Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood.
To investigate the prevalence of coronary artery aneurysms as a cardiovascular sequel of untreated or missed KD in childhood in young adults in Egypt, we reviewed angiograms of patients <40 years who presented to a university hospital, a private clinic, and a private imaging facility with signs and symptoms of myocardial ischemia.
Methods
Subjects who underwent coronary angiography for evaluation of suspected myocardial ischemia from July 2010 through December 2011 at a university hospital (Kasr El Aini Hospital, Cairo, Egypt), and had coronary artery aneurysms detected (n = 9), were prospectively identified and enrolled after providing informed consent. The total number of patients ≤40 years who underwent invasive coronary angiography at this facility during the same time period was also determined (n = 140). The age of 40 years was chosen as an arbitrary cutoff to minimize the number of subjects with aneurysms because of atherosclerosis. The study protocol and consents for prospectively enrolled patients were approved by the Ethics Committee of Kasr Al Aini Hospital.
In addition, we retrospectively reviewed all conventional coronary angiograms (n = 140) and Multi-Slice Computed Tomography (MSCT) coronary angiograms (n = 300) performed at a private, free-standing clinic (Cairo Cath), and a private imaging facility (Alfa Scan) (both facilities are located in Cairo, Egypt) from January 2008 to December 2011 (because of availability of records for this time period only) on patients ≤40 years, with coronary aneurysms noted in their angiograms (n = 13 and n = 24, respectively). The study protocol for the retrospective review was approved by the Clinical Director of each of the private facilities.
Data collected for each patient included demographic characteristics, medical history, clinical and laboratory data, electrocardiographic, and angiographic findings. A medical history consistent with acute KD (history of fever >5 days in childhood associated with rash, conjunctival injection, and periungual desquamation in the convalescent phase) was sought from the patients prospectively enrolled in the study. A history of a KD-compatible illness (e.g., scarlet fever, measles) was also sought. None of the patients had received intravenous immunoglobulin treatment, and none had a diagnosis of vasculitis, connective tissue disease, or autoimmune disorders. Traditional cardiovascular risk factors were recorded including fasting lipid levels, smoking history (current, past, and never), hypertension (defined as a physician-documented history of high blood pressure), diabetes, and family history of coronary artery disease (CAD; defined as mother with CAD at age ≤65 years and/or father with CAD at age ≤55 years). Subjects were given a risk factor score based on the number of cardiovascular risk factors present (maximum score = 5).
All 580 angiograms were reviewed by 2 of the investigators (GES and SRYR). Then angiograms showing coronary aneurysms were reviewed by coinvestigators JBG and LBD who were blinded to the history and risk factors of all patients. Coronary artery aneurysms were confirmed if the internal diameter of the coronary artery segment measured ≥1.5 times that of an adjacent segment. Aneurysms were adjudicated as “definitely attributable to antecedent KD” if the patient had a known history of KD or a KD-compatible illness and the aneurysm location was proximal, and the distal coronary artery segments were angiographically normal. Aneurysms were adjudicated as “probably attributable to antecedent KD” when angiographic findings were as mentioned earlier, but there was no known KD-compatible illness, or medical history was unavailable. Aneurysms adjudicated as “equivocal” had diffuse ectasia or distal CAD consistent with atherosclerosis.
Categorical data are presented as percentages; continuous data are presented as medians and interquartile ranges. The equivocal group was compared with the definite and probable groups combined. Nonparametric data were compared using the Mann-Whitney test. Categorical data were compared using the Fisher’s exact test. All p values are 2 sided with values <0.05 considered statistically significant.
Results
A total of 580 angiograms (conventional and multislice computed tomography) of patients ≤40 years were reviewed from the 3 centers. Coronary artery aneurysms were reported in 46 cases (7.9%). Most of the patients were men. The most commonly encountered risk factors were smoking followed by dyslipidemia ( Table 1 ). The group adjudicated as equivocal had more traditional cardiovascular risk factors compared with the definite and probable groups combined (p <0.05, Table 1 ).
| Characteristic | Definite n = 10 | Probable n = 29 | Equivocal n = 7 | Total n = 46 | P |
|---|---|---|---|---|---|
| Median age, years (range) | 35 (14 – 40) | 39 (25 – 40) | 40 (37 – 40) | 39 (14 – 40) | 0.15 |
| Male (%) | 10 (100%) | 29 (100%) | 6 (86%) | 45 (98%) | 0.15 |
| CAD risk factors, n (%) | |||||
| Smoking | 6 (60%) | 14 (48%) | 4 (57%) | 24 (52%) | 1.00 |
| Diabetes | 0 | 3 (10%) | 3 (43%) | 6 (13%) | 0.04 |
| Hypertension | 0 | 8 (28%) | 4 (57%) | 12 (26%) | 0.06 |
| Dyslipidemia | 6 (60%) | 10 (35%) | 5 (71%) | 21 (46%) | 0.22 |
| LDL >130 mg/dl | 3 (30%) | 5 (17%) | 4 (57%) | 12 (26%) | 0.06 |
| HDL <40 mg/dl | 3 (30%) | 8 (28%) | 3 (43%) | 14 (30%) | 0.66 |
| TC > 200 mg/dl | 3 (30%) | 5 (17%) | 4 (57%) | 12 (26%) | 0.06 |
| TG > 150 mg/dl | 2 (20%) | 5 (17%) | 4 (57%) | 11 (24%) | 0.046 |
| Family history of CAD | 0 | 1 (3%) | 1 (14%) | 2 (4%) | 0.28 |
| Number of risk factors | 0.04 | ||||
| 0 | 2 (20%) | 9 (31%) | 1 (14%) | 12 (26%) | |
| 1 | 4 (40%) | 7 (24%) | 0 | 11 (24%) | |
| 2 | 4 (40%) | 11 (38%) | 3 (43%) | 18 (39%) | |
| 3 | 0 | 1 (3%) | 1 (14%) | 2 (4%) | |
| 4 | 0 | 1 (3%) | 2 (29%) | 3 (7%) | |
| 5 | 0 | 0 | 0 | 0 | – |
Indications for angiographic evaluation of these 46 patients with aneurysms were as follows: 9 had myocardial infarction with elevated troponin-I levels (including 5 with inferior ST-segment elevation myocardial infarction [STEMI], 2 with anterior STEMI, and 2 with non-STEMI), whereas the remaining patients had angina (23 with unstable angina and 14 with exertional angina either not responding to medical treatment or confirmed by positive stress test).
Of the 46 patients with aneurysms, 10 (22%) were adjudicated as definitely because of antecedent KD. All had a history of KD or a KD-compatible illness (history of classic KD that was misdiagnosed in 3, scarlet fever in 1, and measles in 6). One of the 3 patients with missed KD was a 14-year-old men presenting with an anterior STEMI. Seven years earlier, he had presented with clinical criteria for KD but was misdiagnosed with acute rheumatic fever. Echocardiography at presentation showed no coronary artery abnormalities, but a repeat echocardiogram 3 months later revealed aneurysms of the proximal right and left coronary arteries.
An additional 29 patients had no history of a KD-compatible illness but had aneurysms adjudicated as probably because of antecedent KD based on their proximal location and angiographically normal distal vessels without changes suggesting atherosclerosis. Of these 29 patients, 24 patients underwent MSCT and 8 of 24 (33%) had calcification of their aneurysms.
Seven of the 46 patients (15%) were adjudicated as equivocal because their aneurysms were diffuse, with or without significant luminal narrowing suggestive of atherosclerosis. The median size of the largest aneurysm was 9.0 mm (7.0 to 12.0) for the definite group, 7.5 mm (6.5 to 54.0) for the probable group, and 6.5 mm (6.0 to 7.5) for the equivocal group (p = 0.03 for the difference between definite and probable groups vs equivocal group) ( Figure 1 ).
Assessment of the distribution of coronary arteries affected by aneurysms revealed that the left anterior descending artery was the most commonly affected artery followed by the right coronary artery ( Table 2 ). The distribution of patients with 1, 2, or 3 coronary arteries with aneurysms differed by the group classification. Of the 10 patients with only 1 coronary artery affected, 5 (71%) were classified as equivocal, 4 (14%) were probable, and only 1 (10%) was definite. Of the 36 patients with 2 or more coronary arteries affected, only 2 (29%) were classified as equivocal, 25 (86%) were probable, and 9 (90%) were definite (p = 0.003). Giant coronary artery aneurysms (≥8 mm) were present in 22 patients (48%), and 8 patients (36%) had thrombi in their coronary aneurysms.
