Muscular dystrophy (MD) is a group of inherited disorders characterized by the progressive weakening and wasting of skeletal muscles. These genetic conditions result from defects in the proteins necessary for healthy muscle function. While MD is often recognized for its impact on muscles responsible for movement, it is a multisystem disorder that significantly affects the heart. The severity of cardiac involvement varies by the specific genetic type of MD, but heart complications are a major cause of illness and death across many forms of the disease.
The Role of Dystrophin in Cardiac Muscle
The heart is a muscle, and in many forms of MD, the genetic defect compromises the structural integrity of the heart muscle cells, or cardiomyocytes. The most well-studied example involves the protein dystrophin, which acts as a molecular scaffold. Dystrophin links the internal structural framework of the muscle cell to the membrane and the surrounding extracellular matrix.
In the absence of functional dystrophin, the muscle cell membrane becomes highly susceptible to damage from the normal stress of contraction. This continuous mechanical stress leads to micro-tears, which disrupts calcium regulation within the cell. The resulting cellular injury triggers degeneration and cell death.
To repair the damaged tissue, the body initiates a response that leads to the formation of scar tissue, known as fibrosis. Fibrosis involves the replacement of healthy, contractile heart muscle cells with stiff, non-contractile connective tissue. This progressive scarring impairs the heart muscle’s ability to pump blood effectively and often begins before any clinical symptoms are apparent.
Key Muscular Dystrophy Types Affecting the Heart
Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are the most common forms of MD associated with dystrophin deficiency, and both carry a high risk of cardiac disease.
Duchenne and Becker MD (Dystrophinopathies)
DMD involves the complete or near-complete absence of dystrophin. It almost universally leads to severe, progressive cardiomyopathy, typically starting in late childhood or early adolescence. For patients with DMD, heart failure is a leading cause of mortality.
BMD is caused by a partial deficiency of dystrophin, resulting in a milder skeletal muscle disease that progresses more slowly than DMD. Cardiac involvement in BMD is highly variable; some individuals may experience mild muscle weakness yet develop severe heart disease. Up to 70% of BMD patients may show signs of left ventricular dysfunction on imaging, sometimes with the heart condition being the primary manifestation of the disease.
Myotonic Dystrophy (DM)
Other genetic types of MD affect the heart through different mechanisms. Myotonic Dystrophy (DM), the most common adult-onset MD, frequently causes problems with the heart’s electrical system. This leads to conduction defects and arrhythmias. The genetic mutations in DM create toxic RNA aggregates that interfere with proteins involved in electrical signaling, causing issues like atrioventricular block.
Emery-Dreifuss Muscular Dystrophy (EDMD)
Emery-Dreifuss Muscular Dystrophy (EDMD) is characterized by contractures, progressive muscle weakness, and a high incidence of cardiac involvement. EDMD is strongly associated with progressive abnormalities in the heart’s conduction system. This can lead to severe bradycardia or heart block. Patients with EDMD often require a pacemaker due to the high risk of sudden death from these electrical defects.
Common Cardiac Manifestations
The most frequent clinical outcome of MD affecting the heart is cardiomyopathy. This condition primarily affects the left ventricle, the main pumping chamber, diminishing its ability to push oxygenated blood out to the body. As the left ventricle weakens, it can lead to the development of congestive heart failure.
Symptoms of heart failure in MD patients can be subtle or delayed due to limited physical activity resulting from skeletal muscle weakness. The lack of mobility means the heart is not significantly strained by exercise, often masking classic symptoms like shortness of breath or exercise intolerance. Instead, patients or caregivers might notice nonspecific signs such as excessive fatigue, weight loss, or difficulty sleeping.
Irregular heart rhythms, or arrhythmias, are another significant manifestation. They occur either as a result of underlying muscle damage or as a primary electrical issue. Dystrophinopathies like DMD and BMD are associated with both supraventricular and ventricular arrhythmias. In conditions like Myotonic Dystrophy and EDMD, conduction defects like heart block are particularly prevalent.
Monitoring and Treatment Strategies
Proactive and regular cardiac surveillance is a standard part of care for all individuals diagnosed with muscular dystrophy, particularly those with DMD or BMD.
Monitoring
Monitoring typically involves an annual assessment by a cardiologist. This includes a baseline electrocardiogram (ECG) to check the heart’s electrical activity and an echocardiogram (ECHO) to evaluate the heart’s structure and pumping function.
For high-risk patients like those with DMD, cardiac imaging is recommended yearly starting at the time of diagnosis, or no later than age six, to detect heart damage before symptoms appear. Cardiovascular magnetic resonance imaging (CMR) is often utilized. CMR provides a detailed view of the heart muscle and can detect early signs of fibrosis, sometimes before a decrease in function is seen on an ECHO.
Treatment
Medical treatment for MD-related heart disease focuses on managing heart failure using established medications. Angiotensin-converting enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) are typically the first line of therapy. They are often started preventatively, even before signs of heart dysfunction are evident, sometimes as early as age 10 in DMD patients. Beta-blockers are also used to reduce the heart’s workload and are initiated when there is evidence of ventricular dysfunction or persistent tachycardia.
In cases of significant heart failure, mineralocorticoid receptor antagonists, such as eplerenone, may be added. For patients with severe arrhythmias or conduction defects, especially those with EDMD or Myotonic Dystrophy, implantable devices may be necessary. These include pacemakers or implantable cardioverter-defibrillators (ICDs) to regulate the heart rhythm and prevent sudden cardiac death.