Secondary Cardiomyopathy Due to Selenium Deficiency

Abstract

Background

Selenium deficiency can cause cardiomyopathy; however, the underlying mechanisms remain unclear. We report a case of cardiomyopathy associated with selenium deficiency in a patient with long-term enteral nutrition.

Case Summary

A 2-year-old boy with gastrointestinal allergy developed secondary cardiomyopathy due to selenium deficiency resulting from an elemental diet. He presented with reduced left ventricular function and dilated ventricles. Serum selenium levels were undetectable. Myocardial scintigraphy showed perfusion-metabolism mismatches and fibrosis. Selenium supplementation and medications for heart failure led to significant cardiac recovery over a period of 1 year.

Discussion

The patient's congenital heart disease allowed for evaluation before the onset of selenium deficiency cardiomyopathy. Myocardial scintigraphy revealed a characteristic perfusion-metabolism imbalance. Both selenium supplementation and treatment for ischemic heart disease were effective in improving cardiac function.

Take-Home Messages

Myocardial scintigraphy is useful in diagnosing selenium deficiency cardiomyopathy. Selenium supplementation and management of ischemic heart disease are essential for treatment.

Graphical Abstract

History of Presentation and Past Medical History

A 2-year-old boy had been treated since birth for bilateral cleft lip and palate, esophageal atresia, imperforate anus, double-outlet right ventricle, ventricular septal defect, and pulmonary valve stenosis. Enteral nutrition was also used because of severe gastrointestinal allergy in infancy. An infection triggered apnea, raising suspicion of an anoxic spell. Therefore, a light Blalock-Taussig shunt was performed at 52 days of age. Peripheral oxygen saturation began to decline around 7 months of age, and palliative right ventricular outflow tract reconstruction using a tricuspid expanded polytetrafluorethylene conduit was performed at 8 months. The postoperative course was uneventful, and by 1 year and 10 months of age, the patient had grown sufficiently (8 kg) to undergo radical surgery. A Rastelli procedure using a 16-mm expanded polytetrafluorethylene conduit, intraventricular rerouting, and left pulmonary artery plasty were performed. Postoperative follow-up was conducted at regular intervals in the outpatient department (Video 1A). At a routine outpatient visit after intracardiac surgery at 2 years and 5 months of age, a significant decline in left ventricular systolic function, dilated left ventricle (Figure 1A, Video 1B), and elevated B-type natriuretic peptide (BNP) levels were identified, prompting hospital admission for further examination and treatment.

Take-Home Messages

• •Myocardial scintigraphy is useful in diagnosing selenium deficiency cardiomyopathy.
• •Although selenium supplementation is essential for its treatment, it is also important to consider therapies targeting myocardial ischemia.

Figure 1.

Echocardiograms and Progress Chart Before and After Selenium Supplementation

M-mode echocardiogram (A) at the time of selenium deficiency diagnosis and (B) 2.5 years after initiation of selenium supplementation. (C) Treatment course and B-type natriuretic peptide (BNP) levels after the initiation of selenium supplementation (denoted by X).

Differential Diagnosis

The differential diagnosis included progression of congenital heart disease or coronary artery disease after the Rastelli procedure. In addition, since the patient had a history of gastrointestinal allergy during infancy, trace element deficiency, especially selenium deficiency, was suspected.

Investigations

Blood tests on admission showed a negative result for troponin T. An electrocardiogram showed no ST-T wave abnormalities. Diagnostic tests excluded the progression of congenital heart disease and coronary artery disease. Serum selenium levels were undetectable, suggesting secondary cardiomyopathy due to selenium deficiency. Although the patient had been on an elemental diet since infancy because of severe gastrointestinal allergy, selenium supplementation through natural sources such as bonito broth was deemed insufficient.

Myocardial scintigraphy, including ⁹⁹mTc-MIBI resting myocardial perfusion scintigraphy and ¹²³I-BMIPP myocardial fatty acid metabolism scintigraphy, confirmed decreased accumulation in the inferior wall and a perfusion-metabolism mismatch (Figures 2A and 2B). Myocardial biopsy revealed hypertrophy and variability in myocardial fiber size, enlargement and variability in mitochondrial size, diffuse interstitial fibrosis, and the presence of dense granules (Figures 3A to 3D).

Figure 2.

Myocardial Scintigraphy Findings at Selenium Deficiency Diagnosis

(A) The ⁹⁹mTc-MIBI resting myocardial perfusion scintigraphy showed mild perfusion defects in the inferior midventricular wall. (B) The ¹²³I-BMIPP myocardial fatty acid metabolism scintigraphy showed severe uptake defects in the inferior midventricular wall, with a larger area of involvement than the perfusion defects seen in (A), indicating perfusion-metabolism mismatch.

Figure 3.

Electron Micrograph of Myocardial Tissue Sampled From the Interventricular Septum at Selenium Deficiency Diagnosis

Shown are (A) hypertrophy and variability in myocardial fiber size (magnification ×1,000), (B) enlargement and variability in mitochondrial size (magnification ×10,000), (C) diffuse interstitial fibrosis (magnification ×10,000), and (D) presence of dense granules (magnification ×10,000).

Management

Selenium supplements and anti–heart failure drugs, including diuretics, carvedilol, and dapagliflozin propylene glycolate hydrate, were administered (Figure 1C).

Outcome and Follow-Up

Left ventricular asynergy persisted transiently after treatment (Video 1C). However, cardiac function, as well as selenium and BNP levels, improved after more than 1 year of stabilized treatment (Figures 1B and 1C, Video 1D). After the discontinuation of diuretics, BNP levels remained within the normal range. Improvement in the uptake defects in the inferior midventricular wall was confirmed through ¹²³I-BMIPP myocardial fatty acid metabolism scintigraphy performed after cardiac function had recovered. However, ⁹⁹mTc-MIBI resting myocardial perfusion scintigraphy was unable to eliminate extracardiac artifacts, and therefore this could not be properly evaluated (Figures 4A and 4B).

Figure 4.

Myocardial Scintigraphy Findings After Cardiac Function Recovery

(A) The ⁹⁹mTc-MIBI resting myocardial perfusion scintigraphy after cardiac function recovery was performed twice, but extracardiac artifacts could not be eliminated. (B) The ¹²³I-BMIPP myocardial fatty acid metabolism scintigraphy after cardiac function recovery showed improvement in the severe uptake defects in the inferior midventricular wall.

Discussion

Selenium is an essential trace element involved in various metabolic processes, antioxidant defense, and normal cardiovascular function. Selenium deficiency can impair these functions. In the cardiovascular field, selenium deficiency has been associated with myocardial dysfunction, dilated cardiomyopathy, and coronary artery disease.

Although several reports have described selenium deficiency–related cardiomyopathy,1, 2, 3, 4, 5 the underlying mechanisms remain poorly understood. Nevertheless, several important findings have been published that help elucidate these mechanisms. In a multinational prospective observational cohort study, the BIOSTAT-CHF (BIOlogy Study to TAilored Treatment in Chronic Heart Failure), selenium deficiency in patients with heart failure was independently associated with reduced exercise tolerance and a 50% increased risk of mortality.⁶ Additionally, a clinical study involving 2,000 participants in Canada demonstrated that higher selenium levels were associated with a lower prevalence of myocardial infarction.⁷ Another prospective cohort study in Europe revealed that selenoprotein P deficiency was significantly associated with an increased risk of coronary artery disease.⁸

In an animal experiment, a selenium-deficient diet was shown to lower serum selenium levels and glutathione peroxidase activity, leading to severe heart failure.⁹ This study found that a combination of selenium deficiency and low protein intake led to a substantial increase in serum malondialdehyde and reactive oxygen species (ROS) levels, along with a significant reduction in total antioxidizing capacity. Furthermore, elevated levels of cleaved caspase-9 and caspase-3, as well as decreased Bcl-2 expression, indicated that selenium deficiency induces oxidative stress in the myocardium, potentially leading to mitochondrial-mediated apoptosis.⁹ Additionally, in a study of selenium-deficient chicken heart tissue, increased miR-200a-5p expression was found to suppress the expression of its target gene, RFP11, leading to elevated ROS production and activation of RIP3-dependent necroptosis. These findings suggest that selenium deficiency enhances pro-cell-death pathways.¹⁰ In the BIOSTAT-CHF study, human-induced pluripotent stem cell–derived cardiomyocytes cultured under selenium-deficient conditions demonstrated mitochondrial dysfunction and increased ROS, resulting in impairment of major metabolic processes.⁶

In our case, myocardial scintigraphy revealed an imbalance between perfusion and metabolism, with the area of metabolic reduction exceeding that of perfusion reduction, an observation that has not been previously reported. This finding is characteristic of selenium deficiency cardiomyopathy and supports our diagnosis. However, further data are needed to confirm this observation definitively. Based on the studies outlined earlier, there appears to be consistent evidence supporting the proposed mechanisms by which selenium deficiency leads to cardiovascular dysfunction.

Because the myocardial injury in selenium deficiency cardiomyopathy was thought to be caused by micromyocardial ischemia, we believe that treatment for ischemic heart disease, in addition to selenium supplementation, may have contributed to the improvement in our patient. Recovery of cardiac function after selenium supplementation is known to be delayed in patients with selenium deficiency–related cardiomyopathy,⁵ and in some cases, recovery may not occur at all.⁴ Therefore, rather than observing the effects of selenium monotherapy over a prolonged period, we believe that combined therapy involving selenium supplementation and heart failure medications may promote earlier improvement in cardiac function.

Conclusions

Our patient had congenital heart disease and was undergoing regular follow-up after heart surgery, which allowed for the evaluation of cardiac function before the onset of selenium deficiency cardiomyopathy. In addition, the effects of selenium deficiency on mitochondrial function and myocardial microcirculation were able to be assessed from various perspectives. The imbalance between perfusion and metabolism, with a more extensive area of metabolic reduction compared to perfusion reduction, was characteristic of selenium deficiency cardiomyopathy. Furthermore, the results of various tests and treatment courses in this patient suggest that, in addition to selenium supplementation, medical management of ischemic heart disease may also be effective for selenium deficiency cardiomyopathy, even in the absence of coronary ischemia.

Data Availability

The data underlying this article will be shared upon reasonable request to the corresponding author.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Videos 1A-D

Short-Axis Echocardiograms

(A) Echocardiogram after intracardiac repair for congenital heart disease. Mild bilateral pulmonary artery stenosis persisted postoperatively, leading to slight compression of the ventricular septum. (B) Echocardiogram showing decreased cardiac function at the time of selenium deficiency diagnosis. Reduced systolic function was observed throughout the left ventricle. (C) Echocardiogram after initiation of selenium supplementation and medication for heart failure showing left ventricular asynergy. The systolic function of the left ventricular free wall was relatively preserved, whereas that of the ventricular septum remained reduced. (D) Echocardiogram after normalization of B-type natriuretic peptide levels showing improvement in left ventricular asynergy.