Histochemical Studies of the Myocardium and Conduction System in Acquired Iron-Storage Disease

Abstract

SUMMARYThe myocardium, all parts of the conduction system, and the S-A node contained iron in six patients with acquired iron-storage disease. [14][15][16][17][18] A clinicopathological study was undertaken by James'9 to investigate the changes present in the myocardium and conduction system in the hearts of five patients with hemochromatosis. Two had exogenous, and three had endogenous, hemochromatosis. He found extensive iron deposits in the myocardium and in the atrioventricular (A-V) node of each heart, but noted that the sinoatrial (S-A) node was spared in all cases. He postulated that the large amount of iron within the A-V node was responsible for the cellular necrosis and degeneration and that these changes could account for the antemortem conduction disturbances and arrhythmias Concerning the absence of iron in the S-A node, he suggested that a difference in local tissue metabolism resulted in the lack of iron deposition.The purpose of this paper is to report findings from a study of the conduction system and myocardium from the hearts of six young patients with acquired iron-storage disease. The patients studied had no history or anatomic evidence of primary arteriosclerotic, rheumatic, or hypertensive cardiovascular disease. Particular attention was directed to iron deposits and fibrous tissue in the S-A node, A-V node, A-V bundle, right bundle branch (RBB), left bundle branch (LBB), Purkinje fibers, autonomic nerve bundles and ganglia, and in the myocardium. We observed the relationship between the degree of iron deposition and the extent of scarring in these structures. Finally, we attempted to correlate the estimated transfusional intake of iron, the quantitatively analyzed myocardial iron content, and the severity of microscopic iron deposits in the conduction system with the frequency and severity of antemortem arrhythmias and conduction defects. MethodsFour hearts from patients with thalassemia major (cases 1 to 4) and two from patients with chronic, refractory, aregenerative anemia (cases 5 and 6) were studied both in the gross and microscopically. The microscopic changes in the myocardium and in the specialized tissues of the conduction system were studied in detail. The conduction system was dissected from the heart according to the methods described by Hudson20 and Lev and associates. 21 Step sections of the S-A node, A-V node, bundle of His, and the right and left bundle branches from each heart were made. Sections from the moderator band were taken to demonstrate Purkinje fibers22; the posterior walls of the right atria were sectioned to demonstrate autonomic nerves and ganglia.23 The sections were stained with hematoxylin and eosin, Perls' iron, and the Masson trichrome stains.All sections were evaluated with respect to the amount of iron deposited in these regions and in the myocardium. Sections of the S-A node, A-V node, bundle of His, and myocardium were evaluated with respect to the amount of scarring. The iron deposits and the extent of scarring were each described as absent, light...

Iron overload thalassemic cardiomyopathy: Iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity

“…changes, frequent premature ventricular contraction is most commonly found, while sustained ventricular tachycardia is predominantly related to cardiac death (12). Iron levels in the myocardium seem to be associated more with arrhythmias and conduction disturbance than with the conduction system itself (20,21). It has been shown that patients with supraventricular arrhythmias have extensive iron deposition in the atria, and not in the sinoatrial node (20).…”

“…It tends to accumulate in myocardium (especially interventricular septum and ventricular free wall) more often than in the conduction system. Moreover, clinically, antemortem arrhythmias and conduction disturbance have shown no correlation with iron density in the conduction system (21). Other assessments, such as antioxidant levels -particularly vitamin E, which combats oxidative stress from iron toxicity -have been proposed as being indicative of iron overload cardiomyopathy in TM patients (37).…”

Cardiovascular Function and Treatment in β-Thalassemia Major

“…6 Iron deposition is most common in working muscle and tends to spare the conduction system. 72,210 Postulated mechanisms for the electrophysiological effects include inhibition of fast inward sodium currents, blockage of ryanodine calcium release channel, and oxidative stress-mediated changes in sarcoplasmic calcium release and reuptake. 71,[211][212][213] Clinically, intra-atrial reentrant tachycardia and AF are the most common serious rhythm disturbances.…”

“…45 Early pathological examination of hearts affected by iron overload emphasized the patchiness of iron overload, 72 with evidence of atrioventricular nodal and conducting tissue having variable iron content that was not always associated with clinical evidence of arrhythmia or heart block. 210 A role of severe, untreated iron overload in the development of conduction disturbance would appear likely. The incidence of heart block has diminished drastically with effective chelation therapy in TM patients.…”

Evaluation of a novel oral iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) for treatment of iron overload in mice

“…Iron deposition in the heart cells is of outstanding interest [66][67][68]. Heart failure is the leading cause of death among hemosiderotic -thalassemia patients [69][70][71].…”