Cardiomyopathy is the leading cause of death in patients with Duchenne muscular dystrophy. The relationship between cardiac and skeletal muscle progression is unclear. The objective of this study was to evaluate the correlation between muscle activity and cardiomyopathy. We hypothesised that cardiomyopathy and skeletal muscle activity are directly related.

Physical activity was assessed with accelerometers worn for 7 days. Average activity (vector magnitude/min) and percentage of time in different activities were reported. Cardiac MRI was used to assess left ventricular ejection fraction, global circumferential strain (Ecc), late gadolinium enhancement, and cardiac index. Associations were assessed between physical activity and cardiac variables using a Spearman correlation.

Duchenne muscular dystrophy subjects (n = 46) with an average age of 13 ± 4 years had a mean left ventricular ejection fraction of 57 ± 8%. All physical activity measures showed significant correlations with left ventricular ejection fraction (rho = 0.38, p = 0.01) and left ventricular cardiac index (rho = 0.51, p < 0.001). Less active subjects had lower left ventricular ejection fraction (p = 0.10) and left ventricular cardiac index (p < 0.01). Non-ambulatory patients (n = 29) demonstrated a stronger association between physical activity and left ventricular ejection fraction (rho = 0.40, p = 0.03) while ambulatory patients demonstrated a stronger association between physical activity and left ventricular cardiac index (rho = 0.53, p = 0.03). Ecc did not associate with physical activity in either cohort.

Physical activity correlates with left ventricular ejection fraction and left ventricular cardiac index and is modified by ambulation. Future analysis should assess the temporal relationship between physical activity and cardiomyopathy.

Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.

This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.

Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.

The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.

This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.

Distinguishing between hypertrophic cardiomyopathy and other causes ofleft ventricular hypertrophy can be difficult in children. We hypothesised that cardiac MRI T1 mapping could improve diagnosis of paediatric hypertrophic cardiomyopathy and that measures of myocardial function would correlate with T1 times and extracellular volume fraction.

Thirty patients with hypertrophic cardiomyopathy completed MRI with tissue tagging, T1-mapping, and late gadolinium enhancement. Left ventricular circumferential strain was calculated from tagged images. T1, partition coefficient, and synthetic extracellular volume were measured at base, mid, apex, and thickest area of myocardial hypertrophy. MRI measures compared to cohort of 19 healthy children and young adults. Mann–Whitney U, Spearman’s rho, and multivariable logistic regression were used for statistical analysis.

Hypertrophic cardiomyopathy patients had increased left ventricular ejection fraction and indexed mass. Hypertrophic cardiomyopathy patients had decreased global strain and increased native T1 (−14.3% interquartile range [−16.0, −12.1] versus −17.3% [−19.0, −15.7], p < 0.001 and 1015 ms [991, 1026] versus 990 ms [972, 1001], p = 0.019). Partition coefficient and synthetic extracellular volume were not increased in hypertrophic cardiomyopathy. Global native T1 correlated inversely with ejection fraction (ρ = −0.63, p = 0.002) and directly with global strain (ρ = 0.51, p = 0.019). A logistic regression model using ejection fraction and native T1 distinguished between hypertrophic cardiomyopathy and control with an area under the receiver operating characteristic curve of 0.91.

In this cohort of paediatric hypertrophic cardiomyopathy, strain was decreased and native T1 was increased compared with controls. Native T1 correlated with both ejection fraction and strain, and a model using native T1 and ejection fraction differentiated patients with and without hypertrophic cardiomyopathy.

Myocardial strain measurements are increasingly used to detect complications following heart transplantation. However, the temporal association of these changes with allograft rejection is not well defined. The aim of this study was to describe the evolution of strain measurements prior to the diagnosis of rejection in paediatric heart transplant recipients.

All paediatric heart transplant recipients (2004–2015) with at least one episode of acute rejection were identified. Longitudinal and circumferential strain measurements were assessed at the time of rejection and retrospectively on all echocardiograms until the most recent negative biopsy. Smoothing technique (LOESS) was used to visualise the changes of each variable over time and estimate the time preceding rejection at which alterations are first detectable.

A total of 58 rejection episodes were included from 37 unique patients. In the presence of rejection, there were decrements from baseline in global longitudinal strain (−18.2 versus −14.1), global circumferential strain (−24.1 versus −19.6), longitudinal strain rate (−1 versus −0.8), circumferential strain rate (−1.3 versus −1.1), peak longitudinal early diastolic strain rate (1.3 versus 1), and peak circumferential early diastolic strain rate (1.5 versus 1.3) (p<0.01 for all). The earliest detectable changes occurred 45 days prior to rejection with simultaneous alterations in myocardial strain and ejection fraction.

Changes in graft function can be detected non-invasively prior to the diagnosis of rejection. However, changes in strain occur concurrently with a decline in ejection fraction. Strain measurements aid in the non-invasive detection of rejection, but may not facilitate earlier diagnosis compared to more traditional measures of ventricular function.

Outcome analyses in large administrative databases are ideal for rare diseases such as Becker and Duchenne muscular dystrophy. Unfortunately, Becker and Duchenne do not yet have specific International Classification of Disease-9/-10 codes. We hypothesised that an algorithm could accurately identify these patients within administrative data and improve assessment of cardiovascular morbidity.

Hospital discharges (n=13,189) for patients with muscular dystrophy classified by International Classification of Disease-9 code: 359.1 were identified from the Pediatric Health Information System database. An identification algorithm was created and then validated at three institutions. Multi-variable generalised linear mixed-effects models were used to estimate the associations of length of stay, hospitalisation cost, and 14-day readmission with age, encounter severity, and respiratory disease accounting for clustering within the hospital.

The identification algorithm improved identification of patients with Becker and Duchenne from 55% (code 359.1 alone) to 77%. On bi-variate analysis, left ventricular dysfunction and arrhythmia were associated with increased cost of hospitalisation, length of stay, and mortality (p<0.001). After adjustment, Becker and Duchenne patients with left ventricular dysfunction and arrhythmia had increased length of stay with rate ratio 1.4 and 1.2 (p<0.001 and p=0.004) and increased cost of hospitalization with rate ratio 1.4 and 1.4 (both p<0.001).

Our algorithm accurately identifies patients with Becker and Duchenne and can be used for future analysis of administrative data. Our analysis demonstrates the significant effects of cardiovascular disease on length of stay and hospitalisation cost in patients with Becker and Duchenne. Better recognition of the contribution of cardiovascular disease during hospitalisation with earlier more intensive evaluation and therapy may help improve outcomes in this patient population.

Aneurysmal dilation of the right ventricular outflow tract complicates assessment of right ventricular function in patients with repaired tetralogy of Fallot. Tricuspid annular plane systolic excursion is commonly used to estimate ejection fraction. We hypothesised that tricuspid annular plane systolic excursion measured by cardiac MRI approximates global and segmental right ventricular function, specifically right ventricular sinus ejection fraction, in children with repaired tetralogy of Fallot.

Tricuspid annular plane systolic excursion was measured retrospectively on cardiac MRIs in 54 patients with repaired tetralogy of Fallot. Values were compared with right ventricular global, sinus, and infundibular ejection fractions. Tricuspid annular plane systolic excursion was indexed to body surface area, converted into a fractional value, and converted into published paediatric Z-scores.

Tricuspid annular plane systolic excursion measurements had good agreement between observers. Right ventricular ejection fraction did not correlate with the absolute or indexed tricuspid annular plane systolic excursion and correlated weakly with fractional tricuspid annular plane systolic excursion (r=0.41 and p=0.002). Segmental right ventricular function did not appreciably improve correlation with any of the tricuspid annular plane systolic excursion measures. Paediatric Z-scores were unable to differentiate patients with normal and abnormal right ventricular function.

Tricuspid annular plane systolic excursion measured by cardiac MRI correlates poorly with global and segmental right ventricular ejection fraction in children with repaired tetralogy of Fallot. Tricuspid annular plane systolic excursion is an unreliable approximation of right ventricular function in this patient population.