Cardiosclerosis of the heart: new methods of treatment in cardiology

Author Ольга Кияница

2019-04-14

Millions of people around the world suffer from heart failure. With its development, cardiac output decreases and compensatory mechanisms are activated. One of them is cardiac sclerosis, the process of scarring, which over time affects the structure and function of the organ. Previously, cardiosclerosis was not the subject of treatment, but it is now believed that therapy aimed at this pathology can reduce the progression of heart failure and other cardiovascular diseases.

Cardiac sclerosis is a fairly common complication today, most likely due to an increased incidence of heart failure (HF). In heart failure, damage and death of cardiomyocytes (heart cells) are often observed, and then in their place dense connective tissue begins to grow.

To some extent, cardiac sclerosis can be considered as a compensatory state, but with its substantial distribution, the risk of exacerbation of HF and death of a patient increases markedly.

Cardiosclerosis can be diffuse or focal. In the first form of the disease, its more aggressive development is observed, when the quality of life of the patient rather quickly deteriorates and the question of the pacemaker implantation often becomes. Focal cardiosclerosis may be less dangerous, but only if the centers of seals are small. Otherwise, rapid progression of HF is also possible.

Video: Heart Failure

Heart failure - the main cause of cardiosclerosis

Heart failure is a complex clinical syndrome in which structural or functional impairment changes the ability of the heart to fill up or pump blood. This heart disease is the main cause of hospitalization for patients aged 65 years and older, as well as the main cause of deterioration in quality of life and chronic disability.

Heart failure may result from systolic dysfunction, diastolic dysfunction, or both. The most common risk factors for heart failure are as follows:

  • Coronary heart disease (often with myocardial infarction [MI]).
  • Hypertensive disease.
  • Diabetes.
  • Cardiomyopathy.

Heart failure is triggered by any event that impairs the ability of the heart to contract and / or relax, leading to a decrease in cardiac output. As cardiac output decreases, compensatory mechanisms are activated to restore the lost functions of the heart, most often by increasing preload, tachycardia, vasoconstriction, ventricular hypertrophy and remodeling.

At the cellular level, hypertrophy and remodeling of the ventricles are accompanied by an increase in the mass and size of cardiomyocytes, as well as their necrosis, apoptosis, proliferation of fibroblasts, and increased deposition of collagen threads. All conditions are created for the development of cardiosclerosis.

Pathogenesis of cardiac sclerosis

Ventricular remodeling, a natural compensatory process that precedes the development of symptoms of heart failure, leads to progressive changes in the structure and function of the heart. In particular, myocardial hypertrophy, loss of heart muscle cells and changes in structural elements occur.

Some types of hypertrophy are accompanied by fibrosis and sclerosis. Cardiac fibrosis occurs when fibroblasts are activated in myofibroblasts and produce an increased amount of special proteins that form scar tissue and change the normal process of their degradation. Both processes lead to the accumulation of collagen, which affects both systolic and diastolic function. With sclerosis, a more dense tissue is formed, which may be diffuse or focal.

Sclerosis and fibrosis of the heart, which is part of the normal aging process of the body, is often associated with many cardiovascular diseases, including heart failure, hypertension and cardiomyopathy. Also, signs of cardiosclerosis are often found in hearts that have been damaged by myocardial infarction or radiation. The disease progresses with time and is accompanied by continued deterioration of the heart.

Mediators of cardiosclerosis

The increase in various circulating hormones, cytokines and proteins, caused by stress or damage, contributes to the activation and differentiation of fibroblasts and, ultimately, fibrosis and heart sclerosis. Although many substances have been identified as playing a role in this process, some research points to the following key elements in the cascade:

  • Renin-angiotensin system (renin-angiotensin system, RAS).
  • Transforming growth factor (transforming growth factor, TGF) -beta.
  • Endothelin (endothelin, ET).

It is worth pointing out that RAS regulates the production and activity of fibroblasts. When the heart is damaged, macrophages and fibroblasts produce renin and ACE, which, in turn, generate angiotensin II (Ang II). Ang II interacts with Ang II type 1 (AT 1) receptors, which promote hypertrophy, stimulate fibroblast proliferation, and increase collagen synthesis. In addition, Ang II inhibits collagenase (an enzyme that breaks down collagen), which can lead to increased collagen accumulation and cardiosclerosis.

Aldosterone has also been identified as a mediator of the development of cardiosclerosis and fibrosis. It affects the proliferation of fibroblasts and collagen deposition in the protein structure, enhancing the expression of cytokines and chemokines, signal macrophages and activating fibrogenic signals of cardiomyocytes.

TGF-beta is a cytokine located in the heart that is activated as a result of a heart injury, the formation of reactive oxygen species, Ang II, high glucose levels, changes in pH and some proteases. After activation, TGF-beta increases the production of specific proteins and reduces the activity of destruction.

ET is a protein that is secreted by the endothelial cells of the heart. It was found that an increase in fibroblast differentiation into myofibroblasts and the production of specific proteins also contributes to the development of cardiosclerosis.

Diagnosis of cardiac sclerosis

Historically, the only way to determine cardiac sclerosis was echocardiography , which indirectly measures the mass of the left ventricle. Also, if necessary, used such an invasive method of research, as an endomyocardial biopsy . With its help, the volume fraction of collagen was measured. Newer methods are laboratory evaluation of biomarkers and visualization of the heart .

Biomarkers can be used to detect myocardial sclerosis before the onset of symptoms, as well as to evaluate the effectiveness of drugs.

MRI is useful for imaging certain types of cardiosclerosis. A contrast-enhanced MRI of the heart can easily visualize focal cardiosclerosis, as well as myocardial infarction or infiltration. Diffuse cardiosclerosis is much more difficult to visualize. However, a study of advanced MRI methods may be useful in identifying this and other forms of the disease.Other imaging techniques that have shown promise for the identification of cardiac sclerosis include single photon emission tomography and positron emission tomography , but more research is needed to evaluate their effectiveness.

A) SPECT-MRT polar perfusion maps under stress and at rest show a largely reversible anteoapical defect of perfusion.
B) 3D-rendered volumetric images showing coronary vessels with stenosis of the middle left (LAD) and proximal first diagonal branch (DA1).
C) Merged 3D SPECT / CT images that identify stenosis as a functionally significant lesion.
D) Results were confirmed by coronary angiography.

Cardiac sclerosis treatment

For certain conditions that cause cardiosclerosis, such as volume or pressure overload, the best treatment is to prevent the progression of the disease by controlling risk factors. If this method of prevention is not possible or did not give the desired results, the doctor prescribes suitable drugs and new chemicals that are at different stages of development.These drugs can have a significant effect on the treatment of many cardiovascular diseases.

Means that affect RAS:

  • Some antihypertensive classes, including beta-blockers and calcium channel blockers. They are prescribed to increase cardiac output.
  • RAS inhibitors, such as ACE inhibitors, angiotensin receptor blockers (BAR) and aldosterone antagonists, which have a positive effect in most cases.
  • BAR is also effective in reducing cardiosclerosis. In particular, losartan and olmesartan have a beneficial effect on heart function, and candesartan reduces cardio-sclerosis biomarkers in humans.

Unlike ACE inhibitors and ARBs, aldosterone antagonists directly block aldosterone, which may be a more effective way to reduce its profibrotic and cardiosclerotic effects. Spironolactone and eplerenone, as shown in studies, reduce the degree of sclerosis, but the results are not always unequivocal.

  • TGF-beta inhibitors - two drugs are currently being studied, pirfenidone and tranilast. Although the exact mechanisms of their action are not fully understood, these drugs appear to inhibit TGF-beta and other growth factors. Perfenidone, an oral medication, was approved in October 2014 for the treatment of idiopathic pulmonary fibrosis. Tranilast has been used in Japan for over 20 years to treat asthma, allergic rhinitis, and atopic dermatitis. But in the treatment of cardiac sclerosis, serious changes in laboratory parameters have occurred, so for now the drug is being finalized.
  • ET inhibitors. Currently, several inhibitors of ET receptors have been approved for the treatment of pulmonary hypertension in the United States, including inhibitors of dual ET subtype A / ET subtype B (ETA / ETB), bosentan and makitentan, and ETA inhibitor ambrisentan. It is suggested that it may be necessary to target the double inhibition of ETA / ETB, since both receptors affect sclerosis and fibrosis. But while the studies studying the use of drugs for fibrosis and sclerosis, continue.
  • Drugs affecting other fibrosis mediators:
    • Histone deacetylases (HDAC) are enzymes that play a key role in regulating gene transcription throughout the body. HDAC may be associated with signal transduction of certain cellular molecules that affect cardiac fibrillation and inflammation.
    • Ivabradine is an oral medication currently available outside the US that provides a selective reduction in heart rate by inhibiting the f-channel of the sinoatrial node. In August 2014, the FDA provided an accelerated prescription for this compound in the treatment of chronic heart failure.

Additional agents, including diltiazem, tadalafil, isosorbide dinitrate and hydralazine, erythropoietin, cyclosporine, thalidomide and anti-inflammatory drugs that affect cytokines (for example, tumor necrosis factor alpha, interleukin-1), are under development. However, some studies have shown that transplantation of a variety of stem cells after MI reduces the severity of heart fibrosis and cardiosclerosis, as well as apoptosis (death) of the heart muscle.

Conclusion

Cardiac sclerosis is considered to be the last step leading to heart failure, which is extremely common throughout the world. Most of the pathophysiology of cardiac cardiosclerosis is known. Many drugs have been studied and seem promising, but practical use data are limited and ambiguous. Although more research is needed to assess the safety and efficacy of possible treatments for cardiac sclerosis, there are high hopes for the future.

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