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Ideal therapy for secondary mitral regurgitation: should we look under the annulus?
  1. Judy Hung1,
  2. James S Gammie2,
  3. Gorav Ailawadi3
  1. 1 Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2 Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA
  3. 3 Division of Thoracic and Cardiovascular Surgery, University of Virginia, Charlottesville, Virginia, USA
  1. Correspondence to Dr Judy Hung, Division of Cardiology, Massachusetts General Hospital, Boston, MA 02114, USA; jhung{at}partners.org

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Secondary (aka ischaemic or Carpentier surgical classification Type IIIb) mitral regurgitation (MR) is a common complication of coronary artery disease and is associated with adverse prognosis.1 The fundamental mechanism of ischaemic MR relates to remodelling and distortion of the ischaemic left ventricle (LV). As viable myocardial cells are lost following infarction, the wall becomes thinner and bulges outward, a process that begins almost immediately and then progresses over weeks to months. As a result of ischaemic LV distortion and dilation, the  mitral leaflets become tethered towards the apex, restricting leaflet closure.2 Standard mitral valve repair for ischaemic MR at the time of revascularisation involves placing an undersized rigid mitral valve (MV) annuloplasty ring (restrictive mitral annuloplasty, RMA) to restore coaptation by correcting posterior annular dilatation. However, RMA does not eliminate the mechanistic problem in ischaemic MR, which is a subvalvular problem with altered geometry of the chordal apparatus due to ventricular dilation from coronary artery disease or cardiomyopathy.

In their paper in Heart, Harmel and colleagues3 performed a meta-analysis of 1 prospective and 11 retrospective trials examining outcomes of the addition of one of several subannular procedures in addition to RMA for ischaemic MR and conclude that the addition of such procedure(s) is associated with a substantially lower rate of recurrent MR.

Harmel and colleagues3 highlight an important unmet need in MV therapy, which is a need for a more durable MV repair for ischaemic MR. The recent randomised multicentre Cardiothoracic Surgical Trials Network trial compared MV replacement versus MV repair with restrictive mitral ring annuloplasty for severe ischaemic mitral regurgitation4 and found no difference in the primary outcome of left ventricular end-systolic volume index (LV ESVi). However, the repair group had a high rate of moderate or greater recurrent ischaemic MR at 2 years (59% vs 4%). As Harmel et al 3 point out, repaired patients without recurrent ischaemic MR had significantly better LV reverse remodelling (LV ESVi 43 mL/m2 vs 63 mL/m2) compared with those with recurrent ischaemic MR, which also was better than the MV-replacement group (LV ESVi 61 mL/m2). While some have concluded that it is important to do a ‘good repair’, it is unclear if a (vaguely defined) ‘good repair’ leads to better ventricular geometry and less recurrence over time, or if the development of progressive ventricular dilation alone causes the MR recurrence, no matter the quality of the RMA repair. What is clear is that there is a need for a more durable MV repair for ischaemic MR than simple ring annuloplasty.

Mitral ring annuloplasty as a therapy for ischaemic MR was adapted from MV repair developed for degenerative MR with leaflet resection and ring annuloplasty.5 However, the mechanism of ischaemic MR and degenerative MR are completely different and what works for one approach is unlikely to be optimal for another. Additionally, another reason for the high recurrence rate of MR following annuloplasty is that the ischaemic LV can be a moving target. Initially effective, annuloplasty may later fail as the LV continues to remodel and tethering increases. Subannular reconstruction makes mechanistic sense for ischaemic MR as it directly addresses the tethering mechanism in ischaemic MR.

Operations that address the subvalvular region or leaflet augmentation to relieve leaflet tethering have been reported previously, mostly in small case series.6 Small, single-centre studies have been performed for chordal cutting and papillary muscle approximation with encouraging results, demonstrating greater long-term reduction in MR with the addition of subvalvular approaches to ring annuloplasty (references 16, 27 in Harmel et al 3).

This meta-analysis by Harmel et al provides support for the addition of subannular reconstruction techniques to ring annuloplasty as it appears to result in less recurrence of MR and better reverse remodelling than ring annuloplasty alone. All meta-analyses are only as good as the studies that they are built on. The fact that all but one of the studies in this group is retrospective, the heterogeneity of surgical approaches for subvalvular repair, that three of the studies include a substantial overlap of patients (references 14, 24, 26 in Harmel et al 3) and that the claimed minimum duration of echocardiographic follow-up (3 years) is not present in several studies all dilute the impact of this study.

The subannular surgical techniques that are included in the meta-analysis are a potpourri and include unconventional suture annuloplasty techniques, suture approaches to alter papillary muscle position, leaflet augmentation, papillary muscle approximation with expanded polytetrafluoroethylene tubes and plication of the mid-posterior MV leaflet, and second-order chordal cutting leave one with the distinct impression that the best approach is yet to be determined. In the sole randomised trial included in this analysis, Nappi and colleagues (reference 27 from Harmel et al 3) used papillary muscle approximation in addition to RMA and at 5-year follow-up showed a remarkably high MR recurrence (grades 3–4) of 27% in the RMA with papillary muscle approximation group.

One important issue is determining which patients would benefit from annuloplasty alone versus subannular reconstruction and annuloplasty. There is heterogeneity in the geometric factors that account for the ventricular–MV mismatch among individual patients. MV repair in ischaemic MR can potentially be improved by guiding therapy that is tailored to patient-specific geometric measures of the ventricular–MV mismatch. In a post hoc analyses of the Cardiothoracic Surgical Trials Network severe MR trial, Kron et al 7 showed that the presence of a basal aneurysm was associated with recurrence of ischaemic MR and that the mechanism underlying recurrence of ischaemic MR was persistence of leaflet tethering, which was not addressed with ring annuloplasty.

Capoulade et al 8 demonstrated that a large LV diameter to MV ring size ratio (mismatch of LV size to MV ring size) was associated with recurrence of MR. Further study is needed to better select and predict which therapies are optimal for individual patients determined by clinical and patho-anatomy features.

While the Cardiothoracic Surgical Trials Network trial showed equivalence between repair and replacement, we should not lose sight of the fact that a mitral prosthesis confers an amortised risk of prosthetic valve endocarditis, thromboembolism and the risks of either bioprosthetic valve dysfunction and/or warfarin anticoagulation that are substantially greater than for patients undergoing repair.

Overall, patients with ischaemic MR have significant morbidity and poor prognosis and we need to find innovative, efficacious therapeutic options for these patients. The ideal operation for ischaemic MR is yet to be discovered. It should be a repair (rather than a replacement), result in durable relief of MR and it should be reproducible. We should ‘look under the annulus’ as this may hold the key for an improved therapy for ischaemic MR.

References

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Footnotes

  • Contributors All authors contributed to initial draft and final editing of this article.

  • Funding This study was funded by the National Institute of Health/NHLBI.

  • Competing interests JH is on SAB of Chordalign. JSG is consultant for Edwards Lifesciences. GA is consultant for Abbott, Edwards Lifesciences, Medtronic and Cephea.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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