Iron deposition following chronic myocardial infarction as a substrate for cardiac electrical anomalies: initial findings in a canine model.
OBJECTIVE
Iron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies.


METHODS
Two groups of dogs (ex-vivo (n = 12) and in-vivo (n = 10)) were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity ([Formula: see text]) and conductivity ([Formula: see text]). Mass spectrometry was used to classify and characterize tissue sections with (IRON+) and without (IRON-) iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR) for estimation of scar volume (late-gadolinium enhancement, LGE) and iron deposition (T2*) relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR), QT interval (QT), QT corrected for HR (QTc) and QTc dispersion (QTcd). In a fraction of these animals (n = 5), ultra-high resolution electroanatomical mapping (EAM) was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs).


RESULTS
Compared to IRON- sections, IRON+ sections had higher[Formula: see text], but no difference in[Formula: see text]. A linear relationship was found between iron content and [Formula: see text] (p<0.001), but not [Formula: see text] (p = 0.34). Among two groups of animals (Iron (<1.5%) and Iron (>1.5%)) with similar scar volumes (7.28% ± 1.02% (Iron (<1.5%)) vs 8.35% ± 2.98% (Iron (>1.5%)), p = 0.51) but markedly different iron volumes (1.12% ± 0.64% (Iron (<1.5%)) vs 2.47% ± 0.64% (Iron (>1.5%)), p = 0.02), QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05). EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron.


CONCLUSIONS
The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may evolve as an arrhythmogenic substrate in the post MI period.
Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Ivan
I
Cokic
Avinash
A
Kali
Xunzhang
X
Wang
Hsin-Jung
HJ
Yang
Richard L Q
RL
Tang
Anees
A
Thajudeen
Michael
M
Shehata
Allen M
AM
Amorn
Enzhao
E
Liu
Brian
B
Stewart
Nathan
N
Bennett
Doron
D
Harlev
Sotirios A
SA
Tsaftaris
Warren M
WM
Jackman
Sumeet S
SS
Chugh
Rohan
R
Dharmakumar
D000818:Animals; D004285:Dogs; D025802:Electric Capacitance; D004562:Electrocardiography; D006329:Heart Conduction System; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology*
D007501:Iron