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MDF Publishes Clinical Care Recommendations for Cardiologists

Published on Fri, 03/20/2020

Evidence-based Guidelines

Due to the multisystemic nature of myotonic dystrophy type 1 (DM1), it has been a challenge to conduct the studies and collect the rigorous evidence required to create an evidence-based guideline for the cardiac clinical care of patients with myotonic dystrophy type 1. In order to improve the quality of life and standardize care for people living with DM1, MDF organized and supported 10 leading DM1 cardiologists in Canada, Japan, Western Europe, the United Kingdom, and the United States to create the Consensus-based Care Recommendations for Cardiologists Treating Adults with Myotonic Dystrophy Type 1.

Publication Preparation

To promote the development of cardiac care guidelines for myotonic dystrophy, MDF solicited the input of care experts and organized the drafting of these recommendations. The 10 leading DM1 cardiologists created the Consensus-based Care Recommendations for Cardiologists Treating Adults with Myotonic Dystrophy Type 1 through an iterative drafting process. All authors contributed content to create the first draft and leading author Elizabeth McNally, M.D., Ph.D. was in charge of managing further editing cycles. The process began in 2017 and concluded in February 2020, with the article published on the Journal of the American Heart Association website on 2/6/20 and in print on 2/18/20 in Volume 9, Issue 4.

Tell Your Cardiologist

The guidelines review cardiac management of myotonic dystrophy, including surveillance for arrhythmias and left ventricular dysfunction, both of which occur in progressive manner and contribute to morbidity and mortality. Other topics reviewed in the guidelines include heart imaging, cardiomyopathy treatment and stroke risk, concluding in 15 summary recommendations. The recommendations represent expert consensus opinion from those with experience in the management of myotonic dystrophy, in part supported by literature‐based evidence where available.

The guidelines are intended for use by cardiologists but individuals diagnosed with DM1 are encouraged to provide a copy of the recommendations to their cardiologists. The guidelines represent an exciting step in the cardiac treatment and management of DM1 and MDF is thrilled to support this vital educational effort to standardize care.

Resources

Digitally access the full article on the Journal of the American Heart Association website.

You can download the full Consensus-based Care Recommendations for Cardiologists Treating Adults with Myotonic Dystrophy Type 1 as well as other critical care resources to share with your doctor on our Toolkits & Publications page.

If you would like a hard copy of the article or guidelines mailed to you, please email us at info@myotonic.org.

References:

Clinical Care Recommendations for Cardiologists Treating Adults With Myotonic Dystrophy
McNally EM, Mann DL, Pinto Y, Bhakta D, Tomaselli G, Nazarian S, Groh WJ, Tamura T, Duboc D, Itoh H, Hellerstein L, and Mammen PPA
JAHA. 2020 Feb 6. doi 10.1161/JAJA.119.014006 [Epub ahead of print]

 

How Myotonic Dystrophy Affects the Heart - 2024 MDF Regional Conference in Los Angeles, CA

Presented at the 2024 MDF Regional Conference on Saturday, May 18, 2024 at Covel Commons on the UCLA campus in Los Angeles, CA.

This session covers cardiac considerations in myotonic dystrophy including how DM can affect the heart, common issues, the latest research, and best practices for care.

Speakers: Daniel Cruz, MD, PhD, UCLA Health

Click here to earn more about the 2024 MDF Regional Conference in in Los Angeles, CA!

Ask-the-Expert: Myotonic Dystrophy & the Heart


Originally presented on July 25th, 2024.

Do you have questions for myotonic dystrophy (DM) doctors? Join world-class DM cardiologist, Dr. William J. Groh, for an "Ask the Expert" webinar on DM and the heart!

Find all our upcoming Ask the Expert dates and previously recorded sessions! >>>

Myotonic Dystrophy Cardiac / Heart Resources

  • Myotonic Dystrophy and the Heart: A Community Guide: For individuals living with myotonic dystrophy, heart or “cardiac” issues can pose a serious threat to their health. Since the heart is itself a muscle, people living with myotonic dystrophy type 1 (DM1) or type 2 (DM2) can experience cardiac issues. This resource aims to help people living with DM understand heart health risks and how they are managed.
     
  • Consensus-based Care Recommendations for Cardiologists Treating Adults with Myotonic Dystrophy Type 1: In order to improve and standardize care for people living with myotonic dystrophy, 10 leading myotonic dystrophy (DM1) cardiologists in Western Europe, the UK, Canada, Japan and the US joined together to create these Consensus-based Care Recommendations! 

About our Myotonic Dystrophy Expert

Dr. William J. Groh, MD, MPH

Dr. William J. Groh is a board-certified Internal Medicine Specialist, Cardiologist, and Cardiac Electrophysiologist. He has been involved in providing clinical care of patients with myotonic dystrophy and cardiac issues since 1994. Dr. Groh has conducted clinical research to determine how best to assess the heart in myotonic dystrophy. 

Dr. Groh led a multicenter group assessing cardiac outcomes in individuals with myotonic dystrophy type 1. He was the lead author on an international consensus document on cardiac care for patients with neuromuscular disorders published recently. Dr. Groh is currently the Chief of Medicine at the Ralph H. Johnson VAMC in Charleston, SC and holds an academic appointment at the Medical University of South Carolina. Dr. Groh continues to provide care for patients with cardiac and cardiac arrhythmia issues.

Patterns:

  • DM1-related cardiac pathology manifests predominantly as arrhythmias due to progressive abnormalities in the conduction system of the heart. Clinical presentations may include: presyncope, syncope, palpitations, dyspnea and, rarely, chest pain or sudden death from cardiac arrest.

  • Bradyarrhythmias (arrhythmias that cause a slowing of the heart rate) are not reported in literature under the age of ten years. Rarely, life-threatening tachyarrhythmias have been reported as young as ten. Although exact numbers of sudden cardiac death in children with DM1 or CDM are not known, they are thought to be very low.

Symptoms:

  • Symptoms representing arrhythmias, sinus bradycardia, heart block, atrial fibrillation and flutter, orventricular tachycardia on ECG and systolic dysfunction on echocardiogram.

  • Symptom change, abnormal cardiac imaging, abnormal ECG.

  • Palpitations, dizziness, syncope, non–sinus rhythm.

Diagnosis:

  • Discuss the following tests with your doctor:

    • Evaluation of severity of cardiac rhythm disturbance via a 12-lead electrocardiogram (ECG), and long-term ambulatory ECG monitoring.

    • Serial ECG studies are useful to follow progression of conduction system abnormalities over time, as they are often asymptomatic.

    • Transient arrhythmia via 24-48 hour ambulatory holter ECG monitoring. Longer monitoring if the 12-lead ECG is abnormal or if symptoms are suggestive of an arrhythmia.

    • Cardiology evaluation with examination, ECG, echocardiogram, and ambulatory electrocardiographic monitoring should occur at the time of DM diagnosis, regardless of symptoms.

    • For individuals with normal LV ejection fraction and no evidence of the symptoms described prior, it is reasonable to reassess by examination, ECG, and ambulatory electrocardiographic monitoring annually and by echocardiogram every 2 to 4 years.

Treatment:

  • Use of emergency medical alert devices to identify DM1 diagnosis and risk of arrhythmia.

  • Be informed about the risks of arrhythmias and cardiac dysfunction and the importance of prompt medical attention if symptoms are observed (i.e. palpitations, pre-syncope, syncope, dyspnea, chest pain, unexplained fatigue).

  • Serial periodic clinical cardiology evaluation; specialist cardiology consultations are essential with abnormal electrocardiograms or cardiac symptoms.

  • Refer to:

    • In-hospital cardiac monitoring to detect arrhythmias if admitted for longer duration than typical following surgical procedures.

    • In-hospital cardiac monitoring if admitted due to severe illness or infection.

Patterns:

  • DM2-related cardiac pathophysiology, although affecting all myocardial tissue, preferentially targets the cardiac conduction system. Conduction system defects are progressive and, while initially asymptomatic, increase the risk for symptomatic arrhythmias.

  • Pre-syncope, syncope, palpitations, dyspnea, chest pain or sudden death from cardiac arrest.

  • Risk of both bradyarrhythmias and tachyarrhythmias. The most common tachyarrhythmias are atrial fibrillation and atrial flutter, which pose a risk of cardiogenic embolism and stroke. There is an increased risk of ventricular tachyarrhythmias (tachycardia or fibrillation), a mechanism responsible for cardiac arrest, in DM2.

  • Asymptomatic abnormalities are observed in a moderate number of adults with DM2 and are more common in those with conduction system disease.

Symptoms:

  • Palpitations, pre-syncope, syncope, dyspnea and chest pain; if observed, seek prompt attention.

  • Arrhythmias including sinus bradycardia, heart block, atrial fibrillation and flutter, and ventricular tachycardia.

  • Symptom change, abnormal cardiac imaging (MRI or echocardiogram), abnormal ECG.

Diagnosis:

  • Discuss the following tests with your doctor:

    • Cardiac testing, including the 12-lead electrocardiogram (ECG), long-term ambulatory Holter-ECG monitoring and invasive electrophysiological study.

    • Imaging studies, including echocardiography, magnetic resonance (MR), and nuclear imaging to assess the heart’s mechanical status, including left ventricular function.

    • Impulse or conduction abnormalities on a standard 12-lead ECG.

    • Echocardiography and cardiac MRI if abnormal ECG or other symptoms suggestive of heart failure are present.

Treatment:

  • Pacemakers can be implanted either to treat symptomatic bradyarrhythmias or prophylactically in those at high risk for complete heart block.

  • Implantable cardioverter-defibrillators (ICDs) can be installed for ventricular tachyarrhythmia, or prophylactically in those at high risk for a ventricular tachyarrhythmia.

  • Use of emergency medical alert devices.

  • Serial periodic clinical cardiology evaluations; cardiology consultations are recommended in for abnormal electrocardiograms and/or cardiac symptoms.

  • Cardiac imaging at diagnosis and every three to five years thereafter.

  • Invasive electrophysiology when there is concern about a serious conduction block or arrhythmia because of abnormalities detected via noninvasive cardiac testing.

  • Ambulatory Holter ECG monitoring – either short-term (24-48 hours) or long-term (30 days or more) may be considered to detect mechanisms of arrhythmias.

  • Refer to:

    • A cardiology center experienced in care of DM2

    • An anesthesia practitioner, separate from the operating physician, to provide procedural sedation and monitoring for electrophysiology studies and pacemaker or ICD implantation.

Patterns:

  • DM1-related cardiac pathophysiology, although affecting all myocardial tissue, preferentially targets the cardiac conduction system. Conduction system defects are progressive and, while initially asymptomatic, increase the risk for symptomatic arrhythmias.

  • Pre-syncope, syncope, palpitations, dyspnea, chest pain or sudden death from cardiac arrest.

  • The development of a dilated, non-ischemic cardiomyopathy is an infrequent but recognized occurrence. Once a symptomatic dilated cardiomyopathy is present, progression is typically rapid, with congestive heart failure leading to death.

Symptoms:

  • Palpitations, pre-syncope, syncope, dyspnea and chest pain.

  • Arrhythmias including sinus bradycardia, tachyarrhythmias, heart block, atrial fibrillation and flutter, and ventricular tachycardia. The most common tachyarrhythmias are atrial fibrillation and atrial flutter, which pose a risk of cardiogenic embolism and stroke.

  • Symptom change, abnormal cardiac imaging, abnormal ECG.

Diagnosis:

  • Discuss the following tests with your doctor:

    • Cardiac testing, including the 12-lead electrocardiogram (ECG), long-term ambulatory ECG monitoring, and an invasive electrophysiological study.

    • Imaging studies, including echocardiography, computerized tomography (CT), magnetic resonance (MR), and nuclear imaging can be used to assess the heart’s mechanical status, including left ventricular function.

    • Echocardiograph if abnormal ECG indicative of conduction disease or if other symptoms suggestive of heart failure are present.

Treatment:

  • Pacemakers can be implanted to treat symptomatic bradyarrhythmias or prophylactically in those at high risk for complete heart block.

  • Implantable cardioverter-defibrillators (ICDs) can be installed in those who have survived an episode of a ventricular tachyarrhythmia or, prophylactically, in those at high risk for a ventricular tachyarrhythmia.

  • Use of emergency medical alert devices.

  • Serial periodic clinical cardiology evaluations.

  • Ambulatory Holter ECG monitoring – either short-term (24-48 hours) or long-term (30 days or more) – to detect mechanisms of arrhythmias.

  • Mexiletine can provide relief for atrial fibrillation but because it is an anti-arrhythmic, a complete workup must be done first to rule out underlying structural or functional abnormalities that may complicate its use. Mexiletine-related monitoring should be conducted by a cardiologist experienced in the treatment of DM1.

  • Refer to:

    • A cardiology center experienced in care of DM1.

    • An anesthesia practitioner, separate from the operating physician, to provide procedural sedation and monitoring for electrophysiology studies and pacemaker or ICD implantation.

Modifying Gene Editing Technology for DM

Published on Tue, 08/15/2017

Gene Editing for DM

Gene editing has garnered considerable publicity as the newest technology with potential for developing therapies for rare diseases. MDF previously published a primer, titled "Using Gene Editing to Correct DM," on the CRISPR/Cas9 technology that has been heavily promoted in the media.

Gene editing technology uses molecular mechanisms that were first developed in bacteria as a shield against invasion from viruses. This approach is rapidly moving into clinical trials for a select group of diseases—those where cells can be isolated from the body, edited, and then returned to patients as a viable treatment for the disease. These diseases are predominantly disorders of the blood and cancers, and several clinical trials are recruiting patients in China (HIV-infected subjects with hematological malignances; CD19+ refractory leukemia/lymphoma; esophageal cancer; metastatic non-small cell lung cancer; EBV-associated malignancies). At least one trial has been approved in the U.S. by the Food and Drug Administration (FDA) and is expected to start soon (this is also for a set of cancers).

For myotonic dystrophy (DM), multiple organ systems are affected and we cannot take the simple path of editing and returning cells to the body—treatment must address simply too much body tissue mass, including the brain, the heart, skeletal muscles, the gastrointestinal system, and other organs that are affected. Thus, for CRISPR/Cas9 to “work” in DM, the gene editing reagents will have to be efficiently delivered to virtually every cell in patients and effectively execute the deletion of CTG and CCTG repeat expansions from the DNA. The delivery of gene editing reagents into patients is an incredibly difficult undertaking and is likely years away from clinical trials in any disease.

Could a Modified CRISPR Technology be Effective in DM?

Investigators at the University of California San Diego, the University of Florida, and the National University of Singapore have recently reported early research that potentially ‘repurposes’ gene editing technology for a set of RNA disorders—myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), a subset of Lou Gehrig’s disease (ALS) patients and Huntington’s disease. They have modified the Cas9 enzyme so it is targeted to toxic RNA, instead of the expanded DNA repeats in these diseases.

The researchers have optimized Cas9 so that it can specifically target and degrade expanded repeat RNA for DMPK and CNBP genes. In many ways, this is similar to the approach that Ionis Pharma is using to target CUG repeats RNA in DM1. 

Their development of an RNA-targeted Cas9 results in the degradation of toxic RNA, an increase in the MBNL protein, and reduction or elimination of the gene splicing defect that characterizes DM. The strategy uses gene therapy vectors to delivery the modified Cas9 enzyme. If this approach were to be effective, it’s likely that patients would only need a single intravenous injection to treat skeletal muscles, the heart, and the gastrointestinal system; because gene therapy does not cross the blood brain barrier, a second injection may be needed, into the fluid around the spinal cord, to treat the brain. To work toward clinical development, the researchers have formed a biotechnology company to raise funding and move the candidate therapy forward.

We Still Have a Considerable Way to Go Before this Novel Strategy is in the Clinic

While this approach shows promise, we should be cautioned that studies thus far have only tried the new experimental therapy in patient cells in tissue culture. Therapy development has to pass through preclinical testing in appropriate mouse models, preclinical safety testing and approval by the FDA before the first clinical trial can be launched. Importantly, this effort represents yet another shot on goal to develop a novel therapeutic for DM1 and DM2. MDF monitors all drug development efforts and will keep the community informed as to their progress.

Know Your DM1 Repeat Length: It’s Important for Your Cardiac Care

Published on Fri, 08/11/2017

Understanding cardiac and other myotonic dystrophy (DM) risk factors and planning for the known complications of DM that may affect you someday can help protect and maintain your quality of life and that of your loved ones. Cardiac complications are the highest-priority care consideration for doctors treating patients with myotonic dystrophy type 1 (DM1) (as identified by expert clinicians in the forthcoming care guideline, "Consensus-based Care Recommendations for Adults with DM1"). As a result, researchers have been trying to understand the factors that may increase the risks of cardiac disease for DM patients.

Dr. Caroline Chong-Nguyen at the Sorbonne Paris Cité University and her colleagues recently published a study in which they looked at DM1 repeat length and its relationship to the risk of cardiac disease. This was a large study of the data in the French patient registry, which tracks patients' symptoms and information over time to understand disease progression and other important information. Eight hundred fifty-five patients with genetically-confirmed DM1 were followed for an average of 11.5 years in order to gain insight into how repeat length could predict cardiac events. Importantly, the research team considered many other factors (such as age, sex, and presence/absence of diabetes) to ensure that their data was not confounded by other variables.

The research team showed that death, sudden death and other adverse cardiac events were linked to DM1 repeat length. Heart rate was higher and conduction system disease was more prevalent in subjects with larger repeats. They found that each 500 repeat increase was associated with 1.5-fold higher risk of death from all causes. Patients with longer repeat lengths also were more likely to have a permanently-implanted pacemaker. 

These findings support taking a more aggressive approach toward screening DM patients for adverse cardiac events, particularly for DM1 patients at the higher end of the range of repeat lengths. Knowing your repeat will help you have discussions with your physician about monitoring and managing your level of risk for cardiac disease.

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