Assessing Arrhythmic Risk in Adult Patients with Duchenne Muscular Dystrophy
Abstract
Background: Historically, the most common cause of death in Duchenne Muscular Dystrophy (DMD) has been respiratory failure. However, with improved respiratory support, diseases of the heart muscle have become clinically apparent. Cardiac involvement in DMD starts in early childhood, and by the end of the second decade, weakening of the heart muscle is observed in more than 30% of men and can lead to heart failure, heart rhythm abnormalities, and sudden cardiac death. While life expectancy over the past three decades has increased due to better respiratory support, this has also led to a perceived shift from pulmonary to cardiac-related deaths in older Duchenne patients. Many men with DMD die suddenly; however, it remains unclear whether they die of arrhythmias. In line with this notion, a recent document by the DMD Working Group identified screening and therapy for cardiac arrhythmias in DMD as understudied areas. Objective and Study Design: We propose to study the natural history of the rhythm abnormalities in DMD by implanting miniaturized cardiac monitors (ILRs) in 75 DMD patients at risk for developing potentially life-threating heart rhythm disorders (Specific Aim 1). Boys and young men with DMD (age >10 years and with an at least mildly reduced heart pump function) will be recruited from three large DMD centers in the United States. Insertion of the miniaturized ILRs (about 1/3 the size of a AAA battery) which allow continuous monitoring of arrhythmias for 5 years is minimally invasive, requires local anesthesia only and is safe: a recent report of 273 patients who underwent implantation of an ILR showed that 99.3% of patients had no serious adverse events during follow-up. In response to patient activation or based on automated device algorithms, arrhythmia episodes are stored and automatically transmitted to the clinician by wireless telemonitoring. Thus, the current grant proposal will allow us to collect and analyze more than 200 patient-years of continuous electrocardiogram (ECG) recordings from DMD patients deemed at the highest risk of arrhythmias. This represents a significant advantage over currently available rhythm data collected with Holter monitoring (i.e., yearly 24 hour or 48 hour ECG recordings) which give only an incomplete snapshot of arrhythmias and have a very low diagnostic yield. Additionally, computer simulations in personalized 3D heart models generated from cardiac magnetic resonance imaging (MRI) images obtained during clinical visits, will examine whether scar tissue found in DMD hearts will allow for a better identification of patients at highest risk for arrhythmias who may benefit from implantation of a cardioverter-defibrillator (ICD). Conversely, we hope that this approach will allow us to reliably identify low risk patients in whom ICD implantation is not necessary (Specific Aim 2). Impact: By addressing the cardiac DMD Research Program Focus Area, the proposed research will help define the burden of serious arrhythmias in teenage and adult DMD patients (Specific Aim 1) and examine their relationship with scar tissue found in DMD hearts (Specific Aim 2). Estimating the contribution of arrhythmias to sudden death will help to determine whether patients with Duchenne derive benefit from implantable defibrillators. A recent survey of DMD caregivers showed that the perceived risk of cardiac arrhythmias (22.4%) was only second to concerns about treatment effect on muscle function (28.7%). Thus, a better understanding of the arrhythmic burden in DMD patients has the potential to significantly advance the field and improve patient care. We hope that the findings of this study will translate into clinical practice in the next 5 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910304
Entities
People
- Andreas Barth
Organizations
- Johns Hopkins University
- United States Army