Novel treatment for broken heart syndrome with microbubbles and ultrasound

Associate Professor Koya Ozawa , University of Sydney

Vanguard Grant - 1 Year

Years funded: 2025 - 2025

Treating broken heart syndrome with MUSIC

Takotsubo cardiomyopathy (TCM), also known as broken heart syndrome, is a reversible cardiomyopathy, characterised by transient, left ventricular (LV) systolic dysfunction in the absence of angiographic obstructive coronary artery disease. Although the precise pathophysiology of TCM has not been fully elucidated, potential mechanisms are sympathetic stimulation, catecholamine surge, myocardial inflammation, coronary vasospasm, and microvascular dysfunction. Despite recovery of LV ejection fraction and absence of major coronary artery disease, the outcome of patients with TCM is significantly worse than in the general population. Beyond acute events, the all-cause mortality rate in patients with TCM is 5.6%/year and the incidence of major adverse cardiovascular events is 9.9%/year. There are two major unmet needs: 1) the lack of established specific therapy, and 2) the requirement for prolonged hospital stays, including ICU admission.

Myocardial Ultrasound-induced Inertial Cavitation (MUSIC) is the application of ultrasound while infusing an ultrasound contrast agent designed to increase blood flow. MUSIC produces potent vasodilatory effects by reducing free radicals and microvascular tone, which could improve microvascular spasm and microvascular dysfunction, known as the pathophysiology of TCM. In TCM, long-term cardiac dysfunction is related to whether inflammation persists into the chronic phase, and MUSIC could reduce inflammation in the acute phase.

Accordingly, this proposal aims to conduct a proof-of-concept animal study using an established model of TCM. In addition to investigating whether MUSIC facilitates the recovery of myocardial function in the acute phase, we will also examine whether it reduces inflammation and myocardial injury. The results will be used to apply for larger funding for a full-scale translational study to determine whether MUSIC facilitates the recovery of cardiac function in TCM. If successful, this will lead to a multicentre prospective human trial to confirm the findings. Our team is the Australian leader of MUSIC intervention. We are currently running a multicentre RCT in three hospitals in NSW in the heart attack population.