| Dilated cardiomyopathy | |
|---|---|
| Other names | Congestive cardiomyopathy, idiopathic cardiomyopathy, primary cardiomyopathy[1] |
 | |
| Mouse heart slice showing dilated cardiomyopathy | |
| Specialty | Cardiology |
| Symptoms | Feeling tired,leg swelling,shortness of breath,chest pain,fainting[2] |
| Complications | Heart failure,heart valve disease,irregular heartbeat[3][4] |
| Usual onset | Middle age[5] |
| Types | Tachycardia-induced,[6][7] others |
| Causes | Genetics,alcohol,cocaine, certain toxins, complications of pregnancy, in many cases the cause remains unclear, certaininfections[8][9][7] |
| Diagnostic method | Supported byelectrocardiogram,chest X-ray,echocardiogram[9] |
| Differential diagnosis | Coronary artery disease,heart valve disease,pulmonary embolism, othercardiomyopathy[5] |
| Treatment | Lifestyle changes, medications,implantable cardioverter defibrillator, cardiac resynchronization therapy (CRT),heart transplant[9] |
| Medication | ACE inhibitor,beta blocker,diuretic,blood thinners[9] |
| Prognosis | Five-year survival rate ~50%[9] |
| Frequency | 1 in 2500[9] |
Dilated cardiomyopathy (DCM) is a condition in which theheart becomes enlarged and cannot pumpblood effectively.[3] Symptoms vary from none to feeling tired,leg swelling, andshortness of breath.[2] It may also result inchest pain orfainting.[2] Complications can includeheart failure,heart valve disease, or anirregular heartbeat.[3][4]
Causes includegenetics,alcohol,cocaine, certain toxins, complications of pregnancy, and certaininfections.[8][9]Coronary artery disease andhigh blood pressure may play a role, but are not the primary cause.[5][8] In many cases the cause remains unclear.[8] It is a type ofcardiomyopathy, a group of diseases that primarily affects theheart muscle.[3] The diagnosis may be supported by anelectrocardiogram,chest X-ray, orechocardiogram.[9]
In those with heart failure, treatment may include medications in theACE inhibitor,beta blocker, anddiuretic families.[9] Alow salt diet may also be helpful.[5] In those with certain types of irregular heartbeat,blood thinners or animplantable cardioverter defibrillator may be recommended. Cardiac resynchronization therapy (CRT) may be necessary.[9] If other measures are not effective aheart transplant may be an option in some.[9]
During the last two decades, there has been an increase in the number of patients diagnosed, and DCM represents the most common form of cardiomyopathy in adults.[10] The most recent figures indicate that about 3 per 1,000 men and 1 per 1,000 women are affected.[10] It is associated with a substantial excess mortality compared with the general population, ranging from about a 32-fold higher mortality in the youngest adults with DCM to about a 2-fold increase in the oldest patients.[10] It can also occur in children and is the most common type of cardiomyopathy in this age group.[9]
Dilated cardiomyopathy develops insidiously, and may not initially cause symptoms significant enough to impact onquality of life.[11][12] Nevertheless, many people experience significant symptoms. These might include:[13]
A person who has dilated cardiomyopathy may have anenlarged heart, withpulmonary edema and an elevatedjugular venous pressure and a lowpulse pressure. Signs ofmitral andtricuspid regurgitation may be present.[12]
Although in many cases no cause is apparent, dilated cardiomyopathy is probably the result of damage to themyocardium produced by a variety oftoxic,metabolic, or infectious agents. In many cases the cause remains unclear. It may be due to fibrous change of the myocardium from a previousmyocardial infarction. Or, it may be the late sequelae of acute viralmyocarditis, such as withCoxsackie B virus and otherenteroviruses[14] possibly mediated through an immunologic mechanism.[15] Specificautoantibodies are detectable in some cases.[16]
Other causes include:
Recent studies have shown that those subjects with an extremely high occurrence (several thousands a day) ofpremature 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.[20][21]
| Genetic associations with dilated cardiomyopathy | |||
|---|---|---|---|
| Type | OMIM | Gene | Locus |
| CMD1A | 115200 | LMNA | 1q21 |
| CMD1B | 600884 | unknown (TMOD1 candidate) | 9q13 |
| CMD1C | 601493 | LDB3 | 10q22-q23 |
| CMD1D | 601494 | TNNT2 | 1q32 |
| CMD1E | 601154 | SCN5A | 3p |
| CMD1F | 602067 | 6q23 | |
| CMD1G | 604145 | TTN | 2q31 |
| CMD1H | 604288 | 2q14-q22 | |
| CMD1I | 604765 | DES | |
| CMD1K | 605582 | 6q12-q16 | |
| CMD1L | 606685 | SGCD | 5q33 |
| CMD1M | 607482 | CSRP3 | 11p15.1 |
| CMD1N | 607487 | TCAP | 17q12 |
| CMD1O | 608569 | ABCC9 | 12p12.1 |
| CMD1P | 609909 | PLN | 6q22.1 |
| CMD1Q | 609915 | 7q22.3-q31.1 | |
| CMD1R | ACTC | 15q14 | |
| CMD1S | MYH7 | 14q12 | |
| CMD1T | TMPO | 12q22 | |
| CMD1U | PSEN1 | 14q24.3 | |
| CMD1V | PSEN2 | 1q31-q42 | |
| CMD1W | 611407 | VCL | 10q22-q23 |
| CMD1X | FCMD | 9q31 | |
| CMD1Y | 611878 | TPM1 | 15q22.1 |
| CMD1Z | 611879 | TNNC1 | 3p21.3-p14.3 |
| CMD1AA | 612158 | ACTN2 | 1q42-q43 |
| CMD2A | 611880 | TNNI3 | 19q13.4 |
| CMD3A | 300069 | TAZ | Xq28 |
| CMD3B | 302045 | DMD | Xp21.2 |
| ALPK3 | 15q25.3 | ||
About 25–35% of affected individuals have familial forms of the disease,[14] with mostmutations affecting genes encodingcytoskeletal proteins,[14] while some affect other proteins involved in contraction.[22] The disease is genetically heterogeneous, but the most common form of its transmission is anautosomal dominant pattern.[14]Autosomal recessive (as found, for example, inAlström syndrome[14]),X-linked (as inDuchenne muscular dystrophy), andmitochondrial inheritance of the disease is also found.[23] Some relatives of those affected by dilated cardiomyopathy have preclinical, asymptomatic heart-muscle changes.[24]
Other cytoskeletal proteins involved in DCM includeα-cardiac actin,desmin, and the nuclearlamins A and C.[14] Mitochondrial deletions and mutations presumably cause DCM by altering myocardialATP generation.[14] 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.[25]
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 inejection fraction. The concept of cardiac remodeling was initially developed to describe changes that occur in the days and months following myocardial infarction.[26]
As DCM progresses, two compensatory mechanisms are activated in response to impaired myocyte contractility and reduced stroke volume:[12]
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.[citation needed]
Cardiac dilatation is a transverselyisotropic, irreversible process resulting from excess strains on themyocardium.[27] 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:[citation needed]
where is elastic volume stretch that is reversible and is irreversible, isotropic volume growth described by:[citation needed]
where is a vector, which points along acardiomyocyte'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 themyocardium, especially the ventricular myocardium, to support the bloodvolume overload in the chambers. Dilation manifests itself in an increase in total cardiac mass and cardiac diameter. Cardiomyocytes reach their maximum length of 150m in the endocardium and 130m in the epicardium by the addition ofsarcomeres.[27] 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.[citation needed]
As the ventricles enlarge, both the mitral and tricuspid valves may lose their ability to come together properly. This loss of coaptation may lead tomitral andtricuspid regurgitation. As a result, those with DCM are at increased risk ofatrial fibrillation. Furthermore, stroke volume is decreased and a greater volume load is placed on the ventricle, thus increasing heart failure symptoms.[12]
Generalized enlargement of the heart is seen upon normalchest X-ray.Pleural effusion may also be noticed, which is due to pulmonary venous hypertension.[28]
Theelectrocardiogram often showssinus tachycardia oratrial fibrillation,ventricular arrhythmias,left atrial enlargement, and sometimes intraventricular conduction defects and low voltage. Whenleft bundle-branch block (LBBB) is accompanied byright axis deviation (RAD), the rare combination is considered to be highly suggestive of dilated or congestive cardiomyopathy.[29][30]Echocardiogram shows left ventricular dilatation with normal or thinned walls and reducedejection fraction. Cardiaccatheterization andcoronary angiography are often performed to exclude ischemic heart disease.[28]
Genetic testing can be important, since one study has shown that gene mutations in the TTN gene (which codes for a protein calledtitin) are responsible for "approximately 25% of familial cases of idiopathic dilated cardiomyopathy and 18% of sporadic cases."[31] 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.[28]
Cardiac magnetic resonance imaging (cardiac MRI) may also provide helpful diagnostic information in patients with dilated cardiomyopathy.[32]
Drug therapy can slow down progression and in some cases even improve the heart condition. Standard therapy may include salt restriction,ACE inhibitors,diuretics, andbeta blockers.[12]Anticoagulants may also be used for antithrombotic therapy. There is some evidence for the benefits ofcoenzyme Q10 in treating heart failure.[33][34][35]
K-strophanthin may improve functional performance in patients with severecardiac decompensation whiledigoxin raises cardiac output and ejection fraction only at rest.[36]
Artificial pacemakers may be used in patients with intraventricular conduction delay, andimplantable 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.[37] 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.[38] 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.[39]https://www.ikard.pl/SVA/Archived 2021-11-16 at theWayback Machine
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.[37]
Although the disease is more common in African-Americans than in Caucasians,[40] it may occur in any patient population.
Therapies that support reverse remodeling have been investigated, and this may suggests a new approach to the prognosis of cardiomyopathies (seeventricular remodeling).[26][41]
In some types of animals, both a hereditary and acquired version of dilated cardiomyopathy has been documented.[citation needed]
Dilated cardiomyopathy is a heritable disease in some dog breeds, including theBoxer,Dobermann,Great Dane,Irish Wolfhound, andSt Bernard.[42] Treatment is based on medication, including ACE inhibitors,loop diuretics, andphosphodiesterase inhibitors.[citation needed]
An acquired variation of dilated cardiomyopathy describing a link between certain diets was discovered in 2019 by researchers atUniversity 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 inGolden Retrievers.[43] The diets associated with DCM were described as "BEG" (boutique, exotic-ingredient, and/or grain-free) dog foods,[44] as well as legume-rich diets.[45] 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[46]
Dilated cardiomyopathy is also a disease affecting some cat breeds, including theOriental Shorthair,Burmese,Persian, andAbyssinian. In cats, taurine deficiency is the most common cause of dilated cardiomyopathy.[47] 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.[citation needed]
There is also a high incidence of heritable dilated cardiomyopathy in captivegolden hamsters (Mesocricetus auratus), due in no small part to their being highlyinbred. 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.[48]
Tachycardia-induced cardiomyopathy is a reversible cause of heart failure and dilated cardiomyopathy. Tachycardia-induced cardiomyopathy should be considered in all patients with a dilated cardiomyopathy of uncertain origin and who have tachycardia or atrial fibrillation with a fast ventricular rate.
