Cryotherapy for Vulnerable Plaque Stabilization: Preliminary Report From Polarstar: A First-in-Human Study

Abstract

Background Imaging methods can identify coronary plaques at high risk of rupture. Preclinical data have demonstrated the favorable effects of cryotherapy on the stabilization of high-risk plaques. We report the first-in-human (FIH) application of intracoronary cryotherapy for the stabilization of high-risk plaques. Methods This is a multicenter, prospective, single-arm study, including patients presenting with acute coronary syndromes (ST-segment elevation myocardial infarction [STEMI], non-STEMI, or UA) and a high-risk nonobstructive plaque in a nonculprit vessel. After successful PCI of the culprit lesion, patients underwent coronary computed tomography angiography (CTA) to screen for the presence of high-risk plaques. Patients then underwent cryotherapy guided by intravascular ultrasound (IVUS). Coronary cryotherapy is a rapid-exchange balloon-based technology that delivers nitric oxide, reaching temperatures of −20 °C at the level of the lesion. The primary endpoint was the occurrence of any cryotherapy procedure-related complication or any major adverse cardiovascular events at 90 days. Patients were followed noninvasively with coronary CTA at 3 and 9 months. Results We report the preliminary results of the first 12 patients included in the study. The mean age was 65 ± 10 years, and 75% were men. The target lesions for cryotherapy were in the LAD, LCX, and RCA for 25%, 33%, and 42% of patients, respectively. The median diameter stenosis was 40% (Q1, Q3: 36%, 43%). In IVUS, the median reference vessel diameter was 2.90 mm (Q1, Q3: 2.74, 3.26 mm), and the median minimal lumen area was 4.07 mm2 (Q1, Q3: 3.63, 4.43 mm2). The mean cryoballoon size was 3.30 ± 0.40 mm. There were no procedural complications. At 90 days, no major cardiovascular adverse events were reported. At the 9-month coronary CTA follow-up (n = 4), there was a trend toward a reduction in plaque volume (Δ volume = −6 mm³; 95% CI: −94.6 to 107.0 mm³), with stable fractional flow reserve derived from CT values (FFRCT Δ lesion = −0.08; 95% CI: −0.28 to 0.45). Conclusion In this preliminary report of the Polarstar FIH study, the application of cryotherapy for vulnerable plaque stabilization was safe. Coronary CTA results showed a trend toward a reduction in plaque volume with a positive impact on epicardial conductance.