Restrictive cardiomyopathy: causes, symptoms, diagnosis, treatment

Restrictive cardiomyopathy is characterized by non-stretchable ventricular walls that resist diastolic filling. One or both ventricles are affected, most commonly the left. Symptoms of restrictive cardiomyopathy include fatigue and shortness of breath with exertion. Diagnosis is by echocardiography. Treatment of restrictive cardiomyopathy is often ineffective, and is best addressed at the cause. Surgery is sometimes effective.

Restrictive cardiomyopathy (RCM) is the least common form of cardiomyopathy. It is divided into non-obliterating (myocardial infiltration with a pathological substance) and obliterating (endocardial and subendocardial fibrosis). In addition, there is a diffuse and focal type (when changes affect only one ventricle or part of one ventricle).

ICD-10 code

142.5. Other restrictive cardiomyopathy.

Causes of restrictive cardiomyopathy

Restrictive cardiomyopathy belongs to the group of cardiomyopathy of mixed genesis, i.e. having features of both a hereditary and acquired disease.

Restrictive changes in the myocardium can be caused by various local and systemic conditions. It is customary to distinguish between primary (idiopathic) and secondary forms of restrictive cardiomyopathy.

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Causes of restrictive changes in the myocardium

Myocardial:

• Non-infiltrative.
  • Idiopathic RCM.
  • Family KMP.
  • Hypertrophic cardiomyopathy.
  • Scleroderma.
  • Elastoma (pseudoxantoma elasticum).
  • Diabetic cardiomyopathy.
• Infiltrative.
  • Amyloidosis.
  • Sarcoidosis.
  • Fatty infiltration.
  • Gaucher disease.
  • Fabry disease.
• Storage diseases.
  • Hemochromatosis.
  • Glycogenosis.

Endomyocardial:

• Endomyocardial fibrosis.
• Hypereosinophilic syndrome.
• Carcinoid.
• Metastatic lesion.
• Radiation exposure.
• Toxic effects of anthracycline.
• Medicines (mercury preparations, bisulfan, serotonin, methysergide, ergotamine).

Idiopathic restrictive cardiomyopathy is a “diagnosis of exclusion”, a condition in which typical morphological (interstitial fibrosis) and physiological (restriction) changes develop without the ability to determine the specific causes of their occurrence.

It can develop at any age. There are known cases of familial disease. There is an association with skeletal muscle myopathies.

Currently, among the genetic factors causing RCM, the following are distinguished: mutations of sarcomere proteins [troponin I (RCM +/- HCM), light chains of essential myosin], familial amyloidosis [transthyretin (RCM + neuropathy), a polyp allergen (RCM + neuropathy)], desminopathy, elastoma (pseudoxantoma elasticum), hemochromatosis, Andreola-Fabry disease, glycogenoses.

Diseases and conditions that cause secondary restrictive cardiomyopathy (non-familial or non-genetic form, ESC, 2008) include: amyloidosis, scleroderma, endomyocardial fibrosis [hypereosinophilic syndrome, idiopathic fibrosis, chromosomal abnormalities, drugs (serotonin, methysergide, ergotamine, mercury preparations, bisulfan)], carcinoid heart disease, metastatic lesions - radiation, anthracycline.

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Amyloidosis

Cardiac involvement is most likely in primary amyloidosis and is a predictor of poor prognosis. Amyloid deposits infiltrate and even replace normal contractile units of the myocardium. The myocardium becomes rigid, dense, thickened, but dilation of the cavities usually does not develop. During echocardiography, the myocardium infiltrated with amyloid appears bright and granular. Amyloid deposition in the atria and atrioventricular zone leads to various rhythm and conduction disturbances. Endomyocardial biopsy may be used to clarify the diagnosis.

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Scleroderma

Restrictive cardiomyopathy can develop in systemic scleroderma. One of the mechanisms of cardiovascular damage in scleroderma is the development of progressive myocardial fibrosis, which causes severe diastolic dysfunction of the myocardium.

Endomyocardial fibrosis and Loeffler's eosinophilic cardiomyopathy.

Both conditions are associated with hypereosinophilia and eosinophilic endocarditis of Loeffler and are typically found in North Africa and South America.

Infiltration in hypereosinophilic syndrome primarily affects the ventricular endocardium and atrioventricular valves. Endocardial thickening, parietal thrombosis, and endomyocardial fibrosis lead to a decrease in the cavities (partial obliteration) and impaired ventricular filling. Mitral and tricuspid regurgitation are characteristic, as well as an enlargement of the atria. Most patients die within two years of the onset of the disease.

Other infiltrative and storage diseases

Restrictive changes in the myocardium can be detected in many infiltrative diseases.

Gaucher disease is a disease in which there is an accumulation of cerebroside in the organs due to a deficiency of the enzyme beta-glucocerebrosidase.

Hurler syndrome is characterized by the deposition of mucopolysaccharides in the myocardial interstitium, valves, and arterial walls.

Fabry disease is an inherited disorder of glycosphingolipid metabolism leading to intracellular accumulation of glycolipids.

Hemochromatosis is a hereditary disease of iron metabolism, leading to its accumulation in organs, including the myocardium. Heart damage usually develops after diabetes and liver cirrhosis.

In systemic sarcoidosis, interstitial granulomatous inflammation in the myocardium may develop with impaired diastolic function, as well as the development of arrhythmias and blockades. Subsequently, fibrosis and impaired contractility of the myocardium develop. Heart damage in sarcoidosis may have different course options: subclinical, slowly progressing or fatal, with the development of sudden death due to rhythm and conduction disorders. Foci of myocardial involvement can be identified using scintigraphy with [ ²⁰¹ TI | or [ ⁶⁷ Ga] followed by endomyocardial biopsy.

Other restrictive conditions

Carcinoid heart disease is a late complication of carcinoid syndrome. The severity of heart damage correlates with the degree of increase in the level of serotonin and its metabolites in the blood. The main pathological sign is the formation of fibrous plaque on the endocardium of the right heart, including the valves. This leads to diastolic dysfunction of the right ventricle, tricuspid regurgitation and systemic venous congestion.

Drug-induced restrictive cardiomyopathy can develop during treatment with antitumor drugs of the anthracycline group, serotonin, the antimigraine drug methysergide, ergotamine, anorectics (phentermine) and some others (mercury drugs, bisulfan).

Radiation-induced cardiac damage (radiation cardiac disease) can also lead to RCM. Most cases develop as a complication of local radiotherapy to the mediastinum, usually for Hodgkin's disease.

Pathogenesis of restrictive cardiomyopathy

The pathogenesis of restrictive cardiomyopathy is well understood. Some disorders that cause restrictive cardiomyopathy also affect other tissues. Infiltration of the myocardium by amyloid (amyloidosis) or iron (hemochromatosis) usually also affects other organs, sometimes affecting the coronary arteries. Sarcoidosis and Fabry disease may also cause conduction system abnormalities. Löffler syndrome (a variant of hypereosinophilic syndrome with primary cardiac involvement), which occurs in tropical countries, begins as acute arteritis with eosinophilia, followed by thrombus formation on the endocardium, chordae, and atrioventricular valves, and then progresses to fibrosis. Endocardial fibroelastosis, which occurs in temperate zones, affects only the left ventricle.

Endocardial thickening or myocardial infiltration (sometimes with myocyte death, papillary muscle infiltration, compensatory myocardial hypertrophy, and fibrosis) may occur in one (usually the left) or both ventricles. This results in dysfunction of the mitral or tricuspid valve, leading to regurgitation. Functional regurgitation at the AV valves may result from myocardial infiltration or endocardial thickening. If the tissue of the nodes and conduction system is affected, the sinoatrial node functions poorly, sometimes leading to various AV blocks.

The result is diastolic dysfunction with a rigid, non-compliant ventricle, decreased diastolic filling, and high filling pressures, leading to pulmonary venous hypertension. Systolic function may deteriorate if compensatory hypertrophy of infiltrated or fibrotic ventricles is inadequate. Intracavitary thrombi may form, leading to systemic embolism.

Symptoms of restrictive cardiomyopathy

The course of restrictive cardiomyopathy depends on the nature and severity of the cardiac damage and can range from subclinical to fatal, including sudden cardiac death.

The early stages of restrictive heart disease are characterized by the appearance of weakness, rapid fatigue, paroxysmal nocturnal dyspnea. Angina is absent, with the exception of some forms of amyloidosis.

At later stages, congestive heart failure develops without signs of cardiomegaly, with a predominance of right ventricular failure. Typically, there is a significant increase in central venous pressure, the development of hepatomegaly, ascites, and swelling of the jugular veins. Symptoms of restrictive cardiomyopathy may be indistinguishable from those of constrictive pericarditis.

Conduction disturbances are most common in amyloidosis and sarcoidosis, thromboembolic complications - in Löffler cardiomyopathy.

Atrial fibrillation is characteristic of idiopathic restrictive cardiomyopathy.

Symptoms include exertional dyspnea, orthopnea, and (if the right ventricle is affected) peripheral edema. Fatigue may be due to impaired cardiac output due to obstruction of ventricular filling. Atrial and ventricular arrhythmias and atrioventricular block are common, but angina and syncope are rare. Symptoms are similar to those of constrictive pericarditis.

Diagnosis of restrictive cardiomyopathy

Physical examination reveals weakening of the heart sounds, low-amplitude and accelerated pulse in the carotid arteries, pulmonary rales and pronounced swelling of the veins of the neck with a rapid decrease. The fourth heart sound (S4 ₎ is almost always present. The third heart sound (S3 ₎ is detected less often and must be differentiated from the precordial click in constrictive pericarditis. In some cases, the noise of functional mitral or tricuspid regurgitation appears, associated with the fact that myocardial or endocardial infiltration or fibrosis changes the chords or the configuration of the ventricles. Paradoxical pulse is not encountered.

An ECG, chest radiography, and echocardiography are required for diagnosis. The ECG usually shows nonspecific changes in the ST segment and G wave, sometimes low voltage. Pathological Q waves not associated with previous MI may be encountered. Left ventricular hypertrophy due to compensatory myocardial hypertrophy is sometimes detected. On chest radiographs, the heart size is often normal or reduced, but may be enlarged in late-stage amyloidosis or hemochromatosis.

Echocardiography usually shows normal systolic function. Dilated atria and myocardial hypertrophy are common. In RCM, the myocardial echostructure is unusually bright due to amyloidosis. Echocardiography helps differentiate constrictive pericarditis from thickened pericardium, while paradoxical septal motion may occur in either disorder. In cases of doubtful diagnosis, CT is needed to visualize the pericardial structure, and MRI may show myocardial pathology in diseases associated with myocardial infiltration (eg, amyloid or iron).

Cardiac catheterization and myocardial biopsy are rarely necessary. When performed, catheterization reveals high atrial pressures in restrictive cardiomyopathy, with markedly depressed y waves and an early diastolic fall followed by a high diastolic plateau in the ventricular pressure curve. In contrast to the changes in constrictive pericarditis, left ventricular diastolic pressures are usually several millimeters of mercury higher than right ventricular diastolic pressures. Angiography reveals normal-sized ventricular cavities with normal or reduced systolic contraction. AV valve regurgitation may be present. Biopsy may reveal endocardial fibrosis and thickening, myocardial infiltration with iron or amyloid, and chronic myocardial fibrosis. Coronary angiography is normal unless amyloidosis affects the epicardial coronary arteries. Sometimes cardiac catheterization is of no diagnostic help, and occasionally thoracotomy is recommended to examine the pericardium.

Tests are needed to identify the most common causes of restrictive cardiomyopathy (eg, rectal biopsy for amyloidosis, iron metabolism tests or liver biopsy for hemochromatosis).

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Differential diagnosis of restrictive cardiomyopathy

In all cases of unexplained right ventricular failure, restrictive cardiomyopathy must be excluded.

RCM should be differentiated primarily from constrictive pericarditis, which has similar hemodynamic changes. Unlike RCM, constrictive pericarditis can be successfully treated surgically, so it is important to differentiate these conditions in a timely manner.

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Treatment of restrictive cardiomyopathy

At present, there are no specific methods of treating idiopathic and familial forms of restrictive cardiomyopathy. This is possible only for some of its secondary variants (for example, hemochromatosis, amyloidosis, earcoidosis, etc.).

Treatment of restrictive cardiomyopathy is aimed at relieving symptoms and preventing complications.

Improvement of diastolic filling of the ventricles is achieved by controlling the heart rate (beta-blockers, verapamil).

Diuretics are prescribed to reduce pulmonary and systemic congestion.

The role of ACE inhibitors in restrictive myocardial diseases is unclear.

Digoxin should be used only in cases of significant reduction in left ventricular systolic function.

With the development of AV block, there is a sharp decrease in the atrial fraction in ventricular filling, which may require the installation of a dual-chamber electrical pacemaker.

Most patients with restrictive cardiomyopathy require antiplatelet or anticoagulant treatment.

Ineffectiveness of conservative treatment is an indication for heart transplantation or other surgical treatment methods (endocardiectomy, heart valve replacement).

Diuretics should be used with caution because they can reduce preload. Non-distensible ventricles are highly dependent on preload for their ability to maintain cardiac output. Cardiac glycosides improve hemodynamics very little and may be dangerous in amyloid cardiomyopathy, which often causes extreme sensitivity to digitalis. Afterload-reducing agents (eg, nitrates) can cause profound hypotension and are usually ineffective.

If diagnosed early, specific treatment for hemochromatosis, sarcoidosis, and Loeffler syndrome may be effective.

Prognosis of restrictive cardiomyopathy

The prognosis is pessimistic, similar to that of dilated cardiomyopathy, since the diagnosis is often made at a late stage of the disease. Most patients do not respond to any treatment. Only symptomatic and replacement therapy can be offered.

The five-year survival rate is about 64%, the 10-year survival rate of patients with idiopathic RCM is 50%, most survivors have severe heart failure.