Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.
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. It is a type of cardiomyopathy, a group of diseases that primarily affects the heart muscle. The diagnosis may be supported by an electrocardiogram, chest X-ray, or echocardiogram.
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, blood thinners 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.
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. The most recent figures indicate that about 3 per 1,000 men and 1 per 1,000 women are affected. 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. It can also occur in children and is the most common type of cardiomyopathy in this age group.
DCM predominantly affects the left ventricle as it has the highest load. Comparing the left to the right, the right ventricle only needs to circulate blood to the pulmonary arteries, which are relatively close in proximity. The left ventricle however, is responsible for pumping blood to the remaining parts of the body that are not the lungs. This load difference results in the cardiac muscle of the left ventricle getting more wear and stress throughout the course of a day, resulting in a higher vulnerability to DCM than the right ventricle.
Signs and symptoms
Dilated cardiomyopathy develops insidiously, and may not initially cause symptoms significant enough to impact on quality of life. Nevertheless, many people experience significant symptoms. These might include: Shortness of breath Syncope (fainting) Angina, but only in the presence of ischemic heart disease
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.
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 possibly mediated through an immunologic mechanism. Specific autoantibodies are detectable in some cases.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: Chagas disease, due to Trypanosoma cruzi. This is the most common infectious cause of dilated cardiomyopathy in Latin America Pregnancy: Dilated cardiomyopathy occurs late in gestation or several weeks to months postpartum as a peripartum cardiomyopathy. It is reversible in half of cases. Alcohol use disorder (alcoholic cardiomyopathy) Non-alcoholic toxic insults include administration of certain chemotherapeutic agents, in particular doxorubicin (Adriamycin), and cobalt. Thyroid disease Inflammatory diseases such as sarcoidosis and connective tissue diseases Tachycardia-induced cardiomyopathy Muscular dystrophy Tuberculosis: 1 to 2% of TB cases. Autoimmune mechanisms 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 Genetic associations with dilated cardiomyopathy Type OMIM Gene Locus CMD1A
LMNA 1q21 CMD1B
unknown (TMOD1 candidate) 9q13 CMD1C
LDB3 10q22-q23 CMD1D
TNNT2 1q32 CMD1E
SCN5A 3p CMD1F
6q23 CMD1G
TTN 2q31 CMD1H
2q14-q22 CMD1I
DES CMD1K
6q12-q16 CMD1L
SGCD 5q33 CMD1M
CSRP3 11p15.1 CMD1N
TCAP 17q12 CMD1O
ABCC9 12p12.1 CMD1P
PLN 6q22.1 CMD1Q
7q22.3-q31.1 CMD1R ACTC 15q14 CMD1S MYH7 14q12 CMD1T TMPO 12q22 CMD1U PSEN1 14q24.3 CMD1V PSEN2 1q31-q42 CMD1W
VCL 10q22-q23 CMD1X FCMD 9q31 CMD1Y
TPM1 15q22.1 CMD1Z
TNNC1 3p21.3-p14.3 CMD1AA
ACTN2 1q42-q43 CMD2A
TNNI3 19q13.4 CMD3A
TAZ Xq28 CMD3B
DMD Xp21.2 ALPK3 15q25.3
About 25–35% of affected individuals have familial forms of the disease, with most mutations affecting genes encoding cytoskeletal proteins, while some affect other proteins involved in contraction. The disease is genetically heterogeneous, but the most common form of its transmission is an autosomal dominant pattern. 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. Some relatives of those affected by dilated cardiomyopathy have preclinical, asymptomatic heart-muscle changes.
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.
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: Frank-Starling law 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. 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:
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 sarcomeres. 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.
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. 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.
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." 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.
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, ACE inhibitors, diuretics, and beta blockers. Anticoagulants may also be used for antithrombotic therapy. There is some evidence for the benefits of coenzyme Q10 in treating heart failure.