Acute myocardial infarction (MI) remains the focus of intense research and management efforts, despite many recent scientific and clinical breakthroughs.¹ Yet its pathophysiological basis remains at least partly elusive.² The last few decades have established the role of atherothrombosis as the key determinant of acute MI due to coronary artery disease.³ In particular, autopsy series were instrumental in recognizing that the rupture of a complex atherosclerotic plaque with exposure of necrotic core components to the blood leading to superimposed thrombosis was the main underpinning of acute MI.^4-5 Evidence that supports the importance of thrombosis adjacent to plaque rupture came indirectly from the practical successes of thrombolysis and then primary angioplasty. From a pathophysiologic (rather than descriptive) perspective, however, this paradigm was never definitely established given the limitations inherent of autopsy series, the lack (until recently) of suitable tools for accurate in vivo atherothrombotic imaging, and the subsequent proposal that plaque erosion, rather than rupture, was also an important cause of acute MI.^6-8

In the current era, although there is no debate that atherothrombosis is the main cause of acute MI, there is persistent uncertainty about the contribution of plaque rupture versus plaque erosion to atherothrombosis and infarction. According to the landmark contribution of Farb et al. in 1996, which reported that plaque erosion occurred in 44% of patients who died due to acute MI (with an increased prevalence in women), there has been no firm agreement on the precise prevalence of plaque erosion versus rupture (Figures 1 and 2).^6,7,9 Indeed, this is a key issue because the management of rupture would conceivably entail strategies that are different from those used for erosion.

Figure 1: A prototypical case of plaque rupture in the left anterior descending (left panel: angiography; right panels: optical coherence tomography).

Figure 2: A prototypical case of plaque erosion in the left anterior descending (left panel: angiography; right panels: optical coherence tomography).

Luckily, the recent introduction of intravascular coronary imaging with optical coherence tomography (OCT) has provided a novel and accurate tool for appraising the pathophysiologic basis of acute MI, as well as atherothrombosis in other vascular districts, thanks to its very high spatial resolution.¹⁰ As always, there are no two studies on the subject reporting exactly the same effect estimates, but we can rely on aggregate analyses and high-quality prospective studies to inform us with the utmost accuracy. For instance, we may highlight the results of the recent OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) study, which has appraised with pre-angioplasty OCT the culprit lesion in 140 age-matched men and women with ST-segment elevation MI (STEMI).^11-12 After excluding unsuitable cases, 2 dissections, and lesions that could not be accurately classified (yielding 95 appraisable lesions), erosion was found in 25% of cases, in comparison with 75% cases with rupture. Although a suboptimal final Thrombolysis in Myocardial Infarction flow was more common in patients with plaque rupture, no significant difference was found between the erosion versus plaque groups for the incidence of adverse events at short term, the prevalence of uncovered stent struts at midterm, or the incidence of adverse events at long term. In addition, and most notably, no significant gender association with plaque type was found in OCTAVIA, which relied on a stringent age- and gender-matching enrolment algorithm.

Pooled analyses also support the accuracy of such estimates for the prevalence of plaque erosion as the cause of acute MI, as very recently reported by Iannaccone et al.¹³ In their careful review, the authors included 23 studies including 2,711 culprit lesions, with STEMI in 13% and non-STEMI (NSTEMI) in 10%. All were appraised in vivo relying on OCT to evaluate coronary plaque features before intervention. Meta-analysis based on random effect models yielded estimates for the prevalence of plaque rupture in STEMI of 70% of cases, which was clearly higher than the 56% for NSTEMI, 39% for unstable angina, and 6% for stable angina. Significant predictors of plaque rupture in the overall dataset were smoking history and the presence of a thin-cap fibroatheroma, whereas in the STEMI subgroup plaque rupture was significantly associated with hypertension and thin-cap fibroatheroma. These two features also predicted plaque rupture in NSTEMI, together with diabetes and age, whereas in unstable angina the only independent predictors were hypertension, dyslipidemia, smoking history, and thin-cap fibroatheroma. Accordingly, and most notably, gender was never significantly associated with the presence of plaque rupture at the culprit lesion.

In conclusion, recent high-quality studies from primary and secondary research endeavors show that, despite changing definitions and imaging modalities, the relative incidence of plaque rupture underlying STEMI-associated lesion remains in the range of 50-75%. Conversely, in NSTEMI acute coronary syndromes, the observed incidence of plaque rupture is sequentially lower relative to more frequent plaque erosion: the estimated frequency of rupture in NTEMI was 56% and 39% in unstable angina. Reasons for this variation in the incidence of plaque rupture by syndrome potentially involve variable importance of clinical risk factors influencing the integrity of the plague surface. Further evaluation of the causes of this variation of plaque pathophysiology persists, but clearly both plaque rupture and erosion remain important mechanisms.

References

1. Yeh RW, Go AS. Rethinking the epidemiology of acute myocardial infarction: challenges and opportunities. Arch Intern Med 2010;170:759-64.
2. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012;60:1581-98.
3. Maseri A, L'Abbate A, Baroldi G, et al. Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of "preinfarction" angina. N Engl J Med 1978;299:1271-7.
4. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 1983;50:127-34.
5. Davies MJ, Woolf N, Robertson WB. Pathology of acute myocardial infarction with particular reference to occlusive coronary thrombi. Br Heart J 1976;38:659-64.
6. Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000;20:1262-75.
7. Arbustini E, Dal Bello B, Morbini P, et al. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart 1999;82:269-72.
8. Lindahl B. Acute coronary syndrome - the present and future role of biomarkers. Clin Chem Lab Med 2013;51:1699-706.
9. Arbustini E, Narula N, Kodama T. Clinical Imaging of ACS With Ruptured or Intact Fibrous Caps. JACC Cardiovasc Imaging 2015;8:576-8.
10. Sangiorgi G, Bedogni F, Sganzerla P, et al. The Virtual histology In CaroTids Observational RegistrY (VICTORY) study: a European prospective registry to assess the feasibility and safety of intravascular ultrasound and virtual histology during carotid interventions. Int J Cardiol 2013;168:2089-93.
11. Guagliumi G, Capodanno D, Saia F, et al. Mechanisms of atherothrombosis and vascular response to primary percutaneous coronary intervention in women versus men with acute myocardial infarction: results of the OCTAVIA study. JACC Cardiovasc Interv 2014;7:958-68.
12. Saia F, Komukai K, Capodanno D, et al. Eroded Versus Ruptured Plaques at the Culprit Site of STEMI: In Vivo Pathophysiological Features and Response to Primary PCI. JACC Cardiovasc Imaging 2015;8:566-75.
13. Iannaccone M, Quadri G, Taha S, et al. Prevalence and predictors of culprit plaque rupture at OCT in patients with coronary artery disease: a meta-analysis. Eur Heart J Cardiovasc Imaging 2015 Oct 27 [Epub ahead of print].

Keywords: Acute Coronary Syndrome, Algorithms, Angina, Stable, Angina, Unstable, Angiography, Angioplasty, Autopsy, Coronary Artery Disease, Diabetes Mellitus, Dyslipidemias, Hypertension, Infarction, Myocardial Infarction, Plaque, Atherosclerotic, Prevalence, Risk Factors, Smoking, Stents, Thrombosis, Tomography, Optical Coherence

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