Outcomes of coronary artery aneurysms: insights from the Coronary Artery Ectasia and Aneurysm Registry (CAESAR)

DOI: https://doi.org/https://doi.org/10.57187/s.3857

Introduction

Expansive (or positive) coronary artery remodelling occurs in the initial phase of atherosclerotic plaque formation [1]. The migration of leukocytes, foam cell formation in the vessel wall, and subsequent extracellular matrix degradation are considered the fundamental mechanisms underpinning this process [1]. This remodelling can maintain the diameter of the vessel lumen, potentially acting as an early compensatory mechanism to prevent luminal narrowing. However, dysregulation of the inflammatory response and proteolysis of extracellular matrix proteins [2] might lead to reverse remodelling with plaque deposition and luminal narrowing or a further increase in the vessel’s lumen, locally enlarging the vessel’s diameter to the point where it reaches the criteria for coronary ectasia [3]. Degradation or injury to any of the vessel layers, particularly the media, can lead to the formation of an aneurysm [4].

Coronary artery ectasias and aneurysms (CAE/CAAs) have typically been defined as a diffuse or focal coronary dilation that exceeds the diameter of normal adjacent segments or the diameter of the patient’s largest coronary vessel by 1.5 times [5]. CAE/CAAs are uncommon forms of coronary artery disease and have been diagnosed with increasing frequency since the introduction of coronary angiography. Their incidence has been reported to vary from 1.5% to 5.0%, with a suggested male predominance [6]. Although several causes have been proposed, atherosclerosis accounts for more than 50% of CAAs in adults [7]. Reported complications include thromboses and distal embolisations, vasospasms, and ruptures that produce ischaemia, heart failure, or arrhythmias [2]. The natural progression of CAE/CAAs and their long-term outcomes remain uncertain due to the scarcity of definitive data, which are often skewed by varying anatomical definitions and inclusion criteria. Furthermore, a direct comparison between the two forms of dilated coronary artery disease is lacking. Controversies also persist over the use of medical treatment (such as anti-thrombotic therapy) or interventional/surgical procedures.

Therefore, in this study, we aimed to delineate the clinical and angiographic characteristics of patients presenting with CAE, CAA or both, confirmed using invasive coronary angiography. Moreover, clinical outcomes were assessed over an extended period, allowing for a more comprehensive understanding of these conditions.

Methods

Study design

The coronary artery ectasia and aneurysm registry (CAESAR) is a monocentric, retrospective registry that includes all-comer patients with angiographical evidence of CAE or CAA based on invasive coronary catheterisation.

Retrospective patient recruitment consisted of (a) a clinical database query for a CAE/CAA diagnosis dating from January 1, 2006 to December 31, 2021 (see appendix), (b) manual screening of electronic medical records and a review of angiographies, and (c) visual confirmation of the diagnosis and classification of CAE, CAA and CAA-CAE (if combined), performed by catheterisation laboratory personnel. Any ambiguities were resolved through group consensus.

CAA was visually defined as a focal dilation of coronary segments of at least 1.5 times the adjacent normal segment, whereas CAE was associated with a more diffuse dilatation (>20 mm in length). Morphologically, CAAs were defined as “saccular” if the transverse diameter exceeded the longitudinal diameter, “fusiform” in the opposite case, and “giant” if the transverse diameter exceeded 20 mm. CAEs were defined as “diffuse” if they involved more than one vessel segment and “focal” if confined within one vessel segment. CAE “types” were defined according to the combination of diffuse and focal components [2]:

• Type I: diffuse ectasia involving two or three vessels
• Type II: diffuse disease in one vessel accompanied by localized disease in another vessel
• Type III: diffuse ectasia confined to one vessel
• Type IV: localized ectasia

We excluded patients with lesions localised in a bypass graft, those upstream of a chronically occluded vessel (CTO), or patients presenting a stent within the vessel dilation at the time of the index coronary angiography. Patients without coronary angiograms available for visual inspection were also excluded. Coronary artery disease was identified and defined as a visual diameter stenosis above 50%.

Hospital records were screened for baseline clinical characteristics and co-morbidities (including inflammatory and oncologic diseases) as well as for cardiovascular and non-cardiovascular (i.e. the de novo diagnosis of infectious, inflammatory and oncologic diseases) outcomes for each enrolled patient, starting from the index invasive coronary angiography. Major adverse cardiovascular events (MACE) were defined as a composite of any incidental all-cause death, non-fatal myocardial infarctions or acute coronary syndromes (ACSs), unplanned ischaemia-driven percutaneous coronary interventions (PCIs), re-hospitalisation for heart failure (HF), acute cerebrovascular events and clinically overt bleeding (Bleeding Academic Research Consortium [Bleeding Academic Research Consortium] ≥2). Follow-up data collection ended on December 31, 2022.

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the local ethics committee (BASEC 2021-01119). Retrospective patient inclusion was possible for patients who signed the general consent for research at the University Hospital of Zurich and provided an informed written agreement for clinical data usage for research purposes. Approval by the Data Governance Board of the University Hospital of Zurich was obtained for database queries and extractions.

Statistical analysis

All statistical analyses were performed at a per-patient level to compare the three classification groups (CAE, CAA and CAA-CAE). Continuous variables with normal distributions are presented as mean ± standard deviation (SD), and non-normally distributed variables as medians (interquartile range [IQR]). Categorical variables are presented as percentages. The Chi-squared test was used for comparing categorical variables, while the Kruskal-Wallis test was used for continuous variables. Time-to-event data are presented as Kaplan-Meier estimates. Follow-up calculations were based on the time from the index invasive coronary angiography to the occurrence of a major adverse cardiovascular event or the last follow-up date. Censoring events included patients who were lost to follow-up or had not experienced a major adverse cardiovascular event by the end of the study period. Cox proportional-hazards regression models were used to compare the risk of incident events by CAA or CAE. To avoid ambiguity, the CAA-CAE group was omitted from the time-to-event and event prediction analyses. Anatomical and functional variables presenting a univariate relationship with incident events were included in the Cox proportional-hazards regression models. The proportional hazards assumption was verified as part of the Cox regression analysis and the Schoenfeld residual test. All analyses were performed using SPSS Statistics 29 (IBM Corp. Armonk, NY, USA) and MATLAB (Version R2022, MathWorks, Natick, MA, USA).

Results

Over 15 years (figure 1), a total of 281 patients presented with either a CAA (27.8%), a CAE (57.3%) or both (14.9%).

Figure 1Study flowchart. From the initial 352 patients presenting with a coronary aneurysm or ectasia according to the database query, 71 met the study exclusion criteria, and 281 were included in the study. Clinical follow-up was available in 253 cases. CAA: coronary artery aneurysm; CAE: coronary artery ectasia; CTO: chronic total occlusion; ICA: invasive coronary angiography; n/a: not available.

Clinical characteristics

Patients were predominantly male (87.9%), with a median age of 66 (57.7–74.5) years. The CAA group had a higher percentage of female patients (19.2% vs 10.6%, p = 0.045) and a higher median age (70.9 vs 65.4 years, p = 0.077), see table 1. The CAA group also had a lower prevalence of ST segment elevation myocardial infarctions (STEMIs) at the index event than the CAA-CAE and the CAE groups (7.7% vs 26.2% vs 14.3%, p = 0.022, respectively). Among the 40 patients presenting with STEMI, the causal lesion could be identified in 11 cases with an ectatic segment and in 3 cases with an aneurysmatic segment. Approximately one-fourth of the patients were admitted with symptoms or signs of acute heart failure (23.1% overall), while more than half had a preserved left ventricular ejection fraction (median = 53% overall). Nearly one-third of the patients presented ectatic or aneurysmatic vessels in other body areas. CAA patients were more likely to have undergone previous cardiac surgery (19.2% vs 0.0% vs 8.1%, p = 0.002). No differences were found regarding previous occurrences of cancer (19.9% overall) or inflammatory diseases among the groups (11.7% overall). High-sensitivity C-reactive protein (hs-CRP) concentration at baseline was comparable between the groups (3.30 mg/l overall), see appendix table S1.

Angiographic characteristics and treatment strategies at the index event

At the angiographical evaluation, CAAs were primarily found in a single vessel (80%), with a relatively low incidence in all three coronary arteries (6.7%), as reported in table 2. Fusiform aneurysms were the most common CAA type (65.8%). The co-occurrence of fusiform and saccular CAAs within the same patient was rare (5.0%). In contrast, CAE demonstrated a multi-district distribution in nearly half of the cases (45.8%), with types 2 and 4 being the most frequently observed (21.0% and 20.6%, respectively).

Over half of the patients (55.9%) exhibited multi-vessel coronary artery disease, with a trend towards reduced prevalence in those with CAE (absence of coronary artery disease: CAA 15.4% vs CAE 23.0%), although the differences between the three groups were not significant (p = 0.061), as shown in table 3.

A percutaneous coronary intervention was conducted in 43.4% of the cases during the initial procedure, with no significant distinctions between groups (p = 0.166), table 4. Interventions targeting dilated coronary segments occurred more frequently in CAA and CAA-CAE patients compared to those with CAE alone (24.4% vs 35.7% vs 14.3%, p = 0.853, respectively) and drug-eluting stents (DES) were generally used (47/57 of cases, p = 0.948). Patients with CAE had the highest prevalence of conservative medical treatment (49.7%, p = 0.138). Illustrated case examples of percutaneous coronary interventions on dilated coronary arteries are presented in appendix figures S1–S6.

At the vessel level, both saccular and fusiform CAAs were frequently identified in the left anterior descending (LAD) artery (33.0% and 40.5%, p <0.001, respectively), whereas three out of the four giant CAAs (75.0%, p <0.001) were localised in the right coronary artery (RCA). CAEs were often detected in the right coronary artery (46.9%), with type 2 being the most common CAE subtype (33.6%), as illustrated in appendix table S2.

In-hospital and long-term outcomes

Clinical adverse events were documented in 80 cases (28.3%) prior to hospital discharge, with no significant differences between the groups (33.8% vs 21.1% vs 29.1%, p = 0.369, respectively). Rates were primarily driven by periprocedural bleeding (5.49%, p = 0.223) and acute heart failure (6.23%, p = 0.841), as shown in appendix table S3.

Over a median follow-up period of 18.9 months (IQR 6.0–39.9), the incidence of major adverse cardiovascular events was substantial (CAA 44.0%, CAA-CAE 40.5% and CAE 34.5%; p = 0.367). Patients with the mixed disease form exhibited a higher rate of percutaneous coronary interventions targeting the dilated coronary segment (10.7%, 27.0% and 9.7%; p = 0.014), which was driven by a higher acute coronary syndrome rate (6.7%, 18.9% and 7.6%; p = 0.070), as detailed in table 4. Among the twelve reported patients with in-stent restenosis, four occurred in stents deployed in a dilated coronary artery segment (two cases in CAA vessels, one case in a CAE vessel, and one in a vessel presenting a mixed form). Only one stent thrombosis occurred in a dilated coronary artery (an aneurysmatic vessel). The detection of de novo cancers, inflammatory diseases and infectious diseases was reported in 8.2%, 3.1%, and 16.7% of cases for CAA, CAA-CAE, and CAE, respectively, with no significant differences between the groups (p >0.05 in all groups), appendix table S4.

Longitudinally, patients with angiographically identified CAA exhibited worse clinical outcomes than those with CAE, which reflected a higher incidence of acute coronary syndrome at follow-up and higher rates of coronary re-intervention (either at the level of the dilated coronary segment or in any normal coronary artery segment), figure 2 and appendix figure S7.

Figure 2Event incidence at the long-term follow-up. Patients presenting either coronary artery ectasia (CAE) or coronary artery aneurysm (CAA) showed an elevated incidence of adverse events at the long-term follow-up. ACS: acute coronary syndrome; MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention.

The Cox proportional hazards regression analysis found that aneurysmatic coronary artery segments exhibited a higher risk of adverse events compared to CAE (hazard ratio [HR] = 2.75, 95% confidence interval [CI] 1.84–4.10), p <0.0001) and major adverse cardiovascular events (HR = 2.26, 95% CI 1.38–3.69, p = 0.001), driven by a higher acute coronary syndrome hazard (HR = 5.00, 95% CI 1.66–15.02, p = 0.004) and percutaneous coronary intervention hazard (in a dilated coronary segment: HR 3.23, 95% CI 1.40–7.45, p = 0.006; in any coronary segment: HR 3.83, 95% CI 2.08–7.07, p = 0.001), figure 3 and figure S8 in the appendix. The presence of obstructive coronary artery disease did not significantly influence the risk of major adverse cardiovascular events at the follow-up in CAA or CAE patients, appendix figure S9.

Figure 3Time-dependent event risk. Results of the Cox models for coronary artery ectasia (CAE) or coronary artery aneurysm (CAA) and the time-dependent hazard ratio (HR) of adverse events. In dash, the shorter-term outcomes with respect to the one reported in bold (maximum follow-up time). MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention.

Discussion

In this study, a total of 281 patients with dilated coronary artery disease were investigated, and clinical characteristics, angiographic patterns and the long-term adverse outcomes of patients presenting with CAE and CAA were described. The main results of the study were: (a) CAE demonstrated a multi-district distribution, while CAAs were primarily isolated to a single coronary segment; (b) multi-vessel obstructive coronary artery disease was prevalent in more than half of the patients; (c) clinical adverse events were common in-hospital and at the long-term follow-up; and (d) aneurysmatic coronary artery segments were associated with a higher risk of adverse events and major adverse cardiovascular events, which was driven by higher hazards of acute coronary syndrome and percutaneous coronary intervention at the follow-up.

The spectrum of coronary artery remodelling

The initial phase of atherosclerotic plaque formation involves leukocyte migration, foam cell formation, and extracellular matrix degradation, leading to expansive coronary remodelling that maintains lumen diameter and prevents narrowing [1]. Dysregulation of these mechanisms by injury or degradation of the vessel layers, especially the media, can cause either reverse remodelling with luminal narrowing or further dilation, resulting in coronary ectasia and aneurysm formation [2–4]. As such, both obstructive and dilative coronary artery disease can co-exist within the same coronary artery tree. In our analysis, only a small percentage of the vessels included in the study failed to exhibit a (significant) obstructive coronary artery disease form (18.2%). Instead, extensive three-vessel disease was the most common coronary artery disease variant associated with either CAA (34.6%) or CAE (28.6%). This, coupled with the high prevalence of traditional cardiovascular risk factors in both dilative coronary artery disease subgroups, supports the theory of a significant overlap in the pathobiology between obstructive and dilative coronary artery disease [8]. Notably, this disease form appears to predominantly affect males (ca. 88% of male patients in our cohort), a trend consistent with the literature [9].

Coronary aneurysms and ectasia as two different biological conditions

While sharing a similar pathophysiology, in our analysis, CAAs and CAEs appeared to be distinct entities with marginally overlapping clinical characteristics. In the study population, coronary aneurysms and ectasia co-existed, however, only 14.9% of patients presented with both conditions. The CAA group had a higher proportion of female patients, was older, and was more likely to have undergone cardiac surgery than the CAE group. A similar prevalence of inflammatory and oncological conditions was found in both groups. A trend toward higher hs-CRP in the CAA group was also found, suggesting a higher prevalence of residual inflammatory risk [10, 11].

Angiographic characteristics also varied among groups. CAAs were primarily localised in a single vessel, whereas CAE exhibited a multi-district distribution in nearly half of the cases. The distribution of CAA was relatively balanced among the three major coronary arteries, except for the giant form, which was almost invariably located in the right coronary artery. Conversely, CAE was most frequently located in the right coronary artery (46.9% of cases). Furthermore, CAAs had a more extensive representation along the coronary tree, also appearing at the level of diagonal and marginal side branches, a trait not observed in CAE cases. Nevertheless, coronary ectasia had, in 79.0% of cases, a diffuse manifestation (i.e. type 1, type 2 or type 3) with the involvement of more than one segment along the epicardial vessel.

Coronary aneurysms and ectasia present different clinical and risk profiles

The scientific literature regarding clinical outcomes in patients with dilated coronary artery disease is typically sparse, often biased by varying anatomical definitions and inclusion criteria, and marked by controversial conclusions. Luo et al. demonstrated a lower coronary flow (quantified in terms of TIMI frame counts) in patients with CAA compared to those with CAE, suggesting that impaired intravascular haemodynamics could lead to ischaemia [12]. Núñez-Gil et al. reported that morbidity and mortality rates in large European and North American populations with CAA exceeded 30% and 15%, respectively [9]. Several studies have indicated worse post-procedural outcomes in the form of dilated coronaropathy than obstructive coronary artery disease [2]. However, a comprehensive comparison of long-term clinical outcomes in patients presenting with either CAA or CAE has not been adequately addressed.

Our longitudinal analysis of patient outcomes specifically underscored the distinct clinical behaviour of CAAs and CAEs. In our cohort, patients with angiographically identified CAAs demonstrated worse clinical outcomes than those with CAEs. This was not only indicated by a higher incidence of acute coronary syndrome during follow-up but also by an increased rate of coronary re-interventions involving dilated coronary segments and other normal coronary artery segments. The Cox proportional hazards regression analysis further corroborated these findings, revealing that aneurysmal coronary artery segments were associated with a significantly higher risk of adverse events and major adverse cardiovascular events, predominantly driven by a higher incidence of acute coronary syndrome and a subsequent requirement for a percutaneous coronary intervention during follow-up. This was observed in a mixed, real-world study population where patients were equally treated operatively and conservatively at baseline.

Elevated rate of stent failure in dilated coronary disease

The high rates of in-stent restenosis and stent thrombosis in our cohort were noteworthy. Considering only the sub-group of patients who underwent a percutaneous coronary intervention at the baseline coronary angiography, the rates of in-stent restenosis and stent thrombosis were recorded at 9.8% and 2.5%, respectively, over a median follow-up period of 18.9 months. In particular, one-third of the recorded stent failures occurred in stents positioned within a dilated coronary artery segment, where in-stent restenosis and stent thrombosis rates reached 22.2% and 1.8%, respectively. The causes of stent failure within an enlarged vessel segment may be secondary to procedural factors, such as sub-optimal stent apposition, stent fracture or edge dissection due to forceful post-dilation or a lack of post-procedural imaging control [13]. Aneurysm ceilings with covered stents were rare, performed in two out of nineteen treated CAAs. However, the reasons for the increased risk in non-dilated coronary artery segments are less clear. Potential factors could be alterations in intra-coronary haemodynamics, such as a decreased flow speed downstream of a coronary aneurysm or secondary flow patterns with blood re-circulation and platelet activation [14–16]. Alongside these factors, the presence of a biologically favourable environment with heightened pro-inflammatory activity – as the registered elevated hs-CRP levels might suggest – could also play a role in affecting the long-term performance of stents in these patients [17]. Larger studies are needed to substantiate the evidence of an elevated stent failure rate in this population and to properly address its aetiology.

Limitations

This study acknowledges several limitations. Firstly, patient selection was executed using a comprehensive system query based on pre-defined keywords rather than a visual examination of each coronary angiography performed at our institution. Nevertheless, considering the extensive timeframe for patient inclusion (15 years) and the numerous operators performing angiography procedures, the risk of selection bias is minimal. Secondly, the classification of CAA or CAE was based on visual assessments of the coronary angiograms rather than intravascular imaging (e.g. intravascular ultrasound or optical coherence tomography). Consequently, the precision of the assessment may be impaired, and the inadvertent inclusion of coronary pseudoaneurysms cannot be ruled out. However, the implemented methodology better represents current routine clinical practice. Third, the study lacks a comparative analysis with a control group with obstructive coronary artery disease without CAA/CAE. However, it should be noted that obstructive coronary artery disease prevalence in the investigated cohort was large. This fact, in conjunction with the high prevalence of traditional risk factors for coronary artery disease, implies a significant overlap between the two types of coronary diseases, making a direct comparison less informative. Finally, the observed increased risk associated with CAA could be partially attributed to the longer follow-up period for this group (a median follow-up duration of 713 days) compared to the CAE group (a median follow-up duration of 543 days), highlighting the importance of considering the follow-up duration when interpreting these results.

Conclusions

Aneurysmatic coronary segments presented a more aggressive clinical course compared to coronary ectasia, emphasising the need for a nuanced approach to patient management that also accounts for the different manifestations of dilative coronary artery disease. Further research is necessary to elucidate the mechanisms behind these divergent outcomes and to develop targeted therapeutic strategies for patients presenting with either form of dilated coronary artery disease. 

References

1. Stary HC. Natural history and histological classification of atherosclerotic lesions: an update. Arterioscler Thromb Vasc Biol. 2000 May;20(5):1177–8. doi: https://doi.org/10.1161/01.ATV.20.5.1177 

2. Kawsara A, Núñez Gil IJ, Alqahtani F, Moreland J, Rihal CS, Alkhouli M. Management of Coronary Artery Aneurysms. JACC Cardiovasc Interv. 2018 Jul;11(13):1211–23. doi: https://doi.org/10.1016/j.jcin.2018.02.041 

3. Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006 Apr;47(8 Suppl):C7–12. doi: https://doi.org/10.1016/j.jacc.2005.09.068 

4. Antoniadis AP, Chatzizisis YS, Giannoglou GD. Pathogenetic mechanisms of coronary ectasia. Int J Cardiol. 2008 Nov;130(3):335–43. doi: https://doi.org/10.1016/j.ijcard.2008.05.071 

5. Scott DH. Aneurysm of the coronary arteries. Am Heart J. 1948 Sep;36(3):403–21. doi: https://doi.org/10.1016/0002-8703(48)90337-8 

6. Núñez-Gil IJ, Nombela-Franco L, Bagur R, Bollati M, Cerrato E, Alfonso E, et al.; CAAR Investigators. Rationale and design of a multicenter, international and collaborative Coronary Artery Aneurysm Registry (CAAR). Clin Cardiol. 2017 Aug;40(8):580–5. doi: https://doi.org/10.1002/clc.22705 

7. Syed M, Lesch M. Coronary artery aneurysm: a review. Prog Cardiovasc Dis. 1997;40(1):77–84. doi: https://doi.org/10.1016/S0033-0620(97)80024-2 

8. Vergallo R, Crea F. Atherosclerotic Plaque Healing. N Engl J Med. 2020 Aug;383(9):846–57. doi: https://doi.org/10.1056/NEJMra2000317 

9. Núñez-Gil IJ, Cerrato E, Bollati M, Nombela-Franco L, Terol B, Alfonso-Rodríguez E, et al.; CAAR investigators. Coronary artery aneurysms, insights from the international coronary artery aneurysm registry (CAAR). Int J Cardiol. 2020 Jan;299:49–55. doi: https://doi.org/10.1016/j.ijcard.2019.05.067 

10. Carrero JJ, Andersson Franko M, Obergfell A, Gabrielsen A, Jernberg T. hsCRP Level and the Risk of Death or Recurrent Cardiovascular Events in Patients With Myocardial Infarction: a Healthcare-Based Study. J Am Heart Assoc. 2019 Jun;8(11):e012638. doi: https://doi.org/10.1161/JAHA.119.012638 

11. Candreva A, Matter CM. Is the amount of glow predicting the fire? Residual inflammatory risk after percutaneous coronary intervention. Eur Heart J. 2022 Feb;43(7):e10–3. doi: https://doi.org/10.1093/eurheartj/ehy729 

12. Luo Y, Tang J, Liu X, Qiu J, Ye Z, Lai Y, et al. Coronary Artery Aneurysm Differs From Coronary Artery Ectasia: Angiographic Characteristics and Cardiovascular Risk Factor Analysis in Patients Referred for Coronary Angiography. Angiology. 2017 Oct;68(9):823–30. doi: https://doi.org/10.1177/0003319716665690 

13. Esposito L, Di Maio M, Silverio A, Cancro FP, Bellino M, Attisano T, et al. Treatment and Outcome of Patients With Coronary Artery Ectasia: Current Evidence and Novel Opportunities for an Old Dilemma. Front Cardiovasc Med. 2022 Feb;8:805727. doi: https://doi.org/10.3389/fcvm.2021.805727 

14. Fan T, Zhou Z, Fang W, Wang W, Xu L, Huo Y. Morphometry and hemodynamics of coronary artery aneurysms caused by atherosclerosis. Atherosclerosis. 2019 May;284:187–93. doi: https://doi.org/10.1016/j.atherosclerosis.2019.03.001 

15. Kuramochi Y, Ohkubo T, Takechi N, Fukumi D, Uchikoba Y, Ogawa S. Hemodynamic factors of thrombus formation in coronary aneurysms associated with Kawasaki disease. Pediatr Int. 2000 Oct;42(5):470–5. doi: https://doi.org/10.1046/j.1442-200x.2000.01270.x 

16. Burns JC, Glode MP, Clarke SH, Wiggins J Jr, Hathaway WE. Coagulopathy and platelet activation in Kawasaki syndrome: identification of patients at high risk for development of coronary artery aneurysms. J Pediatr. 1984 Aug;105(2):206–11. doi: https://doi.org/10.1016/S0022-3476(84)80114-6 

17. Niccoli G, Montone RA, Ferrante G, Crea F. The evolving role of inflammatory biomarkers in risk assessment after stent implantation. J Am Coll Cardiol. 2010 Nov;56(22):1783–93. doi: https://doi.org/10.1016/j.jacc.2010.06.045 

Appendix

The appendix is available in the pdf version of the article at https://doi.org/10.57187/s.3857.