EMERALD II: Non-Invasive Coronary Anatomy and Physiology (CCTA) in ACS Prediction

Despite steady progress in secondary prevention and medical treatment optimization (OMT), acute coronary syndrome (ACS) remains one of the leading causes of cardiovascular morbimortality. Traditionally, risk assessment has based on anatomical parameters derived from coronary angiography, particularly luminal stenosis degree. However, evidence accumulated over two decades has shown angiographic severity alone results insufficient to identify lesions with higher probability of clinical destabilization. 

In this context, coronary computed tomography angiography (CCTA) enables non-invasive assessment of, not only lumen area, but also plaque composition and burden, introducing the concept of “vulnerable plaque”. In parallel, developing non-invasive coronary physiology with CCTA derived FFR (FFR-CT) has opened a new field to assess the hemodynamic impact of lesions beyond their morphologic appearance. 

The EMERALD II addresses the question of which of these two dimensions — anatomy and/or physiology —  or combination of these, enables better predicting what coronary lesions will evolve into ACS. 

This was a multicenter international study, with internal case-control design, including patients presenting ACS with a CCTA done within one month and 3 years prior index event. Lesions identified by CCTA were classified into culprit or non-culprit according to invasive angiographic findings obtained during ACS treatment, assessed by a core lab. 

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351 patients were looked at, predominantly men, mean age 66. Index event was acute myocardial infarction in nearly two thirds of patients. In total, 2,451 coronary lesions were assessed, 363 were identified as culprit, with one-year mean interval between CCTA and ACS presentation. 

Culprit lesions showed a higher anatomical and physiological risk profile, with higher percentage of stenosis, number of adverse plaque characteristics, and plaque burden, with significantly higher ΔFFR_CT values.

From a diagnostic standpoint, ≥70% plaque burden showed the highest sensitivity (90.6%), identifying the vast majority of culprit lesions, while ≥0.10 ΔFFR_CT evidenced the highest specificity (88,3%), which suggests great discriminating power to identify lesions of real hemodynamic impact. 

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In terms of global performance, ΔFFR_CT showed superior predictive capacity vs each anatomical parameter considered in isolation. However, when integrating anatomical values into a combined model, performance resulted comparable to that of physiology (area under the curve 0.805 vs 0.802; p = 0.748).

Conclusions

The EMERALD II has shown that one single parameter cannot predict the evolution of coronary lesions into ACS. Anatomy, especially plaque burden, contributes with high sensitivity, while non-invasive coronary physiology with ΔFFR_CT offers greater specificity. Integrating both perspectives enables more precise and clinically relevant risk characterization. 

Original Title: Anatomical vs Physiological Lesion Characteristics in Prediction of Acute Coronary Syndrome. 

Reference: Yang S, Chung JW, Park SH, Zhang J, Lee K, Hwang D, Lee KS, Na SH, Doh JH, Nam CW, Kim TH, Shin ES, Chun EJ, Choi SY, Kim HK, Hong YJ, Park HJ, Kim SY, Husic M, Lambrechtsen J, Jensen JM, Nørgaard BL, Andreini D, Maurovich-Horvat P, Merkely B, Penicka M, de Bruyne B, Ihdayhid A, Ko B, Tzimas G, Leipsic J, Sanz J, Rabbat MG, Katchi F, Shah M, Tanaka N, Nakazato R, Asano T, Terashima M, Takashima H, Amano T, Sobue Y, Matsuo H, Otake H, Kubo T, Takahata M, Akasaka T, Kido T, Mochizuki T, Yokoi H, Okonogi T, Kawasaki T, Nakao K, Sakamoto T, Yonetsu T, Kakuta T, Yamauchi Y, Taylor CA, Bax JJ, Shaw LJ, Stone PH, Narula J, Koo BK. Anatomical vs Physiological Lesion Characteristics in Prediction of Acute Coronary Syndrome. JACC Cardiovasc Interv. 2025 Dec 8;18(23):2833-2845. doi: 10.1016/j.jcin.2025.09.006. PMID: 41371781.