Dilated cardiomyopathy

Dilated cardiomyopathy - a violation of myocardial function, leading to heart failure, which is dominated by ventricular dilation and systolic dysfunction.

Symptoms of dilated cardiomyopathy include dyspnea, fatigue, and peripheral edema. Diagnosis is established on the basis of clinical data, chest X-ray and echocardiography. Treatment of dilated cardiomyopathy is aimed at eliminating the cause, there may be a need for heart transplantation.

[1], [2], [3], [4],

Epidemiology of dilated cardiomyopathy

The incidence of dilated cardiomyopathy is 5-7.5 cases per 100 000 population per year. In men, it happens 2-3 times more often, especially at the age of 30-50 years). This disease also causes chronic heart failure in 30% of cases. Among all types of cardiomyopathies, DCMP is 60%.

[5], [6], [7], [8], [9], [10], [11], [12], [13]

Causes of dilated cardiomyopathy

Dilated cardiomyopathy (DCMP) has many known and probably many unrecognized causes. The most common cause is a diffuse lesion of coronary arteries (IHD) with widespread ischemic myopathy. More than 20 viruses can cause dilated cardiomyopathy. In temperate climates, the Coxsackie group B virus is most common. In Central and South America, the most common cause is Chagas disease caused by Trypanosoma cruzi. Dilated cardiomyopathy is increasingly seen among people with AIDS. Other causes include toxoplasmosis, thyrotoxicosis, and beriberi. Many toxic substances, especially alcohol, various organic solvents and certain chemotherapeutic drugs (for example, doxorubicin) cause heart damage.

In most cases, the etiology of this disease is unknown, but in the development of primary dilated cardiomyopathy, at present, much attention is paid to three points:

• family and genetic factors;
• transferred viral myocarditis;
• immunological disorders.

In genetic studies in the development of idiopathic dilated cardiomyopathy, a family predisposition was determined in a third of cases, in which autosomal dominant inheritance predominates (autosomal dominant DCMD). Along with autosomal dominant, autosomal recessive, X-linked and mitochondrial forms of dilated cardiomyopathy are also described.

Autosomal dominant forms are characterized by clinical variability and genetic heterogeneity. They are associated with six different loci: simple dilated cardiomyopathy - with loci lq32, 2p31, 9ql3, 10q21-q23; DCMC with conduction disorders - with loci lql-lql, 3p22-3p25, and it is not known which these cardiac loci are responsible for the synthesis of cardiac proteins.

Mitochondrial dilated cardiomyopathy is associated with anomalies of the mitochondrial structure and dysfunction of the process of oxidative phosphorylation. As a result of the mutation, the energy metabolism of cardiomyocytes is disturbed, which leads to the development of DCMP. Point mutations and multiple fission in mitochondrial DNA are described both in sporadic cases of DCMP and in family cases. Many mitochondrial myopathies are associated with neurologic disorders.

At present, the molecular basis of X-linked DCMP is being studied. The mutations of various parts of the gene responsible for the synthesis of the dystrophin protein (chromosome 21) are described. Dystrophy is a myocardial protein that is part of a multiprotein complex that connects the muscular cytoskeleton of a cardiomyocyte to the extracellular matrix, thereby securing cardiomyocytes in the extracellular matrix. Linking to actin, dystrophy performs a number of important functions:

• membrane-stabilizing;
• transfers the contractile energy of the cardiomyocyte to the extracellular environment;
• provides a membrane differentiation, i.e. Specificity of the cardiomyocyte membrane.

Mutations were found in which nucleotide replacement occurs, leading to an amino acid substitution. This can cause a violation of the polarity of the dystrophin molecule and alter other properties of this protein, reducing its membrane-stabilizing property. As a result, cardiomyocyte dysfunction occurs. Mutations of the dystrophin gene are described in DCMD associated with Duchenne muscular dystrophies, Becker, most often deletions are found in these cases.

Great importance is also attached to the role of enterovirus infection (in particular, to Coxsackie B, hepatitis C, herpes, cytomegalovirus-y) in the development of DCMP. Persistent viruses incorporate their RNA into the genetic apparatus of cardiomyocytes, damaging mitochondria and disrupting the energy metabolism of cells. There is evidence of the presence of cardiospecific autoantibodies, such as antimyosin, anti-actin, antimyolemma, anti-alpha-myosin and anti-beta-myosin heavy chains. An anti-adenosine diphosphate adenosine triphosphate, which is an antibody to the mitochondrial membrane of the cardiomyocyte, is also found to have an adverse effect on the functioning of membrane calcium channels, which in turn leads to a disturbance in myocardial metabolism. Some of the patients showed an increase in pro-inflammatory cytokines (IL-1, IL-6, TNF-a) in the blood. Probably, patients with initial autoimmune deficiency are more susceptible to the damaging effects of viruses and the development of dilated cardiomyopathy.

It is suggested that in some patients dilated cardiomyopathy begins with acute myocarditis (probably viral in the majority of cases), accompanied by a variable occult phase, during which widespread necrosis of cardiomyocytes develops (due to an autoimmune reaction to virus-modified myocytes), and then chronic fibrosis occurs. Regardless of the cause, the surviving myocardium expands, is thinned and compensatoryly hypertrophied, which often leads to functional mitral or tricuspid regurgitation and atrial dilatation.

In most patients, the disease affects both ventricles, some have only the left ventricle (LV), and much less often only the right ventricle (RV).

As the expansion of the heart chambers reaches a considerable size, especially during the acute phase of myocarditis, wall clots are often formed. Arrhythmias often complicate the course of acute myocarditis and late phase of chronic dilatation, it is also possible the development of atrioventricular blockade (AV blockade). Due to dilatation of the left atrium, atrial fibrillation often occurs.

Causes of cardiomyopathy

The form	Etiology
Dilated congestive cardiomyopathy (acute or chronic)	Chronic, widespread ischemia of the myocardium (lesion of coronary arteries). Infections (acute or chronic) caused by bacteria, spirochetes, rickettsia, viruses (including HIV), fungi, protozoa, helminths. Granulomatous diseases: sarcoidosis, granulomatous or giant-cellular myocarditis, Wegener's granulomatosis. Metabolic disorders: nutritional disorders (beriberi, selenium deficiency, carnitine deficiency, kwashiorkor), family illnesses of accumulation, uremia, hypokalemia, hypomagnesemia, hypophosphatemia, diabetes mellitus, thyrotoxicosis, hypothyroidism, pheochromocytoma, acromegaly, pathological obesity. Preparations and toxins: ethanol, cocaine, anthracyclines, cobalt, antipsychotic drugs (tricyclic and quadricyclic antidepressants, phenothiazines), catecholamines, cyclophosphamide, radiation. Tumors. Systemic diseases of connective tissue. Isolated family syndrome (dominant in Mendel). Hereditary neuromuscular and neurological diseases (Friedrich's ataxia). Pregnancy (postpartum period)
Hypertrophic cardiomyopathy	Autosomal dominant inheritance, pheochromocytoma, acromegaly, neurofibromatosis
Restrictive cardiomyopathy	Amyloidosis, systemic sclerosis, endocardial fibrosis, Fabry's disease, fibroelastosis, Gaucher's disease, hemochromatosis, Loeffler's hypereosinophilic syndrome, sarcoidosis, hypereosinophilia syndrome, tumors

About 75 etiological factors are described in the formation of secondary / specific DCMD.

[14], [15]

The main causes of secondary / specific dilated cardiomyopathy

• Electrolyte disturbances.
  • Hypokalemia.
  • Hypophosphatemia.
  • Uremia. 
• Endocrine disorders.
  • Illness of Itenko-Cushing.
  • Diabetes.
  • Acromegaly.
  • Hypothyroidism / hyperthyroidism.
  • Pheochromocytoma.
• Prolonged existing arterial hypertension.
• Cardiac ischemia.
• Infectious diseases.
  • Bacterial (brucellosis, diphtheria, typhoid fever, etc.).
  • Fungal.
  • Mycobacterial.
  • Parasitic (toxoplasmosis, Chagas disease, schistosomiasis).
  • Rickettsial.
  • Viral (Coxsackie A and B virus, HIV, adenovirus).
• Infiltrative disease.
  • Amyloidosis.
  • Hemochromatosis.
  • Sarcoidosis.
• Neuromuscular pathology.
  • Myopathy.
  • Friedreich's Ataxia.
  • Atrophic myotonia.
• Disturbance of nutrition.
  • Deficiency of selenium.
  • Deficiency of carnitine.
  • Deficiency of thiamine.
• Rheumatic diseases.
  • Giant cell arteritis.
  • Systemic scleroderma.
  • Systemic lupus erythematosus.
• Exposure to toxins.
  • Amphetamines.
  • Antiviral drugs.
  • Carbon monoxide.
  • Irradiation, chemotherapeutic drugs.
  • Chloroquine, phenothiazine.
  • Cobalt, lead, mercury.
  • Cocaine.
  • Ethanol. 
• Tachyarrhythmias.
• Congenital and acquired heart defects.

Pathogenesis of dilated cardiomyopathy

As a result of the influence of etiological factors on the heart, cardiomyocyte damage develops with a decrease in the number of functioning myofibrils.

This leads to progression of heart failure, manifested in a significant decrease in the contractility of the myocardium with the rapid development of dilated cardiac cavity. In the first stages, the activation of the sympathoadrenal system with the development of tachycardia is compensatory to maintain the shock volume and ejection fraction. As a result, compensatory hypertrophy of the myocardium is formed, there is a significant increase in myocardial oxygen demand with the appearance of signs of ischemia, the development of cardiofibrosis and the progression of heart failure. As a result of the pathological process, a critical decrease in the pumping function of the heart occurs, the end-diastolic pressure in the ventricles rises and myogenic dilatation of the heart cavities develops with relative insufficiency of the mitral and tricuspid valves. Increased activation of neurohormonal systems of the body leads to more damage to the myocardium, peripheral vasoconstriction, disorders of coagulating and anticoagulating blood systems with the development of intracardiac thrombi and systemic thromboembolic complications.

Symptoms of dilated cardiomyopathy

The disease often occurs in people of young and middle age. The onset is usually gradual, except in cases of acute myocarditis. Symptoms depend on which ventricle is affected. LV dysfunction causes shortness of breath during physical exertion, as well as fatigue due to increased diastolic LV pressure and low cardiac output. Insufficiency of the prostate leads to peripheral swelling and swelling of the veins of the neck. For isolated PI lesions, the development of atrial arrhythmias and sudden death due to malignant ventricular tachyarrhythmias are typical. Approximately 25% of all patients with dilated cardiomyopathy report untypical chest pain.

In the early stages, only certain symptoms of heart failure are identified, and chest radiography of the chest - cardiomegaly. As a result of progressive left ventricular failure, dyspnea, asthma attacks, characterized by rapid fatigue, muscle weakness. At auscultation of the heart, tachycardia is detected, and the third tone ("gallop rhythm") is heard, often (V tone, noise of relative mitral regurgitation.) In 40-50% of cases, the course of dilated cardiomyopathy is complicated by the appearance of ventricular arrhythmias, which is accompanied by syncopal conditions, and in 15-20% of cases develop at first a paroxysmal form of atrial fibrillation, passing into a constant, which sharply increases the risk of thromboembolic complications against the background of existing systolic dysfunction of the myocardium. Oic failure (swelling of the legs, gravity in the right hypochondrium, enlargement of the liver, abdomen in volume due to ascites) appear later. Thus, the clinical symptoms ranging from dilated cardiomyopathy malosimptomno flow to severe heart failure.

Classification of dilated cardiomyopathy

According to the existing WHO classification, the following forms are distinguished among DCMC: idiopathic, familial / genetic, viral and / or immune, alcohol / toxic, and "specific cardiomyopathies" in other heart diseases and systemic processes.

According to the classification of Maron et al. (2006) all cases of dilated cardiomyopathy are divided into two groups: primary (genetic, non-genetic, acquired), in which only the myocardium is affected, and secondary (with various systemic diseases).

The ESC working group (2008) proposed a new classification of cardiomyopathy, which, in fact, returns us to the definition of Goodwin and excludes the presence of such DCMs as ischemic, valvular, hypertensive.

Classification of dilated cardiomyopathy includes family / genetic and non-family / non-genetic forms.

[16], [17], [18], [19], [20]

Diagnosis of dilated cardiomyopathy

Diagnosis of dilated cardiomyopathy is based on anamnesis, physical examination and exclusion of other causes of ventricular insufficiency (eg, systemic arterial hypertension, primary valvular disorders). Thus, it is necessary to perform chest X-ray, ECG and echocardiography. In the presence of acute symptoms or chest pain, the definition of cardiospecific markers is necessary. An increase in troponin is typical of coronary artery disease, but it can occur with heart failure, especially with decreased kidney function. Carry out the identification of possible specific causes (see other sections of the Guide). In the absence of a specific cause, it is necessary to investigate the serum ferritin content and iron binding ability, to determine the concentration of thyroid-stimulating hormones and to perform serological tests for toxoplasm, Coxsackie and ECHO viruses in order to identify disposable causes.

With ECG, sinus tachycardia, low-voltage QRS complexes and nonspecific ST segment depression , inverted R wave can be detected . Sometimes abnormal Q-waves can be present in the thoracic leads, simulating the transferred myocardial infarction. Often, a blockage of the left leg of the bundle is revealed.

On chest radiographs, cardiomegaly is detected, usually with an increase in all the chambers of the heart. Pleural effusion, especially on the right, often accompanies an increase in pulmonary pressure and interstitial edema. The echocardiogram demonstrates the enlargement, hypokinesis of the heart chambers and excludes primary valvular disorders. Focal disturbances of cardiac wall movements, typical of myocardial infarction, are possible with DCMP, because the process can be focal. Echocardiography can also demonstrate the presence of a thrombus in the chambers. MRI is usually not performed, but it can be used for detailed mapping of the structure and functions of the myocardium. With cardiomyopathy, MRI can reveal the pathological structure of myocardial tissue.

Coronarography is indicated if the diagnosis is questionable after non-invasive examinations, especially in patients with chest pain or elderly, in whom IHD is likely. However, non-structural changes in the coronary arteries detected by angiography may not be the cause of DCM. During the catheterization, you can perform a biopsy of the walls of any ventricle, but usually it is not performed, since the effectiveness is often low, the pathological process can be focal, and the results probably will not affect the treatment.

Diagnosis and treatment of cardiomyopathies

Sign or method	Dilated congestive cardiomyopathy	Hypertrophic cardiomyopathy	Restrictive cardiomyopathy
Pathophysiological features	Systolic dysfunction	Diastolic dysfunction obstruction of ejection	Diastolic dysfunction
Clinical examination	Failure Pancreas and LV. Cardiomegaly. Functional regurgitation at the atrioventricular valves, S 3 and S	Angina pectoris, dyspnoea with exertion, syncope, sudden death, nocturnal ejection of mitral regurgitation, biphasic pulse on carotid arteries with rapid ascent and decrease	Dyspnea and weakness in exercise, LV deficiency, functional regurgitation on atrioventricular valves
ECG	Nonspecific changes in ST-T.	Ischemia and LV hypertrophy. Deep teeth in leads from the septic region	Hypertrophy of LV or low voltage
Echocardiography	Dilated hypokinetic ventricles of the thrombus in the cavities of the heart. Low FV	Hypertrophy of the ventricle mitral systolic movement forward asymmetric hypertrophy LV deformation	Increasing the wall thickness reduces the size of the cavity. Diastolic LV dysfunction
X-ray examination	Cardiomegaly. Pulmonary vein pulmonary embolism	No cardiomegaly	Absence or small cardiomegaly
Hemodynamic features	Normal or elevated KDD. Low PV. Diffusively enlarged hypokinetic ventricles regurgitation at the atrioventricular valves	High KDD, high EF large pressure gradient in the subvalvular area of mitral regurgitation. Normal or reduced CB	High CDR, deep and flat wave of LV diastolic pressure. Normal or reduced CB
Forecast	70% mortality over 5 years	4% mortality per year	70% mortality over 5 years
Treatment	Diuretics, ACE inhibitors, APA II, b-adrenoblockers, spironolactone or eplerenone, implantable cardioverter defibrillator, biventricular ECS, inotropic drugs, anticoagulants	Decrease in contractility by the appointment of b-adrenoblockers verapamil disopyramide septaly myotomy catheter ablation with alcohol. Atrioventricular ECS	Phlebotomy with hemochromatosis. Resection of the endocardium. Hydroxy-urea for hypereosinophilia

[21], [22], [23], [24]

Treatment of dilated cardiomyopathy

Eliminate primary causes (eg, toxoplasmosis, hemochromatosis, thyrotoxicosis, beriberi) should be corrected. Otherwise, the treatment is the same as with heart failure: ACE inhibitors, beta-blockers, aldosterone receptor blockers, ARA II, diuretics, digoxin and nitrates. Glucocorticoids, azathioprine and equine antitumocyte globulin are no longer used: although these drugs can reduce the acute phase of certain inflammatory cardiomyopathies (eg, acute viral myocarditis or myocarditis in sarcoidosis), they do not improve the long-term outcome. Antiviral drugs are ineffective.

Since intracavitary thrombi can form, prophylactic anticoagulant administration is used to prevent systemic or pulmonary embolism, although there are no controlled studies confirming the efficacy of this treatment. Severe arrhythmias are treated with antiarrhythmic drugs, although active treatment of heart failure reduces the risk of arrhythmia. When AV blockade passes into the chronic dilatation phase, a permanent pacemaker may be required, but the AV blockade that occurs in the phase of acute myocarditis is often resolved, so permanent pacemakers are usually not needed. If the patient has an extended QRS complex and severe clinical manifestations, one can consider the possibility of biventricular stimulation.

Prevention of dilated cardiomyopathy

Patients at risk of developing dilated cardiomyopathy (family history of this disease, the presence of relatives with the development of severe heart failure at a young age) should avoid professional sports and the choice of professions associated with overload.

When a dilated cardiomyopathy is detected in the patient, the main task is to prevent the progression of heart failure,

The main areas of assessment of risk factors for dilated cardiomyopathy, heart failure and indicators used:

• questioning (questionnaires);
• psychological testing (level of anxiety);
• assessment of the state of health in connection with the functional state and clinical manifestations, the forecast of complications (allocation to risk groups, identification of a group of "high risk");
• monitoring of risks affecting health (monitoring and control of exposure);
• assessment of the effectiveness of preventive intervention and treatment (ways of recovery, implementation of medical recommendations and prescriptions, motivation, training in recovery techniques and their comparative characteristics).

Forecast

Since the prognosis is pessimistic, patients with dilated cardiomyopathy often become candidates for heart transplantation. Selection criteria include the absence of systemic diseases associated with pathology, mental disorders and irreversibly high pulmonary vascular resistance. Since the hearts for transplantation are small, priority is given to younger patients (usually younger than 60 years).

[25], [26], [27], [28]

Background

The term "dilated cardiomyopathy" appeared relatively recently (1957). Nevertheless, one of the first detailed reports of the Russian scientist S.S. Abramova (1897) on an isolated myocardial disease with a subacute current in a previously healthy peasant 28 years old, lethal at 4 months from the onset of the first manifestations of congestive heart failure. S.S. Abramov stated first of all the sharp dilatation of all parts of the heart, while "... The left ventricle is stretched so tightly that the capacity of one alone exceeds the capacity of the three remaining cavities of the heart taken together. Its wall is somewhat refined, the fleshy crossbeams and papillary muscles, as a result of excessive stretching of the ventricles, seem thin. " In the opinion of Yu.I. Novikov and MA Stulovoy, it was SS. Abramov belongs to one of the first descriptions of DCMP. The definition of the concept of "cardiomyopathy", its classification and terminology have been repeatedly considered both in the domestic (Vinogradov AB et al., Mukharlyamov NM, Sumarokov AB, Moiseev BC, Storozhakov GI, Janashia P.Kh., etc.). , and in the foreign literature (Goodwin JF, Elliot P., Maron B. Et al.) and continue to be studied at the present time.

[29], [30], [31], [32], [33], [34], [35], [36], [37]