Dilated cardiomyopathy ( DCM) is a condition in which the Cardiomegaly and cannot pump blood effectively.[ It may also result in chest pain or fainting.]
Causes include genetics, alcohol, cocaine, certain toxins, complications of pregnancy, and certain infections.[ Coronary artery disease and high blood pressure may play a role, but are not the primary cause.][ In many cases the cause remains unclear.][ The diagnosis may be supported by an electrocardiogram, chest X-ray, or echocardiogram.][
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In those with heart failure, treatment may include medications in the ACE inhibitor, beta blocker, and diuretic families.[ A low salt diet may also be helpful.][ In those with certain types of irregular heartbeat, anticoagulants or an implantable cardioverter defibrillator may be recommended. Cardiac resynchronization therapy (CRT) may be necessary.][ If other measures are not effective a heart transplant may be an option in some.][
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About 1 per 2,500 people is affected.[ Five-year survival rate is about 50%.][ It can also occur in children and is the most common type of cardiomyopathy in this age group.][
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Signs and symptoms
Dilated cardiomyopathy develops insidiously, and may not initially cause symptoms significant enough to impact on quality of life.
A person who has dilated cardiomyopathy may have an cardiomegaly, with pulmonary edema and an elevated jugular venous pressure and a low pulse pressure. Signs of mitral and tricuspid regurgitation may be present.
Causes
Although in many cases no cause is apparent, dilated cardiomyopathy is probably the result of damage to the myocardium produced by a variety of toxic, metabolic, or infectious agents. In many cases the cause remains unclear. It may be due to fibrous change of the myocardium from a previous myocardial infarction. Or, it may be the late sequelae of acute viral myocarditis, such as with Coxsackie B virus and other [Yoshikawa T, Baba A, Nagatomo Y. Autoimmune mechanisms underlying dilated cardiomyopathy. Circ J. 2009 Apr;73(4):602-7. doi: 10.1253/circj.cj-08-1151. Epub 2009 Feb 26. PMID 19246813.]
Other causes include:
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Chagas disease, due to Trypanosoma cruzi. This is the most common infectious cause of dilated cardiomyopathy in Latin America
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Pregnancy: Dilated cardiomyopathy occurs late in gestation or several weeks to months postpartum as a peripartum cardiomyopathy.
[ It is reversible in half of cases.][
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Alcohol use disorder (alcoholic cardiomyopathy)
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Non-alcoholic toxic insults include administration of certain chemotherapeutic agents, in particular doxorubicin (Adriamycin), and cobalt.
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Thyroid disease
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Inflammatory diseases such as sarcoidosis and connective tissue diseases
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Tachycardia-induced cardiomyopathy
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Muscular dystrophy
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Tuberculosis: 1 to 2% of TB cases.
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Autoimmune mechanisms
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Thiamine deficiency
Recent studies have shown that those subjects with an extremely high occurrence (several thousands a day) of premature ventricular contractions (extrasystole) can develop dilated cardiomyopathy. In these cases, if the extrasystole are reduced or removed (for example, via ablation therapy) the cardiomyopathy usually regresses.
Genetics
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| >CMD1A | | [[LMNA]] | 1q21
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| >CMD1B | | unknown (TMOD1 candidate) | 9q13
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| >CMD1C | | LDB3 | 10q22-q23
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| >CMD1D | | TNNT2 | 1q32
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| >CMD1E | | SCN5A | 3p
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| >CMD1F | | | 6q23
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| >CMD1G | | Titin]] | 2q31
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| >CMD1H | | | 2q14-q22
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| >CMD1I | | Desmin]]
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| >CMD1K | | | 6q12-q16
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| >CMD1L | | SGCD | 5q33
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| >CMD1M | | CSRP3 | 11p15.1
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| >CMD1N | | TCAP | 17q12
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| >CMD1O | | ABCC9 | 12p12.1
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| >CMD1P | | Phospholamban]] | 6q22.1
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| >CMD1Q | | | 7q22.3-q31.1
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| >CMD1R | | ACTC | 15q14
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| >CMD1S | | MYH7 | 14q12
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| >CMD1T | | [[TMPO]] | 12q22
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| >CMD1U | | PSEN1 | 14q24.3
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| >CMD1V | | PSEN2 | 1q31-q42
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| >CMD1W | | metavinculin]] | 10q22-q23
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| >CMD1X | | fukutin]] | 9q31
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| >CMD1Y | | TPM1 | 15q22.1
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| >CMD1Z | | TNNC1 | 3p21.3-p14.3
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| >CMD1AA | | ACTN2 | 1q42-q43
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| >CMD2A | | TNNI3 | 19q13.4
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| >CMD3A | | Tafazzin]] | Xq28
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| >CMD3B | | dystrophin]] | Xp21.2
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| > | | ALPK3 | 15q25.3
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About 25–35% of affected individuals have familial forms of the disease,[ with most affecting genes encoding Cytoskeleton proteins,][ while some affect other proteins involved in contraction.][
Autosomal recessive (as found, for example, in Alström syndrome][), X-linked (as in Duchenne muscular dystrophy), and mitochondrial inheritance of the disease is also found.]
Other cytoskeletal proteins involved in DCM include α-cardiac actin, desmin, and the nuclear lamins A and C.[ Mitochondrial deletions and mutations presumably cause DCM by altering myocardial ATP generation.][ Nuclear coding variations for mitochondrial complex II have also shown pathogenicity for dilated cardiomyopathy, designated 1GG for SDHA.
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Kayvanpour et al. performed 2016 a meta-analysis with the largest dataset available on genotype-phenotype associations in DCM and mutations in lamin (LMNA), phospholamban (PLN), RNA Binding Motif Protein 20 (RBM20), Cardiac Myosin Binding Protein C (MYBPC3), Myosin Heavy Chain 7 (MYH7), Cardiac Troponin T 2 (TNNT2), and Cardiac Troponin I (TNNI3). They also reviewed recent studies investigating genotype-phenotype associations in DCM patients with titin (TTN) mutations. LMNA and PLN mutation carriers showed a high prevalence of cardiac transplantation and ventricular arrhythmia. Dysrhythmias and sudden cardiac death (SCD) was shown to occur even before the manifestation of DCM and heart failure symptoms in LMNA mutation carriers.
Pathophysiology
The progression of heart failure is associated with left ventricular remodeling, which manifests as gradual increases in left ventricular end-diastolic and end-systolic volumes, wall thinning, and a change in chamber geometry to a more spherical, less elongated shape. This process is usually associated with a continuous decline in ejection fraction. The concept of cardiac remodeling was initially developed to describe changes that occur in the days and months following myocardial infarction.
Compensation effects
As DCM progresses, two compensatory mechanisms are activated in response to impaired myocyte contractility and reduced stroke volume:
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Frank-Starling law
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Neurohormonal feedback, via activation of the sympathetic nervous system and the renin-angiotensin system.
These responses initially compensate for decreased cardiac output and maintain those with DCM as asymptomatic. Eventually, however, these mechanisms become detrimental, intravascular volume becomes too great, and progressive dilatation leads to heart failure symptoms.
Computational models
Cardiac dilatation is a transversely isotropic, irreversible process resulting from excess strains on the myocardium.
where is elastic volume stretch that is reversible and is irreversible, isotropic volume growth described by:
where is a vector, which points along a cardiomyocyte's long axis and is the cardiomyocyte stretch due to growth. The total cardiomyocyte growth is given by:
The above model reveals a gradual dilation of the myocardium, especially the ventricular myocardium, to support the blood volume overload in the chambers. Dilation manifests itself in an increase in total cardiac mass and cardiac diameter. Cardiomyocytes reach their maximum length of 150 m in the endocardium and 130 m in the epicardium by the addition of Sarcomere.
Valvular effects
As the ventricles enlarge, both the mitral and tricuspid valves may lose their ability to come together properly. This loss of coaptation may lead to mitral and tricuspid regurgitation. As a result, those with DCM are at increased risk of atrial fibrillation. Furthermore, stroke volume is decreased and a greater volume load is placed on the ventricle, thus increasing heart failure symptoms.
Diagnosis
Generalized enlargement of the heart is seen upon normal chest X-ray. Pleural effusion may also be noticed, which is due to pulmonary venous hypertension.
The electrocardiogram often shows sinus tachycardia or atrial fibrillation, ventricular arrhythmias, left atrial enlargement, and sometimes intraventricular conduction defects and low voltage. When left bundle-branch block (LBBB) is accompanied by right axis deviation (RAD), the rare combination is considered to be highly suggestive of dilated or congestive cardiomyopathy.
Genetic testing can be important, since one study has shown that gene mutations in the TTN gene (which codes for a protein called titin) are responsible for "approximately 25% of familial cases of idiopathic dilated cardiomyopathy and 18% of sporadic cases."
Cardiac magnetic resonance imaging (cardiac MRI) may also provide helpful diagnostic information in patients with dilated cardiomyopathy.
Treatment
Medical therapy
Drug therapy can slow down progression and in some cases even improve the heart condition. Standard therapy may include salt restriction, , , and .
K-strophanthin may improve functional performance in patients with severe cardiac decompensation while digoxin raises cardiac output and ejection fraction only at rest.[Pier Giuseppe Agostoni M.D., Elisabetta Doria M.D., Marco Berti M.D., Maurizio D. Guazzi M.D.: Long-term use of K-strophanthin in advanced congestive heart failure due to dilated cardiomyopathy: A double-blind crossover evaluation versus digoxin
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In: onlinelibrary.wiley.com
Electrical treatment
Artificial pacemakers may be used in patients with intraventricular conduction delay, and implantable cardioverter-defibrillators in those at risk of arrhythmia. These forms of treatment have been shown to prevent sudden cardiac death, improve symptoms, and reduce hospitalization in patients with systolic heart failure.[Kayvanpour E, Sammani A, Sedaghat-Hamedani F, Lehmann DH, Broezel A, Koelemenoglu J, Chmielewski P, Curjol A, Socie P, Miersch T, Haas J, Gi WT, Richard P, Płoski R, Truszkowska G, Baas AF, Foss-Nieradko B, Michalak E, Stępień-Wojno M, Zakrzewska-Koperska J, Śpiewak M, Zieliński T, Villard E, TeRiele ASJM, Katus HA, Frey N, Bilińska ZT, Charron P, Asselbergs FW, Meder B. A novel risk model for predicting potentially life-threatening arrhythmias in non-ischemic dilated cardiomyopathy (DCM-SVA risk). Int J Cardiol. 2021 Sep15;339:75-82. doi: 10.1016/j.ijcard.2021.07.002. Epub 2021 Jul 7. PMID 34245791.] https://www.ikard.pl/SVA/
Surgical treatment
In patients with advanced disease who are refractory to medical therapy, heart transplantation may be considered. For these people, 1-year survival approaches 90% and over 50% survive greater than 20 years.
Epidemiology
Although the disease is more common in African-Americans than in Caucasians,
Research directions
Therapies that support reverse remodeling have been investigated, and this may suggests a new approach to the prognosis of cardiomyopathies (see ventricular remodeling).
Animals
In some types of animals, both a hereditary and acquired version of dilated cardiomyopathy has been documented.
Dogs
Dilated cardiomyopathy is a heritable disease in some dog breeds, including the Boxer, Dobermann, Great Dane, Irish Wolfhound, and St Bernard.
An acquired variation of dilated cardiomyopathy describing a link between certain diets was discovered in 2019 by researchers at University of California, Davis School of Veterinary Medicine who published a report on the development of dilated cardiomyopathy in dog breeds lacking the genetic predisposition, particularly in .
Cats
Dilated cardiomyopathy is also a disease affecting some cat breeds, including the Oriental Shorthair, Burmese, Persian, and Abyssinian. In cats, taurine deficiency is the most common cause of dilated cardiomyopathy.
Other animals
There is also a high incidence of heritable dilated cardiomyopathy in captive ( Mesocricetus auratus), due in no small part to their being highly Inbreeding. The incidence is high enough that several strains of Golden Hamster have been developed to serve as animal models in clinical testing for human forms of the disease.
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