Course:MEDG550/Student Activities/DCM
Dilated cardiomyopathy is a condition where there is weakening and stretching of heart muscles, causing spaces in the heart (chambers) to expand[1]. The large chambers make it difficult for the heart to function properly, which results in less blood being pumped to the body[1]. Dilated cardiomyopathy can progress towards a long-term condition known as heart failure, where the heart is not pumping enough blood to meet the body's needs. Heart failure can be life-threatening or lead to hospitalization in severe cases[1].
Clinical Characteristics
Signs and Symptoms
Some of the common signs and symptoms of dilated cardiomyopathy include:
- Chest pain
- Swelling
- Fatigue
- Shortness of breath
- Fainting
- Palpitations (racing or pounding heartbeat)
- Dizziness
Individuals with dilated cardiomyopathy may not experience all of these symptoms, as it can differ on a case-by-case basis[2].
Other Complications
Some genetic causes of dilated cardiomyopathy can also lead to an irregular heartbeat, or arrhythmia, where electrical signals that coordinate an individual's heartbeat are not functioning properly, leading to a fast or slow heartbeat[3]. Individuals with dilated cardiomyopathy are also at a greater risk of blood clotting, which can result in a stroke[3].
Diagnosis
The symptoms of dilated cardiomyopathy can look like many other heart conditions, so a diagnosis is necessary to ensure that proper care is provided for this condition. A diagnosis for dilated cardiomyopathy is established when an individual is found to have a very large left ventricle (an important heart chamber) and very low blood levels pumped from the heart to the body[3]. Both of these observations can be found in an individual with dilated cardiomyopathy by using heart imaging tests to produce images of the heart and analyze its structure and function. The two main heart imaging tests used to diagnose dilated cardiomyopathy are an echocardiogram and a cardiac magnetic resonance imaging (MRI)[3].
Nongenetic Causes
Acquired Dilated Cardiomyopathy
There are many causes for the symptoms associated with dilated cardiomyopathy, some of which may be due to separate problems that result in dilated cardiomyopathy. These causes are referred to as secondary or acquired dilated cardiomyopathy[3]. The most common cause of acquired dilated cardiomyopathy is restriction of blood and oxygen flow to the heart muscle, which can occur for individuals with coronary artery disease and have had a previous heart attack[3]. Other less common acquired causes include high blood pressure (hypertension), diabetes, thyroid disease, viral infection, and substance use[3].
Syndromic Dilated Cardiomyopathy
A syndrome is defined as a group of different symptoms that are found to commonly occur together[3]. Individuals with certain genetic syndromes or conditions can experience symptoms of dilated cardiomyopathy in addition to other symptoms or features unrelated to the dilated cardiomyopathy. Some examples of conditions that can include dilated cardiomyopathy as a feature include: Carvajal syndrome and Barth syndrome.
Genetic Causes
Genetic Dilated Cardiomyopathy
Genes are units of information stored in the body that determine individual traits. Changes in a gene are known as mutations, which can impact the function of the gene and as a result, an individual's traits. Genetic causes of dilated cardiomyopathy are due to mutations in genes that affect the production of heart muscles[3].
Every person has two copies of a gene, with one copy coming from each parent. Mutations in genes are passed down to children through a process called inheritance. Since an individual has half of their genes coming from each parent, a specific mutation has a 50% chance of being passed down from a parent to their child. The majority of mutations that are known to cause dilated cardiomyopathy follow an inheritance pattern that is autosomal dominant[4]. This means that an individual only needs one out of two gene copies to have a mutation associated with dilated cardiomyopathy to be affected with the condition. As a result, an individual affected by genetic dilated cardiomyopathy would have a 50% chance of having an affected child.
Some individuals with a genetic mutation associated with dilated cardiomyopathy do not develop symptoms, as the same mutation can have different effects on different individuals. This is a phenomenon known as reduced penetrance, as mutations in genes associated with dilated cardiomyopathy do not always result in noticeable symptoms in an affected individual. Individuals with genetic dilated cardiomyopathy tend to experience symptoms in adulthood (usually between age 20 to 60), but in some rare cases, symptoms may be seen in childhood[3]. Genetic dilated cardiomyopathy is considered to be one of the more common heart conditions and is present in about 1 in every 2500 individuals within the general population[4].
Genetic Testing
Genetic testing for dilated cardiomyopathy allows for identification of a mutation in a gene to establish a genetic cause for the condition. Since genetics are shared with biological family members, finding a genetic cause for dilated cardiomyopathy means that relatives of an affected individual could also have the same mutation, which could place them at risk of developing dilated cardiomyopathy as well[4]. Finding a genetic cause for dilated cardiomyopathy does not impact the diagnosis or management of the condition, but is important for identifying at-risk family members so that they can receive treatment and make lifestyle adjustments[4]. Individuals that have been diagnosed for dilated cardiomyopathy or have a significant family history of heart conditions are eligible to receive genetic testing[4]. The process of genetic testing involves providing a saliva or blood sample, which is analyzed for mutations in genes associated with dilated cardiomyopathy to determine if there is a genetic cause[2].
Results
There are three possible results for a genetic test:
Positive
A positive result means that a mutation that is strongly linked to causing dilated cardiomyopathy has been has been found in the tested genes[3]. For a diagnosed individual, this result can provide an explanation for their condition. For an unaffected individual, this result means that there is an increased risk of developing dilated cardiomyopathy in their lifetime, although it is not guaranteed (due to reduced penetrance, as mentioned previously). It is recommended that unaffected individuals have regular heart evaluations with a cardiologist
to monitor and treat the condition if it is detected[3]. First degree relatives (i.e. siblings, parents, or children) of the individual that tests positive are able to receive a genetic test, whether or not they are affected by the condition. It is important to note that the genetic test that relatives receive afterwards only tests for the specific mutation that was found in the individual that tested positive[3].
Negative
A negative result means that no mutation that can explain a genetic cause for dilated cardiomyopathy was found in the tested genes[3]. However, this result does not mean rule out a genetic cause for dilated cardiomyopathy in diagnosed individuals or unaffected individuals with a significant family history of heart conditions. This is because genetic testing has limitations, as there may be undiscovered genes that were not analyzed by the test or mutations that were found and are currently considered harmless, but are actually contributing to the condition[3]. Affected individuals are advised to continue with current treatment and unaffected individuals should continue with heart evaluations with a cardiologist. The difference between a positive and negative test for first degree relatives is that they are not eligible for genetic testing, but are recommended to continue with heart evaluations as well[3].
Variant of Uncertain Significance (VUS)
This result means that a genetic mutation was found, but at the time that the test was done, there was not be enough information to label it as the cause for dilated cardiomyopathy or as a harmless mutation[3]. Diagnosed and unaffected individuals with this result are recommended to continue with heart evaluations and current management, based on their symptoms[3]. First degree relatives of an individual with this result are likely unable to receive genetic testing, but it is recommended that they continue with heart evaluations. In some cases where there is a family history of heart conditions, first degree relatives might be eligible to receive genetic testing if the mutation is consistently found in family members that also similar symptoms[3].
Associated Genes
Below is a list of genes commonly found to be associated with dilated cardiomyopathy, which may be analyzed on a genetic test. [3]
| Gene | % of Dilated Cardiomyopathies |
|---|---|
| TTN | 20% |
| LMNA | 6% |
| MYH7 | 4% |
| FLNC | 4% |
| BAG3 | 3% |
| TNNT2 | 3% |
| RBM20 | 2% |
| SCN5A | 2% |
Genetic Counselling
Genetic counsellors are trained genetics healthcare providers that can interpret the results of a genetic test, explain what the results mean for an individual and their family, assist with decision making and informing family members about relevant results, and provide emotional support in adapting to the situation.
Management
Evaluation
Laboratory testing is often done before making a genetic diagnosis to determine if there is a secondary acquired cause for dilated cardiomyopathy. This includes HIV tests, iron studies for hemochromatosis, and thyroid function tests[3]. Alcohol level and urine toxicology may be checked if substance use is the suspected cause[3]. If a genetic cause is determined, an electrocardiogram (ECG) might be done to observe the electrical signal from the heart, as some cases of genetic dilated cardiomyopathy involve abnormal heart rhythm[3].
Treatment
There is no cure for dilated cardiomyopathy, but management involves treating the symptoms of heart failure and improving overall heart function. Medications such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers relieve symptoms and reduce the chance of heart failure-related death or hospitalization[2]. Anticoagulants can also help reduce the risk of stroke[2]. An implantable cardioverter defibrillator (ICD) is often used for individuals that experience heartbeat abnormalities (arrhythmias) due to dilated cardiomyopathy[2]. A pacemaker device may also be implanted through cardiac resynchronization therapy (CRT) to improve heart performance and relieve symptoms in certain individuals with severe heart failure[2]. Antiviral drugs should be used in cases where dilated cardiomyopathy is caused by a viral infection and immunosuppression therapy is appropriate for when there is inflammation of heart muscle[2]. In severe cases, heart transplant may be required for survival, but it can be difficult to find a suitable donor[1].
Lifestyle
Living with dilated cardiomyopathy can require changes to one's lifestyle. Light to moderate exercise has been shown to help with heart failure[2]. However, individuals with more severe cases of heart failure have reduced exercise tolerance and in cases where implantable devices are used to monitor heartbeat, restrictions may be placed on exercise and activity[1]. A cardiologist should be consulted for exercise and activity guidelines. A diet consisting of low salt and fluid is also recommended to prevent heart failure[1].
Additional Resources
For a general resource for living with dilated cardiomyopathy:
For more information about services for heart conditions in BC:
For more information on the genetics of dilated cardiomyopathy:
For more information about genetic counselling or to find a genetic counsellor:
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Mahmaljy, H., Yelamanchili, V. S., & Singhal, M. (2022). Dilated Cardiomyopathy. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK441911/
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Schultheiss, H.-P., Fairweather, D., Caforio, A. L. P., Escher, F., Hershberger, R. E., Lipshultz, S. E., Liu, P. P., Matsumori, A., Mazzanti, A., McMurray, J., & Priori, S. G. (2019). Dilated cardiomyopathy. Nature Reviews Disease Primers, 5(1), 32. https://doi.org/10.1038/s41572-019-0084-1
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 Hershberger, R. E., & Jordan, E. (1993). Dilated Cardiomyopathy Overview. In M. P. Adam, D. B. Everman, G. M. Mirzaa, R. A. Pagon, S. E. Wallace, L. J. Bean, K. W. Gripp, & A. Amemiya (Eds.), GeneReviews®. University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1309/
- ↑ 4.0 4.1 4.2 4.3 4.4 Reichart, D., Magnussen, C., Zeller, T., & Blankenberg, S. (2019). Dilated cardiomyopathy: From epidemiologic to genetic phenotypes: A translational review of current literature. Journal of Internal Medicine, 286(4), 362–372. https://doi.org/10.1111/joim.12944