Transseptal transcatheter mitral valve replacement (TMVR) with the SAPIEN M3 system among patients with symptomatic mitral annular calcification (MAC)-related mitral valve dysfunction (MVD) was associated with sustained mitral regurgitation (MR) reduction and improved symptoms and quality of life at one year, according to results from the ENCIRCLE MAC Registry published Oct. 14 in JACC.

The MAC Registry enrolled 364 patients with MAC-related MVD who were not eligible for the main cohort of the prospective, multicenter, single-arm ENCIRCLE trial, which studied the SAPIEN M3 system.

Of these, 258 were not eligible for anatomical reasons (51%), not meeting inclusion criteria (16%) or clinical or other reasons (5%), and six exited before treatment. The study cohort thus included 100 patients (mean age 76 years; 49% women; mean LVEF 55%) in whom TMVR was attempted.

All had significant MAC: 71% of patients had MR ≥3+ (including 21 patients with moderate or severe stenosis), 19% had MR 2+ with at least moderate stenosis and 10.0% had severe stenosis with MR <2+. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality score for mitral valve replacement was 8.4%, and 73% of patients were in NYHA functional class III or IV heart failure. Comorbidities included congestive heart failure (68%), atrial fibrillation (66%), previous stroke (14%) and previous aortic valve replacement (48%).

The SAPIEN M3 valve was successfully implanted in 93% of patients. Seven procedures were aborted due to encircling difficulties (n=6) or failure to gain access to the medial commissure (n=1). Seven major cardiac structure complications occurred during the procedure, resulting in one intraprocedural death. Median procedure time was 119.5 minutes, mean hospital length of stay was 3.2 days and 89% of patients were discharged home. At 30 days, the Kaplan-Meier estimate for all-cause mortality was 6% (n=6), all cardiovascular.

At one year, the Kaplan-Meier estimate for the primary endpoint of all-cause mortality or heart failure hospitalization (HFH) was 34%. The estimates for all-cause mortality, HFH and cardiovascular mortality individually were 21%, 19%, and 15%, respectively.

At one year, 99% of implanted patients had MR ≤1+. Other one-year outcomes included disabling stroke (5%), clinically significant left ventricular outflow tract obstruction (5%), clinically significant valve thrombosis (2%), hemolysis requiring transfusion or mitral valve reintervention (9%) and mitral valve reintervention (11%).

Among patients with available assessments, 88% were in NYHA functional class I/II at one year compared with 27% at baseline (p<0.001). Mean KCCQ-OS score increased by 18.5 points, with 43% of patients exhibiting a ≥20-point improvement compared with baseline, and mean six-minute walk distance increased by 31 m (p<0.05), with 35% of patients experiencing a ≥50 m improvement.

"Fully percutaneous transseptal TMVR may offer a viable treatment pathway for select patients with limited therapeutic options," study authors Mayra E. Guerrero, MD, FACC, and colleagues conclude. "However, successful clinical implementation requires rigorous patient selection, experienced valve centers and careful management of procedural and postprocedural risks. Longer-term follow-up will help define durability, late clinical outcomes and patients most likely to derive meaningful clinical benefit from transseptal TMVR."

"ENCIRCLE MAC represents meaningful progress for a population in which therapeutic options remain limited," write Lucy M. Safi, DO, FACC; Sahil Khera, MD, FACC; and JACC: Case Reports Editor-in-Chief Gilbert H.L. Tang, MD, MSC, MBA, FACC, in an accompanying editorial comment. However, they caution that the high screen-failure rate limits the generalizability of the findings and point to the high one-year mortality and HFH rates. "The next frontier for TMVR in MAC may, therefore, shift toward identifying patients for whom valvular replacement would translate into a more meaningful benefit." They write this requires moving beyond conventional and surgical risk scores toward a comprehensive patient assessment that incorporates anatomy, left and right ventricular function, pulmonary hypertension, frailty, life expectancy and patient-centered goals.