International Journal of Cardiology 172 (2014) e94–e95

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Letter to the Editor

Should we systematically screen for peripheral arterial aneurysms in all patients with Marfan syndrome? Sébastien Gaertner a,⁎, Yves Alembik b, Elena-Mihaela Cordeanu a, Hélène Dollfus b, Anne Lejay c, Nabil Chakfe c, Dominique Stephan a a b c

Department of vascular medicine and clinical pharmacology, Strasbourg University Hospital, France Department of medical genetics, Strasbourg University Hospital, France Department of vascular surgery, Strasbourg University Hospital, France

a r t i c l e

i n f o

Article history: Received 16 October 2013 Accepted 22 December 2013 Available online 4 January 2014 Keywords: Marfan syndrome Peripheral aneurysm Ultrasound

Marfan syndrome is an autosomal dominant genetic disorder in which life expectancy depends on the severity of cardiovascular involvement. An aneurysm of the ascending aorta, resulting from changes in the supportive tissue, exposes affected patients to the risk of aortic dissection or rupture. Follow-up for patients with Marfan syndrome therefore includes regular, systematic investigations of the heart and the thoracic aorta [1]. Since the connective tissue changes in Marfan syndrome are diffuse, it could be expected that the risk of developing an aneurysm may involve other vascular territories besides the ascending aorta. Yet there are no recommendations concerning the necessity or value of performing peripheral vascular examinations as part of the cardiovascular monitoring of these patients [1]. However, Yetman has already shown that one-third of the adults in her cohort of Marfan syndrome patients had peripheral vascular aneurysms, detected incidentally during computed tomography angiography or magnetic resonance angiography of the thoraco-abdominal aorta [2]. We used Doppler ultrasound to systematically examine the supraaortic trunks, the arteries of the upper and lower extremities, the aorto-iliac arteries, and the visceral branches of the abdominal aorta in all patients referred over a one-year period for suspected Marfan syndrome. Informed consent was obtained from each patient. We recorded any aneurysms, defined as an increase in artery diameter of more than ⁎ Corresponding author at: Hypertension et maladies vasculaires, Pharmacologie Clinique, CHRU Strasbourg 67091 BP 426, Cedex, France. E-mail address: [email protected] (S. Gaertner). 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.131

50%, as well as the presence or absence of aneurysm of the ascending aorta, detected by transthoracic echocardiography. Marfan syndrome was confirmed by genetic analysis in 21 of the patients investigated (15 adults and 6 children). Ten (67%) of the 15 adults with Marfan syndrome had peripheral vascular arterial aneurysms outside the thoraco-abdominal aorta (Table 1). These aneurysms involved various territories: three in iliac arteries, two in a vertebral artery, one in brachio-cephalic trunk, one in a renal artery, three in subclavian arteries, one in a common femoral artery, one in a popliteal artery and two in axillary arteries. Only the 16-mm vertebral aneurysm was symptomatic of stroke. Our patients were aged between 27 and 44 years, showing that this problem also affects young adults. Two patients with an aneurysm at high risk of rupture (a 50-mm common iliac aneurysm and a 30-mm renal artery aneurysm) underwent semi-urgent repair. Although these lesions were asymptomatic, surgical exploration of the common iliac aneurysm revealed fissuring indicative of impending rupture. Three of the ten patients with peripheral aneurysms had previously undergone repair for dissection of the ascending aorta. One of them had no abnormalities of the ascending aorta, with a maximum diameter within normal range (b 21 mm/m2, Z-Score b 2), four had a maximum diameter b 21 mm/m2 but a Z-score N 2, and three had dilatation of the ascending aorta with a diameter N 21 mm/m2 and a Z-score N 2. They were all taking beta-blockers. All of the patients with Marfan syndrome had a heterozygous mutation in the fibrillin 1 gene. This observational study of one year of consultations for Marfan syndrome showed that, regardless of whether patients had an aneurysm in the ascending aorta, two-thirds had aneurysmal disease outside the ascending aorta. Despite the small population studied, these results suggest that the prevalence of these lesions is underestimated. There is therefore a risk of peripheral vascular aneurysm in all patients with Marfan syndrome, regardless of their cardiac status. Furthermore, vascular screening proved invaluable for two patients, who rapidly underwent surgery in light of the high risk of rupture of their lesion. Mutations in the transforming growth factor-beta receptor gene are generally acknowledged to carry a risk of more severe and diffuse arterial lesions than mutations in the fibrillin 1 gene [3,4]. It would appear that the risk of diffuse aneurysmal lesions also exists with fibrillin 1

S. Gaertner et al. / International Journal of Cardiology 172 (2014) e94–e95

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Table 1 Characteristics of the patients with Marfan syndrome. Age

Peripheral artery aneurysm (diameter mm)

Diameter of the ascending aorta (mm) (diameter/body surface area: mm/m2) Z-score

Patient 1

40

Previously repaired — dissection

Patient 2

38

Left common iliac (50 mm) Supra-renal abdominal aorta (51 mm) Left subclavian (30 mm) Right popliteal (14 mm)

Patient 3

42

Right subclavian (16 mm)

Patient 4

28

No

Patient 5

35

No

Patient 6

31

Right renal (30 mm)

Patient 7

40

Patient 8

27

Left common iliac (23 mm) Right common iliac (19 mm) Left vertebral (16 mm)

Patient 9

32

Left common iliac (24 mm)

Patient 10

37

Patient 11

19

Left axillary (39 mm) Right axillary (31 mm) Right subclavian (21 mm) No

Patient 12

54

No

Patient 13

28

Right vertebral (5.1 mm)

Patient 14

44

Patient 15

38

Brachio-cephalic trunk (30.4 mm) Right common femoral (20 mm) No

gene mutations, since all of our patients with aneurysms in different vascular territories have this mutation. Doppler ultrasound examination is rapid, non-invasive, and inexpensive, and has been shown to be a sufficient and effective method of screening for peripheral vascular aneurysmal lesions. Adaptation of the management and monitoring of Marfan syndrome would now appear necessary, irrespective of the gene responsible, to include at least screening for peripheral aneurysmal lesions on reaching adulthood and at regular intervals thereafter, alongside the cardiac assessments. Doppler ultrasound is possibly the most cost-effective and safe method for achieving this. Normal cardiac

48 mm (23.4 mm/m2) Z-score = 4.17 49 mm (23.4 mm/m2) Z-score = 4.46 39 mm (18.5 mm/m2) Z-score = 3.56 36 mm (19.15 mm/m2) Z-score = 2.25 43 mm (20.1 mm/m2) Z-score = 3.81 49 mm (19.6 mm/m2) Z-score = 3.61 35 mm (17.05 mm/m2) Z-score = 1.03 44 mm (17 mm/m2) Z-score = 2.58 Previously repaired — dissection

44 mm (22.3 mm/m2) Z-score = 3.60 42 mm (21.6 mm/m2) Z-score = 5.32 47 mm (24 mm/m2) Z-score = 4.21 Previously repaired — dissection 36 mm (19.08 mm/m2) Z-score = 2.29

findings in Marfan syndrome should not rule out the possibility of aneurysms at different sites. References [1] Keane M, Pyeritz R. Medical management of Marfan syndrome. Circulation 2008;117:2802–13. [2] Yetman A, Roosvelt G, Veit N, Everitt M. Distal aortic and peripheral arterial aneurysms in patients with Marfan syndrome. JACC 2011;58:2544–9. [3] Le Maire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM. Severe aortic and arterial aneurysms associated with a TGFBR2 mutation. Nat Clin Pract Cardiovasc Med 2007;4:167–71. [4] Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006;355(8):788–98.