Ambulatory Monitoring and Arrhythmic Outcomes in Pediatric and Adolescent Patients With Duchenne Muscular Dystrophy

Abstract

BackgroundPatients with Duchenne Muscular Dystrophy (DMD) develop cardiac fibrosis and dilated cardiomyopathy. We described the frequency of significant Holter findings in DMD, the relationship between cardiac function and arrhythmia burden, and the impact of these findings on clinical management.Methods and ResultsA retrospective review was done of patients with DMD who received a Holter from 2010 to 2014. Clinical and arrhythmic outcomes were analyzed. Patients were classified based on left ventricular ejection fraction (LVEF): ≥55%, 35% to 54% and <35%. Significant Holter findings included atrial tachycardia, ventricular tachycardia and atrial fibrillation/flutter. Logistic regression was used to assess predictors of significant Holter findings and change in care. The study included 442 Holters in 235 patients. Mean age was 14±4 years. Patients with cardiac dysfunction were older, and had increased late gadolinium enhancement and left ventricular dilation (P<0.01). There were 3 deaths (1%), all with normal function and none cardiac. Patients with LVEF <35% had more arrhythmias including nonsustained atrial tachycardia (P=0.01), frequent premature ventricular contractions, ventricular couplets/triplets, and nonsustained ventricular tachycardia (P<0.001) compared to the other groups. LVEF <35% (P<0.001) was the only predictor of clinically significant Holter finding. Four patients (40%) had change in medication in the LVEF <35% group compared to 9 (3%) in the ≥55% and 4 (4%) in the 35% to 54% groups (P<0.001).ConclusionsSudden cardiac events are rare in DMD patients with an LVEF >35%. Significant Holter findings are rare in patients with DMD who have an LVEF >35%, and cardiac dysfunction appears to predict significant Holter findings. Holter monitoring is highest yield among DMD patients with cardiac dysfunction.

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

“…174,175 However, 2 recent retrospective studies of ambulatory electrocardiographic monitoring by guest on May 9, 2018 http://circ.ahajournals.org/ Downloaded from e210 results in 235 DMD patients 14±4 years of age and 91 patients 17±4 years of age found only LVEF <30% to 35% and increased age (eg, ≥17 years) were associated with abnormal ambulatory electrocardiographic findings, such as nonsustained atrial and ventricular tachycardias. 22,23 Because of limitations in mobility with disease progression, the role of exercise testing in DMD and BMD is somewhat limited. …”

238th ENMC International Workshop: Updating management recommendations of cardiac dystrophinopathyHoofddorp, The Netherlands, 30 November - 2 December 2018

“…The question remains whether this guidance is appropriate for adult patients with BDMD. There is little evidence to guide ICDs use in paediatric patients generally and virtually none in children with DMD [30,31] . One singlecentre study repored a low risk of rhythm abnormalities in paediatric DMD patients whose LVEF was greater than 35% [26] .…”

“…When hypoxaemia / hypercapnia and left ventricular dysfunction interact, the risk of sustained arrhythmias is increased. However, based on the results of ECG-Holter, ECG signal averaging and limited invasive electrophysiology studies in patients with DMD, he concluded that ventricular arrhythmia risk tracks primarily with the severity of left ventricular dysfunction [24,31,65,66] . As such there is little evidence that patients are at risk of sustained atrial or ventricular arrhythmias until cardiomyopathy is advanced.…”

Healing a Heart Through Genetic Intervention

“…The ability to effectively deliver a systemic signal that triggers precise postnatal genetic modification has already been applied to mouse models of Duchenne muscular dystrophy using CRISPR/Cas9 and AAV strtategies. 12–14 The heart is a particularly attractive target for a proactive approach with this disease as heart disease overtly presents later in life, 15 and indeed with improved respiratory care heart failure is now the most common cause of death in in DMD. 16 To effectively treat the skeletal muscle disease, it will probably be necessary to target the mouse satellite cells or muscle stem cells, which may be more refractory to viral mediated interventions.…”