Real-Time Revolution

Mitral regurgitation (MR) is one of the most common valvular heart diseases and has a prevalence of 2% in the general population.¹ MR is a predictor of a 2.3-fold increase in 5-year mortality compared with similar individuals without MR.² For patients with severe disease, transcatheter mitral valve replacement (TMVR) has recently gained recognition as a surgical alternative. However, unlike transcatheter aortic valve replacement, TMVR presents various technical challenges, mostly related to the valve’s irregular, dynamic anatomy, presence of mitral annular calcifications (MAC), and proximity to the left ventricular outflow tract (LVOT).

The screening failure rate for existing pre-sized and pre-shaped TMVR devices is high, with studies reporting rates reaching up to 80%,³ and they are commonly associated with LVOT obstruction (LVOTO) and paravalvular leaks (PVLs).⁴ To overcome existing challenges, the next-generation TMVR device is anticipated to fit a wide range of anatomies, ensure compatibility regardless of MAC, significantly reduce the risk of LVOTO, and improve efficacy by minimizing PVLs.⁵ For a wide adoption, the procedure is expected to be retrievable and have clear procedural steps and guidelines.

“Dynamic device for a dynamic anatomy" defines the ValSync (Symbiosis CM Ltd) device approach, inspired by the principle of “form follows function” in medical design, to address the ever-changing dynamics of the mitral valve. ValSync is a transfemorally delivered TMVR device that can be shaped in real time to fit patients’ unique valvular anatomy through 2 compliant shapeable balloons that adapt to the native valve structure, providing adjustable anchoring and preventing PVLs. Stable positioning is assured by the “sandwich effect” of the 2 balloons and adjustable nitinol stent barbs controlled by the ventricular balloon inflation (Figure 1A). Adjustment to the anatomy is made solely through a simple balloon inflation with saline (Figure 1C).

Figure 1.

ValSync Structure, Implantation Steps, and Attributes

(A) Device description. Note the change in the degree of the barbs as a function of ventricular balloon inflation. (B1 to B3) Procedural steps of the device. (C1) Echocardiographic image of ValSync, demonstrating posteromedial leak and immediate leak elimination post inflation adjustment shown in (C2). (D1 and D2) Inflation of the ventricular balloon in a computed tomography image-based three-dimensional printed heart with mitral annular calcifications. Black arrows point at mitral annular calcifications. Note how the ventricular balloon is overriding the calcified region (D2).

ValSync is designed to provide distinct advantages in 3 key areas: eligibility, efficacy, and applicability. The implant’s novel design enhances patient eligibility by accommodating a broad spectrum of mitral annular sizes and shapes. This is achieved through the balloon’s capability to be inflated from an initial diameter of 28 mm to a maximum of 62 mm. The device’s inherent adjustability and flexibility address the limitations of current devices that require precise sizing, thereby including more patients with challenging anatomies; this specifically includes those with MAC due to the balloons’ ability to provide a tight seal and robust anchoring against a highly amorphic, friable, and irregular tissue (Figure 1D). ValSync is also advantageous for patients with atrial functional MR, secondary to permanent atrial fibrillation and/or heart failure with preserved ejection fraction, in whom small left ventricles and a highly dilated left atrium are seen. This advantage is possible due to the device’s adjustable ability to also anchor into normal nondilated ventricles and optimize the seal with an atrial balloon that can inflate up to 62 mm. Minor modifications enable the use of the device in the tricuspid position in the future.

Given that PVL is an independent risk factor for increased mortality, the ability for real-time treatment and elimination of PVLs (Figure 1C) has the potential to reduce morbidity and mortality rates related to the presence of PVLs. In addition, its design has an adjustable anchoring mechanism, minimizing the risk of LVOTO while maintaining robust anchoring (Figure 1A), thereby improving safety.

Finally, yet significantly, ValSync implantation involves a simplified 3-step procedure (Figure 1B), all achieved by balloon inflation, which is potentially easier to perform compared with traditional TMVR techniques that often require specialized expertise and are limited to select centers. The simplicity and retrievability of the ValSync procedure are intended to make TMVR a more routine intervention with a broader adoption among cardiologists, thus increasing the accessibility of this potentially life-altering treatment to a wider array of patients.

The device was implanted in vivo in 13 pigs and was tested for procedural steps, implantation method, positioning, stabilization, and leak management in real time. During these implantations, we did not observe clinically significant LVOTO and were able to optimize subannular anchoring with inflation adjustment of the balloon as well as elimination of PVLs in real time (Figure 1C). The results of these studies indicate procedural feasibility and highlight the importance of an adjustable device for valve replacement procedures.

In addition, serial balloon testing was conducted to determine the optimal size, wall thickness, and inflation volume for chronic animal studies. The long-term durability of the balloons is continuously assessed under body temperature and accelerated conditions. ValSync has achieved readiness for chronic studies in sheep, and the first-in-human multicenter study is scheduled for 2026.