Author + information
- Received November 8, 2011
- Revision received February 22, 2012
- Accepted March 9, 2012
- Published online September 1, 2012.
- William Chan, MBBS, PhD⁎,†,
- Stephen J. Duffy, MBBS, PhD⁎,†,
- David A. White, BSc†,
- Xiao-Ming Gao, MBBS, MD†,
- Xiao-Jun Du, MBBS, PhD†,
- Andris H. Ellims, MBBS⁎,†,
- Anthony M. Dart, BM, BCh, DPhil⁎,†,‡ and
- Andrew J. Taylor, MBBS, PhD⁎,†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Andrew J. Taylor, Heart Centre, The Alfred Hospital, 3rd Floor, W.S. Philip Block, Commercial Road, Melbourne 3004, Victoria, Australia
Objectives This prospective study aimed to assess regional and temporal patterns of extracellular matrix (ECM) changes post-myocardial infarction (MI).
Background A fundamental process in the development of ischemic left ventricular (LV) dysfunction is LV remodeling, characterized by structural and functional abnormalities throughout the myocardium including the noninfarcted (remote) myocardium and interstitium.
Methods Contrast-enhanced cardiac magnetic resonance (CMR) was performed on MI patients acutely (mean: 5 days post-MI, n = 25) and repeated subacutely (mean: 139 days post-MI, n = 21), and was also performed in a separate group of 15 patients with chronic MI (mean: 2,580 days post-MI, n = 15). Twenty volunteers without a history of MI acted as controls. CMR was used to evaluate LV morphology and function, with post-contrast T1 mapping to semiquantitatively assess changes in the ECM. Putative mediators of myocardial inflammation and fibrosis, including macrophage migration inhibitory factor (MIF), were also measured.
Results Age, sex, and diabetic and hypertensive status did not differ between MI groups and controls. Compared with controls, patients early post-acute MI demonstrated reduced LV ejection fraction (50.25 ± 7.29% vs. 66.7 ± 6.2% [controls], p < 0.0001). Myocardium remote to the infarction early post-acute MI, compared with controls, demonstrated reduced systolic thickening (60 ± 5.0% vs. 106 ± 7.6%, p ≤ 0.0002), and lower post-contrast myocardial T1 times suggestive of ECM expansion (437 ± 113 ms vs. 549 ± 119 ms, p = 0.01). In a subgroup analysis between early post-acute MI and controls of similar age and sex, the remote sector post-contrast myocardial T1 times remained significantly shorter post-acute MI compared with controls (420 ± 121 ms vs. 529 ± 113 ms, p = 0.03). Serum levels of MIF inversely correlated with global myocardial T1 time in patients early post-acute MI (r = −0.6, p = 0.01), suggesting a coupling of regional healing with acute LV remodeling.
Conclusions Within a week of acute MI, the remote myocardium exhibits systolic dysfunction and expansion of the ECM, which is coupled with physiological infarct healing. Further prospective studies with larger sample sizes are needed to verify these important findings.
Dr. Chan is supported by a postgraduate scholarship from the National Health and Medical Research Council of Australia and a support grant from GlaxoSmithKline Australia. Mr. White is supported by an Australian National Heart Foundation PhD Scholarship (PB 10M 5481). Drs. Duffy, Du, Dart, and Taylor are supported by a National Health and Medical Research Council Program Grant. Dr. Taylor is also supported by a National Heart Foundation Grant, Melbourne, Australia. Dr. Gao is supported by a National Health and Medical Research Council Project Grant. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 8, 2011.
- Revision received February 22, 2012.
- Accepted March 9, 2012.
- American College of Cardiology Foundation