Influence of device evolution in MitraClip and PASCAL systems on clinical outcomes in high-risk patients with degenerative mitral regurgitation and complex anatomy: results from the PRIME-MR registry

Abstract Background Mitral transcatheter edge-to-edge repair (M-TEER) has revolutionized the treatment of degenerative mitral regurgitation (DMR) in surgical high-risk patients (pat), as an effective alternative to surgery. Ongoing advancements in the MitraClip (MC) and PASCAL (PAS) systems aim to enhance procedural precision, safety, and reduction of mitral regurgitation (MR). Purpose To evaluate the efficacy and safety of different generations (gen) of the MC and the PAS systems in pat with DMR. Methods 2,312 DMR pat of the PRIME-MR Registry treated by M-TEER between 2008 and 2022 across 24 high-volume centers, were included. Residual MR (resMR) and MVARC defined complications (compl.) based on the use of different MC and PAS gen were evaluated as primary efficacy and safety endpoints. Results Among 2,312 pat (54.6% male, mean EuroSCOREII: 5.3% ± 4.5, median age: 82 interquartile range (IQR) 76; 86), age was the primary reason for surgical denial (44.8%). Leaflet prolapse was the predominant pathology (53.6%), with an eccentric regurgitation jet in 44.8%. The mean effective regurgitant orifice area (EROA) was 0.4 cm² (0.2-0.6 cm²). Pat were categorized into four groups: 971 with MC Gen 1/2, 795 with MC Gen 3, and 457 with either MC Gen 4 or PAS Ace/P10. Anatomical complexity increased with newer gen, reflected in greater anterior-posterior diameters (Gen 1/2: 34.0 mm 30.1-39.0 vs. Gen 3: 37.0 mm 33.0-41.0 vs. Gen 4/PAS: 35.0 mm 32.0-39.0; p 0.001), length of anterior (Gen 1/2: 23.9 mm 20.9-27.3 vs. Gen 3: 26.0 mm 22.7-29.0 vs. Gen 4/PAS: 25.0 mm 22.0-29.0; p 0.001) and posterior mitral leaflet ( Gen 1/2: 13.0 mm 11.0-15.1 vs. Gen 3: 14.0 mm 12.0-16.8 vs. Gen 4/PAS: 14.0 mm 11.0-17.3; p 0.001) as well as greater mitral valve orifice area (Gen 1/2: 4.1 cm2 3.4-5.1 vs. Gen 3: 5.0 cm2 4.0-6.0 vs. Gen4/PAS: 4.8 cm2 4.0-5.9; p 0.001). Technical success remained consistent across all gen, with higher rates of MR ≤1+ at discharge in later gen (Gen. 1/2: 13.7% vs. Gen. 3: 17.1% vs. Gen. 4/PAS: 24.3%; p0.001). The proportion of resMR ≥2+ at discharge tended to be lower in later gen. ( Gen. 1/2: 36.3% vs. Gen. 3: 33.6% vs. Gen. 4/PAS: 30.1%; p=0.069). MVARC-defined compl. were most frequent with earlier gen. (freedom from bleeding compl.: Gen. 1/2: 90.3% vs. Gen. 3: 94.1% vs. Gen 4/PAS: 96.3%; p0.001; freedom from vascular compl.: Gen. 1/2: 86.7% vs. Gen. 3: 96.6% vs. Gen. 4/PAS: 96.9%; p0.001). ResMR remained the primary reason for reintervention, though reintervention rates were higher with earlier gen (Gen. 1/2: n=70 82.4% vs. Gen. 3: n=30 61.2% vs. Gen. 4/PAS: n=9 39.1%; p0.001). At one-year follow-up, pat treated with newer gen demonstrated significant symptom improvement (NYHA class ≤II: Gen. 1/2: 75.5% vs. Gen. 3: 83.6% vs. Gen. 4/PAS: 81.7%; p=0.023). Conclusion Advancements in the MC and PAS gen have improved procedural efficacy and safety while enabling treatment of increasingly complex valve anatomies in DMR.