Learning from Controversy and Revisiting the Randomized Trials of Secondary Mitral Regurgitation.

Until recently, conventional mitral valve surgery has been the treatment of choice even in secondary mitral regurgitation. Recent evidence, however, advocates the use of transcatheter edge-to-edge mitral valve repair (TEER) of the mitral valve. This has been reflected by the change in guidelines of the American College of Cardiology/American Heart Association. We reviewed the literature to shed light on the risks and benefits of all interventions, surgical, transcatheter and guideline-directed medical therapy. Secondary mitral regurgitation occurs due to an imbalance between closing forces and tethering forces. Given the pathology extends beyond the valve alone, treatment should be directed at restoring the geometrical shape of the left ventricle alongside the valve. Myocardial revascularization plays a pivotal role in preventing recurrence. The role of papillary muscle approximation in addition to restrictive mitral annuloplasty should be considered in a select group of patients. We also reviewed the current literature on TEERs from the COAPT and Mitra-FR trials while highlighting the concept of proportionate/disproportionate MR which may help identify which patients benefit from mitral valve restoration. Treatment of this condition will require robust randomized trials alongside the use of state-of-the-art imaging technologies available with the full complement of the multidisciplinary team to ensure the best outcomes for each patient.

Adjuncts to annuloplasty in atrial functional mitral regurgitation.

Atrial fibrillation is the most common cardiac arrhythmia, leading to progressive dilation of cardiac chambers, abnormal contraction patterns of the atria and ventricles and, potentially, atrioventricular valvular insufficiency. Moreover, heart failure with preserved ejection fraction is often present and closely intertwined with disease initiation and progression. Surgical valve repair with a true-sized ring annuloplasty is a well-established treatment option in atrial functional mitral regurgitation. While early results are good, recent studies have brought the durability of this repair approach into question, highlighting the need for further refinement of the surgical strategy. In particular, repair strategies that simultaneously target the mitral valve as well as the left ventricle could provide improved repair durability.

Subannular repair for functional mitral regurgitation with reduced systolic ventricle function: rationale and design of REFORM-MR registry.

BACKGROUND: Functional mitral regurgitation (FMR) is one of the most common heart valve diseases that is a sequel of left ventricular remodelling. Although mitral valve annuloplasty is a standard treatment of FMR, the recurrence of FMR is a major drawback and occurs in 10-50% of patients. The REFORM-MR registry aims to investigate the effectiveness of standardized papillary muscle relocation and ring annuloplasty and to identify the risk factors associated with recurrent FMR. METHODS: REFORM-MR is a prospective, multicenter registry that enrols consecutive FMR patients across five sites in Germany. All patients with FMR and restricted movement of leaflets during systole (i.e., type IIIb mitral regurgitation) undergoing standardized subannular repair in combination with mitral valve annuloplasty are included in the study. The primary objective is to examine the effect of combined papillary muscle relocation and ring annuloplasty on the recurrence of FMR at 2 years postoperatively. The secondary objectives are MACCE rate, reinterventions on the mitral valve and cardiac-related mortality in the study cohort. Echocardiography core-lab and MRI core-lab will provide anonymized analysis of the imaging data in the REFORM-MR registry. Student's t-test or Mann-Whitney U test for continuous variables and the Chi-Square or Fisher exact test for categorical variables are used for group comparisons. Kaplan-Meier analyses is performed for survival and safety outcomes. RESULTS: As of May 2021, a total of 97 patients were enrolled across five sites in Germany. CONCLUSIONS: The results of this study will help define the outcomes of combined papillary muscle relocation and ring annuloplasty in the FMR treatment in a multicentre setting and to improve the understanding of the limitations of subannular repair procedures while treating patients with type III FMR. Trial registration clinicaltrials.gov Identifier: NCT03470155.

Left ventricular reverse remodeling after successful subannular mitral valve repair in end-stage heart failure: a case report.

BACKGROUND: Due to ongoing left ventricular (LV) remodeling and consecutive geometric displacement of both papillary muscles, end-stage heart failure is frequently associated with relevant functional mitral regurgitation (FMR) Type IIIb. Treatment strategies of FMR and their prognostic impact are still controversial. CASE SUMMARY: We present a case of an 80-year-old patient who suffered from recurrent symptoms of congestive heart failure due to dilated cardiomyopathy and concomitant severe FMR. To specifically address severe tethering of both mitral leaflets heart team decision was to perform minimally invasive mitral valve repair (MVR) including a subannular LV remodeling procedure, instead of an interventional edge-to-edge repair (MitraClip® procedure). In addition to mitral valve ring annuloplasty, standardized relocation of both papillary muscles was performed successfully, leading to a complete resolution of mitral leaflet tethering. There were no procedural complications and the patient was discharged with an excellent functional result without residual mitral regurgitation. Furthermore, after 12 and 24 months, he reported an increase of his functional exercise capacity and a remarkable reverse LV remodeling could be demonstrated. DISCUSSION: Novel subannular repair techniques, especially the relocation of both papillary muscles, specifically address severe leaflet tethering in FMR and have an obvious potential to improve long-term competence of MVR. Therefore, they could be considered as a viable therapeutic option even in elderly patients presenting with end-stage cardiomyopathy and severe leaflet tenting.

Standardized subannular repair for type IIIb functional mitral regurgitation in a minimally invasive mitral valve surgery setting†.

OBJECTIVES: Subannular repair techniques in addition to undersized ring annuloplasty have been developed to address high mitral regurgitation (MR) recurrence rates after mitral valve repair in type IIIb MR. We compared the results of annuloplasty with simultaneous standardized subannular repair versus isolated annuloplasty, focusing on the periprocedural outcomes of minimally invasive procedures. METHODS: A consecutive series of 108 patients with type IIIb functional MR with severe signs of bileaflet tethering underwent an annuloplasty + subannular repair (group A; n = 60) versus isolated annuloplasty (group B; n = 48). The primary end point of this prospective, parallel cohort study was death or recurrent MR >2, 1 year postoperatively. The secondary end points were survival and clinical outcomes, with special regard for the minimally invasively treated subgroups. RESULTS: Duration of surgery, cardiopulmonary bypass time and aortic cross-clamp time were comparable between both study groups. Procedural outcomes as well as echocardiographic outcome parameters were similar and independent of access (fully endoscopic versus full sternotomy). At the 12-month follow-up, death or MR >2 occurred in 3.3% (2/60) of patients in group A vs in 20.8% (10/48) of patients in group B (P = 0.037). The overall mortality rate during the follow-up period was 1.7% (1/60) in group A vs 12.5% (6/48) in group B (P = 0.041). CONCLUSIONS: Standardized realignment of papillary muscles is feasible and reproducible via a minimally invasive approach, resulting in excellent periprocedural outcomes, and has a clear potential to significantly decrease MR recurrence and improve 1-year outcomes compared to isolated annuloplasty.

Minimally invasive mitral valve repair for functional mitral regurgitation.

Systolic heart failure is frequently accompanied by a relevant functional mitral valve regurgitation (FMR) which develops as a direct sequela of the ongoing left ventricular remodelling. The severity of mitral regurgitation is further aggravated by progressive left ventricular enlargement causing leaflet tethering and reduced systolic leaflet movement. The prognosis of such patients is obviously limited by an underlying left ventricular disease, and the correction of secondary FMR has been previously suggested as predominantly 'cosmetic' surgery in the setting of ongoing cardiomyopathy. Inferior results of an isolated annuloplasty in type IIIb FMR supported the philosophy of malignant course of progressive cardiomyopathy and resulted in increasingly restricted indications for mitral valve surgery for FMR in the guidelines. The lack of a standardized pathophysiological approach to correct type IIIb FMR led to the development of valve replacement strategy and edge-to-edge catheter-based mitral valve procedures, which became the most frequent procedures in the FMR setting in Europe. Modern mitral valve surgery combines the advantages of 3-dimensional endoscopic minimally invasive surgical approach with standardized subannular repair to address the pathophysiological background of type IIIb FMR. The perioperative results have been significantly improved, and there is a growing evidence of improved long-term stability of subannular repair procedures as compared to isolated annuloplasty. This review article aims to present the current state-of-the-art of the modern mitral valve surgery in FMR and provides suggestions for future trials analysing the potential advantages in these patients.

Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation.

Background Undersized ring annuloplasty is a commonly used surgical repair for ischemic mitral regurgitation, in which annular downsizing corrects regurgitation, but alters valve geometry and elevates tissue stresses. In this study, we investigated if unphysiological leaflet kinematics after annuloplasty might cause pathogenic biological remodeling of the mitral valve leaflets, and if preserving physiologic leaflet kinematics with a better technique can moderate such adverse remodeling. Methods and Results Twenty-nine swine were induced with ischemic mitral regurgitation, and survivors were assigned to groups: 7 underwent annuloplasty, 12 underwent annuloplasty with papillary-muscle approximation, 6 underwent papillary-muscle approximation, and 3 were sham controls. Pre-and post-surgery leaflet kinematics were measured, and valve tissue was explanted after 3 months to assess biological changes. Anterior leaflet excursion was unchanged across groups, but persistent tethering was observed with annuloplasty. Posterior leaflet was vertically immobile after annuloplasty, better mobile with the combined approach, and substantially ( P=0.0028) mobile after papillary-muscle approximation. Procollagen-1 was higher in leaflets from annuloplasty compared with the other groups. Heat shock protein-47 and lysyl oxidase were higher in groups receiving annuloplasty compared with sham. α- SMA was elevated in leaflets from animals receiving an annuloplasty, indicating activation of quiescent valve interstitial cells, paralleled by elevated transforming growth factor-ß expression. Conclusions This is the first study to demonstrate that surgical valve repairs that impose unphysiological leaflet mechanics have a deleterious, pathological impact on valve biology. Surgeons may need to consider restoring physiologic leaflet stresses as well as valve competence, while also exploring pharmacological methods to inhibit the abnormal signaling cascades.