Abstract
Inherited disorders of lipid metabolism may cause a heavy burden of cardiovascular disease early in life. Familial hypercholesterolaemia (FH) with abnormalities of LDL metabolism results in marked LDL elevations and accelerated, multivessel atherosclerosis presenting in teenage or young adulthood.
We describe the case of a 33-year-old woman who presented with exertional angina in the setting of pregnancy who was found post-partum to have severe triple-vessel disease including left main disease on coronary angiography (Figs. 1 and 2). She was also noted to have a typical supravalvular “hourglass” [1] abnormality of the aortic root (Fig. 3), and heavy calcification of the proximal aorta precluding conventional aortic cross clamping and bypass surgery. After discussion with the multidisciplinary team, her disease was felt to be amenable to a beating-heart coronary bypass technique with an anaortic approach to minimise the possibility of cerebral embolism. Significant extracranial cerebrovascular disease, a major risk for cardiopulmonary bypass, reinforced the beating-heart technique. Her ongoing management has consisted of medical therapy with cessation of breast feeding, statins, ezetimibe, and introduction of PCSK9-inhibitor therapy.
This case illustrates a number of the difficulties associated with management of widespread atherosclerotic disease associated with FH, in which an excellent outcome was achieved with the assistance of a multi-disciplinary team.
Highlights
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Management of young, pregnant patients with coronary artery and cerebrovascular disease in the setting of FH is complex
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Revascularisation requires individualised approaches, coordinated by various experienced clinicians
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Patients frequently require multiple procedures in different vascular beds throughout their life.
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Superimposed pregnancy creates further difficulties related to management and procedures requiring radiation and contrast agents.
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Case report
A 33-year-old female (G2, P1) was noted to have significantly elevated fasting total cholesterol of 21 mmol/L on blood testing performed during her 20 week antenatal screening. Her pregnancy had been unremarkable until recently developing symptoms of exertional dyspnoea and angina pectoris. Examination revealed evidence of bilateral xanthomata in the extensor tendons of the hands, the wrists, and patellar tendons; and arcus senilis on examination of the eyes. On examination of the chest, a loud systolic ejection murmur was noted, along with bilateral carotid bruits in the neck.
Her background was notable for a strong family history of cardiovascular issues with her mother and maternal grandfather dying of myocardial infarctions in their 50 s. There was a family background of consanguinity with her parents being cousins. The patient had undergone biopsy of a tendon xanthoma overseas, followed by a computed tomography coronary angiogram (CTCA) confirming the presence of coronary artery disease five years before the current presentation. She had been managed with a combination of rosuvastatin and ezetimibe prior to the pregnancy but was not currently on any lipid-lowering therapy. She has a number of siblings who have normal lipid profiles. Her child has not yet been screened. She was referred to a quaternary lipid service where genetic testing revealed homozygous familial hypercholesterolaemia with a mutation known as p.Asp100Asn (c.298G > A).
Management during pregnancy was complicated both by a desire to avoid x-ray exposure to the foetus, the patient’s chest wall, and the use of iodine based radiological contrast agents. She was managed carefully with a combination of beta blockers and aspirin, following discussion with a high-risk obstetrics service. Discussion was also undertaken regarding the use of a statin in the setting of the pregnancy, although a decision was made to avoid this due to concerns about the developing foetal brain. Statin therapy was reinitiated after delivery. Further discussion occurred about the optimal mechanism of delivery; from a cardiovascular perspective it was decided that vaginal delivery was safe, which subsequently proceeded uneventfully with no peripartum complications to mother or child.
Postpartum, breast feeding was suspended while she underwent coronary angiography and was found to have extensive triple-vessel coronary artery disease including involvement of the left main ( Fig. 1 , Fig. 2 ) Echocardiographic assessment of the aortic root during pregnancy, and also postpartum revealed a characteristic “hourglass” [ ] abnormality with an associated peak flow gradient of 50 mmHg, and mean gradient of 26 mmHg ( Fig. 3 ). The appearances were consistent with the presence xanthomatous-type infiltration and calcification of the aortic wall. The minimum aortic root diameter at the level of this lesion was 1.6 cm compared to a diameter at the sinotubular junction which was in the normal range at 2.9 cm. Magnetic resonance angiography (MRA) of the carotids revealed a 50% left internal carotid artery (LICA) stenosis.
Extensive multi-disciplinary discussion occurred regarding revascularisation options for this symptomatic patient. CT aortography confirmed that the aorta was very heavily calcified, with confirmation of the supravalvular stenosis, and aortic wall abnormalities involving the coronary ostia. Consequently, concern was raised about stroke risk and the efficacy of percutaneous intervention, given extensive calcified left main coronary artery disease. Aortic root replacement was considered high risk due to extensive atherosclerotic disease in conjunction with the absence of normal aortic tissue to allow a distal anastomosis. Following extensive discussion with the cardiothoracic and interventional cardiology service she proceeded to beating-heart coronary artery bypass grafting (CABG) augmented with femoro-atrial cardiopulmonary bypass. She underwent LIMA grafting to the LAD, and an inverted Y left radial graft was anastomosed to the LIMA and applied to the diagonal, and distal circumflex branches. The right coronary artery did not contain disease significant enough to require grafting.
She recovered well from the procedure with abolition of her exertional angina symptoms. She has subsequently been managed with a combination of ezetimibe, rosuvastatin, and a PCSK9 inhibitor with improvement in her lipid levels with the most recent LDL level 10.7 mmol/L.
Follow up in this instance has been done so with yearly clinic appointments where symptoms of ischaemia are the main guide for additional investigations. Baseline testing is done via monitoring of fasting lipid profile, and trans-thoracic echocardiography to monitor the progress of the supravalvular stenosis. At 5 year follow up the patient has not required any invasive angiography to be repeated and has remained functionally well.
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