Cephea Pivotal Bets on Replacement Where Repair Fails Without Randomized Proof

Abbott Initiates Pivotal CROWN-MV Trial for Cephea Mitral Valve System

Abbott has initiated the CROWN-MV pivotal trial to evaluate the safety and effectiveness of its investigational Cephea™ Mitral Valve System. This system is designed to treat symptomatic mitral valve disease in patients who are not candidates for conventional surgery or transcatheter repair. The prospective study aims to enroll up to 585 individuals across the U.S., Canada, and Europe, focusing on those with moderate-to-severe or severe mitral regurgitation or mitral annular calcification. Early feasibility study results for Cephea's third-generation delivery system are slated for presentation at TCT 2026, with initial data expected to demonstrate its efficacy in reducing mitral regurgitation and improving patient quality of life.

• The CROWN-MV pivotal trial is a global, prospective study designed to assess the safety and effectiveness of Abbott's investigational Cephea Mitral Valve System. It targets a high-risk patient population with symptomatic mitral valve disease, specifically those with moderate-to-severe or severe mitral regurgitation or mitral annular calcification, who currently lack suitable options for surgical or transcatheter repair.
• The Cephea system offers a minimally invasive transcatheter mitral valve replacement (TMVR) approach. It involves delivering a bioprosthetic (tissue) valve via a catheter inserted through a vein in the leg, which is then guided to the heart and expanded within the diseased mitral valve to restore normal blood flow. This third-generation delivery technology is engineered to address complex mitral anatomies.
• Initial 30-day outcomes from an early feasibility study for the Cephea system's third-generation delivery technology will be presented at the TCT 2026 annual scientific symposium. These forthcoming data are anticipated to highlight the device's performance in effectively reducing mitral regurgitation and contributing to an improved quality of life for patients, further solidifying Abbott's leadership in structural heart innovations.

Why New Options are Crucial for High-Risk MVD Patients

Symptomatic mitral valve disease, predominantly mitral regurgitation (MR), remains a prevalent cause of morbidity in aging and heart failure populations. Recent literature focuses on expanding less-invasive options for patients excluded from conventional surgery and on improving durability and selection for transcatheter interventions.

• High-risk and inoperable patients excluded from surgery due to advanced age, comorbidities, or high surgical risk are a central target for mitral transcatheter edge-to-edge repair (M-TEER) with MitraClip and PASCAL, annuloplasty devices such as Carillon and Cardioband, and transcatheter mitral valve replacement (TMVR) with Tendyne, Intrepid, and others under development.

• Patients with heart failure-related secondary or functional MR (FMR) with poor left ventricular systolic function, including high-risk cohorts with NYHA class III or IV symptoms, are targeted in comparisons of M-TEER versus surgical repair or replacement, and in strategies combining guideline-directed medical therapy, cardiac resynchronization, rhythm management, and rapid Heart Team referral for TEER.

• Patients unsuitable for both surgery and TEER due to anatomical complexity are targeted by percutaneous transseptal TMVR, including the SAPIEN M3 system, which showed a primary endpoint rate of 25.2% (95% CI 20.6-30.6) for all-cause mortality and heart failure rehospitalisation at 1 year with no intraprocedural deaths and no left ventricular outflow tract obstruction causing haemodynamic compromise.

• Patients with failed M-TEER with persistent or recurrent MR or iatrogenic mitral valve stenosis, in whom surgery carries higher morbidity and mortality, are targeted by redo transcatheter edge-to-edge repair and by electrosurgical leaflet laceration and stabilization of the implant (ELASTA-Clip) followed by transapical TMVR using the Abbott Tendyne system.

• Patients with severe MR due to severe mitral annular calcification (MAC), often elderly, frail, and conservatively managed, are targeted by hybrid and transcatheter approaches requiring meticulous pre-procedural planning and customized device strategies, with mitral valve intervention associated with improved survival regardless of frailty status.

• Patients at risk of M-TEER failure and late recurrence, particularly primary MR where 41% experienced MR recurrence or reintervention at 5 years, and patients with cardiogenic shock with significant MR, frailty, and poor health status requiring pre- and post-procedure cardiac rehabilitation, represent additional unmet needs for durable repair, careful selection by MR etiology and ventricular function, and multidisciplinary management.

Abbott's Innovation: Cephea in the Evolving MVD Landscape

Transfemoral transcatheter mitral valve replacement (TMVR) has emerged as a therapeutic alternative for symptomatic mitral valve disease in patients with high surgical risk. The CHOICE-MI (Choice of Optimal Transcatheter Treatment for Mitral Insufficiency) Registry included patients undergoing TMVR with dedicated devices at 41 international centers, with analysis of 124 patients (median age 79 years [Q1-Q3: 75-83 years], 50% women, median European System for Cardiac Operative Risk Evaluation II score 5.0% [Q1-Q3: 3.3-8.5]) undergoing TF TMVR with 9 different devices. The leading MR etiology was primary MR (n = 49 [39.5%]), with mitral annular calcification in 12.9%. Technical success was achieved in 113 of 124 patients (91.1%), and procedural mortality was low (1 of 124 [0.8%]). Residual MR ≤1+ was achieved in 94.9% at discharge, with stable results at follow-up. The rates of cardiovascular mortality were 14.7% (95% CI: 7.9%-21.5%) and 20.3% (95% CI: 11.4%-29.1%) and of the primary endpoint of all-cause mortality or heart failure hospitalization 44.1% (95% CI: 30.6%-50.0%) and 52.4% (95% CI: 40.2%-62.1%) at 1 and 2 years, respectively, and NYHA functional class had significantly improved at 1- and 2-year follow-up.

The single-stage Cephea TF TMVR system extends this evolution in complex anatomies. Thirty-one consecutive high-risk patients with symptomatic mitral valve disease were enrolled under an early feasibility study protocol (n = 24) or treated under compassionate use (n = 7) from August 2021 to June 2024. The cohort mean age was 75.0 ± 8.1 years, with mean Society of Thoracic Surgeons Predicted Risk of Mortality of 6.4% ± 2.9%. All patients had mitral regurgitation (MR) grade ≥III (93.5%) or isolated mitral stenosis (6.5%); 25.8% had severe mitral annular calcification. The prosthetic valve was implanted in 96.8% of attempted subjects (30 of 31), with a mean device time of 56 ± 32 minutes. One subject was converted to surgical bioprosthetic mitral valve implantation. There were no procedural deaths or strokes. The primary safety endpoint of 30-day survival was achieved in 97% of patients (30 of 31); the primary efficacy endpoint of MR reduction to mild or less was achieved in 100% of patients with evaluable echocardiograms (27 of 27).

In parallel, transcatheter edge-to-edge repair (TEER) has broadened with both established and novel systems. The global, real-world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation treated with the MitraClip NTR/XTR System, with consistent 1-year MR reduction to ≤1+ and significant 1-year improvement in KCCQ scores and NYHA functional class, and the HFH rate decreased by 63% at 1 year post-M-TEER versus 1 year pre-treatment (relative risk 0.4, p < 0.001). The COAPT Post-Approval Study of 5,000 consecutive patients with secondary mitral regurgitation treated with the MitraClip at 406 U.S. centers reported a 97.7% MitraClip implant rate, durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6% in full, COAPT-like and MITRA-FR-like cohorts, respectively), and large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR-like). The novel SQ-Kyrin-M system showed in 125 patients with heart failure and moderate-to-severe or severe functional mitral regurgitation a primary endpoint rate of 16.0% (20/125) at 1 year, MR reduced to ≤2+ in 94.2% of patients, left ventricular reverse remodeling (LVEDV reduction: 33.8 ± 55.4 mL, p < 0.001), KCCQ scores increasing by 15.9 ± 18.8 points (p < 0.001) and 6-minute walk distance improving by 46.7 ± 90.7 m (p < 0.001), with NYHA class I/II increasing from 30.4% to 84.4% (p < 0.001). In 120 patients with symptomatic degenerative mitral regurgitation (grade ≥3+), 12-month Kaplan-Meier estimates were 82.5% for clinical success, 7.6% for all-cause mortality, and 10.8% for major adverse events; MR ≤2+ and MR ≤1+ were achieved in 91.7 and 70.4% of the patients, respectively; 88.9% of patients were in NYHA class I or II; and KCCQ score had improved by 18.9 points.