Iron Deposition following Chronic Myocardial Infarction as a Substrate for Cardiac Electrical Anomalies: Initial Findings in a Canine Model

Abstract

PurposeIron deposition has been shown to occur following myocardial infarction (MI). We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies.MethodsTwo 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 () and conductivity (). 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).ResultsCompared to IRON- sections, IRON+ sections had higher, but no difference in. A linear relationship was found between iron content and (p<0.001), but not (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.ConclusionThe 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.

Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium

“…20 It is well known that iron overload could cause cardiomyopathy with clinical manifestations, including decreasing the cardiac ejection fraction and arrhythmia. [37][38][39] Acidic environments prompt the transformation of iron from the oxidation state (Fe 3+ ) to the reduced state (Fe 2+ ), resulting in the generation of oxygen free radicals. Therefore, the toxic effect of myocardial iron is dynamic and is increased in the presence of metabolic acidosis.…”

Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction

“…Mather et al 25 showed that patients with hemorrhagic infarction have prolonged filtered QRS duration, which they associated with increased late-arrhythmogenic risk. Recent canine studies have also confirmed that hemorrhagic infarctions can lead to chronic iron deposition 26 and that post infarction iron can preferentially alter electrophysiology indices within the infarcted heart 27 . Moreover, forensic studies utilizing clinical cardiac magnetic resonance imaging (CMR) have shown that SCD victims with chronic MI consistently have hypointense zones in the scarred myocardium in T 2 -weighted CMR 28, 29 , which is consistent with iron accumulation.…”

Intramyocardial haemorrhage after acute myocardial infarction

“…Instead, erythrocyte compounds, such as haemoglobin, or iron deposits can be stained with a haemoglobin antibody or Perl's Prussian blue staining, which stains ferritin deposits. 18,20,109 Erythrocytes can also be labelled with radioisotopes or erythrocyte extravasation can be mimicked by injection of radioactive or gold-labelled microspheres, and can be visualized using spectroscopy. 47,51,[110][111][112][113] Predicting the risk of haemorrhage…”

“…13,[15][16][17] Biodegradation of haem molecules leads to deposition of cytotoxic levels of iron in the myocardium. This accumulation triggers macrophage influx and, consequently, a chronic phase involving the generation of reactive oxygen species, [18][19][20] necrosis, inflammation, and fibrosis. Prevention of microvascular injury and intramyocardial haemorrhage in the acute phase could, therefore, be of benefit to patients with STEMI.…”