Full citation: Landfeldt E, Alemán A, Abner S, Zhang R, Werner C, Tomazos I, Lochmüller H, Quinlivan RM, Wahbi K. Predictors of cardiac disease in duchenne muscular dystrophy: a systematic review and evidence grading. Orphanet J Rare Dis. 2024 Sep 28;19(1):359.
The heart is the hardest working muscle in a person’s body. The lack of dystrophin with Duchenne muscular dystrophy (DMD) impacts all muscles in the body, including the heart. This can lead to the cardiac-related (heart-related) symptoms of DMD. Since the use of ventilation (breathing) support has been introduced for people with DMD, cardiac symptoms have become the major cause of death for people with DMD. Unfortunately, the symptoms of heart disease include fatigue (being tired), stomach pain, or inability to do regular daily activities. These are all regular symptoms of DMD, and so are often not recognized as a symptom of emerging cardiac symptoms for people with DMD.
Being able to predict cardiac symptoms of DMD may help to prevent or treat the serious cardiac symptoms of DMD. The authors of this study wanted to find out if there are ways to predict cardiac disease in people with DMD. They did a thorough review of all the publications available in medical journals from the year 2000 until December 31, 2022, that identified death as being due to “cardiac involvement” of DMD. A total of 33 articles were included in the publication based on the high quality of evidence. Below are the high level predictors of cardiac disease in DMD presented.
Predictors of Cardiac Disease in DMD
There are many different types of cardiac symptoms in DMD, such as cardiomyopathy, heart failure, and others. For ease of reading, we summarize cardiomyopathy (which is a group of primary disease of the heart muscle) and other cardiac symptoms in general, rather than describing the specific type of symptom.
Cardiac Medication
People with DMD were found to have an improvement in a range of cardiac symptoms due to treatment with cardiac medications known to be used for managing cardiac disease.
DMD Mutations
Some DMD mutations are more likely to be associated with cardiac symptoms.
- In a study of 47 people with DMD and Becker muscular dystrophy who had genetic analysis done, mutations involving exons 12, 14, 15, 16, and 17 were found to be associated with onset of cardiomyopathy while people with impacted exons 51 and 52 had a lower risk of cardiac involvement.
- In another study of 181 Japanese people with DMD, mutations in the Dp116 coding region had a longer time with no cardiac involvement than those with other mutations.
- In a study of 40 Brazilian people with DMD, those with exons 45, 46, 47, 48, 49, 50, or 52 impacted had increased cardiac involvement.
- In a study of 35 non-ambulatory French patients with DMD, people with DMD mutations amenable to exon 53 skipping had less cardiac manifestations
Genetic Modifiers
A genotype is the genetic makeup of an organism and determines what characteristics are expressed by the organism. Certain genotypes are associated with increased cardiomyopathy.
- In a study of 178 Italians with DMD, people with the LTBP4 rs10880 CC/CT genotype had a higher risk of cardiomyopathy compared with the TT genotype (p < 0.027).
- In 77 Japanese patients with DMD, the ACTN3 null genotype had no cardiac dysfunction at 13.4 years whereas those with the ACTN3 positive genotype had no cardiac dysfunction at 15.3 years.
Glucocorticoid Exposure
Several observational studies (a study that has no treatment, it is just based on observing the regular standard of care a person receives), found a positive impact of glucocorticoids like deflazacort or prednisone on cardiac symptoms. Glucocorticoid treatment was associated with better cardiac symptoms or functioning in six observational studies, two retrospective chart reviews and in five observational studies and two cohort studies.
People with DMD not treated with glucocorticoids were found to have higher risk for developing cardiomyopathy. In an observational study of the 86 Canadians, no one being treated with glucocorticoids died from heart failure, whereas 22% of untreated with glucocorticoids did die of heart failure. Other cardiac-related symptoms were also found to be improved with glucocorticoid treatment in other studies.
Muscle Strength
One medical chart review found a correlation between upper body strength and cardiac manifestations in 77 people with DMD in the United States.
Breathing Support
One medical chart review found that full-time breathing support had a decrease in cardiac function.
Conflict of Interest: Studies are often funded by pharmaceutical companies. This does not mean that the data has been influenced by the company, but it is important that the authors of studies let you know how the study is funded.
Some of the authors in this study are employees of PTC Therapeutics, which currently has two approved medicines for treating Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene in ambulatory patients aged 2 years and older: Translarna™ (ataluren) and Emflaza® (deflazacort). Some of the authors have received grants from PTC and other companies. You can see all of the “conflicts of interest” at the bottom of the publication.
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