Abstract 14111: Feasibility of Therapeutic Ultrasound Delivery for the Treatment of Mitral Stenosis

Introduction: Currently, the only disease-modifying therapy for degenerative mitral stenosis (DMS) due to mitral annular calcification (MAC) is open surgical valve repair or replacement, but it is technically challenging, and patients with DMS are often at elevated risk of surgical complications. As such, there is an unmet need for less-invasive strategies to treat DMS. Given the ability of shock-wave grade therapeutic ultrasound to disrupt calcifications, we set out to determine whether therapeutic ultrasound may be a possible treatment strategy for DMS. Hypothesis: This study aimed to evaluate whether ex vivo histotripsy can produce internal disruption of calcified nodules in the mitral annulus, a precursor to improving valve function in DMS. Methods: All experiments were performed on a formalin-fixed human cadaveric heart with severe MAC (Figure 1 A). Histotripsy cavitation was directed at calcified nodules utilizing a sonic concepts HIFUPlex Focused 128 element,1.1MHz array therapy transducer (Figure 1 E). B-mode ultrasound imaging was used to guide therapy. Transducer settings were PRF: 60 Hz, Duty cycle: 8x10^-4, transmit frequency: 1.1 MHz, HIFU Voltage: 60 V, resulting in an estimated pressure output of 34.6 MPa_pk. Results: A total of three histotripsy experiments were performed on the primary dominant calcium nodule. Visual assessment of treatment X-ray microtomography (Micro-CT) revealed qualitative fracturing of the calcified nodule from baseline (Figure 1 B), after the first treatment (Figure 1 C), and after three treatments (Figure 1 D). Gross visual inspection and Micro-CT demonstrated no changes to the surrounding fibrous annulus. Conclusions: In a feasibility study involving a fixed cadaveric heart, histotripsy therapeutic ultrasound demonstrated the potential to internally disrupt a MAC nodule without injuring the mitral annulus. Further studies are needed to address the ability of histotripsy to improve valve function in DMS.