Keshan disease, also known as endemic cardiomyopathy, is a myocardial disease of unknown origin, first discovered in Keshan County, Heilongjiang Province in 1935, and therefore named after Keshan disease. In the past, the mortality rate of this disease was high, but after the founding of New China, the disease was actively prevented and treated, so that the incidence and mortality rate of this disease have been significantly reduced. In 1993, the National Conference on Key Surveillance of Keshan Disease pointed out that there were no new cases of acute, subacute and slow-onset acute attacks, 109 new cases of potential type were found, with an incidence rate of 4.2‰, and 6 new cases of slow-onset type were found, with an incidence rate of 0.24‰.
1.Epidemic area
In addition to our country, the disease has also been reported in Korea and Japan. China mainly occurs in the northeast to southwest a transition zone, namely, Heilongjiang, Jilin, Liaoning, Inner Mongolia, Hebei, Henan, Shandong, Shanxi, Shaanxi, Gansu, Ningxia, Sichuan, Yunnan, Tibet and other provinces and autonomous regions, the disease area is mainly in the rural areas of the remote hills, plateaus and grassland areas. Urban areas are less likely to develop.
2.Season of onset
The disease has obvious years and seasons of occurrence, with the onset of acute type patients in the cold winter in the northeast, and the hot summer season in the southwest.
3.Population distribution
The disease mainly occurs in young and middle-aged women and children in rural areas. In the northeast and northwest regions, there are significantly more young and middle-aged women than men. In Sichuan and Yunnan, it is more common in children aged 2 to 6 years. There are also cases where several people in a family are affected one after another. According to the survey in the epidemic area, the number of cases in the agricultural population is high, while those in the urban population are rare.
Symptoms
The main symptoms are acute and chronic cardiac insufficiency, heart enlargement, arrhythmia, and embolism of brain, lung, kidney and other organs.
1.Acute type
Healthy people can have sudden onset, or acute onset based on the underlying type or slow type. In the north, the acute type mostly occurs in winter, often due to cold, overwork, infection, binge drinking, overeating or childbirth and other triggers. The onset of the disease is rapid. In severe cases, cardiogenic shock, acute pulmonary edema and severe arrhythmias may be observed. Initially, dizziness, discomfort in the heart fossa, recurrent nausea and vomiting, yellow water, followed by irritability and restlessness are common. In severe cases, death may occur within hours or days. Physical examination shows that the patient is pale, the extremities are cold, the pulse is weak, the body temperature does not rise, the blood pressure is lowered, and the breathing is shallow and rapid. The heart is generally mildly enlarged and the heart sounds are weak, especially the first heart sound is weak, and there may be diastolic gallop rhythm and mild systolic blowing murmur. Arrhythmias are common, mainly ventricular premature beats, paroxysmal tachycardia and atrioventricular block. In addition, hepatomegaly and lower limb edema are also common.
2.Sub-acute type
The onset of the disease is not as acute as that of the acute type. Most of the patients are young children, and 85% of them are between 2 and 5 years old. The onset is mostly in spring and summer. Cardiogenic shock or congestive heart failure may also occur. The initial presentation is depression, cough, shortness of breath, loss of appetite, pallor, and generalized edema. Heart enlargement, gallop rhythm and hepatomegaly may also be present. Embolism of brain, lung and kidney is not uncommon.
3.slow type
The onset of the disease is slow, mostly unconsciously, and can be transformed from acute, subacute or latent type. The clinical manifestation is mainly chronic congestive heart failure, complaining of palpitations, shortness of breath, which is aggravated after exertion, and there may be urinary insufficiency, edema and ascites. Physical examination shows that the heart is significantly enlarged on both sides, with low heart sounds, mild to moderate systolic murmur and diastolic gallop rhythm can be heard, and signs of right heart failure such as jugular vein forgiveness, hepatomegaly and swelling of the lower extremities may be present in advanced stages. In severe cases, there may be pleural or abdominal effusion and cardiogenic cirrhosis. Arrhythmias such as premature ventricular contractions, tachycardia, conduction block, atrial fibrillation, etc. are common.
4.Potential type
It can occur in healthy people, or it can be the stage of improvement of other types. The former is often asymptomatic and can work or work as usual, but is detected in the survey, which is a stable latent type. The former is often asymptomatic and can work as usual. The ECG may have ST-T changes, prolonged QT interval and premature beats. The underlying heart is damaged, but the heart function is well compensated. The heart is not enlarged or mildly enlarged.
Etiology and pathogenesis
It has not been elucidated so far. According to a large number of studies conducted in various places, it may be related to soil and water, nutrition, infection and other factors.
1, soil and nutrition factors
According to the investigation of the disease has obvious regional, the disease area of the soil, water quality and food lack of certain trace elements such as selenium, molybdenum, magnesium or related nutrients needed by the human body, thus interfering with myocardial metabolism, causing myocardial or damage and disease.
The Chinese Academy of Sciences Keshan disease control group conducted the determination of selenium in the environment inside and outside the disease area and non-disease area, and found that the selenium content in water and food in the disease area was significantly lower, and the blood and hair selenium content of the population in the disease area was also low. And the investigation, from the disease area with low selenium content in water and soil to the adjacent area with higher selenium content in water and soil, found that the selenium content in their food increased and the disease decreased.
Over the years, it has been found that selenium deficiency can cause cardiomyopathy in some animals, and cause a decrease in cellular immunity and body immune function, which is manifested as a decrease in antibody production, a decrease in response to antigens, and a decrease in phagocytosis. The appropriate amount of selenium has a significant protective effect and antioxidant capacity against myocardial damage caused by selenium deficiency. It can also improve the body’s ability to resist infection. Selenium is also a component of glutathione peroxidase (GSH-px), the main role of the enzyme is to reduce lipid peroxides, scavenging oxygen radicals and thus protect the integrity of the cell membrane, low selenium can reduce the activity of GSH-px, resulting in myocardial membrane system damage. Recent studies have also found that sodium nitrite can significantly decrease myocardial glutathione peroxidase activity in low selenium organisms, and supplementation with selenium or vitamin E can protect this enzyme activity, suggesting that in addition to low selenium excess nitrite and vitamin E deficiency may be involved in the pathogenesis of Keshan disease. Electron microscopy and cytochemical examination of myocardial specimens from selenium-deficient experimental animals (cytochrome oxidase, acid phosphatase and Ca2+ATPase) showed varying degrees of myocardial membrane damage; impaired myocardial oxidative phosphorylation, low oxygen utilization and reduced ATP synthesis. The intracellular ATP dependence in the organelles is abnormally regulated by calcium, leading to a series of alterations in organelles and contractile components.
In recent years, a study reported that low magnesium (red blood cells and plasma magnesium content significantly reduced), may also be one of the causes of the disease, and put forward magnesium treatment of the disease and its arrhythmia of the necessity.
2, infection
Some people believe that the disease is caused by infection, especially myocardiophilic virus infection, such as coxsackievirus, echovirus, etc. caused by myocarditis or infection allergic myocarditis or mycotoxin caused by toxic myocarditis. The role of infection in the etiology of Creutzfeldt-Jakob disease has yet to be further investigated. It is also believed that viral infection and soil and nutritional factors in the disease area have a synergistic effect and cause the disease.
In conclusion, the etiology of the disease is not completely clear, probably on the basis of low selenium, a variety of combined factors involved in the interaction of the disease.
Pathological changes
The lesions are mainly in the myocardium, which shows degeneration, necrosis and scar formation. The heart is dilated to varying degrees under visual observation, in some cases up to 2-3 times normal, and in severe cases the heart is spherical. Most left ventricles are more dilated than right ventricles. Embolism is more common because of the presence of mural thrombus in the heart chambers in about 1/4 of the cases. Cardiac sections reveal interspersed areas of earthen necrosis and gray-white fibrous scars of varying sizes, especially in the septum, left ventricular wall, left papillary muscle, and the inner layer of the myocardium. Microscopically, myocardial degeneration, myofibrillar enlargement, and myocardial fiber necrosis were seen. Electron microscopy showed swollen mitochondria, degeneration, cristae fracture, or major loss. Myogenic fibers were commonly broken, destroyed and dissolved. The nucleus was deformed, the nuclear membrane was ruptured, the sarcoplasmic reticulum was dilated, and the myocardial intercalated discs were coiled. In addition to necrosis in the myocardium, other transverse muscles also have milder similar lesions.
Diagnosis
The diagnosis is not difficult according to the epidemiological characteristics of Creutzfeldt-Jakob disease: i.e., endemic areas, epidemic seasons, population incidence, combined with the clinical presence of acute and chronic heart failure, heart enlargement, arrhythmias, etc. In areas with large bone disease and endemic goiter disorders in the northeast and northwest, if the patient also has similar manifestations of dilated cardiomyopathy, the heart condition should be considered as possible slow-onset Creutzfeldt-Jakob disease.
Acute Creutzfeldt-Jakob disease needs to be differentiated from shock pneumonia, acute gastroenteritis, acute myocarditis, and acute myocardial infarction. Chronic Keshan disease should be distinguished from primary cardiomyopathy, rheumatic heart disease, pericarditis, etc.
1.Blood test
The total white blood cell count and neutrophils may be increased in acute and subacute patients, and the blood sedimentation may be accelerated. Serum glutamic oxalacetic transaminase (SGOT), creatine phosphokinase (CPK) and its isoenzymes, lactate dehydrogenase (LDH) and its isoenzymes can be increased to different degrees in acute and severe cases. Most of them rise in a few hours after the onset of the disease, reaching a peak in 1 to 3 days, and gradually return to normal after 1 to 2 weeks. In recent years, heavy chain monoclonal antibodies against human myocardial myosin have been successfully prepared, which can also help in the diagnosis of early myocardial necrosis. The slow type and potential type can be seen as albumin bias, globulin increase, serum protein electrophoresis a1 and a2 globulin increase.
2.Electrocardiographic examination
The disease can have a variety of electrocardiographic changes, with cardiac hypertrophy, myocardial damage and arrhythmias being the most common.
(1) dirty heart damage: ST segment rise or depression can be seen, which is related to epicardial or subendocardial myocardial damage, mostly seen in acute type. In a few cases, QS or Qr waves similar to myocardial infarction can be seen in the limb or precordial leads, which is due to myocardial necrosis or myocardial fibrosis. In addition, T-wave hypoplasia, biphasic or inversion, prolonged QT interval, and low voltage are also common.
(2) Arrhythmias: common ones include premature ventricular beats, tachycardia, atrial fibrillation, etc. Conduction disorders such as right bundle branch conduction block, left bundle branch conduction block or atrioventricular block can be seen.
3.X-ray examination
The main manifestation is enlarged heart with myogenic dilatation and weakened pulsation. Among the various types, the slow type of heart enlargement is the most significant, which can be spherical and generally enlarged, often accompanied by pulmonary stasis. The underlying type of heart may be normal in size or mildly enlarged. X-rays in rural areas are an effective means of detecting Keshan disease.
4.Echocardiography
In chronic and subacute forms of Keshan disease, enlarged left atrial, left ventricular, and right ventricular chambers, widened left and right ventricular outflow tracts, thinning of most of the ventricular walls, and weakened heart beats are seen. Thrombus formation can be seen in the ventricular cavity. In a few cases, the septum is thicker than the posterior wall of the left ventricle. The echocardiographic changes of this disease are very similar to those of dilated cardiomyopathy.
5. Systolic time interval requirement
This measurement shows that the ratio of PEP/LVET (the ratio of pre-ejection time to left ventricular ejection time) is higher than normal (normal value 0.345±0.036), reflecting the reduced contractility of the myocardium in this disease.
6, endomyocardial myocardial biopsy
This is a biopsy method combined with cardiac catheterization, in which the obtained endomyocardial myocardial tissue is examined in pathological sections to help diagnose the disease.
Treatment
This disease should be treated with a combination of treatments. Resuscitation of cardiogenic shock, control of heart failure and correction of arrhythmias, etc.
1, acute type of Keshan disease: as far as possible to achieve “three early”, that is, early detection, early diagnosis, early treatment.
(1) high-dose vitamin C intravenous injection: the first dose can be 5-10g, the total amount of 24 hours up to 15-30g. generally can be applied for about a week. Improve myocardial metabolism drugs such as coenzyme A, coenzyme Q10, adenosine triphosphate can be used.
(2) Hibernation therapy: Applicable to frequent vomiting and irritability. After the drug is administered, the myocardial oxygen consumption is reduced due to the reduced metabolic rate of the body, which is conducive to the recovery of cardiac function. Adults use chlorpromazine 50mg intramuscularly (pediatric dosage 1~2mg/kg), or use chlorpromazine 25mg, promethazine 25mg, pethidine 50mg intramuscularly or intravenously. Frequent vomiting can also be treated with metoclopramide and correction of acid-base balance and electrolyte disturbance. Diazepam can also be used. Pay attention to adequate oxygen supply.
(3) Application of vasoactive drugs; for hypotensive or shock patients, if the blood pressure does not rise after the application of vitamin C and blood volume supplementation, vasoactive drugs such as dopamine, alamine and norepinephrine can be applied. If hypotension is accompanied by left heart failure, in addition to cardiac drugs, dobutamine or dobutamine can also be used in combination with sodium nitroprusside, and adjust the drug concentration and drip rate according to blood pressure.
(4) cardiac drugs: acute, subacute type with heart failure, it is appropriate to use rapid digitalis preparations such as mauvein C 0.4mg or poisonous mauvein K 0.25mg diluted intravenous injection. If the above treatment is not effective, dobutamine, aminopyralidone and metanephrine can be used. In addition, the treatment of acute and chronic heart failure with vasodilators is more effective. In case of pulmonary edema, rapid diuretics such as intravenous tachypnea or butanuric acid can also be used.
(5) Anti-arrhythmic: frequent ventricular premature beats, ventricular tachycardia can be intravenous or drip lidocaine and magnesium sulfate, to be basically controlled, the following oral drugs can be used to maintain, such as mexiletine, propafenone, amiodarone, propyzamide, quinidine, beta-blockers, etc. Supraventricular tachycardia or rapid atrial fibrillation can be maintained with intravenous capsaicin. For high or III degree AV block with slow ventricular rate, adrenocorticotropic hormone, atropine, isoprenaline and other treatments can be used, and artificial cardiac pacing treatment can be placed if necessary.
2. Slow-onset Keshan disease
Mainly control heart failure and arrhythmia, and prevent infection, overwork, cold and other triggers, so as not to increase the burden on the heart. Cardiac-strengthening drugs are generally used to take digoxin orally, 0.125-0.25mg/d for adults, according to the principle of individualization, and adjust the amount as needed. Diuretics are suitable for those who have edema and can be given intermittently or daily orally with dihydrochlorothiazide, ambrisentan and furosemide. Water and electrolyte balance should be paid attention to and corrected at any time. Vasodilators can be used for those who have poor results with the above treatments, especially for intractable heart failure. Isosorbide nitrate, prazosin, hydrazin, phentolamine, captopril, sodium nitroprusside, etc. can be used. In addition, non-cordia cardiac agents such as dobutamine, dopamine, and amrinone can be used. The treatment of arrhythmia is the same as that of acute Creutzfeldt-Jakob disease.
3.Sub-acute Creutzfeldt-Jakob disease
The treatment principle is the same as that of the slow type, but those with cardiogenic shock should be treated as the acute type.
4.Potential Creutzfeldt-Jakob disease
Prevent infection, overwork, pay attention to nutrition, and follow up regularly.
Prevention
1.Comprehensive preventive measures
Pay attention to environmental hygiene and personal hygiene. Protect water sources and improve water quality. Improve nutritional conditions, prevent partial diet, especially for pregnant women, maternity and children should strengthen the protein supplement, various vitamins and essential trace elements, including magnesium, iodine, etc., and prevent and control large bone disease, endemic thyroid disease.
2.Promote preventive medicine in endemic areas
The use of sodium selenate as a preventive medicine, after years of promotion, proved to significantly reduce the incidence. It is usually taken orally once every 10 days, 1mg for 1-5 years old, 2mg for 6-10 years old, 3mg for 11-15 years old and 4mg for 16 years old and above.
In addition, the use of selenium-containing salt is recommended in endemic areas. Rural areas are planted using seeds soaked in a selenium-containing solution. Fertilizers containing selenium are applied to the roots of plants to increase the amount of selenium in crops.