Long-Term Outcomes Comparing Minimally Invasive Mitral Valve Repair versus Conventional Mitral Valve Surgery

Objectives: To compare the long term outcomes between minimally invasive mitral valve repair (MiMVR) and conventional surgery. Current retrospective comparisons between the techniques frequently report echocardiographical (echo) outcomes early after surgery and rarely report them later. Methods: Patients were selected for MiMVR by the surgical multi-disciplinary meeting from June 2008-March 2013. Patients included had at least two transthoracic post-operative echocardiograms. Echocardiographic parameters including left ventricular size and systolic function, degree of mitral regurgitation (MR) and mean mitral valve gradient were recorded. Clinical outcomes including all-cause mortality, re-operation, recurrence of at least moderate MR and elevated mean mitral valve gradients > 5 mmHg were recorded and compared using Kaplan-Meier survival analysis. Results: 223 patients were screened, 96 (43%) met the criteria and were included. Thirty-seven patients underwent conventional surgery and 59 underwent MiMVR. Mean clinical follow-up was 6.3 years and echo follow up was 3.2 years. There was a significantly higher recurrence of moderate MR in the conventional group (38% (n = 19) versus 17% (n = 10)). The mean LV end-diastolic diameter was 4.8 cm (conventional) versus 5.0 cm (MiMVR). The incidence of elevated PG was 26% (n = 13, conventional) and 23% (n = 14, MiMVR). There was no significant difference in incidence in re-operation (conventional 12% (n = 6), MiMVR 8.3% (n = 5)). Long-term mortality was higher in the conventional group (1.7% vs. 18% p = 0.004) although the logistic Euroscore was significantly higher 6.8% ± 5.4 vs. 3.6% ± 1.6. Conclusions: Minimally invasive mitral valve surgery is safe and feasible in selected patients with good medium and long-term echocarHow to cite this paper: Jackson, M., Sandhu, M.S., Dong, C., Bawamia, B., Qureshi, M., Khan, K., Goodwin, A., Kendall, S., Hunter, S., Graham, R., Thambyrajah, J. and Akowuah, E.F. (2018) Paper Title. World Journal of Cardiovascular Surgery, 8, 127-139. https://doi.org/10.4236/wjcs.2018.88012 Received: June 22, 2018 Accepted: July 31, 2018 Published: August 3, 2018 Copyright © 2018 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
Left untreated, severe mitral regurgitation (MR) carries a poor prognosis.In asymptomatic patients, estimated 5-year rates of death from any cause, death from cardiac causes and adverse events (death, heart failure or new atrial fibrillation (AF)) are 22%, 14%, and 33% respectively [1].Mitral valve repair (MVR) is the optimal treatment for severe MR caused by degenerative disease carrying lower peri-operative mortality, improved survival, better preservation of left ventricular function and lower long-term mortality [2]- [7].
The first video-assisted minimally invasive mitral valve repair via a lateral thoracotomy was reported in 1996 [8].Such "keyhole" techniques were pioneered to reduce postoperative pain, blood loss, hospital stays and cost compared to the conventional median sternotomy approach [9] [10].In Europe and America, it has since been adopted as the standard of care.However, the International Society of Minimally Invasive Cardiac Surgery published a consensus document in 2010 highlighting the lack of data directly comparing the two techniques, and strongly recommended more studies designed to help determine whether minimally invasive mitral valve repair (MiMVR) is better, worse or the same as conventional surgery with respect to important clinical outcomes [11].We compare clinical and echocardiographic follow-up of our real-world experience of conventional approach versus MiMVR in consecutive patients at a single centre.

Patient Selection and Follow-Up
The James Cook University Hospital (JCUH), Middlesbrough, is a large cardiothoracic tertiary referral centre accepting referrals from across the North East of England as well as from distant referral centres across the United Kingdom.Approximately 120 mitral valve repairs are performed per year.
All patients undergoing elective mitral valve repair without coronary artery bypass grafting between June 2008 and March 2013 were considered for inclusion into our study.Patients underwent conventional or minimally invasive surgery following assessment of their mitral valve and surgical technique was decided by the surgical team.Contraindications to a minimally invasive approach were a heavily calcified immobile annulus, infective endocarditis, aortic regurgitation, a dilated aorta precluding use of endo-balloon to occlude the aorta, previous right sided thoracic surgery and known severe peripheral vascular disease.The operative technique for MiMVR used at our centre has already been described in detail by Akowuah et al. [12].All cases were performed via a 5 -6 cm antero-lateral minithoracotomy, used to enter the thorax through the third or fourth intercostal space.Mitral valve repair was performed using a combination of techniques including triangular resection, anterior neochordae and transfer of native chords.A complete or partial annuloplasty ring was always employed.
Conventional mitral valve repair was performed using conventional surgical techniques decided by the individual surgeon.Patients who required an intraoperative change in strategy from repair to replacement or intra-aortic balloon counterpulsation therapy were excluded.
A cardiac database prospectively recorded data on all mitral valve operations performed during this time period, including peri-operative and postoperative details and events.Data was collected from this database.Further details were obtained from thorough review of individual case notes, echocardiograms obtained from both JCUH and the referring hospitals and discharge letters.
Patients were required to have a transthoracic echocardiogram performed within two months of the initial operation (the "baseline" post-operative scan); this was commonly performed on the ward prior to discharge.At least one further transthoracic echocardiogram, usually performed at JCUH at the time of their cardiothoracic follow-up appointment, was required to be included in the study.Patients were then subsequently followed up by the referring hospital undergoing echocardiography as per local protocol.

Definitions
All chamber dimensions were defined as normal or mild, moderate or severely dilated as per the EAE (European Association of Echocardiography) guidelines [13].Left ventricular function was defined as hyperdynamic, normal or mildly, moderately or severely impaired using the Simpson's Biplane technique if sufficient image quality was obtained to clearly demarcate the myocardial border or visually if there was insufficient image quality.
Mean and peak mitral valve gradients were measured using continuous wave doppler.Mitral regurgitation was graded as normal, trace, mild, mild/moderate, moderate, moderate/severe or severe using ESC guidelines and visual estimation [14].

Outcomes
Mortality outcomes were detected using The United Kingdom Office of National Statistics (ONS) data.Incidences of re-operation on the mitral valve or recurrence of at least moderate mitral regurgitation were also recorded.As only patients with appropriate echocardiograms were included, there was no missing data for the patients included.There was no indeterminate data that arose, as continuous variables were generated from the same echocardiogram software and classified according to EAE guidelines.

Ethics
This was approved by the local Research and Development team as part of an evaluation of our minimally invasive surgery service.

Results
A total of 224 elective and urgent/emergency mitral valve operations were performed during the study period (conventional midline sternotomy (118 cases), minimally invasive approach (106 cases)).Of these, 96 elective cases met the criteria for inclusion into the study (conventional midline sternotomy (37 cases), minimally invasive approach (59 cases)).Seventy-five (78%) cases had three or more post-operative echocardiograms performed.Baseline demographics and surgical procedural data can be seen in Table 1.
The mean left ventricular end-diastolic diameter (LVEDd) immediately post-operatively was 4.9 cm ± 0.8 cm in the conventional surgical cohort and 5.0 cm ± 0.6 cm in the MiMVR cohort (p = 0.516).Over the follow-up period, the mean LVEDd was 4.8 cm ± 0.7 cm and 4.9 cm ± 0.7 cm respectively (p = 0.499), representing a reduction of 2.0% in both cohorts.
Kaplan Meier survival curves for all-cause six-year mortality, re-operation and recurrence of at least moderate mitral regurgitation can be seen in Figures 1-3.
No data outliers were identified and therefore additional analyses were not required.

Discussion
The key findings of this observational study comparing long-term clinical and  1) Mortality and rate of recurrent mitral regurgitation were significantly lower in patients who underwent minimally invasive mitral valve repair.
2) There was no difference between rates of re-operation or elevated postoperative mean mitral valve gradients > 5mmHg.
3) There was no difference in left ventricular end diastolic diameter between the two cohorts.robustly evaluated to understand whether they outweigh the costs before wide scale adoption is implemented.The ongoing UK Mini Mitral trial funded by the NIHR is designed to assess all of these outcomes and will provide clear and definitive evidence [30].

Conclusion
Minimally invasive mitral valve repair is a safe and feasible alternative to conventional mitral valve surgery with comparable rates of long-term mortality, re-operation and recurrence of mitral valve regurgitation in a selected cohort of patients.We await the outcomes of the UK Mini Mitral RCT with interest.

Figure 1 .
Figure 1.Kaplan Meier survival curve for all-cause six-year mortality following mitral valve repair.

Figure 2 .Figure 3 .
Figure 2. Kaplan Meier survival curve for re-operation following mitral valve repair
Mean echocardiographic follow-up was 3.2 ± 1.8 years in the conventional surgery arm and 3.2 ± 1.7 years in the minimally invasive arm.At least moderate mitral regurgitation occurred following valve repair in 15 (41%) of cases due to M. Jackson et al.DOI: 10.4236/wjcs.2018.88012131 World Journal of Cardiovascular Surgery PFO, patent foramen ovale; ASD, atrial septal defect; LV, left ventricle; LA, left Atrium; IABP, intra-aortic balloon pump; RBC, red blood cells; FFP, Fresh Frozen Plasma.Post-operative LV function criteria as per EAE guidelines [13].
[19]ral studies present long-term echocardiographic follow-up after MiMVR but do not provide comparison data for conventional surgical repair.McClure et al. followed up 1000 patients who underwent minimally invasive mitral valve operations (of which 923 patients were repairs) to a median of 7 years[18]; operative mortality was 0.8% with re-operation required in 4.4% of mitral valve repairs.Echocardiographic follow-up was obtained in 615 of 815 eligible mitral valve repairs and demonstrated freedom from recurrent moderate mitral regurgitation at 1, 5 and 10 years in 99% ± 1%, 87 ± 2% and 69% ± 4% patients.Further, analysis of 707 patients undergoing mitral valve repair demonstrated perioperative mortality of 0.4%, late mortality in 49 (6.9%) patients and reoperation in 38 (4.8%) patients[19].Echocardiographic follow-up of 544 patients (mean duration 4.36 years) demonstrated a significant reduction in mean gradient of mitral regurgitation and left ventricular ejection fraction.
Several meta-analyses compare the surgical outcomes from MiMVR compared to conventional mitral valve repair but do not present echocardiographic follow-up data beyond the immediate post-operative period.Cheng et al. included 35 studies including two small randomised controlled trials (RCTs), showing no benefit in mortality up to 9 years but significant improvement in incidence of atrial fibrillation, chest tube drainage, transfusion requirements, sternal infection, time to return to normal activity and patient scar satisfaction [15].Luca et al. also showed no difference in mortality despite longer cross-clamp and cardiopulmonary bypass times; rates of sepsis, shorter hospital stays and lower pain levels were lower following MiMVR [16].Cao et al. note similar findings to the above meta-analyses and comment on the lack of comparative data in the literature [17].DOI: 10.4236/wjcs.2018.88012137 World Journal of Cardiovascular Surgery