with G2 group (1 [IQR 1–1] vs. 1 [IQR 1–2]; P=0.010). Although only 1 in 5 patients required 2 clips in a single procedure in the G4 group, over one-third of patients in the G2 group received 2 clips (17.5% vs. 36.0%, respectively; P=0.02). In the G4 group, 27.0% of patients were treated with at least 1 extended arm clip (XT or XTW), and 48 of 63 patients (76.2%) received at least 1 wide clip (NTW or XTW). Procedural complication was rare in both groups; deployment failure occurred in 1 patient in the G2 group and in 2 patients in the G4 group (P=0.57), and single leaflet device attachment occurred in 1 patient in the G2 group (P>0.99). MVARC technical success was achieved in >95% of patients, with no significant difference between the G4 and G2 groups (96.8% vs. 97.8%, respectively; P>0.99; Figure 1).

Table 3.

Procedural Characteristics and Outcomes in Patients Treated With the MitraClip G2 or G4 System

  G2 (n=89) G4 (n=63) P value
Procedural time (min) 75 [56–109] 73 [58–90] 0.52
No. clips     0.02
 1 57 (64.0) 52 (82.5)  
 2 32 (36.0) 11 (17.5)  
Median no. clips 2 [1–2] 1 [1–1] 0.01
Extended arm clips (XT/XTW) NA 17 (27.0) NA
Wide clips (NTW/XTW) NA 48 (76.2) NA
Technical success 87 (97.8) 61 (96.8) >0.99
 Procedural death 0 (0) 0 (0) NA
 Deployment failure 1 (1.1) 2 (3.2) 0.57
 SLDA 1 (1.1) 0 (0) >0.99
 Emergency surgery/intervention related to
the procedure
0 (0) 0 (0) NA
Device success 54 (60.7) 46 (73.0) 0.12
Echocardiographic outcome
 Residual MR >2+ 2 (2.2) 0 (0) 0.51
 MR grade     0.40
  0 19 (21.3) 19 (30.2)  
  1+ 48 (53.9) 34 (54.0)  
  2+ 20 (22.5) 10 (15.9)  
  3+ 2 (2.2) 0 (0)  
 Mean transmitral gradient (mmHg) 2.9 [2.1–3.5] 2.6 [1.9–3.0] 0.03
 Mean transmitral gradient >5 mmHg 12 (13.6) 2 (3.3) 0.04
 MVA (cm2) 1.85 [1.50–2.28] 1.80 [1.51–2.35] 0.97
 MVA <1.5 cm2 23 (26.1) 15 (25.0) >0.99
 Mitral stenosis 32 (36.0) 15 (25.0) 0.15

Unless indicated otherwise, data are given as the median [interquartile range] or n (%). MR, mitral regurgitation; MVA, mitral valve area; NA, not applicable; SLDA, single leaflet device attachment.

Figure 1.

Procedural outcomes of the G2 vs. G4 MitraClip systems. mPG, mean pressure gradient; MR, mitral regurgitation; MVARC, Mitral Valve Academic Research Consortium; PG, pressure gradient.

Echocardiographic data at discharge are also presented in Table 3. Following the MitraClip procedure, an acceptable level of MR reduction (≤2+) was achieved in almost all patients in both groups, with no significant difference observed between the G4 and G2 groups (100% vs. 97.8%, respectively; P=0.51; Figure 1). Transmitral mean pressure gradients were significantly lower in the G4 than G2 group (2.6 [IQR 1.9–3.0] vs. 2.9 [IQR 2.1–3.5] mmHg; P=0.03). A significantly smaller proportion of patients had high transmitral mean pressure gradients (>5 mmHg) in the G4 compared with G2 group (3.3% vs. 13.6%; P=0.04). MVARC device success was achieved in 73.0% of patients in the G4 group and in 60.7% of patients in the G2 group, with no significant difference between the 2 groups (P=0.12; Figure 1).

Clinical Outcomes

Clinical outcomes at 30 days and 1 year are presented in Table 4. Every patient completed the 30-day follow-up. Within 30 days of the procedure, there were 3 deaths in the G4 group and 2 in the G2 group (4.8% vs. 2.2%; P=0.65). Residual heart failure symptoms (NYHA Class ≥III) were recorded in 3.9% of the G4 group and in 3.6% of the G2 group (P>0.99).

Table 4.

Clinical Outcomes in Patients Treated With the MitraClip G2 or G4 System

  G2 G4 Unadjusted IPTW-adjustedA
HR (95% CI) P value HR (95% CI) P value
At 30 days n=89 n=63        
 All-cause death 2 (2.2) 3 (4.8) NA 0.65 NA NA
 NYHA Class III or IV 3/84 (3.6) 2/51 (3.9) NA >0.99 NA NA
At 1 year n=89 n=38        
 Composite endpoint 15 (20.2) 7 (10.5) 0.52 (0.17–1.53) 0.23 0.39 (0.11–1.32) 0.13
  All-cause mortality 10 (13.5) 4 (5.3) 0.38 (0.09–1.71) 0.21 0.25 (0.05–1.26) 0.09
  HF rehospitalization 8 (10.1) 3 (5.3) 0.52 (0.11–2.43) 0.41 0.47 (0.09–2.55) 0.38
 NYHA Class III or IV 2/75 (2.7) 4/30 (13.3) NA 0.054 NA NA

Unless indicated otherwise, data are given as n (%) or n/N (%). AIPTW=inverse probability treatment weighting. The IPTW analysis was executed using propensity scores, derived from a multivariable logistic regression model based on: age, sex, body mass index, Society of Thoracic Surgeons Predicted Risk of Mortality, NYHA functional Class III or IV, hypertension, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, history of coronary artery disease, atrial fibrillation/atrial flutter, previous permanent pacemaker implantation, and pulmonary hypertension. Multivariable adjustment was further performed with chronic kidney disease in view of the presumed association with outcomes and residual imbalance between the groups. CI, confidence interval; HF, heart failure; HR, hazard ratio; NA, not applicable; NYHA, New York Heart Association.

All patients in the G2 group and 38 of 63 patients in the G4 group completed the 1-year clinical follow-up. At this point, the composite endpoint of all-cause mortality or heart failure rehospitalization occurred in 10.5% and 20.2% of patients in the G4 and G2 groups, respectively (HR 0.52; 95% CI 0.17–1.53; P=0.23). The rate of all-cause mortality was 5.3% in the G4 group and 13.5% in the G2 group (HR 0.38; 95% CI 0.09–1.71; P=0.21). Heart failure rehospitalization was reported for 5.3% of patients in the G4 group, and for 10.1% of patients in the G2 group (HR 0.52; 95% CI 0.11–2.43; P=0.41; Figure 2). At 1 year, residual heart failure symptoms (NYHA Class ≥III) were documented in 13.3% of the G2 group and in 2.7% of the G2 group (P=0.054).

Figure 2.

Event-free survival curves for the G2 and G4 MitraClip systems. (A) Event-free survival curves for the composite endpoint of all-cause death or heart failure rehospitalization. (B) Survival curves for secondary mitral regurgitation patients treated with the MitraClip G2 and G4 systems.

Following application of IPTW, a balance check confirmed that the ASD for all baseline variables was either <0.10 or at most 0.20, suggesting a good or at least acceptable balance of measured confounders between the study groups, except for chronic kidney disease (ASD=0.22; Table 1). After applying IPTW and adjustment for chronic kidney disease, the G4 group showed a trend towards a lower risk of the composite endpoint and its components compared with the G2 group. However, these results did not reach statistical significance (composite endpoint: HRadjusted 0.39 [95% CI 0.11–1.32; P=0.13]; all-cause death: HRadjusted 0.25 [95% CI 0.05–1.26; P=0.09]; heart failure rehospitalization: HRadjusted 0.47 [95% CI 0.09–2.55; P=0.38]; Table 4).

Discussion

The findings from this single-center retrospective analysis examining patients with secondary MR treated with the MitraClip G2 and G4 systems at a high-volume center are as follows:

1. The baseline clinical characteristics of patients treated with the G2 system were generally similar to those treated with the G4 system, except for a lower prevalence of patients with high surgical risk and coronary artery disease in the G4 group.

2. Echocardiographic parameters, including MR severity, LV function/dimensions, right ventricular function, and pulmonary hypertension, did not differ significantly between the 2 groups. However, anatomically, patients with a less favorable (short) coaptation length (<2 mm) were more frequently treated with the G4 device than the G2 device.

3. Nevertheless, procedural complications were rare across both device groups, with MVARC technical success being achieved in most patients in both groups (>95%).

4. An acceptable level of MR reduction (≤2+) was achieved in nearly all patients in both groups, although with fewer clips used in the G4 group. Furthermore, an elevated transmitral mean pressure gradient (>5 mmHg) was less commonly observed in the G4 group.

5. The G4 group demonstrated a numerically lower, albeit not statistically significant, risk of all-cause death at 1 year compared with the G2 group.

Although TEER is increasingly gaining popularity as a therapeutic treatment option for symptomatic heart failure patients with significant secondary MR, the divergent results obtained from 2 pivotal randomized clinical trials, namely MITRA-FR and COAPT, have sparked ongoing debate about the effectiveness of TEER for patients with secondary MR.710 Differences in patient selection, the strictness of adherence to “guideline-directed” medical therapy, sample size, and follow-up period have all been proposed as potential contributors to the varying outcomes. Nevertheless, the difference in the quality of procedures between the trials also deserves consideration as a potential factor contributing to the contrasting results. With the caveat that both trials lacked a common core laboratory evaluation, the procedural success and safety seemed to be superior in COAPT than in MITRA-FR, with COAPT exhibiting lower rates of residual MR (≥3+; 5% vs. 9%) and procedural complications (8.5% vs. 14.6%).7,8 Although technical refinements and accumulated experiences have already seemingly enhanced procedural safety and effectiveness,1114 the introduction of the new device, which addresses the known limitations of the earlier-generation device, may further improve outcomes, potentially replicating or even surpassing the results seen in the COAPT trial.

The recent EXPAND study, a prospective international single-arm study of patients with primary and secondary MR treated with the third-generation MitraClip, reported only 1.2% of secondary MR patients with residual MR (≥3+) after the procedure. Moreover, the 1-year mortality rate for secondary MR patients in the study paralleled the COAPT findings, and was better than earlier real-world data from the US registry (18% vs. 19% vs. 31%, respectively).13 A post-marketing use surveillance study of the MitraClip G2 system in Japan between 2018 and 2019 reported an exceedingly low procedural complication rate, with only 5% of the patients exhibiting residual MR (≥3+), and a 1-year all-cause mortality rate of 15.8%.14 Aligning with these studies, our analysis showed that the earlier-generation G2 device already seemed to deliver superior procedural outcomes compared with the initial randomized trials, with a >95% technical success rate and effective MR reduction.

The newer-generation MitraClip G4 system introduces several improvements over the early-generation devices, including the option to select from 4 different clip sizes tailored to individual mitral valve anatomy and the capability for independent grasping.4 These key enhancements in the G4 device likely contributed to an effective MR reduction, comparable to the G2 device, even while using fewer clips and treating a larger proportion of patients with unfavorable coaptation length (<2 mm) in the G4 group. The anatomical complexity in the G4 group may have extended the procedural time, offsetting the expected time reduction from the use of fewer clips and learning curves. Notably, the decrease in the number of clips used per procedure seemingly resulted in a reduced risk of elevated post-procedural transmitral gradients (Figure 3). The numerically lower risk of all-cause mortality during 1 year after the procedure warrants further investigation through a larger multicenter study. However, the findings of the present study suggest that the MitraClip G4 system could potentially offer outcomes that are similar, or even superior, to those reported in COAPT to a broader spectrum of patients than the G2 system, reinforcing the effectiveness of TEER in heart failure patients with secondary MR.

Figure 3.

Representative cases of secondary mitral regurgitation treated with the (AD) G2 and (EH) G4 MitraClip systems. Prior to procedure, a broad regurgitant jet is evident in the center of the mitral valve in both cases (A,E). In the case of treatment with the G2 device, a reduction to mild mitral regurgitation is seen using 2 clips (B), whereas with the G4 device a similar reduction is achieved with only a single XTW clip (F). Yellow arrows indicate clips. A larger mitral valve area is observed in the case treated with the G4 device (G) compared with the case treated with the G2 device (C), and this is associated with a lower pressure gradient (PG; H vs. D).

Study Limitations

The limitations of this analysis are important to consider when interpreting the results. First, the small to modest size of our study population may have prevented us from detecting minor differences in procedural and clinical outcomes between the devices. Consequently, rare procedural complications should be interpreted with caution. However, the integrity of our findings regarding device outcomes, including MVARC technical and device success,5,6 is enhanced by the independent adjudication based on comprehensive documentation of endpoints collected prospectively in the registry. Second, the nature of this before-and-after study may introduce bias due to temporal changes in clinical practice and the learning curve associated with the procedure. Despite using advanced statistical techniques, we cannot entirely eliminate potential bias from unmeasured or unrecognized confounders, as is case with all observational studies. Finally, our study reflects the experiences of a single high-volume center, limiting the generalizability of the results. Therefore, these findings should be validated through larger multicenter studies.

Conclusions

The introduction of the MitraClip G4 system has broadened the scope of treatable patient populations, particularly those with a short coaptation length. The use of the G4 system has reduced the number of clips per procedure, resulting in a lower risk of elevated transmitral gradients, while achieving effective MR reduction comparable to the G2 device. The potential of this system to enhance clinical outcomes compared with earlier-generation devices warrants further investigation.

Acknowledgments

None.

Sources of Funding

This study did not receive any specific funding.

Disclosures

M.I. is a clinical proctor of Abbott Medical Japan and a screening proctor of Edwards Lifesciences. S.K. is a clinical proctor of Abbott Medical Japan. Y.J.A. is a member of Circulation Journal’s Editorial Team. The remaining authors have no conflicts of interest to declare.

References
 
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