Coronary plaque rupture (RFC-ACS) is known to be the leading pathophysiology causing acute coronary syndrome (ACS). The underlying mechanisms triggering the spark of cracking the fibro-atheromatous plaque cap, however, is unknown. High-resolution intracoronary imaging by optical coherence tomography (OCT) allows for identification of the entire ACS-causing pathophysiology as well as in vivo characterization of different plaque components within the ACS-causing culprit plaque. This study, therefore, aims to investigate the behaviour of different plaque components, especially the interaction between lipid and calcium and their spatial relation to the rupture zone in a large cohort of ACS-patients.

Within the prospective, translational, multicentric OPTICO-ACS study 307 patients with acute coronary syndrome underwent intracoronary imaging via optical coherence tomography (OCT). All pullbacks were analyzed following a central, standardized CoreLab-analysis including comprehensive assessment of the ACS-causing culprit plaque characteristics. After defining the culprit lesion borders (according to the longitudinal plaque extension), ruptured culprit plaques were divided into 3 main segments (rupture segment, proximal segment, distal segment). Proximal and distal segments were each further divided into two equal zones (a=distal plaque zone, b=distal extended rupture zone, d=proximal extended rupture zone, e=proximal plaque zone; see figure 1).

The overlap between calcium and lipid plaque components was assessed by analyzing each frame individually for both components. Frames containing both components were set in a ratio to all evaluated frames in order to determine the percent overlap .

Out of 307 ACS-patients, 204 patients (66.5 %) presented with ruptured culprit plaques (RFC-ACS) being nearly exclusively (96.6%) thin-cap fibroatheroma with a mean longitudinal extent of 16.9 mm (CI=16.0-17.9) with an average minimum cap thickness of  55.8 µm (CI=53.8-57.7). Within the culprit plaques mean lipid content was 86.2% (CI 84.0-88.4) and 29.7% (CI 25.6-33.8) were calcified components  respectively. 

Calcium content was similar among all four zones (p=0.12), whereas lipid content significantly differed among the proximal and distal zones (zone a=52.7% CI=47.4-58.1 vs. zone b =91.6% CI=88.8-94.4; p<0.01; zone d=94.4 CI=91.8-97.1 vs. zone e=78.0 CI 91.8-97.1; p<0.01)

Importantly, with respect to the direct overlap of calcium and lipid components, a highly significant (p<0.01) difference was detectable along the longitudinal plaque extent: Culprit plaque areas, directly neighboring the rupture point (zone b and d; figure1) are characterized by a significantly (p<0.01) increased overlap of calcium/lipid components (zone b=29.5% CI=24.3-34.7; zone d=29.7% CI=24.3-35.1) compared to the distal (zone a=16.0% CI 12.2-19.8) and proximal (zone e=18.9% CI=14.4-23.4) plaque zones. No relevant difference was detected comparing proximal and distal border zones (p=1.00).

This study reveals, for the first time, a significant different overlap of lipid/calcium plaque components near the crack of ACS-causing culprit plaques.This finding indicates that RFC-ACS could be caused by lipid accumulation, bordering incompressible calcium deposits.