As a young cardiologist, Dr. Denis Duboc didn’t think it made much sense that his fellow specialists would treat patients with myotonic dystrophy (DM) and other muscle diseases as if they were treating other cardiology patients. Since becoming a researcher, his work has focused on better ways to provide care for DM patients.

After completing medical school and a residency in cardiology at France’s Paris Descartes University, Dr. Duboc’s interest in understanding the cardiovascular problems associated with muscle disease patients led him to earn a doctorate in the research lab of the noted muscle disease expert Michel Fardeau at the French National Institute of Health and Medical Research, also known as INSERM. His research has since made the case for why it is important for cardiologists to treat DM patients with cardiovascular problems differently than other cardiology patients.

“It was very difficult to convince the cardiological community that there was specificity,” Dr. Duboc said, referring to differences DM patients have with regards to cardiovascular disease and why treatments need to be designed with an awareness of their underlying condition. “The neurological community, however, was pleased to see cardiologists interested in the specific problem.”

Dr. Duboc, professor of cardiology at Paris Descartes University, and head of the department of cardiology at Chez Hopital Cochin, addressed the 11th meeting of the International Myotonic Dystrophy Consortium (IDMC-11) in September 2017. Among the research he discussed is a new study that draws on more than ten years of data collected on 2,000 DM patients, and suggests that DM patients should be stratified on the basis of the severity of their cardiovascular complications. He proposed a method of scoring these patients to do so.

Dr. Duboc said that sudden death from cardiologic complications of DM are the second leading cause of death in DM patients. Rather than follow treatment protocols designed to be appropriate for general cardiology patients, he said it is critical to optimize clinical care of DM patients with cardiovascular complications. “General rules applied by cardiologist do not address this specific population,” he said.

The new research follows a study published two years ago in the Journal of the American Medical Association that showed clinicians were able to improve the prognosis of DM patients with cardiovascular problems by tailoring their approach with the muscle disease in mind. “It is important to think that this is a DM1 patient, not a patient with a heart problem,” he said.

Dr. Duboc said patients with DM should be treated more aggressively than other patients who may present with the same cardiovascular symptoms because of the greater risks these patients face of sudden death due to arrhythmias. While the use of a prophylactic pacemaker is not widely accepted in treating a general cardiology patient, Dr. Duboc’s work has shown that DM1 patients do better when a pacemaker is implanted before classic clinical symptoms would dictate such a course of treatment.

Size Matters

At IDMC-11, Dr. Duboc discussed another study that was published in the journal Circulation: Cardiovascular Genetics. It found that the size of a DM patient’s genetic mutation—the greater the number of repeats in the RNA—correlates with the severity of the cardiac problems they will experience.

By considering the underlying genetics driving an individual patient’s disease, Dr. Duboc argues that doctors can use this as an indicator of how aggressive an approach to interventions a doctor should consider.

In a separate study, Dr. Duboc examined DM patients who appeared to suffer from Brugada Syndrome, a specific type of ventricular arrhythmia that is a major cause of sudden death. DM1 is associated with risk of sudden ventricular arrhythmia that appears to mimic Brugada Syndrome. Dr. Duboc sought to see if DM1 patients with ventricular arrhythmia suffered from Brugada Syndrome, or if they could be shown to have a different cause of their arrhythmias.

When he compared a group of general cardiac patients with Brugada syndrome with DM1 patients with ventricular arrhythmias similar to those found with the condition, he found that DM1 patients with ventricular arrhythmias had an accumulation of toxic RNA in the nuclei of myocardia cells as a result of the genetic mutation driving DM1.

The RNA abnormalities affect the expression of the gene coding the sodium channels (SCN5a) of the heart and can affect the way electrical signals move through the heart and lead to irregular heartbeats. However, the same RNA abnormalities expression was not present in the myocardial cells of the general population patients with Brugada syndrome to explain that irregularity, the SCN5a gene being generally directly mutated in this disease.

“It’s a very elegant example of the collaboration between clinical observation and molecular biology to find new mechanisms implicated in the pathophysiology of the disease,” said Dr. Duboc.

One of the consequences of this finding, according to Dr. Duboc, is that the potential for this type of arrhythmia should provide a warning sign to neurologists who may prescribe DM patients mexiletine, a commonly prescribed drug used to treat myotonia. An effect of mexiletine is that is that it blocks the sodium channels of the heart. As a result, it can induce arrhythmias. If a DM patient already has cardiac involvement from the disease, the neurologist should consult a cardiologist before prescribing because it could exacerbate the problem.

Progress and Promise

Dr. Duboc said that the advances that have been made in the understanding of DM have improved the prognosis for patients through better clinical management of the disease. With the understanding of the molecular mechanism of the disease, the potential for therapies that address the underlying cause of DM is now possible. He said the upcoming IDMC-11 is a chance to bring together a wide range of researchers and clinicians who work on the disease to exchange information and help move toward potential treatments.

“It is very important because it is a specific community working in one disease (or two diseases if you include DM2),” he said of the conference. “It’s very interesting to have all of the specialists of this disease with different talking and working together.”