Abstract:
AIMS :Balance between inflammatory and reparative leucocytes allows optimal healing after myocardial infarction (MI). Interindividual heterogeneity evokes variable functional outcome complicating targeted therapy. We aimed to characterize infarct chemokine CXC-motif receptor 4 (CXCR4) expression using positron emission tomography (PET) and establish its relationship to cardiac outcome. We tested whether image-guided early CXCR4 directed therapy attenuates chronic dysfunction. METHODS AND RESULTS :Mice (n = 180) underwent coronary ligation or sham surgery and serial PET imaging over 7 days. Infarct CXCR4 content was elevated over 3 days after MI compared with sham (%ID/g, Day 1:1.1 ± 0.2; Day 3:0.9 ± 0.2 vs. 0.6 ± 0.1, P < 0.001), confirmed by flow cytometry and histopathology. Mice that died of left ventricle (LV) rupture exhibited persistent inflammation at 3 days compared with survivors (1.2 ± 0.3 vs. 0.9 ± 0.2% ID/g, P < 0.001). Cardiac magnetic resonance measured cardiac function. Higher CXCR4 signal at 1 and 3 days independently predicted worse functional outcome at 6 weeks (rpartial = -0.4, P = 0.04). Mice were treated with CXCR4 blocker AMD3100 following the imaging timecourse. On-peak CXCR4 blockade at 3 days lowered LV rupture incidence vs. untreated MI (8% vs. 25%), and improved contractile function at 6 weeks (+24%, P = 0.01). Off-peak CXCR4 blockade at 7 days did not improve outcome. Flow cytometry analysis revealed lower LV neutrophil and Ly6Chigh monocyte content after on-peak treatment. Patients (n = 50) early after MI underwent CXCR4 PET imaging and functional assessment. Infarct CXCR4 expression in acute MI patients correlated with contractile function at time of PET and on follow-up. CONCLUSION :Positron emission tomography imaging identifies early CXCR4 up-regulation which predicts acute rupture and chronic contractile dysfunction. Imaging-guided CXCR4 inhibition accelerates inflammatory resolution and improves outcome. This supports a molecular imaging-based theranostic approach to guide therapy after MI.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Hess A,Derlin T,Koenig T,Diekmann J,Wittneben A,Wang Y,Wester HJ,Ross TL,Wollert KC,Bauersachs J,Bengel FM,Thackeray JTdoi
10.1093/eurheartj/ehaa598subject
Has Abstractpub_date
2020-10-01 00:00:00pages
3564-3575issue
37eissn
0195-668Xissn
1522-9645pii
5903166journal_volume
41pub_type
杂志文章abstract::Sudden cardiac death (SCD) accounts for approximately one-third of all deaths among patients with non-ischaemic cardiomyopathy (NICM). Implantable cardioverter-defibrillator (ICD) therapy has been the primary intervention for managing individuals at high risk for SCD. However, individual ICD trials in the NICM populat...
journal_title:European heart journal
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doi:10.1093/eurheartj/ehy344
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abstract::The prognostic significance of angina pectoris and the effect of intervention with verapamil on the incidence of angina pectoris were studied in patients recovering from myocardial infarction and included in the Danish Verapamil Infarction Trial II. During the second week after admission patients were doubly-blindly r...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1093/oxfordjournals.eurheartj.a060486
更新日期:1994-02-01 00:00:00
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journal_title:European heart journal
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doi:10.1093/oxfordjournals.eurheartj.a060302
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journal_title:European heart journal
pub_type: 临床试验,杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062100
更新日期:1986-06-01 00:00:00
abstract:AIMS:This study compares the functional outcome and cardiorespiratory response to exercise, in patients who have undergone arterial switch for transposition of the great arteries, with normal controls and patients who have undergone atrial switch operation. METHODS AND RESULTS:Fifteen patients who had undergone arteri...
journal_title:European heart journal
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更新日期:2001-06-01 00:00:00
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journal_title:European heart journal
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doi:10.1093/eurheartj/ehq142
更新日期:2010-07-01 00:00:00
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journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/j.ehj.2003.08.015
更新日期:2003-11-01 00:00:00
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journal_title:European heart journal
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doi:10.1093/eurheartj/ehm262
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journal_title:European heart journal
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,随机对照试验
doi:10.1093/eurheartj/ehm647
更新日期:2008-02-01 00:00:00
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doi:10.1093/eurheartj/4.suppl_d.19
更新日期:1983-07-01 00:00:00
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journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1053/euhj.2001.2623
更新日期:2001-10-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehs436
更新日期:2013-05-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/eht053
更新日期:2013-11-01 00:00:00
abstract:AIMS:Little research exists on exercise performance and training in patients with an implemented cardioverter defibrillator (ICD) and only in a limited number of patients. This study aims to investigate the effect of exercise training in ICD patients in comparison to the effects in other cardiac patients without an ICD...
journal_title:European heart journal
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ehj.2004.04.034
更新日期:2004-07-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a059698
更新日期:1990-03-01 00:00:00
abstract::Diastolic heart disease is common and appears to be the primary abnormality in a substantial proportion of all patients with CHF. The epidemiology and natural history of the condition appears different to that of systolic heart failure, resulting in significant morbidity although contributing little to overall mortali...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/oxfordjournals.eurheartj.a060453
更新日期:1994-12-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1053/euhj.1999.1530
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journal_title:European heart journal
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doi:10.1053/euhj.1999.1582
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journal_title:European heart journal
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journal_title:European heart journal
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journal_title:European heart journal
pub_type: 杂志文章,多中心研究
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更新日期:2009-10-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehm444
更新日期:2007-12-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/ehi327
更新日期:2005-10-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/12.suppl_d.39
更新日期:1991-08-01 00:00:00
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journal_title:European heart journal
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doi:10.1093/eurheartj/eht464
更新日期:2014-07-01 00:00:00
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journal_title:European heart journal
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doi:10.1093/eurheartj/ehx182
更新日期:2017-07-21 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060476
更新日期:1994-02-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/11.suppl_e.122
更新日期:1990-08-01 00:00:00
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journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1995-12-01 00:00:00