OVERVIEW
Amyloidosis cardiomyopathy is a disorder of myocardial dysfunction in which amyloid proteins that stain evenly by hematoxylin-eosin are deposited in myocardial tissue. It is generally classified as primary or secondary: secondary amyloidosis occurs in tuberculosis, rheumatoid arthritis, ulcerative colitis, chronic osteomyelitis, chronic suppurative and wasting diseases, or in multiple myeloma. In the absence of any of these causes, the amyloidosis is primary and most often genetically related.
Causes of amyloidosis
Amyloidosis refers to the accumulation of a large amount of fibrous material with glycoprotein properties in tissues, and its main protein components are immune light chain protein (AC), non-immune amyloid (AA), calcitonin-like protein (AEI), and plasma preproteins (SA) of senile amyloidosis and other 4 kinds of proteins.
1. AC amyloidosis
It is the most common amyloidosis in clinical practice, mostly seen in primary and systemic amyloidosis, which is caused by defective degradation or synthesis of immunoglobulin. This amyloid is secreted by abnormally cloned β-cells; it mainly affects the heart, gastrointestinal tract, muscles and skin. In addition, the liver, spleen, kidneys and thyroid gland are also involved.
2.AA causes amyloidosis
Clinically known as secondary amyloidosis, often caused by tuberculosis, rheumatoid arthritis, ulcerative colitis, chronic suppurative diseases and other chronic infectious diseases, which is caused by inflammatory reaction of macrophages phagocytosis of serum AA protein, and make it decomposed. It mainly involves tissues such as kidney, liver, spleen and adrenal gland. In addition, it is also associated with the formation of atrial mucinous tumor.
3. AEI causing amyloidosis
Most commonly seen in medullary thyroid carcinoma.
4.SA-amyloidosis
Heart, pancreas, prostate and brain are the main affected areas, especially in the elderly, so it is often called senile systemic amyloidosis.
Symptoms
1. Restrictive cardiomyopathy
The most common. It is characterized by right heart insufficiency and peripheral edema without nocturnal paroxysmal dyspnea and sedentary breathing. Due to ventricular stiffness, the left ventricle may have a slowed early diastolic filling rate.
2. Congestive heart failure
More common. Commonly, there are palpitations, shortness of breath, and wet rales at the bottom of both lungs, which are caused by myocardial hypoconstriction, and with the aggravation of the disease, the symptoms of heart failure can be progressively aggravated.
3. Postural hypotension
This symptom may occur in patients, mostly caused by vascular and autonomic amyloidosis; in addition, it is also related to cardiac and adrenal amyloidosis.
4. Arrhythmia
The most common arrhythmias are bundle branch block, high atrioventricular block, and episodic sinus standstill, if the conduction system is involved. In addition, paroxysmal supraventricular tachycardia, atrial fibrillation, frequent ventricular pre-systole, and even ventricular tachycardia and ventricular fibrillation can be detected.
5. Angina pectoris
Amyloidosis involving the coronary arteries can cause angina pectoris. Most patients have pathologic Q waves in the chest leads or poor R wave increment in the transition zone.
6. Physical examination
Jugular venous filling, Kussmaul’s sign, and extra diastolic heart sounds can be found. In some cases, a heart murmur of mitral valve insufficiency may be present.
Examination
Histologic examination of the endocardial myocardium remains the current gold standard for the diagnosis of amyloid cardiomyopathy. The diagnosis is confirmed when polarized light microscopy reveals characteristic green birefringence of Congo red-stained tissue. In case of systemic amyloidosis, myocardial biopsy is not appropriate, histologic examination of the rectum, kidney and liver should be performed as appropriate.
1. Electrocardiogram
Low voltage, ST-T changes, sinus tachycardia, atrioventricular block is the most common arrhythmia, and bundle branch block, premature beats, atrial fibrillation, and occasionally Q-wave or myocardial infarction pattern can be seen.
2. Chest X-ray
When there is pericardial effusion, the heart shape is slightly enlarged.
3.Echocardiography
Main manifestations:
(1) Enlargement of all ventricular cavities except for normal or small left ventricular internal diameter;
(2) Thickening of the interventricular septum and ventricular wall, and symmetrical;
(3) The atrioventricular valve or papillary muscles may also be thickened or coarsened due to lesion involvement;
(4) About half have pericardial effusion;
(5) In about 92% of the patients, scattered small, round or irregular, strongly reflective spots are seen in the thickened myocardium, which is a characteristic feature of this disease.
In order to better recognize this kind of light spot, generally take the parasternal long-axis view and short-axis view, but not take the apical four-chamber view of the heart. It is now believed that these small, strongly reflective spots are caused by nodules formed by glial and amyloidosis tissues.
4. Cardiac catheterization
In amyloidosis cardiomyopathy, the ventricular diastolic pressure is elevated, and the pressure curve decreases in early diastole, then rises abruptly and remains plateaued in a square-root-number shape.
5. Magnetic resonance examination
It is extremely valuable in the diagnosis of amyloidosis in all tissues and organs of the body, with a marked increase in signal in the involved organs and a marked attenuation in the subcutaneous fat.
Diagnosis
Patients over 50 years of age, with clinical manifestations of primary systemic amyloidosis or other diseases predisposing to amyloidosis, should be highly suspected of amyloid cardiomyopathy if they have progressive and persistent heart failure, and the heart is not enlarged in X-ray chest radiographs, and echocardiograms show that the left ventricular cavity is small, and the posterior wall of the left ventricle and the ventricular septum are thickened. Confirmation of the diagnosis depends on endomyocardial biopsy, and rectal mucosal and renal biopsy can also help to clarify the diagnosis in patients who are not eligible for endomyocardial biopsy.
Treatment
1. Special treatment
At present, there is no specific treatment for this disease. In recent years, due to further understanding of the pathogenesis of amyloidosis, there are several ways to treat primary systemic amyloidosis and amyloidosis associated with multiple myeloma:
(1) B-cell disease causing amyloidosis can be treated with cytotoxic agents that reduce the serum concentration of amyloid-like precursors (light chains), such as oxfenarsine (nitrogen mustard phenylpropionate);
(2) Dissemination of amyloid precursor (light chain) can be blocked by plasma exchange or by extracorporeal perfusion of immunoabsorbent substances;
(3) The progression of amyloid precursors to protofibrils can be prevented by certain substances that interfere with lysosomal uptake or degradation of fibril precursor aggregates or polypeptide chains;
(4) Stimulation of tissue phagocytosis, which accelerates the degradation of amyloid-like substances. The aim of therapy for secondary amyloidosis is to treat the primary disease causing the amyloidosis and to eliminate or modify the amyloid-like fibrils by a combination of the four methods described above.
Hemodialysis may be effective in some amyloidosis but is not appropriate in patients with myocardial amyloidosis. Colchicine, which interferes with lysosomal uptake and degradation of fibrinolytic precursors, is effective in abdominal pain due to amyloidosis but not in cardiac amyloidosis.
In amyloidosis, the use of glucocorticoids is debated. Although glucocorticoids can temporarily relieve symptoms, animal experiments have shown that they have the effect of accelerating amyloid deposition.
2. Symptomatic treatment
Digitalis preparations are ineffective in congestive heart failure in amyloid cardiomyopathy and are prone to arrhythmia and sudden death. The use of diuretics should be noted to avoid dehydration and defecation, and postural hypotension can occur. For atrioventricular block, a buried pacemaker should be installed if the life is in danger.
3.Surgical treatment
Liver transplantation can prevent disease progression and may reverse amyloid deposition in some tissues; however, when the myocardium is severely infiltrated, combined liver and heart transplantation is the only potentially effective method.