Dilated cardiomyopathy

From Vero - Wikipedia
Jump to navigation Jump to search

Template:Short description Template:Cs1 config Template:Infobox medical condition (new) Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively.<ref name=NIH2016What>Template:Cite web</ref> Symptoms vary from none to feeling tired, leg swelling, and shortness of breath.<ref name=NIH2016Sym/> It may also result in chest pain or fainting.<ref name=NIH2016Sym>Template:Cite web</ref> Complications can include heart failure, heart valve disease, or an irregular heartbeat.<ref name=NIH2016What/><ref name=NIH2016Type>Template:Cite web</ref>

Causes include genetics, alcohol, cocaine, certain toxins, complications of pregnancy, and certain infections.<ref name=NIH2016Ca/><ref name=Lancet2017/> Coronary artery disease and high blood pressure may play a role, but are not the primary cause.<ref name=Fer2018>Template:Cite book</ref><ref name=NIH2016Ca/> In many cases the cause remains unclear.<ref name=NIH2016Ca>Template:Cite web</ref> It is a type of cardiomyopathy, a group of diseases that primarily affects the heart muscle.<ref name=NIH2016What/> The diagnosis may be supported by an electrocardiogram, chest X-ray, or echocardiogram.<ref name=Lancet2017/>

In those with heart failure, treatment may include medications in the ACE inhibitor, beta blocker, and diuretic families.<ref name=Lancet2017/> A low salt diet may also be helpful.<ref name=Fer2018/> In those with certain types of irregular heartbeat, blood thinners or an implantable cardioverter defibrillator may be recommended. Cardiac resynchronization therapy (CRT) may be necessary.<ref name=Lancet2017/> If other measures are not effective a heart transplant may be an option in some.<ref name=Lancet2017/>

About 1 per 2,500 people is affected.<ref name=Lancet2017>Template:Cite journal</ref> It occurs more frequently in men than women.<ref>Template:Cite web</ref> Onset is most often in middle age.<ref name=Fer2018/> Five-year survival rate is about 50%.<ref name=Lancet2017/> It can also occur in children and is the most common type of cardiomyopathy in this age group.<ref name=Lancet2017/>

Signs and symptoms

Template:Main Dilated cardiomyopathy develops insidiously, and may not initially cause symptoms significant enough to impact on quality of life.<ref>Template:Cite journal</ref><ref name=":0">Template:Cite book</ref> Nevertheless, many people experience significant symptoms. These might include:<ref>Template:Cite web</ref>

A person who has dilated cardiomyopathy may have an enlarged heart, with pulmonary edema and an elevated jugular venous pressure and a low pulse pressure. Signs of mitral and tricuspid regurgitation may be present.<ref name=":0" />

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 enteroviruses<ref name=Robbins8th>Template:Cite book</ref> possibly mediated through an immunologic mechanism.<ref>Template:Cite journal</ref> Specific autoantibodies are detectable in some cases.<ref>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.</ref>

Other causes include:

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Genetics

About 25–35% of affected individuals have familial forms of the disease,<ref name=Robbins8th/> with most mutations affecting genes encoding cytoskeletal proteins,<ref name=Robbins8th/> while some affect other proteins involved in contraction.<ref>Template:Cite journal</ref> The disease is genetically heterogeneous, but the most common form of its transmission is an autosomal dominant pattern.<ref name=Robbins8th/> Autosomal recessive (as found, for example, in Alström syndrome<ref name=Robbins8th/>), X-linked (as in Duchenne muscular dystrophy), and mitochondrial inheritance of the disease is also found.<ref>Template:Cite journal</ref> Some relatives of those affected by dilated cardiomyopathy have preclinical, asymptomatic heart-muscle changes.<ref>Template:Cite journal</ref>

Other cytoskeletal proteins involved in DCM include α-cardiac actin, desmin, and the nuclear lamins A and C.<ref name=Robbins8th/> Mitochondrial deletions and mutations presumably cause DCM by altering myocardial ATP generation.<ref name=Robbins8th/> Nuclear coding variations for mitochondrial complex II have also shown pathogenicity for dilated cardiomyopathy, designated 1GG for SDHA.

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.<ref>Template:Cite journal</ref>

Pathophysiology

Illustration of a Normal Heart vs. Heart with Dilated Cardiomyopathy

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.<ref name=PIESKE2004>Template:Cite journal</ref>

Compensation effects

As DCM progresses, two compensatory mechanisms are activated in response to impaired myocyte contractility and reduced stroke volume:<ref name=":0" />

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.Template:Citation needed

Computational models

Cardiac dilatation is a transversely isotropic, irreversible process resulting from excess strains on the myocardium.<ref name = "Goektepe_2010">Template:Cite journal</ref> A computation model of volumetric, isotropic, and cardiac wall growth predicts the relationship between cardiac strains (e.g. volume overload after myocardial infarction) and dilation using the following governing equations:Template:Citation needed

<math>F = F^e \cdot F^g\,</math>

where <math>F^e</math> is elastic volume stretch that is reversible and <math>F^g</math> is irreversible, isotropic volume growth described by:Template:Citation needed

<math>F^g = \mathbb{I}+[\lambda^{g}-1]f_{0}\otimes f_{0} \,</math>

where <math>f_{0}</math> is a vector, which points along a cardiomyocyte's long axis and <math> \lambda^g </math> is the cardiomyocyte stretch due to growth. The total cardiomyocyte growth is given by:

<math>\lambda = \lambda^e \cdot F\lambda^g\,</math>

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 <math>\mu</math>m in the endocardium and 130 <math>\mu</math>m in the epicardium by the addition of sarcomeres.<ref name = "Goektepe_2010" /> Due to the increase in diameter, the dilated heart appears spherical in shape, as opposed the elliptical shape of a healthy human heart. In addition, the ventricular walls maintain the same thickness, characteristic of pathophysiological cardiac dilation.Template:Citation needed

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.<ref name=":0" />

Diagnosis

File:LBBB+RADandTransplant.png
Serial 12-lead ECGs from a 49-year-old black man with cardiomyopathy. (TOP): Sinus tachycardia (rate about 101/min) with LBBB accompanied by RAD (here about 108°). Frequent multifocal PVCs (both singly and in pairs) and left atrial enlargement. (BOTTOM): Same patient about 5 months later status-post orthotopic heart transplant.
File:DifDilatedCardiomyoMagCXR.png
Dilated cardiomyopathy on CXR
File:DifCardioMag.png
Dilated cardiomyopathy on CT

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.<ref name="Dilated Cardiomyopathy">Template:Cite web</ref>

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Echocardiogram shows left ventricular dilatation with normal or thinned walls and reduced ejection fraction. Cardiac catheterization and coronary angiography are often performed to exclude ischemic heart disease.<ref name="Dilated 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."<ref>Template:Cite journal</ref> The results of the genetic testing can help the doctors and patients understand the underlying cause of the dilated cardiomyopathy. Genetic test results can also help guide decisions on whether a patient's relatives should undergo genetic testing (to see if they have the same genetic mutation) and cardiac testing to screen for early findings of dilated cardiomyopathy.<ref name="Dilated Cardiomyopathy"/>

Cardiac magnetic resonance imaging (cardiac MRI) may also provide helpful diagnostic information in patients with dilated cardiomyopathy.<ref>Template:Cite journal</ref>

Treatment

Medical therapy

Drug therapy can slow down progression and in some cases even improve the heart condition. Standard therapy may include salt restriction, ACE inhibitors, diuretics, and beta blockers.<ref name=":0" /> Anticoagulants may also be used for antithrombotic therapy. There is some evidence for the benefits of coenzyme Q10 in treating heart failure.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

K-strophanthin may improve functional performance in patients with severe cardiac decompensation while digoxin raises cardiac output and ejection fraction only at rest.<ref>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, October 1994, https://doi.org/10.1002/clc.4960171005Citations. In: onlinelibrary.wiley.com</ref>

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.<ref name=":1">Template:Cite book</ref> In addition, an implantable cardioverter-defibrillator should be considered as a therapeutic option for the primary prevention of sudden cardiac death in patients with a confirmed LMNA mutation responsible for dilated cardiomyopathy disease phenotype and clinical risk factors.<ref>Template:Cite journal</ref> A novel risk score calculator has been developed that allows calculation of risk of sustained ventricular arrhythmia in the next 5 years in patients with DCM.<ref>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.</ref> https://www.ikard.pl/SVA/ Template:Webarchive

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 more than 20 years.<ref name=":1" />

Epidemiology

Although the disease is more common in African-Americans than in Caucasians,<ref>Template:Cite journal</ref> it may occur in any patient population.

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).<ref name="PIESKE2004" /><ref>Template:Cite journal</ref>

Animals

In some types of animals, both a hereditary and acquired version of dilated cardiomyopathy has been documented.Template:Citation needed

Dogs

Dilated cardiomyopathy is a heritable disease in some dog breeds, including the Boxer, Dobermann, Great Dane, Irish Wolfhound, and St Bernard.<ref>Template:Cite journal</ref> Treatment is based on medication, including ACE inhibitors, loop diuretics, and phosphodiesterase inhibitors.Template:Citation needed

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 Golden Retrievers.<ref>Template:Cite web</ref> The diets associated with DCM were described as "BEG" (boutique, exotic-ingredient, and/or grain-free) dog foods,<ref>Template:Cite journal</ref> as well as legume-rich diets.<ref>Template:Cite journal</ref> For treating diet-related DCM, food changes, taurine and carnitine supplementation may be indicated even if the dog does not have a documented taurine or carnitine deficiency although the cost of carnitine supplementation may be viewed as prohibitive by some<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> As opposed to these hereditary forms, non-hereditary DCM used to be common in the overall cat population before the addition of taurine to commercial cat food.Template:Citation needed

Other animals

There is also a high incidence of heritable dilated cardiomyopathy in captive golden hamsters (Mesocricetus auratus), due in no small part to their being highly inbred. 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.<ref>Template:Cite journal</ref>

References

Template:Reflist

Template:Medical resources

Template:Circulatory system pathology Template:Cytoskeletal defects Template:ABC transporter disorders

Retrieved from "https://wiki.sarg.dev/index.php?title=Dilated_cardiomyopathy&oldid=366212"