The effects of Duchenne muscular dystrophy (DMD) on the heart are well-documented in the medical literature and are a strong reason for it to be managed in a multidisciplinary setting involving cardiologists.
Lee-Gannon and colleagues have written a paper that discusses the clinical management of DMD-associated cardiomyopathy; their study contains some excellent points on how this particular aspect of DMD should be approached. Another excellent study, written by de Souza et al, highlights the vital role that cardiologists play in improving clinical outcomes.
Cardiomyopathy: A Central Issue
“Over the past decade, cardiomyopathy has become the leading cause of mortality among patients with DMD,” Lee-Gannon et al wrote. This fact alone should challenge us to think about DMD-associated cardiomyopathy as a central medical issue that needs to be adequately addressed in DMD care.
The clinical management of DMD-associated cardiomyopathy has already gotten a boost from recent novel treatments, such as gene therapy, that slow down DMD disease progression as a whole. De Souza and colleagues presented the progress we have made in DMD therapies through the wide lens of history: “For the first time in many decades, or perhaps in the last 150 years, patients with DMD may have hope for genetic treatments that aim, at least partially, to stimulate dystrophin production and thereby slowing, or even stopping, disease progression.”
Read more about DMD epidemiology
Before we get to treating cardiac-related pathology, we first need to diagnose the extent of cardiac involvement. This can prove challenging, since cardiomyopathy progression differs between patients. Studies have shown that around a quarter of DMD patients develop cardiomyopathy by age 6; that figure swells to about 60% by 10 years of age. By age 18, almost all DMD patients can be expected to have some form of cardiac involvement. This is because cardiomyopathy progression accelerates as DMD patients become older.
What kind of symptoms can we expect to see in DMD patients when cardiac involvement becomes significant? Lee-Gannon et al explained, “Fatigue, nausea, dyspnea, palpitations, tachycardia, and chest discomfort may all represent symptomatic manifestations of DMD-associated cardiomyopathy, though many patients remain asymptomatic until later stages in life.”
Assessing the Problem
When it comes to assessing the severity of cardiac abnormalities, the common tools of the trade apply: ECG, transthoracic echocardiography, and cardiac MRI (cMRI). The ever-useful ECG usually demonstrates tall R waves and deep Q wave abnormalities in the anterolateral leads, which typically signifies that lateral wall scarring has occurred.
Concerning echocardiography, de Souza and colleagues wrote, “Transthoracic echocardiography is the main examination for cardiac monitoring in DMD considering the lower cost and greater availability of the method. It should be performed annually in all DMD patients since diagnosis, regardless of symptoms.” Its primary use in DMD is to screen for preclinical changes.
Although transthoracic echocardiography has its uses, it tends to underestimate left ventricular volume and function. Hence, cMRI is preferable as an imaging modality. It allows physicians to assess cardiac health parameters more accurately, such as cardiac size, mass, and function.
In addition, the presence of late gadolinium enhancement in cMRI can indicate various degrees of fibrotic scarring, myocardial inflammation, and myocyte damage. Strain imaging should be able to reveal useful information regarding left ventricular ejection fraction, as well as cardiac dysfunction.
Treating Cardiomyopathy in DMD
Regarding treatment, both papers recommend angiotensin-converting-enzyme (ACE) inhibitors as first-line therapy. A study involving DMD patients demonstrated that the use of ACE inhibitors significantly decreased the percentage of patients who developed a reduced ejection fraction (<45%). In addition, the cohort of DMD patients receiving ACE inhibitors demonstrated lower mortality rates as well.
Aside from ACE inhibitors, Lee-Gannon et al listed 3 other major drug classes used to treat DMD-associated cardiomyopathy: beta-adrenergic receptor blockers, mineralocorticoid receptor antagonists, and corticosteroids.
Read more about DMD treatment
The last resort available to treat DMD-related cardiomyopathy is heart transplantation. However, this procedure is not without its risks, considering that DMD patients who may need a heart transplant tend to have significant skeletal muscle wasting and restrictive lung disease. Hence, this procedure has only been attempted in a limited number of DMD patients. As for DMD patients who have undergone the procedure, reports suggest that short- and long-term survival rates are very favorable.
De Souza and colleagues raised a number of thought-provoking points regarding the importance of access to care for DMD patients. They wrote, “For many patients, it still takes a long time to gain access to a cardiologist, and when they do, they do not have adequate regular follow-up, which is fundamental in a pathology that progresses daily.”
Without access to a cardiologist and basic diagnostic equipment, none of what is written in this article will matter. This is of particular concern in developing countries, especially in rural areas where healthcare access is limited.
In addition, as healthcare professionals, it is our duty to ensure that our patients receive the support they need to be as socially integrated as possible. De Souza et al commented, “The social integration and development of these patients must be encouraged, and in this aspect, organizations for patients with rare diseases and their families are essential.”
Lee-Gannon T, Lehrenbaum H, Sheth R, Mammen PPA. Clinical management of DMD-associated cardiomyopathy. In: Mattsson G, Magnusson P, eds. Cardiomyopathy – Disease of the Heart Muscle. IntechOpen; 2021:chap 14. Accessed November 9, 2021.
de Souza F, Bittar Braune C, Dos Santos Nucera APC. Duchenne muscular dystrophy: an overview to the cardiologist. Expert Rev Cardiovasc Ther. 2020;18(12):867-872. doi:10.1080/14779072.2020.1828065