Chronic coronary syndromes: expanding the spectrum and natural history of ischaemic heart disease

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. In patients with chest pain of cardiac origin, the underlying cause has been described as coronary artery disease (CAD1), ischaemic heart disease, or microvascular disease,2 among other conditions. The new concept of ‘chronic coronary syndromes’ noted in the 2019 ESC Guidelines3 that are part of this issue tries to cover this wide spectrum and changing natural history of the disease involving different parts of the coronary circulation, different mechanisms such as plaques4 or spasm,5 and/or episodes of ischaemia, or even infarction followed by stable periods, respectively. Over the last decades, the profile of chronic coronary syndrome has changed substantially. In a FAST TRACK entitled ‘Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry’, Kim M. Fox from the National Heart and Lung Institute in London, UK and colleagues determined current characteristics and management of 32 703 patients with chronic coronary syndrome over 5 years of follow-up.6 The primary outcome of cardiovascular (CV) death or myocardial infarction was 8.0%. Independent predictors were prior hospitalzation for heart failure, current smoking, atrial fibrillation, living in Central or South America, prior myocardial infarction or stroke, diabetes, current angina, and peripheral artery disease. In those with prior myocardial infarction, angina was associated with a higher event rate of 11.8% vs. 8.2% in those without it (Figure 1). Of note, in patients without prior myocardial infarction, event rates were similar with or without angina. Prescription rates of evidence-based secondary prevention therapies were high. Thus, despite high rates of prescription of evidence-based therapies, patients with both angina and prior myocardial infarction are a high-risk group who may deserve intensive treatment. These clinically most important findings are put into context in an Editorial by Udo Sechtem and colleagues from the Robert Bosch Krankenhaus in Stuttgart, Germany.7 Kaplan–Meier estimate curves for cardiovascular death or myocardial infarction according to angina status and history of prior myocardial infarction. P-value for interaction between angina and prior myocardial infarction in multivariable Cox model. CV, cardiovascular; MI, myocardial infarction (from Sorbets E, Fox KM, Elbez Y, Danchin N, Dorian P, Ferrari R, Ford I, Greenlaw N, Kalra PR, Parma Z, Shalnova S, Tardif J-C, Tendera M, Zamorano JL, Vidal-Petiot E, Steg PG, on behalf of the CLARIFY investigators. Long-term outcomes of chronic coronary syndrome worldwide: insights from the international CLARIFY registry. See pages 347–355). Symptom-based pre-test probability scores that estimate the likelihood of obstructive CAD in stable chest pain including the modified Diamend–Forrester score have moderate accuracy.8 In their article ‘Machine learning of clinical variables and coronary artery calcium scoring for the prediction of obstructive coronary artery disease on coronary computed tomography angiography: analysis from the CONFIRM registry’ James K. Min and colleagues from the Weill Cornell Medical College in New York, USA sought to develop a machine learning model, utilizing clinical factors and the coronary artery calcium score, to predict the presence of obstructive coronary disease on coronary computed tomography angiography or CTA in 35 281 individuals.9 Machine learning with coronary artery calcium score produced the best performance, with an area under the curve (AUC) of 0.881 compared with machine learning alone (0.773), the CAD consortium clinical score (AUC 0.734), the calcium score alone (AUC 0.866), or the updated Diamond–Forrester score (AUC 0.682). Coronary artery calcium score, age, and gender were the highest ranking features. A machine learning model incorporating clinical features in addition to coronary artery calcium score obtained with CTA can therefore accurately estimate the pre-test likelihood of obstructive CAD. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management. The manuscript is accompanied by an interesting Editorial by Partho Sengupta from the West Virginia University in Morgantown, USA.10 Other risk scores are based on CV risk factors such as lipids. Besides LDL-cholesterol,11,12 lipoprotein (a),13,14 and triglycerides,11,15 distinct ceramide lipids have recently attracted attention as they are able to predict CV risk, especially CV death.16 In their article entitled ‘Development and validation of a ceramide- and phospholipid-based cardiovascular risk estimation score for coronary artery disease patients’, Mika Hilvo and colleagues from the Zora Biosciences Oy in Espoo, Finland note that since phospholipids have also been linked with CV risk, they investigated whether the combination of ceramides with phosphatidylcholines would be synergistic.17 Ceramides and phosphatidylcholines were analysed in three studies involving 10 803 patients. A simple risk score based on ceramides and phosphatidylcholines was highly predictive for CV mortality, with hazard ratios between 1.44 and 1.69. In addition, a combination of the risk score with high-sensitivity troponin T increased hazard ratios to 1.63 and 2.04. The C-statistics for the risk score combined with sex and age was 0.76 for CV death. Thus, a simple ceramide–phospholipid-based risk score can efficiently predict residual CV risk in patients with chronic coronary syndromes. These findings are further discussed in an enlightening Editorial by Scott Summers from the University of Utah in Salt Lake City, USA.18 Once lipid-rich coronary plaques have developed, some may cause CV events, even in the statin era.19 Coronary plaques with features of either rupture20 or erosion21 are thought to be vulnerable and to underly acute coronary syndromes. The introduction of optical coherence tomography or OCT has provided unforeseen opportunities to diagnose features of plaque vulnerability.22,23 In their manuscript ‘Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study’ Francesco Prati from the San Giovanni Hospital in Rome, Italy focus on this issue.24 In the CLIMA study, 1003 patients underwent OCT of the untreated proximal left anterior descending coronary artery. At 1 year, the primary clinical endpoint occurred in 3.7%. The presence of minimal lumen area <3.5 mm2, fibrous cap thickness <75 μm, lipid arc circumferential extension >180°, and OCT-defined macrophages were all associated with increased risk (Figure 2). The pre-specified combination of plaque features within the same plaque was observed in 18.9% of patients with a primary endpoint and was an independent predictor of events, with a hazard ratio of 7.54. Thus, the simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events. These novel findings are critically assessed in a balanced Editorial by Ik-Kyung Jang from the Massachusetts General Hospital in Boston, USA.25 One-year event rates for lesions with and without optical coherence tomography-defined high-risk criteria (from Prati F, Romagnoli E, Gatto L, La Manna A, Burzotta F, Ozaki Y, Marco V, Boi A, Fineschi M, Fabbiocchi F, Taglieri N, Niccoli G, Trani C, Versaci F, Calligaris G, Ruscica G, Di Giorgio A, Vergallo R, Albertucci M, Biondi-Zoccai G, Tamburino C, Crea F, Alfonso F, Arbustini E, on behalf of CLIMA Investigators. Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study. See pages 383–391). An overall summary of chronic coronary syndromes and their management is provided in the first of our Year in Cardiology series, the ‘The Year in Cardiology: interventional cardiology’, by Andreas Baumbach from the St. Bartholomew’s Hospital in London, UK, and colleagues.26 They remind us that in 2019, research in percutaneous coronary intervention focused mainly on the optimization of treatment strategies, the development of novel equipment and pharmacotherapies, and on risk stratification and identification of high-risk patients that will benefit from emerging therapies. Also, important clinical studies have been reported that examined the efficacy of different treatment strategies and stent platforms in patients with obstructive coronary artery disease. This issue also contains the ‘2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC)’ by William Wijns and colleagues from the ESC Scientific Document Group.3 Lastly, the issue is complemented by various Discussion Forum contributions. In a first contribution, Manolis S. Kallistratos and colleagues from the Asklepeion General Hospital in Athens, Greece comment on the recently published ‘2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC)’,3,27 Juhani Knuuti and colleagues from the ESC Scientific Document Group respond to the contribution in a separate manuscript.28 In another Discussion Forum contribution entitled ‘Aspirin desensitization procedures in aspirin-intolerant patients: a neglected topic in the ESC 2019 Chronic Coronary Syndrome guidelines’ Matteo Bianco and colleagues from the A.O.U San Luigi Gonzaga, Orbassano in Turin, Italy also comment on the above-mentioned Guidelines.3,29 Robert F. Storey and colleagues on behalf of the ESC Guidelines Task Force respond to this comment in a separate contribution.30 The editors hope that readers of this issue of the European Heart Journal will find it of interest. With thanks to Amelia Meier-Batschelet for help with compilation of this article.