ventricular remodeling
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cardiology Cardiology () is a branch of medicine that deals with disorders of the heart and the cardiovascular system. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular h ...
, ventricular remodeling (or cardiac remodeling) refers to changes in the size, shape, structure, and
function Function or functionality may refer to: Computing * Function key, a type of key on computer keyboards * Function model, a structured representation of processes in a system * Function object or functor or functionoid, a concept of object-oriente ...
of the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
. This can happen as a result of exercise (physiological remodeling) or after injury to the heart muscle (pathological remodeling). The injury is typically due to
acute myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may t ...
(usually transmural or ST segment elevation infarction), but may be from a number of causes that result in increased
pressure Pressure (symbol: ''p'' or ''P'') is the force applied perpendicular to the surface of an object per unit area over which that force is distributed. Gauge pressure (also spelled ''gage'' pressure)The preferred spelling varies by country and e ...
or
volume Volume is a measure of occupied three-dimensional space. It is often quantified numerically using SI derived units (such as the cubic metre and litre) or by various imperial or US customary units (such as the gallon, quart, cubic inch). Th ...
, causing pressure overload or
volume overload Volume overload refers to the state of one of the chambers of the heart in which too large a volume of blood exists within it for it to function efficiently. Ventricular volume overload is approximately equivalent to an excessively high preload ...
(forms of strain) on the heart. Chronic hypertension,
congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
with intracardiac shunting, and
valvular heart disease Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These ...
may also lead to remodeling. After the insult occurs, a series of
histopathological Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
and structural changes occur in the left ventricular myocardium that lead to progressive decline in left ventricular performance. Ultimately, ventricular remodeling may result in diminished contractile ( systolic) function and reduced stroke volume. Physiological remodeling is reversible while pathological remodeling is mostly irreversible. Remodeling of the ventricles under left/right pressure demand make mismatches inevitable. Pathologic pressure mismatches between the pulmonary and systemic circulation guide compensatory remodeling of the left and right ventricles. The term "reverse remodeling" in cardiology implies an improvement in ventricular mechanics and function following a remote injury or pathological process. Ventricular remodeling may include
ventricular hypertrophy Ventricular hypertrophy (VH) is thickening of the walls of a ventricle (lower chamber) of the heart. Although left ventricular hypertrophy (LVH) is more common, right ventricular hypertrophy (RVH), as well as concurrent hypertrophy of both ventr ...
, ventricular dilation,
cardiomegaly Cardiomegaly (sometimes megacardia or megalocardia) is a medical condition in which the heart is enlarged. As such, it is more commonly referred to simply as "having an enlarged heart". It is usually the result of underlying conditions that make t ...
, and other changes. It is an aspect of cardiomyopathy, of which there are many types. Concentric hypertrophy is due to pressure overload, while eccentric hypertrophy is due to
volume overload Volume overload refers to the state of one of the chambers of the heart in which too large a volume of blood exists within it for it to function efficiently. Ventricular volume overload is approximately equivalent to an excessively high preload ...
.


Pathophysiology

The cardiac myocyte is the major cell involved in remodeling. Fibroblasts, collagen, the interstitium, and the coronary vessels to a lesser extent, also play a role. A common scenario for remodeling is after myocardial infarction. There is myocardial necrosis (cell death) and disproportionate thinning of the heart. This thin, weakened area is unable to withstand the pressure and volume load on the heart in the same manner as the other healthy tissue. As a result, there is dilatation of the chamber arising from the infarct region. The initial remodeling phase after a myocardial infarction results in repair of the necrotic area and myocardial scarring that may, to some extent, be considered beneficial since there is an improvement in or maintenance of LV function and cardiac output. Over time, however, as the heart undergoes ongoing remodeling, it becomes less elliptical and more spherical. Ventricular mass and volume increase, which together adversely affect cardiac function. Eventually,
diastolic Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are re-filling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventricu ...
function, or the heart's ability to relax between contractions may become impaired, further causing decline. After a myocardial infarction (MI), cardiac myocyte death can be triggered by necrosis, apoptosis, or autophagy, leading to thinning of the cardiac wall. The surviving cardiac myocytes either arrange in parallel or in series to each other, contributing to ventricular dilatation or ventricular hypertrophy, depending on the loading stress on the ventricular wall. Besides, reduced expression of V1 myosin and L-type calcium channels on cardiac myocytes are also thought to cause cardiac remodeling. Under normal body conditions,
fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...
accounts for 60 to 90% of the energy supply of the heart. Post MI, as fatty acid oxidation decreases, it leads to reduced energy supply for the cardiac myocytes, accumulation of fatty acids to toxic levels, and dysfunction of mitochondria. These consequences also led to the increase in oxidative stress on the heart, causing the proliferation of fibroblasts, activation of
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 myo ...
s, and induction of apoptosis, which would be explained below. Besides, inflammatory immune response after MI also contributes to the above changes. Besides, the cardiac interstitium which consisted of largely Type I and Type III collagen fibres are also involved in cardiac remodeling. Cardiac collagen is synthesized by fibroblasts and degraded by metalloproteinases. Fibroblasts are activated post MI, leading to increased collagen synthesis and fibrosis of the heart. Increase expression of
MMP1 Interstitial collagenase, also known as fibroblast collagenase, and matrix metalloproteinase-1 (MMP-1) is an enzyme that in humans is encoded by the ''MMP1'' gene. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. ...
and
MMP9 Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extrace ...
led to degradation of collagen fibres, and subsequently dilatation of the heart. Several signal pathways such as Angiotensin II,
Transforming growth factor beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other ...
(TGF-beta), and Endothelin 1 are known to trigger synthesis and degradation of collagen fibres in the heart. Other factors such as high blood pressure, activation of sympathetic system which releases
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
, activation of
renin–angiotensin system The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance. When renal blood flow is reduced, ...
which releases
renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...
and anti-diuretic hormones are important contributors of cardiac remodelling. However,
atrial natriuretic peptide Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/p ...
is thought to be cardio-protective.


Evaluation

Remodeling of the heart is evaluated by performing an
echocardiogram An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in th ...
. The size and function of the atria and ventricles can be characterized using this test.


Treatment

Many factors influence the time course and extent of remodeling, including the severity of the injury, secondary events (recurrent ischemia or infarction), neurohormonal activation, genetic factors and gene expression, and treatment. Medications may attenuate remodeling. Angiotensin-converting enzyme (ACE) inhibitors have been consistently shown to decrease remodeling in animal models or transmural infarction and chronic pressure overload. Clinical trials have shown that ACE inhibitor therapy after myocardial infarction leads to improved myocardial performance, improved
ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, ventricle, gall bladder, ...
, and decreased mortality compared to patients treated with placebo. Likewise, inhibition of aldosterone, either directly or indirectly, leads to improvement in remodeling. Carvedilol, a 3rd generation
beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are ...
, may actually reverse the remodeling process by reducing left ventricular volumes and improving systolic function. Cardiac resynchronization therapy (CRT) has shown the ability to reverse left ventricular remodeling in some patients. Early correction of congenital heart defects, if appropriate, may prevent remodeling, as will treatment of chronic hypertension or
valvular heart disease Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These ...
. Often, reverse remodeling, or improvement in left ventricular function, will also be seen.


See also

* Dor procedure *
Athlete's heart Athletic heart syndrome (AHS) is a non-pathological condition commonly seen in sports medicine in which the human heart is enlarged, and the resting heart rate is lower than normal. The athlete's heart is associated with physiological cardiac ...


References


Further reading

* {{Medicine Cardiomyopathy Cardiovascular physiology