CryoTherapeutics treats first patient in ICECAP trial targeting vulnerable coronary plaque

CryoTherapeutics announced it has treated the first patient in its ICECAP clinical trial, a milestone in the evaluation of whether localized cryotherapy can stabilize vulnerable coronary plaques before they cause a myocardial infarction.

The Liège, Belgium-based medical device company is developing a catheter-based cryotherapy system that delivers localized cooling, between -10 and -20 degrees Celsius, to non-obstructive coronary plaques identified through advanced imaging. The device is investigational and is not approved or cleared for commercial use in any jurisdiction.

During ICECAP screening, the first enrolled patient, who presented with stable angina, was found to have a non-obstructive high-risk coronary plaque. Such plaques do not significantly restrict blood flow but are increasingly recognized as a cause of heart attacks because they can rupture without warning.

The trial is designed to assess the efficacy and safety of localized cryotherapy applied to these plaques, identified through a multimodal imaging strategy that combines noninvasive and invasive technologies, while also tracking changes in fibroatheroma cap thickness over time. Patients are screened using coronary CT imaging and AI-enabled plaque characterization tools to flag high-risk features. During the procedure itself, intravascular imaging — including near-infrared spectroscopy and optical coherence tomography — is used to confirm high-risk plaque morphology and guide treatment, with follow-up imaging planned to assess the plaques' biological response to cryotherapy over time.

That imaging-driven approach reflects a broader shift in cardiology toward identifying disease before it becomes obstructive, a trend clinicians have been watching as AI-powered diagnostic tools increasingly supplement coronary CT angiography in risk stratification.

ICECAP draws on a multidisciplinary group of clinical, imaging and data science collaborators, including the Cardiovascular Research Foundation, HeartFlow and Medis Medical Imaging, contributing expertise in intravascular imaging, coronary CT analysis, quantitative image analysis and AI-assisted plaque assessment.

"Treating the first patient in ICECAP is an important milestone for CryoTherapeutics and the clinical development of our technology," said John Yianni, CEO of CryoTherapeutics, in a news release. "We are excited to work with our clinical and technology partners to generate the evidence needed to evaluate localized cryotherapy and advance the field."

"We are in a new phase of the detection and treatment of high-risk plaques," said Carlos Collet, director of cardiovascular imaging, physiology and translational therapeutics at the Cardiovascular Research Foundation, in the release. "In the ICECAP study, we are combining state-of-the-art plaque assessment with a novel therapy to stabilize vulnerable plaques."

Patient recruitment is active and is expected to expand to as many as five centers across Belgium and the United Kingdom in the coming months, according to the company.

A widening focus on vulnerable plaque

CryoTherapeutics' trial arrives amid a broader push in interventional cardiology to address disease that doesn't show up as a blockage on a traditional angiogram. Roughly half of heart attacks are estimated to stem from plaques that were not significantly obstructive beforehand, which has pushed device makers and imaging companies to invest heavily in tools that can flag vulnerable lesions before they rupture rather than waiting to treat blockages after the fact.

That shift has also reshaped the catheter-based device landscape more broadly, as manufacturers compete to refine intravascular tools for increasingly specific presentations of coronary artery disease, from calcified blockages to soft, high-risk lesions that have not yet narrowed a vessel. Combined with advances in noninvasive imaging and machine learning-based risk stratification, these efforts are part of a larger industry bet that earlier identification — paired with a targeted therapy — could meaningfully cut the rate of heart attacks tied to previously undetected disease.

Whether localized cryotherapy proves to be that targeted therapy will depend on results still to come from ICECAP and similar early-stage trials.