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<title>Keshan Disease - StatPearls - NCBI Bookshelf</title>
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="StatPearls [Internet]" /><meta name="citation_title" content="Keshan Disease" /><meta name="citation_publisher" content="StatPearls Publishing" /><meta name="citation_date" content="2024/05/07" /><meta name="citation_author" content="Daniel Fabian" /><meta name="citation_author" content="Intisar Ahmed" /><meta name="citation_pmid" content="38753920" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK603722/" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Keshan Disease" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="StatPearls Publishing" /><meta name="DC.Contributor" content="Daniel Fabian" /><meta name="DC.Contributor" content="Intisar Ahmed" /><meta name="DC.Date" content="2024/05/07" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK603722/" /><meta name="description" content="Keshan disease is an endemic cardiomyopathy first discovered in the northeastern Chinese county of Keshan. This cardiomyopathy primarily occurs in regions with selenium-deficient soils, particularly in specific rural and remote areas, leading to severe health complications and occasional fatalities. Studies directly link low soil selenium and local food sources to reduced selenium levels in affected populations.[1][2] Keshan disease is characterized by myocardial necrosis and fibrosis, resulting in severe heart complications, such as cardiogenic shock and heart failure.[3] Clinical presentations include acute cardiac episodes, arrhythmias, and heart failure.[4] " /><meta name="og:title" content="Keshan Disease" /><meta name="og:type" content="book" /><meta name="og:description" content="Keshan disease is an endemic cardiomyopathy first discovered in the northeastern Chinese county of Keshan. This cardiomyopathy primarily occurs in regions with selenium-deficient soils, particularly in specific rural and remote areas, leading to severe health complications and occasional fatalities. Studies directly link low soil selenium and local food sources to reduced selenium levels in affected populations.[1][2] Keshan disease is characterized by myocardial necrosis and fibrosis, resulting in severe heart complications, such as cardiogenic shock and heart failure.[3] Clinical presentations include acute cardiac episodes, arrhythmias, and heart failure.[4] " /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK603722/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-statpearls-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/statpearls/article-156302/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK603722/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} </style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script>
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. </p></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK603722_"><span class="title" itemprop="name">Keshan Disease</span></h1><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Daniel Fabian</span><sup>1</sup>; <span itemprop="author">Intisar Ahmed</span><sup>2</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> Guthrie Robert Packer Hospital</div><div class="affiliation"><sup>2</sup> Aga Khan University Pakistan</div><p class="small">Last Update: <span itemprop="dateModified">May 7, 2024</span>.</p></div><div class="body-content whole_rhythm" itemprop="text"><div id="article-156302.s1"><h2 id="_article-156302_s1_">Continuing Education Activity</h2><p>Keshan disease, discovered in 1935 in China's Keshan County, is a rare cardiomyopathy primarily found in regions with selenium-deficient soils, notably in specific rural and remote areas. This condition primarily presents as a potentially fatal and progressive form of heart disease, emphasizing the urgency for early identification and intervention due to its significant impact on cardiac health and the potential for chronic complications. The hallmark of the condition is myocardial necrosis and fibrosis, resulting in severe heart complications, such as cardiogenic shock and heart failure, with clinical manifestations ranging from acute cardiac episodes to arrhythmias. Distinguishing early-stage Keshan disease from other cardiomyopathies presents diagnostic challenges. Treatment usually includes diuretics and guideline-directed medical therapy.</p><p>The complex nature of its etiology, multifaceted presentation, and the potential for long-term cardiac sequelae require healthcare professionals to comprehensively understand the disease. By fostering an environment of early detection and intervention, clinicians can substantially mitigate the complications associated with Keshan disease, improving patient outcomes and highlighting the importance of tailored dietary interventions and selenium supplementation. This activity centers on the complexities of Keshan disease, highlighting the critical roles of interprofessional healthcare team members in early recognition and intervention in latent cases to halt disease progression. This activity also emphasizes the importance of involving patients in collaborative decision-making, particularly regarding selenium supplementation or personalized dietary interventions. These strategies help prevent the progression of Keshan disease and significantly enhance the overall quality of life for those affected by this cardiac condition.</p><p>
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<b>Objectives:</b>
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<ul><li class="half_rhythm"><div>Identify the clinical manifestations and risk factors associated with Keshan disease.</div></li><li class="half_rhythm"><div>Screen individuals in selenium-deficient regions for early signs and symptoms of Keshan disease.</div></li><li class="half_rhythm"><div>Select appropriate diagnostic tests and imaging modalities for evaluating cardiac function in Keshan disease.</div></li><li class="half_rhythm"><div>Collaborate with interprofessional healthcare teams to optimize patient care and outcomes.</div></li></ul>
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<a href="https://www.statpearls.com/account/trialuserreg/?articleid=156302&utm_source=pubmed&utm_campaign=reviews&utm_content=156302" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Access free multiple choice questions on this topic.</a>
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</p></div><div id="article-156302.s2"><h2 id="_article-156302_s2_">Introduction</h2><p>Keshan disease is an endemic cardiomyopathy first discovered in the northeastern Chinese county of Keshan. This cardiomyopathy primarily occurs in regions with selenium-deficient soils, particularly in specific rural and remote areas, leading to severe health complications and occasional fatalities. Studies directly link low soil selenium and local food sources to reduced selenium levels in affected populations.<a class="bk_pop" href="#article-156302.r1">[1]</a><a class="bk_pop" href="#article-156302.r2">[2]</a> Keshan disease is characterized by myocardial necrosis and fibrosis, resulting in severe heart complications, such as cardiogenic shock and heart failure.<a class="bk_pop" href="#article-156302.r3">[3]</a> Clinical presentations include acute cardiac episodes, arrhythmias, and heart failure.<a class="bk_pop" href="#article-156302.r4">[4]</a> </p><p>Recent research highlights genetic factors besides selenium deficiency as a possible cause of Keshan disease, revealing various polymorphisms and mutations contributing to the disease's development.<a class="bk_pop" href="#article-156302.r5">[5]</a><a class="bk_pop" href="#article-156302.r6">[6]</a> This interplay between selenium deficiency and genetic predisposition adds complexity to understanding the disease.</p></div><div id="article-156302.s3"><h2 id="_article-156302_s3_">Etiology</h2><p>Keshan disease has numerous potential etiological factors, including selenium deficiency, genetic predispositions, viral and fungal infections, and malnutrition. However, the precise causative factors behind Keshan disease remain poorly understood.<a class="bk_pop" href="#article-156302.r6">[6]</a> Selenium is acquired through diverse foods such as grains, meat, and fish. The selenium levels in terrestrial foods primarily rely on the selenium content in the soil where plants or animal feeds are cultivated.</p><p>Human selenium deficiency arises in regions where the soil's selenium content is notably low, and locally grown foods are the primary source of nutrients.<a class="bk_pop" href="#article-156302.r7">[7]</a> Notably, about half the Chinese population does not meet the World Health Organization's selenium intake recommendation.<a class="bk_pop" href="#article-156302.r8">[8]</a> Selenium deficiency is considered the leading cause of Keshan disease. This theory is supported by the significant decrease in disease prevalence following sodium selenite supplementation in table salt and crops.<a class="bk_pop" href="#article-156302.r9">[9]</a><a class="bk_pop" href="#article-156302.r10">[10]</a> </p><p>However, selenium deficiency alone is not believed to be the sole cause of Keshan disease, as not all selenium-deficient individuals develop manifestations. Keshan disease is considered to involve gene-environment interactions associated with selenium deficiency and other possible factors.<a class="bk_pop" href="#article-156302.r11">[11]</a> Other proposed nutritional factors contributing to the disease include vitamin E, protein, and amino acid deficiencies.<a class="bk_pop" href="#article-156302.r12">[12]</a><a class="bk_pop" href="#article-156302.r13">[13]</a></p></div><div id="article-156302.s4"><h2 id="_article-156302_s4_">Epidemiology</h2><p>The epidemiology of Keshan disease reflects its geographical distribution, mainly prevalent in certain provinces of China and sporadically reported in other countries with similar selenium-deficient environments. Emerging as a significant health concern during the mid-20th century, Keshan disease experienced notable prevalence between 1950 and 1970, marked by 3 major outbreaks in 1959, 1964, and 1970.<a class="bk_pop" href="#article-156302.r14">[14]</a> The disease's reach expanded across multiple regions, encompassing over 2,900 towns in 327 counties within 15 provinces across China, spanning from the northeast to the southwest, an area inhabited by over 60 million people.<a class="bk_pop" href="#article-156302.r15">[15]</a> </p><p>Children aged 2 to 10 and women of childbearing age appear to be most susceptible to Keshan disease.<a class="bk_pop" href="#article-156302.r12">[12]</a><a class="bk_pop" href="#article-156302.r14">[14]</a> The endemic locations where Keshan disease is commonly observed are remote, rural, and economically disadvantaged areas. The high prevalence in these areas may also indicate the socioeconomic vulnerabilities of the inhabitants.<a class="bk_pop" href="#article-156302.r14">[14]</a></p><p>Notably, the average annual incidence stood at 10 per 100,000 population, reaching alarming rates in specific areas. For instance, in 1960, the Chuxiong region in Yunnan Province experienced an unprecedented incidence exceeding 100 per 100,000 population, with a mortality rate surpassing 98%.<a class="bk_pop" href="#article-156302.r16">[16]</a> Although most documented cases originate from China, Keshan disease has also been reported in regions with low selenium levels in Russia, Korea, and Japan.<a class="bk_pop" href="#article-156302.r17">[17]</a><a class="bk_pop" href="#article-156302.r18">[18]</a> Noteworthy instances akin to Keshan disease were observed in Japan's Nagano prefecture and the northern mountains of North Korea during the 1950s.<a class="bk_pop" href="#article-156302.r18">[18]</a> This widespread occurrence across various nations underscores the disease's geographical diversity and relationship with selenium-deficient regions. </p></div><div id="article-156302.s5"><h2 id="_article-156302_s5_">Pathophysiology</h2><p>
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<b>Selenium's Role as an Antioxidant</b>
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</p><p>Dietary selenium is a necessary micronutrient for both humans and mammals.<a class="bk_pop" href="#article-156302.r19">[19]</a> Selenium directly integrates into polypeptide chains as seleno-L-cysteine (SeCys), contributing to 25 identified SeCys-containing proteins known as selenoproteins in humans.<a class="bk_pop" href="#article-156302.r20">[20]</a> Notably, glutathione peroxidases (GPxs) use selenoproteins to catalyze the reduction of peroxide species (R-OOH) into alcohols (R-OH). Selenium is crucial in fortifying the body's antioxidant defense against the oxidative damage induced by respiration.<a class="bk_pop" href="#article-156302.r21">[21]</a> Individuals with Keshan disease exhibit lower expression of glutathione peroxidases in their hearts compared to healthy subjects due to selenium deficiency.<a class="bk_pop" href="#article-156302.r22">[22]</a> This deficiency contributes to the onset of myocardial disease.<a class="bk_pop" href="#article-156302.r7">[7]</a></p><p>The adult heart typically derives 50% to 70% of its adenosine 5’-triphospate from beta-oxidation of fatty acids.<a class="bk_pop" href="#article-156302.r23">[23]</a> Increased fatty acid oxidation amplifies the production of byproducts, such as reactive oxygen species, through mitochondrial oxidative phosphorylation. Selenium-dependent glutathione peroxidases serve an essential function in eliminating these reactive oxygen species, particularly organic hydroperoxidases, from the heart.<a class="bk_pop" href="#article-156302.r7">[7]</a> Additionally, research suggests that selenium could play a role in Keshan disease development by affecting the function of selenium-related genes engaged in apoptosis, ion transport, metabolism, and myocardial growth and development.<a class="bk_pop" href="#article-156302.r5">[5]</a></p><p>
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<b>Genetic Mutations Involved in Keshan Disease</b>
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</p><p>Although selenium deficiency is a significant cause of Keshan disease, it may not exclusively encompass the entire spectrum of Keshan disease's origins. The onset of Keshan disease has also been proposed to be linked with specific genetic mutations or polymorphisms. The selenium-dependent enzyme GPx-1 plays a protective role by detoxifying hydrogen peroxide, and mutations in GPx-1 increase the incidence of Keshan disease.<a class="bk_pop" href="#article-156302.r11">[11]</a></p><p>In individuals carrying the GPx-1 leucine-containing allele and experiencing selenium deficiency, there is a notable decrease in GPx-1 enzyme activity, potentially contributing to the incidence of Keshan disease. A study on mice with a disrupted <i>Gpx-1</i> gene showed a higher susceptibility to developing myocarditis following coxsackie virus infection than infected wild-type mice, demonstrating resistance. This research revealed the protective role of GPx-1 against damage induced by viral infection, illustrating the critical association between GPx-1 and selenium in shielding against viral-induced cardiac damage.<a class="bk_pop" href="#article-156302.r24">[24]</a></p><p>Another study investigated the human <i>SCN5A</i> gene, which encodes a sodium channel within the cardiomyocyte membrane. This study revealed a significant association between the H558R polymorphism in exon 12 of SCN5A and Keshan disease. This genetic variation was significantly associated with increased susceptibility to Keshan disease and demonstrated potential connections with QRS prolongation observed in electrocardiogram (ECG) measurements.<a class="bk_pop" href="#article-156302.r25">[25]</a></p><p>The selenium-related gene <i>ALAD</i> (delta-aminolevulinic acid dehydratase) exhibits high expression in cardiomyocytes. A study revealed that inhibiting ALAD in mice led to a Keshan-like phenotype characterized by cardiac dysfunction and left ventricular enlargement. Remarkably, the administration of sodium selenite effectively reversed these changes caused by ALAD inhibition and was associated with alterations in energy metabolism and improved mitochondrial function. This underscores the essential role of ALAD in maintaining normal mitochondrial activity crucial for cardiac function, offering substantial molecular evidence supporting the hypothesis of selenium deficiency in Keshan disease.<a class="bk_pop" href="#article-156302.r26">[26]</a> </p><p>Another study highlighted heightened expression levels of <i>CYP1A1</i> and <i>CYP2C19</i> genes in individuals affected by Keshan disease. These genes are part of the cytochrome P450 (CYP450) isoforms, responsible for producing metabolites required for crucial bodily functions. These CYP450 metabolites are proposed to have a significant role in the pathogenesis of Keshan disease. The study unveiled that increased expression of the <i>CYP1A1</i> gene might exacerbate myocardial injury, whereas upregulation of the <i>CYP2C19</i> gene could represent a compensatory protective response.<a class="bk_pop" href="#article-156302.r27">[27]</a></p><p>
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<b>Viral Origins of Keshan Disease</b>
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</p><p>A growing consideration suggests that selenium deficiency might not be the sole factor in Keshan disease's origin. Coxsackievirus infection has emerged as a contributing pathogenic element.<a class="bk_pop" href="#article-156302.r16">[16]</a><a class="bk_pop" href="#article-156302.r28">[28]</a> Evidence of coxsackievirus RNA in the myocardium of Keshan disease patients suggests its potential role in the disease.<a class="bk_pop" href="#article-156302.r29">[29]</a> In addition, it is hypothesized that viral infection-induced cardiomyocyte damage triggers myocardial injury, culminating in Keshan disease.<a class="bk_pop" href="#article-156302.r14">[14]</a> An increase in viral genome mutations is observed in selenium-deficient mice infected with the Coxsackie virus, resulting in a more virulent strain targeting the heart.<a class="bk_pop" href="#article-156302.r30">[30]</a> This connection emphasizes the possible interplay between selenium deficiency and viral infection in the manifestation of Keshan disease. </p></div><div id="article-156302.s6"><h2 id="_article-156302_s6_">Histopathology</h2><p>Gross pathology shows myocardial pallor with white streaks, often accompanied by patchy necrosis and fibrosis replacement throughout the myocardium. Depending on the stage of the disease, various degrees of cellular inflammation and calcification may be present. These changes can also be similar to those of dilated cardiomyopathy or myocarditis.<a class="bk_pop" href="#article-156302.r14">[14]</a><a class="bk_pop" href="#article-156302.r31">[31]</a></p></div><div id="article-156302.s7"><h2 id="_article-156302_s7_">History and Physical</h2><p>Documenting the patient's history involves meticulous inquiry into various aspects such as geographic location, dietary habits, family medical history, and exposure to environmental factors prevalent in selenium-deficient regions. The physical examination component of Keshan disease assessment involves a comprehensive evaluation of the patient's cardiac status. Patients with Keshan disease commonly present with a spectrum of cardiac complications, including acute heart failure, congestive heart failure, and cardiac arrhythmia, reflecting the disease's multifaceted impact on the cardiovascular system.<a class="bk_pop" href="#article-156302.r15">[15]</a> Characterized by multifocal necrosis and fibrosis, Keshan disease poses risks of cardiogenic shock and congestive heart failure, adding complexity to its clinical manifestation.<a class="bk_pop" href="#article-156302.r1">[1]</a></p><p>Clinically, patients with Keshan disease are categorized into 4 distinct types—acute, subacute, chronic, and latent—based on the onset of symptoms, clinical features, and cardiac function. The acute form usually manifests abruptly and is characterized by occurrences such as cardiogenic shock, severe arrhythmias, or pulmonary edema, often leading to acute decompensated heart failure.<a class="bk_pop" href="#article-156302.r15">[15]</a> Predominant symptoms in acute Keshan disease involve malaise, dizziness, dyspnea, nausea, and substernal discomfort.<a class="bk_pop" href="#article-156302.r14">[14]</a> </p><p>Patients experience a slower onset in the subacute phase compared to the acute presentation. This phase will display both cardiogenic shock and congestive heart failure symptoms. Cardiomegaly remains common, with significant heart dilation, although myocardial degeneration and necrosis are less severe than in the acute phase. Scattered myocardial fibrosis is typically observed during this phase.<a class="bk_pop" href="#article-156302.r15">[15]</a> </p><p>Chronic Keshan disease is characterized by insidious onset and features severe cardiomyopathy leading to congestive heart failure. Patients exhibit dilated heart chambers, thinning of heart walls, and widespread myocardial fibrosis, reflecting varying degrees of pathological changes.<a class="bk_pop" href="#article-156302.r32">[32]</a><a class="bk_pop" href="#article-156302.r18">[18]</a> The slower onset of the chronic form emphasizes the progressive nature of the disease and its substantial impact on cardiac function.<a class="bk_pop" href="#article-156302.r15">[15]</a> </p><p>Conversely, the latent type of Keshan disease may initially involve minor cardiac abnormalities but maintains compensated heart function.<a class="bk_pop" href="#article-156302.r32">[32]</a> Patients may exhibit ECG changes such as ventricular extrasystole, right bundle branch block, or ST-T changes without evident cardiomegaly, presenting a disguised onset with reasonably preserved heart function.<a class="bk_pop" href="#article-156302.r15">[15]</a></p><p>Evidence also suggests a role of Keshan disease contributing to hypertension, which can worsen cardiac pathology. Lower urinary selenium is positively associated with hypertension in Asian countries, although it is challenging to separate this from other possible contributing dietary and nutritional factors.<a class="bk_pop" href="#article-156302.r8">[8]</a></p><p>Additionally, beyond its cardiovascular implications, selenium deficiency has been associated with various conditions like thyroiditis, Graves disease, and goiter, broadening the scope of health concerns related to inadequate selenium levels.<a class="bk_pop" href="#article-156302.r33">[33]</a> Understanding these correlations underscores the multifaceted nature of selenium's role in health and highlights its relevance beyond the context of Keshan disease. </p></div><div id="article-156302.s8"><h2 id="_article-156302_s8_">Evaluation</h2><p>Diagnostic challenges in distinguishing early-stage Keshan disease from idiopathic dilated cardiomyopathy due to shared features such as an enlarged heart, systolic dysfunction, and arrhythmias pose significant clinical hurdles. A universally acknowledged gold standard for diagnosing Keshan disease does not exist currently.<a class="bk_pop" href="#article-156302.r14">[14]</a> ECG is the primary noninvasive diagnostic tool for identifying latent Keshan disease.</p><p>In a decade-long study monitoring 414 patients with latent Keshan disease and ECG abnormalities, Zhu et al uncovered significant findings. Among these patients, 47% exhibited major ECG abnormalities, including complete heart block, atrial fibrillation, atrial flutter, left ventricular hypertrophy, major ST-T changes, prolonged QT intervals, significant AV conduction abnormalities, and supraventricular tachycardia. Additionally, 53% presented minor ECG irregularities, such as minor ST-T changes, premature beats, incomplete bundle branch block, sinus tachycardia or bradycardia, minor QT prolongation, variations in PR intervals, and deviations in left or right axis, among other minor arrhythmias. Notably, 389 out of 414 patients maintained persistent ECG abnormalities throughout the follow-up period. The presence of major ECG abnormalities in latent Keshan disease patients significantly correlated with an elevated risk of progression to chronic Keshan disease compared to those displaying minor ECG irregularities.<a class="bk_pop" href="#article-156302.r18">[18]</a></p><p>Another analysis of 71 Keshan disease patients and 290 controls identified risk factors associated with Keshan disease development. Among patients with Keshan disease, 31% presented with significant heart dysfunction (The New York Heart Association [NYHA] classes III-IV). Additionally, a notable proportion (61%) of chronic Keshan disease patients had a family history of the disease, indicating a genetic predisposition to Keshan disease. ECG abnormalities were prevalent among most patients. Echocardiography revealed cardiac dilation in all 31 chronic Keshan disease cases, accompanied by ventricular wall motion attenuation and valvular regurgitation. These findings highlight the importance of familial history and pronounced cardiac manifestations in assessing Keshan disease risk and severity.<a class="bk_pop" href="#article-156302.r3">[3]</a></p><p>Integrating study findings emphasizes the diagnostic value of ECG in detecting latent Keshan disease and predicting disease progression. Furthermore, the correlation between familial history and advanced cardiac dysfunction provides insights into the genetic basis and severe cardiac implications of chronic Keshan disease. Despite the absence of a definitive diagnostic criterion, a comprehensive evaluation encompassing ECG assessments, familial history analysis, echocardiographic studies, and cardiac magnetic resonance imaging (MRI) proves invaluable in excluding the other causes of cardiomyopathy, as well as guiding the diagnosis and establishing the prognosis of Keshan disease. </p><p>When measuring selenium levels, serum, whole blood, urine, hair, and nail samples are the most commonly used measurements. Among these, serum levels are the most prone to acute fluctuations, potentially making these values less reliable.<a class="bk_pop" href="#article-156302.r13">[13]</a><a class="bk_pop" href="#article-156302.r34">[34]</a> Glutathione peroxidases have also been used as selenium markers, but levels are prone to hormonal fluctuations.<a class="bk_pop" href="#article-156302.r13">[13]</a> Selenoprotein P, accounting for over 60% of plasma selenium, is an essential indicator of selenium nutrition. Considered the best marker of long-term selenium intake, it correlates highly with serum selenium but exhibits less fluctuation.<a class="bk_pop" href="#article-156302.r35">[35]</a></p></div><div id="article-156302.s9"><h2 id="_article-156302_s9_">Treatment / Management</h2><p>The treatment of Keshan disease–induced cardiomyopathy and heart failure includes diuretics and other guidelines-directed medical therapy.<a class="bk_pop" href="#article-156302.r36">[36]</a> Device-based treatment for the management of heart failure and prevention of sudden cardiac death should be offered as recommended by contemporary guidelines.<a class="bk_pop" href="#article-156302.r37">[37]</a> Disease-specific treatment for Keshan disease primarily focuses on selenium supplementation. Sodium selenite tablets have demonstrated efficacy in reducing mortality rates among patients with Keshan disease.<a class="bk_pop" href="#article-156302.r38">[38]</a> However, it is essential to tread cautiously with selenium intake.</p><p>The US National Academy of Sciences recommends a daily intake of 55 µg of selenium, with 400 µg being the upper limit to avoid toxicity.<a class="bk_pop" href="#article-156302.r39">[39]</a><a class="bk_pop" href="#article-156302.r40">[40]</a> A recent study highlighted improved survival rates in individuals with congestive heart failure when selenium supplementation was combined with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers.<a class="bk_pop" href="#article-156302.r41">[41]</a> However, carefully monitoring selenium intake is imperative due to potential adverse effects. Exceeding 700 µg/d of selenium is deemed toxic to adults, leading to symptoms such as diarrhea, fatigue, hair loss, brittle hair, memory loss, and foul breath.<a class="bk_pop" href="#article-156302.r42">[42]</a></p><p>Notably, selenium overdose has been associated with the development of type II diabetes. While some observational studies suggest a positive correlation between selenium levels and diabetes risk, this association lacks consistency in randomized clinical trials.<a class="bk_pop" href="#article-156302.r43">[43]</a><a class="bk_pop" href="#article-156302.r44">[44]</a> Even at normal selenium plasma concentrations, a 3-month daily intake of 200 µg led to hyperglycemia in diabetic patients.<a class="bk_pop" href="#article-156302.r45">[45]</a> A delicate balance is crucial in selenium supplementation therapy, emphasizing precise dosage monitoring and consideration of individual patient profiles to avoid potential complications. Treatment protocols should integrate selenium supplementation judiciously, weighing its therapeutic benefits against the risk of adverse effects, especially in populations prone to conditions like diabetes. </p></div><div id="article-156302.s10"><h2 id="_article-156302_s10_">Differential Diagnosis</h2><p>The differential diagnosis of Keshan disease involves considering various cardiac conditions that exhibit symptomatic similarities, necessitating a meticulous evaluation for accurate differentiation.</p><ul><li class="half_rhythm"><div>Dilated cardiomyopathy shares features such as heart dilation and dysfunction, demanding thorough assessments involving family history.<a class="bk_pop" href="#article-156302.r46">[46]</a> </div></li></ul><ul><li class="half_rhythm"><div>Ischemic heart disease, encompassing myocardial infarction and chronic ischemic conditions, mirrors Keshan disease in heart failure and arrhythmias, requiring cardiac biomarkers and imaging for accurate distinction.</div></li></ul><ul><li class="half_rhythm"><div>Viral myocarditis, symptomatically similar to Keshan disease, often necessitates viral testing, imaging, and histopathology.<a class="bk_pop" href="#article-156302.r47">[47]</a>  </div></li></ul><ul><li class="half_rhythm"><div>Hypertrophic cardiomyopathy warrants evaluation with imaging and genetic testing.</div></li></ul><ul><li class="half_rhythm"><div>Other cardiomyopathies, including infiltrative or restrictive types such as amyloidosis or sarcoidosis, need imaging and biopsy for accurate differentiation. </div></li></ul><ul><li class="half_rhythm"><div>Nutritional cardiomyopathies, such as wet beriberi, mimic Keshan disease, mandating dietary assessments and specific lab tests.<a class="bk_pop" href="#article-156302.r48">[48]</a></div></li></ul></div><div id="article-156302.s11"><h2 id="_article-156302_s11_">Prognosis</h2><p>The prognosis of Keshan disease varies widely depending on the disease stage and the timing of intervention. In the acute and subacute phases, prompt medical attention is vital to prevent severe complications like cardiogenic shock or heart failure, which significantly affect prognosis. Major ECG abnormalities in patients with latent Keshan disease, such as complete heart block, atrial fibrillation, and significant ST-T changes, have been associated with a higher risk of disease progression to chronic Keshan disease.<a class="bk_pop" href="#article-156302.r18">[18]</a> Selenium supplementation shows promise in improving outcomes.<a class="bk_pop" href="#article-156302.r38">[38]</a> </p><p>A study examined the correlation between serum selenium concentrations and the outcomes of patients with heart failure within a Chinese population. The findings revealed a notable impact on survival rates, particularly in individuals with reduced serum selenium levels. Patients in the bottom quartile, characterized by the lowest serum selenium concentration, exhibited the worst prognosis among heart failure patients, showcasing a significantly heightened risk of all-cause mortality. These findings emphasize that selenium levels are crucial in determining prognosis. Interestingly, no discernible association was noted between serum selenium concentration and incidences of rehospitalization among these patients with heart failure, pointing to the multifactorial etiology of Keshan disease.<a class="bk_pop" href="#article-156302.r49">[49]</a> </p></div><div id="article-156302.s12"><h2 id="_article-156302_s12_">Complications</h2><p>Complications arising from Keshan disease primarily stem from its impact on cardiac function and systemic health. The progressive nature of the disease, characterized by multifocal necrosis and fibrosis in the myocardium, often leads to severe complications. Acute Keshan disease commonly presents with cardiogenic shock and life-threatening arrhythmias, while patients with severe left ventricular systolic dysfunction may experience cardiac arrest and sudden cardiac death due to ventricular arrhythmias.<a class="bk_pop" href="#article-156302.r14">[14]</a> Chronic Keshan disease can lead to debilitating heart failure, compromising the heart's pumping capacity and causing fluid accumulation in the lungs and peripheral tissues. Arrhythmias, including potentially life-threatening ones like complete heart block, atrial fibrillation, and ventricular arrhythmias, pose significant risks. Furthermore, the disease's influence on cardiac structure can result in dilated chambers, weakened heart walls, and valvular abnormalities, amplifying the propensity for congestive heart failure and related complications.<a class="bk_pop" href="#article-156302.r15">[15]</a><a class="bk_pop" href="#article-156302.r18">[18]</a><a class="bk_pop" href="#article-156302.r32">[32]</a></p></div><div id="article-156302.s13"><h2 id="_article-156302_s13_">Deterrence and Patient Education</h2><p>Identifying latent Keshan disease, often asymptomatic and untreated, presents a critical challenge. Recognizing these cases, with their elevated risk of progressing to chronic Keshan disease, is pivotal for effective intervention. In historically severe endemic areas, Keshan disease remains a significant public health concern. Strengthening selenium supplementation initiatives and implementing patient self-management programs emerge as vital strategies to combat the disease's impact. Prevention efforts should prioritize selenium salt supplementation within endemic areas, warranting heightened attention and emphasis in public health agendas.<a class="bk_pop" href="#article-156302.r15">[15]</a> </p><p>Zhou et al's comprehensive meta-analysis assessed selenium supplementation's preventive impact on Keshan disease. Analyzing 17 studies with 1.9 million subjects, their findings highlighted a substantial disparity in disease risk between control and selenium-supplemented groups. The control group showed an 8-fold higher risk of Keshan disease compared to the selenium-supplemented group, validating the significant preventive potential of selenium supplementation.<a class="bk_pop" href="#article-156302.r10">[10]</a></p><p>The historical context of selenium deficiency as a potential contributor to Keshan disease prompted proactive measures in China. Selenium supplementation, primarily through sodium selenite, was implemented in selenium-deficient regions. Notably, a large-scale trial involving 1.05 million individuals supplemented with selenium-fortified table salt showcased remarkable results. The annual incidence of acute and subacute Keshan disease significantly declined in the selenium-supplemented population, illustrating a decrease from 25.23 to 2.7 cases per 100,000 individuals. Concurrently, the detection rate of latent Keshan disease cases was markedly reduced in the supplemented group compared to the control, demonstrating the tangible impact of selenium supplementation in disease deterrence.<a class="bk_pop" href="#article-156302.r50">[50]</a> </p><p>These findings highlight the pivotal role of selenium supplementation in deterring the progression of Keshan disease. The success observed in endemic regions emphasizes the importance of sustained efforts in selenium supplementation and proactive public health measures. Furthermore, prioritizing education and awareness programs among at-risk populations can facilitate early detection, fostering a proactive approach toward managing latent cases and averting the chronic progression of Keshan disease.</p></div><div id="article-156302.s14"><h2 id="_article-156302_s14_">Enhancing Healthcare Team Outcomes </h2><p>The complex nature of Keshan disease's etiology, multifaceted presentation, and the potential for long-term cardiac sequelae require healthcare professionals to have a comprehensive understanding of the disease. Healthcare professionals must strive to enhance outcomes associated with Keshan disease by prioritizing early recognition and implementing strategic interventions, especially selenium supplementation initiatives. Recognizing Keshan disease requires vigilance among healthcare providers to identify clinical signs of cardiomyopathy and heart failure, particularly in regions susceptible to selenium deficiency.</p><p>Physicians, nurses, pharmacists, and public health officials are critical in disseminating knowledge about Keshan disease's clinical presentation, stressing the importance of timely diagnosis and treatment. Educating healthcare teams about the significance of selenium supplementation, dosage, and impact on reducing Keshan disease prevalence is essential. This knowledge empowers healthcare providers to advocate for, administer, and monitor selenium supplementation effectively, ensuring its successful implementation within at-risk communities.</p><p>Given the prevalence of Keshan disease in rural and impoverished areas, outreach workers play a crucial role in community education. By fostering a proactive approach centered on recognition and advocating for selenium supplements, healthcare teams empower themselves to effectively combat Keshan disease and enhance patient outcomes in affected populations. These strategies help prevent the progression of Keshan disease and significantly improve the overall quality of life for those affected by this cardiac condition.</p></div><div id="article-156302.s15"><h2 id="_article-156302_s15_">Review Questions</h2><ul><li class="half_rhythm"><div>
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<b>Disclosure: </b>Daniel Fabian declares no relevant financial relationships with ineligible companies.</p></div></dd><dt></dt><dd><div><p class="no_top_margin">
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<b>Disclosure: </b>Intisar Ahmed declares no relevant financial relationships with ineligible companies.</p></div></dd></dl></div></div></div>
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