Sonothrombolysis for Acute STEMI? High-Frequency Microbubbles Show Promise in MRUSMI

NEW ORLEANS, LA—The application of high mechanical index impulses from a diagnostic ultrasound transducer during microbubble infusion contributes to early patency and enhanced microvascular flow when used before and after PCI in STEMI patients, according results from the MRUSMI trial.

Wilson Mathias Jr, MD (University of São Paulo Medical School, Brazil), presented the results of this small feasibility study using the novel approach last week in a featured clinical research session at the American College of Cardiology 2019 Scientific Session. It was published simultaneously in the Journal of the American College of Cardiology.

The concept is based on multiple observations that the collapse of microbubbles via high-frequency impulses create shear forces that are strong enough to dissolve microvascular thrombi, Mathias explained. On the strength of several promising preclinical studies, he and his colleagues designed the single-center, first-in-human MRUSMI trial, enrolling 100 patients with a first STEMI presenting to their emergency department for PCI. The idea was to give the microbubble infusion as soon as possible after presentation and pop the bubbles with a handheld high-frequency ultrasound device, thereby reducing microvascular obstruction in preparation for PCI.

“This is a proof-of-concept study,” Mathias said in an interview with TCTMD following his presentation. “We were trying to prove that this works in humans. Now we are about to start a multicenter study in Brazil and probably in 2 years’ time we are going to be using this at point of care in ambulances.”

Mathias told TCTMD that in addition to the vascular effects, his group has observed that within 10 to 12 minutes many patients who undergo the technique, known as sonothrombolysis, also feel noticeably less chest pain.

Cindy Grines, MD (Northwell Health, Manhasset, NY), who served as a panelist during the session where Mathias presented the results, noted that the data appear to be more promising than early studies of facilitated PCI where patency was indeed augmented, but at the expense of bleeding complications and reocclusion.

“I think this is very exciting, but it’s also very preliminary, of course,” added session chair Christopher B. Granger, MD (Duke Clinical Research Institute, Durham, NC). “So many times we’ve seen small trials come up with unreliable findings, so we look forward to the further development of this to see if it might be replicated.”

Sustained Improvements at 6 Months

For the MRUSMI study, all STEMI presentations received an IV infusion of commercially available microbubble (Definity; Lantheus Medical Imaging). Those in the control group had application of low mechanical impulses with the transducer and no more than three diagnostic high mechanical index impulses to assess regional wall motion and microvascular perfusion before and after PCI. The experimental treatment group, on the other hand, had frequent image-guided diagnostic high mechanical index impulses (median 18 minutes) applied to the myocardial contrast-enhanced areas in the apical four-, two-, and three-chamber views before and following PCI. Door-to-balloon times did not differ between treatment groups (P = 0.42).

When PCI was begun, 48% of patients in the experimental group had angiographic recanalization, compared with 20% in the control group (P < 0.001). After PCI, infarct size as measured by MRI was smaller in the experimental group, at 29 g versus 40 g (P = 0.026). LVEF, which was the same in both groups at baseline, was slightly higher in the experimental group than the control group immediately after PCI and remained higher at 6 months. Need for implantable defibrillator was much lower in the experimental group, at just 5% of patients versus 18% in the control group (P = 0.045).

Writing in the paper, Mathias and colleagues say the high mechanical index impulses that they used in the study are standard on ultrasound systems “and are, in essence, the same high mechanical index impulses used to evaluate regional and global systolic function and perfusion during a commercially available microbubble infusion.”

To TCTMD, Mathias said the ultimate goal of the research is to be able to equip ambulances with a dedicated sonothrombolysis unit that could be used by emergency technicians en route to the hospital. Bringing that to fruition, however, requires scaling down the size of the device so a paramedic could give the infusion and then place the nonimaging ultrasound device on the chest to break up the clots. Mathias said not having to perform imaging is what allows for the process to work swiftly and not interfere with door-to-balloon times.

“At our university we are developing a very small portable device . . . that would be able to give the ultrasound pulses every 10 seconds to the whole heart,” he commented. “In the study we did the chamber views because we were interested in documenting the myocardial perfusion and what happens in real time when you apply this technique. But to take it to clinical practice you have to make it very easy, so our idea is once you have the EKG with ST-elevation myocardial infarction, you just [give the microbubble infusion], position the ultrasound device over the heart, and push one button and it will automatically send pulses of the ultrasound.”