Does Oxidative Stress Modulate Left Ventricular Diastolic Function in Asymptomatic Subjects with Hereditary Hemochromatosis?

Abstract

Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography derived measure of diastolic function, may detect such changes. Thus, we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Ninety-four consecutive visits of 43 HH subjects, age 30 to 74 (50 ± 10, mean ± SD) and 37 consecutive visits of 21 normal volunteers age 30 to 63 (48 ± 8) were evaluated over a three-year period. SR was obtained from the basal septum in apical 4 chamber views. All patients had confirmed C282Y homozygosity, a documented history iron overload and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. In the HH subjects, the SR demonstrated moderate, but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect.

How I treat hemochromatosis

“…These abnormalities were not observed in control subjects who lacked HFE C282Y and H63D. 26 Cardiac dysfunction as the result of myocardial siderosis is typically more severe in persons with hemochromatosis caused by HJV or TFR2 mutations than in persons with HFE hemochromatosis and may manifest as dyspnea, orthopnea, or arrhythmia that often improves after iron depletion. 26 Diabetes mellitus, infrequently the result of iron overload alone, is often unchanged by phlebotomy therapy, although some patients report improvement in blood glucose management.…”

Cardiac Involvement in Hemochromatosis

“…iron overload-induced oxidative stress correlates with the diastolic dysfunction measured by strain imaging. 81 in addition to the aforementioned advantages of strain imaging, speckle tracking has the added advantage of not being influenced by angle of interrogation. in asymptomatic patients with thalassemia major and cardiac iron overload, rotational dynamics measured using speckle-tracking echocardiography were abnormal before the appearance of overt echocardiographic abnormalities.…”

Resveratrol improves left ventricular diastolic relaxation in type 2 diabetes by inhibiting oxidative/nitrative stress: in vivo demonstration with magnetic resonance imaging

“…A previous study (36) suggested that LV diastolic function is correlated with oxidative stress. Therefore, we evaluated oxidative stress in cardiac tissue of diabetic mice.…”