Calcific valvular disease in the elderly

Introduction to calcified valvular disease in the elderly In 1904, Monckebery first discovered that people undergo degenerative changes during natural aging, leading to calcified aortic stenosis (CAS). In 1910, Dewitsky first described mitral annular calcification (MAC) and considered this calcification to be caused by degenerative changes. After that, pathologists and clinicians systematically observed changes in heart valves with age, confirming calcific valvular heart disease. It is an age-related aging disease caused by aging of the valve, degeneration and calcium deposition. It is also called senile degenerative valvular disease or senile cardiac calcification syndrome. basic knowledge The proportion of sickness: 0.4% -1% Susceptible people: the elderly Mode of infection: non-infectious Complications: cerebral embolism Infective endocarditis Heart failure

The cause of calcified valvular disease in the elderly

(1) Causes of the disease

Fulkerson and Nair believe that senile calcific valvular disease is not associated with systemic metabolic disorders, especially calcium and phosphorus metabolism disorders, and is not associated with coronary heart disease, rheumatoid or other cardiac inflammatory lesions. The following factors:

1 Decalcification of bone, ectopic deposition in the valve or annulus, Sugihara et al. using a human-computer simulation of the system to determine the aortic and mitral calcification detected by ultrasound, to determine the mineral metabolism of the elderly vertebrae The effects of aortic valve and mitral annulus calcification revealed that the calcium salts deposited on the mitral annulus were mainly derived from decalcification of the vertebrae.

2 abnormal carbohydrate metabolism, Bloor study found that senile calcific valvular disease in the incidence of diabetes and osteoarthritis patients, the change of carbohydrate metabolism can significantly reverse the degree of calcification of the valve.

3 The degenerative changes of the valve with age, Thompson study found that more than 90% of CAS patients over 65 years old are caused by degenerative changes of normal valves, and congenital two-valve deformity in the aortic stenosis of the elderly The proportion is very small, the incidence of calcific valvular disease is only 20% in the population <65 years old, and the incidence rate in the elderly over 65 years old is 3-4 times of the above age group, and the study found that valve calcification The degree of aggravation increases with age, and the incidence of multivalve involvement is also significantly increased. Therefore, most scholars believe that calcified valvular disease actually represents the change of age process and is closely related to age. Related degenerative lesions.

4 Gender factors, 50% to 60% of the elderly with calcific valvular disease are women, although there are studies that, regardless of aortic valve calcification or MAC, there is no gender difference, but most studies show that MAC is more common in women, The male to female ratio is between 1:2 and 1:4. One possible explanation is that the incidence of osteoporosis in older women is higher than that of men of the same age. This factor can affect the distribution of calcium between bone and soft tissue, while the elderly women have mitral annulus around Tissues are more sensitive to injury response, which is similar to rheumatic mitral valve disease in women with mitral stenosis.

5 The pressure on the valve is increased. Why the senile calcific valvular disease mainly involves the aortic valve and the mitral valve. The reason has not been known. It may be the most stressful with the two valves, especially the aortic valve, increased valve force and high speed. The blood flow impact easily causes damage to the annulus, causing tissue degeneration, fibrous tissue hyperplasia, neutral fat infiltration or collagen breakage to form a gap, which is conducive to calcium salt deposition, accelerates the process of calcification, and some scholars have found that the mitral valve is increased. Stress factors can accelerate degenerative changes, such as idiopathic hypertrophic aortic stenosis, aortic stenosis, hypertension, etc., which can increase left ventricular systolic pressure, and mitral valve pressure is correspondingly increased, due to The posterior lobe is located in the left ventricular outflow tract, which is perpendicular to the pressure force. Therefore, the lesion is more obvious here. It is clinically observed that the elderly with right heart valve calcification is often accompanied by right heart volume or pressure overload. It also shows that the calcification of the valve is closely related to the pressure on the valve.

(two) pathogenesis

1. Changes in heart valve age

There are three main forms of degenerative changes in the heart, namely calcification, sclerosis and mucinous changes. The most clinically significant factors in elderly degenerative heart disease are CAS and MAC.

From birth to adulthood, the endocardial and atrial muscles of the atrial side of the atrioventricular valve gradually thickened, the closed margin of the valve also slightly thickened, and small nodules began to appear, with the anterior mitral lobes most obvious. It may be related to the pressure exerted by the leaflets. As the age increases, the lipid content in the annulus and fibrous tissue gradually increases. Generally, at 30 years old, the lipid in the valve begins to appear, and the calcification under the microscope is 40 years old. It is more common. After entering the old age, the collagen fibers become dense, the staining is inconsistent, the parallel arrangement disappears, and the number of myocardial nuclei decreases. The 60-year-old calcium begins to deposit along the aortic ring, and the base of the aorta is thickened significantly, forming along the closed edge of the valve. Lambert's creature (an opaque tiny papilla) slows the closure of the leaflets. As you age, the left heart valve thickens, hardens, and restricts activity. The anterior mitral valve can also Yellow lipid streaks appear, and these stripes appear as Sudanese particles and foam cells appear. These changes are mainly concentrated in the fibrous body of the valve. Blood vessels with atherosclerotic lesions can develop blood. , Calcium deposition and bleeding.

2. Anatomical features

Degenerative heart valve calcification mainly involves the left heart valve, most commonly seen in the aortic valve and mitral annulus, usually without valve free edge involvement and interlobular adhesion, which can be distinguished from rheumatism and other inflammation-induced calcification Calcification of the right heart valve is rare. Since 1960, there have been only a few cases of tricuspid annulus calcification, mostly in the elderly with other valvular calcification. Pulmonary valve calcification is more rare in clinical practice. Only one case reported that 5 cases were detected by autopsy, and all of them were coexisting with other valve calcification, and their age was significantly higher than other calcification group (mean age 81.2 years). It is speculated that the pulmonary valve may be in the course of senile calcific valvular disease. Finally, it is also the least affected group of valves. The anatomical features of CAS and MAS are briefly described below.

CAS: The lesions are mainly concentrated in the intima of the aortic side of the valve. Calcium generally begins from the base of the aortic surface and deposits along the aortic ring. As the degree of lesions increases, it gradually expands to the free edge of the valve. Rice granules or needle-shaped calcifications, severe calcified plaques can fill the Valsalth sinus, but there is generally no adhesion, fusion and fixation between the valves. Therefore, even if the valve calcification is severe, the valve can still move, and only the closing speed is significantly slowed down. The transvalvular pressure difference does not change much. The calcification of the aortic valve is mostly affected by two or three leaflets, but the degree of lesion is different. Generally, the coronary valve and the right coronary valve are heavier than the left coronary valve. It extends to the fiber triangle, but when there is calcium deposition at the junction of the muscle and the membrane, it can oppress and involve the heart conduction system, causing different degrees of heart block or causing various arrhythmias.

MAC: The lesion mainly affects the following parts:

1 mitral annulus;

2 between the posterior ventricular surface of the mitral valve and the corresponding left ventricular endocardium, in severe cases, a "C" shaped calcified ring can be formed along the annulus;

3 Calcification extends to the left atrium, around the left ventricle and the mitral valve hole, forming a stiff stent, limiting the movement of the posterior valve, which can lead to mitral stenosis or regurgitation. In general, the valvular calcification is more than the leaflet, and each The leaflets can often be involved at the same time. The posterior lobe thickening and calcification are less severe than the anterior and aortic valves. The lesions mainly involve the fibrous tissue of the valve and the base of the mitral valve leaflets. The cusps and mitral closed margins are often not involved. 2) When calcification involves most of the tissue of the annulus, the tissue on the valve and the valve are thickened, hardened, the leaflets are distorted, and the posterior mitral valve is displaced to the atrial side. As the lesion is aggravated, the annulus Fixed, can not shrink with the contraction of the ventricle, and then cause left ventricular deformation, because generally does not cause adhesion and fusion between the rim, so the valve does not generally have severe stenosis, only when the calcification between the rim is prominently protruding into the heart cavity, Only the valve can be relatively narrowed. Therefore, the actual MAC is caused by the annulus stenosis, rather than the stenosis caused by the fusion of the leaflets like rheumatic valvular disease. In addition, the calcification and atherosclerosis of the fibrous tissue in the annulus Can cause the ring to be lost Normal sphincter, and this is the main reason for the occurrence of mitral regurgitation.

Because of the atrioventricular node, the anatomical relationship between the His bundle and the mitral valve scaffold is very close. Therefore, the degenerative change of the mitral annulus can directly affect the conduction system. The anatomical position of the sinus node is far from the mitral valve. However, the degenerative changes of the mitral annulus and the diffuse sclerosis in the conduction system coexist, and the MAC often extends to the left atrium, blocking the conduction block in the room or the room, and the incidence of MAC combined with sick sinus syndrome is high. It reflects the diffuse degeneration of the whole myocardial fibrous tissue. It is also found that the patients with MAC combined with conduction disorder are significantly higher than CAS. Nair is found in patients with calcific valvular disease who have a severe conduction disorder and need to install a pacemaker. MAC has a permanent pacemaker implant rate of 33%, while MAC-free CAS patients only 10%, so it can be considered that MAC is often a local manifestation of extensive myocardial calcification, the heart of elderly patients with atherosclerosis Transmission system dysfunction is mainly related to MAC.

3. Histological changes

Under light microscopy, the degeneration of the valve begins to change from the basal part. The lesion mainly involves the fibrous layer. With age, the valvular collagen fibers proliferate, dense, blurred edges, disordered and mucoid degeneration, and denatured from deep to shallow layers. Gradually expanded, it is a "petal"-shaped light-stained area with collagen and elastic fiber filaments attached to its edges and inside, with lipid accumulation, nucleus pyknosis, reduction, elastic fiber disintegration, between the valve sponge layer and the fibrous layer. The collagen elastic fiber separation does not destroy and disappear. The fine calcium salt particles are first deposited in the mucoid degeneration and lipid accumulation areas of the collagen fibers in the basal part of the valve, and expand with the expansion of mucoid degeneration and lipid accumulation, and the entire valve is involved in severe cases. Leaf fiber layer, forming multifocal, amorphous calcium spots, surrounded by fibrous tissue, thin-walled vascular hyperplasia and hemorrhage, inflammatory cell infiltration, occasional foreign body-like giant cells, aortic valve and anterior mitral valve Severe calcium plaque formation is mainly seen in the middle and distal part of the valve leaflet, and the semilunar valve nucleus can also be affected, while the posterior calcification of the mitral valve is dominated by the annulus.

Electron microscopy showed that the cell components in the valve were significantly reduced, the fibroblasts shrank in a rhomboid shape, the nucleus was condensed, and the degenerated mitochondria and vacuolar remnants were seen in the cytoplasm. Matrix vesicles were observed in the extracellular matrix, and the latter were calcified and aggregated. Some scholars have confirmed that the vesicles in the valve originate from the autophagic vacuoles of the cytoplasm of senescent fibroblasts, which are released into the matrix as the cells disintegrate. This vesicle with a lipid membrane structure is under light microscope. Lipids, in which acidic phospholipids have a strong binding force with calcium.

4. Valve calcification degree grading

According to the calcification of the valve under light microscopy, it can be divided into 5 grades, 0 grade: no calcium salt deposition under the microscope, with or without connective tissue degeneration of the valve fiber, grade I: focal fine dusty calcium deposit, grade II: Focal intensive coarse dusty calcium deposits or multifocal dusty calcium deposits, grade III: diffuse or multi-focal dense coarse dusty calcium deposits, partially fused into small pieces, grade IV: amorphous calcium Plaque formation, according to the degree of valve stiffness and calcification, it is divided into light and medium weight 3 degrees, mild: mild thickening of the valve, hardening, focal point-like calcium deposition, moderate: valve thickening, Hardening, the sinus sinus has diffuse speckled or needle-like calcium deposits, and the annulus is multifocal calcification. Severe: obvious thickening of the valve leaflets, stiff deformation, or adhesion between the petals, nodular calcium in the sinus Salt deposition, calcification of the annulus area merges into a "C" shape, or calcification involves the surrounding myocardial tissue.

5. Coexistence with other heart diseases

Most of the coexisting hypertensive heart disease, and the main aortic valve, may be due to the patient's long-term high blood pressure, the mechanical stress of the aortic valve is large, causing the collagen fiber to break into a gap and facilitate the deposition of calcium salts. Valve calcification, coronary heart disease detection rate is significantly higher than pulmonary heart disease, but at the same time the coexistence of two heart disease detection rate is low, high heart disease with aortic right coronary valve and no coronary calcification mostly, while coronary heart disease is left crown The valve, aortic annulus, aortic three-valve and aortic valve combined with mitral annulus damage are more common, and the more heart disease, the more serious the heart function damage.

Calcified valvular disease prevention in the elderly

A large number of studies have shown that senile calcific valvular disease is a major age-related degenerative disease. With the prolongation of human life, the disease has become an important cardiovascular disease that affects the daily life of the elderly and threatens their lives. Moreover, the disease itself has complicated clinical complications due to a wide range of heart disease, especially causing various arrhythmias and even sudden death. Therefore, it has attracted the attention of cardiovascular disease clinicians at home and abroad, but The exact cause and pathogenesis of the disease have not yet been fully clarified, so no breakthrough has been made in the study of preventive measures. With the increasing emphasis on the disease and further research on the mechanism, it is believed that in the near future, it will be possible to find a delay. Cardiac degeneration, effective measures to prevent and treat valvular calcification, significantly reduce the incidence and mortality.

Complications of calcific valvular disease in the elderly Complications, cerebral embolism, infective endocarditis, heart failure

The most common clinical complications include cerebral embolism, retinal artery embolization and coronary embolism, followed by infective endocarditis, atrial fibrillation and heart failure.

Symptoms of calcific valvular disease in the elderly Common symptoms Powerless heart rhythm arrhythmia Myocardial infarction Heart failure Heart enlargement systolic murmur fatigue angina dyspnea

Calcified valvular disease in the elderly progresses slowly, causing stenosis and/or regurgitation. It has little effect on hemodynamics, so it has no obvious symptoms for a long time, and even subclinical for life, generally not easy to cause The attention of patients and doctors, Otto et al. Clinically, 123 patients with aortic stenosis symptoms, echocardiography and other results showed that 71% of patients with aortic valve calcification, plus the elderly often combined with other parts Degenerative changes or associated with other cardiopulmonary disorders, such as hypertension, coronary atherosclerosis and lung, cerebrovascular disease, etc., can conceal the original symptoms and signs, once in the clinical stage, angina, syncope and approximate syncope and congestion Sexual heart failure, etc., often indicates that the lesions have been severe. Bloor believes that the symptom period can last from 1 to 18 years, while Braunwald found that the average survival time of patients in this period is only 3 years, and the sudden death rate is about 15%.

In the General Hospital of the People's Liberation Army, 95 patients with calcified valvular disease and valvular calcification in elderly patients with echocardiography were followed up for 6 years. The anterior murmur of the valvular calcification group, heart enlargement, sinus node lesion, conduction Obstruction and atrial fibrillation, heart failure, myocardial infarction, cerebrovascular disease, and the incidence of syncope were significantly increased).

There are many significant differences between senile calcific valvular disease and valvular heart disease in middle-aged people under 65 years of age. As shown in Table 5, the following is a brief description of the clinical features of common calcific valvular disease:

CAS: The most common symptoms of severe calcified aortic stenosis in the elderly are dyspnea and heart failure, while angina is a common symptom of aortic stenosis in young and middle-aged patients. This disease can also produce angina pectoris, its clinical features and coronary heart disease. The angina pectoris is similar, and the two are easily confused. Especially when the two coexist, it is difficult to identify. It is not uncommon to have syncope. It may be related to ventricular arrhythmia, conduction block, etc. If the mitral annulus calcification coexists, the incidence is higher. Exercise syncope may be associated with an increase in cardiac output during exercise and insufficient blood supply to the brain. Other symptoms include weakness, palpitations, long-term atrial fibrillation or slow arrhythmia in some patients, which may cause thrombosis, embolism or calcification in the atria. Block detachment can produce symptoms of systemic embolism. Many patients are admitted to hospital with cerebral infarction and neglect the basic valvular calcification of calcified emboli. Older patients are often accompanied by right colon vascular disease, and lower gastrointestinal bleeding occurs. When extensive calcification occurs in the ventricular septum, the atrioventricular node, the His bundle and its surrounding conduction tissue may be involved. disfunction.

Systolic murmurs in the aortic valve area are more common, but unlike general aortic stenosis, the best auscultation area is often at the apex of the heart, rather than at the bottom of the heart (Callavardin effect), multi-directional inferior orbital conduction, but not Neck conduction, loudness is moderate, moderate, can be music-like, due to valve calcification, elasticity disappears and fixed, often no early contraction (click) sound, Aronow and Roberts and other studies pointed out that elderly aortic stenosis The jet sound lacks specificity, and the intensity of the noise, the most loud part, and the conduction direction are meaningless to distinguish the severity of aortic stenosis. When atrial fibrillation occurs, the heart rhythm is absolutely irregular. Due to arteriosclerosis, vascular compliance is reduced. The systolic blood pressure is not significantly reduced or even increased, but the diastolic blood pressure is lower, so the pulse pressure difference is normal or widened. Unlike general aortic stenosis, the aortic regurgitation murmur is less (only 4%). However, once a diastolic murmur occurs, the degree of calcification of the aortic valve is heavier.

MAC: Most of the mitral calcification in the elderly has no obvious clinical symptoms. When the mitral annulus is involved, the mitral valve activity is limited, but it cannot be reduced in the systolic phase like the normal valve. When the severe annulus calcification involves the posterior valve. When the activity is affected, the mitral regurgitation may occur. When the condition is severe, the patient may have a feeling of extreme fatigue due to low cardiac output, and the activity endurance is limited. Some patients may also cause stenosis of the valve, but the degree is relatively Light, severe stenosis is extremely rare, because the calcification on the mitral annulus generally does not cause hemodynamic changes, but when the calcification is larger, apparently protruding into the heart chamber, the valve can be relatively narrowed. Causes hemodynamic deterioration, even congestive heart failure, and labor or nighttime paroxysmal dyspnea, Aronow study found that in the apex of the elderly, if there is diastolic murmur, the possibility of MAC is up to 90%, and the degree of lesions is mainly focused on those with only systolic murmur.

The signs of mitral regurgitation caused by calcific valvular disease are similar to those of general chronic mitral stenosis. When mitral regurgitation occurs, left atrial pressure can be increased, left atrial enlargement and atrial arrhythmia occur. 68.2% of patients with atrial fibrillation have left atrial enlargement, Aronow reported that the left atrial size of patients with atrial fibrillation is only 27.8%, and mitral regurgitation is easy to be complicated by bacterial endocarditis, even in the valve Abscesses occur around the ring. Thrombosis can occur when calcification invades the valve leaflets. The most fatal aortic emboli are mostly calcified tumor-like masses. Embolization can cause embolism of important organs such as the brain and retina. Nair reports MAC The incidence of cerebral embolism is about 11%.

Patients with this disease have no clinical symptoms in the early stage, and the late symptoms of disease development, such as angina pectoris, heart failure and syncope, are also non-specific. This degenerative change leads to corresponding stenosis or regurgitation, and the noise caused by it can be further examined. The clue, but it is worth noting that there is often no corresponding relationship between the murmur site and the pathological changes of the valve. The aortic valve lesion murmur is not necessarily heard in the aortic valve area, often in the mitral valve area, and the majority of patients with single valve disease can be more The part is murmur, which makes it difficult for clinical diagnosis. However, with the development of ultrasound technology, the diagnostic sensitivity of the disease has reached 70%. Combined with electrocardiogram and X-ray examination, the diagnosis rate can be further improved, and other cardiovascular diseases can be excluded. Calcification caused by disease.

Examination of calcified valvular disease in the elderly

When infected with endocarditis, white blood cells and neutrophils are elevated.

Electrocardiogram

Mild senile calcific valvular disease has normal ECG. Aortic valve disease may have left ventricular hypertrophy. In addition to left ventricular hypertrophy, mitral annulus calcification may have a prolonged or appearing P wave duration due to enlargement of left atrium. Incision, V1 lead ptf negative value increases, because this disease often involves the heart conduction system, it often has I ~ III degree atrioventricular block, left bundle branch block or left front half block figure, 20% ~ 30% Patients may have atrial fibrillation or other arrhythmias.

2. Echocardiography

Takamoto et al. compared ultrasound with autopsy or postoperative pathological examination and found that the sensitivity of ultrasound diagnosis is about 70%. It is the main method for clinical diagnosis of this disease. Two-dimensional echocardiography can directly observe the location, morphology and morphology of valvular calcification. The movement of the leaflets, but it is difficult to quantitatively judge the degree of stenosis. Ultrasound Doppler and color Doppler flow imaging have solved this problem well. Recent studies have found that Doppler is continuous. Wave measurement of the transvalvular pressure gradient and the area of the valve was well correlated with the results measured by the catheter (r = 0.75, P = 0.002), so that ultrasound can detect calcific valvular disease and determine the sensitivity and location of the lesion. The specificity is greatly improved, not only can monitor hemodynamic changes, evaluate valve function, provide assistance for clinical condition analysis, guidance treatment, prognosis judgment, but also provide objective basis for selecting surgical indications and surgical methods.

The characteristic changes of senile aortic valve calcification are obvious abnormal thickening of the valve, the activity is reduced, the valve is dysfunctional, and the echo is obviously enhanced by calcification, especially the annulus and the valve body. If the interventricular septum is involved The Department may also have corresponding echo enhancement. He Jun et al. used the valve valvular calcification to be greater than the aortic root echo as the diagnostic criteria, while the aortic wall as an ultrasound to evaluate the internal reference point of cardiac valve calcification may be an intuitive and practical method. Other signs of general aortic stenosis and dysfunction can be seen.

When the mitral annulus is calcified in the M-mode echocardiography, the anterior wall of the left ventricle can be found. The posterior wall of the left ventricle is anomalous, and the reflection is strong, parallel to the posterior wall of the left ventricle. The echogenic band, suggesting the calcification of the annulus, and showing that the amplitude of the anterior mitral regurgitation is reduced, the EF slope is slow, and the left ventricle is enlarged. The two-dimensional ultrasonography shows the posterior mitral lobes and left ventricle. There is a uniform crescent-shaped echo zone between the posterior wall. The long axis view or apical zone of the anterior region can show an abnormally strong echo zone in front of the junction of the atrioventricular. The direction of motion of this echo and the direction of the posterior wall of the left ventricle Consistent, and not connected to the left atrium and left ventricle, Doppler can show turbulence caused by systolic blood return during left ventricular systolic, and contrast agent can return to the left atrium from the left ventricle during systole.

3. X-ray and CT examination

Ordinary chest radiographs can show aortic calcification, high exposure techniques or tomography can increase the detection rate, such as patchy, linear or banded calcification shadows in the aorta and / or mitral annulus, For the diagnosis, in addition, there may be X-ray signs corresponding to aortic valve and mitral stenosis and regurgitation. In addition, Woodring et al reported that CT can improve detection of early senile calcific valvular disease that cannot be detected by some ultrasound. Rate, and is considered to be more sensitive and specific than ultrasound, but it is not a routine detection method.

Diagnosis and differential diagnosis of calcified valvular disease in the elderly

Diagnostic criteria

The disease lacks a unified diagnostic standard, and comprehensive literature reports propose the following diagnostic criteria:

1 age is over 60 years old;

2 echocardiography has typical valve calcification or annulus calcification, the lesion mainly involves the annulus, the base of the valve and the valve, and the junction of the cusp and the valve leaflet is rarely affected;

3X-ray examination includes image-enhanced fluoroscopy, high-pressure radiography or angiography with calcified shadows of the valve or annulus;

4 clinical or other examination evidence with valvular dysfunction;

5 other factors caused by valvular lesions, such as rheumatic, syphilis, papillary muscle dysfunction, chordae rupture and infective endocarditis, no congenital connective tissue abnormalities and abnormal calcium or phosphorus metabolism disease or medical history.

Differential diagnosis

The disease generally does not occur with valve adhesion and leaflet edge deformation. Combined with medical history, physical examination and biochemical examination can be distinguished from other valvular diseases caused by inflammation, etc. It is worth noting that some elderly patients with rheumatic heart valve disease Calcification occurs in the body of the valve leaflet. What kind of leaflet lesions belong to it? In addition to pathological examination, the existing methods are often difficult to identify, and it is possible for both to coexist.

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