Chronic Arsenic Exposure and Cardiac Repolarization Abnormalities with QT Interval Prolongation in a Population-based Study

Abstract

BackgroundChronic arsenic exposure is associated with cardiovascular abnormalities. Prolongation of the QT (time between initial deflection of QRS complex to the end of T wave) interval and profound repolarization changes on electrocardiogram (ECG) have been reported in patients with acute promyelocytic leukemia treated with arsenic trioxide. This acquired form of long QT syndrome can result in life-threatening arrhythmias.ObjectiveThe objective of this study was to assess the cardiac effects of arsenic by investigating QT interval alterations in a human population chronically exposed to arsenic.MethodsResidents in Ba Men, Inner Mongolia, have been chronically exposed to arsenic via consumption of water from artesian wells. A total of 313 Ba Men residents with the mean arsenic exposure of 15 years were divided into three arsenic exposure groups: low (≤ 21 μg/L), medium (100–300 μg/L), and high (430–690 μg/L). ECGs were obtained on all study subjects. The normal range for QTc (corrected QT) interval is 0.33–0.44 sec, and QTc ≥ 0.45 sec was considered to be prolonged.ResultsThe prevalence rates of QT prolongation and water arsenic concentrations showed a dose-dependent relationship (p = 0.001). The prevalence rates of QTc prolongation were 3.9, 11.1, 20.6% for low, medium, and high arsenic exposure, respectively. QTc prolongation was also associated with sex (p < 0.0001) but not age (p = 0.486) or smoking (p = 0.1018). Females were more susceptible to QT prolongation than males.ConclusionsWe found significant association between chronic arsenic exposure and QT interval prolongation in a human population. QT interval may potentially be useful in the detection of early cardiac arsenic toxicity.

Cardiovascular effects of arsenic: clinical and epidemiological findings

“…As exposure in a wide range of levels is consistently associated with QT prolongation -a risk factor for arrhythmia and sudden cardiac death -torsade de pointes (Ficker et al 2004;Mumford et al 2007;Mordukhovich et al 2009;Wang et al 2009), and increased QT dispersion (Wang et al 2010). As may act on QT by increasing cardiac calcium currents (Ficker et al 2004), but no protective effect of calcium-antagonists has been found (Mordukhovich et al 2009) and there are conflicting data on verapamil enhancing or reducing As cardiotoxicity (Zhao et al 2008a;Luong and Rabkin 2009).…”

Patient-Reported Outcomes of Deferasirox (Exjade®, ICL670) versus Deferoxamine in Sickle Cell Disease Patients with Transfusional Hemosiderosis

“…In one study, more than 40% of patients reported that the primary reason for missing a dose of DFO was drug-related side effects [14]. Additionally, the mode of DFO administration – subcutaneous infusions over an 8- to 12-hour period, 5–7 days per week [15] – is extremely demanding.…”

Progress in the treatment of acute promyelocytic leukemia: optimization and obstruction

“…However, as has long been acknowledged in chemistry and toxicology, chronic arsenic intoxication might induce lesions to multiple organs and systems, involving the liver, skin, cardiovascular, neurologic and GI systems [79,80], and the most frightful adverse effect is carcinogenesis occurring specifically on the skin, lungs and bladder [80]. Smith et al [81] estimated that the lifetime risk of dying from cancer generated by daily ingestion of 1 l of water containing 50 lg/l arsenic could be as high as 13 per 1000 people exposed.…”