Incidence of Cardiac Arrhythmias in Asymptomatic Hereditary Hemochromatosis Subjects With C282Y Homozygosity

Abstract

It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In this study, we examined the incidence of cardiac arrhythmias in cardiac asymptomatic HH subjects (NYHA functional class I), and compared it to that in age/gender-matched normal volunteers. The 42 HH subjects and 19 normal volunteer control subjects recruited through the NHLBI-sponsored "Heart Study of Hemochromatosis" completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The HH subjects were classified as newly diagnosed (Group A) and chronically treated subjects (Group B). All HH subjects had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations which are known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be higher in the combined HH groups than the controls. Supraventricular ectopy was more frequently noted in Group B as compared to the controls (ectopy rate per hour; 11.1±29.9 vs. 1.5±3.5, P < 0.05 by Kurskal Wallis test). No examples of heart block, other than first degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in Group A subjects. No life threatening arrhythmias were observed in our HH subjects. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic HH subjects. A larger clinical study is warranted to further clarify our observation.

Cardiac Involvement in Hemochromatosis

“…Supraventricular ectopy was more frequently noted in the chronically treated hemochromatosis group compared with controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, P < 0.05). 41 the combined incidence of ventricular and supraventricular ectopy tended to be greater in the hemochromatosis group but was not statistically significant. No life-threatening arrhythmias were observed.…”

“…the variation in the grade of stainable iron in endomyocardial tissue is inversely related to lv function. 41 iron deposition in the heart is patchy, and biopsies may be falsely negative. 48 Being an invasive procedure, endomyocardial biopsy is not an ideal tool to screen asymptomatic individuals.…”

“…No life-threatening arrhythmias were observed. 41 Shizukuda et al 42 studied the longterm effect on aerobic exercise capacity in 43 asymptomatic patients with hereditary hemochromatosis and 23 controls. cardiopulmonary exercise testing was performed using the Bruce protocol, and aerobic exercise capacity was assessed with minute ventilation, oxygen uptake, and carbon dioxide production.…”

Iron Overload or Oxidative Stress? Insight into a Mechanism of Early Cardiac Manifestations of Asymptomatic Hereditary Hemochromatosis Subjects with C282Y Homozygosity

“…Subclinical, early cardiac manifestations include altered left ventricular diastolic function (2) and increased arrhythmias (3). Organ damage can be resulted from either iron overload directly or secondary elevation of oxidative stress due to iron overload in HH (1); however, little is known about the precise etiology of the early cardiac manifestations in HH.…”

“…Oxidative stress was measured using plasma malondialdehyde (MDA), erythrocyte glutathione (GSH), and erythrocyte superoxide dismutase (SOD) levels (5). The arrhythmia activity was assessed with an hourly rate of supraventricular (SVE) and ventricular ectopic beats (VE) recorded on 48-hour Holter ambulatory monitoring (3). The correlations between biomarkers and arrhythmia activity were analyzed with a non-parametric Spearman correlation test.…”