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Myocardial scarring is the accumulation of
fibrous Fiber (spelled fibre in British English; from ) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often inco ...
tissue resulting after some form of trauma to the cardiac tissue. Fibrosis is the formation of excess tissue in replacement of
necrotic Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is ...
or extensively damaged tissue. Fibrosis in the heart is often hard to detect because
fibroma Fibromas are benign tumors that are composed of fibrous or connective tissue. They can grow in all organs, arising from mesenchyme tissue. The term "fibroblastic" or "fibromatous" is used to describe tumors of the fibrous connective tissue. Wh ...
s, scar tissue or small tumors formed in one cell line, are often formed. Because they are so small, they can be hard to detect by methods such as
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
. A cell line is a path of fibrosis that follow only a line of cells.


Causes


Myocardial infarction

A
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
, also known as a heart attack, often result in the formation of fibrosis. A myocardial infarction is an
ischemic Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
event, or a restriction of blood flow to body tissue, such as by atherothrombosis. Without blood flow to the myocardium, it is deprived of oxygen, causing tissue death and irreversible damage. The tissue destroyed by the infarction is replaced with non-functioning fibrosis, restoring some of the structural integrity of the organ but resulting in impaired myocardial function.


Coronary heart disease

Coronary heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
, also known as coronary artery disease, is one of the most common causes of myocardial damage, affecting over three million people in the United States. In coronary heart disease, the
coronary arteries The coronary arteries are the arteries, arterial blood vessels of coronary circulation, which transport oxygenated blood to the Cardiac muscle, heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any ...
narrow due to the buildup of
atheroma An atheroma, or atheromatous plaque, is an abnormal accumulation of material in the tunica intima, inner layer of an arterial wall. The material consists of mostly macrophage, macrophage cells, or debris, containing lipids, calcium and a variabl ...
or fatty deposits on the vessel walls. The atheroma causes the blood flow of the arteries to be restricted. By restricting the blood flow, the tissue is still receiving some oxygen, but not enough to sustain the tissue over time. The accumulation of the fibrotic tissue is much slower in coronary heart disease compared to an infarction because the tissue is still receiving some oxygen.


Birth defect repairs

Another form of myocardial scarring results from surgical repairs. Surgical repairs are often necessary for a person born with a congenital defect of the heart. While surgical
laparoscopy Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medli ...
still leaves myocardial scarring, the trauma seems to be less damaging then naturally occurring scarring.


Excessive exercise

Excessive exercise, particularly in endurance athletes, has been linked to myocardial scarring, a condition where
fibrous Fiber (spelled fibre in British English; from ) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often inco ...
tissue in the heart muscle forms. Intense, prolonged physical activity can lead to repetitive stress on the
myocardium Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...
, causing micro-injuries that may trigger inflammation and subsequent scarring. This is especially prevalent in individuals engaging in extreme endurance sports, such as marathons or ultra-marathons, very long
bicycle racing Cycle sport is competitive physical activity using bicycles. There are several categories of bicycle racing including road bicycle racing, cyclo-cross, mountain bike racing, track cycling, BMX, and cycle speedway. Non-racing cycling spo ...
, where sustained high
cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: tha ...
can strain the heart. Studies have shown that some athletes develop focal myocardial fibrosis, detectable via
cardiac imaging Cardiac imaging refers to minimally invasive imaging of the heart using ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), or nuclear medicine (NM) imaging with Positron emission tomography, PET or SPECT. These cardiac techniq ...
( cardiac MRI, etc), which may increase the risk of
arrhythmias Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beats ...
or reduced cardiac function over time. While exercise is generally beneficial for heart health, excessive and prolonged
exertion Exertion is the Action (physics), physical or perceived use of energy.Newton's Third Law, Elert, Glenn. “Forces.” ''Viscosity – The Physics Hypertextbook'', physics.info/newton-first/. Exertion traditionally connotes a strenuous or costly ''e ...
without adequate recovery may contribute to pathological changes in susceptible individuals - genetic tendency toward cardiac fibrosis, undiagnosed heart issues, or a reduced ability to recover from exercise-induced inflammation or micro-injuries.


Hypertension

Chronic hypertension can lead to myocardial scarring by imposing persistent high pressure on heart walls. This stress causes
left ventricular hypertrophy Left ventricular hypertrophy (LVH) is thickening of the heart muscle of the left ventricle of the heart, that is, left-sided ventricular hypertrophy and resulting increased left ventricular mass. Causes While ventricular hypertrophy occurs ...
, increasing oxygen demand and potentially leading to micro-ischemia. Over time, these changes may result in fibrosis as the heart attempts to repair damaged tissue, impairing cardiac function.


Cardiomyopathies

Cardiomyopathies, such as dilated or
hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which muscle tissues of the heart become thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ...
, are associated with myocardial scarring. These conditions alter heart muscle structure and function. Scarring may contribute to
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
or
arrhythmias Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beats ...
.


Myocarditis

Myocarditis, inflammation of the heart muscle often caused by
viral infections A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, ...
, can result in myocardial scarring. The
inflammatory response Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
damages cardiac tissue, triggering repair processes that replace necrotic cells with fibrous tissue. This scarring may increase the risk of arrhythmias.


Cardiac toxins

Exposure to cardiotoxic substances, such as
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
drugs (e.g.,
anthracyclines Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from '' Streptomyces peucetius'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, b ...
),
alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
, or
recreational drugs Recreation is an activity of leisure, leisure being discretionary time. The "need to do something for recreation" is an essential element of human biology and psychology. Recreational activities are often done for enjoyment, amusement, or plea ...
like
cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
, can cause myocardial scarring due to
free radical A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing. Ageing Biogerontology Biological processes Causes of death Cellular processes Gerontology Life extension Metabolic disorders Metabolism ...
damage, strand breakage of DNA in cardiomyocytes. These toxins induce direct damage to heart muscle cells, leading to inflammation and fibrosis as the body attempts to repair the injured tissue.


Aging

Aging is a natural contributor to myocardial scarring. Over time, cumulative stress from
oxidative damage Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...
, low-grade
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
, and microvascular changes can lead to gradual fibrosis in the heart. This age-related scarring may reduce cardiac elasticity and contribute to
diastolic dysfunction Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure in which the ejection fraction – the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the ...
in older individuals.


Formation

Immediately after damage to the myocardium occurs, the damaged tissue becomes inflamed. Inflammation is the accumulations of
neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
s,
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s, and
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...
s at the site of the trauma. In addition, "inflammatory cells upregulate the release of a myriad of signaling
cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
,
growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
, and hormones including transforming growth factor β, interleukins 1, 2, 6, and 10,
tumor necrosis factor α Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
, interferon γ,
chemokines Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...
of the CC and CXC families,
angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...
II,
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
, endothelin, natriuretic peptides, and platelet-derived growth factors". Both the necrotic cells and the inflamed myocardium
secrete Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...
and activate matrix
metalloproteinase A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myoge ...
. Metalloproteinase aids in the destruction and reabsorption of necrotic tissue. After several days,
collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
accumulation at the site of injury begins to occur. As part of the
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
, granulated tissue consisting of
fibrin Fibrin (also called Factor Ia) is a fibrous protein, fibrous, non-globular protein involved in the Coagulation, clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerization, polymerize. ...
,
fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as col ...
,
laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...
, and
glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...
is suspended in a collagen base. The extracellular matrix acts as scaffolding for the fibrillar collagen to form. The fibrillar collagen is the main constitute of what will become the scar tissue.


References

{{Heart diseases Heart diseases Scarring