Case report

A 54 year old woman presented to our hospital with a five month history of exertional chest pain. She had a past history of neurofibromatosis type 1 (NF-1), characterised by axillary freckling and multiple café au lait macules and neurofibromata, and carcinoma of the breast, treated by mastectomy. The diagnosis of NF-1 had never been genetically confirmed. An exercise test was positive at a low workload, and we proceeded to left heart catheterisation which showed inferior akinesia, severe mitral regurgitation, and two circular calcified lesions in the region of the left anterior descending coronary artery (LAD) and the distal right coronary artery near the crux. There was occlusion of the LAD, occlusion of the circumflex artery, and aneurysmal dilatation of the right coronary artery, which also filled the distal LAD through collaterals (figs 1 and2).

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Figure 1

Left selective coronary angiogram in the right anterior oblique projection (RAO 31°) showing occlusion of the left anterior descending coronary artery with a circular calcified lesion immediately distal to the occlusion (short arrow), and similar lesion inferiorly in the region of the right coronary artery (long arrow).

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Figure 2

Right selective coronary angiogram in the right anterior oblique projection (ROA 43°) showing aneurysmal dilatation of the right coronary artery at the crux (long arrow), with no significant coronary disease apparent. The calcified lesion in the left anterior descending coronary artery region is also shown (short arrow).

Transoesophageal echocardiography showed restriction of the P2/P3 portions of the posterior mitral valve leaflet in systole with severe mitral regurgitation, consistent with an ischaemic aetiology.

She was referred for coronary artery bypass grafting and mitral valve repair. At operation two calcified aneurysms were seen at the origin of the LAD and in the mid right coronary artery. Intraoperative intravascular ultrasound (IVUS) showed severe disease of the right coronary artery proximal to the aneurysm, which had not been visible on the coronary angiogram, followed by aneurysmal dilatation, reaching 8 × 9 mm at its largest internal diameter (fig 3).

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Figure 3

Intravascular ultrasound of the right coronary artery showing (A) severe coronary disease immediately before the aneurysm, and (B) aneurysmal dilatation of the right coronary artery measuring 6.5 × 5.5 cm at this point, increasing beyond to 8 × 9 cm.

Discussion

NF-1 is a congenital hereditary disease with generalised neuroectodermal and mesodermal dysplasia that affects the skin, nervous system, skeleton, and vascular system. Diagnosis is based on the presence of at least two of the following seven criteria6:

• Six or more café au lait macules, over 5 mm in prepubertal or 15 mm in postpubertal individuals

• Freckling in the axillary or inguinal region

• Two or more neurofibromata or one plexiform neurofibroma

• Two or more Lisch nodules

• Optic glioma

• A distinctive osseous lesion, for example sphenoid dysplasia or thinning of the long bone cortex, with or without pseudarthrosis

• A first degree relative with NF-1.

Other findings that may occur include tumours of the central and peripheral nervous system and gastrointestinal system, skeletal abnormalities (scoliosis, local gigantism, subperiosteal bone cysts, short stature), intellectual, behavioural, and emotional disturbance, and vascular abnormalities. Phaeochromocytomas may be present but are infrequent.

The vascular manifestations of NF-1 comprise aneurysmal and stenotic changes in large and medium vessels, including coarctation of the aorta. The most common vascular manifestation is proximal renal artery stenosis resulting in hypertension, first described by Debreet al.7 Aneurysms occur less frequently than stenoses8; they have been reported in association with renal artery stenosis but may occur as isolated lesions anywhere. Aneurysms of the aorta, subclavian, and vertebral arteries, carotid artery, thyrocervical trunk,8 and mesenteric9 10 and coeliac branches9have all been described. Multiple intracranial aneurysms may be present.

The electron microscopic examination of the vessel wall reveals two types of vascular lesion.11 Large arteries (including proximal renal arteries) may have intimal proliferation (causing stenoses), medial thinning, and fragmentation of elastic tissue (leading to aneurysm formation). These vessels may also be involved with neurofibromatous tissue. Small arteries show smooth muscle accumulation within the intima with resultant luminal narrowing. It has been postulated that vasospastic changes in the coronary arteries of patients with NF-1 reflect an abnormality of the cardiac sympathetic nerve.4

Coronary artery aneurysm is defined as a coronary dilatation which exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. A giant aneurysm is defined as one with an internal diameter of > 8 mm. The incidence varies from 1.5% to 5%, with male dominance and a predilection for the right coronary artery.12Atherosclerosis accounts for 50% of coronary aneurysms in adults. Other causes of coronary aneurysms include trauma, infective endocarditis, Kawasaki's disease, percutaneous transluminal coronary angioplasty, syphilis, fibromuscular dysplasia, and polyarteritis nodosa; their presence has also been associated with systemic lupus erythematosus, supravalvar aortic stenosis, coronary fistulae, chronic Epstein-Barr virus infection, polycystic kidney disease, Behçet's disease, and Lyme disease. Complications include thrombosis, distal embolisation, rupture, and vasospasm.

There have been two previous descriptions of coronary aneurysms in association with NF-1. Kandarpa et al and Daly et al have both described cases of NF-1 associated with coronary aneurysm and myocardial infarction.2 3 Fuchi et aldescribed a case of NF-1 associated with coronary ectasis, vasospasm, and stenosis causing myocardial infarction.4 Our case is the first description of multiple coronary aneurysms in association with NF-1, and, as far as we are aware, includes the first published intravascular ultrasound picture of a giant coronary aneurysm. There was no evidence of coronary vasospasm at angiography in our case, although this was not specifically tested for by provocation. The mitral regurgitation seen was ischaemic in origin—with restriction of the posterior mitral valve leaflet—and not directly related to NF-1. It is interesting to note that the use of intravascular ultrasound revealed severe right coronary artery disease proximal to the aneurysm, which was presumably responsible for at least some of the patient's anginal symptoms. Masking by the giant aneurysm accounted for the lack of evidence of severe disease in this area on coronary angiography. We urge that consideration be given to the use of IVUS in this setting to examine the coronary vasculature immediately adjacent to an aneurysm.