Selenium and Chronic Heart Failure

To the Editor: We read with interest the article by Inoko et al about selenium deficiency,1 but we do not agree with the interpretation of the data. Selenium deficiency was identified as a factor in the etiology of heart failure syndromes in areas of very low selenium intakes, such as China, where an endemic selenium-responsive cardiomyopathy is called Keshan disease.2 Similar cases of cardiomyopathy were reported in HIV-infected patients3 and in subjects on parenteral nutrition.4 The patient with Crohn’s disease described by Inoko et al falls into the latter category. When the patient developed his first episode of heart failure, the serum selenium level was not very low (62 mg/L). Low selenium was unlikely the single cause of heart failure, although it certainly contributed. Supplementation “improved the condition of the patient but did not normalize the left ventricular dysfunction,” and “despite selenium supplementation for 11 years, the echocardiographic findings gradually deteriorated.”1 The patient “was free from symptoms of heart failure for 11 years” and died suddenly.1 This discrepancy between the symptoms of heart failure and left ventricular dysfunction emphasizes that the pathophysiology underlying the symptoms of chronic heart failure is complex and poorly understood.5 There is no single cause of the main symptoms of heart failure (dyspnea and muscle fatigue), and treatments that correct the hemodynamics of heart failure do not reliably increase exercise tolerance or reduce the severity of dyspnea.5 The case described by Inoko et al suggests that selenium may have a role in the symptoms of heart failure rather than in the development of left ventricular dysfunction. Yet, selenium deficiency is not the only cause of Keshan disease, and it coincides with the clinical severity rather than the prevalence of the cardiomyopathy as assessed by echocardiography.2 Possible causes of Keshan disease are viral infection and nutritional factors (insufficient zinc or molybdenum, excessive barium or lead). However, when serum selenium levels of residents of an endemic area were raised to the levels found in nonendemic areas, mortality from Keshan disease dramatically decreased, but clinically latent cases were still found, and the echocardiographic prevalence of the disease remained high.2 Therefore, selenium deficiency seems to be a predisposing factor rather than a specific cause of Keshan disease.2 Finally, although the exact cause of Keshan disease remains unknown, numerous agents probably work synergistically. Thus, if selenium supplementation did improve the condition of the patient described by Inoko et al, the primary cause of his cardiomyopathy remains unknown.1 The hypothesis that “once fully developed, the left ventricular dysfunction may be irreversible even after use of selenium supplements”1 is not supported by either their own case or the relevant literature.