New Cardiac Insights Show How Neuromuscular Diseases Affect the Heart

Neuromuscular diseases can impact muscles throughout the body, including the heart. Because heart health is essential to overall health, researchers are working to understand how different neuromuscular diseases affect the heart and why effects can vary between people with the same diagnosis.

There are still open questions, but over the last decade, scientists have learned more about cardiac phenotypes in neuromuscular diseases, leading them to recognize the importance of early cardiac screening. Coupled with advances in the treatment and management of heart disease, this could deliver better outcomes for people living with many neuromuscular conditions.

Understanding the impact on the heart

In medicine, a phenotype is how a disease shows up in a person — the signs, symptoms, and test results that doctors can observe and measure. Understanding the cardiac phenotypes associated with a disease helps doctors identify how serious the impacts are and how to treat them.

Common cardiac phenotypes in neuromuscular diseases include:

• Arrhythmias — irregular heart rhythms that can lead to palpitations, fainting, or sudden cardiac events
• Dilated cardiomyopathy — when the heart enlarges and pumps blood less effectively
• Hypertrophic cardiomyopathy — when the heart muscle thickens, stiffens, and doesn’t relax well between beats
• Myocardial fibrosis — scar tissue buildup that stiffens the heart and impairs its ability to function

While some diseases, such as Duchenne muscular dystrophy (DMD), have near-universal cardiac involvement, others are less likely to affect the heart but still carry a risk.

The way neuromuscular diseases affect the heart varies widely depending on factors such as the specific diagnosis and underlying genetics.

“Different neuromuscular conditions have distinct genetic causes,” says Angela Lek, PhD, MDA’s Chief Research Officer. “When a gene is altered or missing, and that gene also plays a role in heart muscle function, it can lead to cardiac complications that manifest in different ways.”

As a result, cardiac involvement can differ significantly, even among individuals with the same diagnosis. Some people may experience a single cardiac phenotype, while others develop a combination of complications over time.

Given this variability, the clinical implications are significant. “Cardiac disease is a leading cause of morbidity and mortality in several neuromuscular conditions, including DMD,” Dr. Lek adds. “That’s why it’s essential for patients to have access to multidisciplinary care, including both neurology and cardiology expertise.”

Growing knowledge

The last few years have seen significant changes in our understanding of cardiac involvement in neuromuscular diseases and how it’s treated.

Genetics in neuromuscular diseases

Importantly, we now have a better understanding of the role of genetics. (Find downloadable fact sheets about genetics in neuromuscular diseases on MDA’s Educational Materials page.)

“We’re doing a better job of taking the broad groups of muscular dystrophies and trying to understand which genes are most at risk and for which cardiac phenotypes,” says Chet Villa, MD, Professor of Pediatrics and Cardiac Director of the Neuromuscular Clinic at Cincinnati Children’s Hospital Medical Center, an MDA Care Center. “Some patients are primarily at risk for cardiac dysfunction and heart failure, while others are more prone to arrhythmias. We now know that specific genetic mutations carry very different cardiac risks.”

Both the genetic mutation and the underlying disease pathway (how a disease progresses) influence how the heart can be affected.

“As we better understand the genetic drivers of these diseases, we can more accurately categorize them and anticipate how they may affect the heart,” says Forum Kamdar, MD, Associate Professor of Medicine in the Cardiovascular Division of the Department of Medicine at the University of Minnesota, an MDA Care Center. “This opens the door to more targeted and personalized treatment strategies.”

Cardiac screening for all neuromuscular diseases

Screening is another area of progress. In the last few years, scientific advances in genetics, imaging, and clinical care have enabled clinicians to better screen for and monitor the heart in patients with neuromuscular diseases.

“There have been major advances in cardiac imaging, especially cardiac MRI,” Dr. Villa says. “We can now detect cardiac muscle abnormalities before measurable dysfunction occurs, which has changed how we track disease progression.”

These screening advances have gone from reactive to proactive. “We now recognize that cardiac involvement often occurs earlier and more quietly than we once appreciated,” says Dr. Kamdar. “Advances in imaging, particularly cardiac MRI with contrast, have allowed us to detect subtle changes in the heart muscle before patients develop symptoms. We can now see myocardial fibrosis (scar tissue) at an early stage, and we know that this fibrosis can precede measurable weakness of the heart muscle. In some cases, it can even help predict future risk of heart failure or arrhythmias.”

As an example, she points to some subtypes of limb-girdle muscular dystrophy (LGMD) that were previously thought not to have cardiac involvement. “Advanced imaging like cardiac MRI is now revealing cardiac fibrosis in patients previously considered low risk.”

The result is that screening is being recommended earlier and for everyone with a neuromuscular condition.

“Instead of waiting for symptoms to appear, many patients now establish care with a cardiologist at the time of diagnosis and are followed regularly in interdisciplinary clinics. Early detection allows us to intervene sooner and potentially slow progression,” Dr. Kamdar says.

Progress in treatment and management

Advances in genetics and screening are even more impactful when combined with advances in cardiac treatment and management.

Optimizing heart failure therapies

One major advance is the earlier and more tailored use of heart failure therapies.

“Medications such as ACE inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors are increasingly being used thoughtfully in neuromuscular populations,” Dr. Kamdar says. “Rather than waiting for significant heart dysfunction, we are asking an important question: When is the optimal time to begin these therapies to slow disease progression and protect the heart long term?”

More advanced cardiac therapy options

In addition, when faced with heart failure, neuromuscular disease patients may have more options than in the past.

“Historically, patients with significant neuromuscular disease were often not offered advanced cardiac therapies like ventricular assist devices, a heart pump, or heart transplantation,” Dr. Villa says. “Now, that perspective is changing. Centers are starting to offer some of these therapies for selected patients with muscular dystrophy, particularly when respiratory issues can be managed appropriately.”

Improving care management

Another area of improvement is in care management. According to Dr. Kamdar, multidisciplinary care, such as at MDA Care Centers, is an important advancement for people living with neuromuscular diseases.

“This model reduces logistical barriers, improves communication among providers, and allows us to screen for and monitor heart disease in a coordinated way,” she says.

These advances are important because the treatment landscape continues to evolve.

“It’s an exciting time because biotechnology and pharmaceutical companies are investing in novel therapies for neuromuscular diseases,” Dr. Kamdar says. “As these treatments evolve, protecting the heart becomes even more critical to improving long-term outcomes and quality of life for patients and families.”

Remaining gaps and future research

Despite this progress, there is still much that’s not known about cardiac involvement and how to treat it. Much of what we know about the treatment of heart failure and arrhythmias comes from non-neuromuscular patients, who may have different phenotypes.

“For example, if patients have functional limitations due to their neuromuscular disorder, they may not show early heart failure symptoms such as exertional shortness of breath,” Dr. Kamdar says. “Future cardiac trials for neuromuscular patients should include the right endpoints, like fibrosis, arrhythmia burden, muscle involvement or progression, functional capacity, and quality of life.”

Increasingly, cardiac endpoints are being included in neuromuscular clinical trials to measure drug efficacy. This is especially important for therapies like gene therapy and exon skipping that are often targeted to skeletal muscle. Cardiac endpoints allow researchers to see whether therapies developed for skeletal muscle also benefit the heart. “This shift acknowledges that protecting the heart is essential to improving survival and quality of life,” Dr. Kamdar says.

Better surveillance tools, especially early in the disease course, are also important. “We need better biomarkers that can predict cardiac risk in patients living with neuromuscular diseases — for example, markers of early cardiac fibrosis,” Dr. Kamdar adds. “This can allow for early targeted treatment. My group and others are working toward this.”

Ultimately, a better understanding of cardiac phenotypes in neuromuscular diseases must include being able to simulate them in the lab. Dr. Kamdar is making strides by 3D bioprinting human heart tissue using patient-derived stem cells.

“This allows us to study what happens at very early stages when there’s a mutation in the dystrophin gene,” she says. “One of my NIH-funded programs examines how we might intervene early to prevent heart disease development and understand how heart failure progresses. We can pressurize these systems and simulate the mechanical stresses that occur in DMD heart failure, which is very hard to do in animal models and difficult using patient samples alone.”

Addressing the gaps

MDA plays a critical role in advancing research, such as Dr. Kamdar’s, focused on understanding cardiac manifestations and addressing key gaps in neuromuscular disease care. Over the past five years, MDA has funded six grants totaling more than $900,000 to support research on cardiac phenotypes across neuromuscular disorders.

“Some of the research MDA is supporting is focused on developing advanced imaging tools that can detect heart inflammation and metabolic dysfunction earlier than standard approaches,” says Dr. Lek. “Earlier detection enables earlier intervention, which can ultimately lead to better outcomes for patients.”

Additional MDA-funded efforts are aimed at improving cardiac muscle function in diseases such as DMD, advancing our understanding of fibrosis and myocardial stiffness as key drivers of cardiac disease in conditions like Friedreich ataxia (FRDA or FA), and expanding access to advanced treatment options, including heart transplantation.

Traditionally, this type of research has been underfunded, and MDA’s support has already made a difference. In 2022, MDA awarded a Clinical Research Network Grant to Dr. Kamdar to study data on healthcare for patients with muscular dystrophy and advanced heart failure. She found that, despite progressing to end-stage heart failure, these patients were rarely offered advanced therapies like heart transplantation or ventricular assist devices — the assumption being that their physical limitations made them poor candidates. Dr. Kamdar’s research built the evidence base needed to change that assumption.

“As an advanced heart failure and transplant cardiologist, applying for heart-specific grants can be difficult because those programs typically focus on very large patient populations — general heart failure research includes many patients, whereas rare neuromuscular diseases involve far fewer patients,” Dr. Kamdar says. “MDA funding allows us to identify important questions that are critical for advancing research in neuromuscular disorders, especially cardiac research.”

Access to multidisciplinary care

It is important for people with neuromuscular diseases to be seen and tracked by a cardiologist familiar with their condition to get ahead of potential issues. “Current guidelines recommend cardiovascular screening for every patient diagnosed with a neuromuscular disorder, especially higher-risk groups,” Dr. Kamdar says.

Many MDA Care Centers have cardiologists on staff with neuromuscular expertise. An MDA Care Center care team can also aid in screening for and tracking other symptoms, such as breathing and sleep disorders, and risk factors for coronary artery disease, which can put additional strain on the heart.

Ultimately, tracking cardiac phenotypes in neuromuscular diseases is a team effort.

“Coming together as a clinical and research community is essential to advancing cardiac care for individuals living with neuromuscular diseases,” Dr. Kamdar says.

Chris Anselmo is an author who lives in Connecticut with limb-girdle muscular dystrophy type 2B (LGMD2B).

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Know the Heart Risks

Researchers and neuromuscular specialists increasingly recognize that cardiac involvement occurs in more neuromuscular diseases — and often earlier in the disease course — than previously appreciated. As a result, proactive cardiovascular screening is now recommended for all individuals diagnosed with neuromuscular disorders, with particular attention to those in higher-risk groups.

Which groups are at higher risk?

Risk varies depending on the specific diagnosis and underlying genetic cause, but several neuromuscular conditions are clearly associated with cardiac involvement:

Dystrophinopathies

Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and symptomatic carriers (typically females with one dystrophin gene mutation) can all develop cardiac disease. In DMD, cardiomyopathy is nearly universal over the lifetime and often begins in childhood. Cardiac involvement in BMD and carriers is variable but can be significant and progressive.

Limb-girdle muscular dystrophies (LGMD)

Cardiac risk varies by subtype. Higher- risk forms include sarcoglycanopathies and FKRP-related LGMD, which may involve dilated cardiomyopathy and/or conduction abnormalities beginning in childhood or early adulthood. Other LGMD subtypes have minimal cardiac involvement, but baseline screening is still recommended.

Myotonic dystrophy (DM)

DM types 1 and 2 are strongly associated with cardiac conduction defects and arrhythmias, which can be asymptomatic yet life-threatening. Structural cardiomyopathy can also occur, and abnormalities may develop early in the disease course.

Friedreich ataxia (FRDA or FA)

FRDA commonly presents in childhood or adolescence and is associated with hypertrophic cardiomyopathy, which can progress to dilation and heart failure. Cardiac disease is a major contributor to morbidity and mortality.

Titinopathies and laminopathies

Disorders caused by mutations in TTN and LMNA genes often have prominent cardiac involvement, sometimes out of proportion to skeletal muscle weakness. These conditions carry a high risk of dilated cardiomyopathy, conduction system disease, and malignant arrhythmias and may require early intervention with a pacemaker or implantable cardioverter-defibrillator (ICD).

Emery-Dreifuss muscular dystrophy (EDMD)

Characterized by early-onset contractures and muscle weakness, EDMD carries a high risk of cardiac conduction defects, arrhythmias, and dilated cardiomyopathy, often requiring pacemaker or ICD placement.

Danon disease

This X-linked disorder is associated with severe hypertrophic cardiomyopathy, frequently presenting in adolescence and often progressing rapidly to heart failure. Many patients require advanced therapies, such as a heart transplant.

Pompe disease

Infantile-onset forms of Pompe, in particular, are associated with hypertrophic cardiomyopathy early in life. While enzyme replacement therapy has improved outcomes, ongoing cardiac monitoring remains essential for all forms of Pompe.