Supra-valvular aortic stenosis in a patient with homozygous familial hypercholesterolaemia

Rajendran, R.; Srinivasa, K; Rangan, Kapil; Hegde, Madhav; Ahmed, Naveed

doi:10.1093/ehjci/jet072

Cited by 10 publications

(10 citation statements)

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“…1,2,21,23 Patients may be initially asymptomatic, presenting only with cutaneous and tendinous xanthomas and possibly, a cardiac murmur in the aortic area. 2,25 Early involvement of the ascending and descending thoracic aorta is frequently observed, 1 accompanied by premature severe aortic calcification in adult patients. 26 Cholesterol deposition on valve leaflets may also cause mitral regurgitation.…”

Section: Cardiovascular Complications and Natural Historymentioning

confidence: 99%

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Cuchel¹,

Bruckert²,

Descamps³

et al. 2014

European Heart Journal

916

1,021

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AimsHomozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH.Methods and resultsEarly diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary.ConclusionThis EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.

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Section: Cardiovascular Complications and Natural Historymentioning

confidence: 99%

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Cuchel¹,

Bruckert²,

Descamps³

et al. 2014

European Heart Journal

916

1,021

View full text Add to dashboard Cite

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“…1,2 ASCVD is the most common cause of premature death in these patients, but other cardiovascular (CV) disease including aortic and supravalvular aortic stenosis and aortic root disease is also common. 3–6 HoFH patients require treatment as soon as the diagnosis is made and need lifestyle, medication and additional modalities. Aggressive treatment of HoFH patients can delay major CV events and early death.…”

Section: Introductionmentioning

confidence: 99%

Microsomal triglyceride transfer protein inhibitor (lomitapide) efficacy in the treatment of patients with homozygous familial hypercholesterolaemia

Kolovou

Diakoumakou

Kolovou

et al. 2019

Eur J Prev Cardiolog

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Aims The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in patients with homozygous familial hypercholesterolaemia. Methods and results In 12 homozygous familial hypercholesterolaemia patients treated with lipid-lowering drugs ± biweekly lipoprotein apheresis sessions (nine patients), daily lomitapide was added. The lipid profile (total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol) before and after lomitapide treatment was evaluated. The follow-up period with lomitapide treatment was 3–24 months (13.8 ± 7.9). The median baseline low-density lipoprotein cholesterol level was 900 mg/dl (348–1070), after lipid-lowering drugs therapy was 383.5 mg/dl (214–866) and after lipid-lowering drugs + time-averaged level was 288 mg/dl (183.7–716.6). The addition of lomitapide lowered low-density lipoprotein cholesterol levels further by 56.8% compared to lipid-lowering drugs alone (mean reduction 262, 95% confidence interval (105.5–418.7), p = 0.005) and by 54% (mean reduction 182.9, 95% confidence interval (−342 – −23), p = 0.031) comparing to lipid-lowering drugs + lipoprotein apheresis (time-averaged level). The time-averaged level of low-density lipoprotein cholesterol in lipid-lowering drugs + lipoprotein apheresis patients compared with lipid-lowering drugs + lomitapide was 54% in favour of lomitapide ( p = 0.031). Conclusions Treatment with lomitapide in homozygous familial hypercholesterolaemia patients has a beneficial effect with a constant decrease of low-density lipoprotein cholesterol by 57% compared with classical lipid-lowering therapy and by 54% compared with classical lipid-lowering therapy and time-averaged level of low-density lipoprotein cholesterol.

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“…HoFH frequently leads to early cardiovascular death if not adequately treated. However, the standard therapy with medications and LDL-apheresis at least in more severe cases often fail to address difficult clinical situation satisfactorily ( 16 – 18 ). The management of patients with HoFH represents a medical challenge despite the approval of new lipid-lowering agents (i.e., mipomersen, lomitapide, PCSK9 inhibitors) ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Liver Transplantation in Homozygous Familial Hypercholesterolemia (HoFH)—Long-Term Follow-Up of a Patient and Literature Review

et al. 2020

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Homozygous familial hypercholesterolemia (HoFH) is a rare inherited metabolic disorder, frequently leading to an early cardiovascular death if not adequately treated. Since standard medications usually fail to reduce LDL-cholesterol (LDL-C) levels satisfactorily, LDL-apheresis is a mainstay of managing HoFH patients but, at the same time, very burdensome and suboptimally effective. Liver transplantation (LT) has been previously shown to be a promising alternative. We report on a 14 year-long follow-up after LT in a HoFH patient. At the age of 4, the patient was referred to our institution because of the gradually increasing number of xanthomas on the knees, elbows, buttocks, and later the homozygous mutation c.1754T>C (p.Ile585Thr) on the LDL-receptor gene was confirmed. Despite subsequent intensive treatment with the combination of diet, statins, bile acid sequestrant, probucol, and LDL-apheresis, the patient developed valvular aortic stenosis and aortic regurgitation by 12 years. At 16 years, the patient successfully underwent deceased-donor orthotopic LT. Nine years post-LT, we found total regression of the cutaneous xanthomas and atherosclerotic plaques and with normal endothelial function. Fourteen years post-LT, his clinical condition remained stable, but LDL-C levels have progressively risen. In addition, a systematic review of the literature and guidelines on the LT for HoFH patients was performed. Six of the 17 identified guidelines did not take LT as a treatment option in consideration at all. But still the majority of guidelines suggest LT as an exceptional therapeutic option or as the last resort option when all the other treatment options are inadequate or not tolerated. Most of the observed patients had some kind of cardiovascular disease before the LT. In 76% of LT, the cardiovascular burden did not progress after LT. According to our experience and in several other reported cases, the LDL-C levels are slowly increasing over time post LT. Most of the follow-up data were short termed; only a few case reports have followed patients for 10 or more years after LT. LT is a feasible therapeutic option for HoFH patients, reversing atherosclerotic changes uncontrollable by conservative therapy, thus importantly improving the HoFH patient's prognosis and quality of life.

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Supra-valvular aortic stenosis in a patient with homozygous familial hypercholesterolaemia

Cited by 10 publications

References 0 publications

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society

Microsomal triglyceride transfer protein inhibitor (lomitapide) efficacy in the treatment of patients with homozygous familial hypercholesterolaemia

Case Report: Liver Transplantation in Homozygous Familial Hypercholesterolemia (HoFH)—Long-Term Follow-Up of a Patient and Literature Review

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