European Heart Journal (2020) 41, 333–336
doi:10.1093/eurheartj/ehaa001
Chronic coronary syndromes:
expanding the spectrum and natural
history of ischaemic heart disease
Thomas F. Lüscher1,2,3, MD, FESC
1
Professor of Cardiology, Imperial College and Director of Research, Education & Development, Royal Brompton and Harefield Hospitals London, UK; 2Professor and Chairman,
Center for Molecular Cardiology, University of Zurich, Switzerland; and 3Editor-in-Chief, EHJ Editorial Office, Zurich Heart House, Hottingerstreet 14, 8032 Zurich, Switzerland
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For the podcast associated with this article, please visit https://academic. ..
oup.com/eurheartj/pages/Podcasts. ..
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In patients with chest pain of cardiac origin, the underlying cause has ..
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been described as coronary artery disease (CAD1), ischaemic heart ..
disease, or microvascular disease,2 among other conditions. The new ..
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concept of ‘chronic coronary syndromes’ noted in the 2019 ESC ..
Guidelines3 that are part of this issue tries to cover this wide spec- ..
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trum and changing natural history of the disease involving different ..
parts of the coronary circulation, different mechanisms such as ..
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plaques4 or spasm,5 and/or episodes of ischaemia, or even infarction ..
followed by stable periods, respectively.
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Over the last decades, the profile of chronic coronary syndrome ..
has changed substantially. In a FAST TRACK entitled ‘Long-term
..
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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 myocar-
dial infarction was 8.0%. Independent predictors were prior
hospitalzation for heart failure, current smoking, atrial fibrillation, liv-
ing 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
Symptom-based pre-test probability scores that estimate the likeli-
hood of obstructive CAD in stable chest pain including the modified
With thanks to Amelia Meier-Batschelet for help with compilation of this article.
C The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
Published on behalf of the European Society of Cardiology. All rights reserved. V
ISSUE @ A GLANCE
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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 angiog-
raphy: 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 fac-
tors 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
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.. learning model incorporating clinical features in addition to coronary
.. artery calcium score obtained with CTA can therefore accurately es-
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.. timate the pre-test likelihood of obstructive CAD. In clinical practice,
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.. the utilization of such an approach could improve risk stratification
.. and help guide downstream management. The manuscript is accom-
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.. panied by an interesting Editorial by Partho Sengupta from the
.. West Virginia University in Morgantown, USA.10
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.. Other risk scores are based on CV risk factors such as lipids.
.. Besides LDL-cholesterol,11,12 lipoprotein (a),13,14 and triglycer-
..
.. ides,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 phos-
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.. pholipids 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
334 Issue @ a Glance

Cumulative incidence of the primary outcome 12.5%

Angina
P < 0.001 Prior MI

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10.0%
P value for interaction between
angina and prior MI= 0.0016

7.5% No Angina
No Prior MI
Angina
5.0% P > 0.99
No Angina

2.5%

0.0%
0 1 2 3 4 5
Time (years)

Figure 1 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).

..
predictive for CV mortality, with hazard ratios between 1.44 and .. associated with increased risk (Figure 2). The pre-specified combin-
1.69. In addition, a combination of the risk score with high-sensitivity .. ation of plaque features within the same plaque was observed in
..
troponin T increased hazard ratios to 1.63 and 2.04. The C-statistics .. 18.9% of patients with a primary endpoint and was an independent
for the risk score combined with sex and age was 0.76 for CV death. .. predictor of events, with a hazard ratio of 7.54. Thus, the simultan-
..
Thus, a simple ceramide–phospholipid-based risk score can efficiently .. eous presence of four high-risk OCT plaque features was found to
predict residual CV risk in patients with chronic coronary syndromes. .. be associated with a higher risk of major coronary events. These
..
These findings are further discussed in an enlightening Editorial by .. novel findings are critically assessed in a balanced Editorial by Ik-
Scott Summers from the University of Utah in Salt Lake City, USA.18
.. Kyung Jang from the Massachusetts General Hospital in Boston,
..
Once lipid-rich coronary plaques have developed, some may cause .. USA.25
CV events, even in the statin era.19 Coronary plaques with features
.. An overall summary of chronic coronary syndromes and their
..
of either rupture20 or erosion21 are thought to be vulnerable and to .. management is provided in the first of our Year in Cardiology series,
..
underly acute coronary syndromes. The introduction of optical co- .. the ‘The Year in Cardiology: interventional cardiology’, by
herence tomography or OCT has provided unforeseen opportuni- .. Andreas Baumbach from the St. Bartholomew’s Hospital in London,
..
ties to diagnose features of plaque vulnerability.22,23 In their .. UK, and colleagues.26 They remind us that in 2019, research in percu-
manuscript ‘Relationship between coronary plaque morph- .. taneous coronary intervention focused mainly on the optimization of
..
ology of the left anterior descending artery and 12 months .. treatment strategies, the development of novel equipment and phar-
clinical outcome: the CLIMA study’ Francesco Prati from the .. macotherapies, and on risk stratification and identification of high-risk
..
San Giovanni Hospital in Rome, Italy focus on this issue.24 In the .. patients that will benefit from emerging therapies. Also, important
CLIMA study, 1003 patients underwent OCT of the untreated prox- .. clinical studies have been reported that examined the efficacy of dif-
..
imal left anterior descending coronary artery. At 1 year, the primary .. ferent treatment strategies and stent platforms in patients with ob-
clinical endpoint occurred in 3.7%. The presence of minimal lumen .. structive coronary artery disease.
..
area <3.5 mm2, fibrous cap thickness <75 lm, lipid arc circumferen- .. This issue also contains the ‘2019 ESC Guidelines for the diag-
tial extension >180 , and OCT-defined macrophages were all
.. nosis and management of chronic coronary syndromes:
Issue @ a Glance 335

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Figure 2 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).

The Task Force for the diagnosis and management of

.. Beattie E, Haddow L, Oldroyd KG, Touyz RM, Berry C. Systemic microvascular
.. dysfunction in microvascular and vasospastic angina. Eur Heart J 2018;39:
chronic coronary syndromes of the European Society of ..
Cardiology (ESC)’ by William Wijns and colleagues from the ESC
.. 4086–4097.
.. 3. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C,
Scientific Document Group.3 .. Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T,
.. Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J,
Lastly, the issue is complemented by various Discussion Forum .. Muneretto C, Valgimigli M, Achenbach S, Bax JJ. 2019 ESC Guidelines for the
contributions. In a first contribution, Manolis S. Kallistratos and col- .. diagnosis and management of chronic coronary syndromes. Eur Heart J 2020;41:
.. 407–477.
leagues from the Asklepeion General Hospital in Athens, Greece ..
comment on the recently published ‘2019 ESC Guidelines for .. 4. Costopoulos C, Timmins LH, Huang Y, Hung OY, Molony DS, Brown AJ, Davis
.. EL, Teng Z, Gillard JH, Samady H, Bennett MR. Impact of combined plaque struc-
the diagnosis and management of chronic coronary syn- .. tural stress and wall shear stress on coronary plaque progression, regression,
dromes: The Task Force for the diagnosis and management .. and changes in composition. Eur Heart J 2019;40:1411–1422.
.. 5. Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Camma G, Lanza
of chronic coronary syndromes of the European Society of .. GA, Crea F. Patients with acute myocardial infarction and non-obstructive cor-
Cardiology (ESC)’,3,27 Juhani Knuuti and colleagues from the ESC .. onary arteries: safety and prognostic relevance of invasive coronary provocative
..
Scientific Document Group respond to the contribution in a separate .. tests. Eur Heart J 2018;39:91–98.

manuscript.28
.. 6. Sorbets E, Fox KM, Elbez Y, Danchin N, Dorian P, Ferrari R, Ford I, Greenlaw N,
.. Kalra PR, Parma Z, Shalnova S, Tardif JC, Tendera M, Zamorano JL, Vidal-Petiot
In another Discussion Forum contribution entitled ‘Aspirin de- .. E, Steg PG. Long-term outcomes of chronic coronary syndrome worldwide:
sensitization procedures in aspirin-intolerant patients: a
.. insights from the international CLARIFY registry. Eur Heart J 2020;41:347–355.
.. 7. Sechtem U, Ong P. How should we manage risks associated with chronic coron-
neglected topic in the ESC 2019 Chronic Coronary .. ary syndromes? Eur Heart J 2020;41:356–358.
..
Syndrome guidelines’ Matteo Bianco and colleagues from the .. 8. Reeh J, Therming CB, Heitmann M, Hojberg S, Sorum C, Bech J, Husum D,
A.O.U San Luigi Gonzaga, Orbassano in Turin, Italy also comment on .. Dominguez H, Sehestedt T, Hermann T, Hansen KW, Simonsen L, Galatius S,
.. Prescott E. Prediction of obstructive coronary artery disease and prognosis in
the above-mentioned Guidelines.3,29 Robert F. Storey and colleagues .. patients with suspected stable angina. Eur Heart J 2019;40:1426–1435.
on behalf of the ESC Guidelines Task Force respond to this comment .. 9. Al’Aref SJ, Maliakal G, Singh G, van Rosendael AR, Ma X, Xu Z, Alawamlh OAH,
.. Lee B, Pandey M, Achenbach S, Al-Mallah MH, Andreini D, Bax JJ, Berman DS,
in a separate contribution.30 .. Budoff MJ, Cademartiri F, Callister TQ, Chang HJ, Chinnaiyan K, Chow BJW,
The editors hope that readers of this issue of the European Heart ..
.. Cury RC, DeLago A, Feuchtner G, Hadamitzky M, Hausleiter J, Kaufmann PA,
Journal will find it of interest. .. Kim YJ, Leipsic JA, Maffei E, Marques H, Goncalves PA, Pontone G, Raff GL,
.. Rubinshtein R, Villines TC, Gransar H, Lu Y, Jones EC, Pena JM, Lin FY, Min JK,
.. Shaw LJ. Machine learning of clinical variables and coronary artery calcium scor-
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