Stable heart health seen long-term for women with BMD, DMD mutations
Study: Monitoring likely not needed for most carriers of 2 MD types
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Among women who carry mutations that can cause Becker muscular dystrophy (BMD) or Duchenne muscular dystrophy (DMD), measures of heart health — important given that heart muscle damage is a key driver of death in most people with these muscular dystrophy (MD) types — are generally stable over time.
Those are the findings of a new long-term study, conducted by a research team in Denmark, that tracked heart health in 34 women with these two MD types.
“Over [seven] years, women carrying [disease-causing] DMD gene variants have very little or no progression of cardiac findings,” the researchers wrote. The team found scant evidence of arrhythmias, or an irregular heartbeat, and little scarring, known as fibrosis, among participants with DMD and BMD mutations in the natural history study.
According to the researchers, these findings suggest that frequent monitoring of heart health is probably not necessary for women who are carriers of these DMD types — though tracking of symptoms may be warranted for individuals who show signs of reduced heart function or scarring in the heart muscle, the team noted.
The study, “Natural history of cardiac involvement in women carrying pathogenic DMD gene variants: a 7-year longitudinal study,” was published in the Journal of Neurology.
BMD and DMD are both genetic disorders caused by mutations in the DMD gene, which encodes dystrophin, a protein vital for muscle health. The milder BMD is generally marked by lower-than-normal dystrophin levels, whereas DMD is generally more severe and characterized by total absence of functional dystrophin. Cardiac, or heart-related, problems are common in both diseases, and can be life-threatening.
The gene that encodes dystrophin is located on the X chromosome, one of the two sex-determining chromosomes. Biological females generally have two X chromosomes, while biological males have one X and one Y. As such, both BMD and DMD mainly affect boys and men; in women with two X chromosomes, a healthy copy of the gene on one X chromosome can usually compensate for a mutated copy on the second. Women with such variants are known as carriers, because they can pass the disease-causing mutation to their offspring.
Investigating heart health in women with BMD, DMD gene mutations
Although women who are BMD or DMD carriers are generally thought of as being unaffected by the disease, some studies have suggested that these individuals may be at increased risk of certain heart-related health problems.
However, according to the researchers, “it remains uncertain whether these subclinical findings are consistent over time or can reliably predict future dysfunction.” The team noted that “this uncertainty likely contributes to the absence of standardized guidelines to date for long-term cardiac monitoring in this group.”
To address this knowledge gap, a team led by scientists from the University of Copenhagen routinely tested carriers of these diseases with a battery of measures of heart health. The study included 19 carriers of DMD and 15 of BMD.
The results broadly indicated that average measures of heart health and heart function did not change substantially over a mean follow-up time of seven years. The only notable exception was an increase in a specific type of abnormal heart rhythm called ventricular premature contractions. Still, the researchers said this change is “likely not clinically meaningful” because this type of heart rhythm abnormality also tends to become more common with age in the general population. Additionally, cases of abnormal heartbeats representing a high burden to patients — with the number of heartbeats above a certain threshold — were uncommon among the partcipants.
Further, a statistical analysis showed no correlation between skeletal muscle involvement, namely muscle strength and muscle function, and cardiac dysfunction.
We observed that overall cardiac function, structure, and [abnormal heart rhythm] burden remained relatively stable on a group level, however, subtle yet clinically important changes were observed in a subset, emphasizing the importance of nuanced cardiac surveillance.
The researchers noted that most women had stable heart health, thought there were a few exceptions: Three women showed a decline in left ventricular ejection fraction, or LVEF, which is the percentage of blood the heart’s main pumping chamber pumps out with each heartbeat. In one, the decline was clinically meaningful. Also, two of the nine women with signs of scarring in the heart muscle throughout the study were additional found to have reduced heart function.
Overall, these data suggest that most women who are carriers of BMD or DMD probably don’t require frequent monitoring of heart health, though more stringent checks may be needed on a case-by-case basis for individuals who show symptoms or signs such as scarring or reduced LVEF.
“We observed that overall cardiac function, structure, and [abnormal heart rhythm] burden remained relatively stable on a group level, however, subtle yet clinically important changes were observed in a subset, emphasizing the importance of nuanced cardiac surveillance,” the scientists concluded.
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