Ultrasound myocardial cavitation enabled treatment (MCET) was applied to the SS-16BN rat model of hypertrophic cardiomyopathy (HCM) for proof of the principle for myocardial reduction therapy. A focused ultrasound transducer was targeted using 10 MHz imaging (10S, GE Vivid 7) to the left ventricular wall of anesthetized rats in a warmed water bath. Pulse bursts of 4 MPa peak rarefactional pressure amplitude were intermittently triggered 1:8 heartbeats during 10 min infusion of a microbubble suspension. Methylprednisolone was given to reduce initial inflammation and Losartan was given to reduce fibrosis in the healing tissue. At 28 d post therapy, MCET significantly reduced the targeted wall thickness by 16.2% (P<0.01) relative to shams, with myocardial strain rate and endocardial displacement reduced by 34% and 29%, respectively, which are sufficient for therapeutic treatment. Premature ECG complexes and plasma troponin measurements were found to identify optimal and suboptimal treatment cohorts and would aid in achieving a desired impact. With clinical translation, MCET treatment should fill the need for a new non-invasive HCM therapy option.
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