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    Evidence summary

    Population and studies description

    This interventional procedures overview is based on 1,249 people from 7 prospective case series, 2 retrospective registry studies, 2 retrospective cohort studies and 1 retrospective case series. Of these 1,249 people, 1,070 people had the procedure. There is likely substantial overlap between these patient populations. This is a rapid review of the literature, and a flow chart of the complete selection process is shown in figure 1. This overview presents 12 studies as the key evidence in table 2 and table 3, and lists 9 other relevant studies in appendix B, table 5.

    Colli (2016) conducted a prospective single centre case-series to evaluate the clinical outcomes of the TOP-MINI procedure using the NeoChord DS1000 system in the early postoperative period. This study was based in Italy and included 49 people with a median age of 72, with 34 males (69%). Acute procedural success was defined as implantation of at least 3 neochordae with residual MR of 2+ or greater. Primary efficacy outcomes were residual MR of 2+ or greater, freedom from reoperation for recurrence of severe MR and clinical improvement in NYHA functional class. Safety outcomes included hospital mortality, perioperative complications, major and minor adverse events. Patient outcomes were assessed at discharge and at 3 months post-procedure.

    Colli (2015) conducted a multicentre prospective case series to evaluate the safety and efficacy of the TOP-MINI procedure in a consecutive cohort of symptomatic patients with severe mitral regurgitation (MR) due to leaflet flail or prolapse. The study was conducted across 2 sites in Italy and Lithuania between February 2013 and June 2014 and included 63 people with a median age of 66, with 42 males (67%). Early procedural success was defined as implantation of at least 2 neochordae with immediate reduction in MR to less than 2+. Primary efficacy outcomes were defined as reduction in MR to less than 2+ at the 30-day follow-up, freedom from reoperation for recurrence of severe MR and clinical improvement (NYHA functional class). Safety outcomes included perioperative complications, in-hospital and 30-day major and minor adverse events. Patient outcomes were assessed at discharge and at 30 days post-procedure.

    Colli (2018a) conducted a prospective single centre case-series to evaluate the learning curve of surgeons performing the NeoChord procedure and monitor the performance of the procedure during the initial phase of its adoption. 112 consecutive patients who underwent the NeoChord procedure between November 2013 and March 2016 were included in the analysis. Participants included in the study had a median age of 68, with 82 males (73%). A composite end-point was used based on MVARC definitions - the treatment was considered a success at 1 year follow up of the following criteria were met: (i) technical success including the placement of at least 2 neochordae and residual mitral regurgitation grade of mild or absent at the end of the procedure; (ii) freedom from major adverse events such as death, stroke, mitral regurgitation grade of greater than moderate, structural or functional valvular failure and/or unplanned interventions related to the procedure or device; (iii) freedom from a decline in baseline symptoms. Patient outcomes were assessed at discharge, 1 month, 3 months, 6 months and 1 year.

    Colli (2018b) conducted a multicentre retrospective registry study to evaluate 1 year clinical results of the procedure using the NeoChord DS1000 device in a consecutive cohort of patients. 213 people were enrolled into the NeoChord Independent International Registry between February 2013 and July 2016. All participants presented with severe mitral regurgitation due to flail/prolapse of one or both leaflets, and they all completed postoperative echocardiographic assessment up to 1 year. Participants included in the study had a median age of 68, with 153 males (72%). The primary end-point was composed of (i) procedural success (defined as the placement of at least 2 neochordae and mild or less MR at the end of the procedure) and (ii) freedom from death, stroke, MR higher than moderate, unplanned interventions related to the procedure or device, cardiac-related rehospitalization or worsening NYHA functional class at 1 year and at each follow-up time. Patient outcomes were assessed at discharge, 1 month, 6 months and 1 year.

    D'Onofrio (2022) conducted a single centre, retrospective study comparing outcomes of the NeoChord procedure and conventional surgical mitral valve repair. Data of patients who underwent isolated mitral valve repair with the NeoChord procedure or conventional surgery from January 2010 to December 2018 were collected. After 1:1 propensity matching, 176 people were included (88 in each group), with a median age of 68 with 77% males in the NeoChord group, and a median age of 64 with 73% males in the conventional surgery group. The primary end point was overall all-cause mortality. Secondary end points were freedom from reoperation, freedom from moderate (2+) and severe (3+) MR and NYHA functional class in the overall population and in patients with isolated P2 prolapse (type A anatomy). Median follow up was 3.4 years in the NeoChord group, and 6.6 years in the conventional group.

    D'Onofrio (2023) conducted a single centre retrospective case-series to evaluate clinical and echocardiographic 5 year outcomes of people who underwent the NeoChord procedure. All patients who underwent the procedure from November 2013 to March 2016 were included. Indications were severe symptomatic degenerative mitral regurgitation due to leaflet prolapse/flail. 100 consecutive patients were included in the analysis, with a median age of 66 and 73% male. Device success was defined by the absence of procedural mortality or stroke, proper placement and positioning of the device, freedom from unplanned surgical or interventional procedures related to the device or access procedure, no evidence of structural or functional failure, no specific device-related technical failure issues and complications, and reduction of MR to either optimal or acceptable levels without significant mitral stenosis. Follow up occurred at 1, 3, 6, 12 months, and annually thereafter for 5 years.

    Gerosa (2021) conducted a single centre retrospective registry study to evaluate the mid-term outcomes of people who underwent the NeoChord procedure. 203 consecutive people with severe symptomatic MR due to prolapse or flail of one or both mitral leaflets that underwent the NeoChord procedure between November 2013 and June 2019 were included (78% male; median age: 64 years). Clinical outcomes and the composite primary endpoint (patient success) were defined according to MVARC criteria. Mitral regurgitation (MR) severity was graded as absent, mild, moderate and severe according to ASE and ESC guidelines. Median follow-up was 24 months, patients underwent clinical and echocardiographic follow-up at 1, 3, 6, 12 months and annually thereafter for 3 years.

    Kurnicka (2019) conducted a prospective case-series to evaluate early results of the NeoChord procedure in the first group of consecutive patients operated on in Poland. 21 people with severe MR due to posterior leaflet prolapse (81% male; mean age: 61, SD 12.7 years) underwent MV repair with the NeoChord DS1000 system between October 2014 and August 2017. 6 month echocardiographic results including MR grade and parameters of the left ventricle and left atrium geometry and function were evaluated. Patient outcomes were assessed at discharge, and 6 months post-procedure.

    Samalavicius (2017) conducted a prospective case-series to describe the anaesthetic management and procedural success of patients undergoing the NeoChord procedure. 76 people (68% male; mean age: 60, SD 13 years) who underwent mitral valve repair with the NeoChord system between December 2011 and December 2016 were included in the study. Perioperative safety data were collected, along with reduction in MR post-procedure.

    Seeburger (2014) conducted a multicentre prospective case-series called the 'TACT' trial to evaluate the safety and performance of the NeoChord DS1000 system. 30 people (60% male; mean age: 64, SD 11.9 years) across 7 centres with severe MR due to isolated posterior prolapse were included in this trial. All participants underwent off-pump transapical implantation of neochordae. The primary performance endpoint was the rate of patients maintaining an MR grade of 2+ or less at 30 days. The safety endpoint was major adverse events such as death, reoperation, and cardiovascular events.

    Wrobel (2019) conducted a prospective case series to evaluate early outcomes of a single-centre experience with transapical beating heart mitral valve repair with the NeoChord system. 37 people (78% male; mean age: 62.3, SD 3.4 years) with severe symptomatic MR were treated with the NeoChord procedure between September 2015 and December 2018. Transapical chordal implantation was considered suitable for patients if severe MR was present due to prolapse or flail of 1 leaflet and had the potential for good coaptation without requiring a prosthetic annuloplasty. Early surgical success defined as the reduction of MR to less than moderate by implantation of at least 2 neochordae was evaluated. Standard cardiac surgery perioperative complications and those related directly to the NeoChord technique were also presented.

    Zorinas (2019) conducted a retrospective cohort study to compare early postoperative outcomes of conventional mitral valve repair surgery with the NeoChord procedure in people with degenerative MR. 169 people who underwent mitral valve repair between 2011 and 2018 were included. 78 people were in the NeoChord group (67.9% male; mean age: 59.5, SD 12.8 years) and 91 were in the conventional surgery group (57.1% male; mean age: 54.2 ±11.1 years). STS and EuroScore II risk scores did not differ between the groups. Performance and safety outcomes were assessed post-operatively, and at 30 days post-procedure.

    Table 2 presents study details.

    Figure 1 Flow chart of study selection

    Table 2 Study details

    Study no.

    First author, date

    Country

    Characteristics of people in the study (as reported by the study)

    Study design

    Inclusion criteria

    Intervention

    Follow up

    1

    Colli, 2018b, Italy (3 centres), Germany (2 centres), Lithuania (1 centre), Poland (1 centre)

    n=213

    Age, median (IQR)

    68 (IQR 56-77)

    Male sex, n (%)

    153 (71.8)

    EuroScore II (%), mean (±SD)

    1.8 (±2.5)

    STS-PROM MV repair score (%), mean (±SD)

    1.5 (±2.1)

    NYHA functional class, n (%)

    I: 14 (6.6)

    II: 92 (43.2)

    III: 101 (47.4)

    IV: 6 (2.8)

    MR Grade, n (%)

    Severe: 213 (100)

    Leaflet involvement, n (%)

    PML: 193 (90.6)

    AML: 11 (5.2)

    AML + PML: 9 (4.2)

    Leaflet prolapse, n (%)

    74 (34.7)

    Leaflet flail, n (%)

    139 (65.3)

    Mitral valve anatomical types, n (%)

    A: 82 (38.5)

    B: 98 (46)

    C: 33 (15.5)

    Retrospective registry study. February 2013 - July 2016

    All enrolled people had indications for surgical MV regurgitation due to degenerative MR according to current guidelines. An additional inclusion criterion was the presence of a consistent overlap of tissue to obtain a potential postoperative coaptation length of 3mm to 5 mm. The evaluation of the potential coaptation was based on an eyeball judgement of the surgeon due to the lack of precise predefined echocardiographic measurements during the initial clinical experience. Exclusion criteria were the presence of active endocarditis and functional MR (Carpentier's Types I and III) or mixed disease.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    1 year

    2

    Gerosa, 2021, Italy (1 centre)

    n=203

    Age, median (IQR)

    64 (54-74)

    Male sex, n (%)

    158 (77.8)

    Euroscore II, median (IQR)

    0.94 (0.61-1.75)

    STS PROM MV repair score (%), median (IQR)

    0.60 (0.32-1.44)

    NYHA functional class, n (%)

    III or IV: 75 (37.0)

    MR grade n (%)

    Severe: 203 (100)

    Leaflet involvement, n (%)

    PML: 187 (92.1)

    AML: 8 (3.9)

    AML + PML: 8 (3.9)

    Mitral valve anatomical types, n (%)

    A: 106 (52.2)

    B: 68 (33.5)

    C: 16 (7.9)

    D: 13 (6.4)

    Retrospective registry study. November 2013- June 2019

    All consecutive patients that underwent MV repair with the NeoChord procedure at University of Padua between November 2013 and June 2019 were included in the current analysis. All the included patients presented with severe symptomatic DMR due to prolapse or flail of one or both mitral leaflets. The surgical indication was based on clinical and anatomical characteristics and the patient's personal preferences regarding treatment independently from age and surgical risk profile.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    3 years

    3

    D'Onofrio, 2022, Italy (1 centre

    n=176

    NeoChord = 88

    Male sex, n (%)

    68 (77)

    Age, median (IQR):

    62 (54-70)

    Euroscore II, median (IQR):

    0.7 (0.5-1.0)

    NYHA functional class, n (%)

    I: 33 (37.8)

    II: 31 (35.4)

    III: 24 (26.8)

    IV: 0

    MR grade, n (%)

    3+: 88 (100)

    Mitral valve anatomical types, n (%)

    A: 43 (49)

    B: 39 (44)

    C: 6 (7)

    Conventional surgery = 88

    Male sex, n (%)

    64 (73)

    Age, median (IQR):

    61 (52.9-71.4)

    Euroscore II, median (IQR):

    0.7 (0.6-1.0)

    NYHA functional class, n (%)

    I: 18 (20)

    II: 64 (72.9)

    III: 6 (7.1)

    IV: 0

    MR grade, n (%)

    3+: 88 (100)

    Mitral valve anatomical types, n (%)

    A: 37 (42)

    B: 40 (45)

    C: 11 (12)

    Retrospective propensity matched cohort

    Data of people who underwent isolated mitral valve repair with NeoChord or conventional surgery from January 2010 to December 2018 were collected. The choice between Neochord and conventional surgery was primarily based on anatomical characteristics but also on surgeon's and the persons preferences. People with previous cardiac surgery, and combined operations were excluded from the analysis. People with type D mitral valve anatomy were also excluded from this analysis.

    TA: Off-pump neochordae implantation with the NeoChord DS1000 device

    CMVR: Conventional on-pump mitral valve repair with full sternotomy

    5 years

    4

    Zorinas, 2019, Lithuania (1 centre)

    n=169

    Neochord = 78

    Age, mean ± SD

    59.5 ± 12.8

    Male sex, n (%)

    53 (67.9)

    STS score (%), median (IQR)

    0.47 (0.24-0.74)

    EuroScore II (%), median (IQR)

    0.83 (0.67-1.35)

    NYHA functional class, n (%)

    I: 4 (5.1)

    II: 45 (57.7)

    III: 28 (35.9)

    IV: 1 (1.3)

    MR grade, n (%)

    Severe: 78 (100)

    Conventional surgery = 91

    Age, mean ± SD

    54.2 ± 11.1

    Male sex, n (%)

    52 (57.1)

    STS score (%), median (IQR)

    0.43 (0.31-0.70)

    EuroScore II (%), median (IQR)

    0.84 (0.67-1.13)

    NYHA functional class, n (%)

    I: 1 (1.1)

    II: 21 (23.1)

    III: 68 (74.7)

    IV: 1 (1.1)

    MR grade, n (%)

    Severe: 91 (100)

    Retrospective cohort study

    All candidates had indications for surgical MV repair according to the current ACC/AHA and ESC/EACTS guidelines. MV pathology included single or bi-leaflet MV prolapse or flail, with or without chordal rupture. Patients with a restrictive mechanism of regurgitation, ischemic mitral regurgitation, MV infectious lesions and patients with a central regurgitation jet were excluded from the study. All patients with degenerative MV disease were discussed by the Heart Team for eligibility to perform either CMVR surgery or a TA procedure. Patients with a favourable MV anatomy who agreed to undergo a transapical procedure were selected for the TA.

    TA: Off-pump neochordae implantation with the NeoChord DS1000 device

    CMVR: Conventional on-pump mitral valve repair with full sternotomy

    30 days

    5

    Colli, 2018a, Italy (1 centre)

    n=112

    Age, median (IQR)

    68 (IQR 57-76)

    Male sex, n (%)

    82 (73)

    EuroScore II (%), median (IQR)

    1.25 (0.67-2.10)

    STS score (%), median (IQR)

    0.90 (0.39-1.74)

    NYHA functional class, n (%)

    I: 11 (10)

    II: 43 (38)

    III: 54 (48)

    IV: 4 (4)

    MR Grade, n (%)

    Severe: 100 (100)

    Leaflet involvement, n (%)

    PML: 101 (90)

    AML: 6 (5)

    AML + PML: 5 (5)

    Leaflet prolapse, n (%)

    48 (43)

    Leaflet flail, n (%)

    64 (57)

    Mitral valve anatomical types, n (%)

    A: 45 (40)

    B: 47 (42)

    C: 20 (18)

    Prospective case series

    People presenting with severe degenerative MR with the prolapse or flail of one or both leaflets were considered candidates for the procedure. Patients with an unfavourable MV anatomy and/or the presence of active endocarditis were excluded. The surgical indication was based on a discussion between the surgeons and cardiologists considering operative risk profile, clinical and anatomical characteristics and the patient's personal preferences regarding the treatment course.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    1 year

    6

    D'Onofrio, 2023, Italy (1 centre)

    n=100

    Age, median (IQR)

    66 (58-76)

    Male sex, n (%)

    73 (73)

    STS PROM MV repair, median % (IQR)

    1 (0.4-1.8)

    EuroScore II

    <4%: 90 (90%)

    4%-8%: 6 (6%)

    >8%: 4 (4%)

    NYHA functional class 3 or 4:

    80%

    Anatomic type, n (%)

    Favourable anatomy: 81 (81)

    Unfavourable anatomy: 18 (19)

    MR grade, n (%)

    Severe: 100 (100)

    Prolapse/flail, n (%)

    Prolapse: 42 (42)

    Flail: 58 (58)

    Retrospective case series

    This study included all patients who underwent the NeoChord procedure at the Division of Cardiac Surgery of the University of Padua between November 2013 and March 2016. Inclusion criteria were based on a careful evaluation of MV anatomy. Exclusion criteria were severe left ventricular (LV) dysfunction (LV ejection fraction <20%), LV aneurysm, apical thrombosis, and presence of associated heart disease requiring surgical correction.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    5 years

    7

    Samalavicius, 2018, Lithuania, (1 centre)

    n=76

    Age, mean (SD)

    60 (±13)

    Male sex, n (%)

    52 (68)

    Euroscore II (%), mean (SD)

    1.23 (±1.16)

    NYHA functional class, n (%)

    I: 4 (5)

    II: 44 (58)

    III: 27 (36)

    IV: 1 (1)

    MR Grade, n (%)

    3+: 51 (67)

    4+: 25 (33)

    Type of mitral pathology, n (%)

    Anterior leaflet prolapse: 3 (4)

    Posterior leaflet prolapse: 68 (89)

    Bileaflet prolapse: 5 (7)

    Prospective case series

    Patients with severe MR who were candidates for surgical MV repair and had a LVEF of >25% were considered. Patients with functional or ischaemic MR or severe LV dysfunction, infective endocarditis, inflammatory valve disorders, leaflet perforation, or heavily calcified valves were excluded from the study. All patients who underwent MV repair using the NeoChord system from December 2011 to December 2016 were included in the study

    Off-pump neochordae implantation with the NeoChord DS1000 device

    Procedural results

    8

    Colli, 2015, Italy (1 centre), Lithuania (1 centre)

    n=63

    Age, median (IQR)

    66 (IQR 52-76)

    Male sex, n (%)

    42 (67)

    EuroScore II (%), median (IQR)

    1 (0.7-2.3)

    STS score (%), median (IQR)

    0.8 (0.4-1.7)

    NYHA functional class, n (%)

    I: 3 (5)

    II: 25 (40)

    III: 31 (49)

    IV: 4 (6)

    MR Grade, n (%)

    3+/4: 7 (11)

    4+/4: 56 (89)

    Prolapsing mitral leaflet, n (%)

    PML: 56 (89)

    AML: 4 (6)

    AML + PML: 3 (5)

    Leaflet involvement, n (%)

    PML: 56 (89)

    AML: 4 (6)

    AML + PML: 3 (5)

    Mitral valve anatomical types, n (%)

    A: 22 (35)

    B: 27 (43)

    C: 14 (22)

    Prospective case series

    All patients were candidates for conventional MV repair surgery, according to the current guidelines. Patients were considered eligible for NeoChord implantation when severe MR was due to isolated prolapse or flail of the posterior, anterior or both MV leaflets. Exclusion criteria were the presence of active endocarditis or unfavourable MV anatomy.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    30 days

    9

    Colli, 2016, Italy (1 centre)

    n=49

    Age, median (IQR)

    72 (IQR 58-78)

    Male sex, n (%)

    34 (69)

    EuroScore II (%), median (IQR)

    1.75 (0.73-2.75)

    STS score (%), median (IQR)

    1.44 (0.73-2.75)

    NYHA functional class, n (%)

    II: 14 (28.6)

    III: 32 (65.3)

    IV: 3 (6.1)

    MR Grade, n (%)

    Severe (3 or 4+/4): 49 (100%)

    Prolapsing mitral leaflet, n (%)

    PML: 44 (89.8)

    AML: 4 (8.2)

    AML + PML: 1 (2)+/4): 49 (100%)

    Prospective case series

    People selected for the NeoChord procedure presented severe degenerative MR due to posterior, anterior or both MV leaflets prolapse/flail. Exclusion criteria were the presence of active endocarditis, secondary MR and unfavourable MV anatomy.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    12 months

    10

    Wrobel, 2019, Poland (1 centre)

    n=37

    Age, mean (SD)

    62.3 (± 13.4)

    Male sex, n (%)

    29 (78)

    Euroscore II, median (range):

    0.92 (0.56-3.73)

    Leaflet pathology, n (%)

    Posterior: 35 (95)

    Anterior: 2 (5)

    Type of pathology, n (%)

    A (Isolated central posterior leaflet prolapse): 25 (67.6)

    B (multiple prolapsing segments): 8 (21.6)

    C (commissural involvement, anterior leaflet): 4 (10.8)

    Prospective case series

    Transapical chordal implantation was considered suitable for patients if severe MR was present due to prolapse or flail of 1 leaflet and had the potential for good coaptation without requiring a prosthetic annuloplasty.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    Procedural results

    11

    Seeburger, 2014, Germany (3 centres), Italy (2 centres), Denmark (1 centre), Lithuania (1 centre)

    n=30

    Age, mean (SD)

    63.5 (± 11.9)

    Male sex, n (%)

    18 (60%)

    MR grade, n (%)

    3+: 3 (10)

    4+ 27 (90)

    NYHA functional class, n (%)

    II: 13 (43.3)

    III: 17 (56.6)

    Prospective case series

    Patients with severe MR due to isolated Carpentier type II prolapse of the posterior MV leaflet and no annulus dilation, with an indication for surgery confirmed according to guidelines, were included in the trial. Key exclusion criteria included secondary MR, severe left ventricular dysfunction, anterior or bileaflet MV prolapse, permanent atrial fibrillation, and concomitant cardiac disease with an indication for surgical treatment.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    30 days

    12

    Kurnicka, 2019, Poland (1 centre)

    n=21

    Age, mean (SD)

    60.7 SD ±12.7

    Male sex, n (%)

    17 (81)

    NYHA functional class, n (%)

    I: 6 (28.6)

    II: 12 (57.1)

    III: 3 (14.3)

    IV: 0

    Posterior leaflet flail, n (%)

    12 (57.1)

    Posterior leaflet prolapse, n (%)

    9 (42.8)

    Mitral valve anatomical types, n (%)

    A: 12 (57.1)

    B: 8 (38.1)

    C: 1 (4.8)

    Prospective case series

    Severe MR, posterior leaflet prolapse or flail, single eccentric MR jet due to prolapse/flail, good potential for coaptation, a healthy long anterior leaflet, technical possibility to place chords. Exclusion criteria included severe LV enlargement, no tissue overlap, functional MR, multiple jets in different areas, endocarditis, significant leaflet and annulus calcifications, bileaflet prolapse, prolapse/flail of the commissural regions, leaflet perforation.

    Off-pump neochordae implantation with the NeoChord DS1000 device

    6 months

    Table 3 Study outcomes

    First author, date

    Efficacy outcomes

    Safety outcomes

    Colli, 2018b

    Early procedural success

    100%

    Median procedure time, min (IQR)

    130 (117.5-150)

    MR at discharge, n (%)

    0+: 32 (51)

    1+: 22 (35)

    2+: 7 (11)

    3+: 1 (2)

    4+: 1 (2)

    MR at 30 days, n (%)

    0+: 29 (46)

    1+: 16 (25)

    2+: 10 (16)

    3+: 7 (11)

    4+: 1 (2)

    NYHA class at 30 days, n (%)

    1: 55 (87)

    2: 4 (6)

    3: 4(6)

    Perioperative complications, n (%)

    Ventricular fibrillation: 3 (5)

    CPB/ECMO: 1

    Bleeding requiting >2 blood units: 3 (5)

    Major adverse events, n (%)

    Myocardial infarction: 1

    Septicaemia: 2 (3%)

    Minor adverse events, n (%)

    Severe pericardial effusion: 2 (3)

    Wound dehiscence: 1

    Persistent AF: 13 (21)

    Permanent AF: 1

    PM implantation: 2 (3)

    Reoperation for NeoChord procedure failure at 30 days, n (%)

    New Neochordae implantation: 1

    Neochordae retensioning: 2 (3)

    Mitral valve repair: 3 (5)

    Mitral valve replacement: 2 (3)

    Median ICU stay, hours

    24

    Median duration mechanical ventilation, hours (IQR)

    3 (2-5)

    Median hospital stay, days (IQR)

    8 (6-11)

    Discharge location, n (%)

    Home: 9 (14)

    Cardiac rehabilitation centre: 54 (86)

    Gerosa, 2021

    Procedural success, n (%)

    200 (99%)

    KM 1 year survival

    99% ±1%

    KM 3 year survival

    94% ±3%

    Operative time, min (IQR)
    120 (106-150)

    Rate of patient success

    1 year: 91% ±2%

    2 year: 90% ±2%

    3 year: 81%±4%

    Patient success by anatomy at 3 years:

    Type A: 88%±5%

    Type B: 83±5%

    Type C: 73% ±12%

    Type D: 57%±19% p=0.001

    MR at discharge, n (%)

    Absent/trivial: 83 (42)

    Mild: 89 (45)

    Moderate: 21 (10)

    Severe: 5 (3)

    MR at 3 years, n (%)

    Absent/trivial: 60 (12)

    Mild: 26 (52)

    Moderate: 15 (30)

    Severe: 3 (6)

    Change in echocardiographic outcomes from preoperation to discharge

    LVEDVi (mL/m2): 12.8±19.6, P<0.001

    LVESVi (mL/m2): −0.4±10.8, P=0.960

    LVEF (%): 8.0±10.2, P<0.001

    LAVi (mL/m2): −11.6±17.3, P<0.001

    sPAP (mmHg): 5.7±12.8, P<0.001

    Change in echocardiographic outcomes from discharge to 3 years

    LVEDVi (mL/m2): 5.8±14.8, P=0.138

    LVESVi (mL/m2): 5.6±14.2, P=0.150

    LVEF (%): −5.1±8.0, P=0.021

    LAVi (mL/m2): 3.2±11.3, P=0.260

    Median mechanical ventilation time, hours (IQR)

    2 (1-3)

    Procedural ECMO, n (%)

    4 (2)

    Median hospital stay, days (IQR)

    7 (6-8)

    Discharge location, n (%)

    Home: 157 (77.7)

    Rehabilitation centre: 41 (20.3)

    In-hospital death, n

    1

    TIA, n (%)

    1

    Major or extensive bleeding, n (%)

    8 (4)

    Major pleural effusion, n (%)

    4 (2)

    AKI stage 3, n (%)

    5 (3)

    Ventricular fibrillation, n

    1

    New-onset atrial fibrillation, n

    1

    D'Onofrio, 2022

    Median follow-up, years

    NeoChord: 3.4

    Conventional: 6.6

    Median surgery duration, hours (IQR)

    NeoChord: 2.0 (1.8-2.5)

    Conventional: 4.0 (3.5-4.0)

    5 year survival

    NeoChord: 92.1% (95% CI, 82.1-100)

    Conventional: 95.5% (95% CI, 90.6-100) p=0.94

    5 year survival (type A anatomy)

    NeoChord: 100%

    Conventional: 92.8% (95% CI, 83.7-100) p=0.94

    NeoChord MR grade at discharge, n (%) p=0.084

    0-1+: 80 (91)

    2+: 4 (5%)

    3+: 4 (5%)

    Conventional MR grade at discharge, n (%) p=0.084

    0-1+: 87 (99)

    2+: 1

    3+: 0

    Freedom from moderate MR at 5 years

    NeoChord: 58% (95% CI 43 - 77)

    Conventional: 85% (95% CI 76-95) p=0.001

    Freedom from severe MR at 5 years

    NeoChord: 78.1% (95% CI 65-93)

    Conventional: 90% (95% CI, 82-98) p=0.032

    Freedom from reoperation

    NeoChord: 79% (95% CI, 59-95)

    Conventional: 92% (95% CI, 85-99)

    Median LVEF at discharge, % (IQR)

    NeoChord: 55 (51-60)

    Conventional: 56 (51-61) p=0.867

    Median LVEF at follow-up, % (IQR)

    NeoChord: 59 (56-63)

    Conventional: 60 (55-64) p=0.89

    Median iLVEDV at discharge, ml/m2 (IQR)

    NeoChord: 76 (59-87)

    Conventional: 50 (63-72) p=0.001

    Median iLVEDV at follow-up, ml/m2 (IQR)

    NeoChord: 66 (66-72)

    Conventional: 62 (60-65) p=0.001

    >90% of patients in both groups were in NYHA class 1 or 2 at follow-up

    30-day mortality, %

    0%

    Mean ICU stay, days

    1

    Conversion to repair, n

    1

    Mean intubation time, hours (IQR)

    NeoChord: 2 (1-3)

    Conventional: 7.5 (5-12)

    Re-exploration for bleeding, n (%)

    NeoChord: 0

    Conventional: 4 (5)

    Atrial fibrillation, n (%)

    NeoChord: 5 (6)

    Conventional: 30 (34)

    Median in-hospital stay, days ((IQR)

    NeoChord: 7 (6-8)

    Conventional: 8 (7-10)

    CVVH, n

    NeoChord: 0

    Conventional: 1

    Wound infection, n

    NeoChord: 0

    Conventional: 1

    Zorinas, 2019

    Median duration of surgery, min (IQR)

    NeoChord: 120 (110-146)

    Conventional: 312 (280-361) p<0.001

    NeoChord postoperative MR, n (%)

    Absent: 43 (56) p<0.001

    Mild: 28 (36) p=0.007

    Moderate: 4 (5) p=0.03

    Severe (failed repair): 2 (3) p=0.12

    Conventional postoperative MR, n (%)

    Absent: 75 (82%) p<0.001

    Mild: 16 (18) p=0.007

    NeoChord severe MR at 30-days, n (%)

    9 (12) p=0.001

    Conventional severe MR at 30-days, n

    0 p=0.001

    Mortality, n

    Neochord: 1

    Conventional: 0 p=0.277

    Mean postoperative blood loss, ml

    NeoChord: 200ml

    Conventional: 300ml p=0.001

    Median time to weaning from ventilation, hours

    NeoChord: 4

    Conventional: 7 p<0.005

    Median length of ICU stay, hours (IQR)

    NeoChord: 22 (20-24)

    Conventional: 67.5 (44-113) p<0.001

    Median length of hospital stay, n (IQR)

    NeoChord: 8 (7-9)

    Conventional: 16 (14-21) p<0.001

    Conversion to full sternotomy, n

    NeoChord: 1

    New atrial fibrillation, n (%)

    NeoChord: 9 (12)

    Conventional: 23 (25) p=0.031

    Stroke, n (%)

    NeoChord: 0

    Conventional: 2 (2) p=0.191

    Wound infection, n

    NeoChord: 0

    Conventional: 1 p=0.354

    Renal failure, n (%)

    NeoChord: 2 (3)

    Conventional: 14 (15) p=0.007

    New PPM within 30-days post-procedure, n (%)

    NeoChord: 2 (3)

    Conventional: 11 (12) p=0.003

    Re-exploration, n (%)

    NeoChord: 3 (4)

    Conventional: 3 (3) p=0.577

    Colli, 2018a

    Treatment success at one year, % (SD)

    89 (2.9)

    Procedural success, n (%)

    110 (98)

    Operative time, min (IQR)

    118 (110-155)

    Survival at one year, n (%)

    104 (96)

    MR at discharge, n (%)

    Trivial: 30 (31)

    Mild: 51 (53)

    Moderate: 14 (15)

    Severe: 1 (1)

    MR at one year, n (%)

    Trivial: 33 (39)

    Mild: 36 (39)

    Moderate: 20 (22)

    Severe: 3 (3)

    Death, n (%)

    2 (2)

    TIA, n (%)

    1

    Myocardial infarction, n (%)

    1 (1)

    AKI, n (%)

    Stage 1: 9 (8)

    Stage 2: 2 (2)

    Stage 3: 2 (2)

    Need for CVVH: 2 (2)

    Bleeding, n (%)

    Minor: 9 (8)

    Major: 3 (3)

    Extensive: 5 (4)

    Conduction disturbance, n (%)

    2 (2)

    New-onset atrial fibrillation, n (%)

    Paroxysmal: 25 (23)

    Persistent: 5 (5)

    Pericardial effusion, n (%)

    Minor: 7 (6)

    Pleural effusion, n (%)

    Minor: 68 (62)

    Major: 2 (2)

    Wound dehiscence. n

    1

    Hospital stay, days (IQR)

    7 (6-9)

    Discharge location, n (%)

    Home: 72 (65)

    Rehabilitation centre: 36 (33)

    D'Onofrio, 2023

    Median follow-up

    5.1 years

    Median operative time, min (IQR)

    123 (105-150)

    Technical success, %

    98

    Procedural success, %

    94

    Device success, %

    30 days: 94

    1 year: 9

    5 year: 78

    Patient success at 1-year, %

    92

    5 year overall survival, %

    84 (95% CI, 76-92)

    No statistically significant difference (p=0.13) between FA and UA in terms of survival

    MR grade at discharge, n (%)

    None/trace: 30 (31)

    Mild: 51 (53)

    Moderate: 14 (15%)

    Severe: 1

    MR grade at 5 years, n (%)

    None/trace: 5 (8)

    Mild: 33 (51)

    Moderate: 19 (30)

    Severe: 7 (11)

    Overall cumulative incidence of severe MR recurrence, %

    1 year: 9 (95% CI, 4-15)

    3 years: 12 (95% CI, 6-19)

    5 years: 24 (95% CI, 15-32)

    Overall cumulative incidence of reoperation, %

    1 year: 7 (95% CI, 2-12)

    3 years: 10 (95% CI, 4-16)

    5 years: 17 (95% CI, 9-24)

    Patients with FA compared with UA had a lower incidence of reintervention (5% vs 19% at 1 year; 6% vs 26% at 3 years; and 15% vs 43% at 5 years; P <.001

    NYHA functional class at 5 years, %

    Class 1: 78

    Class 2: 22

    Median LVEF preoperative, % (IQR)

    61 (57-67)

    Median LVEF at discharge, % (IQR)

    57 (53-60) p=0.09

    Median LVEF at 5 years, % (IQR)

    59 (56-64) p=0.09

    30-day mortality, n (%)

    2 (2)

    Intraoperative complications, n (%)

    ECMO: 2 (2)

    Conversion to conventional surgery: 2 (2)

    Major or extensive bleeding: 5 (5)

    Early mortality, n (%)

    2 (2)

    Median ICU stay, day (IQR)

    1 (1-1)

    Hospital stay, days (IQR)

    7 (6-9)

    Periprocedural complications, n (%)

    Reoperation for severe MR: 2 (2)

    TIA: 1

    AKI stage 2 or 3: 4 (4)

    Renal replacement therapy: 2 (2)

    New onset AF: 28 (28)

    Early reintervention, n (%)

    3 (3)

    Samalavicius, 2018

    Median duration of surgery, min (IQR)

    120 (115-145)

    MR post procedure, n (%)

    Trivial: 42 (56%)

    Grade 1+: 27 (36)

    Grade 2+: 4 (5)

    Grade >2+: 2 (3)

    Procedural success, n (%)

    75 (99)

    Postoperative, n (%)

    New atrial fibrillation: 9 (12)

    Need to inotropic support: 20 (26)

    Median duration of mechanical ventilation, hours (IQR)

    4 (2.6-6)

    Median length of ICU stay, hours (IQR)

    22 (21-24)

    Median length of hospital stay, days (IQR)

    8 (7-11)

    Postoperative mortality, n

    0

    Sepsis, n

    1

    Renal failure, n (%)

    2 (3)

    Re-exploration for bleeding, n (%)

    2 (3)

    Colli, 2015

    Early procedural success

    100%

    Median procedure time, min (IQR)

    130 (117.5-150)

    MR at discharge, n (%)

    0+: 32 (51)

    1+: 22 (35)

    2+: 7 (11)

    3+: 1 (2)

    4+: 1 (2)

    MR at 30 days, n (%)

    0+: 29 (46)

    1+: 16 (25)

    2+: 10 (16)

    3+: 7 (11)

    4+: 1 (2)

    NYHA class at 30 days, n (%)

    1: 55 (87)

    2: 4 (6)

    3: 4(6)

    Perioperative complications, n (%)

    Ventricular fibrillation: 3 (5)

    CPB/ECMO: 1

    Bleeding requiting >2 blood units: 3 (5)

    Major adverse events, n (%)

    Myocardial infarction: 1

    Septicaemia: 2 (3%)

    Minor adverse events, n (%)

    Severe pericardial effusion: 2 (3)

    Wound dehiscence: 1

    Persistent AF: 13 (21)

    Permanent AF: 1

    PM implantation: 2 (3)

    Reoperation for NeoChord procedure failure at 30 days, n (%)

    New Neochordae implantation: 1

    Neochordae retensioning: 2 (3)

    Mitral valve repair: 3 (5)

    Mitral valve replacement: 2 (3)

    Median ICU stay, hours

    24

    Median duration mechanical ventilation, hours (IQR)

    3 (2-5)

    Median hospital stay, days (IQR)

    8 (6-11)

    Discharge location, n (%)

    Home: 9 (14)

    Cardiac rehabilitation centre: 54 (86)

    Colli, 2016

    Acute procedure success

    100%

    Echocardiographic success at 3 months

    90%

    Median operative time, mins (IQR)

    120 (100 - 135)

    Residual MR at discharge, n (%)

    0+: 22 (44.9)

    1+: 14 (28.6)

    2+: 11 (22.4)

    3+: 2 (4.1)

    Residual MR at 3 months, n (%)

    0+: 16 (33.4)

    1+: 15 (31.2)

    2+: 12 (25)

    3+: 5 (10.4)

    NYHA class at discharge, n (%)

    1: 47 (95.9)

    2: 1

    3: 1

    NYHA class at 3 months, n (%)

    1: 41 (85.4)

    2: 2 (4.1)

    3: 5 (10.4)

    3 month freedom from MR 2+ by anatomical type (p=0.43)

    Type A: 100

    Type B: 89 ± 6%

    Type C: 83 ± 11%

    Perioperative complications, n (%)

    Ventricular fibrillation: 1

    CPB/ECMO: 1

    Bleeding requiting >2 blood units: 4 (8.2)

    Major adverse events, n (%)

    Death: 1

    Myocardial infarction: 1

    Septicaemia: 1

    Minor adverse events, n (%)

    Severe pericardial effusion: 3 (6.1)

    Deep wound dehiscence: 1

    ARF: 4 (8.2)

    ARF needing CVVH: 1

    Persistent AF: 20 (40.8)

    Permanent AF: 3 (6.1)

    Reoperation for NeoChord procedure failure at 3 months, n (%)

    4 (8.2)

    Median ICU stay, hours

    24

    Median mechanical ventilation time, hours (IQR)

    2 (0-3)

    Median hospital stay, days (IQR)

    7 (6-10)

    Wrobel, 2019

    Median operative time, min (IQR)

    115 (65-175)

    Post-procedure MR, n (%)

    Trace to mild: 33 (90)

    Mild to moderate: 3 (8)

    Moderate 1 (2)

    Median blood loss, ml (range)

    300 (100-1280)

    Median ICU stay, hours (range)

    32 (22-100)

    Median hospital stay, days (range)

    7 (4-17)

    Surgical complications, n

    0

    Major adverse events, n

    0

    Minor adverse events, n (%)

    Atrial fibrillation: 9 (24)

    Pleural effusion: 2 (5)

    Blood transfusion: 1

    Seeburger, 2014

    Post-procedure MR ≤2+, n (%, 95% CI)

    26 (87, 69-96)

    30-day MR ≤2+, n (%, 95% CI)

    17 (59, 39-77)

    71% of these maintained MR grade ≤1+

    Acute procedural success, n (%)

    26 (87)

    Any major adverse event, n (%)

    8 (27)

    Death, n (%)

    1 (3)

    Reoperation for failed repair, n (%)

    6 (20)

    Procedure-related blood transfusion >2 units of blood, n (%)

    5 (17)

    Procedural ventilation >48 hours, n (%)

    1 (3)

    Stroke (transient), n (%)

    1 (3)

    Kurnicka, 2019

    Procedural success, %

    100

    MR grade post-procedure, %

    Trivial: 43

    Mild: 57

    MR grade 6 months, %

    Trivial: 14

    Mild: 67

    Moderate: 19

    NYHA class at 6 months, %

    Class 1: 100

    Mean LAV, ml (SD)

    Preoperative: 84.5±23.3

    6 months: 58.5±16.6 p<0.0001

    Mean LAVi, ml/m2 (SD)

    Preoperative: 44.9±10.6

    6 months: 31.1±7.5 p<0.0001

    Mean LVEDD, ml (SD)

    Preoperative: 55.4±6.7

    6 months: 50.2±5.6 p<0.0001

    Mean LVESD, ml (SD)

    Preoperative: 37.5±6.9

    6 months: 34.2±4.1 p=0.005

    Mean LVEDV, ml (SD)

    Preoperative: 123.9±44.3

    6 months: 91.1±25.3 p<0.0001

    Mean LVESV, ml (SD)

    Preoperative: 59.8±29.7

    6 months: 42.7±11.4 p=0.006

    Postoperative complications

    0

    Conversion to conventional surgery

    0

    Procedure technique

    All the included studies performed the NeoChord procedure using the NeoChord DS1000 device. Technique was consistent throughout the included studies. Seeburger (2014) revised the surgical access to a posterolateral apical approach (introduced after 15 patients received implants) during the study and presented both separate and combined results.

    Efficacy

    Composite success endpoints

    Success outcomes were reported in 10 studies with varying definitions and use of MVARC criteria.

    In the prospective case series Colli (2015), early procedural success was defined as implantation of at least two neochordae with immediate reduction in MR to less than 2+ after the procedure and was achieved in 100% of people in the study. Considering the different MV anatomical types, the 30-day procedural success rate was 95% in type A, 92% in Type B, and 71% in type C.

    In the prospective case series by Colli (2016), acute procedural success was defined as the successful placement of a least three neochordae with a reduction in residual MR to less than 2+ and was achieved in 100% of people in the study. Echocardiographic success was defined as freedom from residual MR of 2+ or more. At 3 month follow-up, echocardiographic success was achieved in 90% (SD=4%) of people in the study. Considering the different MV anatomy types, 3 month freedom from MR of 2+ or greater was 100% in Type A, 89% (SD= 6%) in Type B and 83% (SD=11%) in Type C. However, the difference was not statistically significant between the groups (p = 0.43).

    In the prospective case series Colli (2018a), procedural success was achieved in 98% of people who had the procedure. A composite 1 year treatment success endpoint was also established based on MVARC criteria. The treatment was considered a success if the person undergoing treatment met the following criteria at the 1 year follow-up: (i) technical success including the placement of at least 2 neochordae and residual mitral regurgitation mild or less at the end of the procedure; (ii) freedom from major adverse events such as death, stroke, mitral regurgitation higher than moderate, structural or functional valvular failure and/or unplanned interventions related to the procedure or device at 1 year and (iii) freedom from a decline in baseline symptoms. This endpoint was achieved in 89% (SD=3%) of patients.

    In the retrospective registry study Colli (2018b), outcome definitions were based on the MVARC guidelines. Procedural success (defined as the placement of at least 2 neochordae and mild or less MR at the end of the procedure) was achieved in 97% of people.

    In the retrospective case series D'Onofrio (2023), outcome definitions for technical, device, procedural and patient success were based on MVARC guidelines. Technical and procedural success were 98% and 94%, respectively. Device success was 94%, 92%, and 78%, at 30 days, 1 year, and 5 years, respectively. Patient success at 1 year was 92%.

    In the retrospective registry study Gerosa (2021), patient and procedural success were defined according to MVARC guidelines. Procedural success was defined as the placement of at least 2 neochordae and achievement of mild or less MR. The primary endpoint was patient success, a composite of procedural success, freedom from death, stroke, MR greater than moderate, unplanned interventions related to the procedure, cardiac-related rehospitalization, or worsening New York Heart Association (NYHA) functional class at each year of follow-up. Procedural success was achieved in 99% of people who had the procedure. The rate of patients achieving the primary endpoint of patient success was 91% (SD=2%) at 1 year, 90% (SD=2%) at 2 years, and 81% (SD=4%) at 3 years. Considering the different MV anatomical types, the rate of patient success at 3 years was 88% (SD=5%) for type A, 84% (SD=5%) for type B, 73% (SD=12%) for type C, and 57% (SD=19%) for type D. The rate was statistically significantly different (P=0.001) between anatomical categorical types.

    In the prospective case series Kurnicka (2019), early procedural success was defined as placement of at least 2 neochordae with a significant reduction of MR (reduction of regurgitation from severe to trace/mild). This outcome was achieved in 100% of people who had the procedure. At 6 month follow-up, MR remained trace or mild in 81% of people.

    In the prospective case series Samalavicius (2018), procedural success was reported in 99% of people who had the procedure. However, this outcome was not defined.

    In the prospective case series Seeburger (2014), acute procedural success was defined as the placement of at least 1 neochordae and reduction of MR to 2+ or less. 87% of people who had the procedure achieved acute procedural success.

    MR reduction

    MR outcomes were reported in 12 studies with varying grading scales and multiple source guidelines used.

    In the prospective case series Colli (2016), MR severity was graded according to ASE guidelines. All people included in the study cohort had severe MR (3 or 4+) at baseline. At discharge, 45% had MR grade 0+, 29% had MR grade 1+, 22% had MR grade 2+, and 4% had MR grade 3+. At 3 month follow-up, 33% had MR grade 0+, 31% had MR grade 1+, 25% had MR grade 2+, and 10% had MR grade 3+. Considering the different MV anatomical types, 3 month freedom from MR greater than 2+ was 100% in type A, 89% (SD=6%) in Type B, and 83% (SD=6%) 11% in Type C. However, this difference was not statistically significant (p=0.43).

    In the prospective case series Colli (2015), MR severity was graded according to ASE guidelines. At baseline, 11% of people included in the study had MR grade 3+, and 89% had MR grade 4+. At discharge, 51% had MR grade 0+, 35% had MR grade 1+, 11% had MR grade 2+, 2% had MR grade 3+, and 2% had MR grade 4+. At 30-day follow-up, 46% had MR grade 0+, 25% had MR grade 1+, 16% had MR grade 2+, 11% had MR grade 3+, and 2% had MR grade 4+. Considering the different anatomical types at 30-day follow-up, type A anatomy was associated with the best outcomes as 95% of people in this group had MR grade of 1+ or less. 46% of people with type B anatomy had MR grade of 0+, 35% had grade 1+, 15% had grade 2+, and 4% had grade 3+. 14% of people with type C anatomy had MR grade of 0+, 7% had grade 1+, 43% had grade 2+, 29% had grade 3+, and 7% had grade 4+.

    In the prospective case series Colli (2018a), residual MR was classified as absent, mild, moderate or severe. MR severity was evaluated using a combination of semi-quantitative (vena contracta width and pulmonary vein flow) and quantitative parameters (regurgitant volume) according to the ASE guidelines. At baseline, all people included in the study cohort had severe MR. At discharge, 31% had no/trivial MR, 53% had mild MR, 15% had moderate MR, and 1% had severe MR. At 1 year follow-up, 39% had no/trivial MR, 39% had mild MR, 22% had moderate MR, and 3% had severe MR.

    In the retrospective registry study Colli (2018b), postoperative MR was assessed with transthoracic echocardiography independently by each centre's investigators according to ASE criteria. All people included in the study cohort had severe MR at baseline. At discharge, 41% had absent/trace MR, 45% had mild MR, 12% had moderate MR, and 2% had severe MR. At 1 year follow-up, 31% had absent/trace MR, 44% had mild MR, 17% had moderate MR, 8% had severe MR. Considering the different anatomical types at discharge, type A anatomy was associated with the best outcomes as 95% of people in this group had MR grade of absent/trace or mild. 35% of people with type B anatomy had MR grade of absent/trace, 51% mild, 13% moderate, and 1% severe. 23% of people with type C anatomy had MR grade of absent/trace, 40% mild, 30% moderate, and 7% severe. At 1 year follow-up, a similar trend was observed with type A anatomy associated with improved MR grade outcomes compared to type B and C.

    In the retrospective propensity-matched cohort study D'Onofrio (2022), the severity of mitral valve regurgitation was graded as mild (1+), moderate (2+) and severe (3+) according to the ASE guidelines. All people included in the study had severe MR at baseline. Patients undergoing the NeoChord procedure showed worse freedom from moderate MR (2+ or more) at 5 year follow up compared to conventional surgery: 58% (95% CI 43-77) and 84.6% (95% CI 76-95) in the NeoChord and conventional groups respectively (p=0.001). Freedom from severe MR at 5 year follow up was also lower in the NeoChord group compared to the conventional group: 78% (95% CI 65-93) and 90% (95% CI 82-98) for the NeoChord and conventional groups respectively (p=0.032).

    In the retrospective case series D'Onofrio (2023), MR severity was graded as absent/trace (0), mild (1+), moderate (2+), and severe (3+) according to the ASE criteria. All people included in the study cohort had severe MR at baseline. At discharge, 31% had absent/trace MR, 53% had mild MR, 14% had moderate MR, and 1% had severe MR. At 5 year follow up, 8% had absent/trace MR, 51% had mild MR, 30% had moderate MR, and 11% had severe MR. Overall cumulative incidence of severe MR recurrence was 9% (95% CI, 4-15) at 1 year, 12% (95% CI, 6-19) at 3 years, and 24% (95% CI, 15-33) at 5 years. Patients with favourable anatomy (type A and B) compared with unfavourable anatomy (type B and C) had a lower incidence of severe MR recurrence over the same period with 6% compared to 22% at 1 year; 8% compared to 33% at 3 years; and 15% compared to 63% at 5 years (P=0.001)

    In the retrospective registry study Gerosa (2021), MR severity was graded as absent/trivial, mild, moderate and severe according to ASE and ESC guidelines. All people included in the study cohort had severe MR at baseline. At discharge, 42% had absent/trivial MR, 45% had mild MR, 10% had moderate MR, and 3% had severe MR. At 3 year follow-up, 12% had absent/trivial MR, 52% had mild MR, 30% had moderate MR, 6% had severe MR. Considering the different MV anatomical types, freedom from MR recurrence of moderate or higher was 88% (SD=5%) in type A, 8% (SD=4%) in type B, 73% (SD=12%) in type C, and 48% (SD=18%) in type D (p=0.001).

    In the prospective case series Kurnicka (2019), MR severity was graded as absent, mild, moderate and severe according to ASE and ESC guidelines. Baseline MR data was not reported. Postoperatively, 43% had trace MR, and 57% had mild MR. At 6 month follow-up, 14% had trace MR, 67% had mild MR, and 19% had moderate MR.

    In the prospective case series Samalavicius (2018), MR severity was graded according to AHA/ACC and ESC guidelines. At baseline, 67% of people had MR grade 3+, and 33% had MR grade 4+. After the procedure, 56% of people had trivial MR, 36% had grade 1+ MR, 5% had grade 2+ MR, and 3% had higher than grade 2+ MR.

    In the prospective case series Seeburger (2014), MR severity was graded according to AHA/ACC guidelines. At baseline, 10% of people included in the study had MR grade 3+, and 90% had MR grade 4+. Post-procedure, 87% (95% CI, 70-96) had MR grade of 2+ or less. At the 30-day follow-up, 59% (95% CI, 39-77) had an MR grade of 2+ or less, with 71% of these people maintaining an MR grade of 1+ or less.

    In the prospective case series Wrobel (2019), MR severity was described according to the EACVI recommendations for the assessment of native valvular regurgitation. Post-procedure, 90% of people in the study had trace/mild MR, 8% had mild/moderate MR, and 2% had moderate MR.

    In the retrospective cohort study Zorinas (2019), source guidelines for the description of MR severity were not reported. All people included in the study had severe MR at baseline. Post-procedure, 100% of people in the conventional surgery group had MR grade absent or mild, compared to 92% in the NeoChord procedure group. At 30-day follow-up, zero patients in the conventional surgery had MR grade severe, compared to 8% in the NeoChord procedure group (p=0.001).

    NYHA functional class

    NYHA functional outcomes were reported in 5 studies. All studies showed a durable improvement from baseline after the NeoChord procedure.

    In the prospective case series Colli (2016), 6% of people were NYHA class 1, 58% class 2, 36% class 3, and 1% class 4 at baseline. All successfully treated patients showed an improvement in NYHA functional class at 3 months; 85% were in NYHA class 1, 4% in class 2, and 10% in class 3. Considering NYHA functional class across the different MV anatomical types at 3 month follow-up; 100% of type A were in class 1, 96% of type B were in class 1, and 67% of type C were in class 1.

    In the prospective case series Colli (2015), 5% were NYHA Class one, 40% NYHA Class 2, 49% in NYHA Class III and 6% in NYHA Class 4 at baseline. Clinical improvement was observed in all successfully treated patients. At the 30-day follow-up, 87% were in NYHA Class one, 6% in NYHA Class 2 and 6% in NYHA Class 3. Considering NYHA functional class across the different MV anatomical types at 30-day follow-up; 100% of type A were in class 1, 88% of type B were in class 1, and 71% of type C were in class 1.

    In the propensity matched study D'Onofrio (2022), significant improvement of NYHA functional class with respect to baseline was observed in both groups (P < 0.001) with more than 90% of patients in NYHA class I and II at follow-up.

    The retrospective case series D'Onofrio (2023) reported 7% of people as NYHA class 1 at baseline, 38% in class 2, and 52% class 3. At discharge, the proportion of people in NYHA class 1 increased to 99%, decreasing to 78% at the 5 year follow-up.

    The prospective case series Kurnicka (2019) reported 29% of people were NYHA class 1 at baseline, 57% in class 2, and 14% in class 3. At 6 month follow up, all people in the study were NYHA class 1.

    Survival

    Survival was reported in 5 studies. Length of follow-up for this outcome ranged from 3 months to 5 years.

    Colli (2016) estimated overall survival using the KM method. Overall survival at 3 months was 97% (SD= 2%), no p-value was reported. In Colli (2018b), overall survival at 1 year was reported as 98%, with 4 high-risk patients dying during the study. In D'Onofrio (2022), overall all-cause mortality was similar between the NeoChord and conventional surgery groups. KM analysis showed 5 year survival of 92% (95% CI, 82 to 100) and 96% (95% CI, 91 to 100) in the NeoChord and conventional surgery groups respectively. In people with type A anatomy, survival was 100% in the NeoChord group, and 93% (95% CI, 84 to 100) in the conventional surgery group. In D'Onofrio (2023), KM analysis estimated overall survival at 5 years of 84% (95% CI, 76% to 92%). There was no statistically significant difference in terms of survival (p=0.13) between favourable anatomy (type A and B), and unfavourable anatomy (type B and C). Gerosa (2021) reported a KM survival estimate of 99% (SD=1%) at 1 and 2 years and 94% (SD=3%) at 3 years. All deaths were cardiovascular, and all deceased patients were elderly with multiple severe comorbidities.

    Reintervention

    Reintervention was reported in 6 studies. Reasons for reintervention were new neochordae implantation, re-tensioning, recurrent severe MR, and failed repair.

    Colli (2016) reported 4 cases (8%) of reoperation for NeoChord procedure failure at 3 months. One person underwent a further NeoChord procedure, and 3 had mitral valve replacement. Colli (2015) reported 8 cases (13%) of reoperation for NeoChord procedure failure at 30 days. One person required new neochordae implantation, 2 required neochordae re-tensioning, 3 underwent conventional mitral valve repair, and 2 underwent mitral valve replacement. Colli (2018a) reported 4 cases (4%) of reintervention due to recurrent MR at 1 year follow-up. Colli (2018b) reported 7 people (4%) with severe MR at 6 month follow up underwent conventional MV reintervention. D'Onofrio (2022) reported that 5 year freedom from reoperation in the NeoChord group was 79% (95% CI, 66 to 95), and 92% (95% CI, 85 to 99) in the conventional surgery group (p=0.022). However, in anatomical type A patients, the difference in freedom from reoperation between NeoChord and conventional surgery groups was not statistically significant. During a median follow-up of 3.4 years, 11 people in the NeoChord group had the reoperation; of these, 4 were re-repair, 6 were replacements and 1 was a further NeoChord procedure. In D'Onofrio (2023) the overall cumulative incidence of reoperation was 17% (95% CI, 9 to 24) at 5 years. People with favourable anatomy (type A and B) had a lower incidence of reintervention at 5 years compared to people with unfavourable anatomy (type B and C); 15% compared to 43% respectively (p=0.001). Gerosa (2021) reported 13 (6%) people required reoperation for recurrent MR at 3 years. Seeburger (2014) reported 6 (20%) cases of reoperation due to failed repair.

    Echocardiographic outcomes

    LVEF

    D'Onofrio (2022) reported a median LVEF of 55% (IQR 59 to 68) at discharge after the NeoChord procedure, a reduction from a median of 64% (IQR 59 to 68) at baseline. This increased to 59% (IQR 55.5 to 62.5) after a median follow-up of 3.4 years. D'Onofrio (2023) showed similar results, with an initial reduction at discharge from median 61% (IQR 57 to 67) to 57% (IQR 53 to 60). Median LVEF at 5 year follow-up was 59% (IQR 56 to 64) (p=0.09). Kurnicka (2019) did not report a statistically significant change between LVEF at baseline compared to 6 month follow-up.

    LVEDV

    D'Onofrio (2022) reported median LVEDVi at discharge 76ml/m2 (IQR 58.5 to 86.5), a reduction from 82ml/m2 (IQR 67.3 to 95) at baseline. This further reduced to 66ml/m2 (IQR 66 to 72) at median follow-up of 3.4 years. D'Onofrio (2023) reported a reduction from 82ml/m2 (IQR 70 to 79) at baseline to 68ml/m2 at discharge, with a further reduction of 6ml/m2 at 5 year follow-up. Kurnicka (2019) reported a statistically significant reduction in LVEDV from 123.9ml (SD= 44.3) at baseline to 91.1ml (SD=25.3) at 6 month follow-up (p<0.0001).

    LVESV

    D'Onofrio (2023) reported a reduction from 33ml/m2 (IQR 25 to 39) at baseline to 29ml/m2 (IQR 24 to 37) at discharge, with a further reduction of 4ml/m2 at 5 year follow-up. Kurnicka (2019) reported a statistically significant reduction in LVESV from 59.8ml (SD=29.7) at baseline to 42.7ml (SD=11.4) at 6 month follow-up (p=0.006).

    LAVi

    D'Onofrio (2023) reported a reduction from 55ml/m2 (IQR 42 to 56) at baseline to 45ml/m2 (IQR 35 to 57) at discharge, with a further reduction of 2ml/m2 at 5 year follow-up. Kurnicka (2019) reported a statistically significant reduction in LAVi from 44.9ml/m2 (SD=10.6) at baseline to 31.1ml (SD= 7.5) at 6 month follow-up (p<0.0001).

    sPAP

    D'Onofrio (2023) reported a reduction from 33mmHg (IQR 26 to 41) at baseline to 29mmHg (IQR 24 to 39) at discharge, with a further reduction of 4mmHg at 5 year follow-up.

    Operative time

    Operative time was reported in 10 studies. Median operative time ranged from 115 minutes to 130 minutes across these studies for the NeoChord procedure. In D'Onofrio (2022) median operative time was 2.0 hours (IQR 1.8 to 2.5) for the NeoChord procedure, and 4.0 (IQR 3.5 to 4.0) for conventional surgery. Similar operative times were reported in Zorinas (2019), with median operative time reported as 120 minutes (IQR 110 to 146) for the NeoChord procedure, and 312 minutes (IQR 280 to 361) for conventional surgery.

    Length of hospital stay

    Length of hospital stay was reported in 10 studies. Median hospital stay ranged from 7 to 8 days across these studies for the NeoChord procedure. In Zorinas (2019), median hospital stay was 8 days (IQR 7 to 9) for the NeoChord procedure, and 16 days (IQR 14 to 21) for conventional surgery.

    Safety

    In-hospital and 30-day deaths

    Early deaths occurred in 7 of the included studies. No procedural deaths occurred in any study. The primary reason for in-hospital death was cardiovascular dysfunction, other reasons included post-cardiotomy syndrome with concomitant sepsis and multi-organ failure, and bleeding-related tamponade. People who died after the procedure were considered high-surgical risk, with multiple comorbidities. In-hospital deaths ranged from 1% to 2% across all studies, and D'Onofrio (2023) reported a 30-day mortality of 2% for the NeoChord procedure.

    Major adverse events

    Cardiovascular or cerebrovascular

    Major cardiovascular or cerebrovascular adverse events such as myocardial infarction and stroke were reported at a rate of 2% or fewer at follow-up in all 12 studies.

    Septicaemia

    In Colli (2015), 2 (3%) of people in the study developed septicaemia after the procedure, similar rates were reported in Colli (2016) and Samalavicius (2018). Seeburger (2014) reported 0 septicaemia occurrences. This outcome was not reported in the remaining studies.

    Major or extensive bleeding

    Bleeding was reported in 7 of the included studies. The proportion of people who experienced major or extensive bleeding ranged from 3% to 5% across all studies. Colli (2016) reported 8% of people had intraoperative bleeding requiring at least 2 units of blood, however none needed surgical revision for bleeding. In Samalavicius (2018), 3% of people who underwent the procedure required re-exploration for bleeding. Zorinas (2019) reported that postoperative blood loss in the NeoChord procedure group was statistically significantly lower compared to the conventional surgery group with 200ml compared to 300ml respectively (p = 0.001).

    Minor adverse events

    Kidney injury

    8% of people in Colli (2016) developed acute renal failure, one of these patients required CVVH. 12% of people in Colli (2018a) developed AKI, the majority of which was stage 1. However, 2 patients developed stage 3 AKI and required CVVH. Four more studies reported the rate of post-procedure kidney injury between 3 to 7%. Notably, Zorinas (2019) reported the proportion of renal failure of the NeoChord procedure compared to conventional surgery as 3% and 15% respectively (p=0.007).

    Atrial fibrillation (AF)

    New onset AF post-procedure was reported in 5 studies. AF can be paroxysmal (intermittent) or permanent. Proportions of people developing AF after the procedure ranged from 12% in Samalavicius (2018) to 28% in D'Onofrio (2023). In Colli (2018b), 19% of people developed paroxysmal AF, and 3% developed persistent AF. In D'Onofrio (2022), 6% of people who underwent the NeoChord procedure developed AF, and 34% of people who underwent conventional surgery developed AF. Similar results were reported in Zorinas (2019) with 12% of people who underwent the NeoChord procedure developing AF compared to 25% in the conventional surgery group (p=0.031).

    Pleural or pericardial effusion

    Pericardial effusion was reported in 4 studies and was categorised as minor or major. The proportion of people who experienced major pericardial effusion varied between 1% in Colli (2018b) and 6% in Colli (2016). Colli (2018a) reported that 6% of people in the study experienced minor pleural effusion.

    Pleural effusion was reported in 4 studies and was also categorised as minor or major. Colli (2018a) reported 62% of people who underwent the procedure experienced minor pleural effusion, and 2% major pleural effusion. Similar results were reported in Colli (2018b) with 40% of people experiencing minor pleural effusion, and 1% major. Gerosa (2021) and Wrobel (2019) reported rates of major pleural effusion of 2% and 5% respectively.

    Anecdotal and theoretical adverse events

    Expert advice was sought from consultants who have been nominated or ratified by their professional society or royal college. They were asked if they knew of any other adverse events for this procedure that they had heard about (anecdotal), which were not reported in the literature. They were also asked if they thought there were other adverse events that might possibly occur, even if they had never happened (theoretical).

    They listed the following anecdotal adverse events:

    • Cardiac arrythmias or conduction disturbances

    • Infection

    They listed the following theoretical adverse events:

    • Heart failure

    • Emergency surgery

    Five professional expert questionnaires for this procedure were submitted. Find full details of what the professional experts said about the procedure here https://www.nice.org.uk/guidance/indevelopment/gid-ipg10216/documents.

    Validity and generalisability

    • Sample sizes were small across all studies due to the limited use of this procedure in clinical practice and novelty of the NeoChord DS1000 device. The largest sample size was 213 in Colli (2018b), while the smallest was 21 in Kurnicka (2019). These smaller studies lack statistical power and are not generalisable.

    • None of the included studies were conducted in the UK or contained UK data. Study centres were located in Italy, Lithuania, Germany, Poland and Denmark. This limits generalisability to the UK context.

    • Follow-up ranged from 30 days to 5 years across all studies, providing some insight into long-term outcomes. However, more robust long-term studies are needed to assess the durability of artificial chordae implanted with the NeoChord procedure. Long-term outcomes are particularly important for this procedure.

    • The potential for bias is very high as all studies are non-randomised and observational, and many are retrospective case series.

    • Patient selection bias is likely across all studies because patients underwent anatomical screening before the NeoChord procedure.

    • Key evidence gaps remain in long-term outcomes beyond 5 years, quality-of-life outcomes and patient-reported outcomes focusing on different subgroups. A larger number of patients and longer follow-up are needed to assess the definitive value of this therapeutic approach.

    • In the comparative studies, people who underwent the NeoChord procedure were strictly followed up through clinical and echocardiographic assessment at scheduled timepoints. However, many people who underwent conventional surgery were followed up by their referral cardiologist, therefore, the possible underestimation of valve-related adverse events in the conventional surgery population cannot be excluded.

    • The determination of the exact positioning, length adjustment, and neochordae tensioning depends exclusively on the ability and training of the operator and echocardiographer. Variations in experience and skill across the operators in the studies could introduce bias into the results.

    • Study endpoints were not consistent across the studies and often contained composite outcomes based to varying degrees on MVARC criteria, limiting comparison of efficacy outcomes across the studies.

    • Different criteria were used to grade residual MR across the studies, limiting comparison of results across the studies.

    • Measurement and interpretation of MR is operator-dependant and therefore a potential source of bias

    • There is likely substantial overlap in the populations of some of the included studies. There is a high potential for selection bias.

    • Many authors of the included studies have potential financial conflicts of interest with the manufacturer of this device (NeoChord, Inc), including providing consulting services, receiving travel grants, and proctoring.

    Ongoing trials

    NCT02803957 Randomized Trial of the NeoChord DS1000 System Versus Open Surgical Repair (ReChord) is a multicentre, open-label trial to assess the safety and effectiveness of the NeoChord DS1000 device in subjects with degenerative mitral valve disease receiving a mitral valve repair without cardiopulmonary bypass (treatment group) when compared to subjects receiving mitral valve repair using standard surgical techniques with cardiopulmonary bypass (control group). Sponsor: NeoChord, USA. Estimated completion: July 2027.

    NCT04190602 Multicentre Post-Market Observational Registry of the NeoChord Artificial Chordae Delivery System (AcChord) is an observational, single-arm, multicentre post-market registry. The objective of this study is to evaluate the 5 year outcomes of participants with degenerative mitral valve disease treated with the NeoChord DS1000 in a post-market setting. Sponsor: NeoChord, USA. Estimated completion: December 2027.