JACC Cardiovasc Imaging

OBJECTIVESThe 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.BACKGROUNDLipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol.METHODSQuantitative 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.RESULTSApheresis acutely decreased low-density lipoprotein cholesterol (234.9 \ub1 103.2 mg/dl vs. 67.1 \ub1 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 \ub1 55.2 nmol/l vs. 47.0 \ub1 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95% confidence interval: 77.2 to 73.1] 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.CONCLUSIONSLipoprotein 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. (Acute Microvascular Changes With LDL Apheresis; NCT02388633).P51 OD011092/ODCDC CDC HHS/Office of the Director/United StatesR35 HL135737/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL106579/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesP01 HL136275/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL111969/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesT32 HL094294/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL128550/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL078610/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL136098/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL130046/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL119828/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesR01 HL120046/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United StatesK08 HL133493/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United States2020-08-01T00:00:00Z29909101PMC64580986559vault:3367