Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century . (1st July 2022)

• Record Type: Journal Article
• Authors: Bélanger, Alexandre M; Akioyamen, Leo E; Ruel, Isabelle; Hales, Lindsay; Genest, Jacques
• Is Part Of: European heart journal. Volume 43:Number 34(2022)
• Page Start: 3227
• Page End: 3239
• Publication Date: 2022-07-01
• Subjects: Homozygous familial hypercholesterolaemia -- Aortic stenosis -- Genetic dyslipidaemias -- Supra-valvular aortic stenosis -- Systematic review; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac339
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Aims: Homozygous familial hypercholesterolaemia (HoFH) is an orphan disease defined by extreme elevations in low-density lipoprotein cholesterol, cutaneous xanthomas, and pre-mature atherosclerotic cardiovascular disease. Survival has more than doubled over the past three decades. Aortic stenosis (AS) [supravalvular aortic stenosis (SVAS) or valvular aortic stenosis (VAS)] is commonly encountered. There are no medical treatments available and complex high-risk surgeries represent the only available option in severe cases. A systematic review was performed to summarize the current evidence on AS in HoFH and to determine whether pharmacological treatment (statins) have had an impact on clinical presentation, phenotype and clinical course over the past nine decades (PROSPERO CRD42021250565). Methods and results: MEDLINE, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, PubMed, AfricaWide, and Scopus were searched from inception to 10 November 2021. Searches identified 381 publications, of which 19 were retained; they were cross-sectional or retrospective studies. Separately, 108 individual case reports were described. Within the 424 HoFH cases, AS was identified in 57% of patients in the pre-statin era vs. 35% in patients reported more recently (>2000, long-term statin period). With an increase in longevity due to statins and lipoprotein apheresis, a change in the proportion of patients with SVAS and VAS with a SVAS:VAS ratio of 47:53 and 10:90 for HoFH patients not on statin and on long-term statin, respectively, was noted. Conclusion: These data suggest that SVAS and VAS are frequent in HoFH and that the phenotype has shifted towards calcific VAS as statins and lipoprotein apheresis improve survival in these patients. Structured Graphical Abstract: Structured Graphical Abstract Change in the aortic valve phenotype from supravalvular to calcific valvular aortic stenosis during the long-term statin era in patients with HoFH. Ao, aorta; AS, aortic stenosis; ASCVD, atherosclerotic cardiovascular disease; AV, aortic valve; HoFH, homozygous familial hypercholesterolaemia; LA, left atrium; LV, left ventricle; RV, right ventricle; SVAS, supravalvular aortic stenosis; VAS, valvular aortic stenosis.