Mitral annular calcification (MAC), which can produce mitral regurgitation (MR), mitral stenosis or both, is among the most challenging conditions to manage in cardiovascular medicine due to anatomic and patient complexity. Therapeutic options for patients with MAC have been medical therapy or surgery, but transcatheter therapies have opened the door to minimally invasive management.

Initially, the SAPIEN valve was promising as a transcatheter therapy for MAC given the ease and familiarity of use as operators have experience with these systems for the treatment of aortic stenosis. However, broad uptake has been limited by variable technical success and inconsistent durability of these valves in the treatment of MAC.

In the valve-in-MAC arm of the MITRAL trial, for instance,¹ transcatheter mitral valve replacement (TMVR) using the SAPIEN valve (Figure) demonstrated procedural feasibility in patients with MAC at high surgical risk and was associated with improvements in NYHA functional class. But procedural success was achieved in only approximately half of treated patients, highlighting the technical challenges of anchoring aortic balloon-expandable valves within heavily calcified mitral annuli.

Moreover, there were substantial risks postprocedure, including a 34.5% risk of mortality at one year. Early mortality was driven largely by left ventricular outflow tract (LVOT) obstruction, the most dreaded complication of TMVR in which the anterior mitral leaflet is displaced into the LVOT, reducing cardiac output, particularly in patients with small or hyperdynamic LV cavities.

Late mortality, in contrast, was due primarily to comorbidity burden and overall poor health substrate.

The ongoing MITRAL II trial (NCT04408430) is studying a larger cohort of patients with MAC being treated with the SAPIEN valve, but at present, the use of the SAPIEN valve for the treatment of MAC remains an off-label procedure. 

In contrast, Tendyne and M3 (Figure) are dedicated TMVR devices which are now approved by the U.S. Food and Drug Administration for use in patients with MAC.

In the SUMMIT-MAC trial, TMVR with Tendyne, a transapical transcatheter device, was feasible and technically successful in 94.2% of patients with mitral valve disease due to MAC.² There were significant improvements in heart failure symptoms, with 87.5% of patients having NYHA class I/II symptoms after treatment.

Additionally, quality of life metrics as evaluated by the Kansas City Cardiomyopathy Questionnaire improved substantially.

Dedicated Mitral Devices

The ENCIRCLE trial evaluated the transseptal mitral-specific system, M3, for the treatment of patients with MR. Although the trial did not have a dedicated MAC arm, 24% of enrolled participants had comorbid MAC. The M3 device was associated with a significant reduction in MR severity, a lower mortality rate (13.9%) than was observed in MITRAL, and substantial improvements in functional status and quality of life.³

Despite the development of dedicated mitral devices, many patients (upwards of 70%) are not candidates for these devices due to anatomic limitations including mitral annulus size and the potential risk for LVOT obstruction. Careful patient selection is crucial when considering transcatheter therapies for the treatment of MAC.

Computed tomography is necessary when planning TMVR as it allows operators to gain a detailed understanding of annular calcium distribution and to obtain an accurate estimation of the neo-LVOT after TMVR.⁴

Such planning also helps the heart team understand a patient's risks and benefits for TMVR and guides adjunctive therapies that may facilitate procedural success, including septal reduction (i.e., with alcohol septal ablation or SESAME) or preemptive leaflet modification (i.e., with the LAMPOON procedure).^5-7

In the Pipeline

Other devices are in development to potentially overcome the concern for LVOT obstruction, including the AltaValve. AltaValve consists of a supra-annular left atrial anchored system (Figure) which avoids LV anchoring altogether, lessening the risk of LVOT obstruction and ventricular device migration.

In an early feasibility study, AltaValve saw a 96% procedural success rate, and the device was safe and associated with good valve function at six months in patients requiring mitral valve replacement for MR.⁸ Randomized data and longer term follow-up in patients with MAC are required to definitively understand the efficacy of the device.

Looking Ahead

Treatment of MAC is an ongoing challenge. Nonetheless, the future of transcatheter therapy for MAC is bright as advances in dedicated, mitral-specific, TMVR platforms offer promising treatment options for this historically undertreated, high risk patient population.

References

1. Eleid MF, Wang DD, Pursnani A, et al. 2-Year outcomes of transcatheter mitral valve replacement in patients with annular calcification, rings, and bioprostheses. JACC. 2022;80:2171-2183.
2. Sorajja P, Thourani VH, Rogers JH, et al. Transcatheter mitral valve replacement for severe mitral annular calcification: primary outcomes from the SUMMIT-MAC Study. JACC. 2025:S0735-1097(25)09942–5.
3. Guerrero ME, Daniels DV, Makkar RR, et al. Percutaneous transcatheter valve replacement in individuals with mitral regurgitation unsuitable for surgery or transcatheter edge-to-edge repair: a prospective, multicountry, single-arm trial. The Lancet. 2025;406:2541-2550.
4. Reid A, Ben Zekry S, Turaga M, et al. Neo-LVOT and Transcatheter Mitral Valve Replacement. JACC: Cardiovasc Imaging. 2021;14:854-866.
5. Greenbaum AB, Ueyama HA, Gleason PT, et al. Transcatheter myotomy to reduce left ventricular outflow obstruction. JACC. 2024;83:1257-1272.
6. Lisko JC, Babaliaros VC, Khan JM, et al. Tip-to-base LAMPOON for Transcatheter mitral valve replacement with a protected mitral annulus. JACC: Cardiovasc Intervent. 2021;14:541-550.
7. Wong N, Lim DS, Yount K, et al. Preemptive alcohol septal ablation prior to transcatheter mitral valve replacement. Catheter Cardiovasc Interv. 2023;102:1341-1347.
8. Généreux P, Wróbel K, Ninios V, et al. 6-Month outcomes of a supra-annular transcatheter mitral valve replacement. JACC: Cardiovasc Intervent. 2025;18:2584-2592.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention

Keywords: Cardiology Magazine, ACC Publications, CM-Jul-Aug-2026, Transcatheter Aortic Valve Replacement, Vascular Calcification, Mitral Valve, Interventional Cardiology