Impact of simulated MitraClip on forward flow obstruction in the setting of mitral leaflet tethering

Abstract

Mitral regurgitation (MR) is the most common valvular disease; significant levels of MR are found in 6.4% of the population between 65 and 74 years of age, and 9.3% of the population over 75 years of age. Surgical repair or replacement of the mitral valve (MV) is the current gold-standard for treatment of MR, and requires open-heart surgery. Many patients with MR in the older population subgroups have co-morbidities and are considered high risk for open heart surgery. In a recent study, among patients with severe symptomatic MR, nearly 50% were denied surgery based on comorbidities. The need for solutions to treat these high-risk patients has inspired a host of new minimally invasive endovascular repair devices. The catheter-based MitraClip device (Abbott Vascular, Santa Clara, CA) is currently the only widely-used and FDA approved endovascular mitral repair device, with over 35,000 patients treated worldwide to-date. MitraClip works by clipping the mitral leaflets together at the site of MR. This closes the regurgitant orifice, while still allowing the leaflets to open to either side of the device, thereby creating a “double orifice”. Although the device is widely used, it is not without flaw. A fundamental issue with MitraClip is the risk of obstructing forward flow of blood into the left ventricle (LV). By clipping the mitral leaflets together, the MitraClip inherently reduces the MV orifice area, and, in certain cases, can elevate the diastolic pressure gradient across the valve. This is known as Mitral Stenosis (MS), and can lead to increased mortality in patients. Recent limited-size studies have shown that risk of creating MS can be greater in certain patients with restricted mitral leaflet motion, or leaflet tethering. Leaflet tethering is often seen in Functional Mitral Regurgitation (FMR), where underlying disease and remodeling of the LV causes papillary muscle displacement and increased tension on the chordae and leaflets. MitraClip is currently not indicated for use in this large population of MR patients, but ongoing large-scale clinical studies are seeking to determine its safety and effectiveness in FMR. The purpose of this study is to quantify MS severity under different levels of leaflet tethering, and with placement of MitraClip in different locations. In the first specific aim of this study, an in vitro model capable of simulating MV function and leaflet tethering on excised ovine MV samples was developed, along with custom-designed and machined MitraClip prototypes. In the second specific aim, these tools were used to evaluate the forward flow performance of the MitraClip prototype devices in the setting of mitral leaflet tethering. This first-of-its-kind study will provide valuable information on MitraClip performance, and aid cardiologists in determining the suitability of different MitraClip treatments for the large population of FMR patients.