The presence of MAC is surgically challenging. Any amount of MAC increases operative mortality and complications [59]. Patients with MAC-related MVD confront two major risks: elevated surgical risk attributed to very old age and multiple comorbidities and anatomical risk determined by the amount of MAC. Both risks guide the selection of interventions [60].
Surgical techniques can be broadly categorized into two groups: MV surgery with MAC resection and annulus reconstruction and MV surgery without MAC resection [61], also termed as resect vs. respect [62]. The resection technique carries risks of atrioventricular groove dissociation, LV perforation, and injury to the left circumflex artery. Conversely, the respect approach presents increased risk of paralvular leak due to suboptimal suture anchoring to the calcified annulus and the tendency to use a smaller valve with the risk of valve prosthesis mismatch [61,62].
In a systematic review [63], 15 surgical studies reported wide ranges of mortalities at 30 days, 1 year, and 5 years: 0% to 27.3% (median 6.3%), 0–17% (median 15.8%), and 0–68.6% (median 38.8%), respectively. Variances in mortality rates are likely attributable to broad surgical and anatomical risks that may he been underreported in some studies. Whether the minimally invasive surgical approaches [64,65,66] can benefit patients with MAC-related MR is unclear.
For patients with low surgical risk and anatomically feasible conditions, the surgical option remains the optimal choice for managing degenerative MVD.
For patients with very high surgical or anatomical risk, or both, the transcatheter approach is being considered increasingly often. The first case of human transcatheter mitral valve replacement (TMVR) was reported in 2009 by Cheung et al. [67] using the transapical approach for the valve-in-valve (ViV) TMVR.
Commonly, TMVR is performed using a transfemoral transeptal approach with a balloon-expandable valve (SAPIEN valve from Edwards Lifesciences LLC) originally designed for transcatheter aortic valve replacement (TR) [68]. Transapical or direct transatrial approaches he also been used [68].
The median age was 75 years in a systematic review of 13 studies encompassing 354 patients who underwent transseptal or transapical TMVR [63]. The technical success rate for transeptal TMVR was 75%, with LV outflow tract (LVOT) obstruction occurring in 11.2%. The median in-hospital, 30-day, and 1-year mortality rates for TMVR in patients with MAC were 16.7%, 22.7%, and 43%, respectively.
The mean age was 79 years and the New York Heart Association (NYHA) functional class was III-IV in an early cohort of 12 patients who underwent TMVR for MAC-related MVD [69]. In total, 67% of patients had mitral stenosis and 25% had mixed MAC-related MVD. One patient developed LVOT obstruction and later died. Three patients displayed valve migration, one with complete embolization to LA requiring bailout surgery and two with slight valve migration resulting in severe paralvular leak. Survival rates at 30 days and 1 year were 83% and 57%, respectively, with 9 out of 10 surviving patients reporting improved exercise tolerance at 30 days and 3 out of 4 patients reporting improved symptoms at 1 year.
Although the survival of patients with MAC was initially poor after TMVR, selection and procedural insights he been gained. Patients with a modest amount of MAC are prone to valve embolization and migration due to insufficient calcium for anchoring. Unexpectedly, a sizeable amount of MAC proved forable for procedural success. Identification of patients prone to LVOT obstruction helped reduce procedural mortality.
The two largest cohorts of TMVR in MAC, the MAC global registry (n = 106) [70] and STS/ACC/TVT registry (n = 100) [71], reported LVOT obstructions in 11.2% and 10% of patients, respectively. Strategies were devised to mitigate LVOT obstruction and reduce procedural mortality. The first strategy, reported in the MITRAL trial [72], involved preemptive alcohol septal ablation 3–4 weeks before TMVR. The strategy was carried out in seven patients who were identified as being at high risk of LVOT obstruction. It was technically successful, and all seven patients survived the 30-day period. The second strategy, tested in a small single-arm trial, included 30 patients with indication for TMVR in MAC or annuloplasty ring. The strategy involved transcatheter intentional laceration of the anterior mitral valve leaflet (LAMPOON) [73] and resulted in an 87% survival rate at 30 days post-op in patients with MAC. The strategy intended to copycat the anterior leaflet resection during surgical MVR. In patients with MAC, TMVR remains a very high-risk intervention that may benefit highly selected patients who failed optimal medical therapy of co-existent conditions like HFpEF and COPD. Further, TMVR should be performed in experienced centers for patients with forable anatomy.
Experience with transcatheter edge-to-edge repair (TEER) is limited in patients with MAC-related MR, as severe MAC was one of the exclusion criteria in the EVERESTII trial [74]. Nevertheless, TEER appears safe in selected patients with moderate-to-severe MAC [75,76,77,78]. Patients with MAC-related MR and mitral valve area < 4cm2, calcification extending to the margin of the leaflets and coexisting MS are not candidates for TEER [76].