IJCA-27729; No of Pages 7

International Journal of Cardiology xxx (xxxx) xxx

Contents lists available at ScienceDirect

International Journal of Cardiology

journal homepage: www.elsevier.com/locate/ijcard

Coronary artery aneurysms, insights from the international coronary

artery aneurysm registry (CAAR)
Iván J. Núñez-Gil a,b,⁎, Enrico Cerrato c, Mario Bollati d, Luis Nombela-Franco a, Belén Terol e,
Emilio Alfonso-Rodríguez f, Santiago J. Camacho Freire g, Pedro A. Villablanca h, Ignacio J. Amat Santos i,
José M. de la Torre Hernández j, Isaac Pascual ak,al,am, Christoph Liebetrau k, Benjamín Camacho l,
Marco Pavani m, Juan Albistur n, Roberto Adriano Latini o, Ferdinando Varbella c, Víctor Alfonso Jiménez-Díaz p,
Davide Piraino q, Massimo Mancone r, Fernando Alfonso s, José Antonio Linares t, Ramón Rodríguez-Olivares u,
Jesús M. Jiménez Mazuecos v, Jorge Palazuelos Molinero w, Alejandro Sánchez-Grande Flecha x,
Joan Antoni Gomez-Hospital y, Alfonso Ielasi z, Íñigo Lozano aa, Pierluigi Omedè ab, Rodrigo Bagur ac,
Fabrizio Ugo ad, Massimo Medda ae, Boshra F. Louka af, Petr Kala ag, Javier Escaned a,b, Daniel Bautista ah,
Gisela Feltes a, Pablo Salinas a, Mohamad Alkhouli ai, Carlos Macaya a,b,
Antonio Fernández-Ortiz a,b,aj, on behalf of theCAAR investigators:

Piter Martínez Benítez 3, Antonio Gomez Menchero 4, Javier León Jimenez 4, José Francisco Díaz Fernandez 4,
Mohammed Makkiya 5, Nurilign Bulcha 5, Sarabjeet Suri 5, Paol Rojas 6, Tamara Garcia Camarero 7,
Pablo Avanzas 28,29,30, Cesar Morís 28,29,30, Christoph Berndt 9, Pedro Trujillo 10, Gustavo Vignolo 10,
Rafael Mila 10, Dario Buccheri 11, Pedro Silva 11, Giorgio Quadri 2, Francesco Tomassini 2, Cristina Rolfo 2,
Etelberto Hernández Hernández 12, José Antonio Baz Alonso 12, Andrés Íñiguez Romo 12, Giulia Teresi 13,
Giuseppe Andolina 13, Simone Calcagno 14, Gonzalo Navarrete 15, Fernando Rivero 15, Javier Cuesta 15,
Daniella Benedetto 16, Fatih Arslan 16, Peter R. Stella 16, Mª. Isabel Barrionuevo Sánchez 17,
Rafael Gómez Vicente 18, Patricia Clares Montón 18, Dámaris Carballeira 18, Geoffrey Yanes Bowden 19,
Manuel Vargas Torres 19, Agustín Fernández Cisnal 20, Juan Pablo Canepa Leite 20, Giulietta Grigis 21,
Claudio Moretti 22, Antonio Montefusco 22, Fabrizio D'Ascenzo 22, Piera Capasso 23, Marta Bande 24,
Francesco Casilli 24, Ramez Morkous 25, Eric Yang 25, Harish Ramakrishna 25, Martin Poloczek 26,
Roman Miklik 26, Ahmad Al Hallak 27, Bernardo Cortese 11, Pilar Jiménez Quevedo 1, Nieves Gonzalo 1,
María del Trigo 1, Alfonso de Hoyos y Fernández de Córdova 1, Jose Alberto de Agustín 1,
Armghan Munir 27, David Vivas 1
1
Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain
2
Interventional Cardiology, Infermi Hospital, Rivoli, Turin, Italy
3
Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba
4
Interventional Cardiology, Hospital Juan Ramón Jiménez, Huelva, Spain
5
Interventional Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, USA
6
CIBERCV, Interventional Cardiology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
7
Cardiology Department, Hospital de Valdecilla, Santander, Spain
9
Kerckhoff Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany; DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Frankfurt am Main, Germany
10
Cardiology, Hospital de Clínicas Dr, Manuel Quintela, Montevideo, Uruguay
11
Cardiology Department, Ospedale Fatebenefratelli, Milan, Italy
12
Interventional Cardiology, Hospital Álvaro Cunqueiro, Vigo, Spain
13
UO di Cardiologia Interventistica ed Emodinamica, Azienda Ospedaliera Universitaria Policlinico “P,Giaccone” Palermo, Italy
14
Is Sapienza University of Rome, Policlinico Umberto I. Department of Cardiovascular, Respiratory, Neurological, Anaesthesiology and Geriatric Sciences
15
Cardiology Department, Hospital Universitario de La Princesa, Madrid, Spain
16
Interventional Cardiology, Utrecht Medisch Centrum, Utrecht, the Netherlands
17
Interventional Cardiology, H General Universitario de Albacete, Albacete, Spain
18
Interventional Cardiology, Hospital central de la Defensa “Gomez Ulla”, Madrid, Spain

⁎ Corresponding author at: Cardiovascular Institute, Hospital Clínico San Carlos, Avda. Profesor Martin Lagos S/N, 28040 Madrid, Spain.
E-mail address: ibnsky@yahoo.es (I.J. Núñez-Gil).

https://doi.org/10.1016/j.ijcard.2019.05.067
0167-5273/© 2019 Elsevier B.V. All rights reserved.

Please cite this article as: I.J. Núñez-Gil, E. Cerrato, M. Bollati, et al., Coronary artery aneurysms, insights from the international coronary artery
aneurysm registry (CAAR), International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.05.067
2 I.J. Núñez-Gil et al. / International Journal of Cardiology xxx (xxxx) xxx

19
Interventional Cardiology, H Universitario de Canarias, San Cristobal de la Laguna, Spain
20
Interventional Cardiology, Hospital de Bellvitge, Barcelona, Spain
21
Cardiology Division, ASST Bergamo Est, Bolognini Hospital Seriate, Italy
22
Cardiology, Città della Salute e della Scienza, Molinnette I, Torino, Italy
23
Interventional Cardiology, H San Giovanni Bosco, Turin, Italy
24
Interventional Cardiology Unit, Istituto Clinico Sant'Ambrogio, Milan, Italy
25
Division of Cardiovascular Diseases, Mayo Clinic Arizona, USA
26
Department of Internal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic
27
Cardiology, West Virginia University Heart and Vascular Institute, Morgantown, WV, United States of America
28
Department of Cardiology, Hospital Universitario Central de Asturias, Oviedo, Spain
29
Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain
30
University of Oviedo, Oviedo, Spain
a
Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain
b
Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
c
Interventional Cardiology, Infermi Hospital, Rivoli, Turin, Italy
d
Interventional Cardiology, Policlinico San Donato, Milan, Italy
e
Cardiology Department, Hospital Severo Ochoa, Leganés, Spain
f
Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba
g
Interventional Cardiology, Hospital Juan Ramón Jiménez, Huelva, Spain
h
Interventional Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, USA
i
CIBERCV, Interventional Cardiology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
j
Cardiology Department, Hospital U. Marques de Valdecilla, IDIVAL, Santander, Spain
k
Kerckhoff Heart and Thorax Center, Department of Cardiology, Bad Nauheim, Germany; DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Frankfurt am Main, Germany
l
Interventional Cardiology, Hospital Arnau de Vilanova, Lérida, Spain
m
Cardiology, Città della Salute e della Scienza, Molinnette II, Torino, Italy
n
Cardiology, Hospital de Clínicas Dr, Manuel Quintela, Montevideo, Uruguay
o
Cardiologia Interventistica, ASST Fatebenefratelli-Sacco Milan, Italy
p
Interventional Cardiology, Hospital Álvaro Cunqueiro, Vigo, Spain
q
UO di Cardiologia Interventistica ed Emodinamica, Azienda Ospedaliera Universitaria Policlinico “P,Giaccone” Palermo, Italy
r
Is Sapienza University of Rome, Policlinico Umberto I. Department of Cardiovascular, Respiratory, Neurological, Anaesthesiology and Geriatric Sciences
s
Cardiology Department, Hospital Universitario de La Princesa, Madrid, Spain
t
Interventional Cardiology, H Lozano Blesa, Zaragoza, Spain
u
Interventional Cardiology, Utrecht Medisch Centrum, Utrecht, the Netherlands
v
Interventional Cardiology, H General Universitario de Albacete, Albacete, Spain
w
Interventional Cardiology, Hospital central de la Defensa “Gomez Ulla”, Madrid, Spain
x
Interventional Cardiology, H Universitario de Canarias, San Cristobal de la Laguna, Spain
y
Interventional Cardiology, Hospital de Bellvitge, Barcelona, Spain
z
Cardiology Division, ASST Bergamo Est, Bolognini Hospital Seriate, Italy
aa
Interventional Cardiology, Hospital de Cabueñes, Gijon, Spain
ab
Cardiology, Città della Salute e della Scienza, Molinnette I, Torino, Italy
ac
Interventional Cardiology, University Hospital, London Health Sciences Centre, London, Ontario, Canada
ad
Interventional Cardiology, H San Giovanni Bosco, Turin, Italy
ae
Interventional Cardiology Unit, Istituto Clinico Sant'Ambrogio, Milan, Italy
af
Division of Cardiovascular Diseases, Mayo Clinic Arizona, USA
ag
Department of Internal Medicine and Cardiology, University Hospital Brno and Medical Faculty of Masaryk University, Brno, Czech Republic
ah
Cardiology, Instituto dominicano de Cardiología, Santo Domingo, Dominican Republic
ai
Cardiology, West Virginia University Heart and Vascular Institute, Morgantown, WV, United States of America
aj
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
ak
Department of Cardiology, Hospital Universitario Central de Asturias, Oviedo, Spain
al
Instituto de Investigación Sanitaria del Principado de Asturias, ISPA, Oviedo, Spain
am
University of Oviedo, Oviedo, Spain

a r t i c l e i n f o a b s t r a c t

Article history: Background: Coronary Aneurysms are a focal dilatation of an artery segment N1.5-fold the normal size of adjacent
Received 27 September 2018 segments. Although some series have suggested a prevalence of 0.3–12%, data are lacking. In addition, they are
Received in revised form 13 May 2019 not mentioned in practice guidelines. Our aim was investigate its prevalence, management and long-term
Accepted 27 May 2019 outcomes.
Available online xxxx
Methods and results: The coronary artery aneurysm registry (CAAR) involved 32 hospitals across 9 countries in
America and Europe. We reviewed 436,467 consecutive angiograms performed over the period 2004–2016. Fi-
nally, 1565 patients were recruited. Aneurysm global prevalence was 0.35%. Most patients were male (78.5%)
with a mean age of 65 years and frequent cardiovascular risk factors. The main indication for angiogram was
an acute coronary syndrome, 966 cases. The number of aneurisms was ≤2 per patient in 95.8% of the cases, mostly
saccular, most frequently found in the left anterior descending and with numbers proportional with coronary ste-
nosis. Aortopathies were related with more aneurysms too. Most patients received any revascularization proce-
dure (69%), commonly percutaneous (53%). After a median follow-up of 37.2 months, 485 suffered a combined
event (MACE) and 240 died. Without major differences comparing CABG vs PCI, MACE and death were more fre-
quent in patients who received bare metal stents.
Conclusions: Coronary artery aneurysms are not uncommon. Usually, they are associated with coronary stenosis and
high cardiovascular risk. Antiplatelet therapy seems reasonable and a percutaneous approach is safe and effective.
© 2019 Elsevier B.V. All rights reserved.

Please cite this article as: I.J. Núñez-Gil, E. Cerrato, M. Bollati, et al., Coronary artery aneurysms, insights from the international coronary artery
aneurysm registry (CAAR), International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.05.067
 I.J. Núñez-Gil et al. / International Journal of Cardiology xxx (xxxx) xxx
1. Introduction
Coronary Aneurysms are classically defined as a focal dilatation
in the diameter of a coronary artery segment of N1.5-fold normal
size, considering as such the adjacent non-dilated segments [1–
3]. The earliest description by Morgagni date back to 1761, being
one of the first series, a report with 21 cases, published in 1929
[2,4].
Since then, some small series have suggested a variable preva-
lence of 0.3–12%, with a 4.9% in the largest one ever published in
adults [3]. This later included 978 patients from the Coronary Artery
Surgery Study (CASS), between 1975 and 1979 [3]. At that time, an-
eurysmal coronary artery disease (CAD) was considered mainly a
variant of coronary atherosclerosis [5]. Thence, CAD management
options have evolved rapidly and greatly, with novel interventional
procedures and antithrombotic drugs known to improve symptoms
and survival in this setting. Despite this, coronary aneurysms are
not mentioned in current -European or American- CAD guidelines
and several clinical or treatment questions on this matter remain un-
answered together with the current natural history of this condition
[4].
Moreover, to the best of our knowledge, no prospective studies
assessing the contemporary outcomes or addressing the therapeutic
management for this condition have been reported [4–14].
The objective of this study was to investigate the clinical profile,
prognostic predictors, and the long term-outcome of coronary artery
aneurysms.
2. Methods
2.1. Study population
The coronary artery aneurysm registry (CAAR, Clinical Trial registration-Clinical Trials.
gov: NCT02563626) is a multicenter study involving, at the moment, 32 hospitals across 9
countries (Canada, Cuba, Czech Republic, Germany, Italy, The Netherlands, Spain, United
States and Uruguay). Protocol data were collected in accordance with regulations set
forth by institutional review boards and complied with the declaration of Helsinki, as pre-
viously reported [15,16]. Patients were ambispectively included in the registry on the basis
of the angiographic classical coronary aneurysm definition (focal 1.5× dilation compared
with a healthy vessel segment). Aneurysms were considered as giant when their size
reached about 4× dilation [15].
All patients (≥18 years) after an invasive angiography with one or various established
coronary aneurysms fulfilling the previous criteria were eligible, unless they refused.
The review of all coronary angiograms was done in each institution. The period of time
was locally chosen on investigator's criteria, but procedures were strictly consecutive.
During the mentioned chosen time frame, all consecutive patients were recruited after re-
view by two experienced interventional cardiologists. When eligibility for inclusion was
uncertain, cases were reviewed by a core lab team to reach consensus [15]. Standardized
and anonymized forms were used to collect patient data, including baseline characteris-
tics, management and long term outcomes.
2.2. Outcomes and follow up
We recorded the clinical features, all in-hospital medications and complications, in-
cluding cardiogenic shock, bleeding and death from any cause. After discharge, the follow-
ing events were recorded: any cause death, readmission because of unstable angina, re-
infarction, heart failure, bleeding, stroke, embolic events, and any reason for new coronary
angiography. In addition, for statistical purposes, we considered a combined variable
(MACE), as a combination of all cause death or heart failure, unstable angina pectoris
and re-infarction. A detailed data gathering on in-hospital and after discharge medical
treatment was performed, focusing on antiplatelet and anticoagulation management. Re-
vascularization procedures were assessed and recorded paying attention to the procedure
chosen (interventional –PCI- vs surgical –CABG-) and, if PCI was performed, the type of
stent and technique used. Follow-up data was prospectively obtained by researchers
based on clinical visits, medical records, or telephone interviews.
The development of a new aneurysm was defined upon iterative coronariography fol-
lowing the previous criteria. The growing of a previous one was considered after a new
cardiac catheterization following researchers criteria as any increase in size, demonstrated
in 2 or more cine loops.
A total of 83 patients, discharged alive, were considered as lost to follow up due to in-
ability to complete a follow N30 days. Those patients who died during that period were in-
cluded in the overall cohort and regular analysis. Nevertheless, all were included in the
Kaplan Meier estimates.
Please cite this article as: I.J. Núñez-Gil, E. Cerrato, M. Bollati, et al., Coronary artery aneurysms, insights from the international coronary artery
aneurysm registry (CAAR), International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.05.067
3
2.3. Statistical analysis
For statistical analysis we used the SPSS v23.0 (IBM-SPSS, USA), OFFICE 2010 software
package (Microsoft, USA) and STATA v14.9 (Statacorp, USA) for graphs compiling. The
data is presented as mean ± standard deviation or median and range, as applicable. Cate-
gorical variables are provided with percentages. Comparisons between groups were per-
formed using the appropriate test for qualitative or continuous variables. Long-term
event free survival curves for the different exploratory analysis and groups were obtained
using the Kaplan-Meier method and comparisons between groups were performed using
the log-rank test. The level of statistical significance was set at a two-tailed p ≤ 0.05.
3. Results
We reviewed a total of 436,467 consecutive invasive coronary angio-
grams performed over the period 2004 and 2016. Of those, we found
1561 consecutive patients fulfilling criteria for at least one coronary an-
eurysm. Appendix Table A1 displays the numbers of patients recruited
by each center, the period of time and the number of coronariographies
reviewed by each group. Other 4 nonconsecutive cases were recruited
by researchers because presented inclusion criteria and thus were con-
sidered, outside the prevalence estimation, for the rest of the analysis,
Fig. 1. Finally, 1565 patients were included in this analysis of the
registry.
3.1. Prevalence and clinical features
Overall prevalence was calculated in relation to the number of car-
diac catheterization procedures. It was estimated as 0.35% (minimum:
0.07-maximum: 3.19%, between centers, Table A1). With a mean age
of 65.5 years, patients were predominantly male (78.5%) with frequent
cardiovascular risk factors. The clinical profile is shown in Table 1 and
more detailed in Table A2.
Additional peripheral arterial occlusive disease was seen in 11.1% of
the cases; an history of aortopathy was reported in 137 (8.7%) patients,
any type of collagenopathy (2.2%) and a confirmed Kawasaki disease
was rare (0,3%).
3.2. Coronary aneurysms description and anatomy
The main indication for coronariography was an acute coronary syn-
drome in 966 (61.5%) cases, being 318 with ST segment elevation. Stable
angina was the reason in 244 (15.6%) and chest pain in 175 (11.2%)
cases; Table 1.
Through angiography, right coronary dominance was shown in
83.8%. Most patients presented a severe coronary stenosis: 1-vessel dis-
ease, 434 patients; 2-vessel disease, 394 and 3-vessel disease 517 cases.
Regarding the aneurysm features, most of them were saccular (834
cases). The presence of diffuse disease or ectasia was a common finding
in 30.0% of the cases, added to “focal” aneurysms. In 82 cases the aneu-
rysms were considered as giant.
Most patients presented only one (83.0%) or two coronary aneu-
rysms (12.8%). Only three patients had 6 (2 cases) or 7 (1 case) aneu-
rysms. The number of aneurysms was higher and proportional in
patients with more severe CAD. Thus, patients with severe stenosis in
one vessel displayed N1 aneurysm in the 13%, while two vessel
disease-patients depicted N1 aneurysm in 16% and those with three ste-
notic vessels presented N1 aneurysm in 22.4% (p = 0.002).
Overall, the most affected vessel with aneurysms was the left ante-
rior descending artery (762 cases, 48.6%), followed by the right coronary
artery (498, 31.8%) and the circumflex (441, 28.1%). We observed a left
main involvement in 84 patients, Fig. 2. One case had an aneurysm in
the left internal mammary graft and another case in a saphenous vein
graft.
The presence of aortic aneurysm diagnosis was found to be related
with a higher number of coronary aneurysms (mean numbers: 1.42 vs
1.21, p = 0.000).
4 I.J. Núñez-Gil et al. / International Journal of Cardiology xxx (xxxx) xxx

Fig. 1. Total population assessed, CAAR recruitment, management and follow-up.

3.3. Revascularization strategy, outcomes and discharge antiplatelet received a BMS, 221 patients at least a DES and 17 patients a stent graft.
therapy Two hundred and fourteen patients received a bypass graft in that
segment.
Most patients received any revascularization procedure (1079, Regarding the other stenotic coronary segments, 221 patients were
68.9%) during their index hospitalization. The coronary territory treated with CABG and 684 were managed percutaneously.
where they had aneurysms was treated in 561 (33.4%) and other coro- Overall, there were no differences on aneurysm complications, un-
nary segments in 905 cases (57.8%). stable angina, infarction, embolism, stroke, bleeding, MACE (31.6% vs.
Most patients (n = 829) underwent PCI, with any type of stent in 31.4%; p = 0.963) or death either (15.6% vs. 15.9%, p = 0.925) regarding
776 patients (BMS in 259, DES in 493, covered stents/grafts 17, not spec- CABG vs PCI, but we found higher rates of heart failure in the CABG
ified 7), Fig. 1. In patients who received any revascularization procedure, group (10.8% vs. 5.9%; p = 0.009), in the univariate assessment.
we found less frequently heart failure (7.3% vs. 10.7%; p = 0.024) but no New aneurysms (3.3% vs. 2.2%, p = 0.70) or aneurysm growing (8.8%
differences regarding unstable angina, infarction, MACE, embolism, vs. 4.4%, p = 0.72) did not reach a statistical difference between the
bleeding, cardiovascular/any cause death, aneurysm growing or compli- treatment groups (PCI vs CABG). Since PCI vs. CABG displayed no differ-
cations at this level. ences, we compared the use of BMS with DES. No restenosis was found
With regard to the aneurysmal segments: 12 patients received a bal- in aneurysms treated with DES, 0 over 161 patients, but those with BMS
loon angioplasty, 2 were treated with a drug eluting balloon, 95 patients displayed 4 cases over 70; p = 0.002. The comparison favored the use of
DES for MACE and death, without differences in bleeding or aneurysm
complications (any type, growing or new aneurysms development),
Fig. 3.
Table 1
Clinical Features of the study patients. Regarding the antithrombotic treatment, most patients received as-
pirin at discharge (1412, 90.2%), any type of dual antiplatelet therapy
Overall aneurysms cohort
(DAPT) in 1013 (64.8%) and 211 (13.4%) were on anticoagulation. In
(n = 1565)
89 cases, the initial purpose was to maintain DAPT indefinitely. Consid-
Gender/male (%) 1229 (78.5%) ering for these patients a duration equal to their follow-up, the median
Age (mean ± SD) 65.5 ± 12.7
Hypertension (%) 1131 (72.3%)
DAPT length was 12 months (IQR: 6–12).
Dyslipemia (%) 931 (59.3%)
Diabetes Mellitus (%) 400 (25.5%)
Smoking habit (%) 644 (41.2%) 3.4. Long-term Follow up and outcomes
Renal failure/CrCl b 30 (%) 128 (8.2%)
Peripheral vascular disease (%) 173 (11.1%)
Working diagnosis (%) The median follow-up was 37.2 months (interquartile range,
– Chest pain. 175 (11.2%) IQR:15.5–72.1). Two hundred forty (15.3%) patients died during the
– Stable angina 244 (15.6%) follow-up, 31 (2.0%) of them during the first 30 days. Eighty five pa-
– NSTEACS 645 (41.2%) tients died of a known cardiovascular cause.
– STEACS 318 (20.3%)
– Ventricular tachycardia/fibrillation/sudden death 13 (0.8%)
Four hundred eighty five patients (31.0%) displayed a MACE event.
– Heart failure/dyspnea/dilated myocardiopathy 41 (2.6%) Table A3 depicts the events registered during follow-up stratified by
– Valvular study 95 (6.1%) the main cause for the index cardiac catheterization.
– Presurgery (non cardiac) 14 (0.9%) A follow-up catheterization was performed in 395 cases (25.2%)
– Syncope 3 (0.2%)
after a median of 12.6 months (IQR: 3.3–39.1). Out of these, 36 were
– Others. 17 (1.1%)
Coronary artery disease, number of vessels (%) 1.77 ± 1.05 elective PCIs, 78 for control purposes only and the remaining cases for
– 1 434 (27.7%) new symptoms or prior surgery -no cardiac- (3). Any significant grow-
– 2 394 (25.2%) ing in previous aneurysm was found in 25 cases (after a median follow-
– 3 517 (33.0%) up of 41.2 months) and a new aneurysm development was depicted in
Left ventricular ejection fraction (mean ± SD), % 54.8 ± 13.2%
16 patients (median follow-up: 24.2 months).

Please cite this article as: I.J. Núñez-Gil, E. Cerrato, M. Bollati, et al., Coronary artery aneurysms, insights from the international coronary artery
aneurysm registry (CAAR), International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.05.067
 I.J. Núñez-Gil et al. / International Journal of Cardiology xxx (xxxx) xxx 5

Fig. 2. Anatomic distribution of coronary aneurysms regarding its morphology. Among the 1565 study patients, the most common type of coronary aneurysm was the saccular form (834;
53.29% patients), panels A and B depict the coronary distribution of this type of aneurysm. C and D refer to the fusiform aneurysms (in 671 patients; 38.01%). E and F show the coronary
territory distribution for giant aneurysms (see definition in methods; 48 were saccular, 25 fusiform, 7 mixed morphology and 2 no specified). Overall, sixty cases were considered to be
mixed or not specified (17), and thus were not included in this graph. The same aneurysm could be present in two or more coronary territories. A, C and E display the right coronary
territory and B, D and F the left coronary.

Aneurysm complication was seen in 32 cases (8.2%) with 19 throm-
bosis, 9 progression of existing coronary stenosis or stent restenosis and
only 1 rupture.
This unique rupture was documented 30.9 months after the index
angiography. The patient was admitted with NSTEMI symptoms and
the ruptured aneurysm was successfully treated with a stent graft.
4. Discussion
The coronary artery aneurysm registry is the largest multicenter reg-
istry designed to study the contemporary prevalence, clinical profile
and long-term outcomes of coronary aneurysms. With N1500 adult pa-
tients from 32 hospitals over 9 countries, CAAR shows that this condi-
tion is infrequent but not rare, accounting for about 0.35% over
N435,000 cardiac catheterizations. The diagnosis of this disease, with
the widespread of non-invasive coronary imaging techniques and the
increasing use of invasive cardiac catheterization in the acute setting
is likely to increase in the next years, posing the physicians in front of
a disease with a lack of evidence based medicine data.
CAAR patients presented a high cardiovascular risk burden, with a
high proportion of cases with renal insufficiency and peripheral arterial
occlusive disease. This fact, points out an advanced or aggressive athero-
sclerotic CAD as a common underlying condition. Despite that, the cur-
rent practice guidelines on ischemic heart disease, do not include any
recommendation about patients with coronary aneurysms, neither
regarding antithrombotic therapy or when/how/where perform a re-
vascularization procedure.
Other comorbidities, such aortopathies probably mark a patho-
physiologic link, with abnormalities of the vessel media and subse-
quent dilation [4]. This relationship has been recently suggested
also by a retrospective study including pediatric and adult patients
from Taiwan [17]. When we reviewed patients (n = 174) without
previous revascularization and no severe stenosis during the index
admission, they were younger with less cardiovascular risk factors
(less males, hypertension, dyslipemia, diabetes, smoking habit and
peripheral vessel disease) than in the remaining cohort with
coronary stenosis. In addition, the percentage of any aortopathy in
these patients was higher (13.8% vs 7.7%, 0.006) supporting the pre-
viously mentioned link.
Despite the typical and well known association of coronary artery
aneurysms with some inflammatory (Kawasaki, Takayasu, lupus,
Churg Strauss, rheumatoid arthritis…) and connective tissue disorders
(Marfan syndrome, Ehlers-Danlos syndrome…) in the CAAR registry
the number of patients with those conditions was low, suggesting
those diseases as relatively uncommon in patients with aneurysms di-
agnosed in the adulthood.
Thus, considering the clinical profile, the cardiovascular risk burden
and the most frequent presentation (ischemic) the attending physician
should probably manage this condition such an aggressive CAD with
high ischemic risk.

Please cite this article as: I.J. Núñez-Gil, E. Cerrato, M. Bollati, et al., Coronary artery aneurysms, insights from the international coronary artery
aneurysm registry (CAAR), International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.05.067
 6
aneurysm registry (CAAR), International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.05.067
Please cite this article as: I.J. Núñez-Gil, E. Cerrato, M. Bollati, et al., Coronary artery aneurysms, insights from the international coronary artery

I.J. Núñez-Gil et al. / International Journal of Cardiology xxx (xxxx) xxx

Fig. 3. Kaplan Meier free survival curves for the combined event –MACE- (A, B) and death (C, D), regarding the use of bare metal stents (BMS) or drug eluting stents (DES). A and C depict the whole cohort group treated with those devices. B and D refer
only to those patients with specific treatment at the segment with aneurysm. 95% Confidence intervals are depicted.
 I.J. Núñez-Gil et al. / International Journal of Cardiology xxx (xxxx) xxx
Other important point is the antithrombotic therapy. CAAR findings
suggest that antiplatelet therapy without additional long-term
anticoagulation after revascularization (PCI or CABG) in acute and
non-acute patients might be enough. However, the most advanced
stages of the disease (aneurysms with multivessel disease) could have
a benefit with prolonged antiplatelet strategy or anticoagulation. This
approach could be more even compelling in the presence of other
prothrombotic comorbidities (acute setting, smoking habit, VIH [18],
or others…).
Regarding the revascularization procedures, the interventional ap-
proach seems to be long-term safe and effective, when compared with
CABG. In addition, aneurysms rupture was rare in our series.
Published studies showed that the use of first-generation DES might
be associated with aneurysm development compared with BMS (e.g.
Taxus-V trial, 1.4% vs 0.2%; p = 0.07) [19,20]. Our data, in contrast to
these findings, displayed a clear advantage in terms of decreasing com-
bined events and even mortality with the use of DES. This way, CAAR
points out that the default preferred strategy for this patients would
be last generation DES, something reasonable if we consider these pa-
tients as having high ischemic risk. DES would have a low rate of
long-term complications, like some series have suggested previously
[21]. The use of other devices, such as covered stents performed well
for huge aneurysms exclusion, but numbers are low and longer
follow-up data is needed. Due to its full coverage with polymer, re-
endothelialization within the covered stent is delayed, and reported
data indicate that restenosis rates are higher than with conventional
stents [22]. Gercken et al. implanted 78 PTFE-covered stents in 70 pa-
tients and performed invasive follow-up examinations after a mean of
159 days [23].Restenosis occurred in 31.5% of cases and in the majority
was located at the stent edges. However, more studies investigating
covered stents in the setting of aneurysm sealing are needed in order
to know their actual long-term performance [24].
4.1. Limitations
The prevalence calculation was adjusted to the number of coronary
angiographies performed, which probably does not allow direct extrap-
olations to the general or “healthy” population. Recently, a retrospective
population based study from Taiwan's National Health Insurance Re-
search Database, between 2005 and 2011, including adult and pediatric
patients reported an incidence rate – of aneurysms/ectasias- of 0.85 per
105 person-years [25]. We did not report the percentage of patients
with complete revascularization, but this issue could explain, at least
in part, differences of MACE and mortality. While our observations
give us with an overall idea of the prognosis of the disease, they do
not provide information as robust as a clinical trial would do. We can
only generate hypotheses regarding therapeutics; however, when we
consider data from the long-term follow-up, CAAR probably reveals a
realistic depiction of the results and the contemporary real life progno-
sis of patients who are diagnosed with a coronary aneurysm.
5. Conclusion
Aneurysmal coronary artery disease is not uncommon. It is usually
associated with severe underlying coronary stenosis and a high cardio-
vascular risk burden, pointing out an aggressive atherosclerotic status.
Antiplatelet therapy, without anticoagulation, seems a reasonable anti-
thrombotic option along with a percutaneous approach was safe and
effective.
Please cite this article as: I.J. Núñez-Gil, E. Cerrato, M. Bollati, et al., Coronary artery aneurysms, insights from the international coronary artery
aneurysm registry (CAAR), International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.05.067
7
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ijcard.2019.05.067.
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