Acute and chronic coronary syndromes: coronary dissection, intraplaque haemorrhage, and late lumen loss

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts For consistency, we should not only talk about acute coronary syndrome (ACS) as it encompasses ST-segment myocardial infarction (STEMI), Non ST-segment myocardial infarction (NSTEMI) unstable angina, myocardial infarction with non-obstructive coronary artery disease (MINOCA),1,2 and Takotsubo syndrome,3,4 but also about chronic coronary syndromes. Indeed, chronic coronary syndromes not only include stable coronary artery disease due to an obstructing plaque,5 but also coronary spasm6 and microvascular angina7,8 among others. Spontaneous coronary artery dissection has long been recognized as a cause of ACS,9 but its management remains unclear and challenging. In a Current Opinion entitled ‘European Society of Cardiology - Acute Cardiovascular Care Association, SCAD Study Group - A position paper on spontaneous coronary artery dissection’, David Adlam from the University of Leicester in the UK notes that, although initially considered very rare and associated primarily with pregnancy and the peripartum period, the use of higher-sensitivity troponin assays and early angiography in ACS, coupled with greater awareness of the condition, has led to increased recognition of it as a significant cause of ACS, predominantly in young to middle-aged women.10 Although there are no randomized controlled trials in spontaneous coronary dissection, knowledge has advanced recently, mainly based on large registries. Not only is spontaneous coronary dissection a distinct entity, but there are key differences in its management and outcomes compared to ACS of atherosclerotic aetiology. This position paper presents the consensus on contemporary management and areas of controversy and uncertainty, which remain a focus of ongoing research. Besides mechanical forces, spasm, and inflammation, haemorrhage may also elicit plaque rupture.11,12 In their article ‘Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study’,13 Blerim Mujaj and colleagues from Erasmus MC in Rotterdam, The Netherlands remind us that antithrombotic treatment plays a key role in stroke prevention, but that its direct effects on the composition of carotid artery atherosclerotic plaques are unknown. Thus, they investigated carotid artery plaque composition during antithrombotic treatment. In total, 1740 individuals with carotid atherosclerosis underwent magnetic resonance imaging.14 Interestingly, current and past use of vitamin K antagonists (odds ratio 1.9) and antiplatelet agents (odds ratio 1.22) was associated with a higher presence of intraplaque haemorrhage. Also, a longer duration of use was associated with a higher frequency of intraplaque haemorrhage with an odds ratio of 3.15 for the use of vitamin K antagonists, and a trend for antiplatelet agents (odds ratio 1.21). Of note, higher levels of International Normalized Ratio (INR) > 2.97 for vitamin K antagonists (odds ratio 1.48) and daily defined dosages > 1.0 for antiplatelet agents (odds ratio 1.50) were related to a higher frequency of intraplaque haemorrhage (Figure 1). Thus, antithrombotic treatment is associated with a higher frequency of intraplaque haemorrhage in carotid plaques. These provocative findings are put into context in a thoughtful Editorial by Aloke Virmani Finn from CVPATH in Gaithersburg, Maryland, USA.15 Duration and dosage of use of antithrombotic treatment play important role in the presence of intraplaque haemorrhage (IPH) in the atherosclerotic plaque of the carotid artery (from Mujaj B, Bos D, Muka T, Lugt Avd, Ikram MA, Vernooij MW, Stricker BH, Franco OH. Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study. See pages 3369--3376). In device trials, the values of angiographic late lumen loss have become extremely low16–18), and the current relationship between late lumen loss and clinical endpoints is not known. In their article ‘Angiographic late lumen loss revisited: impact on long-term target lesion revascularization’, Patrick W. Serruys and colleagues from Imperial College London, UK investigated the impact of late lumen loss on target lesion revascularization in a meta-analysis of seven randomized controlled trials including 2426 patients treated with first- and second-generation drug-eluting stents.19 In the patient-level analysis, the probability regression curve showed an exponential relationship between the 2 year incidence of target lesion revascularization. The optimal cut-off value of late lumen loss was 0.50 mm. Indeed, late lumen loss > 0.50 mm was associated with an increased incidence of target lesion revascularization up to 4 years. These results are further discussed in an Editorial by Lorenz Räber from the Bern University Hospital in Switzerland.20 In another Current Opinion, ‘“Cardioprotection research must leave its comfort zone’, Gerd Heusch from the Center for Internal Medicine in Essen, Germany reflects on the translational gap between robust experimental studies on the reduction of infarct size by cardioprotective interventions and substances as adjunct to reperfusion and clinical trials with reduced events during follow-up.21 He emphasizes the need for better pre-clinical studies using large animal models with comorbidities and co-medications, and longer follow-up (Figure 2). Schematic diagram of the biological process from acute myocardial infarction with subsequent reperfusion, repair, remodeling to left ventricular dysfunction, heart failure, and clinical events. Experimental studies have their strength in early stages, whereas clinical studies have limited data on the initial event but their strength during follow-up. The proposal is to use an integrative large animal model and pursue the entire process, from acute myocardial infarction to events with a 1 year follow-up (from Heusch G. Cardioprotection research must leave its comfort zone. See pages 3393--3395). This issue is further complemented by two Discussion Forum contributions. The first relates to the article ‘Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial’, by Javier Bermejo et al.22 In their contribution ‘The elephant in the room’, Hayan Al Maluli and colleagues from Sanford Medical Center Fargo in North Dakota, USA comment on the article,23 and Bermejo et al. respond to it in a separate contribution.24 The second discussion relates to the article ‘Liver fat content, NAFLD, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals’ by Anne Tybjaerg-Hansen and colleagues from the Rigshospitalet in Copenhagen, Denmark.25 In their contribution entitled ‘Liver fat content, non-alcoholic fatty liver disease, and risk of ischaemic heart disease’, Giovanni Targher and Christopher Byrne from the Ospedale Civile Maggiore in Verona, Italy comment on this article,26 and Tybjaerg-Hansen et al. respond to it in a comprehensive manner.27 The editors hope that this issue of the European Heart Journal will find the interest of its readers. With thanks to Amelia Meier-Batschelet for help with compilation of this article.