PMID- 32305466
OWN - NLM
STAT- MEDLINE
DCOM- 20210721
LR  - 20220403
IS  - 1876-7591 (Electronic)
IS  - 1936-878X (Print)
IS  - 1876-7591 (Linking)
VI  - 14
IP  - 2
DP  - 2021 Feb
TI  - Substrate for the Myocardial Inflammation-Heart Failure Hypothesis Identified 
      Using Novel USPIO Methodology.
PG  - 365-376
LID - S1936-878X(20)30153-4 [pii]
LID - 10.1016/j.jcmg.2020.02.001 [doi]
AB  - OBJECTIVES: The purpose of this study was to identify where ultrasmall 
      superparamagnetic particles of iron oxide (USPIO) locate to in myocardium, 
      develop a methodology that differentiates active macrophage uptake of USPIO from 
      passive tissue distribution; and investigate myocardial inflammation in 
      cardiovascular diseases. BACKGROUND: Myocardial inflammation is hypothesized to 
      be a key pathophysiological mechanism of heart failure (HF), but human evidence 
      is limited, partly because evaluation is challenging. USPIO-magnetic resonance 
      imaging (MRI) potentially allows specific identification of myocardial 
      inflammation but it remains unclear what the USPIO-MRI signal represents. 
      METHODS: Histological validation was performed using a murine acute myocardial 
      infarction (MI) model. A multiparametric, multi-time-point MRI methodology was 
      developed, which was applied in patients with acute MI (n = 12), chronic ischemic 
      cardiomyopathy (n = 7), myocarditis (n = 6), dilated cardiomyopathy (n = 5), and 
      chronic sarcoidosis (n = 5). RESULTS: USPIO were identified in myocardial 
      macrophages and myocardial interstitium. R1 time-course reflected passive 
      interstitial distribution whereas multi-time-point R2* was also sensitive to 
      active macrophage uptake. R2*/R1 ratio provided a quantitative measurement of 
      myocardial macrophage infiltration. R2* behavior and R2*/R1 ratio were higher in 
      infarcted (p = 0.001) and remote (p = 0.033) myocardium in acute MI and in 
      chronic ischemic cardiomyopathy (infarct: p = 0.008; remote p = 0.010), and were 
      borderline higher in DCM (p = 0.096), in comparison to healthy controls, but were 
      no different in myocarditis or sarcoidosis. An R2*/R1 threshold of 25 had a 
      sensitivity and specificity of 90% and 83%, respectively, for detecting active 
      USPIO uptake. CONCLUSIONS: USPIO are phagocytized by cardiac macrophages but are 
      also passively present in myocardial interstitium. A multiparametric 
      multi-time-point MRI methodology specifically identifies active myocardial 
      macrophage infiltration. Persistent active macrophage infiltration is present in 
      infarcted and remote myocardium in chronic ischemic cardiomyopathy, providing a 
      substrate for HF.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Lagan, Jakub
AU  - Lagan J
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom; Division of Cardiovascular Sciences, University of Manchester, 
      Manchester, United Kingdom.
FAU - Naish, Josephine H
AU  - Naish JH
AD  - Division of Cardiovascular Sciences, University of Manchester, Manchester, United 
      Kingdom.
FAU - Simpson, Kara
AU  - Simpson K
AD  - Division of Diabetes, Endocrinology and Gastroenterology, University of 
      Manchester, Manchester, United Kingdom.
FAU - Zi, Min
AU  - Zi M
AD  - Division of Cardiovascular Sciences, University of Manchester, Manchester, United 
      Kingdom.
FAU - Cartwright, Elizabeth J
AU  - Cartwright EJ
AD  - Division of Cardiovascular Sciences, University of Manchester, Manchester, United 
      Kingdom.
FAU - Foden, Phil
AU  - Foden P
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom.
FAU - Morris, Julie
AU  - Morris J
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom.
FAU - Clark, David
AU  - Clark D
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom.
FAU - Birchall, Lindsay
AU  - Birchall L
AD  - Division of Diabetes, Endocrinology and Gastroenterology, University of 
      Manchester, Manchester, United Kingdom.
FAU - Caldwell, Jessica
AU  - Caldwell J
AD  - Division of Cardiovascular Sciences, University of Manchester, Manchester, United 
      Kingdom.
FAU - Trafford, Andrew
AU  - Trafford A
AD  - Division of Cardiovascular Sciences, University of Manchester, Manchester, United 
      Kingdom.
FAU - Fortune, Christien
AU  - Fortune C
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom; Division of Cardiovascular Sciences, University of Manchester, 
      Manchester, United Kingdom.
FAU - Cullen, Michael
AU  - Cullen M
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom.
FAU - Chaudhuri, Nazia
AU  - Chaudhuri N
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom; Division of Infection, Immunity and Respiratory Medicine, 
      University of Manchester, Manchester, United Kingdom.
FAU - Fildes, James
AU  - Fildes J
AD  - Manchester Collaborative Centre for Inflammation Research, University of 
      Manchester, Manchester, United Kingdom; The Transplant Centre, Manchester 
      University NHS Foundation Trust, Wythenshawe Hospital, Manchester, United 
      Kingdom.
FAU - Sarma, Jaydeep
AU  - Sarma J
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom; Division of Cardiovascular Sciences, University of Manchester, 
      Manchester, United Kingdom.
FAU - Schelbert, Erik B
AU  - Schelbert EB
AD  - Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, 
      Pennsylvania, USA; UPMC Cardiovascular Magnetic Resonance Center, Heart and 
      Vascular Institute, Pittsburgh, Pennsylvania, USA; Clinical and Translational 
      Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Schmitt, Matthias
AU  - Schmitt M
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom; Division of Cardiovascular Sciences, University of Manchester, 
      Manchester, United Kingdom.
FAU - Piper Hanley, Karen
AU  - Piper Hanley K
AD  - Division of Diabetes, Endocrinology and Gastroenterology, University of 
      Manchester, Manchester, United Kingdom; Wellcome Centre for Cell-Matrix Research, 
      University of Manchester, Manchester, United Kingdom.
FAU - Miller, Christopher A
AU  - Miller CA
AD  - Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, 
      United Kingdom; Division of Cardiovascular Sciences, University of Manchester, 
      Manchester, United Kingdom; Wellcome Centre for Cell-Matrix Research, University 
      of Manchester, Manchester, United Kingdom. Electronic address: 
      Christopher.Miller@manchester.ac.uk.
LA  - eng
GR  - AMS-SGCL12-MILLER/AMS_/Academy of Medical Sciences/United Kingdom
GR  - FS/17/47/32805/BHF_/British Heart Foundation/United Kingdom
GR  - MR/P023541/1/MRC_/Medical Research Council/United Kingdom
GR  - AA/18/4/34221/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200415
PL  - United States
TA  - JACC Cardiovasc Imaging
JT  - JACC. Cardiovascular imaging
JID - 101467978
RN  - 0 (Contrast Media)
RN  - 0 (Dextrans)
RN  - 0 (Magnetite Nanoparticles)
RN  - 0 (ferumoxtran-10)
SB  - IM
CIN - JACC Cardiovasc Imaging. 2021 Feb;14(2):377-378. PMID: 33541529
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Contrast Media
MH  - Dextrans
MH  - *Diabetes Mellitus, Type 2
MH  - Female
MH  - *Heart Failure
MH  - Humans
MH  - Inflammation
MH  - Magnetic Resonance Imaging
MH  - Magnetite Nanoparticles
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - *Myocarditis
MH  - *Percutaneous Coronary Intervention
MH  - Predictive Value of Tests
PMC - PMC7854561
OTO - NOTNLM
OT  - heart failure
OT  - magnetic resonance imaging
OT  - myocardial inflammation
OT  - ultrasmall superparamagnetic particles of iron oxide
COIS- Funding support and Author Disclosures Dr. Lagan is funded by a Clinical Research 
      Training Fellowship from the British Heart Foundation (FS/17/47/32805). Dr. Karen 
      Piper Hanley is funded by the Medical Research Council Grant (MR/P023541/1). Dr. 
      Miller is funded by a Clinician Scientist Award (CS-2015-15-003) from the 
      National Institute for Health Research. The work was also supported in part by a 
      British Heart Foundation Accelerator award to The University of Manchester 
      (AA/18/4/34221). The views expressed in this publication are those of the authors 
      and not necessarily those of the NHS, the National Institute for Health Research 
      or the Department of Health. The authors recognize the support from AMAG 
      Pharmaceuticals who provided the USPIO. AMAG Pharmaceuticals had no role in study 
      design, data collection, analysis, interpretation or writing of the report. All 
      other authorshave reported that they have no relationships relevant to the 
      contents of this paper to disclose.
EDAT- 2020/04/20 06:00
MHDA- 2021/07/22 06:00
PMCR- 2021/02/01
CRDT- 2020/04/20 06:00
PHST- 2019/11/20 00:00 [received]
PHST- 2020/01/27 00:00 [revised]
PHST- 2020/02/03 00:00 [accepted]
PHST- 2020/04/20 06:00 [pubmed]
PHST- 2021/07/22 06:00 [medline]
PHST- 2020/04/20 06:00 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - S1936-878X(20)30153-4 [pii]
AID - 10.1016/j.jcmg.2020.02.001 [doi]
PST - ppublish
SO  - JACC Cardiovasc Imaging. 2021 Feb;14(2):365-376. doi: 10.1016/j.jcmg.2020.02.001. 
      Epub 2020 Apr 15.