Takayasu arteritis (TA) may affect myocardium and cause coronary stenosis. The aim of this study was to assess the prevalence and pattern of myocardial disease in patients with TA, using late gadolinium enhancement (LGE) of cardiac magnetic resonance imaging (CMRI). Twenty-seven consecutive patients with TA and 80 age- and gender-matched controls without known cardiovascular disease underwent CMRI. The prevalence of myocardial ischemic disease, as revealed by LGE, was compared between patients with TA and controls, and factors associated with myocardial disease were identified in patients with TA. Myocardial ischemic disease, as characterized by LGE on CMRI, was present in 7 (25.9%) of 27 patients with TA, and imaging with LGE showed a typical pattern of myocardial infarction in 6 patients (22.2%). Although both patients with TA and control subjects shared a similar risk of cardiovascular events, the prevalence of myocardial ischemia was >5× greater in patients with TA (p = 0.002 vs controls). No association was found between myocardial disease in patients with TA and cardiovascular atherosclerotic risk factors. The presence of myocardial scarring tended to be more closely associated with specific features of TA such as renovascular hypertension, older age at the onset of TA symptoms, male gender, aneurysmal dilatation, and Numano type V. In conclusion, finding of a significant and unexpectedly high prevalence of occult myocardial scarring in patients with TA indicates the usefulness of CMRI with LGE for the identification of occult myocardial disease in such patients.
Takayasu arteritis (TA) is a rare vasculitis of unknown cause affecting large vessels, predominantly the aorta and/or its main branches. Arterial inflammation leads to wall thickening, fibrosis, stenotic lesions, aneurysms, and thrombus formation. Although once believed to be a disorder that mostly affected young Asian women, TA has been identified in both genders and many ethnic and racial groups worldwide. Myocardial infarction (MI) is rarely reported as a clinical manifestation of patients with TA, and coronary arteries are involved in <10% of patients. However, myocardial perfusion abnormalities using myocardial scintigraphy and myocardial scarring on cardiac magnetic resonance imaging (CMRI) have been observed in 53% to 78% and 27%, respectively, in patients with asymptomatic TA. Myocardial involvement in TA is considered as a major cause of morbidity and mortality, but it is rarely clinically evident. Late gadolinium enhancement (LGE) of cardiac images obtained by contrast-enhanced CMRI may detect and characterize small-sized myocardial scars that are undetectable by other noninvasive imaging techniques. The aims of our study were to assess the prevalence and pattern of occult myocardial ischemic disease, as characterized by LGE, in patients with TA and to identify the factors associated with occult myocardial ischemic disease in patients with TA.
Methods
Twenty-seven consecutive patients with TA were prospectively recruited from our department of internal medicine (Groupe Hospitalier Pitié-Salpêtrière, Paris, France) from December 2010 to December 2012. All patients met ≥3 of the 1990 American College of Rheumatology classification criteria for TA. Potential confounding conditions (giant cell arteritis, Cogan syndrome, Behçet disease, Kawasaki disease, syphilis, tuberculosis aortitis, vascular Ehlers-Danlos syndrome, Marfan syndrome, and neurofibromatosis) were excluded. Diagnosis of TA was based on clinical, biologic, and imaging data (i.e., vascular echography, arteriography, computed tomography angiography, and/or magnetic resonance angiography). We classified patients according to the Numano classification into 6 types. Disease activity of patients with TA was evaluated according to the National Institute of Health criteria defined by Kerr et al. For each patient, the following data were recorded at the time of CMRI: age at the onset of TA symptoms, gender, geographic origin, cardiovascular risk factors (i.e., smoking, hypertension [systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg], hypercholesterolemia [low-density lipoprotein cholesterol >130 mg/dl], overweight [body mass index >25 kg/m 2 ], diabetes), clinical features of TA (systemic and/or vascular symptoms), current treatment(s), and laboratory data (erythrocyte sedimentation rate, C-reactive protein, troponin, and creatininemia). The cut-off titers used to define abnormal C-reactive protein and erythrocyte sedimentation rate were >4 mg/L and >15 mm/h, respectively. Physical examination, electrocardiography, and transthoracic echocardiography were performed. All patients provided their informed consent to undergo CMRI and to participate in the observational study. This study was approved by our institutional review board.
One hundred three age- and gender-matched and unselected subjects with end-stage renal disease (ESRD) who underwent delayed-enhancement CMRI at the same department of medical imaging during the same period of time, all for preoperative risk evaluation before renal transplantation, were screened for inclusion in the control group. Twenty-three control subjects were excluded for insufficient data (n = 6), history of MI or acute coronary syndrome (n = 12), cardiac arrest (n = 1), heart transplantation (n = 1), or associated inflammatory disease (n = 3). Finally, 80 age- and gender-matched control subjects with ESRD but without personal or familial history of cardiac disease were included in the control group. A propensity score analysis has confirmed the similarities of the TA and control groups.
For all subjects included in this study, the risk of cardiovascular events was calculated as the absolute risk within the next 10 years using the Framingham risk equation, which includes adjustments for age, gender, total cholesterol level, high-density lipoprotein cholesterol level, smoking history, and systolic blood pressure.
A standard 12-lead electrocardiogram at rest was recorded and analyzed by an experienced physician. Echocardiographic examinations were performed in standard parasternal, apical, and subxiphoidal views. The left ventricular (LV) ejection fraction (LVEF) was calculated in a standard manner and was used to assess global left ventricular systolic function. Abnormalities were reported as wall motion abnormalities, myocardial hypertrophy, and valvular regurgitation.
CMRI was performed using a 1.5 T system (Gyroscan Intera; Philips, Best, The Netherlands), with a 5-element phased-array thoracic coil and the SENSE technique. All acquisitions followed a standard protocol with T2-weighted short tau inversion recovery (STIR)–black-blood imaging, cine SSFP dynamic acquisitions in short and long axis (2 and 4 chambers), first-pass perfusion imaging, and LGE sequences. LGE CMR was performed 10 to 20 minutes after the intravenous dimeglumine gadobenate injection (0.2 ml/kg). From 12 to 16 short-axis slides were acquired (repetition time 4 ms, echo time 2 ms, flip angle 20°, matrix size 256 × 256, slice thickness 6 mm, no gap), covering the whole LV from base to apex. The inversion time was optimized using scouting look-locker sequence to minimize the signal in the remote myocardium (inversion time range was 170 to 200 ms). Image acquisition and the LGE analysis were performed by a single expert blinded to all clinical data. The expert visually judged the occurrence (absence vs presence), localization, and pattern of LGE imaging of myocardial scarring. The pattern and extent of LGE-detected myocardial scarring were assessed by using short- and long-axis views, and myocardial scarring was defined as present only if it was detectable by LGE on 2 orthogonal planes. Areas of LGE were allocated to the American Heart Association 17-segment model. Regions of LGE were defined to reflect myocardial fibrosis and described as indicative of either typical MI (involving the subendocardium) or atypical MI (subepicardial, patchy midwall, or diffuse circumferential pattern).
Data are expressed as median (interquartile range) for quantitative variables or counts and percentages (%) for categorical variables. Comparisons between quantitative variables were performed using the nonparametric paired Wilcoxon test and Fisher’s exact test for categorical variables. p Values of <0.05 were considered to be significant. Tests were performed using SPSS Statistics, version 17.0, for Windows (SPSS Inc., Chicago, Illinois).
Results
The clinical characteristics and disease features of the patients with TA are listed in Table 1 . The prevalence of traditional cardiovascular risk factors such as hypertension, dyslipidemia, tobacco use, and diabetes was low among the patients with TA, as listed in Table 2 .
| Variable | All Patients (n = 27) | LGE+ (n = 7) | LGE− (n = 20) | p |
|---|---|---|---|---|
| Age (yrs) | 48 (34–61) | 48 (46–65) | 44.5 (29.5–60.5) | 0.135 |
| Female sex | 19 (70.4) | 4 (57.1) | 15 (75) | 0.373 |
| White | 18 (66.7) | 5 (71.4) | 13 (65) | 0.756 |
| Age at onset of symptoms (yrs) | 36 (26–50) | 39 (36–45) | 30.5 (25–50) | 0.352 |
| Median age of disease duration (yrs) | 9 (3–13) | 10 (6–20) | 9 (3–12) | 0.737 |
| Angiographic classification of TA, Numano type | 0.408 | |||
| I | 6 (22.2) | 1 (14.3) | 5 (25) | |
| IIa | 1 (3.7) | 1 (14.3) | 0 | |
| IIb | 2 (7.4) | 0 | 2 (10) | |
| III | 6 (22.2) | 1 (14.3) | 5 (25) | |
| IV | 1 (37) | 0 | 1 (5) | |
| V | 11 (40.7) | 4 (57.1) | 7 (35) | |
| Ishikawa clinical classification | 0.426 | |||
| 1 | 9 (333) | 1 (14.3) | 8 (40) | |
| 2 | 12 (44.4) | 4 (57.1) | 8 (40) | |
| 3 | 6 (22.2) | 2 (28.6) | 4 (20) | |
| Major complication at diagnosis | ||||
| Aortic regurgitation | 6 (22.2) | 1 (14.3) | 5 (25) | 0.557 |
| Aneurysm | 9 (33.3) | 4 (57.1) | 5 (25) | 0.121 |
| Retinopathy | 3 (11.1) | 0 | 3 (15) | 0.277 |
| Disease activity, NIH | 0.630 | |||
| 0 | 13 (48.1) | 4 (57.1) | 9 (45) | |
| 1 | 4 (14.8) | 1 (14.3) | 3 (15) | |
| 2 | 6 (22.2) | 2 (28.6) | 4 (20) | |
| 3 | 4 (14.8) | 0 | 4 (20) | |
| Abnormal heart murmurs | 5 (18.5) | 2 (28.6) | 3 (15) | 0.426 |
| Heart frequency | 74 (67–80) | 73.5 (66.5–85.75) | 74 (67.5–80) | 0.580 |
| SBP (mm Hg) | 130 (120–144) | 144 (122–148) | 129 (119–137) | 0.211 |
| DBP (mm Hg) | 76 (69–80) | 76 (66–80) | 76 (69–81) | 0.370 |
| Number of arterial territory involved | 5 (3–7) | 5 (2–7) | 5 (3–8) | 0.628 |
| BMI (kg/m 2 ) | 24.7 (22.3–28.7) | 24.5 (22.5–25) | 25.1 (22.2–31) | 0.439 |
| Diabetes mellitus | 4 (14.8) | 1 (14.3) | 3 (15) | 0.963 |
| Renovascular hypertension | 10 (37) | 5 (71.4) ∗ | 5 (25) ∗ | 0.029 |
| Dyslipidemia | 9 (33.3) | 3 (42.9) | 6 (30) | 0.535 |
| Tobacco use | 7 (25.9) | 3 (42.9) | 4 (20) | 0.235 |
| Family history of CAD | 3 (11.8) | 0 | 3 (15) | 0.277 |
| ECG | ||||
| Normal | 23 (85.2) | 5 (71.4) | 18 (90) | 0.234 |
| Q waves | 0 | 0 | 0 | NA |
| Conduction blocks | 4 (14.8) | 2 (28.6) | 2 (10) | 0.204 |
| Oral corticosteroids | 25 (92.6) | 7 (100) | 18 (90) | 0.385 |
| Prednisone dose (mg/day) | 15 (10–20) | 10 (10–20) | 15 (7–20) | 0.418 |
| Current immunosuppressor | 21 (77.8) | 7 (100) | 14 (70) | 0.100 |
| Methotrexate | 18 (66.7) | 6 (85.7) | 12 (60) | 0.214 |
| Azathioprine | 2 (7.4) | 0 | 2 (10) | 0.385 |
| Mycophenolate mofetil | 1 (3.7) | 1 (14.3) | 0 | 0.085 |
| Anti-TNF | 4 (14.8) | 1 (14.3) | 3 (15) | 0.963 |
| Statin | 24 (88.9) | 7 (100) | 17 (85) | 0.277 |
| Aspirin | 20 (74.1) | 5 (71.4) | 15 (75) | 0.853 |
| Clopidogrel | 8 (29.6) | 3 (42.9) | 5 (25) | 0.373 |
| Antihypertensive agents | 9 (33.3) | 4 (57.1) | 5 (25) | 0.121 |
| Oral anticoagulant | 4 (14.8) | 2 (33.3) | 2 (9.5) | 0.204 |
| Troponin (ng/ml) | All negative | All negative | All negative | NA |
| Abnormal CRP (>4 mg/L) | 8 (29.6) | 2 (28.6) | 6 (30) | 0.943 |
| CRP, mg/L | 8 (4–11.5) | 7.5 (2.5–18) | 8 (4–11.5) | 0.456 |
| Abnormal ESR (>15 mm/h) | 10 (40) | 1 (20) | 9 (45) | 0.702 |
| ESR, mm/h | 14 (10.5–28.5) | 12.5 (2–16) | 25 (11–38) | 0.594 |
| Total cholesterol | ||||
| g/L | 1.7 (1.5–2.6) | 1.79 (1.43–2.6) | 1.65 (1.51–2.45) | 0.382 |
| mg/dl | 170 (150–260) | 179 (143–260) | 165 (151–245) | |
| Creatininemia (μmol/L) | 76.5 (69.75–88) | 83 (79–91) | 73 (65–81) | 0.554 |
| Echocardiography | ||||
| Segmental wall motion abnormality | 4 (14.8) | 2 (28.6) | 2 (10) | 0.244 |
| Septal and/or LV hypertrophy | 4 (14.8) | 1 (14.3) | 3 (15) | 0.963 |
| Mitral and/or aortic valvulopathy | 12 (44.4) | 3 (42.9) | 9 (45) | 0.922 |
| LVEF (%) | 57 (52–61) | 60 (54–65) | 56.5 (51.5–59.75) | 0.346 |
| Variable | Patients With TA (n = 27) | Control Subjects (n = 80) | p |
|---|---|---|---|
| Age (yrs) | 48 (34–61) | 51 (4–59) | 0.304 |
| Female sex | 19 (70.4) | 48 (60) | 0.368 |
| Diabetes mellitus | 4 (14.8) | 26 (32.5) | 0.088 |
| Hypertension (history) | 10 (37) ∗ | 55 (68.8) ∗ | 0.006 |
| Dyslipidemia (history) | 9 (33.3) | 31 (38.8) | 0.653 |
| Tobacco use | 7 (25.9) | 16 (20) | 0.590 |
| Family history of CAD | 3 (11.8) | NA | NA |
| Total cholesterol | |||
| g/L | 1.7 (1.5–2.6) | 1.73 (1.54–2.08) | 0.235 |
| mg/dl | 170 (150–260) | 173 (154–208) | |
| Absolute cardiovascular risk (%) | 5 (2–8) | 5 (3–9.5) | 0.219 |
| LGE revealed on CMR | 7 (25.9) ∗ | 4 (5) ∗ | 0.002 |
None of the control subjects had a known history of cardiac disease, and all were asymptomatic. Although the percentage of subjects with a history of hypertension was higher among the control group than among patients with TA, no significant differences in the prevalence of classic coronary risk factors were observed between the groups ( Table 2 ).
Myocardial ischemic disease characterized by LGE of CMRI was present in 7 (25.9%) of 27 patients with TA and in 4 (5%) of 80 control subjects. The difference of LGE-detected myocardial disease prevalence was statistically significant and >5× greater in patients with TA compared with controls (p = 0.002). Patients and controls shared similar cardiovascular risk factors ( Table 2 ), except for a less frequent history of hypertension in TA group (37% vs 68.8% in the control group, p = 0.006). In patients with TA, LGE displayed a typical pattern of MI in 6 (22.2%) of 27 patients, in showing scarring of the subendocardium with partial (n = 1) or complete (n = 5) transmural spreading ( Figures 1 and 2 ). By assigning myocardial segments (MSs) to coronary artery territories, the findings revealed by LGE were ascribed to a single coronary artery in all 6 patients with TA in whom a typical pattern of MI was observed. LGE of CMRI revealed scarring in the right coronary artery territory (MSs 4, 9, and 10) in 3 patients, in the left circumflex coronary artery territory (MSs 6 and 11) in 2 patients, and in the left anterior descending coronary artery territory (MS 8) in 1 patient. These 6 patients were asymptomatic with no evidence of clinical symptom of MI or Q wave on electrocardiogram for the diagnosis of MI. LGE pattern of midwall scarring ( Figure 3 ) was seen in 1 patient. Four of 7 patients with LGE on CMRI underwent coronary arteriography. Among patients with TA with LGE on CMRI, coronary arteriographies were normal for 2 of 4 patients in whom they had been performed. In 1 patient, coronary arteriography revealed ectatic right coronary artery with no significant occlusive thrombus (i.e., stenosis <50%), and in other patient, ostial occlusive lesion of right coronary artery was observed but not in the same territory as LGE on CMRI. The patterns of LGE-detected myocardial scarring that were observed in the 4 control subjects were midwall (n = 1) and subendocardial (n = 3).
