The PASCAL System – Promising Results for Complex Degenerative Mitral Regurgitation

The PASCAL system for transcatheter edge-to-edge repair (TEER) for degenerative mitral regurgitation (DMR) demonstrates favorable outcomes in those with complex mitral valve anatomy.¹

The advent of Mitral TEER (M-TEER) has revolutionized the management of both primary (a.k.a. degenerative) and secondary (a.k.a. functional) mitral regurgitation by offering a safe, effective, and minimally invasive alternative to open heart surgery in select patients. For DMR, the 2020 ACC/AHA Guideline for valvular heart disease (VHD) offer a Class 2a recommendation for M-TEER in severely symptomatic patients (NYHA class III or IV) with primary severe MR and high or prohibitive surgical risk if mitral valve anatomy is favorable and life expectancy is at least 1 year.² Similarly, the 2021 ESC/EACTS Guidelines for VHD give M-TEER a Class 2B in symptomatic patients who fulfil the echocardiographic criteria of eligibility, are judged inoperable or at high surgical risk by the Heart Team and for whom the procedure is not considered futile.³

These recommendations are largely based on the results of EVEREST II, a randomized trial comparing TEER with the MitraClip system (Abbott) versus surgery in a 2:1 randomization of 279 patients with moderately severe or severe (grade 3+ or 4+) MR.⁴ The primary composite endpoint for efficacy – freedom from death, from surgery for mitral valve dysfunction, and from grade 3+ to 4+ mitral regurgitation at 12 months – favored surgery primarily driven by increased rate of mitral valve surgery in the MitraClip group due to severe residual MR. Nevertheless, 78% of patients treated with M-TEER had ≤ 2+ MR and 33% had ≤ 1+ MR at 1 year. At 5 year follow-up, the surgical group continued to experience a greater reduction in MR; however, the TEER group had durable reduction in MR severity associated with reverse left ventricular (LV) remodeling and sustained improvements in symptoms and quality of life.⁵ Overall, the EVEREST II trial showed that M-TEER is a viable alternative to surgery in appropriately selected patients with favorable anatomy and who are deemed to have high operative risk.

Importantly, EVEREST II outcomes must be interpreted within the context of strict anatomic feasibility criteria including primary regurgitant jet cause by a central A2/P2 malcoaptation and mitral valve area (MVA) > 4.0 cm². Those with fail segment width ≥ 15mm, flail gap ≥ 10mm, severe bileaflet prolapse, and calcification in the grasping zone were excluded. While M-TEER is increasingly utilized for complex mitral valves with features outside these parameters, outcomes data to support this clinical application creep remains limited.

Hausleiter and colleagues now reveal results from PASCAL IID, a prospective, multicenter, single-arm registry of 98 patients with symptomatic 3+ (29.9%) or 4+ (69.1%) DMR, complex mitral valve anatomy, and prohibitive surgical risk who were treated with M-TEER using the PASCAL system (Edwards). Patients had at least one of the following complex mitral valve anatomic features: moderate to severe calcification in the grasping area, severe bileaflet/multiscallop prolapse, significant cleft or perforation in the grasping area, leaflet mobility length < 8 mm, ≥ 2 independent significant jets, 1 significant jet in the commissural area, or MVA < 4.0 cm².

Of the 98 patients enrolled (mean age 81.1 years, 82.7% considered frail, 61.2% men, and 69.4% with NYHA functional class III/IV), 37.2% had ≥ 2 independent significant jets, 15% had severe bileaflet/multiscallop prolapse, 13.3% had an MVA < 4.0 cm², and 10.6% had a large flail gap and/or width. Despite this, implant success rate was 92.9%. At 6 months, 92.4% had ≤ 2+ MR and 56.1% had ≤ 1+ MR (P < 0.001 vs baseline) with significant symptomatic and functional improvement compared with baseline. Kaplan-Meier estimates for survival, freedom from major adverse events, and heart failure hospitalizations at 6 months were 93.7%, 85.6%, and 92.6%, respectively. The 30-day composite major adverse event rate was 11.2%, comprising cardiovascular mortality (N = 1), stroke (N = 1), myocardial infarction (N = 1, new need for renal replacement therapy (N = 1), and nonelective mitral valve intervention (N = 1), and severe bleeding events (N = 7).

The PASCAL IID registry provides encouraging results for M-TEER with the PASCAL system in frail and elderly inoperable DMR patients with complex anatomy. Caution should be exerted in younger and low or medium-risk patients for whom surgery remains the de facto Class I recommendation.

References

1. Hausleiter J, Lim DS, Gillam LD, et al. Transcatheter Edge-to-Edge Repair in Patients With Anatomically Complex Degenerative Mitral Regurgitation. J Am Coll Cardiol. 2023;81(5):431-442. doi:10.1016/j.jacc.2022.11.034
2. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Vol 143.; 2021. doi:10.1161/CIR.0000000000000923
3. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease: Developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Rev Esp Cardiol (Engl Ed). 2022;75(6):524. doi:10.1016/j.rec.2022.05.006
4. Feldman T, Foster E, Glower DG, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011. doi:10.1056/NEJMoa1009355
5. Feldman T, Kar S, Elmariah S, et al. Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation 5-Year Results of EVEREST II. J Am Coll Cardiol. 2015;66(25):2844-2854. doi:10.1016/j.jacc.2015.10.018