bubble_chart Overview

Keshan disease is a disease of unknown cause primarily characterized by myocardial lesions, also known as endemic cardiomyopathy. It was first discovered in Keshan County, Heilongjiang Province in 1935, hence the name Keshan disease. In the past, the mortality rate of this disease was relatively high. After the founding of the People's Republic of China, active prevention and treatment measures were implemented, leading to a significant decrease in both the incidence and mortality rates of the disease. Important progress has also been made in the areas of prevention, treatment methods, and research on disease causes. The 1993 National Keshan Disease Key Monitoring Work Conference pointed out that there were no new cases of acute, subacute, or chronic acute episodes nationwide, with 109 new cases of the potential type discovered, an incidence rate of 4.2%, and 6 new cases of the chronic type discovered, an incidence rate of 0.24%.

bubble_chart Epidemiology

(1) Epidemic Areas: In addition to occurring in our country, this disease has also been reported in North Korea and Japan. In our country, it mainly occurs in a transitional zone from the northeast to the southwest, including provinces and autonomous regions such as Heilongjiang, Jilin, Liaoning, Inner Mongolia, Hebei, Henan, Shandong, Shanxi, Shaanxi, Gansu, Ningxia, Sichuan, Yunnan, and Tibet. The disease areas are primarily in remote mountainous, plateau, and grassland rural areas. Urban areas have fewer cases.

(2) Epidemic Season: This disease has distinct peak years and seasons. In the northeast region, acute cases mostly occur during the cold winter, while in the southwest region, the hot summer is the peak season for outbreaks.

(3) Population Distribution: This disease mainly affects rural middle-aged and young women and children. In the northeast and northwest regions, middle-aged and young women are significantly more affected than men. In Sichuan and Yunnan, children aged 2 to 6 are more commonly affected. It is also possible for multiple members of a family to fall ill successively. According to surveys in epidemic areas, the agricultural population has a higher incidence rate, while the urban population rarely gets affected.

bubble_chart Etiology

The cause has not yet been elucidated. Based on extensive research conducted in various regions, it may be related to factors such as soil and water, nutrition, infection, and others.

(1) Soil, Water, and Nutritional Factors: Investigations have shown that this disease has a distinct regional distribution. The soil, water quality, and grain in the affected areas are deficient in certain trace elements essential for human health, such as selenium, molybdenum, magnesium, or related nutrients, which interfere with myocardial metabolism, leading to myocardial injury and disease.

The Keshan Disease Prevention and Control Group of the Chinese Academy of Sciences conducted measurements of selenium in the internal and external environments of both affected and non-affected areas. They found that the selenium content in water and grain was significantly lower in the affected areas, and the blood and hair selenium levels of the population in these areas were also low. Further investigation revealed that as the selenium content in soil and water increased from low-selenium affected areas to adjacent areas with higher selenium content, the selenium content in grain also increased, and the incidence of the disease decreased.

Years of research have found that selenium deficiency can cause myocardial lesions in some animals and lead to a decline in cellular and body immune functions, manifested as reduced antibody production, decreased response to antigens, and diminished phagocytic ability. Adequate selenium has a significant protective effect against myocardial damage caused by selenium deficiency and enhances antioxidant capacity. It can also improve the body's ability to resist infections. Selenium is a component of glutathione peroxidase (GSH-px), an enzyme that primarily reduces lipid peroxides and clears oxygen free radicals, thereby protecting the integrity of cell membranes. Low selenium levels can decrease GSH-px activity, leading to injury in the myocardial membrane system. Recent studies have also found that sodium nitrite can significantly reduce the activity of myocardial glutathione peroxidase in selenium-deficient organisms, and supplementation with selenium or vitamin E can protect the enzyme's activity, suggesting that in addition to selenium deficiency, excessive nitrites and vitamin E deficiency may also be involved in the pathogenesis of Keshan disease. Electron microscopy and cytochemical examination (cytochrome oxidase, acid phosphatase, and Ca²⁺ATPase) of myocardial specimens from selenium-deficient experimental animals showed varying degrees of myocardial membrane injury; impaired myocardial oxidative phosphorylation, low oxygen utilization, and reduced ATP synthesis. Abnormal ATP-dependent calcium regulation and transport within organelles led to a series of changes in organelles and contractile components.

Recent research reports suggest that low magnesium (significantly reduced magnesium content in red blood cells and plasma) may also be one of the disease causes, and the necessity of magnesium treatment for this disease and its arrhythmias has been proposed.

(2) Infection: Some believe that the disease is caused by infection, particularly by myocardiotropic viruses such as Coxsackievirus, Echovirus, etc., leading to myocarditis, infectious allergic myocarditis, or toxic myocarditis caused by mycotoxins. The role of infection in the disease cause of Keshan disease remains to be further studied. Some also believe that viral infection has a synergistic effect with the soil, water, and nutritional factors in the affected areas, leading to the disease.

In summary, the disease cause of Keshan disease is not entirely clear, and it may involve various comprehensive factors interacting on the basis of selenium deficiency, leading to the disease.

bubble_chart Pathological Changes

The pathological changes are mainly in the myocardium, which shows degeneration, necrosis, and scar formation. Upon gross examination, the heart exhibits varying degrees of dilation, with some cases reaching 2-3 times the normal size, and in severe cases, the heart may appear spherical. The left ventricle is often more dilated than the right ventricle. Approximately one-fourth of cases have mural thrombi in the cardiac chambers, making embolism relatively common. On cross-section, the heart shows alternating areas of yellowish necrosis and grayish-white fibrous scars, particularly prominent in the interventricular septum, left ventricular wall, left papillary muscles, and the inner layers of the myocardium. Microscopically, myocardial degeneration is observed, with enlarged muscle fibers and myocardial fiber necrosis. Electron microscopy reveals mitochondrial swelling, degeneration, cristae rupture, or significant loss. Myofibrils are generally fractured, destroyed, and dissolved. The nuclei are deformed, with nuclear membrane rupture, sarcoplasmic reticulum dilation, and tortuous intercalated discs. In addition to myocardial necrosis, other striated muscles also show milder similar lesions.

bubble_chart Clinical Manifestations

Mainly includes acute and chronic cardiac insufficiency, cardiac enlargement, arrhythmias, and embolisms in organs such as the brain, lungs, and kidneys. According to the classification at the 1982 National Keshan Disease Prevention and Treatment Experience Exchange Conference, it is as follows.

(1) Acute Type: Healthy individuals may suddenly fall ill, or it may occur as an acute episode on the basis of a latent or chronic condition. In the north, the acute type often occurs in winter and can be triggered by cold, overwork, infection, binge eating or drinking, or childbirth. The onset is abrupt. Severe cases may present with cardiogenic shock, acute pulmonary edema, and severe arrhythmias. Initially, patients often feel dizzy, discomfort in the epigastric region, repeated nausea and vomiting, and yellow water vomiting, followed by dysphoria and restlessness. Severe cases may die within hours or days. Physical examination shows pale complexion, cold limbs, weak and thin pulse, low body temperature, decreased blood pressure, and shallow rapid breathing. The heart is generally grade I enlarged, with weak heart sounds, especially the first heart sound, and may have diastolic gallop rhythm and grade I systolic blowing murmur. Arrhythmias are common, mainly ventricular premature beats, paroxysmal tachycardia, and atrioventricular block. In acute heart failure, rales appear in the lungs, and hepatomegaly and lower limb edema are also common.

(2) Subacute Type: The onset is not as abrupt as the acute type. Patients are mostly young children, with 85% aged 2-5 years. It occurs more frequently in spring and summer. Cardiogenic shock or congestive heart failure may also occur. The initial stage of the disease presents with listlessness, cough, shortness of breath, poor appetite, dull complexion, and generalized edema. Cardiac enlargement, gallop rhythm, and hepatomegaly may also be present. Embolisms in the brain, lungs, kidneys, etc., are not uncommon.

(3) Chronic Type: The onset is slow, often occurring imperceptibly, or it may develop from the acute, subacute, or latent types. The clinical manifestations are mainly chronic congestive heart failure, with complaints of palpitations, shortness of breath, worsening with exertion, and possibly oliguria, edema, and ascites. Physical examination shows significant bilateral cardiac enlargement, low heart sounds, with possible grade II systolic murmur and diastolic gallop rhythm. In advanced stages, signs of right heart failure such as jugular vein distension, hepatomegaly, and lower limb edema may appear. Severe cases may have pleural and peritoneal effusions, cardiogenic cirrhosis, etc. Arrhythmias such as ventricular premature beats, tachycardia, conduction block, and atrial fibrillation are common.

(4) Latent Type: It can occur in healthy individuals or be a stage of improvement from other types. The former often has no symptoms and can perform normal labor or work, being discovered during screening, which is a stable latent type. Those transformed from other types may have symptoms such as palpitations, shortness of breath, dizziness, and lack of strength. The ECG may show ST-T changes, prolonged QT interval, and premature beats. Although the heart is damaged in the latent type, cardiac function is well compensated. The heart is not enlarged or only grade I enlarged.

bubble_chart Auxiliary Examination

(1) Blood Test In acute and subacute patients, the total white blood cell count and neutrophils may increase, and the erythrocyte sedimentation rate may accelerate. In severe acute cases, serum glutamic-oxaloacetic transaminase (SGOT), creatine phosphokinase (CPK) and its isoenzymes, lactate dehydrogenase (LDH) and its isoenzymes may show varying degrees of elevation. These levels typically rise within a few hours after the onset of the disease, peak in 1-3 days, and gradually return to normal within 1-2 weeks. In recent years, monoclonal antibodies against the heavy chain of human cardiac myosin have been successfully prepared, which also aids in the early diagnosis of myocardial necrosis. In chronic and latent types, albumin may be low, globulin may be elevated, and serum protein electrophoresis shows an increase in a₁ and a₂ globulins.

(2) Electrocardiogram (ECG) Examination This disease can present with various ECG changes, with cardiac hypertrophy, myocardial damage, and arrhythmias being the most common.

1. Myocardial Damage ST segment elevation or depression may be observed, which is related to damage to the myocardium beneath the epicardium or endocardium, commonly seen in acute cases. A few cases may show QS or Qr waves resembling myocardial infarction in limb leads or precordial leads, caused by myocardial necrosis or fibrosis. Additionally, T wave flattening, biphasic or inversion, prolonged QT interval, and low voltage are also common.

2. Arrhythmias Common arrhythmias include ventricular premature beats, tachycardia, and atrial fibrillation. Conduction disorders such as right bundle branch block, left bundle branch block, or atrioventricular block may also be observed.

(3) X-ray Examination The main manifestation is cardiac enlargement, presenting as myogenic dilation with weakened pulsations. Among the various types, chronic cardiac enlargement is the most significant, often presenting as a spherical general enlargement, frequently accompanied by pulmonary congestion. In latent types, the heart size may be normal or grade I enlargement. X-ray examination in rural areas is an effective method for detecting Keshan disease.

(4) Echocardiogram Examination In chronic and subacute Keshan disease, enlargement of the left atrium, left ventricle, and right ventricle, widening of the left and right ventricular outflow tracts, thinning of the ventricular walls, and weakened cardiac pulsations may be observed. Thrombosis may be seen within the ventricular cavities. A few cases may show a thicker interventricular septum compared to the posterior wall of the left ventricle. The echocardiographic changes in this disease are very similar to those of dilated cardiomyopathy.

(5) Systolic Time Interval Measurement This measurement shows a higher PEP/LVET (pre-ejection period to left ventricular ejection time) ratio than normal (normal value 0.345±0.036), reflecting the weakened myocardial contractility in this disease.

(6) Endocardial Myocardial Biopsy This is a biopsy method combined with cardiac catheterization, where the obtained endocardial myocardial tissue is examined by pathological sectioning, aiding in the diagnosis of this disease.

bubble_chart Diagnosis

According to the epidemiological characteristics of Keshan disease: namely, the epidemic areas, epidemic seasons, and population morbidity, combined with clinical diagnoses of acute and chronic heart failure, cardiac enlargement, arrhythmia, etc., the diagnosis is not difficult. In regions of the northeast and northwest with large joint disease and endemic goiter, if patients also exhibit manifestations similar to dilated cardiomyopathy, the cardiac condition should be considered as possibly chronic Keshan disease.

Acute Keshan disease needs to be differentiated from shock-type pneumonia, acute gastroenteritis, acute myocarditis, and acute myocardial infarction. Chronic Keshan disease needs to be differentiated from primary cardiomyopathy, rheumatic heart disease, pericarditis, etc.

Broadly speaking, Keshan disease is a type of primary cardiomyopathy, with clinical manifestations, electrocardiogram, X-ray, and echocardiogram findings similar to those of dilated cardiomyopathy. However, Keshan disease has significant regional epidemic characteristics, and the following points can be used for differential reference: ① Age: Keshan disease is more common in women of childbearing age and children, while dilated cardiomyopathy is more than 70% prevalent after the age of 30 according to domestic statistics; ② Gender: Keshan disease is more common in females, while dilated cardiomyopathy is more common in males; ③ Keshan disease mainly occurs in self-sufficient agricultural populations, with non-agricultural populations rarely affected. Dilated cardiomyopathy does not have this characteristic; ④ Course of disease: The course of chronic Keshan disease seems to be longer than that of dilated cardiomyopathy. Additionally, the incidence of the disease can be reduced by oral administration of sodium selenite to populations in epidemic areas over the years, indicating that selenium can prevent the disease. Finally, endomyocardial biopsy also aids in the differentiation between the two.

bubble_chart Treatment Measures

This disease should be treated with comprehensive therapy, including rescuing cardiogenic shock, controlling heart failure, and correcting arrhythmias, among others.

(1) Acute Keshan Disease: Strive to achieve the "three earlys," namely early detection, early diagnosis, and early treatment.

1. Large dose of Vitamin C intravenous injection: The initial dose can be 5-10g, with a total of 15-30g over 24 hours. Generally, it can be applied for about a week. Drugs that improve myocardial metabolism such as Coenzyme A, Coenzyme Q₁₀, and Adenosine Triphosphate can also be selected.

2. Hibernation Therapy: Suitable for those with frequent vomiting and dysphoria. After medication, due to the reduced metabolic rate of the body, myocardial oxygen consumption decreases, which is beneficial for the recovery of heart function. Adults can be given Chlorpromazine 50mg intramuscularly (children's dosage 1-2mg/kg), or Chlorpromazine 25mg, Promethazine 25mg, and Pethidine 50mg intramuscularly or intravenously. For frequent vomiting, Metoclopramide can also be used, and acid-base balance and electrolyte disorders should be corrected. Diazepam can also be applied. Ensure adequate oxygen supply.

3. Application of Vasoactive Drugs: For patients with hypotension or shock, if blood pressure does not rise after the application of Vitamin C and blood volume replenishment, vasoactive drugs such as Dopamine, Aramine, and Norepinephrine can be used. If hypotension is accompanied by left heart failure, in addition to cardiac drugs, Dopamine or Dobutamine can be combined with Nitroprusside, and the drug concentration and infusion rate should be adjusted according to blood pressure.

4. Cardiac Drugs: For acute and subacute types with heart failure, fast-acting digitalis preparations such as Lanatoside C 0.4mg or Strophanthin K 0.25mg diluted for intravenous injection are preferred. For those with poor response to the above treatments, Dobutamine, Amrinone, and Milrinone can also be selected. In addition, vasodilators are effective in treating acute and chronic heart failure. For pulmonary edema, fast-acting diuretics such as Furosemide or Bumetanide can be injected intravenously.

5. Antiarrhythmic: For frequent ventricular premature beats and ventricular tachycardia, Lidocaine and Magnesium Sulfate can be injected or infused intravenously. After basic control, the following oral medications can be selected for maintenance, such as Mexiletine, Propafenone, Amiodarone, Disopyramide, Quinidine, β-blockers, etc. For supraventricular tachycardia or rapid atrial fibrillation, Lanatoside C can be injected intravenously. For high-grade or III-degree atrioventricular block with slow ventricular rate, corticosteroids, Atropine, Isoproterenol, etc., can be selected for treatment, and artificial cardiac pacing may be necessary.

(2) Chronic Keshan Disease: Mainly control heart failure and arrhythmias, and prevent triggers such as infection, overwork, and cold to avoid increasing the heart's burden. Cardiac drugs generally choose Digoxin orally, 0.125-0.25mg/d for adults, adjusted according to individual needs. Diuretics are suitable for those with edema and can be taken intermittently or daily, such as Hydrochlorothiazide, Spironolactone, and Furosemide. Water and electrolyte balance should be noted and corrected at any time. Vasodilators can be used for those with poor response to the above treatments, especially for refractory heart failure. Isosorbide Dinitrate, Prazosin, Hydralazine, Phentolamine, Captopril, Nitroprusside, etc., can be selected. In addition, non-digitalis cardiac drugs such as Dopamine, Dobutamine, Amrinone, etc., can also be selected. The treatment of arrhythmias is the same as for acute Keshan disease.

(3) Subacute Keshan Disease: The treatment principle is the same as for the chronic type, and those with cardiogenic shock should be treated as for the acute type.

(4) Latent Keshan Disease: Prevent infection and overwork, pay attention to nutrition, and follow up regularly.

bubble_chart Prevention

(1) Comprehensive Preventive Measures: Pay attention to environmental and personal hygiene. Protect water sources and improve water quality. Enhance nutritional conditions, prevent dietary imbalances, especially for pregnant women, postpartum women, and children, by strengthening the supplementation of proteins, various vitamins, and essential trace elements including magnesium and iodine, and prevent and treat large joint disease and endemic goiter.

(2) Promotion of Preventive Medication in Endemic Areas: Sodium selenate is used as a preventive medication, and years of promotion have proven that it can significantly reduce the incidence rate. It is usually taken orally once every 10 days, with 1mg for ages 1-5, 2mg for ages 6-10, 3mg for ages 11-15, and 4mg for those aged 16 and above. The medication can be paused for three months during non-epidemic seasons.

In addition, the use of selenium-enriched salt is recommended in endemic areas. In rural areas, seeds soaked in selenium solution are used for planting. Selenium-containing fertilizers are applied to the roots of plants to increase the selenium content in crops.