European Heart Journal - Cardiovascular Imaging (2021) 22, 34–36 EDITORIAL doi:10.1093/ehjci/jeaa233

Imaging quest for vulnerable plaque: is coronary computed tomography running out of steam? Downloaded from https://academic.oup.com/ehjcimaging/article/22/1/34/5896827 by guest on 25 September 2021 Mariusz Kruk*

Department of Coronary and Structural Heart Diseases, National Institute of Cardiology, ul. Alpejska 42, 04-628, Warsaw, Poland

Online publish-ahead-of-print 25 August 2020 . This editorial refers to ‘Age and sex-related features of ath- . the invasive to the non-invasive imaging diagnostic environment. Not . erosclerosis from CCTA in patients prior to acute coronary . only the high-risk plaque features were validated within the newer syndrome: results from the ICONIC study’, by E. Conte . methods, but unique attributes were added, including napkin ring . 5 et al.,pp.24–33. . sign. Moreover, the high volumes of clinical and imaging data, includ- . ing serial studies, provided by coronary CTA allowed to gain unpre- . 4,6 Prospective identification of patients who will develop acute coron- . cedented insight into the dynamics of coronary . ary syndrome (ACS) is a holy grail of preventive cardiology, as it . The resulting, clinically relevant knowledge on the vulnerable plaque . would allow focused, intensive intervention, likely averting the . derived from the coronary imaging studies may be briefly summar- patients’ fate. Coronary imaging holds the leading position in this . ized as follows: (i) increased risk of ACS is associated with the pres- . quest since a high proportion of ACS is related to the existence of . ence of any coronary plaque (vs. no plaque); (ii) around one-half of all pre-event identifiable, high-risk coronary plaques. The role of invasive . . ACS are related to the presence of pre-event identifiable high-risk plaque imaging methods in this research has been gradually eroded in . plaque features, whereas the other half is not; (iii) based on the cur- . favour of the non-invasive coronary computed tomography angiog- . rent diagnostics, the increased risk can be attributed at the patient ra- raphy (CTA) in recent years (Figure 1). The rising importance of CTA . ther than the specific lesion level, pointing at multisite vulnerable . in coronary diagnostics may provide the long-awaited breakthrough . plaque development/vulnerable patient, and devaluing the concept of for better tailored preventive treatments based on the presence of . preventive ‘spot’ coronary intervention; (iv) plaque regression is . the substrate for ACS (high-risk plaque) instead of the proxy (risk . associated with the decreased cardiovascular risk, whereas plaque 1,2 . 1,4,6 factors). . progression is associated with the increased risk. The invasive coronary imaging has multiple shortcomings including . On the other hand, there was no major clinical trial aimed to im- . its intrusive nature, and related higher risks and costs, difficulty to ob- . . prove patient prognosis based on the high-risk plaque entry criteria, tain pan-coronary (all vessels) or serial (follow-up) images, dubious . therefore the utility of the above knowledge in guiding patient man- . differentiation between the plaque components, with at most medi- . agement remains largely unproven. The major gaps in evidence in- ocre diagnostic value in predicting ACS.3 In the PROSPECT study, it . clude the recognition of more specific (new?) attributes associated . was shown that plaques with a thin cap fibroatheroma characteristics, . with the occurrence of acute coronary syndrome both at the local with a minimum lumen area <4 mm2, and plaque burden >70% had . and systemic level and their interplay, the identification of subgroups . 17.2% risk of clinical destabilization during a median of 3.4 years of . with distinctive pathophysiology of ACS, or the significance of dynam- 3 . observation (5%/year). The potential to predict ACS on the basis . ic changes in coronary plaque components. Critically, the current of coronary CTA is at least non-inferior to . knowledge on plaque vulnerability does not translate into official . (IVUS). Motoyama et al.4 showed that the presence of high-risk cor- . management recommendations, yet. Recent ESC guidelines regarding . onary plaque features and >_70% on coronary CTA con- . chronic coronary syndromes refer to either known risk factors com- ferred 19% risk of ACS during a median of 4 years, and in case of the . prising SCORE scale, or the presence of haemodynamically significant . plaque progression on serial coronary CTA the risk increased . coronary disease as the basis for implementation of risk man- to 27%. . agement therapies.2 The respective prevention guidelines mention . The ‘vulnerable plaque’ conceptual apparatus, including the high- . coronary artery calcium score, likely reflecting the overall coronary risk plaque characteristics, was fluently transferred and adapted from . atherosclerotic plaque burden, as a potential risk modifier.7

The opinions expressed in this article are not necessarily those of the Editors of EHJCI, the European Heart Rhythm Association or the European Society of Cardiology. * Corresponding author. Tel: þ48 22 3434342. E-mail: [email protected]; [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. VC The Author(s) 2020. For permissions, please email: [email protected]. Editorial 35

. . importance of the high-risk features irrespective of plaque burden. . Based on previous research, there seems to be interaction between . . sex and the factors contributing to ACS; women tend to have smaller . vessel size which may increase propensity for local thrombosis in . . case of coronary plaque rupture, ulceration, or stenosis, despite less- . 10,11 . er plaque volume. Another important factor specifically modify- . ing risk of ACS in women is the hormonal imbalance during . . menopause, likely increasing the systemic pro-thrombotic state ra- . 11 . ther than the plaque structure. Moreover, ACS without obstructive . . disease, likely due to coronary spasm, microvascular, and endothelial . dysfunction, is more prevalent in women.10 Regarding the age- . Downloaded from https://academic.oup.com/ehjcimaging/article/22/1/34/5896827 by guest on 25 September 2021 . related insight offered by the current study, it seems that not only the . higher plaque burden but also more vulnerable plaques may be asso- . . ciated with increasing age. On the other hand, the younger patients . had less calcium, lower plaque burden but similar absolute levels of . . the high-risk plaque component, stressing the prognostic importance . 11 . of this specific attribute. Despite paucity of the official recommen- . dations, current study findings added to already accumulated imaging . . data seem to support carefully tailored antiatherosclerotic therapies . in patients with the presence of high-risk plaques, irrespective of age, . . gender, overall plaque burden or coronary stenosis degree. . Another conjecture that may be inferred from Conte et al.studyis . . that ‘conservative’ CTA imaging approach may be running out of the . potential to significantly expand the current knowledge on ACS . . pathophysiology. This assumption may be reflected by a plateau . . reached by the number of publications combining ‘coronary plaque’ . AND ‘computed tomography’ terms, as shown in Figure 1B. . . Advancing the knowledge and subsequently patients’ management . will likely require more dynamic approach with serial imaging studies, . . or trials testing the impact of therapeutic interventions based on . CTA findings. High expectations with this regard are also related to . . novel technologies like augmented image analysis techniques includ- . ing radiomics, big-data analytics, artificial intelligence, in silico simula- . . tions of physiological processes, or new hardware including spectral Figure 1 The number of publications (y-axis) in a given year (x- . . or photon-counting computed tomography (Figure 1C).12,13 axis). The results of PubMed database search (performed on 12 July . 2020) of a combination of respective terms suggests a gradual shift . Conflict of interest: none declared. . of the balance of coronary plaque imaging evidence from invasive . (A) towards the non-invasive methods. On the other hand, the CT- . References based coronary plaque imaging (B) seems to reach a plateau. The . . 1. Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR et al.; SCOT-HEART rise of novel technologies is illustrated on (C). . Investigators. Coronary CT angiography and 5-year risk of myocardial . . . N Engl J Med 2018;6:924–33. . 2. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C et al. . 2019 ESC Guidelines on the diagnosis and management of chronic coronary syn- . . dromes: the Task Force for diagnosis and management of chronic coronary syn- However, coronary calcium is not indicative of the presence of a vul- . dromes of the European Society of Cardiology (ESC). Eur Heart J 2020;41: nerable plaque, and its role for therapy efficacy monitoring is a puzzle, . 407-477. . 3. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS et al.; as the conversion of non-calcified into calcified plaques marks their . . PROSPECT Investigators. A prospective natural-history study of coronary ath- 8 . stabilization and not progression. . erosclerosis. N Engl J Med 2011; 364:226–35. Current study adds to the understanding of the pathophysiology . 4. Motoyama S, Ito H, Sarai M, Kondo T, Kawai H, Nagahara Y et al. Plaque charac- . terization by coronary computed tomography angiography and the likelihood of of ACS by uncovering differences in pre-event coronary plaque . . acute coronary events in mid-term follow-up. J Am Coll Cardiol 2015;66:337–46. morphology based on age and sex, which may hold potential for . 5. Maurovich-Horvat P, Schlett CL, Alkadhi H, Nakano M, Otsuka F, Stolzmann P et 9 . improved patient mangement. The study may be praised for a robust . al. The napkin-ring sign indicates advanced atherosclerotic lesions in coronary . CT angiography. JACC Cardiovasc Imaging 2012;5:1243–52. design, including relatively large group of patients with coronary CTA . . 6. Chang HJ, Lin FY, Lee SE, Andreini D, Bax J, Cademartiri F et al. Coronary ath- examination preceding ACS. According to Conte et al. women with . erosclerotic precursors of acute coronary syndromes. J Am Coll Cardiol 2018;71: future ACS have smaller , with slightly less vulnerable plaque . 2511–22. . 7. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al.; ESC content than men, but with equal proportion of the qualitative high- . . Scientific Document Group. 2016 European Guidelines on cardiovascular disease risk coronary plaques. Those findings may implicate diagnostic . prevention in clinical practice. Eur Heart J 2016;37:2315–81. 36 Editorial

. 8. Sandfort V, Lima JAC, Bluemke DA. Noninvasive imaging of atherosclerotic pla- . 11. Kruk M, Pregowski J, Mintz GS, Maehara A, Tyczynski P, Witkowski A et al. . que progression: status of coronary CT angiography. Circ Cardiovasc Imaging . Intravascular ultrasonic study of gender differences in ruptured coronary 2015;8:e003316. . plaque morphology and its associated clinical presentation. Am J Cardiol 2007; 9. Conte E, Dwivedi A, Mushtaq S, Pontone G, Lin FY, Hollenberg EJ et al. Age and . 100:185–9. sex-related features of atherosclerosis from CCTA in patients prior to acute . 12. Nicol ED, Norgaard BL, Blanke P, Ahmadi A, Weir-McCall J, Horvat PM et al. . coronary syndrome: results from the ICONIC study. Eur Heart J Cardiovasc . The future of cardiovascular computed tomography: advanced analytics and clin- Imaging 2020;22:24–33. . ical insights. JACC Cardiovasc Imaging 2019;12:1058–72. 10. Chandrasekhar J, Mehran R. Sex-based differences in acute coronary syndromes: . 13. Kolossva´ry M, Kellermayer M, Merkely B, Maurovich-Horvat P. Cardiac com- insights from invasive and noninvasive coronary technologies. JACC Cardiovasc . puted tomography radiomics: a comprehensive review on radiomic techniques. Imaging 2016;9:451–64. . J Thorac Imaging 2018;33:26–34. Downloaded from https://academic.oup.com/ehjcimaging/article/22/1/34/5896827 by guest on 25 September 2021