Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia

JACC-CARDIOVASCULAR IMAGING

卷:12

Article

Wu, Melinda D.^1,2  Moccetti, Federico¹  Brown, Eran¹  Davidson, Brian P.^1,3  Atkinson, Tamara^1,3  Belcik, J. Todd¹  Giraud, George^1,3  Duell, P. Barton¹  Fazio, Sergio¹  Tavori, Hagai¹  Tsimikas, Sotirios⁴  Lindner, Jonathan R.^1,5 

[1] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA

[2] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Portland, OR 97239 USA

[3] Oregon Hlth & Sci Univ, Portland Vet Adm Hosp, Portland, OR 97239 USA

[4] Univ Calif San Diego, Div Cardiovasc, San Diego, CA 92103 USA

[5] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR 97239 USA

关键词: apheresis;    contrast ultrasound;    familial hypercholesterolemia;    myocardial contrast echocardiography;   

DOI  :  10.1016/j.jcmg.2018.05.001

来源: Elsevier

【 摘 要 】

OBJECTIVES This study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations. BACKGROUND Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol. METHODS Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia. Myocardial perfusion imaging was also performed in 14 normal control subjects. Changes in myocardial work and left ventricular function were assessed by echocardiography. Ex vivo ovine coronary and femoral artery ring tension assays were assessed in the presence of pre-and post-apheresis plasma. RESULTS Apheresis acutely decreased low-density lipoprotein cholesterol (234.9 +/- 103.2 mg/dl vs. 67.1 +/- 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 +/- 55.2 nmol/l vs. 47.0 +/- 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95% confidence interval: 77.2 to 73.1] IU/s vs. 135 [95% confidence interval: 81.2 to 189.6] IU/s; p = 0.01), without changes in myocardial work. Myocardial longitudinal strain improved in those subjects with reduced pre-apheresis function. Skeletal muscle perfusion at rest and during contractile exercise was unchanged by apheresis. Acetylcholine-mediated dilation of ex vivo ovine coronary but not femoral arteries was impaired in pre-apheresis plasma and was completely reversed in post-apheresis plasma. CONCLUSIONS Lipoprotein apheresis produces an immediate improvement in coronary microvascular function, which increases myocardial perfusion and normalizes endothelial-dependent vasodilation. These changes are not observed in the periphery. (C) 2019 by the American College of Cardiology Foundation.

【 授权许可】

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